Glaucoma For The Everyday Optometrist Eric E. Schmidt, O.D., - - PDF document

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Glaucoma For The Everyday Optometrist

Eric E. Schmidt, O.D., F.A.A.O. Omni Eye Specialists Wilmington, NC schmidtyvision@msn.com

Disclosures For Dr. Schmidt

• Dr Schmidt is a consultant or advisor for:

 Allergan  Aerie Pharmaceuticals  B & L  AMO  Optovue  Glaukos  Sensimed

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Glaucoma Risk Factors

• FINDACAR
• The more risk factors one has, the more

likely one is to develop glaucoma

• The more risk factors one has, the lower

the IOP target should be

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A Review Of Risk Factors

• FINDACAR

 Family history  IOP  Nearsightedness  Diabetes/Vascular disease  Age  Corneal thickness  Asymmetry  Race

A risk factor analysis is critical

• For the diagnosis
• To increase your level of suspicion
• For initiating therapy
• For changing therapy
• BUT…are any of these more important

than others?

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OHTS

• Goal of tx – 20% drop in IOP
• 24mm target IOP

RESULTS: At 5 years 4.4% of tx group developed POAG 9.5% of no tx group developed POAG So - lowering IOP in Oc Hx reduced the likelihood of glaucoma by 50% - RIGHT?

OHTS – A Closer Look

• 90% of untreated group did not progress
• 95.6% of tx group did not progress
• It proved that in those individuals who

are going to progress to POAG lowering IOP by 22.4% will delay the onset by at least 5 yrs.

• Who are “ those individuals at risk”?

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OHTS – The Nitty Gritty

• The most predictive factors for conversion:

 Older age

• 22% increase/ decade

 Larger horizontal and vertical C/D

• 32% increase/0.1 larger

 Higher baseline IOP

• 10% increase/ mm Hg

 Thinner corneas

• 71% increase in risk/ 40 microns thinner

Risk Factors For Conversion

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The pachymetry issue

• Juicy Data

 36% of pxs w/ IOP >25.75 AND K thickness < 555

microns developed POAG

 6% of pxs w/ same IOP but K thickness > 588

converted toPOAG

• Juicy Data II

 15% pxs w/ C/D .3/.3 and K thickness < 555 microns

converted but

 4% of pxs w/ same disk parameters and K thickness>

588 microns converted

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More Pachymetry Chatter

• African-Americans have thinner corneas
• Perhaps thin corneas translate to poor

connective tissue at the disk as well

• Is there a fudge-factor for K thickness?

 Baseline of 545 microns  Add or subtract 2.5mm Hg for every 50

microns deviation (Doughty and Zaman, Surv Ophthalmol, 2000).

• How should you use this data?

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Corneal Thickness And Glaucoma The Latest Scoop

• CCT and VF loss –

 CCT is a strong predictor for field loss in both

NTG and POAG

 CCT-adjusted IOP does not predict VF loss

• Sullivan-Mee, Halverson, et.al. Optometry

2005;76:228-38.

Corneal Thickness and Glaucoma

• CCT and Visual Function In OHT pxs

 OHT pxs with abnormal SWAP results had

significantly thinner CCT than normals or OHT pxs with no VF defects

 Abnormal VF – 545microns  OHT w/ normal VF – 572 microns  Normals – 557 microns

• Medeiros, Sample, Weinreb – AJO Feb, 2003 135,No.2
• So????

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CCT And Glaucoma- More latest scoop

• RNFL thickness and CCT in OHT pxs

 RNFL in OHT pxs with CCT < 555 was

significantly thinner than in those with CCT >555.

 RNFL of normals and OHT pxs with CCT

>555 were similar

 Points to an inherent structural predispositon

to glaucomatous damage?

 Kaushik,S, et.al, AJO May 2006, 884-890.

CCT and Treatment Response

• OHTS group –AJO, November, 2004
• Pxs with thinner corneas responded better to

PGA and beta-blockers

 1mm difference for beta-blockers  1.5-2.5 mm difference for PGAs  550 microns was tipping point

• Fan and Camras reported similar results with

brimonidine (ARVO, 2004)

• Why??? And what clinical implications are

there?

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EMGT Conclusions

1) Reducing IOP (by 25%) prevents or slows VF

defect and progression

2) For each 1mm of IOP reduction there is a 10%

lower risk of VF loss

3) Study design and outcome show that these

results are only due to IOP reduction (non IOP related factors showed difference between the 2 groups)

4) Tx effect was equal across age and glaucoma

categories

Eric’s spin on the EMGT

• 1-2 extra mm Hg may indeed be important-

especially in advanced cases.

