Tunnel Vision - International Council of Ophthalmology · Tunnel Vision The Economic Impact of...

Tu n n e l V i s i o n The Economic Impact of

Primary Open Angle Glaucoma -

A Dynamic Economic Model

Centre for Eye Research Australia Centre for Eye Research Australia

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This report was prepared jointly by the Centre for Eye Research Australia and Access Economics Pty Limited.

We acknowledge particularly the expert input and prior research of

Professor Hugh Taylor AC Centre for Eye Research Australia and University of Melbourne

Professor Jonathan Crowston Centre for Eye Research Australia and University of Melbourne

Associate Professor Jill Keeffe OAM Centre for Eye Research Australia and University of Melbourne

Ms Lynne Pezzullo Access Economics Pty Ltd

Ms Penny Taylor Access Economics Pty Ltd

Mr Peter Moore Access Economics Pty Ltd

Acknowledgments and Disclaimer

While every effort has been made to ensure the accuracy of this document, the uncertain nature of economic data, forecasting and analysis means that Access Economics Pty Limited is unable to make any warranties in relation to the information contained herein. Access Economics Pty Limited, its employees and agents disclaim liability for any loss or damage which may arise as a consequence of any person relying on the information contained in this document.

Publication of this work has been made possible by an unrestricted grant from Allergan who had no part in the direction or findings contained in this report.

Centre for Eye Research Australia, University of Melbourne, Australia, February 2008.

Centre for Eye Research Australia Tu n n e l V i s i o n

Weih L, Van Newkirk M, McCarty C, Taylor H (1998) “Patterns of glaucoma medication use in urban and rural Victoria” Australian and New Zealand Journal of Ophthalmology, 26[Suppl]: S12 S15.

Weinand F, Althen F (2006) “Long term clinical results of SLT in the treatment of POAG” Eur J Ophthalmology, 16: 100-4.

Weinreb RN, Khaw PT (2004) “Primary open-angle glaucoma” The Lancet, 363: 1711-20.

Weinreb RN, Friedman DS, Fechtner RD, Cioffi GA, Coleman AL, Girkin CA, Liebmann JM, Singh K, Wilson MR, Wilson R, Kannel WB (2004) “Perspective: Risk Assessment in the Management of Patients with Ocular Hypertension” American Journal of Ophthalmology, 138[3]: 458-67.

Wensor M, McCarty C, Stanislavsky Y, Livingston P, Taylor H (1998) “The prevalence of glaucoma in the Melbourne Visual Impairment Project” Ophthalmology, 105: 733-9.

Wilson MR, Coleman AL, Fei Yu, Sasaki IF, Kim MH (2002) “Depression in patients with glaucoma as measured by self-reported surveys” Ophthalmology, 105[5]: 1018-22.

Wolfs RC, Klauver CC, Ramrattan RS, van Duijin CM, Hofman A, de Jong PT (1998) “Genetic risk of primary open-angle glaucoma. Population based familial aggregation study” Arch Ophthal, 116: 1640-45.

Zahari M, Mukesh B, Rait J, Taylor H, McCarty C (2006) “Progression of visual field loss in open angle glaucoma in the Melbourne Visual Impairment Project” Clinical and Experimental Ophthalmology, 34: 20–6.

Zeiter JH, Shin DH (1994) “Diabetes in primary open-angle glaucoma patients with inferior visual field defects” Graefes Archive for Clinical & Experimental Ophthalmology, 232[4]: 205-10.

Zghal I, Jeddi A, Hadj Alouane WB, Malouche N, Ayed S, Gaigi S (2000) “Primary open-angle glaucoma and diabetes [French]” Tunisie Medicale, 78[8-9]: 518-21.

Zwerling C, Sprince NL, Davis CS, Whitten PS, Wallace RR, Herringa SG (1998) “Occupational injuries among older workers with disabilities: a prospective cohort study of the Health and Retirement Survey, 1992 to 1994” American Journal of Public Health, 88: 1691-16.

11. References

The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model 105

1The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model

Main heading to go here

EXECUTIVE SUMMARY 7

1. Background 10

2. Primary Open Angle Glaucoma 11

3. Risk Factors 13

3.1 Intraocular pressure 133.2 Age 153.3 Cup-to-disc ratio 163.4 Central corneal thickness 163.5 Family history and genetics 173.6 Ethnicity 173.7 Diabetes mellitus 183.8 Other potential risk factors 19

4. Epidemiology 20

4.1 Definition of disease stage 204.2 Remission 204.3 Mortality 204.4 Population 214.5 Progression 214.6 Prevalence and incidence 294.7 Disease stages defined 33

5. Treatment 34

5.1 Medication 345.2 Laser treatment 395.3 Conventional surgery (trabeculectomy) 415.4 Prevalence estimates for each treatment group 435.5 Treatment efficacy 445.6 Side effects 50

6. Disease Costs 55

6.1 Discount rates 556.2 The cost to quality of life and wellbeing 566.3 Health system costs 606.4 Indirect costs 686.5 Deadweight losses 69

7. Summary of Model Parameters 70

8. The Model 73

9. Intervention Scenarios 76

9.1 The base case 769.2 Improved diagnosis rate 809.3 Change in the treatment protocol (Primary laser) 839.4 Research and development 879.5 Combinations 89

Contents

Tu n n e l V i s i o nCentre for Eye Research Australia

10. Appendix 1: Meta-Analysis - Falls and Hip Fractures 92

10.1 Fixed-effects versus random-effects 92

10.2 Heterogeneity 92

10.3 Forest plots 93

10.4 Publication bias 96

10.5 Additional supportive literature 97

11. References 98

FiguresFigure 1.1: Peripheral visual field loss in POAG 10

Figure 2.1: The glaucoma continuum 11

Figure 2.2: Healthy optic nerve 12

Figure 2.3 Glaucomorous optic nerve 12

Figure 3.1: Goldmen tonometery 14

Figure 3.2: Demographic distribution of glaucoma, Australians over 40 15

Figure 3.3: Cup-To-Disk ratio 16

Figure 3.4: Corneal thickness 17

Figure 3.5: Pseudoexfoliation pupil margin 19

Figure 4.1: Schematic of the level of impairment for definite glaucoma 29

Figure 4.2: Original prevalence rates 30

Figure 4.3: Smoothed prevalence rates (moving average across three age groups) 31

Figure 5.1: Glaucoma medication dispensed by year and type of script(% of total scripts) 35

Figure 5.2: MBS Trabeculoplasty Procedures, 1994-2005 40

Figure 5.3: Trabeculectomy 41

Figure 5.4: MBS Total of Trabeculectomy Procedures, 1994-2005 42

Figure 8.1: Main Menu 73

Figure 8.2: Options Sheet 74

Figure 8.3: Model Design 75

Figure 9.1: Prevalence OHT and POAG, base case 77

Figure 9.2: Value burden of disease due to POAG ($m), base case 78

Figure 9.3: Impact of increased diagnosis rates on DALYs(a) 82

Figure 9.4: Impacts of increased diagnosis rates on treatment costs 82

Figure 9.5: Cost Effectiveness Plane - Increase Diagnosis Rate(a) 83

Figure 9.6: Cost-savings resulting from a protocol change(a) 85

Figure 9.7: Burden of Disease 85

Figure 9.8: Decline in DALYs from new efficacious treatment 88

Contents

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The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model


3

Figure 9.9: Treatment costs with new treatment costing $1000 per person per year 88

Figure 9.10: Reduction in DALYs, combined interventions 90

Figure 9.11: Treatment costs, combined interventions 91

Figure 9.12: Total costs, combined scenarios 91

Figure 9.13: Cost effectiveness plane, Combined Scenarios(a) 91

Figure 10.1: Annotated Forest Plot (Random Effects Model) for Visual 94Impairment and Falls

Figure 10.2: Annotated Forest Plot (Random Effects Model) Glaucome/VFL and Falls 95

Figure 10.3: Annotated Forest Plot (Random Effects Model) for Visual Impairmentand Hip Fractures 95

TablesTable 1.1: Disease stage 7

Table 3.1: Significant risk factors for OHT progression to glaucoma,identified by the OHTS 14

Table 3.2: Hazard ratios for development of POAG from OHT 14

Table 3.3: Risk factors for glaucoma progression, identified by the earlymanifest glaucoma trial 15

Table 3.4: Association Between Diabetes Mellitus and Glaucoma 19

Table 4.1: Relative risk of mortality by stage of Visual Impairment 21

Table 4.2: Natural progression rates (cumulative probability) 15 year period 25

Table 4.3: Estimates of disease progression in untreated patients 27

Table 4.4: Definitions of level of impairment for definite glaucoma 29

Table 4.5: OHT and Glaucoma prevalence rates 30

Table 4.6: Incidence and prevalence of ocular hypertension (% of age group) 32

Table 4.7: Proportion of people with glaucoma by age and severity (%),smoothed (moving average across three age groups) 32

Table 4.8: Disease Stage 33

Table 5.1: IOP lowering medications 35

Table 5.2: Proportion of each drug class by state, 2005 36

Table 5.3: Number of medications taken in combination 37

Table 5.4: Trabeculectomy - MBS services processed by jurisdiction by year 42

Table 5.5: Incidence and treatment failure rate for each stage of treatmentfrom dismod II 44

Table 5.6: Progression rates (cumulative probability) in treated patients (15 year period) 46

Table 5.7: Studies of the efficacy of laser treatment 47

Table 5.8: Success rates for trabeculectomy 49

Table 5.9: Medication side effects 50

Table 5.10: Risk of COPD (% of Population), 2001 51

Table 5.11: Health System Cost of COPD ($ per Person), 2005 52

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4 Tu n n e l V i s i o nCentre for Eye Research Australia

Table 5.12: Trabeculectomy Side-Effects 53

Table 5.13: Prevalence of Cataract (% of Population) 54

Table 5.14: Health System Cost of Cataract ($ per Person), 2005 54

Table 6.1: AIHW Disability Weightings 59

Table 6.2: Health Costs by Who Bears the Cost, 2004-05 60

Table 6.3: Cost of Medication per Person per Annum 61

Table 6.4: Total Cost of Trabeculoplasty Per Treatment 61

Table 6.5: Total Cost of Trabeculectomy Per Treatment 62

Table 6.6: Probability of Residing in an Aged Care facility, 2004-05 63

Table 6.7: Increased Risk of Falls From Visual impairment 64

Table 6.8: Meta-Analysis, Falls (Random Effects Model) 64

Table 6.9: Relative Risk of an accidental fall by Severity 65

Table 6.10: Risk of Accidental Fall (% of Population), 2001 65

Table 6.11: Health System Cost of an Accidental Fall ($ per Person), 2005 66

Table 6.12: Depression and Vision Loss 67

Table 6.13: Risk of Depression (% of Population), 2001 67

Table 6.14: Health System Cost of Depression ($ per Person), 2005 68

Table 6.15: Indirect Costs ($ per annum), 2005 69

Table 7.1 Prevalence of OHT and POAG 70

Table 7.2 Severity of visual impairment — initial proportional split 71

Table 7.3: Modelled treatment assumptions 71

Table 7.4: Modelled treatment costs $ 2005 (including side-effects and adverse events) 72

Table 7.5: Other modelled variables 72

Table 9.1: Prevalence of OHT and POAG, base case (number of people) 77

Table 9.2: Costs of POAG, 2005 and 2025, base case 78

Table 9.3 Base case (standard treatment) net present value of DALYs and costs 78

Table 9.4 Comparison of prevalence of OHT and POAG with original andsmoothed data 79

Table 9.5 Net present value of DALYs and costs, sensitivity analysis on OHTPrevalence and incidence for those aged 80+ years 79

Table 9.6: Model Results – Increased Diagnosis Rate, Net present value 2005 to 2025 81

Table 9.7: Model Results – Protocol Change – Trabeculoplasty as primary treatment 84

Table 9.8: Sensitivity Analysis - A conservative approach to surgery failure rates 86

Table 9.9: Model Results – Research and Development - showing the impact ofnew treatment to reduce progression by 50% and 75% 89

Table 9.10: Model Results - Combined Scenarios 90

Table 10.1: Fixed Effects and Random Effects, Meta-Analysis Results 92

Table 10.2: Heterogeneity within the Combined Studies 93

Table 10.3: Measures of Publication Bias 96

Table 10.4: Non-quantitative supporting literature 97

Contents



ABS Australian Bureau of Statistics

AGIS Advanced Glaucoma Intervention Study

AIHW Australian Institute of Health and Welfare

ALT Argon Laser Trabeculoplasty

AMD Age related macular degeneration

AWE Average Weekly Earning

BMES Blue Mountains Eye Study

CERA Centre for Eye Research Australia

CI Confidence interval

EDS Early Disease Stage

CIGTS Collaborative Initial Glaucoma Treatment Study

CNTGS Collaborative Normal Tension Glaucoma Study

COPD Chronic Obstructive Pulmonary Disease

DALYs Disability adjusted life years

DRG Diagnosis Related Group

EGPS European Glaucoma Prevention Study

EMGT Early Manifest Glaucoma Trial

GLT, GLTFU Glaucoma Laser Trial, Glaucoma Laser Trial Follow Up

HAP Hodapp-Anderson-Parrish grading system for disease stage

IOP Intraocular pressure

mm Hg Millimetres of mercury, Measure of intraocular pressure.

MBS Medicare Benefits Schedule

MMC Mitomycin C - an anti fibrotic drug which inhibits scarring.

MVIP Melbourne Visual Impairment Project

OHT Ocular hypertension

OHTS Ocular Hypertension Treatment Study

OR Odds ratio

POAG Primary Open Angle Glaucoma

PR Prevalence Ratio

Pseudoexfoliation Pseudoexfoliation syndrome is a systemic condition characterised byglaucoma/ the production and progressive accumulation of pseudoexfoliative pseudoexfoliation material in many ocular tissues. Glaucoma occurs more commonly insyndrome eyes with this syndrome than in those without it. Exfoliative glaucoma

has a more rapid clinical course and worse prognosis than primaryopen-angle glaucoma.

RR Relative risk

SD Standard deviation

SLT Selective Laser Trabeculoplasty

VA Visual acuity

VF Visual field - the ability to detect objects to either side, or above or below, the direction of vision. It is measured in terms of degrees fromthe point of fixation, for example, <10 degree field means that the person can only see in a visual field of less than 10 degrees radius fromthe point of fixation (CERA 2004).

VFL Visual field loss

Glossary and Acronyms



Access Economics was commissioned by the Centre for Eye Research Australia (CERA) toconstruct a dynamic model of primary open angle glaucoma (POAG) in Australia, to informpolicy development in relation to this serious source of visual impairment and blindness.

The model is based on data from a wide variety of sources, and an intensive literature reviewinformed the estimation of parameters, such as risk factors for POAG, natural progression of thedisease, treatment efficacy, quality of life, and comorbid conditions (falls and depression).

• Intraocular pressure (IOP) was identified as the only modifiable risk factor for thedevelopment and progression of POAG. Current medical and surgical treatments are centredon reducing IOP and maintaining it at lower levels.

• Age, cup-to-disc ratio and central corneal thickness are non-modifiable risk factorsfor glaucoma.

• Studies of links between POAG and diabetes mellitus have shown mixed results, so diabeteswas not incorporated in the modelling. As future studies are completed this association willbecome better understood.

• Studies of family history suggest it is an apparent non-modifiable risk factor, but support foran association is not strong possibly because of ascertainment bias.

The incidence, prevalence and mortality associated with POAG and the incidence and prevalenceof ocular hypertension (OHT) were based on data from the Melbourne Visual ImpairmentProject (MVIP) and the Blue Mountains Eye Study (BMES) and use of the DISMOD II model,and based on severity of visual impairment (with severity splits based on MVIP and BMESdata). Disease stages are defined in Table 1.1. Demographic groups within the population areprojected on the basis of Access Economics Dynamic model population by gender and year ofage projections to 2025.

TABLE 1.1: DISEASE STAGE

Disease stage Description Visual Visual field acuity loss (VFL)

No POAG No visual impairment (OHT or normal tension)

Early Disease Stage Definite or Probable Better And No VFL (EDS) Glaucoma. No visual than 6/12 impairment but changes to optic nerve and/or retinal nerve fibre layer

Mild Definite Glaucoma with mild <6/12 Or Any loss of visual impairment visual field (VF)

Moderate Definite Glaucoma with <6/18 Or <20o field moderate visual impairment

Severe Definite Glaucoma with severe <6/60 Or <10o field or profound visual impairment

Executive Summary

Australian health care cost of glaucoma in 2005 was $342 million.

The total annual cost of glaucoma in 2005 was $1.9 billion.

The total cost is expected to increase to $4.3 billion by 2025.


In studies of glaucoma, disease progression is not always measured in terms of vision loss. Clinical studies often use a combination of changes in VF, IOP and optic disc as indicators ofprogression. Further, definitions of vision loss vary across researchers, and different researchershave developed different grading systems to measure progression. The application of progressionrates from the literature therefore proved too problematic. Initially, the approach was to applythe progression rates from the Weinreb et al, (2004) synthesis in the modelling. Unfortunately,it was not possible to match the Weinreb et al, (2004) rates with the available incidence andprevalence data from the MVIP and BMES to obtain sensible projections. To overcome theseproblems natural progression rates were derived from prevalence data from the MVIP and BMESto achieve sensible projections and mindful of the approach used to synthesise progressionrates in Weinreb et al, (2004). This led to annual progression rates that are for the most partsubstantially higher than expected so more research and population data — particularly bystage of visual impairment for POAG — are clearly required.

The progression rates for people with treated glaucoma are half of those for untreatedglaucoma, in line with the literature on treatment efficacy (key clinical trials such as the EarlyManifest Glaucoma Trial EMGT and the Ocular Hypertension Treatment Study (OHTS)) and themethodology from Weinreb et al, (2004). (For treatment efficacy, Weinreb et al, (2004) usedthe results from the OHTS and the EMGT as the only trials which compared treatment with notreatment.)

Treatment failure rates are around 4% of patients per annum failing medication (consistentwith Australian data on rates of trabeculoplasty), 50% of patients per annum failing lasertherapy (consistent with the literature on the efficacy of laser treatment) and 50% of patientsper annum failing surgery (a conservative estimate which is higher than the literature butsensitivity analysis provided in the report shows it makes little difference to the results).Remission was modelled as nil, with relative risks for mortality depending on vision loss(1.67 for mild POAG, 2.34 for moderate POAG and 3.01 for severe POAG decreasing in linewith older age).

The costs of POAG include:

• health system costs — derived from data from the Australian Institute for Health and Welfare, Medicare fees and the Department of Health and Ageing National HospitalCosts Data Collection. Health cost data are also included in the model in relation to thecosts of falls and depression that are associated with vision loss from POAG.

• Indirect costs — including productivity losses (lower than average employment rates ofpeople with visual impairment). Productivity losses are low since POAG generally affectsolder people. Carer costs and the costs of aids and equipment and deadweight losses basedon CERA’s research and previous Access Economics calculations are also included.

• Loss of wellbeing (measured as the burden of disease — Disability Adjusted LifeYears (DALYs).

The model itself is constructed on a user-friendly Excel platform to enable ease of policysimulations. Three scenarios were analysed in relation to the base case. The results reportedhere are calculated for smoothed prevalence rates and reflect the net present value of costs andbenefits over the period 2005 to 2025.

A dynamic model of POAG was developed

to inform policy development on an

ongoing basis.

Executive Summary

The savings from a new treatment will

depend on the annual treatment cost.

Initial laser trabeculoplasty gives significant

cost savings.

Increasing the rate of diagnosis to 80% would cost $80,189

per DALY.

Centre for Eye Research Australia


• The first scenario reflects an improvement in diagnostic methods. More than 50% ofindividuals with glaucoma in the developed world are unaware they have the disease(Quigley, 1996). In a population based study (the MVIP), Wensor et al, (1998) found that50% of those with definite POAG had not been diagnosed previously, and Wong et al, (2004)examined MVIP data and found that 59% of definite cases of OAG were undiagnosed inpeople who had visited an eye care provider in the previous year. Even at zero additionalcosts (ie. no additional costs of educating clinicians) and improved diagnosis rates of 70%,80% and 90%, the modelling suggests that these scenarios are cost effective but relativelyexpensive, at between $153,000 to $167,000 per DALY avoided. Improved diagnosis ratesare associated with a rise in health system costs as more people are treated. However, theburden of disease (DALYs) falls.

• The second scenario is a change in the treatment protocol, with laser replacing medicationas first line therapy. The Glaucoma Laser Trial (GLT) showed that Argon Laser Therapy wasas efficacious as timolol (prostaglandins and Selective Laser Therapy were not in use atthat time). However, Argon Laser Trabeculoplasty (ALT) was not commonly adopted as aprimary treatment because of concern about side effects and the reduced efficacy of repeatALT treatments. More recent evidence for the effectiveness of laser treatments as a primarytherapy include the EMGT, Nagar et al, (2005), and McIlraith et al, (2006). The modellingshows that changing the treatment protocol (based on the assumption that current lasertreatments are as efficacious as medication) is cost saving, reflecting the assumption thatprimary laser would be provided alone whereas as a second line treatment (as per currentapproaches), laser and medication are provided together. Even tripling the cost of lasertrabeculoplasty or increasing it five fold (from $724 to $3,622) to account for the possibilityof side effects (and assuming these don’t affect quality of life), a change in the treatmentprotocol remains cost saving.

• The final scenario modelled a new potential therapy to delay progression (for exampleavailability of a neuroprotectant drug that protects by means other than IOP lowering ).The model allows for a new therapy that reduces the progression of glaucoma by a further50% or 75% over and above the reduction in progression from current treatments tobe analysed. Cost effectiveness depends on the cost per person per annum of the newtreatment. At treatment costs of $1,000 per person per annum, new treatments arecost saving. New treatments remain cost effective and relatively cheap at $5,000 perdiagnosed patient per annum ($44,700/DALY avoided if progression is delayed by 50% overthe base case and $23,400/DALY avoided if progression is delayed by 75% over the basecase). At $10,000 per diagnosed patient per annum, new treatments are still cost effectivebut become relatively expensive ($114,400/DALY avoided and $71,914/DALY avoidedrespectively).

The POAG dynamic model enables rapid comparison of the cost-effectiveness of various interventions for the disease and is a valuable tool for ongoing policy formulation and best practice treatment to address visual impairment and blindness from POAG.

1 Memantine is used for Alzheimers disease and in phase III trials for glaucoma at the time of writing.

Executive Summary


Access Economics Pty Limited was commissioned by the Centre for Eye ResearchAustralia (CERA) to:

1. Construct a dynamic model of primary open angle glaucoma (POAG) in Australia,that encompassed prevalence, incidence, risk factors, health and indirect financial costs,treatment options and measures of wellbeing; and

2. Document the model and report on the impacts over the period 2005-2025 of:

< better detection of POAG;

< a change in treatment protocol; and

< a potential new therapy to delay disease progression.

A similar model was previously developed to examine the impact of a number of newtreatments modes on age-related macular degeneration: a quit smoking program; new researchthat delays progression; and a new therapy that enhances treatment efficacy (CERA 2006).The model has the capacity to be adapted to incorporate other sources of visual impairmentin the future, such as diabetic retinopathy, cataract, and refractive error.

This project follows on from earlier reports2:

• Clear Insight: The Economic Impact and Cost of Vision Loss in Australia (CERA 2004);

• Investing in Sight: Strategic Interventions to Prevent Vision Loss in Australia(CERA 2005); and

• Centrally Focused: The Impact of Age-related Macular Degeneration, A Dynamic Economic Model (CERA 2006).

Due to the technical nature of the modelling, this report assumes familiarity with theterminology used in these previous reports.

This report is structured as follows:

• Description of POAG;

• Epidemiology of the disease (including remission, mortality, progression of the disease whenuntreated and incidence and prevalence);

• Treatment of the disease (including a description of the conventional treatment steps, theirside effects and efficacy);

• The costs of the disease (including its impact on quality of life, the health system costs,productivity costs and other indirect costs);

• Description of the Model, its structure and user interface; and

• Discussion of the scenarios that the model can be used to analyse.

1. Background

Glaucoma causes characteristic loss of peripheral vision and optic nerve changes.

2 Available online at www.cera.org.au.

Figure 1.1: Peripheral visual field loss in POAG.



2. Primary Open Angle Glaucoma

Moderate glaucoma is characterised by loss of peripheral vision and sparing of central vision.

Glaucoma is a progressive, neurodegenerative disease that causes accelerated loss of optic nerve neurons. Initial changes to the optic nerve and retina are asymptomatic and oftenundetectable with current diagnostics (Weinreb et al, 2004). Glaucoma can be described as acontinuum (Figure 2.1) where undetectable disease progresses to asymptomatic disease withoptic nerve and visual field (VF) change, and finally to symptomatic visual impairment andblindness.

FIGURE 2.1: THE GLAUCOMA CONTINUUM

Source: reproduced from Weinreb et al, (2004).

Box 1: Vision loss from POAG

Central vision is the detailed vision people use to read and recognize faces, whileperipheral vision is the side vision that is used for navigating obstacles in the environment(like doorways and coffee tables) and for detecting oncoming vehicles from a side street.The diagnosis of glaucoma is often made late in the disease course, because early stages ofglaucoma are usually asymptomatic. Moderate glaucoma is characterised by loss ofperipheral vision and sparing of central vision. Patients often fail to notice peripheral visionloss until it has progressed towards the centre of vision.

Source: Reproduced from Kwon et al (2007), A patient’s guide to glaucoma, http://www.medrounds.org/glaucoma-guide/2006/02/table-of-contents-patients-guide-to.html, accessed 4 May 2007

In advanced glaucoma central vision may be lost.

1 in 10 Australians over 80 will develop glaucoma.


There are several different types of glaucoma: primary open angle, angle closure, congenitaland secondary glaucoma. Primary open angle glaucoma (POAG) is the most common worldwideand the topic of this report (Box 2). POAG is characterised by3:

• open anterior-chamber angles;• loss of neuroretinal rim and nerve fibre layer defects;• VF abnormality;• adult onset; and• absence of other known mechanisms.

While many POAG patients present with elevated intraocular pressure (IOP), a significantnumber of patients with POAG do not have detectable IOP elevation. Elevated IOP is a riskfactor for glaucoma and not necessarily an integral part of the disease.

Box 2: Primary Open Angle Glaucoma

Glaucoma is a degenerative disease of the optic nerve that can lead to vision loss andblindness. The optic nerve comprises over a million nerve fibres (axons) that connect theretina with the brain. In the front of the eye is a space called the anterior chamber -clear fluid (aqueous humour) flows in to this space and leaves the chamber at the anglewhere the cornea and iris meet. When the aqueous humour reaches the angle, it flowsthrough a meshwork and leaves the eye. Increased IOP occurs when there is increasedresistance to outflow.

Elevated intraocular pressure is a risk

factor for glaucoma although not

necessarily an integral part of the

disease.

2. Primary Open Angle Glaucoma

3 American Academy of Ophthalmology (2005).

Figure 2.2: Healthy optic nerve Figure 2.3: Glaucomorous optic nerve



Not all cases of glaucoma have an endpoint of unilateral or bilateral blindness. There isconsiderable variation in the risk of progression across patients (Weinreb et al, 2004). Thissection discusses the current theory on the risk factors associated with glaucoma. Moreresearch is needed to fully establish the role and impact of these.

3.1: INTRAOCULAR PRESSURE

IOP is a measurement of the fluid pressure within the eye. IOP is determined by aqueoushumour flow into and out of the anterior chamber (the space between the lens and cornea.This fluid is produced in the ciliary body and flows through the pupil and the trabecularmeshwork or through non-trabecular pathways, commonly called uveoscleral pathways.The balance between the production and outflow of aqueous humour controls the IOP.

The normal range for IOP is between 10 and 21 millimetres of mercury (mm Hg) with anaverage of 16 mm Hg, but average IOP varies across populations. High IOP for populations isusually defined as being greater than two standard deviations (SDs) from the population mean.IOPs that are within the normal population range may still be too high for individual patients.

Increased IOP is a risk factor for the development and progression of POAG. However, thelevel of IOP that causes nerve damage varies between individuals. A certain proportion of thosewith elevated IOP (ocular hypertension or OHT) will develop glaucoma. However, a significantproportion of those with POAG do not appear to have increased IOP.

A univariate and multivariate analysis completed by the Ocular Hypertension Treatment Study(OHTS) showed that for the OHTS population, every 1mm Hg increase in mean IOP level wasassociated with a 10% increased risk of progression from OHT to glaucoma (Table 3.1) (Gordon,Beiser and Brandt et al, 2002). The OHTS Group and the European Glaucoma PreventionStudy Group et al, (2007) confirmed that IOP is a risk factor for the development of POAG inuntreated individuals with OHT (Table 3.2).

3. Risk Factors

Intraocular pressure is a measurement of the fluid pressure within the eye.

Intraocular pressure is a risk factor for glaucoma.

A significant proportion of glaucoma patients have IOPs in the normal range.

�� Tu n n e l V i s i o nCentre for Eye Research Australia

Inaliteraturereviewofprogressionrates,Friedmanetal,(2004)alsofoundthatIOPwasariskfactorforprogressionofglaucoma(Table3.3).Inparticular,theEMGTfoundthattheriskofdeteriorationoftheopticnerveinapopulationofpatientswithPOAGdecreasedby10%foreach1mmHgreductioninIOP(forexample,Leskeetal,2003).JayandMurdoch(1993)alsofoundprogressionwasfasterwithhigherIOP.

IOPiscurrentlytheonlytreatableriskfactorthathasbeenidentifiedtodelayprogressionofglaucoma.CurrentmedicalandsurgicaltreatmentsarecentredonreducingIOPandmaintainingitatlowerlevels.

TABLE 3.1: SIGNIfICANT RISK fACTORS fOR OhT PROGRESSION TO GLAUCOMA,

IDENTIfIED BY ThE OhTS

hazard Ratio (95% Confidence Interval - CI)

Putative Predictive factor Univariate Multivariate

Age(perdecade) 1.43(1.19-1.71) 1.22(1.01-1.49)

Blackrace 1.59(1.09-2.32) 0.98(0.65-1.46)*

Sex(male) 1.87(1.31-2.67) 1.42(0.98-2.05)*

Heartdisease 2.11(1.23-3.62) 1.71(0.95-3.09)*

IOP(permmHg) 1.11(1.04-1.18) 1.10(1.04-1.17)

Cornealthickness(per40mmthinner)(seesection3.4) 1.88(1.55-2.29) 1.71(1.40-2.09)

PatternSD(per0.2dBgreater)(seeBox3) 1.36(1.16-1.60) 1.27(1.06-1.52)

Horizontalcup-to-discratio(per0.1larger)(seesection3.3) 1.25(1.14-1.38) 1.27(1.14-1.40)

Verticalcup-to-discratio(per0.1larger)(seesection3.3) 1.32(1.19-1.46) 1.32(1.19-1.47)

*Notsignificantatp<=0.05.mm=micrometer.dB=decibels.Source:reproducedfromGordon,BeiserandBrandtetal,(2002).

TABLE 3.2: hAZARD RATIOS fOR DEVELOPMENT Of POAG fROM OhT

Source:OcularHypertensionTreatmentStudyGroupandtheEuropeanGlaucomaPreventionStudyGroupetal,(2007).

3. Risk factors

IOP is currently the only treatable

risk factor that has been identified to

delay progression of glaucoma.

Figure3.1:Goldmentonometery

In the following example, we estimate the 5-year risk of de-veloping POAG for a 55-year-old male whose baseline IOPs forright and left eyes are 22 and 26 mmHg; vertical C/D ratios, 0.4and 0.4; CCT measurements, 532 and 548 �m; and PSDs, 2.2 and2.2 dB. Means of the values for the right and left eyes are averagedfor each eye-specific predictor and the points are summed (Table6) to estimate the 5-year risk of developing POAG. The sum ofpoints for this theoretical patient is 11, which yields an estimated5-year risk of developing POAG of 20% (Table 6). The estimatedrisk for this same patient from the Cox proportional hazards modelis 16.9%.

Discussion

Using data from the OHTS observation group, we devel-oped a multivariate model that identified baseline older

age, higher IOP, larger vertical C/D ratio, thinner centralcorneal measurement, and greater PSD as predictive fac-tors for the development of POAG in ocular hypertensiveindividuals. When the generalizability of the OHTSmodel was tested by applying it to data from the placebogroup of the EGPS, the same predictive factors wereidentified. The hazard ratios for the predictive factorswere very similar in the separate models, the pooledmodel, as well as recently published models by Medeiroset al22 and the EGPS Group.23 Thus, the OHTS predictivemodel, including CCT, has been replicated in a Europeansample and a separate U.S. sample. The pooled OHTS–EGPS sample has a large number of participants andlarge number of POAG end points, which yield greaterstability of the hazard ratios and narrower CIs forpredictions.

Table 5. Univariate and Multivariate Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) for the Development of POAGin the Pooled OHTS and EGPS Control Groups

Baseline Variables

Model

Univariate Final Multivariate

nNo. ofEvents HR

95% LowerCI

95% UpperCI P Value n

No. ofEvents HR

95% LowerCI

95% UpperCI P Value

Age (decade) 1312 165 1.41 1.20 1.65 �0.0001 1123 154 1.26 1.06 1.50 0.0072Male gender 1312 165 1.23 0.91 1.67 0.1772Mean IOP per mmHg* 1312 165 1.10 1.03 1.17 0.0052 1123 154 1.09 1.03 1.17 0.0067Mean CCT per 40 �m thinner 1128 156 2.16 1.81 2.59 �0.0001 1123 154 2.04 1.70 2.45 �0.0001Mean vertical C/D ratio per

0.1 larger1311 165 1.21 1.12 1.32 �0.0001 1123 154 1.19 1.09 1.31 0.0001

Mean PSD per 0.2 dB greater 1308 163 1.12 1.04 1.21 0.0019 1123 154 1.13 1.04 1.24 0.0065History of heart disease 1312 165 1.62 1.00 2.61 0.0488Mean deviation defect per 0.1

dB greater1308 163 0.93 0.81 1.06 0.2799

History of high blood pressure 1312 165 1.14 0.83 1.56 0.4300History of migraine 1312 165 0.90 0.51 1.58 0.7073Current use systemic

�-blockers1309 165 0.99 0.49 2.01 0.9736

Current use systemiccalcium-channel blockers

1309 165 1.00 0.61 1.66 0.9876

Myopia ��1 D sphericalequivalent

1312 165 0.89 0.64 1.25 0.5108

CCT � central corneal thickness; CID � cup-to-disc; D � diopters; dB � decibels; IOP � intraocular pressure; PSD � pattern standard deviation.*Eye-specific variables are the mean of right and left eyes for each participant.

Table 6. A Point System for Estimating an Ocular Hypertensive Patient’s 5-Year Risk of Developing PrimaryOpen-Angle Glaucoma (POAG)

Baseline Predictor

Points for Baseline Predictor

0 1 2 3 4

Age (yrs) �45 45 to �55 55 to �65 65 to �75 �75Mean IOP (mmHg)* �22 22 to �24 24 to �26 26 to �28 �28Mean CCT (�m)* �600 576–600 551–575 526–550 �525Mean vertical cup-to-disc ratio by contour* �0.3 0.3 to �0.4 0.4 to �0.5 0.5 to �0.6 �0.6Mean PSD (dB)* �1.8 1.8 to �2.0 2.0 to �2.4 2.4 to �2.8 �2.8

Sum of points 0–6 7–8 9–10 11–12 �12Estimated 5-yr risk of POAG �4.0% 10% 15% 20% �33%

CCT � central corneal thickness; dB � decibels; IOP � intraocular pressure; PSD � pattern standard deviation.*Eye-specific variables are the mean of right and left eyes.

