Megatrends in Optometry:

Evidence Based Medicine-Evaluating Risk VS Benefit in Ocular

Disease Management

Bruce E. Onofrey, OD, RPh, FAAOProfessor, U. HoustonUniversity Eye Institute

Bruce E. Onofrey, OD, RPh, FAAOProfessor, U. HoustonUniversity Eye Institute

QUESTIONS? KEEP IN TOUCH

EYEDOC3@AOL.COM orBONOFREY@OPTOMETRY.

UH.EDU

EVIDENCE BASED MEDICINEEVIDENCE BASED MEDICINE

• Rational care requires a scientific approach to patient management

• Sound clinical research should be the basis for therapeutic decisions

• Know the Disease: Pathophysiology• Know the patient: Histories • Know the therapy: Pharmacology

• Rational care requires a scientific approach to patient management

• Sound clinical research should be the basis for therapeutic decisions

• Know the Disease: Pathophysiology• Know the patient: Histories • Know the therapy: Pharmacology

EVIDENCE BASED MEDICINE

TOPICS

EVIDENCE BASED MEDICINE

TOPICS• MANAGING THE STROKE PATIENT (THE

PC OD)

• LAB TESTING• GLAUCOMA STUDIES• NSAID’s and GLAUCOMA• ANTIBIOTICS AND DRUG RESISTANCE• MANAGEMENT OF SCLERITIS• ANTI-INFLAMMATORY MANAGEMENT IN

DRY EYE

• MANAGING THE STROKE PATIENT (THE PC OD)

• LAB TESTING• GLAUCOMA STUDIES• NSAID’s and GLAUCOMA• ANTIBIOTICS AND DRUG RESISTANCE• MANAGEMENT OF SCLERITIS• ANTI-INFLAMMATORY MANAGEMENT IN

DRY EYE

WHAT IS THE BEST WAY TO REDUCE STROKES?

WHAT IS THE BEST WAY TO REDUCE STROKES?

THE TRENDStroke Prevention

IT’S EVERYBODIES BUSINESS – WHY?

THE TRENDStroke Prevention

IT’S EVERYBODIES BUSINESS – WHY?

• Leading cause of disability• Third leading cause of death• Financial and emotional economies• Modifying risk factors to prevent first

stroke (primary prevention) or recurrent stroke (secondary prevention)

• Leading cause of disability• Third leading cause of death• Financial and emotional economies• Modifying risk factors to prevent first

stroke (primary prevention) or recurrent stroke (secondary prevention)

CHECK PRESURESSSSS!!

CONSIDER IN-OFFICE TESTING YOUR CLUELESS DIABETICS

CONSIDER IN-OFFICE TESTING YOUR CLUELESS DIABETICS

LIFESTYLE CHANGES/BPMetabolic syndrome

LIFESTYLE CHANGES/BPMetabolic syndrome

• Weight loss• Support dietary changes• Exercise, daily activity levels• Educate, motivateTOBACCO CESSATION• Patient education and support-not criticism• Provide TX information• Co-benefit: Reduces risk of eye disease

(AMD)

• Weight loss• Support dietary changes• Exercise, daily activity levels• Educate, motivateTOBACCO CESSATION• Patient education and support-not criticism• Provide TX information• Co-benefit: Reduces risk of eye disease

(AMD)

Diabetes MellitusDiabetes Mellitus• Don’t just examine eyes-discuss

ways to minimize morbidity• Tight diabetes control• 40% - 60% of type 2 DM have

hypertension• Aggressive hypertension

management can lead toIncreased glc/ION risk? (Perf. Pres)

• Don’t just examine eyes-discuss ways to minimize morbidity

• Tight diabetes control• 40% - 60% of type 2 DM have

hypertension• Aggressive hypertension

management can lead toIncreased glc/ION risk? (Perf. Pres)

Atrial FibrillationAtrial Fibrillation

• Can lead to thrombus formation• Warfarin (Coumadin) therapy• Reduces relative risk of stroke

by 70% - 80% in highest-risk groups

• SYMPTOMS INCLUDE HX OF TIA’S – BE VIGILANTE

• Can lead to thrombus formation• Warfarin (Coumadin) therapy• Reduces relative risk of stroke

