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Monitoring Ocular Hypertension in Patients

Content written by: Osuagwu Levi RO, RCLP

Content originally published in the Fall 2011 and Winter 2012 editions of The Eighth Line

Table of Contents • Introduction• IOP’s and OH• Fluctuations During Wake-Sleep Cycles

o Optic Nerve Blood Flow• The Probability of Developing Glaucoma• Assisting Patients with OH and POAG• Assessing Patients with OH and POAG

o Cup Disc Ratioo Fundus Photographyo Visual Field Evaluation

• Treatment• References• Post Test

Introduction Eye care practitioners are faced with the challenge of maintaining good sight for each and every patient that walks into

our clinics. Many times we come across patients whose prescriptions keep changing and wonder if we have continuously

refracted these patients incorrectly or if something else is going on. Inquiries into our patient’s systemic conditions will

often times resolve the problem. As opticians, we will do these patients a lot of good if we advise them properly

concerning issues that surround their health. Most times, we might be the first point of call for some of these patients

who haven’t had the opportunity to visit either an optometrist or an ophthalmologist. An understanding of the some

more ‘complex’ eye conditions will be of value in such cases in delivering comprehensive eye care service.

IOP’s and OH Intraocular pressure (IOP) is the result of a dynamic balance between aqueous humor formation and outflow, which are

nearly equal under normal conditions (Kniestedt et al, 2008). Elevated IOP’s are the main indicator of the development

and progression of primary open-angle glaucoma (POAG) (Cronemberger et al, 2010).

Ocular hypertension (OH) has been defined as an increased IOP greater than two standard deviations above 21mmHg

(mean=16mmHg, normal range 10-21mmHg) in the absence of optic nerve damage or visual field loss (NICE, 2009;

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Grissom et al, 2004). Ocular hypertension increases the risk of developing glaucoma especially in persons at high risk.

Risk factors include increased age, thin corneas, family history of glaucoma, increased systemic blood pressure, and

diabetics (Garudadri et al, 2010; Leske et al 1995; Tielsh et al, 1994; Klein et al. 1992; Sommer et al. 1991). It is important

to note that OH can increase the risk of glaucoma, but it doesn’t necessarily cause glaucoma. OH has been recognized as

the most important risk factor for the development of POAG (Leske et al, 1995; Sommer et al, 1991) and the only factor

that can be medically or surgically controlled (EGPS, 2004). Lowering intraocular pressure in both ocular hypertensive

and glaucoma patients has proven to be a great benefit in preventing the progression of ocular hypertension to POAG

and management of POAG(NICE, 2009; Bron et al, 2003).

Fluctuations During Wake-Sleep Cycles The major aim of monitoring Ocular hypertensive patients/POAG is to make sure their IOPs are maintained at baseline

levels to preserve sight for the patient’s life time.

Monitoring the IOP of ocular hypertension and glaucoma patients is a bit complex as studies (Cronemberger et al, 2010;

Liu et al, 2005; Liu, 2001& 1998) have continually shown that human IOP fluctuates significantly throughout the wake-

sleep cycle. This was thought to be influenced by various physiological and environmental conditions in the

diurnal/wake, nocturnal/sleep, and 24-hour period (Liu et al, 2005).

Optic Nerve Blood Flow Studies (Hayreh et al, 1999; Cronemberger et al, 2010) have also reported that reducing the optic nerve head (ONH)

blood flow below a crucial level during sleep in patients with ocular hypertension with vulnerable optic nerve head may

play a role in the pathogenesis of AION and glaucomatous optic neuropathy (GON) and progression of visual field loss.

This goes further to show that IOP routinely measured in clinic hours isn’t usually a true representation of the patients

IOP. Since most practitioners categorize subjects based on IOP values obtained during clinic hours, many of the patients

categorized as ocular hypertensive patients may actually have been POAG patients. It has been reported that IOP peaks

at 6:00am in suspects and glaucomatous patients with inadequate treatment (Cronemberger et al, 2010). We run the

risk of misdiagnosing these patients and subsequently delaying treatment, which may result in optic disc damage and

visual field deterioration. 0.22% of subjects in whom treatment was delayed (Kass et al, 2010) had an increased risk of

developing POAG compared to 0.16% of individuals on medication.