OHTS Group and EGPS Group � Validated Prediction Model for POAG

7

ARTICLE IN PRESS


��The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model

TABLE 3.3: RISK fACTORS fOR GLAUCOMA PROGRESSION, IDENTIfIED BY ThE EARLY

MANIfEST GLAUCOMA TRIAL

hazard Ratio (95% CI)

Baseline factors Univariate Multivariate

Age(≥68,<68years*) 1.42(1.01-1.98)† 1.47(1.04-2.09)†

IOP(≥21,<21mmHg*) 1.67(1.19-2.35)‡ 1.70(1.18-2.43)‡

PatternSD(≤-4,>-4*) 1.46(1.04-2.05)† 1.58(1.10-2.28)†

Pseudoexfoliation(yes,no*) 3.15(1.93-5.15)§ 2.22(1.31-3.74)‡

Botheyeseligible(yes,no*) 1.92(1.34-2.75)§ 1.96(1.36-2.82)§

Post Baseline factors ||

InitialchangeinIOPat3months(permmHg) 0.90(0.86-0.94)§

IOPatfirstfollow-upvisit(permmHg ) 1.11(1.06-1.17)§

MeanIOPatallfollow-upvisits(permmHg ) 1.13(1.07-1.19)§

Percentofvisitswithdischaemorrhage(per% )(a) 1.02(1.01-1.03)§

*Referencecategoryformultivariateanalysis;†P≤0.05;‡P<0.005;§P<0.001;||AdjustedforbaselineIOP,pseudoexfoliation,numberofeligibleeye,meandeviationandage.

(a)Haemorrhagesorbleedingaroundtheopticnervecanindicateongoingdamagetotheopticnerveandinadequatecontrolofglaucoma.

Source:reproducedfromLeskeetal,(2003)

�.�:AGE

Theprevalenceofglaucomaincreasesmarkedlywithage(Figure3.2).Intheirliteraturereviewofprogressionrates,Friedmanetal,(2004)foundthattherewasstrongevidenceofalinkbetweenolderageandtheriskofprogressionfromOHTtoglaucoma(Table3.1)andforprogressionofglaucoma(Table3.3).TheOHTSGroupandtheEuropeanGlaucomapreventionStudyGroupetal,(2007)confirmedthatage(bydecade)isasignificantriskfactorforprogressionfromOHTtoglaucoma(Table3.2).

fIGURE 3.2: DEMOGRAPhIC DISTRIBUTION Of GLAUCOMA, AUSTRALIANS OVER 40

Source:Taylor(2001)

The prevalence of glaucoma increases markedly with age.

Undiagnosed

Diagnosed

Perc

ent

10%

8%

6%

4%

2%

0%

Age40-49 50-59 60-69 70-79 80-89 90+

3. Risk factors

The cost of eye care will continue to increase as the population ages.


�.�:CUP-TO-DISCRATIO

Theopticdiscistheregionoftheeyewherethenervefibresconvergetoformtheopticnerveandexitthebackoftheeyeintotheorbit.Theopticcupisthecentreportionoftheopticdiscandissmallerbycomparison.The loss of optic nerve cells causes the cup to become larger relativetotheopticdisc,increasingthecup-to-discratio.4Thecuptodiscratiocomparesthediameterofthecuptotheentirediameteroftheopticdisc.Thecup-to-discratioisoftenmeasuredbothintheverticalandhorizontalpositiontoestimatetheamountofcuppingandamountofopticnervedamage.Thecuptodiscratioalsoincreasesinnon-glaucomatousnerveswithincreasingdiscdiameter(Crowstonetal,2004).

Largecup-to-discratioshavebeenidentifiedasabaselineriskfactorfordiseaseprogressionwithvaluesof>0.4and≥0.5associatedwithanincreasedriskofprogression.TheunivariateanalysiscompletedintheOHTSshowsthattheriskofglaucomaissignificantlyincreasedwithincreasesincup-to-discratios(Table3.1)asdidtheOHTSGroupandtheEuropeanGlaucomapreventionStudyGroupetal,(2007)(Table3.2).However,largercup-to-discratiosinocularhypertensivepatientsmaybeanindicationofearlystructuraldamageandthereforeserveasadiseasemarkerratherthanariskfactor.

fIGURE 3.3: CUP-TO-DISK RATIO

Cup-to-diskratioreferstotheratioofthecupdiametertotheverticaldiscdiameter.

Source:http://hubnet.buffalo.edu/ophthalmology/site/Home/Physical_Exam/Cup-to-Disc_ratio_normal_.jpgaccessedSeptember2006

�.�:CENTRALCORNEALTHICKNESS

AthincentralcorneahasbeenshowntohaveastrongassociationwiththeprogressionfromocularhypertensiontoPOAG(Table3.1andTable3.2).Thisrelationshiphasbeenexplainedbythepossibilitythatlowcornealthicknessmaybeassociatedwithstructuraldifferencesintheopticnervearchitecturethatpredisposetothedevelopmentofglaucoma.AnotherexplanationisthatmeasurementofIOPisaffectedbythethicknessofthecornea.Inthickercorneas,thetrueIOPislowerthanthemeasuredIOP.Ontheotherhand,inthinnercorneas,thetrueIOPishigherthanthemeasuredIOP.IntheOHTS,thinnercorneaswereassociatedwithahigherriskofdiseaseprogression(Gordonetal,2002).

A thin central cornea has been shown to

have an independent association with the

progression from ocular hypertension

to POAG

4Axonsfromtheopticnerveformtheopticrim.Centralexcavation(thecup)isfreefromopticnerveaxons.Theneuroretinalrimthinsfocallyordiffuselyduetoaxonlossinglaucoma.Thisleadstoenlargementofthecupinrelationtotheopticnerve(increasingthecuptodiscratio).

3. Risk factors



fIGURE 3.4: CORNEAL ThICKNESS

Source:UniversityofIllinoisEyeandEarInfirmaryPositions,TheEyeDigest,http://www.agingeye.net/mainnews/glaucomapachymetry.php

�.�:FAMILYHISTORYANDGENETICS

first-degree relatives of individuals with primary open-angle glaucoma have up to an eight-fold increase in the risk of developing the diseasecomparedtothegeneralpopulation(Wolfsetal,1998;Tielschetal,1994).Weihetal,(2001)foundthat,inmultivariatelogisticregressionmodelsandadjustedforage,thestrongestriskfactorforglaucomawasafamilyhistoryofglaucoma(OddsRatio-OR3.5,95%CI:1.9to6.7).Friedmanetal,(2004)ontheotherhandconcludedthatstrongsupportforanassociationbetweenfamilyhistoryandprogressionfromOHTtoPOAGislacking,reflectingthatmanystudiesofthelinkbetweenfamilyhistoryandPOAGmaybeaffectedbyascertainmentbiasduetopoorrecallorlackofknowledgeoffamilyhistory.Forexample,McNaughtetal,(2000)foundthat27%ofpreviouslydiagnosedPOAGpatientswereunawareoftheirpositivefamilyhistory,suggestingthatahigherpercentageofadultPOAGmaybeinheritedthanhithertoreported.

POAGhasanapparentcomplexormultifactorialaetiology(WeinrebandKhaw,2004).Thechromosomallocationsofseveralgenesthatcanindependentlycausethediseasehavebeenmapped.More than 43 different glaucoma gene mutationshavebeenreportedinopen-angleglaucomapatients,andseverallargestudieshavesuggestedthatasagroupthesemutationsareassociated with 3-4% of patients withtheconditioninpopulationsworldwide(Fingertetal,2002).TheglaucomageneatGLC1Alocus(myocilin)hasbeenshowntobeassociatedwithbothjuvenileandadult-onsetprimaryopen-angleglaucoma(Sheffieldetal,1993;Stoneetal,1997;Alwardetal,1998;Fingertetal,1999;Polanskyetal,2000;Clarketal,2001).Thelowattributableriskportionofgeneticfactorsindicatesthatnon-geneticfactorsplayaninfluentialroleinthedevelopmentandprogressionofglaucoma.

�.�:ETHNICITY

Ethnicityhasbeenproposedasariskfactorinmanystudies.Inparticular,AmericanbasedstudieshavenotedahigherprevalenceandrateofprogressioninAfrican-Americanpopulations.ResultsfromtheOHTSsuggestthattheAfrican-Americanraceitselfdoesnotincreasetheriskofglaucomaprogressionbutreflectsahigherprevalenceofotherriskfactorswithinthatpopulation.AfricanAmericanstendtohavethinnercorneas,higherIOPandlargercuptodiscratiosonaveragethanCaucasians(Friedmanetal,2004).

3. Risk factors

POAG has a complex, multifactorial aetiology.

first degree relatives of OAG patients have an 8-fold increased risk of developing glaucoma.

Corneal thickness


�.�:DIABETESMELLITUS

TheOHTSshowedthatdiabetesmellitusmayprotectagainstprogressionfromOHTtoPOAG-(hazardratio0.37inmultivariateanalysis,p<0.05)-however,thepeoplewithdiabetesenrolledinthestudywerecarefullyselected(thosewithdiabeticretinopathywereexcluded)andmayrepresentanunusuallyhealthydiabeticpopulation(OHTSGroup;EuropeanGlaucomaPreventionStudyGroupetal,2006).

Twoglaucomamanagementtrialsshowedalinkbetweenthelikelihoodofglaucomaprogressionandthepresenceofdiabetesmellitus(theAdvancedGlaucomaInterventionStudy(AGIS,2002)andtheCollaborativeInitialGlaucomaTreatmentStudy-CIGTS(Lichteretal,2001)),whilemanyothershaveeitherexcludedindividualswithdiabetesornotexaminedanyrelationships(Friedmanetal,2004).

Populationbasedstudiesaswellasretrospectiveandprospectivecohortstudiesalsoprovidemixedresults(seeTable3.4)-includingpopulationbasedstudiesinAustralia.WhileMitchelletal(1997)foundanincreasedprevalenceofglaucomaforthosewithdiabetes(OR=2.12)andOHT(OR=1.86),astudybyWeihetal,(2001)foundthatwithadjustmentforage,therewasnosignificantdifferenceintheprevalenceofglaucomaamongthosewithdiabetesandthosewithout(resultsfordiabetesnotpresentedinthearticle).

VariationsinthedefinitionofPOAGmayexplainsomeofthedifferentfindings(deVoogdetal,2006).Forexample,deVoogdetal,(2006)notethatarevisionintheirdefinitionofPOAGledtoarevisionintheresultsfromtheRotterdamEyeStudy-fromaninitiallysignificantrelativerisk(RR)oftheprevalenceofPOAGinparticipantswithdiabetesmellitusof3.11(95%CI1.12to8.66)toanon-significantRRof1.40(95%CI0.96to2.03)(DeVoogdetal,2006:1830).DeVoogdetal,(2006)alsonotedthattheresultsfromthemetaanalysisbyBonovasetal(2004)(seeTable3.4)werebasedonpreviousworkfromtheRotterdamEyeStudywhichhasbeenrevisedbasedonanewdefinitionofPOAG5.

The association between POAG and

Diabetes is not clear.

3. Risk factors

5TheresultschangedfromaninitiallysignificantRRoftheprevalenceofPOAGinparticipantswithdiabetesmellitusof3.11(95%CI1.12to8.66)toanon-significantRRof1.40(95%CI0.96to2.03).(DeVoogdetal,2006:1830).

Over 40 gene mutations have been

reported in POAG.



TABLE 3.4: ASSOCIATION BETWEEN DIABETES MELLITUS AND GLAUCOMA

Source Details Assoc.

Bonovasetal,2004* Statisticallysignificantassociationassumingarandomeffects 3 model(OR=1.50,95%CI1.16to1.93)orfixedeffectsmodel (OR=1.27,95%CI1.10to1.45)

deVoogdetal,2006† RRofincidentopen-angleglaucomawithdiabeteswas0.82 x (95%CI0.33to2.05)

Dielemansetal,1996† Associationbetweennewlydiagnoseddiabetesmellitusandhighlevelsof 3 bloodglucosewithhigh-tensionglaucoma,OR=3.11(95%CI,1.12to8.66)

Kleinetal,1994§ Open-angleglaucomaincreasedwithage-relateddiabetes ?^ (4.2%versus2.0%,inpeoplewithdiabetesversuspeoplewithout)

Weihetal,2001 Withadjustmentforage,morepeoplewithselfreporteddiabetes x hadpossible,probablyordefiniteglaucoma(12/230,5.2%)than thosewithoutdiabetes(175/4392,2.5%)butthedifferencewas notstatisticallysignificant(chisqtest,1df=0.86,p=0.36)

Mitchelletal,1997‡ PrevalenceofglaucomaandOHTincreasedinpeoplewithdiabetes 3 OR=2.12,95%CI1.18to3.79)(OHT:OR=1.86,95%CI1.09to3.20)

Tielschetal,1995# DiabeteswasnotassociatedwithPOAG(OR=1.03,95%CI0.85to1.25)

Pasqualeetal,2006 Type2diabeteswasassociatedtoPOAGinwomenwitha 3 RR=1.82(95%CI,1.23to2.70)

Zghaletal,2000 volutionofopen-angleglaucomaindiabetesdidnot x significantlydifferenttopeoplewithoutdiabetes

Buddeetal,1998 Patientswithorwithoutdiabetesdidnotsignificantly x differinthemorphologyoftheopticdisc

Zeiteretal,1994 Peoplewithprimaryopen-angleglaucomaandpredominantly 3 inferiorVFdefectsinoneorbotheyesaremorelikelytohavediabetes

*-Meta-analysis;†-RotterdamStudy;§-BeaverDamEyeStudy;‡-BMES;#-BaltimoreEyeSurvey^Theseresultswereobtainedfromthestudyabstract.Itwasunclearwhetheragewascontrolledinthiscomparison,thereforetheresultcannotbedeterminedtobeeithersupportiveonnon-supportiveofanassociation.

Withsuchmixedresults,theassociationbetweendiabetesmellitusandglaucomahasnotbeenmodelledhere.Asfuturestudiesarecompletedthisassociationwillbecomebetterunderstoodandcanthusbeincludedinmodellingsomeindirectinterventionscenariossuchasimproveddiagnosisofdiabetesandbetterglycemiccontrol.

�.�:OTHERPOTENTIALRISKFACTORS

Anumberofotherpotentialriskfactorshavebeenhighlightedincluding:• migraine:theOHTSshowedapositiveassociationalthoughnotstatisticallysignificant;• myopia(nearsightedness);• hyperopia(farsightedness);• pseudoexfoliation:foundtobeamajorriskfactorforprogressionintheEMGTwhich

includedasmallnumberofpatientswiththiscondition;• outflowfacility:conflictingresultsfromprogressionstudies;• malegender;• opticdischaemorrhage;• sleepapnoea;and• peripheralvasospasm6.

Ingeneral,thelimitednumberofstudiesinwhichtheseadditionalsuspectedriskfactorswereevaluateddoesnotsupportfirmconclusionsconcerningtheirrelativeimportance.

3. Risk factors

6Aperipheralvasospasmisacontractionofabloodvessel—reducingitsinternaldiameterandbloodflow—intheouterpartofthevisualfield.

Figure3.5:Pseudoexfoliationpupilmargin.


The effect of the disease and its treatment on a patient’s health

and quality of life is a key outcome

for measuring the economic impact

of disease.

In this section, the characteristics of the disease are discussed - remission, mortality, progressionand finally, prevalence and incidence. Estimates of prevalence and incidence were modelledbased on Melbourne Visual Impairment Project (MVIP) and BMES data and knowledge ofremission, and mortality drawn from the literature. Progression rates were modelled based onthe literature, previous modelling work and taking into account the available data on prevalenceand incidence by age and visual impairment.

The key outcome for measuring the economic impact of disease is the effect of the disease andits treatment on a patient’s health and quality of life. For eye disease, the key outcome is visionloss. Deterioration in vision is a fundamental determinant of the costs of glaucoma (particularlyindirect costs such as participation in the workforce, need for care and vision aids, as well asquality of life). In the case of glaucoma, however, non-vision, physiological changes (changes inIOP or optic disc for example) may also determine treatment, and therefore health system costs. While the costs of the disease are measured and incurred by individuals, diagnosis and qualityof life depend on the interrelationship between vision in each eye. In some patients, glaucomamay affect only one eye. If it affects both eyes, disease severity and progression in each eye candiffer, so there is often a better eye and a worse eye. Further, eyes that were originally “better”may become the “worse” eye over time. While a diagnosis of glaucoma is based on the worst eye, quality of life - on the other hand - is determined by the best eye (Brown, 1999, Kobeltet al, 2006:369).

4.1: DEFINITION OF DISEASE STAGE

There are five disease stages in the model which are discussed and defined throughout the textbelow. For ease of reference, a summary of the disease stages is provided in Table 4.8.

4.2: REMISSION

Currently there is no natural remission in open angle glaucoma (to either no disease oran earlier stage of the disease), nor any current treatments that improve VF or acuity.Consequently the remission rate for every stage of the disease is nil.

4.3: MORTALITY

General population mortality rate forecasts are from the Access Economics Demographic Model(AE-DEM) of the Australian population (see Section 4.4 for more information).

The rate of mortality from glaucoma is assumed to be determined by the person’s level of visualimpairment — people do not die from glaucoma itself but from associated complications suchas higher rates of accidental falls, isolation and depression (which are implicit in the calculationof the RR of mortality). McCarty et al, (2001) estimated that visual impairment (best correctedvisual acuity of <6/12) was associated with a significantly increased risk of mortality (ORadjusted for age, sex, country of birth, smoking, hypertension and arthritis of 2.34), whichconverted to a RR is 2.15.

The RRs of mortality from vision loss by disease stage used in the model are loosely based onMcCarty et al (2001)7 and fall with age as per Table 4.1.

4. Epidemiology

7 2.34 plus 0.67 (the difference between 1 and 1.67 or between 1.67 and 2.34).



The impact of disease on vision determines the impact on health and quality of life.

TABLE 4.1: RELATIVE RISK OF MORTALITY BY STAGE OF VISUAL IMPAIRMENT

Age OHT/EDS Mild Moderate Severe

40-44 1.00 1.67 2.33 3.00

45-49 1.00 1.67 2.33 3.00

50-54 1.00 1.67 2.33 2.99

55-59 1.00 1.66 2.32 2.98

60-64 1.00 1.66 2.31 2.95

65-69 1.00 1.65 2.29 2.91

70-74 1.00 1.64 2.26 2.85

75-79 1.00 1.62 2.20 2.75

80-84 1.00 1.59 2.11 2.59

85-89 1.00 1.53 1.98 2.37

90+ 1.00 1.45 1.79 2.06

Source: Loosely based on McCarty et al, (2001).

The aetiological fraction for mortality due to glaucoma (as opposed to the number ofpeople who died) is 1.27% based on the same techniques used in CERA (2004: 37) but usingupdated data.

4.4: POPULATION

Forecasts of the Australian population are from AE-DEM which uses a combination of fertility,mortality and migration rates to project the future Australian population. Base fertility andmortality profiles for each age and gender (for mortality) are sourced from ProductivityCommission (2005), and adjust over time to match the projection for the total value. Migrationrates are projected in line with the assumptions in the Australian Bureau of Statistics (ABS)publications: Australian Demographic Statistics (catalogue number 3101.0) and OverseasArrivals and Departures (catalogue number 3401.0), with adjustments for changes to Australia’smigration program and to reflect the latest actual migration (international and interstate) results.

4.5: PROGRESSION

For this dynamic study, a key parameter is the rate at which POAG causes vision to deteriorate(the rate of disease progression). The impact of disease on vision determines the impact on health and quality of life. Unfortunately, in studies of glaucoma, disease progression is notalways measured in terms of vision loss. Clinical studies often use a combination of changes inVF, IOP and optic disc as indicators of progression. As IOP is the focus of treatment, treatmentefficacy is generally measured according to its impact on IOP. Further, definitions of vision loss vary across researchers.

4. Epidemiology


Measuring and grading glaucomatous vision lossMeasuringtheprogressionofVFLinglaucomaiscomplex(seeBox3foranexplanationofthemethodoftestingVF).

• Glaucomatouschangeneedstobeisolatedfromotherfactorssuchaschangesinlensopacityduetocataract,orphysiologicalchangeduetoageing.

• Therecanbesubstantialmeasurementvariability(causedforexamplebylossoffixation),andthereisalearningeffect,bothofwhichneedtobeaccommodatedwhenexaminingpatients.

• Glaucomatousvisiondeteriorationisveryslow.Evenwhenachangeinfieldisdetectedviaperimetry,thepatientmaynotnoticeanyvisionloss.ClinicalstudieshavefoundthatonlyasubsetofpatientswithOHTdevelopglaucoma,andofthese,asmallproportionlosefunctionalvisionduringthecourseoftheirlifetime.

Further,differentresearchershavedevelopeddifferentgradingsystemstomeasureprogression.Forexample,theAGIS,EMGTandCIGTSalluseddifferentgradingsystemstomeasureprogression.OthergradingsystemsincludethosedevelopedbyAnderson,Blumenthal,andHodapp-Anderson-Parrish(HAP).

Differentgradingsystemsshowdifferentratesofprogressioninthesamepopulation(Zaharietal,2006,Wilsonetal,2002).Thereisnogoldstandard,soitisdifficulttocompareprogressionratesderivedfromstudiesusingdifferentmethodologies(Katzetal,1999).ComparisonsofprogressionratessuggestthatratesproducedusingtheAGISmethodmightrepresentalowerboundinjudgingprogression,andtheCIGTSandEMGTmethodsproducerelativelysimilarresults(Katzetal,1999,Wilsonetal,2002,Zaharietal,2006).

Weinrebetal,(2004)developedamethodologyforovercomingthisproblem(section4.5.1.).

Box�:MeasuringchangeinVF

VFistestedbyexaminingapatient’sabilitytodetectlightatvariousintensitiesatvarioustestlocationsintheVF.Thedimmerthelightdetected,thebetterthevisionatthatpointinthefield.Theresultsoftestsaregenerallyexpressedinadecibelscalederivedfromthereciprocalofthelogintensityofthelightprojected.Thusdetectionofdimmerlight(representingbettervision)isindicatedbyhighernumbers.ThesenumberscanbeusedtocreateagradingsystemforVFL.ParametersfromVFtestsusedtomeasurefieldlossare:

a) Meandeviationordefect-themeasurementofhowthemeanofthepatient’sresponsesvariesfromthemeanoftheresponsesofaseriesofnormalpatientsofsimilarageundersimilartestingconditions.Meandeviationisaffectedbymediaopacity,refractiveerrorandglaucoma.

b)PatternSD,alsoknownascorrectedlossvariance,representsnon-uniformlossoffieldthusprovidinganindicationoffocaldefectsasoccuringlaucoma.

4. Epidemiology

Patients enrolled in clinical trials do not

necessarily represent the community norm.

Where possible population-based

data has been used.


4. Epidemiology

The importance of study population characteristics in selecting progression rates for modelling

Ideally,inselectingprogressionratesformodelling,dataneedtobedrawnfromstudiesthatarebasedonpopulationswithsimilarcharacteristicstothatbeingmodelled.Asnotedinsection3,anumberoffactorscanaffectprogressionratesincludingage,IOP,centralcornealthicknessandcuptodiscratio,orAfricanAmericanorigin(forexample).Inaddition,patientswithpseudoexfoliationsyndromeandpigmentaryglaucomaareoftenincludedtogetherwithPOAGpatientsinstudiesoftreatmentefficacyanddiseaseprogression.Whiletheidealwouldinvolverecalculationoftheresultswheretheinclusionofthesepatientshasamaterialimpactontheprogressionestimates,thereportedresultsoftenprecludere-calculationexcludingtheseparticipants.

Further,theparametersselectedforthemodellingneedtoreflectthelikelyoutcomesofadministeringtherapyinthecommunity,ratherthansimplyreplicatingthetrials.Progressionratesbasedonestimatesfromclinicaltrialsdonotnecessarilyreflecttheexperienceinthecommunity.Those enrolled in clinical trials often do nothavediseaseriskprofilesorhealthserviceutilisationhabitsthatrepresent the average or community ‘norm’.Asanexample,Hensonetal,(2006)suggestedthatglaucomaprogressionratesfoundinretrospectivestudiestendtobehigherthanratesderivedfromprospectivestudiesbecausepatientswillingtoenrolinprospectivestudiesmaybemoreconcernedabouttheirconditionandarelikelytobemoreattentive,demandingandcompliantwiththeirtherapythanaverage.

Constant or variable linear progression

Somestudieshavefoundthatprogressionratesspeedupasdamageworsens(forexample,Martusetal,2005),whileothershavefoundtheopposite(eg.Raskeretal2000).Thereisalsosomeevidencethatprogressionisepisodicratherthanconstant,forexample,Kwonetal,(2001)foundthataround25%patientsshowednon-lineardiseaseprogression.

4.5.1: NATURAL (UNTREATED) PROGRESSION

Dataondiseaseprogressioninuntreatedpatientsisavailablefromtheplaceboorobservationarmsofclinicaltrials(withtheprovisoabovethattheexperienceofparticipantsinclinicaltrialsmaynotmatchthatofthecommunityatlarge).Inaddition,JayandMurdoch(1993)estimateduntreatedprogressionandWilsonetal,(2002)examineduntreatedprogressioninblackpatients.ThesestudiesaresummarisedinTable4.3.Despiteexaminingprogressionratesintreatedpatients,Hattenhaueretal,(1998)isincludedinthetableforthereasonsoutlinedbelow.ThedatainthetablesuggestthefollowingnaturalpopulationprogressionratesforOhT to POAG(notingthatthedistinctionbetweenOHTandglaucomaisbasedonclinicianobservationofclinicalsignsaswellasinmostcasesdetectionofVFL):

• DatafromtheOHTSsuggestprogressionratesforwhitepatientsof2%peryear.Forallparticipants,theratewasjustunder2%peryear.

• DatafromtheEGPSsuggestannualprogressionratesforOHTtoPOAGofaround3.4%.


4. Epidemiology

DatafromTable4.3suggestthefollowingprogression rates for POAG(notingthatprogressionisdefinedindifferentwaysasperthediscussionabove):

• FortheEMGT,themostrecentdata(Leskeetal,2007)suggestannualprogressionratesofbetween9and10%,whereasLeskeetal,(2003)foundannualprogressionratesofjustover10%.

• FromWilsonetal(2002),progressiontoatleastunilateralblindnessinblackpatientswas1.6%peryearaccordingtotheAGIScriteria,and3.5%accordingtotheCIGTScriteria.

• DatafromtheCNTGSsuggestanannualprogressionrateof6.6%.

Weinrebetal,(2004)synthesisedtheseresultsbymodellingtheriskofblindnessinpatientswithOHTusingtheOHTS,Hattenhaueratal,(1998),andWilsonetal,(2002).TheselectedendpointwasunilateralblindnessasanindicatoroftheseverityofVFdeteriorationthatcanbecomparedacrossdifferentstudies.Weinrebetal,(2004)assumedthatprogressionratesfromOHTtoblindnesscanbeestimatedbyaddingthetimereportedforprogressionofOHTtoglaucomafromonestudywiththetimereportedforprogressionfromglaucomatoblindnessinanotherstudy(Weinrebetal,2004:462).Inaddition,progressionwasassumedtobelinear(Weinrebetal,2004:462).ProgressionratesfromHattenhaueretal,(1998)werealsouseddespiteostensiblybeingbasedontreatedpatients.Weinrebetal,(2004)arguedthatthetreatmentregimensintheHattenhauerpopulation—basedonpatientsnewlydiagnosedwithPOAGbetween1965and1980—maynotreflectcurrentorevenrecenttherapyandthusthesepatientscouldbeconsideredonlypartiallytreated—oruntreated.TheHattenhaueretal(1998)progressionratesmightalsobeerroneouslyhighbecauseoflackofdataonothercausesofvisionloss,thusWeinrebetal,(2004:465)usedtheseasanupperbound.TheestimatesoftheprobabilityofapatientwithOHTdevelopingglaucomaandfinallybecomingblindinoneeyeover15yearscalculatedbyWeinrebetal,(2004)were:

• 1.5%—OHTSandWilsonetal,(2002)AGIS;

• 2.6%—OHTSandHattenhaueretal,(1998);

• 3.3%—OHTSandWilsonetal,(2002)CIGTS;and

• 10.5%—Hattenhaueretal,(1998).

ResultsfromtheEGPS(2005)werenotavailablefortheWeinrebanalysis.IfthesearesubstitutedfortheOHTS,thecalculatedprobabilitiesare:2.7%,4.5%,5.9%and10.5%respectively.

ItisworthnotingthattherelativevalueofHattenhaueretal,(1998)isthatthedataweredrawnfromadatabaseofmedicalrecordsforallsourcesofmedicalcareusedbythelocalpopulationofOlmstedCounty(USA).Asapopulationbasedstudy,theresultsareprobablymorereflectiveofexperienceinthecommunity.Bycomparison,longitudinalstudiesofmedicalrecordsfromspecificmedicalcentresmaybebiasedbecauseofthetypesofpatientspresentingtotheclinic,orbecauseofthetreatmentapproachattheclinic(forexample,treatmentmaybemoreaggressive).



TwoexamplesofratesmarkedlylowerthanthoseofHattenhaueretal,(1998)arebelow:

• Chen(2003)examinedrecordsfor186patients,(82%white),diagnosedwithPOAGin1975orlaterandwhopresentedtoatertiaryreferralclinic(UniversityofWashingtonMedicalCentre).Heestimatedthattheprobabilityofprogressionfromglaucomatounilateralblindnessat15yearswas14.6%(95%CI7.6-21.6)andtobilateralblindnesswas6.4%(95%CI0-14.4).

• Similarly,Kwonetal,(2001)studied40eyesof40patientsfollowedataUniversityclinicsince1972withPOAGandfoundthataround13%ofeyeswerelegallyblindafter15years,noting,however,thattheselectionofpatientsmayhavebeenbiasedtowardsthosewithworseglaucoma.

Table4.2providesasummaryofthefindingsofthestudiesofnaturalprogression.Notably,progressionfromOHTtounilateralblindnessislowerthanfromPOAGtounilateralblindnesssincesomeofthosewithdetectedOHTdonotprogresstoglaucoma.

TABLE 4.2: NATURAL PROGRESSION RATES (CUMULATIVE PROBABILITY) 15 YEAR PERIOD

Start point Unilateral blindness Bilateral Blindness

OHT 1.5%to10.5%(Weinrebetal,2004) 3%(Hattenhaueretal,1998)

Glaucoma 40.5%(Hattenhaueretal,1998) 16.5%(Hattenhaueretal,1998)

Initially, the approach was to apply the progression rates from the Weinreb et al, (2004) synthesis in the modelling. Unfortunately,itwasnotpossibletomatchtheWeinrebetal,(2004)rateswiththeavailableincidenceandprevalencedatafromtheMVIPandBMEStoobtainsensibleprojections(seeSection4.6).Inaddition,forthemodelitwasnecessarytomeasureprogressofmildormoderatevisionloss,buttheWeinrebetal,(2004)rateswereonlyforblindnessasdefinedintheUSA.TheestimatesoftheproportionofpeoplewithPOAGineachvisualimpairmentseveritygroup(earlystage,mild,moderateandsevere)fromMVIP/BMESdatawerebasedonsmallsamplesizes.Further,MVIPandBMESdataarebasedonamixedpopulationwithbothtreatedanduntreateddisease.

final progression rates were therefore derived using the available MVIP and BMES incidence and prevalence data and the splits of disease severity(themethodologyisoutlinedinmoredetailinSection4.6below).Smoothedprevalencerateswereused,andthediagnosisratewassetat50%(consistentwithresearchfindings).Thisledtoannualprogressionratesthatareforthemostpartsubstantiallyhigherthanexpected(andhigherthanWeinrebetal,(2004))butinternallyconsistentwiththeotherparametersfromtheliteratureandpopulationstudiesusedinthemodel.Clearlymoreresearchandpopulationstudiesinvestigatingincidence,prevalenceandprogressionofbasedonstandardclassificationsofvisualimpairmentareclearlyrequired.

4. Epidemiology


Insummaryandforthepurposesofmodelling,the annual natural progression rates are:

• OHTtoEDS:31.2%oftheOHTpopulationperannum(markedlyhigherthanstudiessuggest)8;

• NormotensivetoEDS:approximateaverageof0.22%oftheAustralianpopulationperannum;

• EDStoMild:1.5%ofthosewithPOAGperannum(intherangeofwhatstudiessuggest);

• MildtoModerate:85.0%(markedlyhigherthanstudiessuggest);and

• Moderatetosevere:30.0%(markedlyhigherthanstudiessuggest).

4. Epidemiology

8Whilethisnumberappearshigh,itisimportanttonotethattheprevalenceofOHTwasonlyrecordedforindividualsthatwere40yearsandoverandasdiscussedearlierinSection2theaetiologyofPOAGresemblesthatofacontinuum.Itisthereforeverylikelythat,byonlyincludingpeopleagedover40yearsofage,thetotalprevalenceofOHTisbeingunderestimated.



TAB

LE 4

.3:

EST

IMA

TES

Of

DIS

EASE

PR

OG

RES

SIO

N I

N U

NT

REA

TED

PA

TIE

NT

S

Re

fere

nce

Stud

y ty

pe

Defi

niti

on o

f pr

ogre

ssio

n fo

llow

-up

Sam

ple

size

Pr

ogre

ssio

n ra

te

(%

whi

te)

Pr

ogre

ssio

n of

Oh

T to

gla

ucom

a

O

HTS

(Ka

ss

rand

omis

ed

Dev

elop

men

tof

VF

abno

rmal

ity

usin

gco

rrec

ted

patt

ern

60m

onth

s1,

636

pati

ents

A

t60

mon

ths,

cum

ulat

ive

prob

abili

tyo

f

et

al,

2002

)

clin

ical

tria

lSD

or

ifth

egl

auco

ma

hem

ifiel

dte

str

esul

tsw

ere

outs

ide

(7

5%w

hite

)de

velo

ping

gla

ucom

afo

rth

ose

int

heo

bser

vati

on

ob

serv

atio

ngr

oup

no

rmal

lim

its

OR

opti

cdi

scd

eter

iora

tion

gr

oup

was

9.5

%o

fpa

tien

ts.

POA

Gd

evel

oped

(thi

nnin

gof

neu

ror

etin

alr

im)

in6

3(1

0.2%

)of

614

non

-Afr

ican

Am

eric

an

obse

rvat

ion

grou

ppa

rtic

ipan

ts.

EG

PS(

2005

)

rand

omis

ed

Wor

seni

ngo

fVF

(3o

rm

ore

horiz

onta

llyo

rve

rtic

ally

60

mon

ths

1,07

7pa

tien

ts

At

60m

onth

s,th

eKa

plan

Mei

erc

umul

ativ

e

plac

ebo

grou

pcl

inic

alt

rial

adja

cent

poi

nts

diff

er5

dBo

rm

ore

from

bas

elin

e(2

)2

or

prob

abili

tyo

fde

velo

ping

PO

AG

was

mor

eho

rizon

tally

or

vert

ical

lya

djac

ent

poin

tsd

iffer

10d

B

16

.8%

of

pati

ents

int

hep

lace

bog

roup

orm

ore

from

bas

elin

e(3

)a

diff

eren

ceo

f10

dBo

rm

ore

acro

ss

th

ena

salh

oriz

onta

lmer

idia

nat

2o

rm

ore

adja

cent

poi

nts)

orc

hang

ein

opt

icd

isc

Pr

ogre

ssio

n of

Oh

T to

blin

dnes

s

H

atte

nhau

ere

tal

,Re

tros

pect

ive

Prob

abili

tyo

ftr

eate

dpa

tien

tsg

oing

blin

dfr

omn

ewly

m

ean

290

pati

ents

U

nila

tera

lblin

dnes

s:O

HT:

cum

ulat

ive

19

98

exam

inat

ion

diag

nose

dan

dtr

eate

dO

HT

orO

AG

.Bl

indn

ess

defin

eda

s15

yea

rs

(96%

whi

te)

prob

abili

ty1

4%a

t20

yea

rs(

95%

CI7

-20%

).

of

cas

ere

cord

sV

isua

lAcu

ity

(VA

)of

≤20

/200

,VF

cons

tric

tion

of

200

(SD

8y

ears

)(a

roun

d9%

Bi

late

ralb

lindn

ess:

OH

T:c

umul

ativ

epr

obab

ility

in

pop

ulat

ion

of

orle

ssin

wid

est

diam

eter

.

wit

hex

folia

tion

4%

at

20y

ears

(C

I1-9

%).