by 70% - 80% in highest-risk groups

• SYMPTOMS INCLUDE HX OF TIA’S – BE VIGILANTE

Asymptomatic Carotid Artery StenosisAsymptomatic Carotid Artery Stenosis

• Carotid endarterectomy• WATCH FOR TIA’S/CHECK

CAROTID PULSES/BRUIT’S-Look for Hollenhorst plaques

• evidence of ischemia, ie uniterallow IOP, Unilateral GLC, diplopia, etc

• ASK THE RIGHT QUESTIONS

• Carotid endarterectomy• WATCH FOR TIA’S/CHECK

CAROTID PULSES/BRUIT’S-Look for Hollenhorst plaques

• evidence of ischemia, ie uniterallow IOP, Unilateral GLC, diplopia, etc

• ASK THE RIGHT QUESTIONS

Sleep ApneaSleep Apnea

• Oximetry – measures oxygen saturation

• Polysomnogram – sleep study test

• CPAP – continuous positive airway pressure: RED EYE

• Increased risk of glaucoma• NO OPIATES

• Oximetry – measures oxygen saturation

• Polysomnogram – sleep study test

• CPAP – continuous positive airway pressure: RED EYE

• Increased risk of glaucoma• NO OPIATES

Estrogen TherapyEstrogen Therapy

• Research on this topic is changing its use

• Advised against in patients with history of stroke without a medically compelling reason

• BE ALERT TO TIA SIGNS AND SYMPTOMS IN PATIENTS ON HORMONE REPLACEMENT THERAPY-ASK ABOUT SYMPTOMS

• Research on this topic is changing its use

• Advised against in patients with history of stroke without a medically compelling reason

• BE ALERT TO TIA SIGNS AND SYMPTOMS IN PATIENTS ON HORMONE REPLACEMENT THERAPY-ASK ABOUT SYMPTOMS

StressStress

• Offer ways to improve stress levels (be a source of information)

• Knowledge reduces stress-Talk to patients about reducing risk

• Offer ways to improve stress levels (be a source of information)

• Knowledge reduces stress-Talk to patients about reducing risk

NEW FOR YOU!!!NEW FOR YOU!!!

• Fun with Herpes• Fun with HerpesAN ORAL FOR ALLZIRGAN FOR ALLKNOW YOUR HEDSSCOPER STUDY-CYCLOSPORIN A IS OK

New for youNew for youTETRACYCLINE FOR ALL

INFLAMMATION

THE TRENDRATIONAL USE OF LAB TESTS IN

OPTOMETRY-WHY

THE TRENDRATIONAL USE OF LAB TESTS IN

OPTOMETRY-WHY• Verify DX• Medico-legal documentation• Evaluate effectiveness of therapy-TA• Monitor for drug side-effects – CAI-

CBC• Don’t need to do tests-can ask PCP

to order tests-Must be able to explain why the test needs to be done

• Need to be able to interpret the results accurately

• Verify DX• Medico-legal documentation• Evaluate effectiveness of therapy-TA• Monitor for drug side-effects – CAI-

CBC• Don’t need to do tests-can ask PCP

to order tests-Must be able to explain why the test needs to be done

• Need to be able to interpret the results accurately

Important Lab/clinical TestsImportant Lab/clinical Tests• TA: ESR/CBC/CRP/TA biopsy

• Uveitis: ESR, RF, ANA, RPR, VDRL, TB skin test, chest xray/ACE levels

• Infectious keratitis: Culture scraping on blood/chocolate-special tests include Sabourauds and Ecoli plate

• Conjunctivitis: Chlamydia/diff-quick

• MRI/MRA/CT Scans

• Abnormal bleeding?

• TA: ESR/CBC/CRP/TA biopsy

• Uveitis: ESR, RF, ANA, RPR, VDRL, TB skin test, chest xray/ACE levels

• Infectious keratitis: Culture scraping on blood/chocolate-special tests include Sabourauds and Ecoli plate

• Conjunctivitis: Chlamydia/diff-quick

• MRI/MRA/CT Scans

• Abnormal bleeding?

KNOW YOUR PATHOPHYSIOLOGY-EXAMPLE: A TALE OF TWO BLEEDERS

KNOW YOUR PATHOPHYSIOLOGY-EXAMPLE: A TALE OF TWO BLEEDERS

• 50 y/o hispanic male presents to acute care eye clinic with complaint of “bleeding eyes”

• VA w/o correction 20/25 OD, OS• IOP 16 OU• Pupils: 4mm, +3RX, RD, (-) APD

• 50 y/o hispanic male presents to acute care eye clinic with complaint of “bleeding eyes”

• VA w/o correction 20/25 OD, OS• IOP 16 OU• Pupils: 4mm, +3RX, RD, (-) APD

Bleeders: Clin. info Bleeders: Clin. info • #1

• Ecchymosis of lids• bruising on arms• Multiple, recent

episodes of epistaxis• (-) Hx trauma• (-) anticoagulant TX

• #2

• Same + topical CAI use

• #1

• Ecchymosis of lids• bruising on arms• Multiple, recent

episodes of epistaxis• (-) Hx trauma• (-) anticoagulant TX

• #2

• Same + topical CAI use

How does the body prevent hemorrhage? Hemostasis-THE PHYSIOLOGY

How does the body prevent hemorrhage? Hemostasis-THE PHYSIOLOGY

• 1. Small vessels: Vasoconstriction• 2. Larger vessels: Clot formation

• Clot formation• 1. Cellular component: Platelets

• 2. Humoral components: extrinsic pathway-factors III and VII

• 1. Small vessels: Vasoconstriction• 2. Larger vessels: Clot formation

• Clot formation• 1. Cellular component: Platelets

• 2. Humoral components: extrinsic pathway-factors III and VII

Cont’dCont’d• Intrinsic pathway: factors VIII, IX, X,

XII• Liver (Vit K) factors: I, II, V, VII, IX, X• PT: Protime: Measures extrinsic