• For those pxs who need treatment, aggressive

therapy is warranted

• It is probably better to treat early than late
• You do not necessarily need to wait until the VF

defects arise before therapy is initiated

• The benefit of treatment does last throughout the

lifetime of the px – just remember the risk/benefit

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AGIS Results

• Pxs who achieved IOP < 18mm on 100%
• f f/up visits showed no VF progression

(avg IOP 12.3mm)

• Pxs w/ IOP < 18mm on<50% of f/up visits

showed VF progression (mean IOP 20.2mm)

Low IOP Slows or Halts Vision Loss in Open-Angle Glaucoma

Mao et al, AJO, 1991

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Aggressive IOP Lowering Needed In Advanced POAG IOP <15 mm Hg

Shirakashi et al, Ophthalmologica, 1993

Diurnal IOP Fluctuations Speed Glaucomatous Progression

Asrani et al, J Glauc, 2000

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AGIS Results

• Diurnal Curve Is Real Important

 Avg IOP of 15mm with a curve btwn 13mm –

17mm progresses less than if curve is btwn 11mm – 19mm

• The peak IOP is important
• Which tx best affect the diurnal curve?
• Also remember risk/benefit ratio

Consistently Low IOP Reduces Vision Loss

Mean IOP 20.2 mm Hg 16.9 mm Hg 14.7 mm Hg 12.3 mm Hg

AGIS 7, AJO, 2000

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SOOOO…….

• How can we best determine IOP

fluctuation?

• How can we plot a curve?

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CNTGS Results

• 35% untreated progressed over 3 yrs
• 7% of treated eyes progressed
• 30% IOP reduction achieved w/ drops,

laser or surgery

• Showed that several VF were needed

before progression was shown

• A very low IOP is beneficial

Predictive Factors For Progressing POAG

• Older age
• Advanced VF damage
• Worsening MD (-4)
• Smaller neuroretinal im
• Larger zone Beta

 Martus, Jonas, et.al. AJO, June 2005

• Baseline IOP, but not Mean IOP
• Martinez-Bello, et al, AJO March 2000.
• Lower CH

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Risk factors for progression

• Predictive Factors for Progressive Optic Nerve Damage

in Various Types of Chronic Open-Angle Glaucoma -

 Martus, Budde, Jonas, et.al. – AJO 6/05

• POAG-

 Older age  Advanced perimetric damage  Smaller neuroretinal rim  Larger Beta zone

• NTG-

 Baseline disk hemorrhage

• Also – CORNEAL HYSTERESIS!!!!

When deciding to treat …

• Identify…

 Risk factors for conversion  Risk factors for progression  Risk factors for rate of progression

• Initial peak IOP
• Age
• C/D ratio
• Systemic/vascular status

 Noscitur a sociis!

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IOP and Glaucoma

• Which IOP is most important?

 Mean IOP  Peak IOP  Trough IOP  IOP range

• For pxs who showed progression of

glaucoma despite IOP at acceptable range

 3% showed a peak IOP >21mm  35% showed a range of IOP >5mm

 Collaer, Caprioli, et.al, J Glaucoma 2005;14(3): 196-200

• Underscores the importance of serial

tonometry even in well controlled pxs

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When Is The Peak IOP?

• 3,025 IOP readings on 1,072 eyes
• NTG, POAG, Pre-perimetric G, OHT
• Results:

 Peak IOP – 7AM – 20.4% 

Noon – 17.8%



5PM - 13.9%



9PM – 26.7%

 Jonas, Budde, et al. AJO, June 2005;139:136-137

Jonas study conclusion

• “Any single IOP measurement taken

between 7AM and 9PM has a higher than 75% chance to miss the highest point of the diurnal curve.”

• Stresses the need for serial tonometry.

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IOP and Glaucoma

• Which IOP is most important?

 Mean IOP  Peak IOP  Trough IOP  IOP range  Intervisit IOP Range

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Intervisit IOP Range

• A measure of long-term IOP fluctuation
• Intervisit IOP range calculated by:

 Highest IOP minus lowest IOP at 4 different

measurements

 Calculated both pre- and post-treatment

• Range is considered high (> 6mm) 0r low (</

6mm)

• High intervisit IOP range should be

considered a risk factor for progression

• Varma et al AJO 2/09

Risk factors for high post-treatment IOP range

• High pre-treatment intervisit IOP range
• African-American
• Higher mean pretreatment IOP
• Longer time since diagnosis
• Multiple pre and post-treatment readings

are necessary to find the true level

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Using this marker:

• Doctors able to predict (estimate) peak

IOP 70% of time

• Able to estimate IOP fluctuation ~50% of

time

IOP Standard Deviation

• Another predictor of progression
• Mean IOP 16.5mm Hg
• SD calculated to be 2.0 or 2.7mm Hg
• Each unit increase in SD results in a 4.4 –

5.5 times higher risk for progression

• Clinically, what does this mean?
• Lee, Walt, et al AJO 7/07

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So What Do Standard Deviations Mean To Me?