O

lmst

edC

ount

y,

glau

com

a)

Min

neso

taU

SA

Prog

ress

ion

of g

lauc

oma

EM

GT

(Les

ke

rand

omis

ed

Gla

ucom

ach

ange

pro

babi

lity

map

sba

sed

onp

oint

wis

e8

year

s

59%

of

trea

ted

and

76%

of

untr

eate

dpa

tien

ts

et

al,

2007

)

clin

ical

tria

lpa

tter

nde

viat

ions

fro

mt

hea

ge-c

orre

cted

nor

mal

thr

esho

ld

(Med

ian)

prog

ress

ed.

The

med

ian

tim

eto

pro

gres

sion

No

trea

tmen

t

va

lues

.At

leas

t3

test

poi

nts

show

ing

sign

ifica

ntd

iffer

ence

w

as6

0m

onth

s.

gr

oup

at

the

sam

elo

cati

ons

on3

con

secu

tive

map

s.

Mul

itiv

aria

tea

naly

sis

sugg

este

dtr

eatm

ent

O

Rop

tic

disc

cup

ping

re

duce

dth

eH

Rfo

rpr

ogre

ssio

nby

47%

(H

R,0

.53)

EM

GT

(Les

ke

As

abov

eA

sab

ove

6ye

ars

255

pati

ents

62

%o

fun

trea

ted

pati

ents

pro

gres

sed.

eta

l,20

03)

(a

lmos

tal

lA

llpa

tien

tsw

ith

prog

ress

ion

met

the

VF

No

trea

tmen

t

whi

te)

(pat

ient

scr

iter

iaw

ith

one

exce

ptio

n,w

hom

ett

he

gr

oup

wit

hex

folia

tion

op

tic

disc

crit

erio

non

ly.

sy

ndro

me

com

pris

eda

roun

d

10%

of

the

no

tr

eatm

ent

grou

p)


TAB

LE 4

.3:

EST

IMA

TES

Of

DIS

EASE

PR

OG

RES

SIO

N I

N U

NT

REA

TED

PA

TIE

NT

S co

nti

nu

ed

Re

fere

nce

Stud

y ty

pe

Defi

niti

on o

f pr

ogre

ssio

n fo

llow

-up

Sam

ple

size

Pr

ogre

ssio

n ra

te

(%

whi

te)

Pr

ogre

ssio

n of

gla

ucom

a

A

GIS

(N

ouri-

Lo

ngit

udin

al

Com

pare

dpo

intw

ise

linea

rre

gres

sion

,8

year

s15

6ey

eso

f15

6V

isua

lfiel

dpr

ogre

ssio

nat

8y

ears

was

Mah

davi

et

al,

inte

rven

tion

stu

dy

Gla

ucom

ach

ange

pro

babi

lity

map

san

d

pati

ents

de

tect

edin

35%

,31%

,and

22%

of

pati

ents

2007

)

AG

ISp

rogr

essi

onc

riter

ia.

byp

oint

wis

elin

ear

regr

essi

on,G

lauc

oma

Cha

nge

Prob

abili

tyA

naly

sis,

and

the

AG

ISm

etho

d,

resp

ecti

vely

.

C

NTG

Sgr

oup

pros

pect

ive

Wor

seni

ngo

fan

exi

stin

gV

Fde

fect

,5

year

s14

5ey

es,1

45

At

5ye

ars,

33%

of

the

untr

eate

dgr

oup

(1

998)

ra

ndom

ised

ap

pear

ance

of

new

VF

defe

cts

ora

new

pati

ents

pr

ogre

ssed

.Th

em

ean

tim

eto

pro

gres

sion

int

his

N

otr

eatm

ent

clin

ical

tria

lth

reat

to

cent

ralv

isua

lfixa

tion

.

gr

oup

was

1,6

95(

±14

3)d

ays.

Whe

nth

eda

ta

gr

oup

wer

ead

just

edfo

rca

tara

ct,a

tth

ree

year

s,

40

%o

fpa

tien

tsin

the

con

trol

arm

exp

erie

nced

vi

sion

loss

,and

at

5ye

ars,

60%

exp

erie

nced

vi

sion

loss

Pr

ogre

ssio

n of

gla

ucom

a to

blin

dnes

s

W

ilson

et

re

tros

pect

ive

U

sed

AG

ISa

ndC

IGTS

to

grad

epr

ogre

ssio

n10

yea

rs

205

pati

ents

C

umul

ativ

epr

obab

ility

of

reac

hing

end

-sta

ge

al

(20

02)

stud

y-

clin

ical

(1

00%

bla

ck)

dise

ase

ina

tle

ast

one

eye

from

dia

gnos

is

A

llun

trea

ted.

ex

amin

atio

n

wit

hgl

auco

ma

was

abo

ut1

6%b

yA

GIS

of

pat

ient

sat

crit

eria

and

was

35%

by

CIG

TS.

two

poin

tsin

ti

me

inS

tLu

cia

W

est

Indi

es.

H

atte

nhau

ere

t

Retr

ospe

ctiv

ePr

obab

ility

of

trea

ted

pati

ents

goi

ngb

lind

from

new

ly

mea

n29

0pa

tien

ts

Gla

ucom

ato

uni

late

ralb

lindn

ess:

al,(

1998

)ex

amin

atio

nof

di

agno

sed

and

trea

ted

OH

Tor

OA

G.

Blin

dnes

s15

yea

rs

(96%

whi

te)

cum

ulat

ive

prob

abili

ty5

4%a

t20

yea

rs

case

rec

ords

in

defin

eda

sVA

of≤2

0/20

0,V

Fco

nstr

icti

on

(SD

8y

ears

)

(95%

CI4

2-72

%).

popu

lati

ono

f

of2

00 or

less

inw

ides

tdi

amet

er.

Gla

ucom

ato

bila

tera

lblin

dnes

s:

O

lmst

edC

ount

y,

cu

mul

ativ

epr

obab

ility

22%

M

inne

sota

USA

at2

0ye

ars

(CI8

-38%

).

Ja

yan

d

Cas

ese

ries

Mea

nra

teo

fVFL

inu

ntre

ated

PO

AG

est

imat

edb

y

177

For

pres

sure

sof

21

to2

5m

mH

g,u

ntre

ated

Mur

doch

of

pat

ient

sco

mpa

ring

the

mea

nag

eat

pre

sent

atio

nof

pat

ient

s

pati

ents

di

seas

eis

like

lyt

opr

ogre

ssf

rom

ear

lyfi

eld

(1

993)

w

ith

new

ly

wit

hea

rlyr

elat

ive

VFL

wit

hth

em

ean

age

oft

hose

ch

ange

sto

end

sta

gein

an

aver

age

of1

4.4

year

s.

diag

nose

dw

hop

rese

nted

wit

hab

solu

tefi

eld

loss

wit

hin

The

sam

ein

terv

alfo

rpr

essu

res

of2

5to

30

mm

PO

AG

fiv

ede

gree

sof

fixa

tion

.

H

gw

as6

.5y

ears

and

for

pres

sure

sov

er3

0m

m

Hg,

2.9

yea

rs.



4. Epidemiology

�.�:PREVALENCEANDINCIDENCE

Asforeshadowedpreviously,theincidenceandprevalenceestimatesusedinthemodelarederivedfrombothMVIP9andBMESdata.

• Dataforpersonswereused,ratherthanbygendertoensurethelargestsamplesizepossible.Noconsistentgenderdifferencesarereportedinglaucomaincidence,prevalenceofseveritystudies.

• TheEDSgroupisbasedonMVIPdataforpeoplewithprobableordefiniteglaucoma.Thisstagelackedvisionlossbydefinitionandsothediagnosishadbeenmadeonopticdiscchangesorapreviousdiagnosisofglaucoma.TheotherstagesofPOAGarebasedoncombinedMVIPandBMESdataforpeoplewithdefiniteglaucoma.

• Thedataweredisaggregatedintodegreeofvisualimpairment,withVImeasuredusingacombinationofVAandVFloss(seedefinitionsandschematicinTable44andFigure4.1).TheVAcategoriesarecreatedfromthebest-presentedVAdata,andVFL(constriction)categoriesarecreatedfromPatternDeviationdata.

• Forthisanalysis,severeandprofoundwerecombined.

• IncidenceandprevalenceofOHTisbasedonMVIPdataforthosewithIOP≥21mmHgusingtonopenmeasurements.

• TheprogressionratesbetweenthestagesofglaucomahavebeenpreviouslydescribedinSection4.5.1.

TABLE 4.4: DEfINITIONS Of LEVEL Of IMPAIRMENT fOR DEfINITE GLAUCOMA

VA VfL

EDS/None Betterthan6/12 AND NoVFL

MildImpairment <6/12 OR AnylossofVF

ModerateImpairment <6/18 OR <20ofieldloss

SevereorprofoundImpairment <6/60 OR <10ofieldloss

fIGURE 4.1: SChEMATIC Of ThE LEVEL Of IMPAIRMENT fOR DEfINITE GLAUCOMA

for both OhT and POAG an increase in prevalence is observable with age, althoughthistailsoffforOHT,asprogressiontoglaucomabecomesmorelikelyandtherebytreatmentstoreduceIOP(Table4.5).AsmallnumberofindividualswererecordedintheoldestagegroupforpeoplewithOHT,whichresultedinaprevalencerateestimateofzero.ItispossiblethatoncepeoplereachacertainagewithoutcontractingOHTorglaucoma,theyareunlikelyevertodevelopit,however,thismayalsoresultfromthesmallsamplesize(Table4.5).

Loss of visual acuity and visual field affect quality of life.

Visual Acuity No Loss

Some VF

Loss

VF <20 - !10

degrees

VF <10 - !5

degrees

VF <5

degrees

VA <3/60 or worse

VA <6/60 - !3/60 Severe

VA <6/18 - !6/60 Moderate

VA <6/12 - !6/18 Mild

VA <6/6 - !6/12 None

VA !6/6

Visual Field Loss

9SeeforexampleMukeshetal,(2002),Wensoretal(1998)andWeihetal,(2001).

�0 Tu n n e l V i s i o nCentre for Eye Research Australia

TABLE 4.5: OhT AND GLAUCOMA PREVALENCE RATES

OhT prevalence - Glaucoma prevalence - Original (%) (%)

Age Males females Original Smoothed

0-39 0.00 0.00 0.00 0.00

40-44 0.13 0.13 0.00 0.07

45-49 0.13 0.13 0.22 0.14

50-54 0.31 0.31 0.21 0.60

55-59 0.31 0.31 1.45 0.94

60-64 0.37 0.37 1.50 2.29

65-69 0.37 0.37 4.22 3.46

70-74 0.49 0.49 5.30 5.51

75-79 0.49 0.49 6.85 5.78

80-84 0.00 0.00 6.19 6.74

85-89 0.00 0.00 9.09 9.66

90+ 0.00 0.00 18.18 20.66

Source:specialrequestfromCERAbasedonMVIPandBMES

DISMODIIwasusedtocalculateincidenceandprevalencebyageforOHTandPOAG.Anumberofstepsweretaken.

First,glaucoma prevalence data from the MVIP and BMES database were smoothed by taking a moving average across three age groups to remove prevalence fluctuations between age-cohorts.Whilethedynamicmodelallowstheusertoswitchbetweentheoriginalprevalenceratesandthesmoothedprevalencerates,thesmootheddataispreferredformodellingpurposes,asthetrendsfollowamorelogicalpathway.

ThedifferencesbetweentheoriginalprevalenceratesandthesmoothedratesareshowninFigure4.2andFigure4.3.

fIGURE 4.2: ORIGINAL PREVALENCE RATES

4. Epidemiology

Economic impact of primary open angle glaucoma Commercial-in-Confidence

26

FIGURE 4-2: ORIGINAL PREVALENCE RATES

0-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95+

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

EDS

Mild

Moderate

Severe

FIGURE 4-3: SMOOTHED PREVALENCE RATES (MOVING AVERAGE ACROSS THREE AGE GROUPS)

0-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95+

0%

5%

10%

15%

20%

25%

30%

35%

40%

EDS

Mild

Moderate

Severe

Second, raw OHT prevalence estimates (based on a special data request from the MVIP

database) were then run through DISMOD II (assuming no remission) and the resulting totalprevalence numbers formed the denominator for the progression rate in step three.

A progression rate from OHT to glaucoma was calculated by dividing half the number of

incident cases of glaucoma by total prevalence of OHT. This was justified by findings from the

Early Manifest Glaucoma Trial where 52% of glaucoma cases identified through populationscreening had an IOP <21mmHg (Grodum et al, 2002). This resulted in a progression rate of



4. Epidemiology

fIGURE 4.3: SMOOThED PREVALENCE RATES

(MOVING AVERAGE ACROSS ThREE AGE GROUPS)

Second,rawOHTprevalenceestimates(basedonaspecialdatarequestfromtheMVIPdatabase)werethenrunthroughDISMODII(assumingnoremission)andtheresultingtotalprevalencenumbersformedthedenominatorfortheprogressionrateinstepthree.

AprogressionratefromOHTtoglaucomawascalculatedbydividinghalfthenumberofincidentcasesofglaucomabytotalprevalenceofOHT.ThiswasjustifiedbyfindingsfromtheEarlyManifestGlaucomaTrialwhere52%ofglaucomacasesidentifiedthroughpopulationscreeninghadanIOP<21mmHg(Grodumetal,2002).Thisresultedinaprogressionrateofapproximately31.2%perannum.Asnotedearlier,thisnumberappearshighandmoreresearchanddataareneeded.ItisalsoimportanttonotethattheprevalenceofOHTwasonlyrecordedforindividualsthatwere40yearsandoverandasdiscussedearlierinSection2theaetiologyofPOAGresemblesthatofacontinuum.Itisthereforepossiblethat,byonlyincludingpeopleagedover40yearsofage,thetotalprevalenceofOHTmaybeunderestimated.

TheincidenceofearlystagePOAGfromnormotensiveAustralianswasthenestimatedusingDISMODII,withanapproximateannualincidencerateof0.22%oftheAustralianpopulation.

IncidenceandprevalenceratesforOHTwerethenrecalculatedusingtheratesofprogressionfromOHTtoearlystagePOAG,aswellasanORofmortalityof1.TheresultingoutputisshowninTable4.6.WhileOHTamongstthoseinolderagegroupswaszerointheoriginaldata(Table4.4),thisislikelyafunctionofthesmallsamplesizeandsoprevalenceratesofthoseaged80orolderhavebeenassumedthesameasthoseaged75-79years.The results of sensitivity analysis of maintaining the incidence and prevalence of OhT for those aged 80 or over at zero are presented in Chapter 9, Section 9.1.2.

Basedontheprevalenceofglaucomausingthesmoothedrates,theproportionofpeoplewithineachdiseasestagebyageisshowninTable4.7.


26

FIGURE 4-2: ORIGINAL PREVALENCE RATES

0-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95+

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

EDS

Mild

Moderate

Severe

FIGURE 4-3: SMOOTHED PREVALENCE RATES (MOVING AVERAGE ACROSS THREE AGE GROUPS)

0-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95+

0%

5%

10%

15%

20%

25%

30%

35%

40%

EDS

Mild

Moderate

Severe

Second, raw OHT prevalence estimates (based on a special data request from the MVIP

database) were then run through DISMOD II (assuming no remission) and the resulting totalprevalence numbers formed the denominator for the progression rate in step three.

A progression rate from OHT to glaucoma was calculated by dividing half the number of

incident cases of glaucoma by total prevalence of OHT. This was justified by findings from the

Early Manifest Glaucoma Trial where 52% of glaucoma cases identified through populationscreening had an IOP <21mmHg (Grodum et al, 2002). This resulted in a progression rate of


4. Epidemiology

TABLE 4.6: INCIDENCE AND PREVALENCE Of OCULAR hYPERTENSION (% Of AGE GROUP)

Prevalence - Original Incidence - DISMOD II Prevalence - DISMOD II Age Males females Males females Males females

0-39 0.00 0.00 0.00 0.00 0.00 0.00

40-44 0.13 0.13 0.02 0.02 0.08 0.08

45-49 0.13 0.13 0.03 0.03 0.15 0.15

50-54 0.31 0.31 0.05 0.05 0.23 0.23

55-59 0.31 0.31 0.08 0.08 0.30 0.30

60-64 0.37 0.37 0.11 0.11 0.35 0.35

65-69 0.37 0.37 0.13 0.13 0.39 0.39

70-74 0.49 0.49 0.14 0.14 0.44 0.44

75-79 0.49 0.49 0.15 0.15 0.49 0.49

80-84 0.49 0.49 0.15 0.15 0.49 0.49

85-89 0.49 0.49 0.15 0.15 0.49 0.49

90+ 0.49 0.49 0.15 0.15 0.49 0.49

Source:AccessEconomicsandMVIP

TABLE 4.7: PROPORTION Of PEOPLE WITh GLAUCOMA BY AGE AND SEVERITY (%),

SMOOThED (MOVING AVERAGE ACROSS ThREE AGE GROUPS)

EDS Mild Moderate Severe

0-39 0.0 0.0 0.0 0.0

40-44 100.0 0.0 0.0 0.0

45-49 100.0 0.0 0.0 0.0

50-54 100.0 0.0 0.0 0.0

55-59 100.0 0.0 0.0 0.0

60-64 95.1 0.2 1.7 2.9

65-69 94.3 0.4 2.8 2.6

70-74 92.5 0.5 3.7 3.3

75-79 88.6 1.2 8.4 1.8

80-84 84.4 1.7 11.5 2.5

85-89 78.0 2.2 15.1 4.8

90+ 70.6 1.1 7.7 20.6



�.�

:DIS

EASE

STA

GES

DEF

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TAB

LE 4

.8:

DIS

EASE

STA

GE

D

isea

se s

tage

D

escr

ipti

on

VA

VfL

M

orta

lity

(RR

) Pr

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ssio

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ate

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reat

ed)#

N

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N

ovi

sual

impa

irmen

t

1~

31.2

%pa

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HT

toP

OA

G

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alt

ensi

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fAus

tral

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to

POA

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(n

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sive

)

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lauc

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but

chan

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85

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pa

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M

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ate

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mod

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18

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30

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Se

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and

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and

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RR=

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Current treatment regimens centre on the only known treatable risk factor for glaucoma - intraocular pressure (IOP). Management is directed at establishing and maintaining targetsfor reducing IOP. No level of IOP is safe for every patient. In general, the initial target aims toachieve a 20-50% reduction from the initial pressure at which damage occurred.

Patients with a lower than average risk of glaucoma (<5%) could be observed and monitoredwithout treatment. For those patients who are at moderate risk of glaucoma (5% to 15%),a well-informed patient can decide with his or her physician whether to treat or not.In patients with a higher than average risk (>15%), treatment for all should be considered(Weinreb et al, 2004).

Clinicians attempt to achieve IOP reductions and control glaucoma by stepping patients throughthe following course of treatment:

1) Medication;

2) laser therapy (ALT or Selective Laser Trabeculoplasty (SLT) and medication combined;and finally

3) surgery.

The treatment pattern in most cases is the same regardless of the stage at which the diseaseis diagnosed - that is, patients presenting with both early stage disease and severe diseasecommence treatment with medication. Occasionally, laser (if compliance is likely to be poor)or surgery (if medical therapy is likely to fail or not be tolerated) are used as first line therapy.The side effects of treatment are discussed later in Section 5.6.

5.1: MEDICATION

Medication is the first stage of treatment, usually in a topical form (eye drops), but an oral formalso exists. A range of medications are available for the reduction of IOP, summarised in Table5.1. Prostaglandin analogues and beta (β)-adrenergic antagonists are the most frequently used,with topical prostaglandins now the drug of choice in Australia - Lumigan (bimatoprost), Xalatan(latanoprost), Travatan (travoprost). The proportions of medication types used have shifted overtime, particularly since the introduction of prostaglandin analogues in 1997 (Figure 5.1). Basedon MVIP data, Weih et al (1998) found that the most common glaucoma medications used were(β)-adrenergic antagonists (63%), followed by sympathomimetics (18%) and cholinergic agents(16%). The authors also noted the shift to (β)-adrenergic antagonists and away from the use ofpilocarpine over the previous 20 years.

Medications reduce the amount of aqueous humour being produced and/or increase the outflowof aqueous humour from the eye. This can be via the conventional outflow pathway throughthe trabecular meshwork or by the non-conventional outflow pathway (uveo-scleral outflowpathway). Some medications do both.

A topical medication can enter the blood supply through the naso-lacrimal drainage systemleading to systemic side-effects (ie. side effects in the rest of the body as well as the eye).Systemic side-effects can be reduced substantially with the use of punctal occlusion and gentleeye lid closure for more than two minutes. Side effects are discussed in Section 5.6.

5. Treatment

Current treatment regimens centre

on the only known treatable risk factor

for glaucoma - intraocular pressure

(IOP).



TABLE 5.1: IOP LOWERING MEDICATIONS

Medication Features

Prostaglandin analogues (prostamides) Improve the flow of aqueous humour out of the eye through the non-conventional (uveo-scleral) outflow pathway. First-line treatment. Once daily application. Effective IOP reduction (bimatoprost, latanoprost, travoprost)

β adrenergic blockers Reduces the production of aqueous humour (betaxolol, carteolol, levobunolol, metipranolol, timolol).

Alpha (α) 2 adrenergic agonists Reduce secretion of aqueous humour, and increase aqueous outflow. Less effective in reducing IOP than prostaglandin analogues (apraclonidine, brimonidine).

Carbonic anhydrase inhibitors Reduce aqueous secretion, used two to four times a day (dorzolamide and brinzolamide - topical - acetazolamide and methazolamide - oral). Topical forms are not as effective as oral forms.

Cholinergic agonists Increase aqueous outflow through the conventional outflow pathway, used up to four times daily (pilocarpine, carbachol).

Source: Weinreb and Khaw (2004:1716).

FIGURE 5.1: GLAUCOMA MEDICATION DISPENSED BY YEAR AND TYPE OF SCRIPT

(% OF TOTAL SCRIPTS)

Source: Australian Statistics on Medicine 1997, 1998, 1999-2000, 2001-2002, 2003.

If a medication fails to reduce IOP, it is generally replaced with an alternative agent or combinedwith other agents until effective IOP control is established. Some recent studies10 from theliterature show the number of medications taken in combination (Table 5.3).

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1997 1998 1999 2000 2001 2002 2003

%to

tals

crip

ts

Other Anti GlaucomaPreparations

Carbonic AnhyraseInhibitors

Cholinergic Agonists

2α Adrenergic Agonists

Beta Blocking Agents

ProstaglandinAnalogues

5. Treatment

10 Recent studies are preferred because medication efficacy has been improving over time.


Ingeneral,mostpatientsaretakingtwoormoremedicationsbythetimetheyareconsideredinneedoflasertreatmentorsurgery.Formodelling,thetotalcostsofmedicationsusedweredividedbythenumberofpeopleaffected(thisisexplainedinsection6.3.2).Theproportionofeachmedicationtypedispensedwastakenintoaccountinthecalculationfortotalmedicationcosts,withsimilarproportionsofmedicationsreportedbystateandterritory.

TABLE 5.2: PROPORTION Of EACh DRUG CLASS BY STATE, 2005

Prostaglandin b-blocker Carbonic a2 Cholinergic Anhydrase Adrenergic Agonist Inhibitor Agent

NSW 51.2 26.2 12.4 7.2 3.0

VIC 53.6 24.2 12.5 7.5 2.3

QLD 55.4 26.4 10.4 4.6 3.3

SA 54.2 28.9 8.5 5.8 2.6

WA 52.9 29.0 10.2 5.9 2.0

TAS 54.2 29.5 9.5 5.2 1.8

ACT 56.2 22.6 14.3 4.4 2.4

NT 61.8 19.6 11.3 5.5 1.7

Source:PBSItemdatabase.

5. Treatment



5. Treatment

TABLE 5.3: NUMBER Of MEDICATIONS TAKEN IN COMBINATION

Source Number medications in combination

OHTS(Kassetal,2002) SeeBox4foradescriptionoftheOHTS.At60months,inthe medicationgroup,39.7%ofparticipantswerereceivingtwoor moremedicationsand9.3%werereceivingthreeormore.

WeinandandAlthen(2006) Nonrandomisedprospectivenon-comparativeclinicalstudyof 52eyesof52patientsoftheeffectofSLTasanadjunctivetreat mentoneyeswithadvancedglaucomatousdamage.Patients wereincludediftheyhaduncontrolledIOP(≥20mmHg)onmaxi mumtolerablemedicaltherapy,orhadfailedpreviousALT. Patientshadalonghistoryofglaucomatreatmentandweresent forfurthertreatmenttothehospitalandsomaybeconsidered tohaveglaucomathatismoredifficulttocontrol.Theaverage numberofhypotensivemedicationstakenincombinationprior totreatmentwas2.5.

Damjietal,(2006)(a) InCanada,176eyesof152patientswereincludedina randomisedclinicaltrialcomparingALTandSLTintermsoftheir abilitytolowerIOPinpatientswithOAG.Patientsweregiven laseriftheyhaduncontrolledIOP(≥16mmHg),wereon maximummedicaltherapyorhadfailedprevious180/360ALT (>6monthspreviously),wereover18andhadtwosightedeyes. PatientswereexcludediftheyhadadvancedVFdefectwithin 10degreesoffixation,orhadpreviousglaucomasurgery. Themeannumberofmedicationspretreatmentwas2.4for ALTpatientsand2.6forSLTpatients.

Fontanaetal,(2006)(a) 292eyesand225patientswereincludedinaretrospective cohortstudyofphakicpatientswithOAGwhounderwentinitial trabeculectomywithadjunctiveMitomycinC(MMC)between August1997andDecember2003.Eyesthathadundergone previoussurgeryforcataractorglaucomawereexcluded. 97%ofeyeswerereceivingmedicaltreatmentbeforesurgery withameanof2.7medications(SD±1.0).

Ehrnroothetal,(2002)(a) InFinland,aretrospectiveevaluationofpatientsundergoing trabeculectomywithoutantimetaboliteswasconducted. IndicationsfortrabeculectomywereuncontrolledIOPdespite maximaltoleratedmedicationanddiseaseprogression.Priorto surgery,POAGpatientshadbeenonglaucomamedicationfora mean(±SD)of7.8(±5.6)years.Around2%ofpatientswereon zeromedication,12-15%ononemedication,55-64%ontwo medications,20-29%onthreemedications.Around55%were onoralmedications.

(a)Theremaybeselectionbiasinthesestudiesandthereforeahigherrateofprescribing.

5.1.1: COMPLIANCE AND PERSISTENCE WITh MEDICATIONS

Thedefinitionsofadherence,complianceandpersistenceinthissectionaredrawnfromthejournalarticlesthemselves.Definitionsandmethodsofmeasurementdifferacrossstudies.

Adequate treatment of glaucoma and preservation of vision requires adherence to therapy (Schwartz,2005;Chen,2003),althoughtheexactrelationshipbetweencomplianceand


progressionofdiseasehasnotbeenquantified(Olthoffetal,2005).Studiesindicate relatively poor adherence to therapy in one-third or more of patients,dependingonthemedicationsused(AAO,2005:13).

• Nordstrometal,(2005)calculatedthedurationofcontinuoustreatmentwiththeinitiallyprescribedmedication(definedinthearticleaspersistence)andtheprevalenceofuseoftheinitialmedicationatvarioustimepoints(definedinthearticleasadherence)fromhealthinsuranceclaimsdata.Claimsfrom3,623peoplewithnewlydiagnosedglaucomaandfrom1,677glaucomasuspectswereexamined.Fourdrugclasseswereincluded:beta-blockers,alpha-agonists,carbonicanhydraseinhibitors,andprostaglandinanalogs.Nearlyhalfofthosewhohadfilledaglaucomaprescriptiondiscontinuedalltopicalhypotensivetherapywithinsixmonths,and37%hadrefilledtheirinitialmedicationat3yearsafterthefirstdispensing.Prostaglandinswereassociatedwithbetterpersistenceandbetteradherencethanotherdrugs.Patientswithdiagnosedglaucomaweremorelikelytoadheretotreatmentthanglaucomasuspects.

• Schwartz(2005)conductedaliteraturereviewofresearchpublishedbetween1980andOctober2004oncomplianceandpersistencewithtreatmentbypatientswithPOAGorOHT.Compliancewasdefinedastheextenttowhichpatients’behaviourscorrespondedwithprovidersrecommendations.Schwartz(2005)foundthatnon-complianceratesof25%werecommonlyreported.Usingelectronicmonitoring(themostaccuratemethodofestimatingpatientcompliance),non-complianceratesrangedfrom14%to24%.Persistenceover12months(thetotaltimeontherapy)wasaround25%(rangingfrom20%to64%).

• Olthoffetal,(2005)conductedaliteraturereviewofarticlespublishedfrom1970toFebruary2004oncompliancewithglaucomamedications.(POAGaswellasothertypesofglaucomawereincluded.)Compliancewasdefinedasthedegreeofcorrespondencebetweentheprescribedtreatmentregimeandthepatient’sactualdosinghistory.Theproportionofpatientswhodeviatedfromtheirprescribedmedicationregimenrangedfrom5%to80%(thefigureof5%camefromastudyonPOAGpatients).30%ofpatientsforwhomtimololwasprescribeddeviatedfromtheirtreatmentregimen.

• Tsai(2006)undertookaliteraturereviewofarticlespublishedonMedlineduringthe18monthstoOctober2005andfoundthatnon-adherence(extentofdisagreementbetweentheprescribedmedicalregimenandactualpatientpractice)tomedicinalregimensinpatientswithglaucomavariedfrom24%to59%.

• Reardonetal,(2004)examinedpatientpersistenceusingrecordsfromamanagedcaredatabaseintheUS.PatientshadinitiatedmonotherapybetweenJuly1996andJune2002withbetaxolol,bimatoprost,brimonidine,dorzolamide,latanoprost,timolol,ortravoprost.Thenumberofpatientsincludedintheanalysiswas28,741.Discontinuationwasdefinedasnofurtherindexdrug(monotherapydrug)refill90days(ifdispensedonebottle)or180days(ifdispensedtwobottles)afterthelastprescriptionfill.Persistencewasdefinedasthenumberofdaysfromdispensedatetodiscontinuationdateorchangeofmedicationdate(whicheverisearlier).Latanoprostwasthereferencegroupagainstwhichdiscontinuationdateswerecompared.At12months,33%ofpatientswerepersistingwithlatanoprost(hadnotdiscontinued);and19%ofthosetreatedwithotherocularhypotensiveshadnotdiscontinued.Thedifferencebetweenlatanoprostandotheragentswassignificant(p<0.001).Inthepopulation(28,741patientsonmonotherapy),thethreemostfrequentlyprescribeddrugsweretimolol(43%),latanoprost(33%)andbrimonidine(18%).Relativelyfewpatientswereprescribedeithertravoprostorbimatoprost(1%ofpatientsforeach).

5. Treatment

Ongoing adherence with daily glaucoma

drops is a major problem.



5. Treatment

Meta-analysisisnotusefulinsynthesisingtheresultsofthesestudiesbecauseofthedifferencesindefinitionsandmethodsofmeasurement.However,compliance rates of 75% seem a reasonable assumption, with persistence rates of 33% for latanoprost and 19% for other medications at 12 months(basedonReardonetal,2004).ThemedicationcostestimatesusedinthemodellingarecalculatedbasedonthecostsofdispensedmedicationsforPOAGinAustralia,andsoimplicitlyincludepersistence.

�.�:LASERTREATMENT

ThosewhoseIOPisnotcontrolledonmedicationareconsideredforlasertherapy.Twotypesoflasertherapyareavailable,forthereductionofIOP,butvaryinusagedependingonthestateinwhichglaucomahasprogressed.

• Lasertrabeculoplastyisthemainformoftreatment.

• LaserdiodecyclophotocoagulationisrarelyusedinPOAGandnotthereforeincludedinmodelling.

LASER TRABECULOPLASTY

Lasertrabeculoplastyaimsto improve outflow through the trabecular meshwork. Itisusuallyperformedundertopicalanesthesia.Therearetwotypesoftrabeculoplasty.Argon Laser Trabeculoplasty (ALT)wasdevelopedseveraldecadesago.ItwasfollowedmorerecentlybythedevelopmentofSelective Laser Trabeculoplasty (SLT). WhilethereissomeevidencethattherearefewersideeffectswithSLT(LatinaanddeLeon2005),thisremainsunproveninarandomisedclinicaltrialsetting.Forthepurposesofthisstudy,theefficacyofALTandSLTareconsideredthesame.StudieshaveshownequivalencyofSLTtoALTinpatientsinwhommaximalmedicaltherapyhasbeenunsuccessful(McIlraithetal,2006,Juzychetal,2004andDamjietal,2006).

Thelaseriseitherappliedtoallofthetrabecularmeshworkatonce(360degrees)ortojusthalf(180degrees).Thereisnoconsensusaboutwhichapproachispreferable,butwhere180degreelaserisundertakenfirstandglaucomaremainsuncontrolled,afurther180degreetreatmentwillbeconductedonthepreviouslyuntreatedsegmentofthetrabecularmeshwork.

Thepressureloweringeffectoflaserdiminishesovertime(Feldmanetal,1991).Repeatlaser(anyALTofthetrabecularmeshworkafteracomplete360degreeALT(Feldmanetal,1991))iscontroversial.RepeatALThasamarkedlyreducedeffectcomparedwithinitiallaser11andisassociatedwithanincreaseintheriskofanadverseriseinIOP.

DatafromtheMedicareBenefitsSchedule(MBS)forlasertrabeculoplastyarepresentedinFigure5.2.ThedataareforMBSitemnumber42782(definedaseachtreatmenttooneeyetoamaximumoffourtreatmentstothateyeinatwoyearsperiod)12.TheMBSfeeforitemnumber42782fromthe1November2006ScheduleisA$398.65.

11Forexample,Feldmanetal,(1991)concludedthatrepeatALTwasnotgenerallyeffectiveforthelongtermcontrolofOAG.Intheirstudy,repeatALTwassuccessfulin21%ofeyesatoneyear,and5%ofeyesat48months.Richteretal,(1987)foundthatIOPcontrolwassuccessfulin33%ofeyesoneyearafterrepeatALTandinonly14%ofeyesafter1.75years.Bothstudiesdefinedsuccessasa3mmHgorgreaterdecreaseinIOPtolessthan22mmHgandnofurthersurgicalintervention.

12MBSitemnumber42783(Lasertrabeculoplasty–eachtreatmentto1eyewhereitcanbedemonstratedthata5thorsubsequenttreatmenttothateye(includinganytreatmentstowhichitem42782applies)isindicatedina2yearperiod)isextremelyrarelyused—oneprocedurerecordedagainstthisitemnumberin2002,threeproceduresrecordedin2003andnegativeoneprocedurein2005.Otherwisezeroproceduresfortherestoftheperiodbetween1994and2006.

Laser trabeculoplasty aims to improve outflow through the trabecular meshwork.


TheMedicaredatainFigure5.2includeonlyprocedurescoveredbyMedicare—ie.theyexcludeproceduresundertakenonpublicpatients(bothadmittedandnon-admitted)inpublichospitals(fundedbythehospital)andproceduresoncompensablepatients(forexample,fundedbyworkerscompensationorganisations).13However,ingeneral,trabeculoplastiesareundertakenatadoctor’spracticeandadmittedpatienthospitalproceduresrepresentanexception.Hence,forthemodelling,theMedicaredataareassumedtoadequatelyrepresentthenumberoftrabeculoplastyproceduresundertakeninAustralia.