The Probability of Developing Glaucoma Long-term IOP fluctuation is associated with a progression of visual filed loss in patients with low mean IOP but not in

patients with high mean IOP (Caprioli and Coleman, 2008). Using the baseline clinical factors (race, age, IOP, cornea

thickness) to predict subjects with ocular hypertension that would develop glaucoma, the OHTS (2002) was able to

reduce by 60% the cumulative probability of them developing glaucoma just by initiating treatment with topical ocular

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hypotensive medication. At 60 months, the probability of the patients on medication developing glaucoma was reduced

to 4.4% as compared to 9.5% in the observation group. This has been confirmed by few other studies (Pozarowska,

2010; Bron et al, 2003) that demonstrated the importance of initiating treatment early to reduce IOP. Their objective

was to reach a target IOP in 46.0% of their cohorts. Treatment was initiated because of unsatisfactory IOP value.

OHTS (2002b) also showed that topical ocular hypotensive medication is effective in reducing the incidence of

glaucomatous visual field loss and/or optic nerve damage in individuals with elevated IOP between 24mmHg and

32mmHg. Again, 0.22% of subjects in whom treatment was delayed in a study (Kass et al, 2010) had an increased risk

of developing POAG compared to 0.16% of individuals on medication. They therefore concluded that individuals at risk

of developing POAG may benefit from more frequent examinations and early preventive treatment.

Assisting Patients with OH and POAG Patients with ocular hypertension and POAG should also be monitored to ensure compliance with medication. High IOP

can be a predictor of noncompliance. Studies (Patel et al, 1995; windfiled et al, 1990) have identified a 50%

noncompliance rate when patients with ocular hypertension/POAG are treated with one medication with a 20% increase

when more than one medication is being used. They also concluded that forgetfulness was the main reason for

noncompliance (Patel et al, 1995; Windfiled et al, 1990). Patel and cohorts indicated that compliance increases before

patients visit the clinic, thereby making IOP measurements misleading and not reflect variations when medication was

omitted (Windfield et al, 1990; Kass et al, 1986).

Patients also need to be monitored because it has been observed from practice that even the most effective IOP-

lowering medication, the prostaglandins, do not get all patients to low target IOP. Not being able to predict which

patients are able to get to low-target IOP makes it mandatory that patients be monitored at regular intervals.

Monitoring intervals should also be dependent on level of risk factors of each individual.

Assessing Patients with OH and POAG In the early stages of ocular hypertension there are usually no symptoms just as it occurs in glaucoma. This

asymptomatic condition therefore makes diagnosis very difficult and often, initiation of therapy is delayed. For this

reason, to properly categorize these patients, specific tests needs to be conducted. The tests include tonometry

(Goldmann applanation), optic disc evaluation (stereoscopic evaluation & fundus photography), visual field

testing, pachymetry, and gonioscopy.

Careful assessment of the optic nerve is essential for detection and longitudinal evaluation of glaucoma. The cup-disc

ratio, vertical elongation of the optic disc, presence of disc hemorrhage, and nasal displacement of retinal vessels are

few of the indications of optic disc deterioration. The neuroretinal rim in normal eyes shows a characteristic

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configuration. It follows the ISNT (affecting the inferior, then superior, nasal and finally temporal) rule which was

originally described by Jonas and cohorts (1992).

Cup Disc Ratio Evaluation of the cup disc ratio has been a controversy in ocular hypertensive and Glaucoma patient examination. Some

scientist might argue that a larger cup-disc ratio is not a risk factor for developing POAG but rather an indicator of early

glaucomatous damage. However, when a clinician first examines a patient, there is no way to determine whether the

cup-disc ratio observed has been stable during the patient’s lifetime, or has enlarged as part of a disease process,

assuming no previous photographs or measurements exist for comparison (OHTS, 2002). This further substantiates the

fact that regular eye examination at specified intervals depending on level of risk factors should be scheduled for every

ocular hypertensive patient. While the ocular hypertensives might deceive practitioners with their small optic discs, we

now know from a study (Coffey et al, 1993) that persons with small optic discs may get glaucomatous visual field defects

without developing a pathological appearance to the disc until much later. Taking a cut off at 0.5 for cup-disc ratio for

glaucoma cases and suspects will tend to underestimate prevalence of glaucoma suspects. This finding emphasizes the

fact that IOP alone- which often times is used in classifying the ocular hypertensives in clinic practice, is a poor tool for

glaucoma screening.