system and coumadin activity• INR: Latest way to standardize the PT• PTT: Measures intrinsic system:

Used to measure heparin activity

• Intrinsic pathway: factors VIII, IX, X, XII

• Liver (Vit K) factors: I, II, V, VII, IX, X• PT: Protime: Measures extrinsic

system and coumadin activity• INR: Latest way to standardize the PT• PTT: Measures intrinsic system:

Used to measure heparin activity

THE TESTSTHE TESTS• BLEEDING TIME• CBC• INR• LIVER PANEL

• BLEEDING TIME• CBC• INR• LIVER PANEL

BLEEDER #1 : Significant Lab ResultsBLEEDER #1 : Significant Lab Results

• CBC: Generally Normal• INR = 1• Hepatic: Alk Phos 281 VH,

Bili.1.8H Alt (SGPT) 55H (OFF THE SCALE)

• Glucose: Normal• Bleeding time: 23 minutes• ESR: 36H

• CBC: Generally Normal• INR = 1• Hepatic: Alk Phos 281 VH,

Bili.1.8H Alt (SGPT) 55H (OFF THE SCALE)

• Glucose: Normal• Bleeding time: 23 minutes• ESR: 36H

Bleeding timeBleeding time• Very simple test• 1-9 minutes normal• Over 15 minutes is definitely

abnormal

• NOT DIAGNOSTIC-Doesn’t tell WHY the person bleeds abnormally

• Very simple test• 1-9 minutes normal• Over 15 minutes is definitely

abnormal

• NOT DIAGNOSTIC-Doesn’t tell WHY the person bleeds abnormally

Cause of hemorrhage?Cause of hemorrhage?1. Hepatic failure2. Reduced platelets3. Renal failure4. Leukemia5. Drug induced aplastic anemia

1. Hepatic failure2. Reduced platelets3. Renal failure4. Leukemia5. Drug induced aplastic anemia

WHAT’S NEW IN GLAUCOMA?

AIN’T TECHNOLOGY GREAT

• We have those fancy machines-the GDXand a new Cirrus OCT, as well as a CBS, FBI , JFK ETC

Don’t forget-we also have all those nifty new drugs

• Xalatan• Lumigan• Travatan Z• Trusopt• Azopt• Cosopt• Alphagan• Combigan

BUTTTT….The REAL Advancement isn’t technological ie drugs and

equipment, IT’s…IT’s…(WAIT FOR IT)

• KNOWLEDGE !! • ie. INDIVIDUALIZED RISK

ASSESSMENT

The impact of clinical research on current glaucoma management

• Who we treat and who we watch• Initial drug selection/ maximizing drug

combinations / max medical therapy• How we (most accurately) assess disease

progression• The relationship between IOP and BP in GLC

patients• Evaluating and resolving similar studies with

differing outcomes (sponsor bias?): Parrish (XLT) vs Noecker (LX)

THE MEGA-TREND

Managing Glaucoma by the Numbers

THE MEGA-TREND

Managing Glaucoma by the Numbers

Live and die by studies-both good and badLive and die by studies-both good and badOHTS:• RISK FACTORS OF GETTING GLC 5 YRS

EMGT: • IDENTIFIED RISK FACTORS FOR PROGRESSION • TX REDUCES RISK OF PROGRESSION 10%/MM DROP

AGIS:• TARGET IOP BELOW 18

ASRANI:• MINIMIZE DIURNAL FLUCTUATION

NTG:• MUST LOWER IOP A MIN OF 30%

LALES:• C/D > 0.6 IS 93% SENSITIVE & 96% SPECIFIC FOR POAG

DPP• DIASTOLIC PERFUSION PRESSURE AND GLC

OHTS:• RISK FACTORS OF GETTING GLC 5 YRS

EMGT: • IDENTIFIED RISK FACTORS FOR PROGRESSION • TX REDUCES RISK OF PROGRESSION 10%/MM DROP

AGIS:• TARGET IOP BELOW 18

ASRANI:• MINIMIZE DIURNAL FLUCTUATION

NTG:• MUST LOWER IOP A MIN OF 30%

LALES:• C/D > 0.6 IS 93% SENSITIVE & 96% SPECIFIC FOR POAG

DPP• DIASTOLIC PERFUSION PRESSURE AND GLC

LIES, DAMN LIES AND STATISTICSLIES, DAMN LIES AND STATISTICS• ACCORDING TO OHTS:

• TX ALL OC. HYPERTENSIVES REDUCES GLC PREVALENCE BY 50%

• FROM 10% TO 5% IN 5 YEARS• NNT = 22-42• IMPORTANT MESSAGE:

DETERMINATION OF RELATIVE RISK-TX DECISION IS MORE OBJECTIVE

• ACCORDING TO OHTS:

• TX ALL OC. HYPERTENSIVES REDUCES GLC PREVALENCE BY 50%

• FROM 10% TO 5% IN 5 YEARS• NNT = 22-42• IMPORTANT MESSAGE:

DETERMINATION OF RELATIVE RISK-TX DECISION IS MORE OBJECTIVE

POAG Endpoints by Central Corneal Thickness

and Baseline IOP (mmHg) in Observation Group*

POAG Endpoints by Central Corneal Thickness

and Baseline IOP (mmHg) in Observation Group*

Baseline IOP (mmHg)

Central Corneal Thickness (microns) * through 8 Nov 2001

< 23.75

>23.75 to < 25.75

>25.75

< 555 >555 to < 588 >58817% 9% 2%

12% 10% 7%

36% 13% 6%

Vertical C/D Ratio

Central Corneal Thickness (microns) * through 8 Nov 2001

< 0.30

>0.30 to <0.50

>0.50

< 555 >555 to < 588 >588

15% 1% 4%

26% 16% 4%

22% 16% 8%

POAG Endpoints by Central Corneal Thicknessand Baseline Vertical C/D Ratio in Observation Group*

POAG Endpoints by Central Corneal Thicknessand Baseline Vertical C/D Ratio in Observation Group*

The OHTS Lesson

• Treating all ocular hypertensives is not safe/effective or cost effective

• Pachymetry is important• Conversion best determined by Optic Nerve

(Nerve fiber layer) changes HOLD THAT THOUGHT

• TX is optional if risk is acceptable• IF NFL changes or disc changes TX-DON’T

wait for VF changes (thank Harry Quigley )

EMGT: Does TX HelpBest measure of Progression

EMGT: Does TX HelpBest measure of Progression

• Lower IOP Lower risk

• VF vs Disc evaluation

• If TX-What target IOP? Look at AGIS

• Lower IOP Lower risk

• VF vs Disc evaluation

• If TX-What target IOP? Look at AGIS

Lower IOP Stabilizes Glaucoma ProgressionLower IOP Stabilizes Glaucoma Progression

% ofPatients

100%

0%

20%

40%

60%

80%

12/13 14/15 16/17 18/19 20/21 ≥22/23Intraocular Pressure (mm Hg)

Glaucoma Stable Glaucoma Progressing

Additional Support (AGIS):“The AGIS data support the suggestive evidence from earlier studies that achieving low levels of intraocular pressure slows the progressionof glaucomatous optic neuropathy”

Adapted from: Mao LK, et al. Am J Ophthalmol 1991;111:51-55.(AGIS):7 Amer Jrl Ophthalmol 2000;130(4):429-440

Maximize patients with IOP ≤17

Low Pressures Should Be Maintained Over 24 HoursLow Pressures Should Be Maintained Over 24 Hours

12

43

57

88

0102030405060708090

100

Highest Diurnal IOP Fluctuation

Lowest Diurnal IOP Fluctuation

Risk Associated With Diurnal IOP Variations

Asrani S, et al.. J Glaucoma. 2000;9(2):134–142.

Stable Vision Loss

Collaborative NTG Treatment TrialCNTG Group. Am J

Ophthalmol.1998;126:487-497

30% IOP reduction limits VF progression by 2/3 @@@@@@

140 eyes

Collaborative NTG Treatment TrialCNTG Group. Am J

Ophthalmol.1998;126:487-497

30% IOP reduction limits VF progression by 2/3 @@@@@@

140 eyes

0

0.2

0.4

0.6

0.8

1

1 2 3 4 5 6 7 8

Proportion of patients

with protocol-defined

endpoints

Years

Treated

Controls

P < 0.0001

PSEUDO NTGTHIN CORNEADIURNAL FLUCTUATION

LALES StudyC/D Ratio as screening tool

• Los Angeles Latino Eye Study• Comprehensive evaluation for predictors

of eye disease in this population• 6,357 latinos over 40Y/O• Vertical C/D > 0.6 cutoff for glc screening• 92.3% sensitive for glc• 95.3% specificity for glc

Low ocular perfusion pressure has been shown to be strongly associated with the prevalence of glaucoma progression in multiple population-based surveys