ThenumberofMBSproceduresfellfrom16,809in1996,to6,201in2003,beforeincreasingagainto11,113in2006.Thisprobablyreflectstosomeextentgreateruseofprostaglandinanalogueswhichreplacedordelayedtrabeculoplastyprocedures.ItmayalsoreflecttheincreaseduseofSLToverALT.

Itisestimatedthathalfthepeoplethatreceiveatrabeculoplastyprocedurehavetwo180degreetreatmentswhiletheremaininghalfreceiveone(personalcommunication,ProfessorJonathanCrowston15thMay2007).Thecostsoftrabeculoplastyhavebeenadjustedupwardsby1.5inthemodelaccordingly(seeSection6.3.2).

fIGURE 5.2: MBS TRABECULOPLASTY PROCEDURES, 1994-2005

Source:MedicareAustraliastatistics,MBSitemnumber42782(Lasertrabeculoplasty-eachtreatmentto1eye,toamaximumof4treatmentstothateyeina2yearperiod).

13TheAustralianHealthCareAgreementsspecifythataneligiblepatientpresentingatapublichospitaloutpatientdepartmentwillbetreatedfreeofchargeasapublicpatientunless:(a)thereisathirdpartypaymentarrangementwiththehospitalorQueenslandtopayforsuchservices;or(b)thepatienthasbeenreferredtoanamedmedicalspecialistwhoisexercisingarightofprivatepracticeandthepatientchoosestobetreatedasaprivatepatient.AustralianHealthCareAgreementbetweentheCommonwealthofAustraliaandtheStateofQueensland,2003-08,http://www.health.qld.gov.au/publications/aust_hlth_care_agreement/Queensland.pdfaccessed7May2007.

5. Treatment

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Year

Nu

mb

er

of

pro

ced

ure

s



LASER DIODE CYCLOPhOTOCOAGULATION

Cyclodiodelaserlightisdirectedtopassthroughthesurfaceoftheeyeandbehindtheiristoaffecttheciliarybodyinorderto reduce the production of aqueous humourandthereforedecreasetheIOPwithintheeye.Thistechniqueisusedforrefractorycasesthatdon’trespondtoconventionaltreatment.Notmanyoftheseproceduresareundertakeneachyear.Forthefinancialyears2004-05and2005-06,MedicareAustraliadatasuggestthat,respectively,137and145cyclodestructiveproceduresforintractableglaucomawereperformed(itemnumbers42770and42771).TheseproceduresarerarelyusedforPOAGandsonotincludedinthemodel.

�.�:CONVENTIONALSURGERY(TRABECULECTOMY)

If medical and laser therapies fail, surgery is performed. Trabeculectomyisperformedunderlocalorgeneralanaesthesiaandcreatesanalternativepathwayfortheoutflowofaqueoushumour.Atinyportionofthetrabecularmeshworkorsurroundingtissueisremoved,andasmallflapinsertedtoproduceapassagewayfromtheanteriorchamberoftheeyetoa“pocket”betweentheconjunctivaandsclera.Asmallblister(filteringbleb)isformedundertheupperlid,calledatrabeculectomybleb.

fIGURE 5.3: TRABECULECTOMY14

Insomecases,scartissuedevelopsandpreventstheoperationfromworking.Incasesthoughttobeatincreasedriskofscarformation,thesurgeonmaygivethepatientantifibrotics-drugstoinhibitscaringsuchas5-fluoracil or MMC to reduce scarring andimprovetheoutcomesofsurgery.

Aswithtrabeculoplasty,itisdifficulttoestimatethetotalnumberofproceduresundertakenforPOAGeachyear.Medicaredatadonotincludeproceduresundertakenonpublicpatientsinpublichospitals

(admittedornon-admitted).Hospitaldataincludebothpublicandprivateadmittedpatientsarethereforethemorereliableinthecaseoftrabeculectomy.

ThetotalnumberoftrabeculectomyproceduresforpeoplewithPOAGduringtheperiodof200405hasbeensourcedfromtheAustralianInstituteofHealthandWelfare(AIHW)asaspecialdatarequest.

• ThetotalnumberofproceduresforICD-10-codesH401andH409(whichrelatetopatientswithPOAGandUnspecifiedGlaucoma)havebeenincludedinthemodelling.Fortheperiod200405,1,683trabeculectomyprocedureswereperformed.Ofthese,583procedureswereperformedinapublichospitalwhile1,060wereperformedinaprivatehospital.

14InternationalGlaucomaAssociationwebsite,accessed10thMay2007http://www.glaucoma-association.com/nqcontent.cfm?a_id=382&=fromcfc&tt=article&lang=en&site_id=176

5. Treatment


Somepatientshavemorethanonetrabeculectomy.ItisnotpossibletodeterminetheextentofrepeatsurgeryfromtheAIHWdata.TheMBSdatasuggestthataround1,435trabeculectomyprocedureswereundertakenin2004-05,with212repeatoperationsinthesameyear(Table5.4)andwhile1302filteringoperationswereundertakenin2005-06,therewerealso230repeatoperations.Repeattrabeculectomieswerealsohighercost(Table5.4).Thecostsoftrabeculectomyinthemodelhavebeenadjustedupwardsaccordinglybasedonthesefiguresbysummingthetwoyearstofindthatrepeatsmadeup16%offilteringoperationsandcost25%morewhichsuggeststhecostoftrabeculectomiesneedstobeadjustedupwardsbyaround20%(seeSection6.3.2).

TABLE 5.4: TRABECULECTOMY — MBS SERVICES PROCESSED BY JURISDICTION BY YEAR

(Anaes.)Meanstheserviceattractsananaesthetic.(Assist.)Medicarebenefitsarepayableunderitem51300forassistancerenderedatanyoperationidentifiedbytheword“Assist.”forwhichthefeedoesnotexceedthefeethresholdspecifiedintheitemdescriptor,orataseriesorcombinationofoperationsidentifiedbytheword“Assist.”forwhichtheaggregateSchedulefeethresholdspecifiedintheitemdescriptorhasnotbeenexceeded.

Source:MedicareAustraliastatistics,FeesbasedonMBS1November2006.

AtimeserieswasnotavailablefromtheAIHW,butMedicaredatasuggestthatthenumberofinitialMBStrabeculectomyprocedures(item42746)hasfallenfrom3,996in1996to1,246in2006(Figure5.4).Thisprobablyresultsfromtheflowoneffectoftheintroductionofprostaglandinanalogueeyedrops(discussedearlier),whichhaveimprovedIOPcontrolanddelayedtheneedfordownstreamtreatments.

fIGURE 5.4: MBS TOTAL Of TRABECULECTOMY PROCEDURES, 1994-2005

Source:MedicareAustraliastatistics,MBSitemnos.42746(Filteringoperationforglaucoma)and42749(Filteringoperationforglaucoma,wherepreviousfilteringoperationhasbeenperformed).

Decreasing rates of surgery reflect better

medical treatment.


38

trabeculectomy procedures were undertaken in 2004-05, with 212 repeat operations in the

same year (Table 5-4) and while 1302 filtering operations were undertaken in 2005-06, there

were also 230 repeat operations. Repeat trabeculectomies were also higher cost (Table 5-4).

The costs of trabeculectomy in the model have been adjusted upwards accordingly based onthese figures by summing the two years to find that repeats made up 16% of filtering

operations and cost 25% more which suggests the cost of trabeculectomies needs to be

adjusted upwards by around 20% (see Section 6.3.2).

TABLE 5-4: TRABECULECTOMY — MBS SERVICES PROCESSED BY JURISDICTION BY YEAR

Item No. Description Fee ($) Year NSW VIC QLD SA WA Tas ACT NT Total

2004-05 559 337 234 110 118 57 20 0 1,435

2005-06 513 311 232 81 117 36 9 3 1,302

2004-05 77 62 36 17 10 4 5 1 212

2005-06 77 62 49 17 17 6 1 1 230

42749

Filtering operation for glaucoma, where

previous filtering operation has been

performed (Anaes.) (Assist.) 1056.55

42746Filtering operation for glaucoma (Anaes.)

(Assist.)843.85

(Anaes.) Means the service attracts an anaesthetic. (Assist.) Medicare benefits are payable under item 51300 forassistance rendered at any operation identified by the word "Assist." for which the fee does not exceed the fee

threshold specified in the item descriptor, or at a series or combination of operations identified by the word "Assist."for which the aggregate Schedule fee threshold specified in the item descriptor has not been exceeded.

Source: Medicare Australia statistics, Fees based on MBS 1 November 2006.

A time series was not available from the AIHW, but Medicare data suggest that the number of

initial MBS trabeculectomy procedures (item 42746) has fallen from 3,996 in 1996 to 1,246 in

2006 (Figure 5-4). This probably results from the flow on effect of the introduction of

prostaglandin analogue eye drops (discussed earlier), which have improved IOP control anddelayed the need for downstream treatments.

FIGURE 5-4: MBS TOTAL OF TRABECULECTOMY PROCEDURES, 1994-2005

0

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

4,500

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Year

Nu

mb

er

of

pro

ce

du

res

42746 42749

Source: Medicare Australia statistics, MBS item nos. 42746 (Filtering operation for glaucoma) and 42749 (Filtering

operation for glaucoma, where previous filtering operation has been performed).


38

trabeculectomy procedures were undertaken in 2004-05, with 212 repeat operations in the

same year (Table 5-4) and while 1302 filtering operations were undertaken in 2005-06, there

were also 230 repeat operations. Repeat trabeculectomies were also higher cost (Table 5-4).

The costs of trabeculectomy in the model have been adjusted upwards accordingly based onthese figures by summing the two years to find that repeats made up 16% of filtering

operations and cost 25% more which suggests the cost of trabeculectomies needs to be

adjusted upwards by around 20% (see Section 6.3.2).

TABLE 5-4: TRABECULECTOMY — MBS SERVICES PROCESSED BY JURISDICTION BY YEAR

Item No. Description Fee ($) Year NSW VIC QLD SA WA Tas ACT NT Total

2004-05 559 337 234 110 118 57 20 0 1,435

2005-06 513 311 232 81 117 36 9 3 1,302

2004-05 77 62 36 17 10 4 5 1 212

2005-06 77 62 49 17 17 6 1 1 230

42749

Filtering operation for glaucoma, where

previous filtering operation has been

performed (Anaes.) (Assist.) 1056.55

42746Filtering operation for glaucoma (Anaes.)

(Assist.)843.85

(Anaes.) Means the service attracts an anaesthetic. (Assist.) Medicare benefits are payable under item 51300 forassistance rendered at any operation identified by the word "Assist." for which the fee does not exceed the fee

threshold specified in the item descriptor, or at a series or combination of operations identified by the word "Assist."for which the aggregate Schedule fee threshold specified in the item descriptor has not been exceeded.

Source: Medicare Australia statistics, Fees based on MBS 1 November 2006.

A time series was not available from the AIHW, but Medicare data suggest that the number of

initial MBS trabeculectomy procedures (item 42746) has fallen from 3,996 in 1996 to 1,246 in

2006 (Figure 5-4). This probably results from the flow on effect of the introduction of

prostaglandin analogue eye drops (discussed earlier), which have improved IOP control anddelayed the need for downstream treatments.

FIGURE 5-4: MBS TOTAL OF TRABECULECTOMY PROCEDURES, 1994-2005

0

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

4,500

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Year

Nu

mb

er

of

pro

ce

du

res

42746 42749

Source: Medicare Australia statistics, MBS item nos. 42746 (Filtering operation for glaucoma) and 42749 (Filtering

operation for glaucoma, where previous filtering operation has been performed).

5. Treatment



5. Treatment

DRAINAGE IMPLANTS

Inpatientsforwhomtrabeculectomyislikelytofailbecauseofinflammationorscarring,adrainagedeviceisimplanted(calledaglaucomadrainagedevice)tocreateadrainagepathway.Variousdevicesexist(eg.Moltenovalves).DrainageimplantsarerarelyusedinPOAG,butaremorecommonlyusedinsecondaryglaucoma.

• DatafromtheAIHWhospitalmorbiditydatabasefor2004-05suggestthat136aqueousshuntinsertion15procedureswererecordedforglaucoma.

• Forthefinancialyears2004-05and2005-06,MedicareAustraliadatasuggestthat,respectively,57and70Moltenovalveinsertionswereperformed(itemnumber42752).Theseproceduresarerelativelyexpensive—theMBSfeeforthe1November2006was$1,182.75.

Sincetheyarerelativelyrareinprimaryopenangleglaucomapatients,theseproceduresarenotincludedinthemodel.

�.�:PREVALENCEESTIMATESFOREACHTREATMENTGROUP

Asnotedearlier,oncediagnosedwithPOAG,patientsgenerallyfollowastandardtreatmentprotocol.Theprotocolisindependentoftheseverityofthediseasestageatdiagnosis.Patientsusuallycommencewithmedicationswhethertheyhaveseverediseaseorearlystagedisease.

Initially,DismodIIwasusedtomodeltheprogressionfromonetreatmentphasetothenext,byusingthetotalnumberofpeoplenewlydiagnosedwithPOAGin2005astheincidencerateforthemedicationtreatmentphase,thetotalnumberoftrabeculoplastyproceduresastheindicatoroftreatmentfailureforthemedicationgroup,andthetotalnumberoftrabeculectomyproceduresasanindicatoroftreatmentfailureforthetrabeculoplastygroup(theoverallRRofmortalityof1.18–theweightedaverageRRofmortalityfromallprevalentseveritygroups–wasappliedinthemodellingforeachtreatmentphase).

Inthecaseoftrabeculoplasty,thetotalnumberofMBSproceduresneededtobescaleddowntoreflect‘first-time’procedures.Asnotedearlier,itisestimatedthathalfofthepeopleinthetrabeculoplastytreatmentphasereceivetwo180degreetreatmentswhiletheotherhalfreceiveone.Thetotalnumberoftrabeculoplastyprocedureswasscaleddownby1.5accordingly.

DismodIIwasalsoinitiallyusedtomodeltheremainingtreatmentphases(Table5.5)toensurethattheflowthrougheachphasewasinternallyvalidandreflectedthenumberofproceduresoccurringinpractice.

However,thesemodelledrateswerenotconsistentwiththeliteratureonfailureratesforlasertherapyandsurgery.Inparticular,anumberofstudiesoutlinedinTable5.7andTable5.8suggestedfailureratesforlaserandsurgerywereoftheorderof50%(withfailuredefinedasthepatientrequiringfurthertreatment).failure rates applied in the model are therefore:

• 50% per year for laser trabeculoplasty (consistent with Weinand and Althen 2006); and

• 50 % for trabeculectomy. While this is a very conservative estimate — higher than the literature — sensitivity analysis shows that it makes little difference to the results. Sensitivity analysis is presented in Section 9.3.3

15ICD10AMcode42752.


TABLE 5.5: INCIDENCE AND TREATMENT fAILURE RATE fOR EACh STAGE Of TREATMENT

fROM DISMOD II.

Age Group Incidence of Medication Medication Trabeculoplasty Trabeculectomy (% of population in each failure rates (% of failure rates failure rates age group) those on medication

40-44 0.02 4.3% 3.2% 2.0%

45-49 0.05 4.3% 3.2% 2.0%

50-54 0.07 4.3% 3.2% 2.0%

55-59 0.10 4.3% 3.2% 2.0%

60-64 0.12 4.3% 3.2% 2.0%

65-69 0.14 4.3% 3.2% 2.0%

70-74 0.17 4.3% 3.2% 2.0%

75-79 0.22 4.3% 3.2% 2.0%

80-84 0.26 4.3% 3.2% 2.0%

85-89 0.32 4.3% 3.2% 2.0%

90+ 0.35 4.3% 3.2% 2.0%

�.�:TREATMENTEFFICACY

ForthereasonsoutlinedearlierinSection4.5,manyofthestudiesoftreatmentefficacy(ie.theimpactoftreatmentcomparedwithalternativesincludingnotreatment)aredifficulttoapplytoacosteffectivenessstudybecauseprogressionisnotdefinedconsistentlyandbecauseofthenatureoftheendpointsselected.ThemajorclinicaltrialsoftreatmentefficacyareoutlinedinBox4.

Box�:Majorclinicaltrialsofglaucomatreatmentefficacy

TheOcular hypertension Treatment Study (OhTS) intheUSAexaminedpatientswho,atentrytothetrial,hadOHT,butnoevidenceofglaucomatousdamage.Enrolmentendedin1996.1,636participantswererandomisedeithertoobservation,ortoreceivetreatmentwithcommerciallyavailabletopicalhypotensivemedicationsusedsinglyorincombination.TheaimoftreatmentwastoachieveatargetIOPof24mmHgorlessandaminimum20%reductioninIOP.ProgressionwasdefinedaseitherthedevelopmentofaVFdefectordeteriorationintheopticdisc.

TheEuropean Glaucoma Prevention Study (EGPS) enrolled1,081patientsbetween1997and1999inBelgium,Germany,ItalyandPortugal.ParticipantshadOHT,butnormalVFandopticdisc.Patientswererandomisedtotreatmentwithdorzolamide(topicalcarbonicanhydraseinhibitor)oraplacebo.Participantsandinvestigatorswerebothmasked.TheaimwastoreduceIOP,buttheprotocoldidnotspecifyatargetIOPreduction.EndpointswerechangesinVFand/ortheopticdisc.

AtentryintheCollaborative Normal Tension Glaucoma Study (CNTGS),145patientsfromspecialtycentresintheUSAhadnormalIOP,butopticdiscabnormalitiesandVFdefects.Participantswererandomlyassignedtotreatmentornotreatment.ProgressionwasbasedonachangeintheVForachangeintheopticnerveappearance.Inthetreatmentgroup,theaimwastoreduceeyepressureby30%in6monthsusingeyedrops,laserand/orfilteringsurgery.

5. Treatment



5. Treatment

TheEarly Manifest Glaucoma Trial (EMGT)wasconductedinSweden,andincluded255participantsscreenedbetween1992and1997.Atentry,patientswerenewlydiagnosedwithVFdefects,butwerepreviouslyuntreated.PatientswithadvancedVFdefectswereexcludedfromentry.Participantswererandomisedtoeither360olasertreatment(ALT)plusbetaxololhydrochloride(topicalbetablocker)ornoinitialtreatment.Theaimwastoevaluatetheeffectofimmediatetreatmentcomparedwithnoinitialtreatmentorlatertreatment.ProgressionwasbasedonnewVFdefectoropticdiscdeteriorationorboth.

TheCollaborative Initial Glaucoma Treatment Study (CIGTS)wasconductedintheUSA.Enrolmenttookplacebetween1993and1997.607patientswithnewlydiagnosedglaucoma,withlimitedornopriortreatment,IOPof20mmHgorgreaterandevidenceofopticnervedamageand/orVFLinoneorbotheyeswereenrolled.Participantswererandomisedtoinitialtrabeculectomy(withorwithout5-fluorouacil)ortopicalmedication(topicalbeta-blocker,followedbyanalternatesingletopicaltherapeuticagent,dualtopicaltherapy,tripletopicaltherapy,analternatecombinationoftripletopicaltherapyandoptionaladditionaltopicalandororalmedications).Furthertreatment,ifconsiderednecessary,followedstandardtreatmentpatterns(variouscombinationsofALT,medicationsandtrabeculectomy).ProgressionwasbasedonchangesinVF.

TheGlaucoma Laser Trial (GLT)andtheGlaucoma Laser Trial follow Up (GLTfU) StudywereconductedintheUSA.TheGLT(271participants)endedin1989,butaproportionofGLTpatients(203participants)werethenobservedaspartoftheGLTFUfrom1990to1993.ParticipantsintheGLTwerenewlydiagnosedwithPOAGandhadanIOPofatleast22mmHgineacheyeplusoneof:aVFdefect,orcertainOHTandcuptodiscratiocharacteristics.OneeyeofeachpatientwasrandomisedtoALTandtheothereyetotimolol.EndpointswereVFandIOP.

TheAdvanced Glaucoma Intervention Study (AGIS)conductedintheUSAfocusedonthosewhosediseasewasnolongercontrolledbymedication.Between1988and1992,591patientswereenrolled.Atentry,patientshadconsistentlyelevatedIOP,opticdiscrimdeteriorationandaVFdefectscorebasedontheAGISgradingsystemofbetween1and1616.Patientsweregivenadifferentsequenceofinterventionsineacheye—inoneeye,thesequencewasALT,trabeculectomy,trabeculectomy;intheothereye,thesequencewastrabeculectomy,ALT,trabeculectomy.ThegoalwastoreduceIOPtolessthan18mmHg.TheprimaryoutcomevariableintheAGISwastheaveragepercentofeyeswithadecreaseofvision(eitherVForVA).

OtherstudiesfocussinginparticularontheefficacyoflasertreatmentandtrabeculectomyadministeredtopatientsfollowingfailureofmaximumtolerablemedicationtocontrolthediseasegenerallyfocusontheimpactoftreatmentonIOPandtheneedforadditionalintervention.VeryfewmeasuretheeffectoftreatmentonVF.Thestudieshavedifferentendpointsanddefineprogressiondifferently.Somearenotbasedonintenttotreat.SomeexamplesofstudiesoftheefficacyoftrabeculoplastyareoutlinedinTable5.7andexamplesofstudiesoftheefficacyoftrabeculectomyareoutlinedinTable5.8.

16AGISVFdefectscoresrangefrom0(nodefect)to20(advancedglaucoma).Iftheeyehasinsufficientvisionforapatienttocountfingersat30cm,theVFdefectscoreisrecordedas20.


Inordertosynthesisetheimpactoftreatmentonprogression,Weinrebetal,(2004)usedtheresultsfromtheOHTSandtheEMGTastheonlytrialswhichcomparedtreatmentwithnotreatment.Asnotedearlier,theEGPS(2005)resultswerenotavailableatthetimeWeinrebetal,(2004)wasreleased.Inanycase,theEGPS(summarisedinBox4)facedcertaindesignproblemsandsoisnotusedherefortheimpactoftreatmentontheriskofdevelopingPOAG17.

Weinrebetal,(2004:464)combinedtheimpactoftreatmentonconversionratesfromOHTtoglaucomafromtheOHTSwithresultsfromtheEMGTontheimpactoftreatmentontheriskofprogressionofdisease.

• TheOHTS(summarisedinBox4)foundthatafter60months,thosewhowerenotreceivingtreatmentweremorethantwiceaslikelytodevelopPOAGthanthoseontopicalmedicationswhohadtheirIOPreducedby20%,ie.thecumulativeprobabilityofdevelopingPOAGwas4.4%inthemedicationgroupand9.5%intheobservationgroup(hazardratioof0.4,witha95%CIof0.27to0.59).Thedifferenceinprogressionrateswas46%(4.4/9.5).

• TheEMGT(summarisedinBox4)showedthatearlyinitialtreatmentwith360oALTplusbetablockereyedropsdelayedprogressioncomparedwithnotreatment.Themediantimetoprogressionwas48monthsinthecontrolgroupand66monthsinthetreatmentgroup(althoughtimetoprogressionvariedgreatly).At48months,49%ofcontrolshadprogressedcomparedwith30%inthetreatmentgroup(Heijletal,2002).Leskeetal,(2003)foundthatafter6years,53%ofpatientsprogressed.Inmultivariateregressionanalysis,progressionriskwashalvedbytreatment(HR=0.5,witha95%CIof0.35to0.71).

Thus,Weinrebetal,(2004)estimatedthattreatment reduced the risk of progression from OhT to blindness by 77%(ie.progressionratesintreatedpatientsare46%x50%=23%thatofprogressionratesinuntreatedpatients).Progressionfromglaucomatoblindnessintreatedpatientsisassumedtobe50%ofthatinuntreatedpatients.RatesofprogressionintreatedpatientsbasedonWeinrebetal,(2004)arepresentedinTable5.6.

TABLE 5.6: PROGRESSION RATES (CUMULATIVE PROBABILITY)

IN TREATED PATIENTS (15 YEAR PERIOD)

Start point Unilateral blindness Bilateral Blindness

OHT 0.3%to2.4%(Weinrebetal,2004) 0.7%(Hattenhaueretal,1998)

Glaucoma 20.25%(Hattenhaueretal,1998) 8.25%(Hattenhaueretal,1998)

17IntheEGPS,therewasnostatisticallysignificantdifferencebetweenmedicaltherapyandplaceboinreducingtheincidenceofPOAG,althoughtheactivelytreatedarmhadameanIOPreductionrangingbetweenapproximately15%to22%throughoutthe5yearsofthetrial.TheresultsaremostlyexplainedbyaclinicallysignificantplaceboeffectonIOPofapproximately9%to19%,whichincreasedduringthestudy.

5. Treatment



TAB

LE 5

.7:

STU

DIE

S O

f T

hE

EffI

CA

CY

Of

LASE

R T

REA

TM

ENT

So

urce

A

ppro

ach

Defi

niti

on o

f pr

ogre

ssio

n O

utco

me

Gla

ucom

aLa

serT

rial

Rese

arch

Gro

up(

1995

)

Wei

nand

and

Alt

hen

(200

6)

Dam

jiet

al,

(200

6)

Juzy

che

tal

,(20

04)

GLT

=2

71n

ewly

dia

gnos

edP

OA

Gp

atie

nts

wit

hno

his

tory

of

topi

calo

rsy

stem

ica

nti-

glau

com

am

edic

atio

nus

ew

ithi

nth

epr

evio

us6

mon

ths

wer

een

rolle

d19

841

987

and

then

rea

sses

sed

1989

.M

edia

nfo

llow

upw

as3

.5y

ears

.

The

GLT

follo

w-u

pst

udy

=2

03o

fth

eor

igin

alG

LT

pati

ents

con

tinu

eda

ndw

ere

reas

sess

ed1

990-

1993

.M

edia

nfo

llow

-up

was

7y

ears

The

aim

was

to

com

pare

ALT

(2

1800

trea

tmen

ts

spac

ed4

wee

ksa

part

)w

ith

0.5%

tim

olol

as

first

lin

etr

eatm

ent

for

new

lyd

iagn

osed

PO

AG

.Ea

ch

pati

ent

rece

ived

bot

htr

eatm

ents

,one

to

each

eye

.

Non

-ran

dom

ised

,pro

spec

tive

,non

-com

para

tive

,cl

inic

alc

ase

serie

sof

52

eyes

of

52p

atie

nts.

Impa

cto

f18

0de

gree

SLT

as

adju

ncti

vet

reat

men

ton

eye

sw

ith

adva

nced

gla

ucom

atou

sda

mag

e.

Rand

omis

edc

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alt

rial.

Prim

ary

outc

ome

was

th

eIO

Plo

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effe

cto

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LT

at1

2m

onth

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red

180

degr

eeA

LTa

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LT

int

erm

sof

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low

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gin

pat

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sw

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Pati

ents

rec

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axim

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ther

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.

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ospe

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e(n

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ised

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revi

ew.

Com

pare

d18

0de

gree

ALT

wit

hSL

Tin

pat

ient

sw

ith

unco

ntro

lled

OA

G.

Mea

nch

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inIO

P,V

A,V

Fan

dop

tic

disc

wer

eas

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ed

byc

linic

ians

(su

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tive

ass

essm

ent)

.Fi

elds

judg

ed

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tion

able

wer

eco

nsid

ered

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ed.

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Pin

crea

sed

afte

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Tan

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(med

ical

,las

ero

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the

trea

tmen

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as

cons

ider

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oha

vefa

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Succ

ess

defin

eda

sm

eeti

nga

llof

the

follo

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iter

ia:

1)a

red

ucti

ono

f≥2

0%o

fpr

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eatm

ent

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at

one

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stt

reat

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t.

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oad

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onal

med

icat

ions

nee

ded

over

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e.

3)n

oad

diti

onal

gla

ucom

asu

rgic

alt

reat

men

tne

eded

.

Succ

ess

defin

eda

s:

(1)

IOP

redu

ctio

nof

3m

mH

gor

mor

ew

itho

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ddit

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lm

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nso

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onal

gla

ucom

asu

rger

yor

(2)

sam

eas

crit

erio

n(1

)bu

tth

eIO

Pre

duct

ion

was

20%

or

mor

eof

the

pre

tre

atm

ent

IOP.

Whi

let

hed

iffer

ence

sbe

twee

nA

LTa

ndm

edic

atio

nw

ere

not

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e,t

her

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tss

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stt

hatA

LTis

at

leas

tas

ben

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ala

sst

arti

ngt

reat

men

tw

ith

tim

olol

.O

ver

the

cour

seo

fth

eG

LT

and

the

GLT

follo

w-u

pst

udy,

the

eye

str

eate

din

itia

llyw

ith

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ha

dlo

wer

IOP,

bet

terV

Fan

dbe

tter

opt

icd

isk

stat

ust

han

thei

rfe

llow

eye

str

eate

din

itia

llyw

ith

topi

cm

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atio

n.

Kapl

anM

eier

sur

viva

lana

lysi

sre

veal

eda

one

yea

rsu

cces

sra

te

of6

0%,t

wo

year

suc

cess

rate

of

53%

,thr

eey

ear

succ

ess

rate

of

44%

and

four

yea

rsu

cces

sra

teo

f44

%.

The

prop

orti

ono

fey

est

hat

achi

eved

at

leas

t20

%lo

wer

ing

ofIO

Pou

tto

one

yea

rw

ass

imila

rbe

twee

nth

etw

ogr

oups

(5

9.7%

SLT

(n=

43)

and

60.3

%A

LT(n

=48

)).

At

one

year

aft

er

trea

tmen

t82

%o

fey

esin

the

SLT

gro

upw

ere

mai

ntai

ned

on

the

sam

enu

mbe

rof

med

icat

ions

and

18%

had

add

edo

ne

med

icat

ion.

Int

heA

LTg

roup

69%

of

eyes

rem

aine

don

the

sa

me

num

ber

ofm

edic

atio

nsa

nd2

9%r

equi

red

one

addi

tion

al

med

icat

ion.

In

the

ALT

gro

up,p

erip

hera

lant

erio

rsy

nech

iae

form

edin

1.2

%(

1/87

),A

LTt

reat

men

toc

curr

edw

ithi

non

eye

ar

in5

.7%

(5/

87)

SLT

trea

tmen

toc

curr

edw

ithi

non

eye

arin

4.6

%

(4/8

7)a

ndt

rabe

cule

ctom

yoc

curr

edw

ithi

non

eye

arin

8%

(7

)pa

tien

ts.I

nth

eSL

Tgr

oup

the

equi

vale

ntp

ropo

rtio

nsw

ere:

1.

1%(1

/89)

,3.4

%(3

/89)

6.7

%(6

/89)

and

9%

(8/8

9).

ALT

and

SLT

sim

ilarly

eff

ecti

vein

dec

reas

ing

IOP

ate

ach

follo

w-

upt

ime

com

pare

dw

ith

the

pre-

trea

tmen

tIO

P.S

LTs

ucce

ss

rate

sat

one

,thr

eea

ndfi

vey

ears

wer

e:6

8%,4

6%a

nd3

2%b

ycr

iter

ion

(1)

and

58%

,38%

and

31%

by

crit

erio

n(2

).Eq

uiva

lent

A

LTs

ucce

ssra

tes

wer

e54

%,3

0%a

nd3

1%b

ycr

iter

ion

(1)

and

46%

,23%

and

13%

by

crit

erio

n(2

).


TAB

LE 5

.7:

STU

DIE

S O

f T

hE

EffI

CA

CY

Of

LASE

R T

REA

TM

ENT

co

nti

nu

ed...

So

urce

A

ppro

ach

Defi

niti

on o

f pr

ogre

ssio

n O

utco

me

Shin

glet

one

tal

,(19

93)

Retr

ospe

ctiv

est

udy

in1

18e

yes

of9

3

pati

ents

of

360

degr

eeA

LT.

Clin

ical

crit

eria

for

succ

ess

incl

uded

no

prog

ress

ive

opti

cne

rve

dam

age

org

lauc

omat

ousV

FL,n

ola

ser

retr

eatm

ent

org

lauc

oma

surg

ical

inte

rven

tion

and

fina

lIO

Pof

less

th

ano

req

ualt

o19

mm

Hg

and

atle

ast

3mm

Hg

belo

wt

he

pre-

trea

tmen

tle

vel

The

prob

abili

tyo

fre

mai

ning

suc

cess

fulu

pto

ten

yea

rsw

as

32%

for

all9

3ey

es.C

umul

ativ

epr

obab

ility

of

succ

ess

was

77

%a

fter

one

yea

r,40

%a

fter

five

yea

rsa

nd3

2%a

fter

ten

ye

ars.

The

high

est

prob

abili

tyo

ffa

ilure

was

int

hefi

rst

year

w

ith

acu

mul

ativ

efa

ilure

rate

of

23%

.In

subs

eque

nty

ears

th

epr

obab

ility

of

failu

rew

asa

ppro

x5%

to

9%p

ery

ear.

Life

ta

ble

anal

ysis

of

the

60e

yes

wit

hPO

AG

dis

clos

eda

sim

ilar

prob

abili

tyo

fre

mai

ning

suc

cess

fulu

pto

ten

yea

rso

f31

%.

Age

or

prev

ious

IOP

did

not

sign

ifica

ntly

aff

ect

succ

ess

rate

s.Pr

obab

ility

suc

cess

giv

ens

urvi

valf

oro

ney

ear

was

64%

aft

er

five

year

san

d42

%a

fter

ten

yea

rs.I

fa

pati

ent

was

suc

cess

ful

atfi

vey

ears

,pro

babi

lity

ofr

emai

ning

suc

cess

fula

tte

nye

ars

was

65%

.

Spae

tha

ndB

aez

(199

2)Re

tros

pect

ive

reco

rdr

evie

wo

f10

9ey

eso

f78

pa

tien

ts.

ALT

was

em

ploy

eda

sa

subs

titu

tefo

rtr

abec

ulec

tom

y.E

ithe

r18

0de

gree

or

360

degr

ee

trea

tmen

tsw

ere

appl

ied.

ALT

was

con

side

red

asu

cces

sw

hen

nofi

ltra

tion

sur

gery

w

asr

equi

red

ora

failu

rew

hen

surg

ery

was

req

uire

d.Su

bseq

uent

sur

gery

bec

ame

nece

ssar

yin

32%

of

alle

yes

wit

hon

eye

aro

fALT

.By

five

year

s,65

%o

fal

leye

sha

dfa

iled

(ie.

35%

eye

sst

illc

onsi

dere

dsu

cces

sful

).Fo

rey

esw

ith

POA

G,

19.3

%o

fey

esfa

iled

(80%

suc

cess

)af

ter

one

year

,and

56.

7%

had

faile

dby

yea

rfiv

e(ie

.suc

cess

rate

at

five

year

sof

43.

3%).



TAB

LE 5

.8:

SUC

CES

S R

AT

ES f

OR

TR

AB

ECU

LEC

TOM

Y

So

urce

A

ppro

ach

Defi

niti

on o

f Vf

prog

ress

ion

and

defi

niti

on o

f su

cces

s Su

cces

s ra

tes

Edm

unds

et

al,2

001

Surv

eyo

fop

htha

lmol

ogis

tsin

the

UK.

Mai

nre

ason

fo

rsu

rger

y:F

ailu

reo

fm

edic

atio

nto

con

trol

IOP

in

57.1

%c

ases

;VF

dete

riora

tion

in2

6.5%

of

case

s.Pr

ogre

ssiv

eop

tic

disc

cha

nges

,int

oler

ance

of

med

icat

ion

and

non-

com

plia

nce

wer

eal

sor

easo

ns

for

surg

ery.

145

4pa

tien

ts(

96%

whi

te)

(Clin

ical

ou

tcom

eda

tafo

rth

evi

sit

clos

est

too

ney

ear

follo

win

gsu

rger

yw

ere

avai

labl

efo

r12

40c

ases

—

85.

3%).

1298

had

PO

AG

Defi

niti

ono

fsu

cces

sof

sur

gery

was

defi

ned

asa

nIO

Pat

one

yea

rfo

llow

ing

trab

ecul

ecto

my

ofle

sst

han

two

third

sth

epr

eope

rati

veIO

P(a

sm

easu

red

whe

nlis

ting

th

epa

tien

tfo

rsu

rger

y).S

econ

dary

mea

sure

sof

suc

cess

w

ere

anIO

Ple

sst

han

21m

mH

ga

ndV

Fst

abili

tya

ton

eye

ar.Q

ualifi

eds

ucce

ssw

asif

the

pat

ient

was

on

post

op

anti

glau

com

am

edic

atio

n.