Fundus Photography The importance of fundus photography and imaging as a baseline data and for documentation /follow up cannot be

overemphasized. Current practice is to obtain baseline ONH photographs and to repeat these for comparison during

follow-up, or to compare the appearance of the ONH at the slit lamp to the baseline photograph. Kamal and colleagues

(2000) estimated limits for change exhibited by normal eyes imaged on two occasions. Thirteen of 21 (62%) ocular

hypertensive eyes that subsequently developed visual-field loss, and 47 of 164 (29%) ocular hypertensive eyes without

visual-field progression, had a change in rim or cup parameters greater than the limits for change. The results of the

OHTS (kamal et al, 2000) underlined the importance of ONH photography to detect progression of patients at risk of

visual-field loss. Other evidence also suggests that quantitative imaging devices have a role in detecting progression

even when visual-field loss is established (Burgoyne, 1994).

Visual Field Evaluation Visual field deterioration follows the progression of Glaucoma. Visual-field changes were defined as abnormalities based

on the Glaucoma Hemifield Test (GHT). Initially two consecutive, reliable, abnormal visual fields were required to define

glaucoma progression. Based on the OHTS recommendation, protocol was changed, requiring three consecutive,

abnormal, and reliable visual-field tests for a patient to reach a glaucomatous endpoint to increase specificity and

stability (Giangiacomo et al, 2006).

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Treatment The OHTS (2002b) further recommends that the decision to place an individual with elevated IOP on topical ocular

hypertensive medications should be based on the following factors:

1. The overall incidence of POAG among individuals in same population

2. The burden of long term treatment, including possible adverse effects

3. Cost of treatment and inconvenience

4. The benefit of the treatment to the individual

5. The individual’s health status and life expectancy.

They also advised that in clinical practice, ocular hypertensive patients be classified into 3 groups of conversion to

glaucoma risk: high, medium and low, depending on the value of key baseline risk factors. Initiation of medical

treatment in the high risk patients is encouraged, the low risk patients should be regularly observed without treatment

and reassessment of any change from baseline (OHTS, 2010).

Further Risk FactorsThe OHTS group also observed that African Americans had thinner central corneas, indicating that central corneal

thickness is an important risk factor in monitoring of these patients. Various other studies have also identified a direct

linear relationship with CCT and IOP, with an increase in IOP associated with thicker corneas. The Ocular Hypertension

Treatment Study (OHTS) showed central corneal thickness (CCT) to be a powerful predictor of development of

glaucoma. Eyes with corneal thickness of 555 microns or less (i.e. eyes with relatively thin corneas) had a threefold

greater risk of developing glaucoma than those who had corneal thickness of more than 588 microns (Ogbuehi and

Almubrad, 2005). The implication was that a corneal thickness of less than 555 microns should be viewed as a risk factor

for development of glaucoma. Taken together, high eye pressure (more than 24 mmHg) and a cornea thinner than 555

microns may form the basis of starting treatment, the aim being to reduce the likelihood of developing glaucoma in the

future.

Corneal Thickness and Glaucoma ManagementRationale has stimulated immense interest and debate regarding the importance of corneal thickness in glaucoma

management. Although there is no evidence as of yet to implicate corneal thickness as an 'independent' risk factor for

development of Glaucoma, there is ample evidence that thicker corneas cause falsely higher eye pressure readings and

thinner corneas cause falsely lower eye pressure readings (Mederios et al, 2005; Ehlers et al, 1975). The level of IOP,

however that kept patients with thinner corneas stable (17mmHg) was no different than for those with thicker corneas

(Konstas et al. 2009).