Tielsch JM, et al. Arch Ophthalmol. 1995.Leske MC, et al. Arch Ophthalmol. 1995.Leske MC, et al. Arch Ophthalmol. 2002.Quigley HA, et al. Arch Ophthalmol. 2001.Bonomi L, et al. Ophthalmol. 2000.Leske et al.Ophthalmology 114 (11), November 2007

BP – IOP = Ocular Perfusion Pressure (OPP)(BP is mean arterial pressure, diastolic BP, or systolic BP)

Ocular Perfusion Pressure and Glaucoma Progression

Perfusion Pressures

• Mean arterial pressure (MAP) = 2/3 diastolic + ½ systolic

• Mean Arterial OPP = MAP- IOP• Systolic OPP = Systolic - IOP• Diastolic OPP = Diastolic - IOP

Lower Diastolic,Systolic, or

Mean PressureReduces Perfusion

Pressure

HigherIOP

Negatively ImpactsPerfusion Pressure

Perfusion PressureIs a Result of

A Delicate BalanceBetween IOP

and Blood Pressure

LowerPerfusion PressureIs Associated withIncreased Risk for

Open Angle GlaucomaLeske MC, et al. Ophthalmology 2007; 114,: 1965-72Leske MC, et al. Ophthalmology 2008;115, 65-93. Hayreh SS. Trans Am Acad Ophthalmol 1974;78:240-54

Ocular Perfusion Pressure and Glaucoma Progression

OPP and Glaucoma Progression:Population Studies

• Baltimore Eye Survey (AA and Caucasian)1

- 6x excess of POAG in subjects with lowest category of Ocular Perfusion Pressure (OPP)

• Egna-Numarkt Study (Caucasian)2

- Lower Diastolic Ocular Perfusion Pressure (DOPP) associated with marked, progressive increase in frequency of POAG

• Barbados 4 yr Eye Study (African-Caribbean)3

- 4-year risk of developing glaucoma increased dramatically at lower perfusion pressure

• Proyecto Ver (Hispanic)4

- Found lower Diastolic Perfusion Pressure (DPP) associated with increased risk of POAG

1. Tielsch, Katz, Sommer, Quigley, Javitt. Arch Ophthalmol 1995;113:216-21 2. Bonomi L, Marchini G, Marraffa M et al. Ophthalmology 2000;107:1287-933. Leske MC, Wu S-Y, Nemesure B, et al. Arch Ophthalmol 2002;120:954-9.4. Quigley HA, West SK, Rodriguez J, et al. Arch Ophthalmol. 2001;119:1819-26.

Ocular Perfusion Pressure and Glaucoma Progression: New

Evidence• Barbados Eye Study 9-year Risk

Factor Study• EMGT Predictors for Long-term

Progression• Thessaloniki Eye Study• EGPS Inter-current Risk Factors

OPP: Barbados 9-year• Cohort study of African-Caribbeans

residing in Barbados, West Indies

• 9-year risk of developing glaucoma increased dramatically at lower perfusion pressure

Leske MC, Wu S-Y, Nemesure B, et al. Arch Ophthalmol 2002;120:954-9.

POAG Risk Factors 9-year BES

Leske MC, Wu S-Y, Nemesure B, et al. Ophthalmol 2008;115:85-93.

Barbados Eye Study Conclusions

• Correlates indicating increased risk of GLC progression (in order of significance)

Low mean perfusion pressureFamily HX of GLCCorneal thicknessElevated IOPAgeIncreased Systolic BP was a protective

Thessaloniki Eye Study

• Performed HRT in 263 subjects

• Excluded those subsequently identified with glaucoma

• Patients with DBP < 90 as a result of systemic anti-HTN treatment had larger C:D ratios and cup areas on HRT compared to normals with DBP < 90 and HTN patients with BP ≥ 90

Topouzis et al. Am J Opthalmol 2006;142:60-67

FINALLY, how does perfusion pressure data effect drug selection and treatment

methods?• What’s happening to IOP at night?• What drugs work well on a 24 hour?

cycle (particularly during sleep)?• Which drugs maximize 24 hour IOP

control with minimal effect on BP?• First, the LIU studies from Weinrebs

GLC lab

Both healthy eyes and eyes with glaucomatous changes showed higher nocturnal supine IOP than diurnal sitting IOPSupine IOP is higher than sitting IOP, regardless of time of day

Healthy supine IOPHealthy habitual IOP

IOP Is Higher at Night

IOP

(mm

Hg)

Glaucoma supine IOP

Glaucoma habitual IOP

3:30

AM

3:30

PM

5:30

PM

7:30

PM9:

30 P

M11

:30

PM1:

30 A

M

5:30

AM

7:30

AM

9:30

AM

11:3

0A

M1:

30 P

M

252423222120191817161514

26

Clock Time

n=24

NocturnalSupine

Diurnal SittingDiurnal SittingNocturnalSupine

Diurnal SittingDiurnal Sitting

Clock Time

1:30

PM

IOP

(mm

Hg)

252423222120191817161514

26

3:30

AM

3:30

PM

5:30

PM

7:30

PM

9:30

PM

11:3

0 PM

1:30

AM

5:30

AM

7:30

AM

9:30

AM

11:3

0 A

M

n=24

NocturnalSupine

Diurnal SupineDiurnal SupineNocturnalSupine

Diurnal SupineDiurnal Supine

Liu et al. Invest Ophthalmol Vis Sci. 2003;44:1586-1590.