Afte

ron

eye

ar,u

nqua

lified

suc

cess

was

ach

ieve

din

66.

6%o

fca

ses

(823

cas

es).

Aq

ualifi

eds

ucce

ss(

incl

udin

gpa

tien

tso

nm

edic

atio

n)w

asa

chie

ved

in7

1%o

fca

ses

(878

).In

ter

ms

of

achi

evin

gan

IOP

<21

mm

Hg,

the

unq

ualifi

eds

ucce

ssra

tew

as

84%

and

the

qua

lified

suc

cess

rate

92%

.An

IOP

<16

mm

Hg

was

ach

ieve

din

54.

6%o

fca

ses.

Parc

Ce

tal

,200

1Re

tros

pect

ive

popu

lati

onb

ased

.Res

ults

rep

orte

dhe

refo

r49

pat

ient

sw

hou

nder

wen

tco

nven

tion

al

filtr

atio

npr

oced

ures

.

VF

scor

eda

ccor

ding

to

the

8st

age

Qui

gley

sca

le.

Succ

essf

ulc

ontr

olo

fIO

Pw

asc

onsi

dere

dIO

P<

21m

mH

gw

ith

orw

itho

uta

ntig

lauc

oma

med

icat

ion

ora

red

ucti

on

ofa

tle

ast

33%

ifp

reop

erat

ive

IOP

was

<21

mm

Hg.

The

succ

ess

rate

of

IOP

cont

rola

sca

lcul

ated

by

Kapl

anM

eier

an

alys

isw

as8

0%a

ton

eye

arp

ost-

oper

atio

n,6

4%a

tth

ree

year

spo

sto

pera

tion

.Kap

lan

Mei

era

naly

sis

show

edt

he

cum

ulat

ive

prob

abili

tyo

fbl

indn

ess18

was

22%

at

five

year

san

d46

%a

tte

nye

ars

post

-ope

rati

vea

nd5

4%p

roba

bilit

yof

sur

gery

at

15

year

saf

ter

filtr

atio

n.

Font

ana

He

tal

,200

6Re

tros

pect

ive

coho

rts

tudy

of

phak

icp

atie

nts

wit

hO

AG

who

und

erw

ent

init

ialt

rabe

cule

ctom

yw

ith

adju

ncti

veM

MC

.IO

Pde

emed

by

the

trea

ting

phy

sici

ant

obe

ass

ocia

ted

wit

ha

high

ris

kof

gla

ucom

apr

ogre

ssio

nan

dgl

auco

mat

ous

wor

seni

ngo

fth

eV

For

opt

icd

isc.

292

eye

s22

5pa

tien

ts(

73%

Cau

casi

an)

Crit

eria

for

succ

ess:

(A)

final

IOP≤

18m

mH

gan

don

eof

th

efo

llow

ing:

≥20

%r

educ

tion

of

IOP

ora

red

ucti

ono

f2

med

icat

ions

wit

hfin

alIO

Pre

quire

dto

be

less

tha

nor

equ

alt

oba

selin

eIO

Pif

base

line

IOP≤

18.

(B)

Fin

al

IOP≤

15a

ndo

neo

fth

efo

llow

ing:

≥25

%r

educ

tion

of

IOP

ora

red

ucti

ono

f2

med

icat

ions

wit

hfin

alIO

Pre

quire

dto

be

less

tha

nor

equ

alb

asel

ine

IOP

ifba

selin

eIO

P≤15

.(C

)Fi

nalI

OP≤

12a

ndo

neo

fth

efo

llow

ing:

≥30

%r

educ

tion

in

IOP

ora

red

ucti

ono

f2

med

icat

ions

wit

hfin

alIO

Pre

quire

dto

be

less

tha

nor

equ

alt

oba

selin

eIO

Pif

base

line

IOP≤

12.

Kapl

anM

eier

suc

cess

rate

sat

firs

tan

dth

irdy

ears

aft

erfo

llow

-up

:A8

5%(±

2%)

and

62%

(±4%

),B

84%

(±2%

)an

d56

%(±

4%).

C7

9%(±

2%)

and

45%

(±

4%)

O’B

rart

De

tal

,200

4Ra

ndom

ised

clin

ical

tria

lcom

parin

gtr

abec

ulec

tom

yw

ith

visc

ocan

alos

tom

y.

(Res

ults

for

trab

ecul

ecto

my

only

rep

orte

dhe

re).

Ant

imet

abol

ites

use

das

per

sta

ndar

dpr

acti

ce

for

pati

ents

at

high

ris

kof

dra

inag

efa

ilure

.U

ncon

trol

led

prim

ary

ors

econ

dary

OA

Go

nm

axim

ally

tol

erat

edm

edic

atio

n.5

0ey

es(

16e

yes

Cau

casi

an,2

9ey

esb

lack

),45

pat

ient

s

Succ

essf

uld

rain

age

defin

eda

san

IOP

of≤

21m

mH

gw

itho

uta

ntig

lauc

omat

ous

med

icat

ions

A

t12

mon

ths,

the

prop

orti

ono

fsu

cces

sful

eye

sw

as9

1%w

ith

trab

ecul

ecto

my.

At

the

last

follo

w-u

pvi

sit

(mea

n20

mon

ths)

co

mpl

ete

succ

ess

was

see

nin

68%

aft

ert

rabe

cule

ctom

y.

18D

efini

tion

of

blin

dnes

sus

edin

thi

sst

udy:

cor

rect

edV

Ao

f20

/200

or

wor

sea

ndo

rVF

cons

tric

tion

to

20d

egre

eso

rle

ssin

its

wid

est

diam

eter

.


�.�:SIDEEFFECTS

5.6.1: MEDICATIONS

Topicalanti-glaucomamedications can result in an array of side effects,rangingfromminorimpactssuchaseye-lashelongationanddarkeningoftheiristomajorimpactssuchascardiovascularevents(Table5.9).

TABLE 5.9: MEDICATION SIDE EffECTS

Medication Side effect

Prostaglandinanalogues(prostamides) Browndiscolouringoftheiris,lengtheninganddarkeningof eyelashes,ocularirritationandredness,macularoedemaor iritisinsusceptiblepatients.

badrenergicblockers Ocularirritationanddryeyes.Contraindicatedinpatients withbradycardia,heartblock,heartfailure,asthmaor obstructiveairwaydisease.Canhavesubstantial cardiovascularandrespiratoryside-effects,especially intheelderly.

Alpha(a)2adrenergicagonists Redeyeandocularirritation,centralnervoussystem effectsandrespiratoryarrestinyoungchildren,allergic conjunctivitis,sedation,cautionadvisedinpatientswith cerebralorcoronaryinsufficiency,Raynaud’sdisease, posturalhypotension(dizzyspells),hepatic(liverfailure) orrenalimpairment.

Carbonicanhydraseinhibitors Topicalformshavefewsideeffects,howeveroralforms maycausetransientmyopia,nausea,diarrhoea,lossof appetiteandtaste,parasthesiae,lassitude,renalstones andhaematologicalproblems.

Cholinergicagonists Substantialocularside-effectsincludingblurringofvision duetothesmallpupilandinducedmyopia,ciliaryspasm leadingtoheadachesespeciallyinyoungerpatients. Cataractsandiris-lensadhesionsinthelong-term.

Prostaglandinandb-blockersarethemostfrequentlyusedantiglaucomamedicationsinAustralia.

• Thesideeffectprofileforprostaglandinmedicationsisrelativelyminor.Topicalprostaglandinsarerapidlybrokendowninthebloodstreamasaresult,systemicsideeffectsarerare.Ocularsideeffectscanincludeconjunctivalhyperemia,increasedirispigmentationandpigmentationoftheperiocularskinaswellaslengtheningoftheeyelashes.Becausetheyarerare,nosideeffectsforprostaglandinsareincludedinthemodelling.

• Moresignificantsideeffectsarepossibleforpatientstakingb-blockers.Twotypesoftopicalb-blockersarecommerciallyavailable,nonselective(timolol,levobunolol,metipranololandcarteolol)andcardioselective(betaxolol),(BrooksandGillies,1992).TheIOPloweringabilityofthenonselectiveb-blockersisgreaterthanthecardioselectivebblockers,providingagreatertreatmentefficacy,althoughthesideeffectprofilemaybemoresignificantinthenonselectivebblockermedicationgroup.Thesesideeffectsinclude:stinging,achingorrednessintheeyesafterusingdrops;dryeyesandforeignbodysensation(thefeelingofaforeignbodyintheeye);bradycardia(slowheartbeat);spasmsofthetubesleadingto

5. Treatment

Prostaglandin analogues are the

most frequently used anti glaucoma

medications in Australia.



thelungs(bronchospasmorasthma);heartfailureduetothebuildupoffluid;depression;confusion;fatigue,dizzinessandinabilitytotolerateexercise;and/orreducedlibido.Bronchospasmcanexacerbateasthmaandchronicobstructivepulmonarydisease(COPD)whilebradycardiacanexacerbatecongestiveheartfailure19.Prolongeduseoftopicalb-blockershasalsobeenlinkedtodepression,moodalterations,memoryloss,hallucinations,decreasedlibidoaswellasimpotence.

Themostsignificantsideeffect(whichhasbeenincludedinthedynamicmodelling)associatedwithbblockersisCOPD.ApopulationbasedcohortstudyconductedintheUK,examiningwhethertopicalbblockersareassociatedwithexcessrespiratorydiseaseinelderlypatientsnotconsideredtobeatexcessrisk(Kirwanetal,2002)showedahigherriskofrespiratorydiseasethanwouldnormallybeexpected.Ahazardratiousedinthemodelof2.29(95%CI1.71to3.07)wasproducedforpeopletreatedwithbblockerstoreceiveafirst-timemedicaltreatmentforreversibleairwaysobstruction,althoughthisriskceasestobesignificantafterthefirstyearoftreatmentwithtopicalbblockers.TheriskofCOPDforapersonnotbeingtreatedwithtopicalbblockersisassumedtobeequaltotheprevalenceofCOPDinthegeneralpopulation.

TABLE 5.10: RISK Of COPD (% Of POPULATION), 2001

Age Males females Persons

0-4 0.00 0.00 0.00

5-14 0.00 0.00 0.00

15-24 0.05 0.01 0.03

25-34 0.44 0.22 0.33

35-44 1.15 0.57 0.86

45-54 2.61 1.06 1.84

55-64 5.71 2.08 3.92

65-74 10.42 3.61 6.91

75-84 14.22 5.26 9.01

85+ 16.01 6.37 9.35

AllAges 2.51 1.09 1.80

Source:AIHWspecialrequest.

ThecostofCOPDperpersonisbasedonAIHWdata,indexedto2005dollars(Table5.11).

19www.agingeye.net/glaucoma/glaucomadrugtreatment.php

5. Treatment


TABLE 5.11: hEALTh SYSTEM COST Of COPD ($ PER PERSON), 2005


0-4 0 0 0

5-14 255,006 476,620 304,254

15-24 2,893 13,717 5,167

25-34 88 527 233

35-44 291 978 522

45-54 373 962 543

55-64 858 1,843 1,117

65-74 1,427 2,717 1,775

75-84 1,904 2,524 2,115

85+ 2,010 2,224 2,111

AllAges 1,191 2,085 1,465


5.6.2: LASER TREATMENT

Anumberofstudiesnotethatthesideeffectsoflaserincludeformationofperipheralanteriorsynechiae(LatinaanddeLeon,2005;GLTandGLTFU),uveitis(Nagaretal,2005)andtransientIOPspikes(LatinaanddeLeon,2005).Theseareexcludedfromthemodellingasforthemostparttheydonotaffectqualityoflife.Othermoreserioussideeffects,suchasretinaldetachment,arealsoexcludedfromthemodellingbecausetheyoccuratsuchalowrate.

5.6.3: SURGERY

Thecomplicationsoftrabeculectomyincludecataractandanincreasedriskofeyeinfection.Cataractisthemostsevereandcostlyofthese(becauseofthenumberinvolved)andthushasbeenincludedinthemodelling.

Trabeculectomyisaninvasiveprocedurethathasaknownassociationwiththedevelopmentofcataractsfollowingsurgery.Lichteretal,2001(CIGTS)foundthatinitialsurgicaltreatmentresultedinthedevelopmentofmorecataractsrequiringremovalthaninitialmedicaltreatment.Kaplan-Meierestimatesshowedthatbythreeyearsaftertreatmentinitiation,theprobabilityofcataractextractionwas11.6%(standarderror,1.9%)inthesurgicalgroupversus2.7%(standarderror,1.0%)inthemedicalgroup.Thedifferencewassignificant(p=0.0001).Cataractsoccurredinapproximately20%to35%ofpatientsfollowingfirsttimetrabeculectomyover20monthsto10years(Table5.12).Theoccurrenceofcataractfollowingtrabeculectomypresentsasasignificantsideeffectthatresultsdirectlyfromglaucomatreatment,withanassociatedmorbidityfromVAlossaswellascostsfromsubsequentcataractsurgery.

Other more serious side effects, such as retinal detachment,

are also excluded from the modelling

because they occur at such a low rate.

5. Treatment



5. Treatment

TABLE 5.12: TRABECULECTOMY SIDE-EffECTS

Source Incidence of Cataract following Trabeculectomy Timeframe

Edmundsetal, Cataractsdevelopedin20.2%ofeyesfollowingsurgery. *Cross-sectional 1999 survey

Parcetal,2001 Probabilityofcataractsurgeryatfiveyears(aftersurgery) 5,10and was15%andattenyearswas37%.Nostatistical 20years differencebetweenpatientsandtherestofthecohort at20years.

Fontanaetal, Cataractextractionoccurredin35%ofeyesfollowing 36months 2006 trabeculectomy.

AGIS TheRRofcataractfollowingfirsttrabeculectomywas 10years 1.78.WhencomplicationsoccurredinsurgerytheRR= 2.04andwhentheydidnotoccurRR=1.47.

Ehrnroothetal, Cataractsurgerywascompletedin35%ofeyes 3.5years 2002 followingtrabeculectomyduringthefollowupperiod (mean3.5years).

Ehrnroothetal, Cataractsurgerywascompletedin34.8%ofeyes. 3.5years 2005

O’Brartetal, Cataractformationwassimilarbetweenthe 20months 2004 trabeculectomyandviscocanalostomygroups.

*Edmundsetal,1999isacrosssectionalsurveyoftrabeculectomypatientsintheNationalHealthServiceintheUK.Notimeframewasprovidedinthissurveybetweentrabeculectomyandcataractoccurrence

ThemajorityofstudiesshowninTable5.12measuretheincidencerateofcataractdevelopmentorsurgeryfollowingafirsttimetrabeculectomy.Thesemeasuresdonottakeintoaccounttherateofcataractdevelopmentorsurgeryinpeopleofanidenticaldemography.Ifanincidentrateofbetween20%and35%fromthesestudieswereusedtheincreasedmorbidityandhealthsystemcostwouldbeoverestimated.

TheAGISstudyontheotherhandmeasuredtheRRofcataractfollowingtrabeculectomy.People that undergo a first time trabeculectomy procedure have a 78% increased chance of developing a cataract (RR=1.78)accordingtoAGIS.Thisincreasedriskisappliedinthemodeltopeoplethathaveundergoneatrabeculectomyprocedure,withtheriskofcataractforapersonthathasnotundergonethisprocedureassumedtobeequaltotheprevalenceofcataractinthegeneralpopulation.


5. Treatment

TABLE 5.13: PREVALENCE Of CATARACT (% Of POPULATION)

Age Persons

40-44 0.0000

45-49 0.0000

50-54 0.0000

55-59 0.0844

60-64 0.0107

65-69 0.1620

70-74 0.7254

75-79 2.3713

80-84 5.4910

85-89 8.7109

90+ 15.1689

Source:MVIP&BMESspecialdatarequest.

ThecostofcataractsperpersonisbasedonAIHWdata,indexedto2005dollars.

TABLE 5.14: hEALTh SYSTEM COST Of CATARACT ($ PER PERSON), 2005


0-4 0 0 0

5-14 0 0 0

15-24 0 0 0

25-34 0 0 0

35-44 70 71 73

45-54 107 113 110

55-64 118 112 115

65-74 171 178 176

75-84 206 219 215

85+ 210 132 152

AllAges 178 177 178


5.6.4: SUMMARY Of SIDE EffECTS INCLUDED IN ThE MODELLING

Insummary,twosideeffectshavebeenincludedinthemodellingforglaucoma.Theseare:

• cataract,RRof1.78followingtrabeculectomy;and,

• COPD,RRof2.29followinguseofab-blockertopicaleyemedication.

Healthsystemcostsforthesesideeffectshavebeenincludedintotheperpersontreatmentcostsofmedicationandtrabeculectomy.Themodelallocatesthesecostsbyincreasingthebasecostoftreatmenttoincorporatethetotalexpectedhealthsystemcostsofthesesideeffects.



Main heading to go here5. Treatment

The calculation of disease costs over time is discussed in this section, including:

• the impact of glaucoma on a patient’s quality of life (wellbeing);

• the health system costs of glaucoma; and

• the indirect costs of glaucoma (including the impact on employment, the need for informaland paid formal care, the impact on the paid employment of informal carers, aids andequipment, and the economic costs of welfare payments).

However, first, discount rates are discussed, as the model is dynamic and calculates theeconomic impact of glaucoma in net present value terms over time (2005 to 2025).

6.1: DISCOUNT RATES

Choosing an appropriate discount rate for present valuations in cost analysis is a subject of some debate, and can vary depending on which future income or cost stream is beingconsidered. There is a substantial body of literature, which often provides conflicting advice, onthe appropriate mechanism by which costs should be discounted over time, properly taking intoaccount risks, inflation, positive time preference and expected productivity gains.

The absolute minimum option that one can adopt in discounting future income and costs isto set future values in current day dollar terms on the basis of a risk free assessment about thefuture (that is, assume the future flows are similar to the certain flows attaching to a long termGovernment bond).

Wages should be assumed to grow in dollar terms according to best estimates for inflation andproductivity growth. In selecting discount rates for this project, we have thus settled upon thefollowing as the preferred approach.

• Positive time preference: We use the long term nominal bond rate of 5.8% pa (from recenthistory) as the parameter for this aspect of the discount rate. (If there were no positive timepreference, people would be indifferent between having something now or a long way off inthe future, so this applies to all flows of goods and services.)

• General Inflation: The Reserve Bank has a clear mandate to pursue a monetary policy thatdelivers 2 to 3% inflation over the course of the economic cycle. This is a realistic longer rungoal and we therefore endorse the assumption of 2.5% pa for this variable. (It is importantto allow for inflation in order to derive a real (rather than nominal) rate.)

• Productivity growth: The Commonwealth Government’s Intergenerational report assumedproductivity growth of 1.7% in the decade to 2010 and 1.75% thereafter. We suggest1.75% for the purposes of this analysis.

• Health Inflation: Health cost inflation from 2005 onwards is assumed to be 3.2%, based onestimates of increases in health expenditure from the AIHW estimates that health inflationin the eight years to 2004-05 has been around 3.2% per annum (AIHW 2006). This rate ispartially general price inflation and partially productivity growth. To be on the conservativeside, productivity growth in the health sector is assumed to be equal to generalproductivity growth.

6. Disease Costs

Glaucoma hassignificant social and economic costs.


Therearethendifferent discount rates that should be applied:

• Todiscountincomestreamsoffutureearnings,thediscountrateis:

5.8-2.5-1.75=1.55%

• Todiscounthealthcosts,thediscountrateis:

5.8-(3.2-1.75)-1.75=2.6%

• Todiscountotherfuturestreams(healthylife)thediscountrateis:

5.8–2.5=3.3%

Whiletheremaybesensibledebateaboutwhetherhealthservices(orothercostswithahighlabourcomponentintheircosts)shouldalsodeductproductivitygrowthfromtheirdiscountrate,wearguethatthesecostsgrowinrealtermsovertimesignificantlyasaresultofotherfactorssuchasnewtechnologiesandimprovedquality,andwecouldreasonablyexpectthistocontinueinthefuture.

�.�:THECOSTTOQUALITYOFLIFEANDWELLBEING

6.2.1: DISEASE WEIGhTS

Asnotedabove,the impact of treatment on a patient’s health and quality of life is of primary importanceinmodellingtheeconomicimpactofdisease.Inthisstudy,eachstageintheprocessofvisionlossneedstobematchedwithautilityweight(apatient’smeasureofhisorherqualityoflife)reflectingthelossofqualityoflifeexperiencedatthatpointintheprogressionofthedisease.ThisisverydifficultforPOAGbecause:

• changesinIOPdonoteasilytranslateintoahealthbenefitforpatients(Kobeltetal,2006,Hymanetal,2005,Jampeletal,2002andMillsetal,2001);and

• thereisnoagreeddiseasestagingsystembasedonvisionloss(seeSection4.5).Thevariousvisiongradingsystemscannotbeeasilytranslatedintoaquantifiableimpactonqualityoflife.

Thereisagrowingliteraturethatattemptstomeasuretheimpactofglaucomaonqualityoflife,althoughthelackofaconsistentdiseasestagingsystemremainsaproblemindrawingconclusionsfromthesestudies.Theliteraturesuggeststhatduringtheearlystagesofdisease,glaucomahaslittleimpact,withquality of life deteriorating over time, particularly in the later stages of the disease. Someexamplesareasfollows.20

1) Kobeltetal,(2006)undertookacrosssectionalpilotstudytotestwhetherutilitiesfordifferentlevelsofVFdefectcouldbeassessedusingageneralquestionnairesuchastheEQ5D.UtilityweightsdevelopedusingtimetradeoffunderlietheEQ5D.InSweden,199patientswithOHTorPOAGweregroupedaccordingtosixstagesofvisionlossbasedonVFdefectsintheworsteye.ThediseasestageswereadaptedfromtheHAPscale—fromnodefect(OHT)toendstagediseasewhereVFmeasurementwasdifficultornolongerpossible.Theauthorsfoundthatutilitywasstronglycorrelatedwithoverallvision,andpatientswithsevereglaucomatousdamagehavesignificantlylowerutility.However,whileutilitydecreasedwithincreasingglaucomatousdamage,thedifferencebetweenthestageswasnotstatisticallysignificantwhencontrollingforco-morbidity.When17outlierswereremoved,utilityscoresforpatientswithsevereglaucomatousdamageweresignificantlyworse.Patientsinstage5hadameanutilityof0.71(autilitylossof0.29),comparedto

6. Disease Costs

20Foranexplanationofthelinearratingscale,standardgamble,timetrade-off,persontrade-offandEQ-5D,seeMathersetal,(1999:10).



0.88instage1andameanof0.84(autilitylossof0.16)instages2.4.Thesamplesizewassmallandthenumberofpatientswithmoderatetoseverebilateralvisionlosswaslimited,however,theresultswereconsistentwithotherstudies(Kobeltetal,2006).

2) Jampeletal,(2002)examinedhow191glaucomapatients’and46glaucomasuspects’ratingoftheirvisioncorrelatedwithEstermanbinocularVFtestingandothervisualfunctiontests.TheyfoundthatutilityvaluesthatpatientsassigntotheirvisiondonotcorrelatewellwithEstermanresultsandsuggestedthiswasbecause,“there may not be a close relationship between visual function and patient perception of that function, especially when the vision loss is mild ... Perhaps early visual field loss really does not affect patient assessment of their vision and in fact is more of an all or none phenomenon with patients only noticing marked visual field loss.” (Ontheotherhand,appropriatetestsmaynothavebeendeveloped.)Alinearratingscaleandtimetradeoffwereusedtogaugethepreferencesofpatientswithglaucomaforvisualstates.Basedonthelinearratingscale,glaucomapatientsratedtheirvisionas0.72andsuspectsratedtheirvisionas0.71(ona0to1scale).Blindglaucomapatients(withaVAnobetterthancountingfingersinthebettereyeandwhohadbeenblindfor10years)ratedtheirvisualstateas0.54.Glaucomapatientsandsuspectsassignedavalueof0.38and0.34respectivelytototalblindness.Timetradeoffresultswerelessinformativeasfewwerewillingtogiveuptimeforimprovedvision.

3) AUKstudy(Brownetal,2001)usedatimetradeoffandastandardgambletomeasureutilityassociatedwithblindnessfrom65patientswithvariousvisiondiseasesincludingglaucoma,cataract,agerelatedmaculardegeneration(AMD)anddiabeticretinopathy.Autilityvalueof1.0indicatesastateofperfecthealthwhereasautilityvalueof0indicatesdeath.Participantsweregroupedaccordingtovariousmeasuresofblindnessasfollows:

b) totallyblind:15patientswithnolightperceptioninatleastoneeyeandwhowereaskedtoassumeascenarioofnolightperceptioninthesecondeyeaswell;

c) somelightperception:17patientswithlightperceptiontocountingfingersinthebetterseeingeye;

d) justoverthelineforlegalblindness:33patientswith20/200-20/400visioninthebetterseeingeye.

Thetimetradeoffresultssuggestedutilityvaluesforeachgroupof(a)0.26QALYs(95%CI0.19to0.33);(b)0.47QALYs(95%CI0.33to0.61);and(c)0.65QALYs(95%CI0.58to0.72).Thus patients with no light perception in one eye who were presented with the same scenario in the second eye as well were willing to trade almost 3 out of every 4 years of remaining life in return for perfect vision in each eye. Thosewithlightperceptiontocountingfingerswouldtradeapprox1of2remainingyearsandthosewith20/200-20/400wouldtradeapprox1of3remainingyears.

Thestandardgambleutilityresultsweresubstantiallyhigher:(a)0.32(95%CI0.2to0.44);(b)0.60(95%CI0.46to0.74);and(c)0.80(95%CI0.73to0.87).However,theauthorssuggestedthestandardgambleresultsoverestimateriskaversionbecauseparticipantshavedifficultyunderstandingthisapproach.

Notably,inblindpatients,utilityimprovedovertimesuggestingadaptationtoblindness(thereweresignificantdifferencesbetweenthoseblindforlessthanoneyearandthoseblindformorethanoneyear)andtheworsethevisioninthebettereye,thelowertheutility.Brownetal,(2001)concludedthat:

6. Disease Costs

Vision loss has a very significant impact on the quality of life that is highly valued.


There is a wide range of utility values associated with legal blindness … the preservation of even small amounts of vision in patients with legal blindness is critically important to their wellbeing and functioning in life. (Brown et al, 2001:327)

AIHWWEIGHTS

The choice of disease weights is very important.Iftheutility(QALY)weightsassociatedwithvisionlossaretooloworthedisabilityweights(DisabilityAdjustedLifeYears-DALYs)aretoohigh,theresultswilloverestimatethecosteffectivenessofinterventions(andviceversa).Previousmodelsinthisseries(seetheBackground—Section1ofthisreport)appliedthedisabilityweightsusedbytheAIHWintheirlossofwellbeingstudy(Mathersetal,1999,Table6.1).Theseweightsaredrawnfroma Dutch study that used a person trade off methodtoestimateweightsfor53diseases,includingtheestimationofweightsfor175diseasestages,sequelaeandseveritylevels(citedinMathersetal,1999:11).TheDutchweightsarebasedondiseasestagesdefinedasfollows(Mathersetal,1999:159):

• Milddisease:Somedifficultywithnewspaper,nodifficultyrecognisingfacesat4m;

• Moderatedisease:Greatdifficultynewspaper,somedifficultyrecognisingfacesat4m;and

• Severedisease:Unabletoreadnewspaperorrecognisefacesat4m.

WhileitisdifficulttorelatethesedefinitionstostagesofVFLinthestudiesoutlinedabove,andspecificallytoadiseasesuchasglaucomawhichinitiallyaffectsmid-peripheralVF,theAIHWweightsarenotinconsistentwiththepreviousliteraturereview—notingthattheAIHWweightsreflectdisabilityweights(DALYs)ratherthanutilityweights(QALYs).

• ManypatientswithOHTortheclinicalsignsofglaucomadonotexperiencevisionlossforseveralyears.Thusthereisnolossofutilityduringearlystagediseaseandthedisabilityweightis0.0.

• TheAIHW(Dutch)weightformoderatediseaseliesbelowthelowestweightforseverediseasefoundintheliteraturereview(0.17comparedwith0.26).However,ifglaucomareallyonlyaffectsqualityoflifeinthelatterstagesofdisease,thenthedisabilityweightsformildandmoderatediseasemightbetoohigh.

• LegalblindnessinAustraliaisdefinedasVAof<6/60inthebettereyewithcorrection(spectacles)oraVFoflessthan10degreesorboth(CERA2004:11).Totalblindnessreferstopeoplewhoareunabletoseelight.TheseareencompassedintheAIHWweightforseverediseasewhichis0.43(comparedwiththerangeofestimatesof0.26tomorethan0.6inthestudiesoutlinedabove).

The AIhW disease weights will be used here. Theyaredrawnfromastudyofanumberofdiseasesandcomparisonwithotherdiseasesandinterventionsisimportantforbudget/resourceallocationdecisions.Inaddition,itisalsopreferabletouseweightsfromthesamestudysothatthesamemethodologyhasbeenusedandthesetofweightsisinternallyconsistent.TheAIHWweightsarealsoconsistentwiththepreviousmodelsdevelopedbyCERAandsoallowforeasycomparisonsacrossthese.

BasicAIHWweightsareonlyforthediseaseanddonottakeintoaccountco-morbidities.Glaucomaisassociatedwithbothaccidentalfallsanddepression.AccidentalfallsanddepressionarediscussedbelowinSections6.3.4and6.3.5.Thediseaseweightsarenotadditive—addingtheweightsforapersonwithsevereglaucomaandseveredepressionresultsinaweightgreaterthan1whichisnotintuitivelypossible.

Many patients with OhT or the clinical

signs of glaucoma do not experience vision loss for several years.

6. Disease Costs



Consequently,thefollowingformulaeareused:

whereWisthedisabilityweight,VI

denotestheseverityofvisualimpairment(EDS,Mild,ModerateorSevere),

DEPdenotesdepressionand

FALLdenotesafall.TheAIHWweighting

foraccidentalfallsis0.141andfordepressionis0.223basedon20%ofglaucomasuffersexperiencingmilddepressionwithaweightingof0.140and5%ofglaucomasuffersexperiencingmoderatetosevererdepressionwithaweightingof0.555(seeSection6.3.5fortheevidencebasisforcomorbiddepression)(seeMathersetal,1999,forthederivationoftherespectivedisabilityweights).

TABLE 6.1: AIhW DISABILITY WEIGhTINGS

EDS Mild Moderate Severe

Glaucomaonly 0.000 0.020 0.170 0.430

Glaucomaandaccidentalfalls 0.141 0.158 0.287 0.510

Glaucomaanddepression 0.223 0.239 0.335 0.557

Glaucoma,accidentalfallsanddepression 0.333 0.346 0.446 0.620

CERAWEIGHTS

CERAweightsarealsoavailableforusewithinthemodel.ThesearenotcorrelatedwithseverityofdiseasebasedonafindingfromresearchduringthedevelopmentoftheVisQoL,thetooltoderivevision-relatedutilities.Therewasnosignificantdifferencebetweenmild,moderateandseverevisionloss.TheCERAQALYweightforvisualimpairmentof0.83(utilitylossorDALYof0.17)appliestoalllevelsofvisualimpairmentandisconsistentwithresultsfromtheVIPsuggestingthat,withcancer,blindnessisthemostfearedhealthcondition.NoadditionaladjustmentforfallsanddepressionaremadeifCERAweightsareused.Itshouldbenotedthatusingthesamedisabilityweightforalllevelsofseverityofglaucomareducesthebenefitsofslowingprogressionofglaucoma.

6.2.2: PLACING A DOLLAR VALUE ON ThE LOSS Of WELLBEING

LossofwellbeingisestimatedusingDALYsandapplyingthelowerboundVSLof$3.7milliontoyieldthe estimated value of a life year of $162,561 (CERA, 2004).

DEPVIVIDEPVI WWWW !"+= )1(,

FALLVIVIFALLVI WWWW !"+= )1(,

FALLDEPVIDEPVIFALLDEPVI WWWW !"+= )1( ,,,,

6. Disease Costs


�.�:HEALTHSYSTEMCOSTS

Thehealthsystemcostsofglaucomaarecategorisedanddiscussedinthissectionasfollows:

• thecostofmonitoringanindividualwithglaucoma(notincludingtreatmentcosts);

• thecostsoftreatmentforPOAG;

• theincreasedlikelihoodofbeingadmittedtoanagedcarefacilityandtheassociatedcosts;

• thecostsassociatedwithanincreasedlikelihoodoffallsandhipfractures;and

• thecostsassociatedwithanincreasedlikelihoodofdepression.

DataonthehealthsystemcostsofPOAGarefromaspecialrequestfromtheAIHW.Themostrecentdataforexpenditurebydiseaseareforthefinancialyear2000-01andhavebeenfactoredupforhealthinflation.BasedonestimatesofincreasesinhealthexpenditurefromtheAIHW,healthinflationinthelasteightyearsto2004-05hasbeenaround3.2%perannum(AIHW2006).

TheAIHWincludeonly87.5%(AIHW2005)oftotalrecurrenthealthexpenditureintheirestimatesofexpenditurebydiseaseandinjury,referredtoas‘allocated’healthexpenditure.The‘unallocated’remainderincludescapitalexpenditures,expenditureoncommunityhealth(excludingmentalhealth),publichealthprograms(exceptcancerscreening),healthadministrationandhealthaidsandappliances—thecodingfortheseareasofexpendituredoesnotallowallocationbydiseasecategory.Toensurecomprehensiveness,theseaspectsofhealthsystemcostshavebeenincorporatedbymultiplyingtheAIHW‘allocated’expenditureestimatesby1.143(=1/0.875).Factoringuptheallocatedexpenditureinthiswaymeansthatcareneedstobetakentoavoiddoublecounting.Forexample,manyaidsandappliancecostsareprovidedbycommunityprograms(ratherthangovernmentprograms),andarenotincorporatedintheAIHWexpenditure.

Theproportionofhealthcostsbornebythegovernment(68.2%)andtheindividual(19.0%)isbasedonAIHW(2006:30).

TABLE 6.2: hEALTh COSTS BY WhO BEARS ThE COST, 2004-05

federal State/Territory Private health Individuals Other Total Government Government Insurance

% 45.6% 22.6% 6.5% 19.0% 6.3% 100.0%

Source:AIHW(2006:30).

6.3.1: ThE COST Of MONITORING AN INDIVIDUAL WITh GLAUCOMA

Thecostofmonitoringanindividualwithglaucomain2005—notincludingmedical,laserandsurgicaltreatmentsis$649perpersonperyear.Thiswascalculatedbyadjustingthetotalhealthcostsforglaucoma($148.3min2000-01)inthefollowingways:

• adjustforthechangeinthepopulationbetween2000-01and2005;

• includeunallocatedhealthexpenditure(factoredupby1.143);

• indexspendingto$2005(healthinflationof2.6%pa);and

• removeexpenditureontreatment(medication,laserandsurgery)andagedcare;

• dividebythenumberofpeoplereceivingtreatmentin2005.

6. Disease Costs

Overall, individuals still pay 19% of

health costs.



6. Disease Costs

6.3.2: COST Of TREATMENT

Medication

ThecostestimateswerederivedusingdatafromtheDepartmentofHealthandAgeingwebpublicationAustralian Statistics on Medicines 2005,andAustralianMedicareBenefitsSchedulefees.Thetotalcostofanti-glaucomamedicationsfor2005isinTable6.3,andisdividedbythetotalnumberofpeoplereceivingmedicationin2005(ie.thenumberofpeoplewithdiagnosedPOAGin2005estimatedinthedynamicmodel)toderivethecostofmedicationperpersonperannum.