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A considerable number of patients diagnosed as having ocular hypertension may simply have thicker than average

corneas that result in an overestimation of what is likely a normal, true eye pressure. As a consequence, patients with

ocular hypertension with thicker corneas may be at a much lower risk for glaucoma development than previously

recognized. In contrast, thinner corneas result in an underestimation of the true eye pressure. Therefore even if the eye

pressure is within the normal range, if the cornea is thin, that eye pressure should be viewed with suspicion.

The predictive factors for the development of open-angle glaucoma in individuals with ocular hypertension may be older

age, thinner central corneal thickness, higher cup-disc ratios, and higher pattern standard deviation values on the

automated perimeter at baseline (Coleman and Miglior, 2008). Konstas and cohorts (2009) therefore concluded that

based on pachymetry values, ocular hypertensive patients with thinner corneas more often progressed to glaucoma.

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importance of intraocular treatment decisions in France.

2. Burgoyne CF, Varma R, Quigley HA, et al. Global and regional detection of induced optic disc changeby digitized image analysis. Arch Ophthalmol 1994; 112:261–268.

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4. Centofanti M, Oftalmico O, Zeyen T, et al. The European Glaucoma Prevention Study (EGPS) Group.Results of the European Glaucoma Prevention Study. The European Glaucoma Prevention Study.Ophthalmology 2005; 112:366-375.

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6. Coffey M, Riedy A, Wormald R, Xian WX, et al. Prevalence of glaucoma in the west of Ireland. Br JOphthalmol 1993;77:17-21.

7. Cronemberger S, Lopez Da Silva AC, Calixto N. Importance of intraocular pressure measurements at6.00a.m. in bed and in darkness in suspected and glaucomatous patients. Arq Bras Oftalmol. 2010;73(4): 346-9.

8. Dielemans I, Vingerling JR, Algra D, et al. Primary open-angle glaucoma, intraocular pressure, andsystemic blood pressure in the general elderly population: the Rotterdam Study. Ophthalmology1995;102:54-60.

9. Ehlers N , Bransen T, Sperling S. Applanation tonometry and central corneal thickness. ActaOphthalmol 1975;53:34–43

10. European Glaucoma Prevention Study (EGPS)Group. Predictive factors for open-angle glaucomaamong patients with ocular hypertension in the European Prevention Study. Ophthalmology 2007;114:3-9.

11. Garudadri C, Senthil S, Khanna RC, et al. Prevalence and risk factors for primary glaucoma in adulturban and rural populations in the Andhra Pradesh Eye Disease Study. Ophthalmology2010;117:1352-1359.

12. Giangiacomoa,AC, David Garway-Heathb and Joseph Capriolia. Diagnosing glaucoma progression:current practice and promising technologies. Curr Opin Ophthalmol 2006;17:153–162.

13. Gordon MO, Kass MA, Torri V, Miglior S et al. The ocular Hypertension Treatment study group andthe European Glaucoma Prevention Study Group. The accuracy and clinical application of predictivemodels for primary Open angle glaucoma in ocular hypertensive individuals. Ophthalmology2008;115:2030-2036.

14. Gordon MO, Beiser JA, Brandt JD, Heuer DK et al. The Ocular Hypertension Treatment Study.Baseline factors that predict the onset of Primary Open-Angle Glaucoma. Arch Ophthalmol 2002;120:714-720.

15. Gordon MO, Beiser JA, Brandt JD, et al, Ocular Hypertension Treatment Study Group. The OcularHypertension Treatment Study: baseline factors that predict the onset of primary open-angleglaucoma. Arch Ophthalmol 2002; 120:714-20.

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16. Grissom H, Smith ME, Netland PA. Current management of Ocular Hypertension. ComprehensiveOphthalmology update, LLC 2004(www.medscape.com).

17. Hayreh S, Podhajsky P, Zimmerman MB. Role of Nocturnal arterial hypotension in optic nerve headischemic Disorders. Ophthalmologica 1999; 213: 76-96.

18. Jonas JB, Gusek GC, Naumann GO. Optic disc, cup and neuroretinal rim size, configuration andcorrelations in normal eyes. Invest Ophthalmol Vis Sci. 1992;32:474-475.