Glaucoma Medications and their effects on Ocular Perfusion Pressure (OPP)

27 Patients treated with BID timolol 0.5%, BID brimonidine 0.2%, TID dorzolamide 2% or QHS latanoprost 0.005% for six weeks, followed by a 4-week washout period between different treatments

24-hour IOP monitoring in habitual position24-hour systemic blood pressure monitoring

Quaranta L et al. Invest Ophthalmol Vis Sci. 2006;47:2917-2923.

GOAL: Based upon drug effect on IOP and BP find the best mono therapeutic agent and best drug combination

Baseline Timolol Brimonidine Dorzolamide Latanoprost

Mean 24-Hour Diastolic Ocular Perfusion Pressure(mm Hg)1

50.7 53.0 46.2Significant

reduction in DOPP

(p < 0.0001)

55.9Significant

improvementin DOPP

(p < 0.0001)

56.4Significant

improvementin DOPP vs.

baseline(p < 0.0001)

1. Quaranta L et al. Invest Ophthalmol Vis Sci. 2006;47:2917-2923.2. Quigley HA, West SK, Rodriguez J, et al. Arch Ophthalmol. 2001;119:1819-26

Diastolic Ocular Perfusion Pressure (DOPP) Results

* Reduction in DOPP is a risk factor for glaucoma progression2

Baseline Timolol Brimonidine Dorzolamide Latanoprost

Mean 24-Hour Diastolic Ocular Perfusion Pressure(mm Hg)1

50.7 53.0 46.2Significant

reduction in DOPP

(p < 0.0001)

55.9Significant

improvementin DOPP

(p < 0.0001)

56.4Significant

improvementin DOPP vs.

baseline(p < 0.0001)

1. Quaranta L et al. Invest Ophthalmol Vis Sci. 2006;47:2917-2923.2. Quigley HA, West SK, Rodriguez J, et al. Arch Ophthalmol. 2001;119:1819-26

Diastolic Ocular Perfusion Pressure (DOPP) Results

* Reduction in DOPP is a risk factor for glaucoma progression2

Brimonidine46.2

Significant reduction in

DOPP (p < 0.0001)

Relationship between Nocturnal Hypotension and OPP

• Low BP at night, coupled with high IOP in supine position, compromise OPP

• Use systemic BP meds in the AM to minimize nocturnal hypotention

• Use IOP lowering drugs that lower IOP during BOTH the diurnal and nocturnal period (CAI’s and prostaglandins)

• Avoid IOP meds that lower systemic BP at night (beta blockers, alpha agonists)

Graham, Drance. Surv Ophthalmol. 1999;43(suppl 1):S10-16Hayreh, Zimmerman, Podhajsky. Am J Ophthalmol. 1994;117:603-624Colligan, Dewe, Guillaume, Colligan-Brach. Int Ophthalmol 1998;22:19-25

Think holistically

• Consider measuring perfusion pressures

• Monitor those at greatest risk-low BP/over-aggressive BP control

• Nocturnal hypotension can produce NA-ION

• Talk with PCP

The influence of diclofenac ophthalmic solution on the intraocular pressure-lowering effect of topical 0.5% timolol and 0.005% latanoprost in primary open-angle glaucoma patients.

Costagliola C, Parmeggiani F, Antinozzi PP, Caccavale A, Cotticelli L, Sebastiani A.

Department of Ophthalmology, University of Ferrara, Ferrara, Italy. costaciro@libero.it

PURPOSE: To verify the influence of a non-steroidal anti-inflammatory drug ophthalmic solution on intraocular pressure reduction induced by 0.5% timolol and 0.005% latanoprost eyedrops in patients affected by primary open-angle glaucoma.

CONCLUSION:

In primary open-angle glaucoma patients, diclofenac significantly enhances the hypotensive effect of latanoprost (approx 25% below treatment

baseline) without influence on timolol efficacy. Because non-steroidal anti-inflammatory drugs

are widely employed in medical practice, supplementary ophthalmologic checks should be scheduled during the co-administration of these

compounds and prostaglandin analogues.