TABLE 6.3: COST Of MEDICATION PER PERSON PER ANNUM

TotalCostofAnti-glaucomaMedications $99,694,643

TotalNo.ofPeopleonMedication 103,820

CostofMedicationperPerson $960

Source:AustralianStatisticsonMedicines2005andAccessEconomicsEconomicModeloftheImpactofPrimaryOpenAngleGlaucoma.

Thecostofthesideeffectsofmedicationswereaddedtothecostofmedicationsperperson.TheORofCOPDfollowingtheuseofatopicalbeta-blockerappliedtotheaverageriskofCOPDinTable510is2.29andthecostofCOPDperpersonisinTable5.11.ThetotalcostofmedicationwithsideeffectsincludedbyageandgenderisinTable7.1.

Trabeculoplasty

Thecostofatrabeculoplastyisappliedinthemodelonceatthepointwhenapatienttransitionsintothe‘laser’treatmentphase.To account for people that have more than one trabeculoplasty procedure, the cost calculated inTable6.4is inflated by 1.5 in the modelling calculations (see Section 5.2). ThecostofthisprocedureisbasedonthetreatmentfeeintheMBSforthetreatmentaswellasthecostoftheanaesthesiaservice(Table6.5).Basedonclinicaladviceforthisreport,thecostofanassistanthasnotbeenincluded.

TABLE 6.4: TOTAL COST Of TRABECULOPLASTY PER TREATMENT

MBS Code Description Cost

42782 LaserTrabeculoplasty–eachtreatmentto1eye,toamaximum $398.65 of4treatmentstothateyeina2yearperiod(Anaes.)(Assist.)

20140 Initiationofmanagementofanaesthesiaforproceduresoneyes, $84.25 notbeingaservicetowhichanotheriteminthisgroupapplies (5basicunits)

Total $482.90

Source:MBSBook,1November2006

Medication costs on average: $960.80 per person per year.

Trabeculoplasty costs on average $482.90.


6. Disease Costs

Trabeculectomy

Aswithtrabeculoplasty,thecostofatrabeculectomyisappliedinthemodelonce,whenthepersonmovesintothe‘surgery’treatmentphase.To account for people that have a second trabeculectomy procedure, the total cost of surgery in Table6.6is scaled up by 1.2 to $4,122.50.

Thecostofthisprocedureisbasedontheaveragediagnosisrelatedgroup(DRG)costfortrabeculectomy,weightedforpublicandprivatehospitals,fromtheNationalHospitalCostDataCollection.ThecodethatrelatestotrabeculectomyproceduresisDRGC15AGlaucomaandComplexCataractProcedures.ThetotalcostsofprivatehospitaltrabeculectomyproceduresareinTable6.5.

TABLE 6.5: TOTAL COST Of TRABECULECTOMY PER TREATMENT

Total Cost No. of Procedures Weighted Average

PrivateHospital $3,027 656 0.3993

PrivateFreeStandingHospital $3,027 404 0.2459

PublicHospital $4,178 583 0.3548

$3,435.42

Source:PersonalCommunication(MarcFoley,EarandEyeHospital);NationalHospitalCostDataCollectionRound9PublicHospitalCostsandAIHWspecialdatarequest

6.3.3: AGED CARE

Visual impairment compounds the presence of other disabling conditions,leadingtoanincreasedlikelihoodofutilisinginstitutionalisedagedcare.UsingBMESdata,Wangetal,(2003)foundaRRofpermanentnursinghomeadmission—afteradjustingfornon-cognitivefactorsthatpredictednursinghomeplacement—forpeoplewithbestcorrectedvisualimpairment(≤6/12)agedover40years,of1.8(95%CI1.1–2.9).InthismodelforpeoplewithEDStheRRofbeinginanagedcarefacilityisassumedtobeunity,whileforMild,ModerateandSeverevisualimpairmenttheRRofbeinginanagedcarefacilityisbasedonalinearadjustment,withmoderatevisualimpairmentasthemidpoint:

• 1.4formild;

• 1.8formoderate;and

• 2.2forseverevisualimpairment.

TheRRisappliedtothegeneralpopulationofbeinginanagedcarefacility,andtheaveragecostperyearof$52,800,fromtheAccessEconomicsAgedCareDynamicCohortModel.


Trabeculectomysurgery cost on average $3435.


6. Disease Costs

TABLE 6.6: PROBABILITY Of RESIDING

IN AN AGED CARE fACILITY, 2004-05

Age % of Population

0-54 0.0002

55-59 0.02

60-64 0.14

65-69 0.29

70-74 0.60

75-79 1.40

80-84 3.40

85-89 8.51

90+ 25.40

Source:AccessEconomicsAgedCareDynamicCohortModel

6.3.4: fALLS AND hIP fRACTURES

Itiswellestablishedthatolderpeopleareatahigherriskoffalls,approximatelyhalfofwhichresultinaninjury.Manystudieshaveexaminedthefactorsunderlyingtheincreasedpropensityoffallsintheelderlyandseveralhavefoundasignificantlinkbetweenfallsandvisionloss.Elderlyindividualsprogressivelyrelyonvisualfeedbacktomaintainbalancewithincreasingagebecauseproprioceptivefeedback,musculoskeletalstrengthandoftenvestibularfunctiondeclinewithage(Ramrattanetal,2001).Thedeteriorationofvisualfunctioncoupledwiththelossofothersensoryfunctionsresultinthehigher risk of falls in elderly visually impaired people.

Theriskofafallhasbeenlinkedtomanydifferentmeasuresofvisualimpairment.ThemajorityofstudiescomparetheriskoffallstoVAoranothermeasureofvisualimpairmentwithveryfewstudiesexaminingthelinksbetweenglaucomaandfalls.Ofthesmallnumberofstudieslinkingglaucomaandfallssomeusedtheconsumptionofnon-miotictopicaleyemedicationsasaproxyforVFL,whileonlyonestudyconductedadiagnostictesttodeterminethepresenceofglaucomaandtheextentofVFL.

Ameta-analysisoftheavailableliteraturethatexaminedtherelationshipbetweenvisualimpairmentandtheriskofanaccidentalfallwasconducted(Table6.10).Additionalsupportivearticleswerefoundduringtheliteraturesearches,butcouldnotbeincludedduetoalackofquantitativeinformation.ThesearticlesarelistedandsummarisedinAppendix1,Table10.4.ArandomeffectsmodelhasbeenappliedtothedatainTable6.7andTable6.8,withstudiesthatusedVFLandglaucomaproxiesormeasuresevaluatedseparately.

Older people with vision impairment are at a higher risk of falls, approximately half of which result in an injury.


6. Disease Costs

TABLE 6.7: INCREASED RISK Of fALLS fROM VISUAL IMPAIRMENT

Source Impairment RR / OR 95% CI

Arfkenetal,1994 ImpairedVA RR=0.91 0.45to1.83

Colemanetal,2004 Lossof0-5letters OR=2.08 1.39to3.12



Colemanetal,2004 Lossof>15letters OR=2.08 1.01to4.30

DolinisJetal,�� Medicalhistoryofglaucoma RR=�.�� .��to�.��

GlynnRJetal,�� 0%orgreaterVFLloss RR=�.00 0.��to�.�0

GlynnRJetal,1991 Mioticeyemedication RR=3.20 1.00to10.10

GlynnRJetal,�� Non-mioticeyemedication RR=�.�0 �.�0to��.�0

HaymesSAetal,�00� Glaucoma OR=�.�� .��to��.0�

IversRQetal,1998 Posteriorsubcapsularcataract PR=2.10 1.00to4.30

IversRQetal,1998 Non-mioticeyemedication PR=2.00 1.10to3.60

IversRQetal,1998 LowVA PR=1.90 1.20to3.00

IversRQetal,1998 Lowcontrastsensitivity PR=1.20 1.10to1.30

IversRQetal,�� Glaucoma PR=�.�0 �.00to�.�0

Ramrattanetal,�00� UnilateralVFL RR=�.�� .��to�.��

Ramrattanetal,�00� BilateralVFL RR=�.�� .��to��.��

TinettiMEetal,1988 VisuallyImpaired RR=1.70 1.20to2.30

Vuetal,2005 <6/12bettereye OR=0.98 0.12to7.70

Vuetal,2005 <6/12worseeye OR=2.86 1.16to7.08

ZwerlingCetal,1998 Visuallyimpaired RR=1.60 1.10to2.40

HighlightedstudiesprovideVFand/orglaucomarelatedestimates.RR=RelativeRisk,OR=OddsRatio,PR=PrevalenceRatio

TABLE 6.8: META-ANALYSIS, fALLS (RANDOM EffECTS MODEL)

RR 95% CI

RiskofAccidentalFall–VisualImpairment 2.05 1.54to2.71

RiskofAccidentalFall–VFLorGlaucoma 3.18 1.82to5.55

VFL=VisualFieldLoss

TheRRofanaccidentalfallinpeoplewhosevisualimpairmentwascausedbyVFLorglaucomawashigherthantheoverallvisualimpairmentgroup.AlthoughcautionisadvisedwiththisgroupastheVFL/glaucomashowedahigherlevelofestimatedpublicationbiasthanthevisualimpairmentgroup.Itmaybethecasethatthesmallnumberofpublished(andincluded)trialswhereVFLwasincludedmaybepushingtheRRhigherthanitshouldbe.ThiscanonlyberesolvedwiththecompletionandinclusionofmorestudiesonVFL.

TheRRsofaccidentalfallsaresplitbyvisualimpairmentseveritybyapplyingtheRRinTable6.10tothosewithmoderatestagedisease,allocatingaRRof1.0totheOHTgroupandapplyingalinearextrapolationtodeterminetheRRsforthemildandseveregroup(Table6.11).



6. Disease Costs

TABLE 6.9: RELATIVE RISK Of AN ACCIDENTAL fALL BY SEVERITY

Visual Impairment VfL / Glaucoma

OHT 1.00 1.00

Mild 1.52 2.09

Moderate 2.05 3.18

Severe 2.57 4.27

Source:AnalysisbyAccessEconomics.

TheseresultsareconsistentwithBlackandWood(2005)whoconcludedthattheORoffallsandfracturesfromreducedvisionlaybetween1.5and2.0.

Theriskofhavinganaccidentalfallforapersonwithoutglaucomaisassumedtobeequaltotheprevalenceofaccidentalfallsinthegeneralpopulation.

TABLE 6.10: RISK Of ACCIDENTAL fALL (% Of POPULATION), 2001


0-4 0.64 0.50 0.57

5-14 0.83 0.551 0.68

15-24 0.74 0.27 0.51

25-34 0.55 0.24 0.40

35-44 0.44 0.28 0.36

45-54 0.42 0.34 0.38

55-64 0.47 0.56 0.51

65-74 0.75 1.16 0.96

75-84 1.78 3.21 2.61

85+ 5.07 7.80 6.95

AllAges 0.68 0.70 0.69

Source:AIHW,specialrequest.

ThecostofanaccidentalfallperpersonisbasedonAIHW2000-01data,indexedto2005dollars.

The risk of having an accidental fall for a person without glaucoma is assumed to be equal to the prevalence of accidental falls in the general population.


TABLE 6.11: hEALTh SYSTEM COST Of AN ACCIDENTAL fALL ($ PER PERSON), 2005


0-4 8,829 8,071 8,505

5-14 7,718 12,166 9,363

15-24 8,307 7,967 8,218

25-34 7,324 8,394 7,655

35-44 7,522 9,905 8,455

45-54 8,861 12,613 10,561

55-64 11,291 11,011 11,140

65-74 13,660 14,224 14,012

75-84 14,659 11,464 12,375

85+ 15,246 12,381 13,025

AllAges 9,737 11,500 10,643


6.3.5: DEPRESSION

StudiesexaminingthelossofVAandlinkstotheonsetofdepressivestatehaveshownahigherRRofsufferingdepressionincomparisontothegeneralpopulation.Thesedonotnecessarilyrelatetoopenangleglaucoma—studiesforPOAGarerequired.

Onestudy,however,reportedthatglaucomadoesnotsharethesameRRassociationasothervisualimpairments.Wilsonetal,(2002)reportedthatthereisnoassociationbetweendepressionandVAlevel,VFseverityortheuseoftopicalbblockersinpeoplewithglaucoma.Howeverthisstudywasconductedonasmallnumberofpatientsandreliedonselfreportedsurveys.

Prevalenceratesofdepressioninelderlyvisuallyimpairedpopulationsareestimatedtorangebetween25%45%(Burmedietal,2002).Withinthegeneralelderlypopulation,lessthan20%havemilddysphoriawithlessthan5%sufferingfromseveredepression.Comparingrisksfromthesestudies,theRRofdepressionislikelytobeintheorderof35%/10%=3.5timeshigher.SummaryresultsfromthesestudieslinkingvisionimpairmentarepresentedinTable6.12.

6. Disease Costs

Depression occurs three times more

commonly in those with vision loss.



6. Disease Costs

TABLE 6.12: DEPRESSION AND VISION LOSS

Source finding

Brodyetal,2003 33%depressed

Karisson,1998 Lessthan10%depressed

Kleinschmidt,1995 22%mildly;4%moderatelytoseverelydepressed

Rovneretal,1997 39%-70%depressiondependingonmeasurementscaleused

Wahl,1994 43%ofblind,29%ofvisuallyimpaireddepressed

Robbinsetal,1988 Meanscoreof10.3(10+indicatesdepression)

Vuetal,2005 OR6.28forhealthandemotionalproblems;OR4.7for‘notfulloflife’

Wilsonetal,2002 Nodifferenceindepressivestate

ChenandHe2005 Measuresformildanxietyandmoderatesevereanxietywereallhigherfor bothacuteangleclosureglaucomaandchronicangleclosureglaucomathan thenationalnorm.

Forthemodelbasecase,people with glaucoma have an OR of depression which is approximately 3.5. Theriskofhavingdepressionforapersonwithoutglaucomaisassumedtobeequaltotheprevalenceofdepressioninthegeneralpopulation.ThecostofdepressionperpersonisalsobasedonAIHW2000-01data,indexedto2005dollars(Table6.14).

TABLE 6.13: RISK Of DEPRESSION (% Of POPULATION), 2001


0-4 0.00 0.00 0.00

5-14 0.02 0.01 0.01

15-24 0.95 1.02 0.99

25-34 3.29 4.45 3.87

35-44 4.38 5.95 5.17

45-54 4.35 6.32 5.33

55-64 3.82 5.72 4.76

65-74 2.77 3.97 3.39

75-84 1.93 2.37 2.19

85+ 1.34 1.45 1.41

AllAges 2.53 3.52 3.03



TABLE 6.14: hEALTh SYSTEM COST Of DEPRESSION ($ PER PERSON), 2005


0-4 0 0 0

5-14 18,544 75,852 36,831

15-24 2,793 5,659 4,250

25-34 1,555 2,296 1,983

35-44 1,346 1,831 1,627

45-54 1,634 1,870 1,774

55-64 1,799 2,167 2,017

65-74 2,657 3,610 3,233

75-84 5,872 9,304 8,033

85+ 17,672 12,551 14,052

AllAges 1,915 2,632 2,334


�.�:INDIRECTCOSTS

Theindirectcostsofglaucomacanincludeareducedlikelihoodofemployment,theneedforformalaswellasinformalpersonalcare(andtheassociatedimpactontheemploymentofinformalcarers),aidsandequipment,andtheeconomiccostsofwelfarepayments.Manyoftheseindirect costs are related to the level of visual impairment rather than glaucoma per se,andarethereforesimilartotheindirectcostsassociatedwithothereyediseasessuchasAMD.

EMPLOYMENT

Glaucomaoverwhelminglyaffectstheelderlysoveryfewpeoplewithseverevisualimpairmentarelikelytobeemployed.Forthepurposesofmodelling,peoplewithEDSareassumedtohaveanORofbeingemployedofunity,whileforMild,ModerateandSeverevisualimpairmenttheORofbeingemployedisbasedonalinearadjustmentoftheORcontainedinCERA(2004:66),withmoderatevisualimpairmentasthemidpoint:

• 0.75formild;

• 0.5formoderate;and

• 0.25forseverevisualimpairment.

TheRRsareappliedtothegeneralemploymentratesbyagefromABS(2005)andtheAverageWeeklyEarnings(AWE)ratesfromABS(2004),indexedto2005dollars.

OThER INDIRECT COSTS

Otherindirectcostsperperson(suchastheimpact on employment of informal carers, formal care costs, aids and modifications, and other indirect costs)wereextractedfromtheMVIPdatabaseforthosepeoplewithVAloss(indirectcostsforpeoplewithoutvisualimpairmentareassumedtobenil).DuetohighSDsinthedata,themeanindirectcostsacrossalllevelsofvisualimpairmentwereused,insteadofindirectcostsbymild,moderateandseverevisualimpairment.

6. Disease Costs

Glaucoma overwhelmingly

affects the elderly - fewer people

with severe visual impairment are likely

to be employed.



6. Disease Costs

“Informalcareandsupport”issplitbetweencostsandlostproductivityofthecarerbasedontheratiocontainedinCERA(2004:75).Theproportionof“Medicines,productsandequipment”thatareaidsandmodificationsisbasedonthesplitusedinCERA(2004:70-72).Carerproductivitycostswereindexedto2005accordingtoAWEovertime,whiletheremainingindirectcostswereindexedtohealthinflation.

TABLE 6.15: INDIRECT COSTS ($ PER ANNUM), 2005

Cost

FormalCare 439

LostProductivityofCarer 1,544

AidsandModifications 337

OtherExpenses 630

Sources:MVIP,CERA(2004).

�.�:DEADWEIGHTLOSSES

Thefollowingparameterswereusedtoestimatelost taxes and additional welfare paymentsfromglaucoma,whichinturnunderlietheestimationofdeadweightlossestotheeconomy.

• Averagepersonalincometaxrateof21.20%andaverageindirecttaxrateof15.51%,basedonAccessEconomicsMacroeconomicmodel(AEM).

• Thelevelofdisabilitysupportperannumof$10,340.20($397.70x26–fromwww.centrelink.gov.auin2005),isindexedtotheAWEandisreceivedbyallindividualswithVAworsethan6/60whoareaged15to65(afterthisageitislikelytheywouldreceivetheagedpensionregardlessoftheirVA)21.

• Therateofdeadweightlossis0.275per$1oftaxrevenueraised,basedonProductivityCommission(2003),plus0.0125per$1oftaxrevenueraisedforAustralianTaxationOffice(ATO)administration,andisappliedtohealthsystemcostsincurredbythegovernment,losttaxesandwelfarepayments.

21Ifapersononthedisabilitypensionisemployed,then(dependingonthelevelofincomeandhoursofemployment)theamountreceivedmaybeadjustedslightlydownwards.However,givenglaucomamainlyaffectsolderpeople,andthosethatreceivethepensionarepermanentlyblind,thenumberofpeopleemployedwouldbelowandanyslightadjustmentsdownwardswouldmakenegligibleimpactontheresults(especiallysinceweonlyincludethedeadweightlossofthegovernmentexpenditureratherthantheexpenditureitself).

Indirect costs of vision loss are often overlooked.


This section summarises the parameters used in the model.

• Modelled prevalence rates are in Table 7.1.

• Initial severity of visual impairment splits are in Table 7.2.

• Modelled treatment assumptions are in Table 7.3.

• The costs of treatment including the expected health system costs of side-effects andadverse events are in Table 7.4. There is also a cost of monitoring those who are diagnosedwith POAG at $649 per patient per year.

• The Sections explaining the other parameters used within the model are listed in Table 7.5.

TABLE 7.1: PREVALENCE OF OHT AND POAG

OHT POAGAge Males Females Males Females

0-4 0% 0% 0.0% 0.0%

5-9 0% 0% 0.0% 0.0%

10-14 0% 0% 0.0% 0.0%

15-19 0% 0% 0.0% 0.0%

20-24 0% 0% 0.0% 0.0%

25-29 0% 0% 0.0% 0.0%

30-34 0.00% 0.00% 0.00% 0.0%

35-39 0.02% 0.02% 0.00% 0.00%

40-44 0.08% 0.08% 0.07% 0.07%

45-49 0.15% 0.15% 0.14% 0.14%

50-54 0.23% 0.23% 0.60% 0.60%

55-59 0.30% 0.30% 0.94% 0.94%

60-64 0.35% 0.35% 2.29% 2.29%

65-69 0.39% 0.39% 3.46% 3.46%

70-74 0.44% 0.44% 5.51% 5.51%

75-79 0.49% 0.49% 5.78% 5.78%

80-84 0.49% 0.49% 6.74% 6.74%

85-89 0.49% 0.49% 9.66% 9.66%

90+ 0.49% 0.49% 20.66% 20.66%

Source: BMES and MVIP data

7. Summary of Model Parameters


Main heading to go here7. Summary of Model Parameters

TABLE 7.2: SEVERITY OF VISUAL IMPAIRMENT — INITIAL PROPORTIONAL SPLIT

Age EDS Mild Moderate Severe

0-4 0% 0% 0% 0%

5-9 0% 0% 0% 0%

10-14 0% 0% 0% 0%

15-19 0% 0% 0% 0%

20-24 0% 0% 0% 0%

25-29 0% 0% 0% 0%

30-34 0% 0% 0% 0%

35-39 0% 0% 0% 0%

40-44 100.0% 0.0% 0.0% 0.0%

45-49 100.0% 0.0% 0.0% 0.0%

50-54 100.0% 0.0% 0.0% 0.0%

55-59 100.0% 0.0% 0.0% 0.0%

60-64 95.1% 0.2% 1.7% 2.9%

65-69 94.3% 0.4% 2.8% 2.6%

70-74 92.5% 0.5% 3.7% 3.3%

75-79 88.6% 1.2% 8.4% 1.8%

80-84 84.4% 1.7% 11.5% 2.5%

85-89 78.0% 2.2% 15.1% 4.8%

90+ 70.6% 1.1% 7.7% 20.6%

Source: BMES and MVIP data

TABLE 7.3: MODELLED TREATMENT ASSUMPTIONS

Treatment efficacy Compliance Treatment Incidence (reduction in and failure rates progression of visual impairment)

Medication 50% Inherent in the data See Table 5.5 and calculation (total costs of medications for POAG in 2005 divided by prevalence of diagnosed POAG)

Trabeculoplasty 50% 100% 50% of patients fail each year

Trabeculectomy 50%# 100% 50% of patients fail each year

#Based on equivalence between medication and trabeculectomy demonstrated in CIGTS.


7. Summary of Model Parameters

TABLE 7.4: MODELLED TREATMENT COSTS $ 2005

(INCLUDING SIDE-EFFECTS AND ADVERSE EVENTS)

Medication (a) Trabeculoplasty (b) Trabeculectomy (c) Male Female Male Female

40-44 964.58 967.45 724.35 4122.50 4122.50

45-49 972.82 973.42 724.35 4122.50 4122.50

50-54 972.82 973.42 724.35 4122.50 4122.50

55-59 1023.46 1009.71 724.35 4122.58 4122.58

60-64 1023.46 1009.71 724.35 4122.51 4122.51

65-69 1152.08 1086.79 724.35 4122.72 4122.73

70-74 1152.08 1086.79 724.35 4123.47 4123.51

75-79 1309.53 1131.53 724.35 4126.31 4126.55

80-84 1309.53 1131.53 724.35 4131.33 4131.88

85-89 1375.39 1143.02 724.35 4136.77 4131.47

90+ 1375.39 1143.02 724.35 4147.35 4138.12

Calculation of these estimates is explained in Section 6.3.2. a) Cost of anti-glaucoma medications plus the costs ofthe risk of COPD. b) Cost of trabeculoplasty adjusted upwards by 1.5 to account for people who have a second lasertreatment. c) Trabeculectomy adjusted upwards by 1.2 to account for people who have a second trabeculectomy andalso adjusted upwards in the older age groups to account for the increasing risk of cataract surgery as a side effect.

TABLE 7.5: OTHER MODELLED VARIABLES

Item Reference

Disability weights Table 6.1, page 59

Health System Costs Page 60

Aged Care Table 6.6, page 63

Accidental Falls Table 6.9, Table 6.10 and Table 6.11, pages 65 to 66

Depression Table 6.13 and Table 6.14, pages 67 to 68

Employment Page 66

Other Indirect Costs Table 6.15, page 69

Deadweight losses Page 69

Other indirect costs include formal care, lost productivity of carers, aids and modifications and other expenses.


8. The Model

The model was built in Microsoft Office Excel 2003 which ensures portability. The model canbe navigated by clicking on the relevant button on the Main Menu (see Figure 8.1) or by clickingon the sheet tabs at the bottom of the window. In order to access and view the sheets with theparameters and the model’s workings, click the Show/Hide Parameter Sheets button.

Prevalence rates are assumed to be the number of people with the disease at the start of theyear. During the year people are treated, progress, or die, with the impacts of these pathways onprevalence rates occurring at the start of the following year (see Figure 8.3 for a diagram of themodel’s logical structure).

To select scenarios, click on the User Options sheet button (see Figure 8.2). To view output, clickthe Cost-effectiveness Analysis, PopChart, CostChart or CE-PlaneChart buttons.

FIGURE 8.1: MAIN MENU

Cost effectiveness analysis can be conducted comparing various scenarios with the base case.To set the base case, tick the “No new intervention (Standard treatment)” box on theOptions sheet.

Three treatment phases are modelled, consistent with the current treatment regimen:medication, laser (trabeculoplasty) and surgery (trabeculectomy). The order in which thesetreatments is applied can be switched in the “Select intervention” and “Select interventiondetail” windows on the options sheet.


8. The Model

fIGURE 8.2: OPTIONS ShEETCost effectiveness analysis can be

conducted by running various scenarios of

current treatment and comparing with

the base case.


72

FIGURE 8-2: OPTIONS SHEET



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The model has been adapted so that users can test the economic impact of changes to currenttreatment patterns. The scenarios are as follows:

• the base case (No new intervention (standard treatment));

• an increase in the rate at which POAG is diagnosed (to 70%, 80% or 90%);

• a change in the treatment protocol (using laser trabeculoplasty as the primary treatmentinstead of medication, with medication becoming the second treatment phase and surgerythe third phase);

• research to delay progression (by 50% or 75%); and

• combination scenarios — an increase in the rate at which POAG is diagnosed from 50% to80% together with:

- A change in the treatment protocol; or

- The introduction of a new treatment to delay progression by a further 50%.

9.1: THE BASE CASE

The base case scenario can be set to either the current situation (no new intervention/standardtreatment) or an other intervention which can be chosen using the “Select intervention” and“Select intervention detail” from the “Options” sheet.

9.1.1: TO RUN A BASE CASE …

To select the current situation (No new intervention (Standard treatment)) as the base case for comparison:

• tick the “No new intervention (Standard treatment)” box on the “Options” sheet (note: it willtake a little while to reset all the parameters to reflect the current situation).

• Select frequency every year.

• click the “Set as Base Case” button.

In brief, the base case parameters are: a POAG diagnosis rate of 50%, treatment regimen ofmedication first, followed by laser and then finally by surgery, and an impact of treatment(treatment efficacy) of a 50% reduction in the progression of visual impairment. The previouschapters explain the base case in more detail.

If you wish to chose another scenario as the base case (for example, increased diagnosis rates),you must first un-tick the “No new intervention (Standard treatment)” box. Then choose anintervention from the “Select Intervention” box and the “Select Intervention Detail” box.Then click the “Set as Base Case” button.

9.1.2: RESULTS

If current standard treatments continue for the next 20 years, and no new intervention scenariosare applied:

• the prevalence of OHT in Australia will increase from 26,000 people in 2005, to 41,000people in 2025;

• the prevalence of POAG in Australia will increase over the same period from 208,000 people to 379,000; and

9. Intervention Scenarios



• the prevalence of visual impairment from POAG in Australia is expected to grow from 24,000 people in 2005 to 52,000 people in 2025 (Table 9.1).

The prevalence estimates here vary somewhat from those in Clear Insight, (CERA 2004) thatused age and gender specific prevalence rates from the MVIP and BMES, with visual impairmentbased on loss of VA. This analysis also uses data from the combined MVIP/BMES data set,but for persons rather than by gender, and measuring visual impairment measured using acombination of VA and VF.

Figure 9.1 shows a steady increase in the prevalence of POAG from 2005 and 2025, driven by anageing population.

TABLE 9.1: PREVALENCE OF OHT AND POAG, BASE CASE (NUMBER OF PEOPLE)

2005 2025

OHT 25,986 40,004

POAG

Early stage 183,530 326,659

Mild stage 1,872 3,667

Moderate stage 12,914 26,047

Severe stage 9,312 22,613

POAG (all stages) 207,628 378,985

Visual Impairment from POAG 24,098 52,327

Prevalence (Total OHT & POAG) 233,614 419,989

Source: Access Economics/CERA dynamic model

FIGURE 9.1: PREVALENCE OHT AND POAG, BASE CASE

The health system costs of glaucoma in 2005 were $355 million and the total annual cost ofglaucoma in 2005 was $1.9 billion. In real dollar terms, these costs are expected to increase to$784 million and $4.3 billion respectively by 2025 (Table 9.2). The net present value of DALYsand other costs of POAG are depicted in Table 9.3.

The total cost of glaucoma will increase in 2005 to $1.92 billion, and $4.3 billion in 2025.


Prevalence (diagnosed and undiagnosed)


TABLE 9.2: COSTS OF POAG, 2005 AND 2025, BASE CASE

2005 2025

DALYs 6,940 15,592

YLD 6,678 15,184

YLL 262 408

Burden of Disease Costs ($) 1,043,713,812 2,325,613,694

Health System Costs ($) 355,121,086 783,978,738

Comorbid Health Costs ($) 166,419,635 423,192,582

Treatment Costs ($) 188,701,450 360,786,156

Productivity Costs ($) 60,406,596 130,614,278

Other Indirect Costs ($) 109,422,685 240,987,552

Total Costs ($) 1,923,785,265 4,265,173,000

TABLE 9.3: BASE CASE (STANDARD TREATMENT) NET PRESENT VALUE OF DALYS AND COSTS

Net present value 2005 to 2025

DALYs 155,150

Burden of Disease Costs ($ million) 23,896

Health System Costs ($ million) 8,759

Comorbid Health Costs ($million) 4,505

Treatment Costs ($million) 4,254

Productivity Costs ($ million) 1,665

Other Indirect Costs ($million) 2,695

Total Costs ($million) 37,015

The value of the burden of disease due to POAG over time is depicted in Figure 9.2.

FIGURE 9.2: VALUE OF BURDEN OF DISEASE DUE TO POAG ($M), BASE CASE

Sensitivity analysis — zero prevalence and incidence of OHT among those aged 80 and over


Over half the costs of glaucoma relate to

loss of well being.

0

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2005 2010 2015 2020 2025

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9.1.3: SENSITIVITY ANALYSIS — ZERO PREVALENCE AND INCIDENCE Of OhT AMONG

ThOSE AGED 80 AND OVER

Asnotedearlier,prevalencedataweresmoothedinpartbecauseofthesmallsamplesizesintheoriginaldataset.UnsmoothedoriginaldatashowedzeroprevalenceratesforOHTamongthoseaged80yearsorover.TheimpactofusingsmoothedratherthanoriginaldataispresentedinTable9.4andTable9.5.ThetotalcostsofPOAGareslightlylower(Table9.5).

TABLE 9.4: COMPARISON Of PREVALENCE Of OhT AND POAG WITh ORIGINAL AND

SMOOThED DATA

Original OhT prevalence Smoothed OhT data (Zero OhT prevalence prevalence data and incidence for those aged 80 years or over)

�00� �0�� 00� �0��

PrevalenceOHTandPOAG 227,827 406,840 233,614 419,989

PrevOHT 23,684 36,340 25,986 41,004

PrevearlystagePOAG 180,149 318,477 183,530 326,659

PrevMildPOAG 1,826 3,550 1,872 3,667

PrevModeratePOAG 12,871 25,918 12,914 26,047

PrevSeverePOAG 9,297 22,555 9,312 22,613

TABLE 9.5: NET PRESENT VALUE Of DALYS AND COSTS, SENSITIVITY ANALYSIS ON OhT

PREVALENCE AND INCIDENCE fOR ThOSE AGED 80+ YEARS

Net present value Net present value 2005 to 2025 2005 to 2025

Zero OhT prevalence and Smoothed data incidence for those aged 80 years or over

DALYs 154,656 155,150

BurdenofDiseaseCosts($million) 23,836 23,896

HealthSystemCosts($million) 8,636 8,759

ComorbidHealthCosts($million) 4,474 4,505

TreatmentCosts($million) 4,162 4,254

ProductivityCosts($million) 1,660 1,665

OtherIndirectCosts($million) 2,666 2,695

TotalCosts($million) 36,798 37,015


�.�:IMPROVEDDIAGNOSISRATE

Morethan50%ofthoseindevelopedcountrieswithglaucomaareunawaretheyhavethedisease(Quigley,1996).Inapopulationbasedstudy(theMVIP),Wensoretal,(1998)foundthat50%ofthosewithdefinitePOAGhadnotbeendiagnosedpreviously,andWongetal,(2004)examinedthepresenceofundiagnosedOAGinpeoplewhohadvisitedaneyecareproviderinthepreviousyearusingVisualImpairmentProjectdatafromMelbourneandruralcommunitiesinVictoria.Theyfoundthat81%ofpossiblecases,72%ofprobablecasesand59%ofdefinitecasesofOAGwerepreviouslyundiagnosed.Ofthe115participantswithprobableordefiniteOAG,72(63%)werepreviouslyundiagnosed.Oftheseundiagnosedprobableanddefinitecases,35(49%)hadvisitedaneyecareproviderwithintheprevious12monthperiod.The35undiagnosedpatientswerecomparedwith43diagnosedpatientswhohadvisitedanoptometristorophthalmologistorbothintheprevious12months.Thetypeofeyeprofessionalseen,andthepresenceofVFdefectsweretheonlystatisticallysignificantvariablesbetweenthediagnosedandundiagnosedglaucomagroups.

DiagnosisratesforPOAGcouldbeimprovedby:

1) atthecurrentdiagnosisthreshold,enhancingthequalityofcarebyensuringophthalmologistsincludetheappropriateVFtestswhenexaminingpatients’eyes;

2) carefulexaminationoftheopticdiscinallpatientsregardlessofIOP;and

3) improvingthefocusonfamilyhistorysincepeoplewithafamilyhistoryofglaucomahaveahigherchanceofdevelopingPOAG.

Underthebasecasescenario,50%ofpeoplewithPOAGarediagnosedandtreated.Underthisscenario,theimpactofincreasingtheproportionofpeoplediagnosedwithPOAGto(i)70%,(ii)80%and(iii)90%canbeassessed.Nocostshavebeenaddedtothemodeltoallowforeducationofclinicians.

Underthisscenariotheonlyparameterthatisvariedistherateatwhichpeoplearediagnosed.ThecostsandbenefitsthatresultfromthisanalysisreflectmorepeoplereceivingtreatmenttoslowprogressionofPOAG.

9.2.1: TO RUN ThIS INTERVENTION ThROUGh ThE MODEL …

• Tickthe“NonewIntervention(Standardtreatment)”boxandclickonthe“SetasBaseCase”buttontoensurethecurrentsituationisthecomparator.

• Un-tickthe“NonewIntervention(Standardtreatment)”boxandmakesurethatthe“Frequency–EveryYear”boxisticked.

• OntheOptionssheet,choose“ImprovedDiagnosisRate”intheSelectInterventionboxand“DiagnosisRate70%”,or“DiagnosisRate80%”,or“DiagnosisRate90%”intheSelectInterventionDetailbox.

• Thenclickthe“SetasScenario1”button,torunthenewscenario.

• Asecondscenariocanbeevaluatedbyreselectingfromthe“SelectIntervention”and“SelectInterventionDetail”windows.Thenclickthe“SetasScenario2”button,torunthenewscenario.

• ClickCompareScenarios(CEA).


At present, 50% of people with POAG are

undiagnosed.