19. Kamal DS, Garway-Heath DF, Hitchings RA, Fitzke FW. Use of sequential Heidelberg retinatomograph images to identify changes at the optic disc in ocular hypertensive patients at risk ofdeveloping glaucoma. Br J Ophthalmol 2000; 84:993–998.

20. Kass MA, Gordon MO, Gao F, Heuer DK et al.The ocular hypertension treatment study. DelayingTreatment of ocular Hypertension. Arch Ophthalmol. 2010;128(3): 276-287.

21. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomizedtrial determines that topical ocular hypotensive medication delays or prevents the onset of primaryopen-angle glaucoma. Arch Ophthalmol 2002; 120:701–713.

22. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, et al. The Hypertension Treatment Study. Arandomized trial determines that topical ocular hypotensive medications delays or prevents theonset of primary Open-angle Glaucoma. The Ocular Hypertensive Treatment Study Group. ArchOphthalmol 2002b; 120:701-713.

23. Kass MA, Meltzer DW, Gordon MO, Cooper D, Goldberg I. Complaince with topical pilocarpinetreatment. Am J Ophthalmol. 1986;101:515-523.

24. Kniestedt C, Punjabi O, Lin S, Stamper RL. Tonometry through the ages. Surv Ophthalmol 2008;53:568-591.

25. Konstas AGP, Irkec MT, Teus MA, et al. Mean intraocular pressure and progression based on cornealthickness in patients with ocular hypertension. Eye 2009; 23: 73-78.

26. Leske C, Connell AM, Wu SY, et al. Risk factors for open-angle glaucoma. The Barbados Eye Study.Arch Ophthalmol 1995;113:918-24

27. Levine RA, Demirel S, Fan J, et al, Ocular Hypertension Treatment Study Group. Asymmetries andvisual field summaries as predictors of glaucoma in Ocular Hypertension Treatment Study. InvestOphthalmol Vis Sci 2006; 47:3896-903.

28. Liu JH, Sit AJ, Weinreb RN. Variation of 24-hour intraocular pressure in healthyindividuals.Ophthalmology 2005;112:1670-1675.

29. Liu JH. Diurnal measurement of intraocular pressure. J Glaucoma 2001;10(suppl):S39-41.

30. Liu JH. Circardian rhythm of intraocular pressure. J Glaucoma 1998;7:141-7.

31. Mederios FA, Weinreb RN, Sample PA, et al. Validation of a predictive model to estimate the risk ofconversion from ocular hypertension to glaucoma. Arch Ophthalmol 2005; 123:1351-60.

32. Munoz-Negrete FJ, Rebolleda GT, Ruiz-Casas DB. Ocular Hypertensive treatment study 13 yearslater. Arch Soc Esp oftalmol. 2010;85(3):95-6.

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33. National Institute for Health and Clinical Excellence. Understanding NICE guidance. Diagnosing andtreating glaucoma and raised eye pressure, 2009.

34. Ogbuehi KC, Almubrad TM. Repeatability of central corneal thickness measurements measured withthe Topcon SP2000P specular microscope. Graefes Arch Clin Exp Ophthalmol 2005; 243: 798-802

35. Patel PC, Spaeth GL. Complaince in patients prescribed eyedrops for glaucoma. Oph Surg 1995;26:233-236.

36. Pozarowska D. Safety and tolerability of tafluprost in treatment of elevated intraocular pressure inopen-angle glaucoma and ocular hypertension. Clinical Ophthalmology 2010; 4:1229-1236.

37. Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol 1996;80(5):389-393

38. Saw SM, Wong TY, Ting S, et al. The relationship between anterior chamber depth and the presenceof diabetes in the Tanjong Pagar Survey. Am J Ophthalmol 2007; 144:325- 6.

39. Sommer A, Tielsch JM, Katz J, et al. Relationship between intraocular pressure and primary openangle glaucoma among white and black Americans. The Baltimore Eye Survey. Arch Ophthalmol1991; 109:1090-5.