CONCLUSION:

In primary open-angle glaucoma patients, diclofenac significantly enhances the hypotensive effect of latanoprost (approx 25% below treatment

baseline) without influence on timolol efficacy. Because non-steroidal anti-inflammatory drugs

are widely employed in medical practice, supplementary ophthalmologic checks should be scheduled during the co-administration of these

compounds and prostaglandin analogues.

Proposed mechanism of synergism of NSAID and Xalatan

Proposed mechanism of synergism of NSAID and Xalatan

• NSAID inhibits endogenous prostaglandin cmpds

• Lowered prostaglandin levels stimulate an increase in prostaglandin tissue receptors.

• Increased tissue sensitivity to exogenous prostaglandins

• NSAID inhibits endogenous prostaglandin cmpds

• Lowered prostaglandin levels stimulate an increase in prostaglandin tissue receptors.

• Increased tissue sensitivity to exogenous prostaglandins

THE TREND:

Reducing Bacterial Resistance

THE TREND:

Reducing Bacterial Resistance

QUICK QUIZ!!QUICK QUIZ!!• How does bacterial resistance

develop?

• A. Rapid reproduction leads to spontaneous mutation

• B. Bacteria have a mid-life crisis, buy a sports car, new clothes, new shoes, become a blonde, and mutate

• C. They intentionally mutate• D. I SAID “What the heck is for

dinner”.

• How does bacterial resistance develop?

• A. Rapid reproduction leads to spontaneous mutation

• B. Bacteria have a mid-life crisis, buy a sports car, new clothes, new shoes, become a blonde, and mutate

• C. They intentionally mutate• D. I SAID “What the heck is for

dinner”.

How do bacteria become resistant and what are you going to do about it?!!

How do bacteria become resistant and what are you going to do about it?!!

RESISTANCE IS NOT FUTILE!! or spontaneous

RESISTANCE IS NOT FUTILE!! or spontaneous

Fluoroquinolone (Cipro) use stimulates mutation in E.coli

Induction and Inhibition of Ciprofloxacin Resistance-conferring Mutations in Hyper-mutator

BacteriaCirz, RT, Romesberg, FE Antimicrobial agents and

chemotherapy, Vol. 50, #1, 220-25, Jan. 2006

Fluoroquinolone (Cipro) use stimulates mutation in E.coli

Induction and Inhibition of Ciprofloxacin Resistance-conferring Mutations in Hyper-mutator

BacteriaCirz, RT, Romesberg, FE Antimicrobial agents and

chemotherapy, Vol. 50, #1, 220-25, Jan. 2006

• Resistance is not a passive process-it is an active defensive process that is stimulated by bacterial stress

• Lex A protein inhibits mutation genes• Cipro use produces cleavage of the Lex A protein that

suppresses the activation of mutagenic genes. • Polymerases are released that stimulate rapid mutations

that lead to production of drug resistant bacteria-a defensive mechanism of the bacteria. Resistant bacteria do not bind cipro to DNA gyrase.

• By dosing fluoroquinolone with a cmpd that inhibits Lex A protein cleavage, mutagenesis and subsequent resistance was eliminated

• Resistance is not a passive process-it is an active defensive process that is stimulated by bacterial stress

• Lex A protein inhibits mutation genes• Cipro use produces cleavage of the Lex A protein that

suppresses the activation of mutagenic genes. • Polymerases are released that stimulate rapid mutations

that lead to production of drug resistant bacteria-a defensive mechanism of the bacteria. Resistant bacteria do not bind cipro to DNA gyrase.

• By dosing fluoroquinolone with a cmpd that inhibits Lex A protein cleavage, mutagenesis and subsequent resistance was eliminated

Episcleritis and scleritis: clinical features and treatment results.

Jabs DA, Mudun A, Dunn JP, Marsh MJ.

Department of Ophthalmology, The Johns Hopkins University School of Medicine,

Baltimore, Maryland, USA. dajabs@jhmi.edu

PURPOSE: To evaluate the clinical experience with episcleritis and scleritis at a tertiary care eye

center. drugs.

CONCLUSIONS: Scleritis is a severe ocular inflammation, often associated with ocular complications, and nearly always treated with systemic medications. Nearly 60% of these patients will need oral corticosteroids or immunosuppressive drugs to control the disease.

AUTOIMMUNE DISEASEAUTOIMMUNE DISEASE

• Episcleritis VS Scleritis• Differential DX of Scleritis-Underlying

systemic disease is common-Can I use a topical steroid? If systemic, what TX has greatest safety/efficacy?

• 4 types of scleritisAnterior diffuseAnterior nodularNecrotizing anterior-97% syst. Disease

(Avoid topical steroids-scleral melting)Posterior------High flow vs low flow??