9.2.2: RESULTS

Inthebasecase,50%ofpeoplewithPOAGarediagnosed.TheresultsofincreasingtherateofdiagnosisarepresentedinTable96.Theestimatesinthetablereflectthenetpresentvalueofcostsandbenefitsovertheentireperiod(2005to2025).Incomparisonwiththebasecase,theincreaseddiagnosisratereducesthetotalnumberofDALYs(Table96)asmorepeoplereceivebeneficialtreatment,however,thismeansthattreatmentcostsrise.Productivitycostsandcomorbidhealthcostsarelessthanforthebasecasebecauseagreaterproportionofpeoplereceivetreatmentwhichslowdiseaseprogression—allowingthemtospendmoretimeinemployment,andtoavoidcomorbidconditionssuchasdepression,fallsandfracturesassociatedwiththelaterstagesofglaucoma.

TABLE 9.6: MODEL RESULTS – INCREASED DIAGNOSIS RATE, NET PRESENT VALUE 2005 TO 2025

Net Present Values, Base Case 2005 to 2025 (Standard Diagnosis rate Diagnosis rate Diagnosis rate treatment) 70% 80% 90%

DALYs 155,150 146,141 142,248 138,702

BurdenofDiseaseCosts($m) 23,896 22,249 21,529 20,866

HealthSystemCosts($m) 8,759 10,091 10,747 11,400

ComorbidHealthCosts($m) 4,505 4,403 4,354 4,307

TreatmentCosts($m) 4,254 5,687 6,393 7,093

ProductivityCosts($m) 1,665 1,514 1,443 1,373

OtherIndirectCosts($m) 2,695 2,894 2,993 3,092

TotalCosts($m) 37,015 36,748 36,711 36,731

CEratio:Returnon$�spent(a) $�.�� $�.�� $�.�0

$/DALYavoided(b) $��,�� $��,�0� $��,��

(a)CEratioisthechangeintotaldiseasecostsdividedbythechangeintreatmentcosts.(b)$/DALYavoidedisthechangeinhealthsystem,productivityandotherindirectcostsdividedbythedifferenceinDALYs.

Figure9.3showstheoutcomeofadiagnosisrateof70%and90%.Inthebasecase,DALYsriseto15,600in2025(Table9.2).Withimproveddiagnosis,theburdenofdiseaseislowerin2025thaninthebasecase—14,300DALYs(70%diagnosed)and13,200DALYs(90%)diagnosedin2025(Figure9.3).However,withhigherdiagnosisrates,treatmentcostsarealsohigherthaninthebasecase(Figure9.4).



fIGURE 9.3: IMPACT Of INCREASED DIAGNOSIS RATES ON DALYS(A)

fIGURE 9.4: IMPACTS Of INCREASED DIAGNOSIS RATES ON TREATMENT COSTS

TherelativecosteffectivenessofeachscenarioisdepictedinFigure9.5.Thebasecaseisrepresentedattheorigin.EffectivenessismeasuredasthetotalnumberofDALYsavoidedandcostsaretotalcosts(excludingthevalueoftheburdenofdisease).

• Atzeroadditionalcosts(ie.noadditionalcostsofeducatingcliniciansinordertoimprovediagnosisrates),improveddiagnosisratesfrom50%to70%,80%and90%,are costeffective at between $153,000 and $167,000 per DALY avoided.

• Ifeducatingclinicianswerecostly,thesescenarioswouldbecomelesscosteffective.


80

diagnosed in 2025 (Figure 9-3). However, with higher diagnosis rates, treatment costs are

also higher than in the base case (Figure 9-4).

FIGURE 9-3: IMPACT OF INCREASED DIAGNOSIS RATES ON DALYS(A)

DALYs

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

2005 2010 2015 2020 2025

Base Case (Standard treatment)

Diagnosis rate 70%

Diagnosis rate 90%

FIGURE 9-4: IMPACTS OF INCREASED DIAGNOSIS RATES ON TREATMENT COSTS

Treatment Costs

0

100,000,000

200,000,000

300,000,000

400,000,000

500,000,000

600,000,000

700,000,000

2005 2010 2015 2020 2025


Diagnosis rate 70%

Diagnosis rate 90%

The relative cost effectiveness of each scenario is depicted in Figure 9-5. The base case is

represented at the origin. Effectiveness is measured as the total number of DALYs avoided

and costs are total costs (excluding the value of the burden of disease).

At zero additional costs (ie. no additional costs of educating clinicians in order to improve

diagnosis rates), improved diagnosis rates from 50% to 70%, 80% and 90%, are costeffective at between $153,000 and $167,000 per DALY avoided.

If educating clinicians were costly, these scenarios would become less cost effective.


80

diagnosed in 2025 (Figure 9-3). However, with higher diagnosis rates, treatment costs are

also higher than in the base case (Figure 9-4).

FIGURE 9-3: IMPACT OF INCREASED DIAGNOSIS RATES ON DALYS(A)

DALYs

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

2005 2010 2015 2020 2025


Diagnosis rate 70%

Diagnosis rate 90%

FIGURE 9-4: IMPACTS OF INCREASED DIAGNOSIS RATES ON TREATMENT COSTS

Treatment Costs

0

100,000,000

200,000,000

300,000,000

400,000,000

500,000,000

600,000,000

700,000,000

2005 2010 2015 2020 2025


Diagnosis rate 70%

Diagnosis rate 90%

The relative cost effectiveness of each scenario is depicted in Figure 9-5. The base case is

represented at the origin. Effectiveness is measured as the total number of DALYs avoided

and costs are total costs (excluding the value of the burden of disease).

At zero additional costs (ie. no additional costs of educating clinicians in order to improve

diagnosis rates), improved diagnosis rates from 50% to 70%, 80% and 90%, are costeffective at between $153,000 and $167,000 per DALY avoided.

If educating clinicians were costly, these scenarios would become less cost effective.

Increasing the diagnosis rate to 80% would cost $160,000/DALY.




fIGURE 9.5: COST EffECTIVENESS PLANE – INCREASE DIAGNOSIS RATE(A)

(a)EffectivenessmeasuredasDALYsavoided.Costsreflecthealthsystem,productivityandotherindirectcosts.(CosteffectivenessismeasuredasthecostperDALYavoided.ThevalueoftheburdenofdiseaseisexcludedfromthecostestimateinthenumeratorsincethisisrepresentedbyDALYsavoidedinthedenominator).

�.�:CHANGEINTHETREATMENTPROTOCOL(PRIMARYLASER)

Asnotedabove,inbrief,thebasecaseparametersare:aPOAGdiagnosisrateof50%,treatmentregimenofmedicationfirst,followedbylaserandthenfinallybysurgery,failureratesformedicationof4.3%ofpatientsperannum,50%forlasertrabeculoplastyand50%fortrabeculectomy,andanoverallimpactoftreatmentonvision(treatmentefficacy)ofa50%reductionintheprogressionofvisualimpairment.Underthisscenario—“Changeinthetreatmentprotocol”—laserreplacestopicalmedicationasfirstlinetherapyfrom2005onwardssothatpatientsbegintreatmentwithalasertrabeculoplasty,thenfollowwithmedicationandfinallytrabeculectomy.

Treatmentcost-savingsarepossiblefromthisscenario,asmedicationisnolongerrequiredincombinationwithlasertreatment.Underthebasecase,ontheotherhand,wherelaserissecondlinetherapy,itiscombinedwithmedication.

TheGLT(whichcomparedtwo180degreeALTtreatmentswithtimolol)showedthatALTwasatleastasefficaciousasmedicationasaninitialtreatmentforglaucoma(GlaucomaLaserTrialResearchGroup,1995).However,ALTwasnotcommonlyadoptedasaprimarytreatmentbecauseofconcernaboutsideeffectsandthereducedefficacyofrepeatALTtreatments.Inaddition,atthetimeoftheGLT,prostaglandinswerenotinuseastopicalmedicationsforglaucoma(asMcIlraithetal,(2006)noted).Evidencefortheeffectivenessoflasertreatmentsasaprimarytherapyinclude:

• TheEMGT,arandomisedclinicaltrialcomparingALTandmedicationwithnotreatment,foundthat,whenadjustedforcensoringandothercovariates,progressionriskwashalvedbytreatment.After6years,theHRwas0.5(95%CI0.35to0.71).

• Nagaretal,2005,whoconductedarandomisedprospectivestudycomparing360degreeselectivelasertherapy(SLT)with0.005%latanoprostatnight,foundnodifferencesinmeanVFdefectsbetweengroupsafter12months.

• McIlraithetal,2006,inanon-randomisedpilotstudyof100eyesnewlydiagnosedPOAGandOHTin61patients,andcomparing180degreeSLTwithlatanoprost,foundthatthetwotreatmentswereequallyefficaciousinreducingIOPinover12months.

Commercial-in-Confidence Economic impact of primary open angle glaucoma

81

FIGURE 9-5: COST EFFECTIVENESS PLANE – INCREASE DIAGNOSIS RATE(A)

Diagnosis rate 70%

Diagnosis rate 90%

0

500,000,000

1,000,000,000

1,500,000,000

2,000,000,000

2,500,000,000

3,000,000,000

0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 18,000

Effectiveness

Co

sts

(a) Effectiveness measured as DALYs avoided. Costs reflect health system, productivity and other indirect costs.

(Cost effectiveness is measured as the cost per DALY avoided. The value of the burden of disease is excludedfrom the cost estimate in the numerator since this is represented by DALYs avoided in the denominator).

9.3 CHANGE IN THE TREATMENT PROTOCOL (PRIMARYLASER)

As noted above, in brief, the base case parameters are: a POAG diagnosis rate of 50%,

treatment regimen of medication first, followed by laser and then finally by surgery, failurerates for medication of 4.3% of patients per annum, 50% for laser trabeculoplasty and 50% for

trabeculectomy, and an overall impact of treatment on vision (treatment efficacy) of a 50%

reduction in the progression of visual impairment. Under this scenario — “Change in thetreatment protocol” — laser replaces topical medication as first line therapy from 2005

onwards so that patients begin treatment with a laser trabeculoplasty, then follow with

medication and finally trabeculectomy.

Treatment cost-savings are possible from this scenario, as medication is no longer required incombination with laser treatment. Under the base case, on the other hand, where laser is

second line therapy, it is combined with medication.

The GLT (which compared two 180 degree ALT treatments with timolol) showed that ALT wasat least as efficacious as medication as an initial treatment for glaucoma (Glaucoma Laser

Trial Research Group, 1995). However, ALT was not commonly adopted as a primary

treatment because of concern about side effects and the reduced efficacy of repeat ALT

treatments. In addition, at the time of the GLT, prostaglandins were not in use as topicalmedications for glaucoma (as McIlraith et al, (2006) noted). Evidence for the effectiveness of

laser treatments as a primary therapy include:

The EMGT, a randomised clinical trial comparing ALT and medication with no treatment,found that, when adjusted for censoring and other covariates, progression risk was

halved by treatment. After 6 years, the HR was 0.5 (95% CI 0.35 to 0.71).

Nagar et al, 2005, who conducted a randomised prospective study comparing 360degree selective laser therapy (SLT) with 0.005% latanoprost at night, found no

differences in mean VF defects between groups after 12 months.



• Sanfilippo(1999)citedresearchsuggestingALTwasmoreefficaciousthatpilocarpine.TwoyearsuccessrateswhenassessingIOPwere63%and44%fortheALTandpilocarpinegroupsrespectively.ItwasfoundthatALTgaveasignificantlybetterpreservationoftheVFthanpilocarpine.Throughregressionanalysisthe‘timelefttoblindness’fortheALTgroupwas31yearsandforthepilocarpine-treatedgroup,12years(assumingalineardecay)(SanfilippoP,1999).


• Toensureyoustartwitha“blankpage”,ontheOptionssheet,clickthescenarioresetbuttons.• Tickthe“Nonewintervention(Standardtreatment)”box• Selectfrequencyeveryyear• clickonthe“SetasBaseCase”button(sothatstandardtreatmentisthecomparator).• Un-tickthe“Nonewintervention(Standardtreatment)”box.• Makesurethatthe“Frequency–EveryYear”boxisticked.• OntheOptionssheets,choose“ChangeTreatmentProtocol”intheSelectInterventionbox

and“Primarylasertrabeculoplasty”intheSelectInterventionDetailbox.Thenclickthe“SetasScenario1”button,torunthenewscenario.


9.3.2: RESULTS

TheresultsarepresentedinTable9.7.Thechangeintreatmentprotocoliscost-saving(consistentwiththehypothesisabove).Thereislittleimpactontheresultsifthecostoflaseristripledorincreasesfivefoldtoaccountforthecostofsideeffects(assumingthesecanbefixedrelativelyquicklysothereisnoimpactonthepatient’squalityoflife)(Table9.7).

Figure9.6showsthatthecost-savingsassociatedwiththenewprotocolincreaseovertimeasmorepeoplearediagnosedandtreatedforPOAGbecauseofpopulationageing.TheburdenofdiseaseisdepictedinFigure9.7.

TABLE 9.7: MODEL RESULTS – PROTOCOL ChANGE – TRABECULOPLASTY AS PRIMARY TREATMENT

Net Present Standard Primary Standard Primary Standard Primary Values Laser treatment treatment Laser treatment Laser ($724) ($2,173) ($3,622)

DALYs 155,150 155,974 155,150 155,974 155,150 155,974

BurdenofDisease 23,896 24,095 23,877 24,070 23,858 24,046Costs($m)

HealthSystem 8,759 8,392 8,865 8,548 8,971 8,703Costs($m)

ComorbidHealth 4,505 4,519 4,505 4,519 4,505 4,519 Costs($m)

TreatmentCosts($m) 4,254 3,873 4,360 4,029 4,465 4,184

ProductivityCosts($m) 1,665 1,671 1,665 1,671 1,665 1,671

OtherIndirectCosts($m) 2,695 2,628 2,715 2,658 2,736 2,689

TotalCosts($m) 37,015 36,787 37,122 36,948 37,230 37,109

CEratio:Returnon $0.�0 $0.�� $0.�� $�spent(a) Cost- Cost- Cost- $/DALYavoided Saving Saving Saving

(a)Definedasthedifferenceinindirectcostsbetweenprimarylaserandthebasecaseforeveryadditionaldollarspentontreatment.




fIGURE 9.6: COST-SAVINGS RESULTING fROM A PROTOCOL ChANGE(A)

(a)Lasercosting$724pertreatment.

fIGURE 9.7: BURDEN Of DISEASE


84

FIGURE 9-7 BURDEN OF DISEASE

DALYs

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

2005 2010 2015 2020 2025


Primary laser trabeculoplasty

Scenario 2

9.3.3 SENSITIVITY ANALYSIS— THE IMPACT OF THE CONSERVATIVE

APPROACH TO SURGERY FAILURE RATES

Taking a conservative approach to the surgery failure rate doesn’t substantively affect theresults because treatment efficacy is measured according to whether a patient is treated or not

rather than the particular treatment the patient receives. In other words, all treated patients

(no matter what order they receive treatments) experience a reduction in progression of visualimpairment by 50% compared with people who have undiagnosed POAG. Taking a

conservative approach to the surgery failure rate means that more patients progress more

quickly to medications — bringing forward the costs of medications for those patients andleading to higher health system cost estimates (Table 9-8) . Repeat surgery may also be

performed. Based on MBS data surgery is performed at a rate of 1.2 and costs have been

factored accordingly.


83

TABLE 9-7: MODEL RESULTS – PROTOCOL CHANGE — TRABECULOPLASTY AS PRIMARY

TREATMENT

Net PresentValues

Standardtreatment

PrimaryLaser($724)

Standardtreatment

PrimaryLaser

($2,173)

Standardtreatment

PrimaryLaser

($3,622)

DALYs 155,150 155,974 155,150 155,974 155,150 155,974

Burden ofDiseaseCosts ($m) 23,896 24,095 23,877 24,070 23,858 24,046

HealthSystemCosts ($m) 8,759 8,392 8,865 8,548 8,971 8,703

ComorbidHealth Costs($m) 4,505 4,519 4,505 4,519 4,505 4,519

TreatmentCosts ($m) 4,254 3,873 4,360 4,029 4,465 4,184

ProductivityCosts ($m) 1,665 1,671 1,665 1,671 1,665 1,671

Other IndirectCosts ($m) 2,695 2,628 2,715 2,658 2,736 2,689

Total Costs($m) 37,015 36,787 37,122 36,948 37,230 37,109

CE ratio:Return on $1spent(a) $0.40 $0.47 $0.57

$/DALYavoided

Cost-Saving

Cost-Saving

Cost-Saving

(a) Defined as the difference in indirect costs between primary laser and the base case for every additional dollarspent on treatment.

FIGURE 9-6: COST-SAVINGS RESULTING FROM A PROTOCOL CHANGE(A)

Treatment Costs

0

50,000,000

100,000,000

150,000,000

200,000,000

250,000,000

300,000,000

350,000,000

400,000,000

2005 2010 2015 2020 2025


Primary laser trabeculoplasty

Scenario 2

(a) Laser costing $724 per treatment.

Laser trabeculoplasty actually saves money when used as the initial treatment.



9.3.3: SENSITIVITY ANALYSIS — ThE IMPACT Of ThE CONSERVATIVE APPROACh

TO SURGERY fAILURE RATES

Takingaconservativeapproachtothesurgeryfailureratedoesn’tsubstantivelyaffecttheresultsbecausetreatmentefficacyismeasuredaccordingtowhetherapatientistreatedornotratherthantheparticulartreatmentthepatientreceives.Inotherwords,alltreatedpatients(nomatterwhatordertheyreceivetreatments)experienceareductioninprogressionofvisualimpairmentby50%comparedwithpeoplewhohaveundiagnosedPOAG.Takingaconservativeapproachtothesurgeryfailureratemeansthatmorepatientsprogressmorequicklytomedications—bringingforwardthecostsofmedicationsforthosepatientsandleadingtohigherhealthsystemcostestimates(Table9.8).Repeatsurgerymayalsobeperformed.BasedonMBSdatasurgeryisperformedatarateof1.2andcostshavebeenfactoredaccordingly.

TABLE 9.8: SENSITIVITY ANALYSIS — A CONSERVATIVE APPROACh TO SURGERY

fAILURE RATES

Net Present Standard Primary Laser Standard Primary Laser Values treatment ($724) treatment ($724)

Laser failure rate 50%, Laser failure rate 50%, surgery failure rate 50% surgery failure rate 10%

DALYs 155,150 155,974 155,150 155,974

BurdenofDiseaseCosts($m) 23,896 24,095 23,950 24,144

HealthSystemCosts($m) 8,759 8,392 8,468 8,128

ComorbidHealthCosts($m) 4,505 4,519 4,505 4,519

TreatmentCosts($m) 4,254 3,873 3,963 3,609

ProductivityCosts($m) 1,665 1,671 1,665 1,671

OtherIndirectCosts($m) 2,695 2,628 2,638 2,576

TotalCosts($m) 37,015 36,787 36,721 36,520

CEratio:Returnon$�spent(a) $0.�0 $0.��

$/DALYavoided Cost-Saving Cost-Saving

(a)Definedasthedifferenceinindirectcostsbetweenprimarylaserandthebasecaseforeveryadditionaldollarspentontreatment.




�.�:RESEARCHANDDEVELOPMENT

ThisscenariolooksatthepossiblereturnsfromnewtreatmentsthatmightbedevelopedtofurtherslowtheprogressionofPOAG.OnepossibleexamplecurrentlyunderinvestigationmightbeneuroprotectionwiththedrugMemantine(anNMDA22-receptorantagonistcurrentlyusedforAlzheimersdisease).MemantineiscurrentlyinphaseIIItrialsforglaucomaandatthetimeofwritingtreatmentefficacyresultswerenotavailable.

Themodelallowsfortwopossiblenewtreatmentefficacyoptions—thenewtherapyreducestheprogressionofglaucomabyafurther50%or75%overandabovethereductioninprogressionfromcurrenttreatments.ItisassumedthatthehypotheticaltreatmentisgiventoeachpersonbeingtreatedforPOAG,regardlessoftheirtreatmentstage.The new therapy is taken continuously over the patient’s remaining life. Thetreatmentisaddedtocurrenttreatmentsratherthansubstitutingforthem.Inthismodel,theannualcostperpersonforthistreatmenthasbeensetat$1,000regardlessofefficacy.


• Toensureyoustartwitha“blankpage”,ontheOptionssheet,clicktheresetbuttons.

• OntheOptionssheets,choose“ResearchandDevelopment”intheSelectInterventionboxand“R&DReducesProgression(50%)”,or“R&DReducesProgression(75%)”.

• Tickthe“NonewIntervention(StandardTreatment)”boxandclickonthe“SetasBaseCase”buttontosetthecurrentsituationasthebasecomparator.

• Un-tickthe“NonewIntervention(StandardTreatment)”boxandmakesurethatthe“Frequency–EveryYear”boxisticked.Thenclickthe“SetasScenario1”button,torunthenewscenario.


9.4.2: RESULTS

Theresultsofintroducingtwonewtherapiesthatreduceprogressionby50%andby75%overthebasecasearepresentedinTable9.8.Comparedwiththebasecase,thenetpresentvalueofDALYs,productivitycostsandcomorbidcostsarelower.Theresultsreflectthebenefitsofdelayingprogression,allowingpeopletoremaininwork,andexperiencefewercomorbidconditionsthatareassociatedwiththelaterstagesofglaucoma.ThedeclineinDALYsovertimeassociatedwithdelayingprogressionby50%and75%overthebasecaseisdepictedinFigure9.8.

22N-methyl-D-aspartate

The impact of new treatments to reduce progression was examined.



Treatments with annual costs over

$5000 are expensive but cost effective.

fIGURE 9.8: DECLINE IN DALYS fROM NEW EffICACIOUS TREATMENT

Healthsystemcostsontheotherhandarehigherwiththenewtreatmentbecausethetreatmentisaddedtocurrentlyavailabletherapies(Figure9.9).

fIGURE 9.9: TREATMENT COSTS WITh NEW TREATMENTS COSTING $1000 PER PERSON PER YEAR

Overall,costeffectivenessdependsonthecostperpersonperannumofthenewtreatment(Table9.8).Attreatmentcostsof$1,000perpersonperannum,newtreatmentsarecostsaving.However,ifthenewtreatmentsthatdelayprogressionby50%overthebasecasecostmorethan$5,000perpersonperannum,theywouldbecomerelativelyexpensive(costeffectivenessratiosofbeyond$60,000perDALYavoided).


86

Tick the “No new Intervention (Standard Treatment)” box and click on the “Set as Base

Case” button to set the current situation as the base comparator.

Un-tick the “No new Intervention (Standard Treatment)” box and make sure that the

“Frequency – Every Year” box is ticked. Then click the “Set as Scenario 1” button, to runthe new scenario.

Click Compare Scenarios (CEA).

9.4.2 RESULTS

The results of introducing two new therapies that reduce progression by 50% and by 75% overthe base case are presented in Table 9-9. Compared with the base case, the net present

value of DALYs, productivity costs and comorbid costs are lower. The results reflect the

benefits of delaying progression, allowing people to remain in work, and experience fewer

comorbid conditions that are associated with the later stages of glaucoma. The decline inDALYs over time associated with delaying progression by 50% and 75% over the base case is

depicted in Figure 9-8.

FIGURE 9-8: DECLINE IN DALYS FROM NEW EFFICACIOUS TREATMENT

DALYs

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

2005 2010 2015 2020 2025


R&D reduces progression 50%


Health system costs on the other hand are higher with the new treatment because the

treatment is added to currently available therapies (Figure 9-9).


87

FIGURE 9-9 TREATMENT COSTS WITH NEW TREATMENTS COSTING $1000 PER PERSON PER YEAR

Treatment Costs

0

50,000,000

100,000,000

150,000,000

200,000,000

250,000,000

300,000,000

350,000,000

400,000,000

450,000,000

2005 2010 2015 2020 2025




Overall, cost effectiveness depends on the cost per person per annum of the new treatment(Table 9-9). At treatment costs of $1,000 per person per annum, new treatments are costsaving. However, if the new treatments that delay progression by 50% over the base casecost more than $5,000 per person per annum, they would become relatively expensive (costeffectiveness ratios of beyond $60,000 per DALY avoided).




TABLE 9.9: MODEL RESULTS – RESEARCh AND DEVELOPMENT – ShOWING ThE IMPACT Of

NEW TREATMENT TO REDUCE PROGRESSION BY 50% AND 75%

Costofnew $�,000perperson $�,000perperson $�0,000perperson treatment perannum perannum perannum

NetPresent Base �0% ��% �0% ��% �0% ��% Values Case

DALYs 155,150 134,793 125,718 134,793 25,718 134,793 125,718 Burdenof DiseaseCosts ($m) 23,896 20,660 19,240 20,510 19,091 20,324 18,905

HealthSystem 8,759 8,843 8,773 9,793 9,729 10,980 10,924 Costs($m)

Comorbid 4,505 4,319 4,227 4,319 4,227 4,319 4,227 Health Costs($m)

Treatment 4,254 4,524 4,545 5,474 5,501 6,661 6,697 Costs($m)

Productivity 1,665 1,428 1,317 1,428 1,317 1,428 1,317 Costs($m)

OtherIndirect 2,695 2,623 2,575 2,808 2,762 3,040 2,995 Costs($m)

TotalCosts($m) 37,015 33,553 31,905 34,539 32,899 35,772 34,141

CEratio:Return $��.�� $��.�� $�.0� $�.�0 $�.�� $�.�� on$�spent

$/DALYavoided Cost- Cost- $��,��0 $��,��0 $��,�� $��,�� Saving Saving

�.�:COMBINATIONS

Thissectionexaminestheimpactofcombiningtheinterventionswemodel.Twoscenariosareavailablehere.Bothinvolveanincreaseinthediagnosisrateforglaucomafrom50%to80%,togetherwitheither:

• theadditionofanewtherapythatdelaysprogressionbyafurther50%;or

• achangeinthetreatmentprotocolsothatlaserbecomesthefirstlinetherapyinsteadofmedication.


• Toensureyoustartwitha“blankpage”,ontheOptionssheet,clicktheresetbuttons.

• OntheOptionssheets,choose“5.Combinedscenarios”intheInterventionFocusboxand“5.1Scenario1.2and4.1”,or“5.1Scenario1.2and3.1”intheInterventionDetailbox.

• Tickthe“NoIntervention(CurrentSituation)”boxandclickonthe“SetasBaseCase”buttontosetthecurrentsituationasthebasecomparator.

• Un-tickthe“NoIntervention(CurrentSituation)”boxandmakesurethatthe“Frequency–EveryYear”boxisticked.Thenclickthe“SetasScenario1”button,torunthenewscenario.

• Asecondscenariocanbeevaluatedbyreselectingfromthe“InterventionsFocus”boxaswellasthe“InterventionsDetail”box.Thenclickthe“SetasScenario2”button,torunthenewscenarios.


The combined effects of better diagnosis and laser first, or better diagnosis and a new treatment were examined.




90

FIGURE 9-10: REDUCTION IN DALYS, COMBINED INTERVENTIONS

DALYs

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

2005 2010 2015 2020 2025


Diagnosis rate 80% and R&D

reduces progression 50%

Diagnosis rate 80% and primary

laser trabeculoplasty

Treatment costs increase over time (driven by an ageing population and an increase in theproportion of people with POAG who are diagnosed from 50% in the base case to 80% in each

of the combined scenarios) (Figure 9-11). The pattern of total costs over time are shown inFigure 9-12.

FIGURE 9-11: TREATMENT COSTS, COMBINED INTERVENTIONS

Treatment Costs

0

100,000,000

200,000,000

300,000,000

400,000,000

500,000,000

600,000,000

700,000,000

2005 2010 2015 2020 2025






9.5.2: RESULTS

TheresultsofthecombinedscenariosarereflectedinTable9.10.BothscenariosreducethetotalDALYscomparedwiththebasecase(Table9.10).

TABLE 9.10: MODEL RESULTS – COMBINED SCENARIOS

Net Present Base Case Diagnosis rate Diagnosis rate Values standard 80% and 80% and treatment R&D reduces primary laser progression 50% trabeculoplasty

DALYs 155,150 121,220 149,999

BurdenofDiseaseCosts($m) 23,896 18,184 21,752

HealthSystemCosts($m) 8,759 10,921 10,156

ComorbidHealthCosts($m) 4,505 4,132 4,367

TreatmentCosts($m) 4,254 6,789 5,789

ProductivityCosts($m) 1,665 1,133 1,448

OtherIndirectCosts($m) 2,695 2,918 2,882

TotalCosts($m) 37,015 33,157 36,237

CEratio:Returnon$�spent $�.�� $�.��

$/DALYavoided $��,�0� $��,��

TheimprovementstototalDALYsincreaseoverthedurationofthemodel(Figure9.10)withtheincreasedbenefitfromthefirstScenariobecomingmoreprominentovertime.

fIGURE 9.10: REDUCTION IN DALYS, COMBINED INTERVENTIONS

Treatmentcostsincreaseovertime(drivenbyanageingpopulationandanincreaseintheproportionofpeoplewithPOAGwhoarediagnosedfrom50%inthebasecaseto80%ineachofthecombinedscenarios)(Figure9.11).ThepatternoftotalcostsovertimeareshowninFigure9.12.

Treatment costs increase over time

because of an ageing population and

an increase in the proportion of people with POAG who are

diagnosed from 50% in the base case to 80% in each of the

combined scenarios.




Thecosteffectiveness(relativetothebasecase)ofthetwoscenariosisshowninFigure9.13.Thebasecaseisrepresentedattheorigin.

fIGURE 9.13: COST EffECTIVENESS PLANE, COMBINED SCENARIOS(A)

(a)EffectivenessmeasuredasDALYsavoided.Costsreflecthealthsystem,productivityandotherindirectcosts.(CosteffectivenessismeasuredasthecostperDALYavoided.ThevalueoftheburdenofdiseaseisexcludedfromthecostestimateinthenumeratorsincethisisrepresentedbyDALYsavoidedinthedenominator).

Combining better diagnosis rates with a hypothetical new therapy to further reduce progression is more cost effective than combining better diagnosis rates with primary trabeculoplasty.

fIGURE 9.11: TREATMENT COSTS, COMBINED INTERVENTIONS

fIGURE 9.12: TOTAL COSTS, COMBINED SCENARIOS


90

FIGURE 9-10: REDUCTION IN DALYS, COMBINED INTERVENTIONS

DALYs

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

2005 2010 2015 2020 2025






Treatment costs increase over time (driven by an ageing population and an increase in theproportion of people with POAG who are diagnosed from 50% in the base case to 80% in each

of the combined scenarios) (Figure 9-11). The pattern of total costs over time are shown inFigure 9-12.

FIGURE 9-11: TREATMENT COSTS, COMBINED INTERVENTIONS

Treatment Costs

0

100,000,000

200,000,000

300,000,000

400,000,000

500,000,000

600,000,000

700,000,000

2005 2010 2015 2020 2025







91

FIGURE 9-12: TOTAL COSTS, COMBINED SCENARIOS

Total Costs

0

500,000,000

1,000,000,000

1,500,000,000

2,000,000,000

2,500,000,000

3,000,000,000

3,500,000,000

4,000,000,000

4,500,000,000

2005 2010 2015 2020 2025


Diagnosis rate 80% and R&Dreduces progression 50%Diagnosis rate 80% and primarylaser trabeculoplasty

The cost effectiveness (relative to the base case) of the two scenarios is shown in Figure 9-13.The base case is represented at the origin.

FIGURE 9-13: COST EFFECTIVENESS PLANE, COMBINED SCENARIOS(A)

Diagnosis rate 80% and R&Dreduces progression 50%

Diagnosis rate 80% andprimary laser trabeculoplasty

0

500,000,000

1,000,000,000

1,500,000,000

2,000,000,000

2,500,000,000

0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000Effectiveness

Cos

ts

(a) Effectiveness measured as DALYs avoided. Costs reflect health system, productivity and other indirect costs.(Cost effectiveness is measured as the cost per DALY avoided. The value of the burden of disease is excludedfrom the cost estimate in the numerator since this is represented by DALYs avoided in the denominator).


91

FIGURE 9-12: TOTAL COSTS, COMBINED SCENARIOS

Total Costs

0

500,000,000

1,000,000,000

1,500,000,000

2,000,000,000

2,500,000,000

3,000,000,000

3,500,000,000

4,000,000,000

4,500,000,000

2005 2010 2015 2020 2025


Diagnosis rate 80% and R&Dreduces progression 50%Diagnosis rate 80% and primarylaser trabeculoplasty

The cost effectiveness (relative to the base case) of the two scenarios is shown in Figure 9-13.The base case is represented at the origin.

FIGURE 9-13: COST EFFECTIVENESS PLANE, COMBINED SCENARIOS(A)

Diagnosis rate 80% and R&Dreduces progression 50%

Diagnosis rate 80% andprimary laser trabeculoplasty

0

500,000,000

1,000,000,000

1,500,000,000

2,000,000,000

2,500,000,000

0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000Effectiveness

Cos

ts

(a) Effectiveness measured as DALYs avoided. Costs reflect health system, productivity and other indirect costs.(Cost effectiveness is measured as the cost per DALY avoided. The value of the burden of disease is excludedfrom the cost estimate in the numerator since this is represented by DALYs avoided in the denominator).


10. Appendix 1: Meta-Analysis - Falls and Hip Fractures

Section 6.3.4 presents the results of a meta analysis of literature that examined the increasedlikelihood of an accidental fall and hip fracture with a visual impairment as well as specific VFLor glaucoma impairment. The list of articles used in the meta-analysis is presented in Table 10.4,Table 6.7 and Table 6.8. From those lists, studies that reported the risks of an accidental fall orhip fracture as an OR were excluded, due to their technical incompatibility with RR (as well as alack of data to accurately convert the ORs into RRs).

Meta-analysis refers to the statistical analysis of analyses, where the results of multiple trials arecombined to estimate an overall effect size. A number of studies have been published examiningthe impact that visual impairment has on the risk of an accidental fall and/or hip fracture. Theresults of these studies have been combined to estimate an overall RR of an accidental fall forpeople that have a visual impairment.

10.1: FIXED-EFFECTS VERSUS RANDOM-EFFECTS

An inverse variance methodology has been used to weight the study trials for both the fixedeffects and random effects models23. The results of which are presented in Table 10.1.

TABLE 10.1: FIXED EFFECTS AND RANDOM EFFECTS, META-ANALYSIS RESULTS

Accidental Falls Hip Fractures Visual Impairment VFL / Glaucoma

No. of Studies 13 6 9

Weighting Method, Inverse variance Inverse variance Inverse variance FE RE Inverse variance + τ Inverse variance + τ Inverse variance + τ

Fixed Effects 1.33 (1.24 – 1.43) 2.52 (1.92 – 3.30) 1.43 (1.25 – 1.64) (95% CI)

Random Effects 2.05 (1.54 – 2.71) 3.18 (1.82 – 5.55) 1.46 (1.24 – 1.73) (95% CI)

The studies that specifically examined VFL/Glaucoma are a subset of the visual impairmentgroup of studies. Overall the RR of an accidental fall was higher for people with glaucoma(or VFL) than people with any type of visual impairment and the RR of an accidental fall ishigher than the RR of a hip fracture.

For all three groups, the RR of an accidental fall is greater in the random effects model than thefixed effects model. This indicates that heterogeneity exists between the combined studies.The presence of heterogeneity is not unexpected as the studies incorporated into the meta-analysis include different definitions, measures and severity criteria for visual impairment.

10.2: HETEROGENEITY

Heterogeneity between studies can be problematic when using a fixed effects model (whichassumes that the studies used to determine the treatment effect have the same criteria). In thisinstance the studies use a variety of different visual impairment, severity and other criteria andit is not unexpected that (as seen in Table 10.1) heterogeneity exists. Table 10.2 displays a seriesof statistical tests that estimate the presence of heterogeneity within the meta-analysis.