40. Strouthidis NG, Scott A, Viswanathan AC, Crabb DP, Garway-Heath DF. Monitoring glaucomatousvisual field progression: The effects of a novel spatial filter. Invest Ophthalmol Vis Sci. 2007;48:251-257.

41. Tielsh JM, Katz J, Sommer A et al. Family history and risk factors for primary open angle glaucoma.The Baltimore Eye Study. Arch Ophthalmol 1994;112:69-73.

42. Winfield AJ, Jessiman D, Williams A, Esakowitz L. A study of non-complaince by patients prescribedeyedrops. Br J Ophthalmol 1990;74:477-480.

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Post Test: Monitoring Ocular Hypertension in Patients Complete the following quiz based on the above information and submit the quiz via email, fax, or mail to the ACAO to

receive 2EC credits. Note: More than one answer may apply

Name: _______________________________________

License #: _________________________________________

Date: _________________________________

1. What is the most important risk factor for the development of POAG?

a. age

b. ocular hypertension

c. family history

d. diabetes

e. thinning corneas

2. If treatment is not adequate in ocular hypertensive or glaucoma suspect patients, it is thought that their IOP peaks at what time?

a. 3:00 a.m.

b. 4:00 a.m.

c. 5:00 a.m.

d. 6:00 a.m.

e. 7:00 a.m.

3. If no visual field loss or optic nerve damage is present, a patient is considered to have ocular hypertension if theirIOP is 2 standard deviations above:

a. 17 mmHg

b. 18 mmHg

c. 19 mmHg

d. 20 mmHg

e. 21 mmHg

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4. What have studies shown to be the non-compliance rate when ocular hypertensive patients, or patients withprimary open angle glaucoma are prescribed one medication?

a. 22%

b. 39%

c. 50%

d. 54%

5. What is the risk of developing POAG for ocular hypertensive patients for whom treatment is delayed?

a. 0.16%

b. 0.18%

c. 0.20%

d. 0.21%

e. 0.22%

6. Initiating treatment of ocular hypertensive patients with topical ocular hypotensive medication may reducethe cumulative probabilty of developing glaucoma by as much as:

a. 10%

b. 25%

c. 60%

d. 75%

7. Topical ocular hypotensive medications are effective in reducing optic nerve damage and visual field loss inpatients whose IOP measurements are between which of the following?

a. 22 mmHG and 28 mmHg

b. 22 mmHG and 30 mmHg

c. 24 mmHG and 34 mmHg

d. 20 mmHG and 30 mmHg

e. 24 mmHG and 32 mmHg

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a. prostaglandins

b. carbonic anhydrase inhibitors

c. beta-blockers

d. epinephrine

9. Why is initiation of therapy for ocular hypertension and POAG often delayed?

a. ophthalmologists require several readings on different days prior to the start of treatment

b. patients do not like using ocular drops

c. patients are asymptomatic

d. patients do not want to undergo necessary tests

10. Which clinical tests are performed for the purpose of detecting the presence of ocular hypertension andopen angle glaucoma?

a. fundus photography

b. Goldmann applanation

c. biomicroscope examination

d. corneal topography

11.What indicates optic disc deterioration?

a. hemorrhages within the optic disc

b. corneal anomalies

c. temporal displacement of retinal vessels

d. horizontal elongation of the optic disc

8. What are the most effective IOP lowering medications?

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a. two

b. three

c. four

d. five

13. The decision to treat patients who exhibit elevated IOP with topical ocular hypertensive medications should bebased on:

a. cost of treatment

b. inconvenience of treatment to the patient

c. incidence of the disease among those in the same population

d. age of patient

14. How much greater is the risk of developing glaucoma for patients who have relatively thin central corneas?

a. two times

b. three times

c. four times

d. five times

15. Once baseline fundus photography of the optic nerve head has been done on suspect eyes, follow up comparisonto original photographs may be done by:

a. examination of the ONH using a biomicroscope

b. examination of the ONH by gonioscopy

c. additional fundus photography

12. How many abnormal visual field tests are now required to determine if a patient has actually developed glaucoma as aresult of the OHT study?

a. Caucasians

b. Asians

c. African Americans

indigenous Australians

16.Which group typically presents more often with thinner central corneas?