• Episcleritis VS Scleritis• Differential DX of Scleritis-Underlying

systemic disease is common-Can I use a topical steroid? If systemic, what TX has greatest safety/efficacy?

• 4 types of scleritisAnterior diffuseAnterior nodularNecrotizing anterior-97% syst. Disease

(Avoid topical steroids-scleral melting)Posterior------High flow vs low flow??

Mycophenolate mofetil (Cellcept) therapy for inflammatory eye disease.

Thorne JE, Jabs DA, Qazi FA, Nguyen QD, Kempen JH, Dunn JP.

Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. jthorne@jhmi.edu

CONCLUSIONS: These data suggest that mycophenolate mofetil may be an effective corticosteroid-sparing agent in the treatment of inflammatory eye disease with a manageable side effect profile.

RESULTS: Of the 84 patients treated with mycophenolate mofetil, 61% had uveitis, 17% had scleritis, 11% had mucous membrane pemphigoid, and 11% had orbital or other inflammatory disease. Forty-three percent of patients treated with mycophenolate mofetil had been treated with at least one other immunosuppressive drug previously. The median dose of prednisone at the start of mycophenolate mofetil therapy was 40 mg, and 82% of the patients were considered a treatment success, as judged by the ability to control the inflammation and taper prednisone to < or =10 mg daily.

CellceptCellcept• T-cell inhibitor• Used to prevent transplant

rejection• Start with 500mg BID• Go to 1000mg BID if necessary• GI upset most common• Monitor renal and hepatic

function

• T-cell inhibitor• Used to prevent transplant

rejection• Start with 500mg BID• Go to 1000mg BID if necessary• GI upset most common• Monitor renal and hepatic

function

Dry eye-Management of INflammation is IN

Dry eye-Management of INflammation is IN

• Who would have ever thought steroids would be indicated for dry eye management

• It’s simple logic• Dry eye = injury = inflammation

• Who would have ever thought steroids would be indicated for dry eye management

• It’s simple logic• Dry eye = injury = inflammation

Stern et al. Cornea. 1998:17:584

Lacrimal Glands:• Neurogenic

inflammation• T-cell activation• Cytokine secretion into

tears

Interrupted Secretomotor Nerve Impulses

Tears Inflame Ocular Surface

Cytokines Disrupt Neural Arc

Inflammation disruptsnormal neuronalcontrol of tearing

Dry Eye Disease: An Immune-Mediated Inflammatory Disorder

Dry Eye Disease: An Immune-Mediated Inflammatory Disorder

Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjogren syndrome.

Marsh P, Pflugfelder SC.

Ocular Surface and Tear Center, Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, Florida 33136, USA.

CONCLUSIONS: These findings indicate that topical nonpreserved methylprednisolone is an effective treatment option for patients suffering from severe keratoconjunctivitis sicca who continue to experience bothersome eye irritation despite maximum aqueous enhancement therapies. They also suggest that inflammation is a key pathogenic factor in this condition.

WHICH CAME 1ST-THE PUNCTAL PLUG OR THE STEROID

WHICH CAME 1ST-THE PUNCTAL PLUG OR THE STEROID

[Nonpreserved topical steroids and lacrimal punctal occlusion for severe keratoconjunctivitis sicca]

Sainz De La Maza Serra M, Simon Castellvi C, Kabbani O.

Servicio de Oftalmologia, Unidad de Inmunologia Ocular y Uveitis, Hospital Clinico y Provincial de Barcelona, Espana.

CONCLUSIONS: Topical nonpreserved steroid therapy for two weeks before punctal occlusion is effective in controlling symptoms and corneal fluorescein staining in patients with severe keratoconjunctivitis sicca associated with Sjogren's syndrome.

KNOW YOUR AUTONOMICSKNOW YOUR AUTONOMICS

THE BAD 3 D’STHE BAD 3 D’S

• DRY• DROWSY• DILATED

• PARASYMPATHOLYTICS

• DRY• DROWSY• DILATED

• PARASYMPATHOLYTICS

THE GOOD 3 ’STHE GOOD 3 ’S

• DROOL• DIARRHEA• DAMP

• PARASYMPATHOMIMETICS

• DROOL• DIARRHEA• DAMP

• PARASYMPATHOMIMETICS

SalagenPilocarpine

• Oral parasympathomimetic agent@@@@

• Stimulates exocrine gland secretion• Monitor for GI upset@@@@• Don’t use in asthmatics• Expensive

SalagenIndications/Dosage forms

• Indications:• Advanced, non-responsive

Sjogrens@@@@• 5mg QID• Dosage form:• 5mg tablets

Evoxac: New and improved pilocarpine

• Parasympathomimetic• Better tolerated• 30mg TID• No titration necessary• NEVER in asthmatics

THE END

Thank you for your hospitality and attention

THE END

Thank you for your hospitality and attention