23 An inverse variance plus tau weighting method has been used for the random effects model.


Main heading to go here10. Appendix 1: Meta-Analysis - Falls and Hip Fractures

TABLE 10.2: HETEROGENEITY WITHIN THE COMBINED STUDIES

Accidental Falls Hip Fractures Visual Impairment VFL / Glaucoma

Fixed Effects

Q-statistic 55.11 17.44 9.66

p-value (two-tailed) <0.0001 0.0037 0.2894

H-statistic (95% CI) 2.14 (1.65 – 2.78) 1.87 (1.23 – 2.85) 1.10 (1.00 – 1.57)

I2-statistic (95% CI) 78.22% 71.33% 17.22%

(63.23% - 87.10%) (33.42% - 87.66%) (0.00% - 59.21%)

Random Effects

τ2-statistic 0.1630 0.3191 0.0110

• Q statistic: is the main analysis of heterogeneity and tests whether the assumption that allof the effect sizes are estimating the same population is reasonable. The test statistic has achi-square distribution with k-1 degrees of freedom. If the test is rejected, the distributionof effect sizes is assumed to be heterogeneous.

• H-statistic: describes the relative excess in Q over its degrees of freedom. Whenconsidering a regression of a standardised treatment effect on the standard error, the slopeof an unweighted least squares regression line corresponds with the fixed effect pooledvalue. The H statistic is the residual SD from this regression. A low H statistic means highconsistency among study results.

• I2-statistic: describes the percentage of total variation across studies that cannot beattributed to chance or sampling error and varies between 0% and 100%. In the case ofconsistent study results, the I2 is 0 or very low. P-values and CI’s can be used to describe thecompatibility of the data-based statistic with a null-hypothesis.

• τ2-statistic: is an estimate of the between study variance. The τ-value is used in therandom effects model as an addition to the inverse variance study weight.

The statistical tests for heterogeneity presented in Table 10.2 indicate that heterogeneityis present in the results of the accidental falls studies, however heterogeneity for studiesexamining the relationship between visual impairment and falls is small.

The random effects methodology of meta-analysis has been used to control for this inter studyheterogeneity, for each interest group. The results are presented in the following section.

10.3: FOREST PLOTS

Figure 10.1, Figure 10.2 and Figure 10.3 display the forest plots of each study group using arandom effects meta-analysis methodology. The effect size of each trial is represented by thered square with a black line indicating the 95% CI. The size of the red square for each trialindicates the relative weight applied to each study result (using an inverse variance plus tau)weighting methodology. This gives studies with lower standard errors higher weights, as resultswith more accurate estimations are assumed to provide better estimations of the true effectsize. The overall effect size is displayed at the bottom of the figure as a grey diamond with ahorizontal line providing the 95% CI.


10. Appendix 1: Meta-Analysis - falls and hip fractures

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�0.�:PUBLICATIONBIAS

Publicationbiaspresentsasauniqueproblemformeta-analyses.Whiletheinclusionandexclusionofstudiescanimpartsomecontroloverpublicationbias,thepotentialforitsexistenceisstillpresentwithstudiesshowinganeffectmorelikelytobepublishedthanstudiesthatshownoeffectatall.Tosomeextentpublicationbiaswillalwaysbepresentwithinameta-analysis,theproblemisthentoestimatehowlargeandwhateffecttheproblemhasontheresult.

TABLE 10.3: MEASURES Of PUBLICATION BIAS

Accidental falls hip fracture Visual Impairment VfL / Glaucoma

Model RandomEffects RandomEffects RandomEffects

WeightingMethod IV+τ IV+τ IV+τ

OriginalOutcome 2.05(1.54–2.71) 3.18(1.82–5.55) 1.46(1.24–1.73) (95%CI)

EffectAssessment

RegressionModel Egger Egger Egger

Intercepts(95%CI) 2.22(1.17–3.27) 3.44(-1.11–7.99) 0.22(-1.65–2.09)

p-value(two-tailed) 0.0007 0.1036 0.7884

Sensitivity

Trim-and-fillmethod L0 L0 L0

Numberofimputed 5 0 0 studies

Resultingoutcome (1.55(1.18–2.02) 3.18(1.82–5.55) 1.46(1.24–1.73) 95%CI)

Aswithheterogeneityafewstatisticaltestshavebeendevelopedtoexaminetheextentofpotentialpublicationbiaswithinameta-analysis(Table10.3).Twomainstatisticaltestsareappliedtotheresults,theseare:

• Egger’s small study effects:Aformaltestforpublicationbias.Thetestinvolvesregressionofthez-scoresupontheinverseofthestandarderrorandtheinterceptoftheregressionlineisusedtomeasureasymmetry(aroundthestandardisedpooledvalue,0)whichisregardedasasignofpublicationbias.

• Trim-and-fill method: usesfunnelplotsymmetryasanindicatorforpublicationbiasandestimatesthenumberofstudiesthathavenocounterpartontheothersideofthesymmetryaxis.Thesestudiesareremoved(trimmed)andanewsymmetry-axisiscalculated.Theprocedureisrepeateduntilthereisnoasymmetryfound.Finally,thetrimmedstudiesareputbackinthefunnelplottogetherwithhypotheticalcounterpartsandnewcombinedempiricalvaluescanbecalculatedwithbothoriginalandimputedstudiesincluded.

Thep-valueforstudiesexaminingaccidentalfallsandvisualimpairmentislessthan5%indicatingthatpublicationbiasispresentwithinthismeta-analyses,whilepublicationbiasfortheVFL/Glaucomaandhipfracturestudiesappearstoolow(pvaluesaregreaterthan5%).Theeffectofthispublicationbiascanbeseenwiththetrim-and-fillmethod,whichindicatesthatthetreatmenteffectshouldhaveaRRofapproximately1.55forpeoplewithavisualimpairment.

To some extent publication bias will

always be present within a meta-

analysis, the problem is then to estimate

how large and what effect the bias has on

the result.




�0.�:ADDITIONALSUPPORTIVELITERATURE

Anumberofadditionalarticleswerefoundduringtheliteraturesearchprocess,whichcouldnotbeincludedwithinthemeta-analysisbecauseofincompleteorthelackofquantitativeinformationrequired.TheseadditionalarticlesareshowninTable10.4.

TABLE 10.4: NON-QUANTITATIVE SUPPORTING LITERATURE

Visual Impairment Increased Risk Source

Visualimpairment Risk of first, multiple and injurious falls: Arfkenetal,1994 wasnotsignificantlyassociatedwith visualimpairment

Visualimpairment Risk of fallwasnotsignificantly Campbelletal,1989 (nospecificdefinitionprovided) associatedwithvisualimpairment

≤60/60(facerecognition) ORofhip fracture=3.1 deBoeretal,2004*

Blindness/poorvision Risk of fall: wassignificantlyassociated Gaebleretal,1993 (nospecificdefinition withblindnessandpoorvision provided)

Poorvision(nospecific Risk of wrist fracturewaslowerinthe Haboubietal,1991 definitionprovided) groupwithpoorvision

Best(corrected)VA Risk of fall: significantdifferencebetween Jacketal,1995 of<6/18 lowvisionofpatientsattendingforfalls comparedwiththoseattendingforother medicalproblems

Patientsdiagnosedwith: Risk of fall: amongpatientswithdiabetic Kameletal,2000 refractiveerrors,cataracts, retinopathyandglaucomathevision glaucoma,diabetic questionnairehada100%sensitivityin retinopathyand/orAMD identifyingpatientswithahistoryoffalls

ParticipantsoftheBeaver Risk of fall and hip fracture: was Kleinetal,1998 DamEyeStudy: significantlyassociatedwithVAinthe VAbasedmeasures over60s,intheunder60sriskwasonly associatedwithsomevisionmeasures

<6/12 ORofmultiple falls=1.75 Koski,1998*

Poordistancevision ORofmultiple falls=2.3 Koski,1998*

LowcontrastVAand Risk of multiple falls significantly Lordetal,1994 contrastsensitivity increasedinsubjectswithpoorVA and/oralowabilitytoperceivecontrast

Blindness(nospecific Risk of second hip fracturewas Saxenaetal,2000 definitionprovided) significantlyincreasedintheblind/and thosewithlowvision

Visuallyimpairedandblind Risk of fall: theblinddemonstrateda Tobisetal,1990 (nostrongerdefinitions higherriskthanthedeafornon- provided) impairedpopulations

*Notenoughinformationcouldbeobtainedfromtheabstractstobeincludedinthemeta-analysis


11. References

Access Economics (2005) Business Outlook, June.

The AGIS Investigators (2002) “The Advanced Glaucoma Intervention Study (AGIS): 12. BaselineRisk Factors for Sustained Loss of Visual Field and Visual Acuity in Patients With AdvancedGlaucoma” Am J Ophthalmol, 134:499-512.

Australian Institute of Health and Welfare (2006), Health expenditure Australia 2004–05, Healthand Welfare Expenditure Series No. 28, Cat No HWE 35, Canberra.

Australian Institute of Health and Welfare (2005a) Statistics on Drug Use in Australia, 2004, Drug Statistics Series No. 15, Cat No PHE 62, June.

Australian Institute of Health and Welfare (2005b) Health system expenditure of disease and injury in Australia, 2000-01, Health and Welfare Expenditure Series No 21, Second edition,Cat No HWE 28, Canberra.

Alward WL, Fingert JH, Coote MA, Johnson AT, Lerner SF, Junqua D, Durcan FJ, McCartney PJ,Mackey DA, Sheffield VC, Stone EM (1998) “Clinical features associated with mutations inthe chromosome 1 open-angle glaucoma gene (GLC1A)” N Engl J Med, 338: 1022-27

American Academy of Ophthalmology (2005) Preferred Practice Pattern: Primary Open-Angle Glaucoma, American Academy of Ophthalmology, The Eye MD Association.

Arfken CL, Lach HW, McGee S, Birge SJ, Miller JP (1994) “Visual acuity, visual disabilities andfalling in the elderly” J Aging Health, 4: 38-50.

Australian Bureau of Statistics (2005) Australian Labour Market Statistics, ABS CatNo 6105.0, July.

Australian Bureau of Statistics (2004) Employee Earnings, Benefits and Trade Union Membership, ABS Cat No 6310.0, August.

Black A, Wood J (2005) “Vision and Falls: Review” Clinical experimental Optometry,88[4]: 212-22.

Bonovas S, Peponis V, Filioussi K (2004) “Diabetes mellitus as a risk factor for primary open-angle glaucoma: a meta-analysis” Diabetic Medicine, 21[6]: 609-14.

Brody BL, Gamst AC, Williams RA et al (2001) “Depression, visual acuity, comorbidity anddisability associated with age-related macular degeneration” Ophthalmology, 108[10]:1893-901.

Brooks ANV, Gillies WE (1992) “Ocular β-blockers in glaucoma management” Drugs and Aging, 3: 208-11.

Brown G (1999) “Vision and Quality of Life” Trans Am Ophthalmol Soc, 97: 473-511.

Brown M, Brown G, Sharma S, Kistler J, Brown H (2001) “Utility values associated with blindnessin an adult population” Br J Ophthalmology, 85: 327-331.

Budde WM, Jonas JB (1998) “No effect of diabetes mellitus on the morphology of the opticnerve papilla in primary open angle glaucoma [German]” Klinische Monatsblatter fur Augenheilkundle, 212[1]: 37-9.

Burmedi D, Becker S, Heyl S, Wahl HW, Himmelsbach L (2002) “Emotional and socialconsequences of age-related low vision” Visual Impairment Research, 4[I]: 47-71.


Main heading to go here11. References

Campbell AJ, Michael JB, Spears GS (1989) “Risk factors for falls in a community-basedprospective study of people 70 years or older” J Gerentol, 44: M112-17.

Centre for Eye Research Australia (2004) Clear Insight: The Economic Impact and Cost of Vision Loss in Australia, prepared by Access Economics, published by Centre for Eye ResearchAustralia, Melbourne.

Centre for Eye Research Australia (2005) Investing in Sight: Strategic Interventions to Prevent Vision Loss in Australia, prepared by Access Economics, published by Centre for Eye ResearchAustralia, Melbourne.

Centre for Eye Research Australia (2006) Centrally Focussed: The Impact of Age related Macular Degeneration, A Dynamic Economic Model, prepared by Access Economics, published by theCentre for Eye Research Australia, Melbourne.

Chen P (2003) “Blindness in patients with treated open angle glaucoma” Ophthalmology,110: 726-33.

Chen P, HE XG (2005) “Mental status and personality characteristics of patients suffering fromacute or chronic glaucoma” Zhongguo Linchuang Kangfu, 9: 58-60.

Clark AF, Kawase K, English-Wright S et al (2001) “Expression of the glaucoma gene myocilin(MYOC) in the human optic nerve head” FASEB J, 15: 1251-53.

Coleman AL, Stone K, Ewing S et al (2004) “Higher risk of multiple falls among elderly womenwho lose visual acuity” Ophthalmology, 111: 857-62.

Crowston J, Hopley C, Healey P, Lee A, Mitchell P (2004) “The effect of optic disc diameter onvertical cup to disc ratio percentiles in a population based cohort: the Blue Mountains EyeStudy” Br J Ophthalmology, 88: 766-70.

Cummings SR, Nevitt MC, Browner WS et al (1995) “Risk factors for hip fracture in whitewomen. Study of Osteoporotic Fractures Research Group” New England Journal of Medicine, 332: 767-73.

Damji K, Bovell A, Hodge W, Rock W, Shah K, Buhrman R, Pan I (2006) “Selective LaserTrabeculoplasty v ALT: Results from a one year randomised clinical trial” [online], Br JOphthalmol, Published Online First: 9 August 2006. doi:10.1136/bjo.2006.098855.

Dargent-Molina P, Favier F, Grandjean H et al (1996) “Fall-related factors and risk of hip fracture:the EPIDOS prospective study” Lancet, 348: 145-9.

de Boer MR, Pluijm SM, Lips P, et al (2004) “Different aspects of visual impairment as risk factorsfor falls and fractures in older men and women” Journal of Bone and Mineral Research, 19: 1539-47.

de Voogd S, Ikram MK, Wolfs RC, Jansonius NM, Witteman JC, Hofman A, de Jong PT (2006)“Is diabetes mellitus a risk factor for open-angle glaucoma? The Rotterdam Study”Ophthalmology, 113[10]: 1827-31.

Dielemans I, de Jong PT, Stolk R, Vingerling JR, Grobbee DE, Hofman A (1996) “Primary open-angle glaucoma, intraocular pressure, and diabetes mellitus in the general elderly population.The Rotterdam study” Ophthalmology, 103[8]: 1271-5.

Dolinis J, Harrison JE, Andrews GR (1997) ”Factors associated with falling in older Adelaideresidents” Aust N Z J Public Health, 21: 462-8.


11. References

EdmundsB,ThompsonJR,SalmonJF,WormaldRP(1999);ThenationalsurveyoftrabeculectomyIIIEarlyandlatecomplications;EyeMay200216(3):297-303

EdmundsB,ThompsonJ,SalmonJ,WormaldR(2001)“ThenationalsurveyoftrabeculectomyIIVariationsinoperativetechniqueandoutcome”Eye,15:441-8.

EhrnroothP,PuskaP,LehtoI,LaatikainenL(2002)“LongtermoutcomeoftrabeculectomyintermsofIOP” Acta Ophthalmologica Scandinavia,80:267-71.

EhrnroothP,PuskaP,LehtoI,LaatikainenL(2005)“Progressionofvisualfielddefectsandvisuallossintrabeculectomizedeyes”Graefe’s Arch Clin Exp Ophthalmol, 243:741-7.

EuropeanGlaucomaPreventionStudyGroup(2005)“ResultsoftheEuropeanGlaucomaPreventionStudy”Ophthalmology,112:366-75.

FeldmanR,KatzJ,SpaethG,CrapottaJ,FahmyI,MoonesA(1991)“Long-termefficacyofrepeatargonlasertrabeculoplasty”Ophthalmology,98:1061-5.

FelsonDT,AndersonJJ,HannanMTetal(1989)“Impairedvisionandhipfracture.TheFraminghamStudy”Journal of the American Geriatric Society,37:495-500.

FingertJH,HeonE,LiebmannJMetal(1999)“Analysisofmyocilinmutationsin1703glaucomapatientsfromfivedifferentpopulations”Hum Mol Genet,8:899-905.

FingertJH,StoneEM,SheffieldVC,AlwardWL(2002)“Myocilinglaucoma”Surv Ophthalmol,15:1251-53.

FontanaH,Nouri-MahdaviK,LumbaJ,RalliM,CaprioloJ(2006)“TrabeculectomywithMitomycinC,OutcomesandriskfactorsforfailureinphakicOAG”Ophthlamology,113:930-6.

FriedmanDS,WilsonMR,LiebmannJM,FechtnerRD,WeinrebRD(2004)“AnEvidence-basedAssessmentofRiskFactorsfortheProgressionofOcularHypertensionandGlaucoma”Am J Ophthalmol, 138:S19-S31.

GaeblerS(1993)“Predictingwhichpatientwillfallagain…andagain” J Adv Nurs,18:1895-902.

GlaucomaLaserTrialResearchGroup(1995)“GlaucomalasertrialandglaucomalasertrialfollowupstudyNo7results”Am J Ophthalmol,120:718-31.

GlynnRJ,SeddonSM,KrugJetal(1991)“Fallsinelderlypatientswithglaucoma”Arch Ophthalmol, 109:205-10.

GordonM,BeiserJ,BrandtJetal,fortheOcularHypertensionTreatmentStudyGroup(2002)“TheOcularHypertensionTreatmentStudy:baselinefactorsthatpredicttheonsetofprimaryopen-angleglaucoma”Arch Ophthalmol,120:714-20.

GrissoJA,KelseyJL,StromBL,etal(1991)“Riskfactorsforfallsasacauseofhipfractureinwomen.TheNortheastHipFractureStudyGroup”N Engl J Med,324:132631.

GrødumK,HeijlA,BengtssonB.A(2002)“Acomparisonofglaucomapatientsidentifiedthroughmassscreeningandinroutineclinicalpractice”Acta Ophthalmol Scand.80(6):627-31

HaboubiNY,HudsonPR(1991)“FactorsassociatedwillColles’fractureintheelderly”Gerontology,37:335-8.


�0�The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model

11. References

HattenhauerMG,JohnsonDH,IngHH,HermanDC,HodgeDO,YawnBP,ButterfieldLC,GrayDT(1998)“TheProbabilityofBlindnessfromOpen-angleGlaucoma”Opthalmology,105:2099-104.

HaymesSA,LeBlancRP,NicolelaMT,ChiassonLA,ChauhanBC(2007)“RiskofFallsandMotorVehicleCollisionsinGlaucoma”Invest Ophthalmol VisSci,48:1149-15.

HeijlA,LeskeC,BengtssonB,HymanL,BengtssonB,HusseinM(2002)“Reductionofintraocularpressureandglaucomaprogression,ResultsfromtheEarlyManifestGlaucomaTrial”Arch Ophthalmol, 120:126879.

HensonD,ShambhuS(2006)“RelativeRiskofProgressiveGlaucomatousVisualFieldLossinPatientsEnrolledandNotEnrolledinaProspectiveLongitudinalStudy” Arch Ophthalmol,124:1405-8.

HymanL,KomaroffE,HeijlA,Bengtsson,LeskeC(2005)“Treatmentandvisionrelatedqualityoflifeintheearlymanifestglaucomatrial”Ophthalmology,112:150513.

IversRQ,CummingRG,MitchellP,etal(1998)“Visualimpairmentandfallsinolderadults:theBlueMountainsEyeStudy” J Am Geriatr Soc,46:58-64.

IversRQ,NortonR,CummingRG,etal(2000)“Visualimpairmentandriskofhipfracture”American Journal of Epidemiology,152:633-9.

JackCI,SmithT,NeohC,etal(1995),PrevalenceoflowvisioninelderlypatientsadmittedtoanacutegeriatricunitinLiverpool:elderlypeoplewhofallaremorelikelytohavelowvision,Gerontology;41:280-5

JampelH,SchwartzA,PollackI,AbramsD,WeissH,MillerR(2002)“Glaucomapatients’assessmentoftheirvisualfunctionandqualityoflife”Journal of Glaucoma, 11:154-63.

JayJ,MurdochJ(1993)“Therateofvisualfieldlossinuntreatedprimaryopenangleglaucoma”British Journal of Ophthalmology,77:176-8.

JuzychM,ChopraV,BanittM,HughesB,KimC,GoulasM,ShinD(2004)“ComparisonofLong-termOutcomesofSelectiveLaserTrabeculoplastyversusArgonLaserTrabeculoplastyinOpen-AngleGlaucoma”Ophthalmology,111:1853–59.

KamelHK,GuroRS,ShareeffM(2000)“Theactivitiesofdailyvisionscale:ausefultooltoassessfallriskinolderadultswithvisionimpairment” J Am Geriatr Soc,48:1474-7.

KarlssonJS(1998)“Self-reportsofpsychologicaldistressinconnectionwithvariousdegreesofvisualimpairment”Journal of Visual Impairment & Blindness,92[7]:483-90.

KassMA,HeuerDK,HigginbothamEJetal(2002)“TheOcularHypertensionTreatmentStudy:arandomisedtrialdeterminesthattopicalocularhypotensivemedicationdelaysorpreventstheonsetofprimaryopen-angleglaucoma”Arch Ophthalmol,120:701-13.

KatzJ,CongdonN,FriedmanD(1999)“Methodologicalvariationsinestimatingapparentprogressivevisualfieldlossinclinicaltrialsofglaucomatreatment” Arch Ophthalmol,117:1137-42.

KirwanJF,NightingaleJA,BunceC,WarmaldR(2002)“bBlockersforglaucomaandexcessriskofairwaysobstruction:populationbasedcohortstudy”BMJ,325:1396-7.

�0� Tu n n e l V i s i o nCentre for Eye Research Australia

KleinBE,KleinR,JensenSC(1994)“Open-angleglaucomaandolder-onsetdiabetes.TheBeaverDamEyeStudy”Ophthalmology,101[7]:1173-7.

KleinBEK,KleinR,LeeKE,etal(1998)“Performance-basedandself-assessedmeasuresofvisualfunctionasrelatedtohistoryoffalls,hipfractures,andmeasuredgaittime:theBeaverDamStudy”Ophthalmology,105:160-4.

KleinschmidtJJ,TrunnellEP,ReadingJC,WhiteGL(1995)“Theroleofcontrolindepression,anxietyandlifesatisfactionamongvisuallyimpairedolderadults”Journal of Health Education,26[1]:26.

KobeltG,JonssonB,BergstromA,ChenE,LindenC,AlmA(2006)“Cost-effectivenessanalysisinglaucoma:whatdrivesutility?ResultsfromapilotstudyinSweden”Acta Ophthalmol Scand, 84[3]:363-71.

KoskiK,LuukinenH,LaippalaPetal(1998)“Riskfactorsformajorinjuriousfallsamongthehome-dwellingelderlybyfunctionalabilities.Aprospectivepopulation-basedstudy”Gerontology,44:232-8.

KwonY,FingertJ,GreenleeE(2006)“Apatient’sguidetoglaucoma”[online],Availablefrom:http://www.medrounds.org/glaucoma-guide/2006/02/table-of-contents-patients-guide-to.html[accessed4May2007].

KwonY,KimC,ZimmermanB,AlwardW,HayrethS(2001)“Rateofvisualfieldlossandlong-termvisualoutcomeinprimaryopen-angleglaucoma”Am J Ophthalmol,132:47-56.

LatinaM,deLeonJ(2005)“Selectivelasertrabeculoplasty”Ophthalmol Clin North Am,18:40919.

LeskeMC,HeijlA,HusseinM,BengtssonB,HymanL,KomaroffEfortheEarlyManifestGlaucomaTrialGroup(2003)“Factorsforglaucomaprogressionandtheeffectoftreatment,Theearlymanifestglaucomatrial”Arch Ophthalmol,121:48-56.

LichtensteinMJ,GriffinMR,CornellJE,etal(1994)“RiskFactorsforhipfracturesoccurringinthehospital”Am J Epidemiol, 140:830-8.

LichterP,MuschD,GillespieB,GuireK,JanzN,WrenP,MillsR,andtheCIGTSStudyGroup(2001)“InterimclinicaloutcomesintheCollaborativeInitialGlaucomaTreatmentStudycomparinginitialtreatmentrandomizedtomedicationsorsurgery”Ophthalmology,108:194353.

LordSR,WardJA,WilliamsP,etal(1994)“Physiologicalfactorsassociatedwithfallsinoldercommunity-dwellingwomen”J Am Geriatr Soc,42:1110-14.

MartusP,StrouxA,BuddeW,MardinC,KorthM,JonasJ(2005)“PredictiveFactorsforProgressiveOpticNerveDamageinVariousTypesofChronicOpen-angleGlaucoma”Am J Ophthalmol,139:999–1009.

MathersC,VosT,StevensonC(1999) The loss of well being and injury in Australia,TheAustralianInstituteofHealthandWelfare,CatNoPHE17,Canberra.

McCartyC,NanjanM,Taylor,H(2001)“Visionimpairmentpredicts5yearmortality”British Journal of Ophthalmology, 85[3]:3226.

McIlraithI,StrasfeldM,ColevG,HutnikC(2006)“SelectiveLaserTrabeculoplastyasInitialandAdjunctiveTreatmentforOpen-AngleGlaucoma”J Glaucoma,15:124-30.

11. References


�0�The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model

McNaughtAI,AllenJG,HealeyDL,CooteMA,WongTL,CraigJE,GreenCM,RaitJL,MackeyDA(2000)“Accuracyandimplicationsofareportedfamilyhistoryofglaucoma:experiencefromtheGlaucomaInheritanceStudyinTasmania”Arch Ophthalmol,118:900-4.

MillsR,JanzN,WrenP,GuireK,CIGTSStudyGroup(2001)“CorrelationofvisualfieldwithqualityoflifemeasuresatdiagnosisintheCollaborative.InitialGlaucomaTreatmentStudy(CIGTS)”Journal of Glaucoma, 10:192-8.

MitchellP,SmithW,CheyT,HealeyPR(1997)“Open-angleglaucomaanddiabetes:theBlueMountainsEyeStudy,Australia”Ophthalmology,104[4]:712-8.

MukeshB,McCartyC,RaitJ,TaylorH(2002)“Fiveyearincidenceofopenangleglaucoma,thevisualimpairmentproject”Ophthalmology,109:104751.

NagarM,OgunyomadeA,O’BrartD,HowesF,MarshallJ(2005)“ArandomisedprospectivestudycomparingSLTwithlatanoprostforthecontrolofIOPinOHTandOAG”Br J Ophthalmol, 89:1413-7.

NordstromBL,FriedmanDS,MozaffariE,QuigleyHA,WalkerAM(2005)“Persistenceandadherencewithtopicalglaucomatherapy”Am J Ophthalmol,140:598-606.

OcularHypertensionTreatmentStudyGroup,EuropeanGlaucomaPreventionStudyGroup,GordonMO,TorriV,MigliorS,BeiserJA,FlorianiI,MillerJP,GaoF,AdamsonsI,PoliD,D’AgostinoRB,KassMA(2007)“Validatedpredictionmodelforthedevelopmentofprimaryopen-angleglaucomainindividualswithocularhypertension”Ophthalmology,114[1]:10-9.

OlthoffC,SchoutenJ,vandeBorneB,WebersC(2005)“Noncompliancewithocularhypotensivetreatmentinpatientswithglaucomaorocularhypertension”Ophthalmology,112:953-61.

PasqualeLR,KangJH,MansonJE,WillettWC,RosnerBA,HankinsonSE(2006)“Prospectivestudyoftype2diabetesmellitusandriskofprimaryopen-angleglaucomainwomen”Ophthalmology,113[7]:1081-6.

PolanskyJR,FaussDJ,ZimmermanCC(2000)“RegulationofTIGR/MYOCgeneexpressioninhumantrabecularmeshworkcells”Eye,14:503-14.

ProductivityCommission(2003)Evaluation of the Pharmaceutical Industry Investment Program,ResearchReport,AusInfo,Canberra.

ProductivityCommission(2005)Economic Implications of an Ageing Australia,April.

QuigleyH(1996)“Numberofpeoplewithglaucomaworldwide”Br J Ophthalmol,80:389-93.

RamrattanRS,WolfsRCW,Panda-JonasS,JonasJB,BakkerD,PolsHA,HofmanA,deJongPTVM(2001)“PrevalenceandCausesofVisualFieldLossintheElderlyandAssociationwithImpairmentinDailyFunctioning”Arch Ophthalmol,119:1788-94.

RaskerM,denEndenA,BakkerD,HoyngP(2000)“Rateofvisualfieldlossinprogressiveglaucoma”Arch Ophthalmol,118:481-8.

ReardonG,SchwartzG,MozaffariE(2004)“Patientpersistencywithtopicalocularhypotensivetherapyinamanagedcarepopulation”Am J Ophthalmology,137:S3-S12.

RichterC,ShingletonB,BellowsR,HutchinsonB,JacobsonL(1987)“RetreatmentwithArgonLaserTrabeculoplasty”Ophthalmology,94:1085-9.

11. References

�0� Tu n n e l V i s i o nCentre for Eye Research Australia

RobbinsHG,McMurrayNE(1988)“Psychologicalandvisualfactorsinlowvisionrehabilitationofpatientswithage-relatedmaculopathy” Journal of Vision Rehabilitation, 2:11-21.

RovnerBW,Shmuely-DulizkiY(1997)“Screeningfordepressioninlow-visionelderly” Int J Geriatr Psychiatry, 12[9]:955-9.

SanfilippoP(1999)“Areviewofargonandselectivelasertrabeculoplastyasprimarytreatmentsofopen-angleglaucoma”Clinical and Experimental Optometry, 82[6]:225-9.

SaxemaP,ShankarJ(2000)“Contralateralhipfractures–canpredisposingfactorsbedetermined?”Injury,31:421-4.

SchwartzG(2005)“Complianceandpersistencyinglaucomafollow-uptreatment”Current Opinion in Ophthalmology, 16:114-21.

SheffieldVC,StoneEM,AlwardWLetal(1993)“Geneticlinkageoffamilialopenangleglaucomatochromosome1q21-q31”Nat Genet,4:47-50.

ShingletonB,RichterC,DharmaS,TongL,BellowsR,HutchinsonT,GlynnR(1993)“Longtermefficacyofargonlasertrabeculoplasty”Ophthalmology,100:1324-9.

SpaethG,BaezK(1992)“Argonlasertrabeculoplastycontrolsonethirdofcasesofprogressiveuncontrolledopenangleglaucomafor5years”Arch Ophthalmology,110:491-4.

StoneEM,FingertJH,AlwardWLetal(1997)“Identificationofagenethatcausesprimaryopenangleglaucoma”Science,275:668-70.

TaylorH(2001) Eye care for the community, CentreforEyeResearchAustralia.

TielschJM,KateJ,SommerA,QuigleyHA,JavittJC(1994)“TheBaltimoreEyeSurvey”Arch Ophthmol, 112:69-73.

TielschJM,KatzJ,QuigleyHA,JavittJC,SommerA(1995)“Diabetes,intraocularpressure,andprimaryopen-angleglaucomaintheBaltimoreEyeSurvey”Ophthalmology,102[1]:48-53.

TinettiME,SpeechleyM,GinterRN(1988)“Riskfactorsforfallingamongelderlypersonslivinginthecommunity”N Engl J Med,319:1701-6.

TobisJS,BlockM,SteinhausDC,etal(1990)“Fallingamongthesensoriallyimpairedelderly”Arch Phys Med Rehabil,71:144-7.

TsaiJC(2006)“Medicationadherenceinglaucoma:approachesforoptimizingpatientcompliance”Current Opinion in Ophthalmology,17:190-5.

VuHTV,KeeffeJE,McCartyCA,TaylorHR(2005)“ImpactofUnilateralandBilateralVisionLossonQualityofLife”British Journal of Ophthalmology,89:360-3.

WahlHW(1994)“Seeinginthedark:limitedvisionintheagedasaprototypical“environmentallyrelevant”lossincompetence” Z Gerontol, 27[6]:399-409.

WangJJ,MitchellP,CummingR,SmithW(2002)“VisualimpairmentandnursinghomeplacementinolderAustralians:theBlueMountainsEyeStudy”Opthalmic Epidemiology, 10[1]:3-13.

WeihL,MukeshN,McCartyC,TaylorH(2001)“Prevalenceandpredictorsofopenangleglaucoma,resultsfromthevisualimpairmentproject”Ophthalmology,108:1966-72.

11. References


This report was prepared jointly by the Centre for Eye Research Australia and Access Economics Pty Limited.

We acknowledge particularly the expert input and prior research of

Professor Hugh Taylor AC Centre for Eye Research Australia and University of Melbourne

Professor Jonathan Crowston Centre for Eye Research Australia and University of Melbourne

Associate Professor Jill Keeffe OAM Centre for Eye Research Australia and University of Melbourne

Ms Lynne Pezzullo Access Economics Pty Ltd

Ms Penny Taylor Access Economics Pty Ltd

Mr Peter Moore Access Economics Pty Ltd

Acknowledgments and Disclaimer

While every effort has been made to ensure the accuracy of this document, the uncertain nature of economic data, forecasting and analysis means that Access Economics Pty Limited is unable to make any warranties in relation to the information contained herein. Access Economics Pty Limited, its employees and agents disclaim liability for any loss or damage which may arise as a consequence of any person relying on the information contained in this document.

Publication of this work has been made possible by an unrestricted grant from Allergan who had no part in the direction or findings contained in this report.

Centre for Eye Research Australia, University of Melbourne, Australia, February 2008.

Centre for Eye Research Australia Tu n n e l V i s i o n

Weih L, Van Newkirk M, McCarty C, Taylor H (1998) “Patterns of glaucoma medication use in urban and rural Victoria” Australian and New Zealand Journal of Ophthalmology, 26[Suppl]: S12 S15.

Weinand F, Althen F (2006) “Long term clinical results of SLT in the treatment of POAG” Eur J Ophthalmology, 16: 100-4.

Weinreb RN, Khaw PT (2004) “Primary open-angle glaucoma” The Lancet, 363: 1711-20.

Weinreb RN, Friedman DS, Fechtner RD, Cioffi GA, Coleman AL, Girkin CA, Liebmann JM, Singh K, Wilson MR, Wilson R, Kannel WB (2004) “Perspective: Risk Assessment in the Management of Patients with Ocular Hypertension” American Journal of Ophthalmology, 138[3]: 458-67.

Wensor M, McCarty C, Stanislavsky Y, Livingston P, Taylor H (1998) “The prevalence of glaucoma in the Melbourne Visual Impairment Project” Ophthalmology, 105: 733-9.

Wilson MR, Coleman AL, Fei Yu, Sasaki IF, Kim MH (2002) “Depression in patients with glaucoma as measured by self-reported surveys” Ophthalmology, 105[5]: 1018-22.

Wolfs RC, Klauver CC, Ramrattan RS, van Duijin CM, Hofman A, de Jong PT (1998) “Genetic risk of primary open-angle glaucoma. Population based familial aggregation study” Arch Ophthal, 116: 1640-45.

Zahari M, Mukesh B, Rait J, Taylor H, McCarty C (2006) “Progression of visual field loss in open angle glaucoma in the Melbourne Visual Impairment Project” Clinical and Experimental Ophthalmology, 34: 20–6.

Zeiter JH, Shin DH (1994) “Diabetes in primary open-angle glaucoma patients with inferior visual field defects” Graefes Archive for Clinical & Experimental Ophthalmology, 232[4]: 205-10.

Zghal I, Jeddi A, Hadj Alouane WB, Malouche N, Ayed S, Gaigi S (2000) “Primary open-angle glaucoma and diabetes [French]” Tunisie Medicale, 78[8-9]: 518-21.

Zwerling C, Sprince NL, Davis CS, Whitten PS, Wallace RR, Herringa SG (1998) “Occupational injuries among older workers with disabilities: a prospective cohort study of the Health and Retirement Survey, 1992 to 1994” American Journal of Public Health, 88: 1691-16.

11. References

The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model 105

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