• If mean IOP is 16 then:

 Acceptable range should be 14 – 18 mm Hg  If the IOP exceeds that by 1 SD (2.0 -2.5

mmHg) then the likelihood of progression increases by 4.2 -5.5 times

• Further evidence to set a target IOP AND

STICK TO IT!!

By The Way…

• Latanoprost results in 6% of pxs with high

IOP fluctuation

• Timolol ½% yields 11% with high IOP

fluctuation

• So…..?????

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What to do if IOP increases between visits?

• IOP fluctuation between 2 visits is not predictive of

long term success or failure of medication.

• True whether using monocular trial or unadjusted

IOP change

• Multiple pre-and post-treatment IOP readings are

necessary

• Multiple VF and imaging studies are necessary

Measuring IOP

• 5 methods:

 Goldmann applanation  Tonopen  Non-Contact  Direct Applanation (Pascal)  Pneumotonometry

• Is 1 method more accurate?
• What about telemetry?

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“New” Goal of treatment in Glaucoma

• Low and Stable IOP
• Minimize the diurnal curve
• Prevent IOP peaks

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Treatment Goals of Glaucoma

• Maximum IOP reduction—achieve lower IOP

to help preserve sight; historically physicians tried to achieve pressures below 20 mm Hg

• Maintaining low IOP over 24 hours—avoid

pressure spikes associated with visual field progression

• Ease of use—patient compliance is best with

simple, easy-to-use medication regimen (typical glaucoma patient uses at least 3 other systemic medicines); monotherapy is preferred

• Safety—minimize systemic safety issues

Gottfredsdottir et al. J Glaucoma. 1997.

EMGT: Every mm Hg of IOP Lowering Matters

Leske et al. Arch Ophthalmol. 2003.

Change in Risk (95% CI)

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Recommendations

• Minimum initial target IOP reduction of 25%

recommended for glaucoma patients

• More aggressive initial target IOP reductions
• f 30% or 35% recommended for most

patients: especially those at higher risk

• Target IOP must be DYNAMIC, re-evaluated

periodically, and lowered if patient progresses despite meeting the initial target IOP

 Re-evaluate and adjust patient’s target IOP

at least every 5 years, and in light of newest information

The Delphi Panel. PDR. 2003.

General Rule #1

• 30% decrease as an initial target
• Target decrease from highest untreated

IOP

• CNTGS, OHTS

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General Rule #2

• Mild glaucoma – decrease IOP 30%
• Moderate glaucoma – decrease IOP 40%
• Severe glaucoma – decrease IOP 50% (at

least)

When should the target IOP be changed?

• VF progression (even at target IOP)
• Neuroretinal rim recession (even at target

IOP)

• Parametric changes
• Long term stability – even if on multiple

meds

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Importance of IOP Stability

• IOP variation is a risk factor for VF

loss in glaucoma

• VF protected best when pressures

are consistently kept under 18 mm Hg

• Wide swings in IOP during the day or

from visit to visit should be avoided

• Stabilizing IOP is vital

AGIS: Need to Maintain Low IOP Over Time

• ALT or surgery in

uncontrolled glaucoma

• Target IOP <18 mm Hg
• 100% of visits <18 mm

Hg: on average no loss in VF

• Any visits with IOP

target not met: on average significant VF loss

 2-unit loss in VF over 7

years when target met at <75% of visits

AGIS:7. Am J Ophthalmol. 2000.

CONCLUSION: Progression is minimized when IOP is kept consistently low (<18 mm Hg)

Mean Change in VF Score

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AGIS: Patients With Small IOP Variation Had Stable Fields

• Eyes with variation < 3 mm Hg: no average progression
• Eyes with variation ≥ 3 mm Hg: on average, significant

progression

Nouri-Mahdavi et al. Ophthalmology. 2004.

Visual Fields and Glaucoma

• Are they still cool?
• Are they considered the standard of care?
• How often?
• Do they better measure early detection or

progression?

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Are certain VF parameters more predictive for progression?

• Johnson, Sample et al. – AJO 8/2002 177-

185

• Highest predictors of conversion

 GHT “outside normal limits”  2 hemifield clusters worse than 5% level  4 abnormal (P<.05) locations on pattern

deviation probability plot

 Specificity increased with 2nd confirmatory VF

test

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Which VF instrument is best?

• SAP, SWAP or FDT



FDT and SWAP similar in flagging abnormal locations



FDT defects were more extensive in 62%

• SWAP more specific and accurate than

SAP but harder to administer

• FDT questionable in end stage glaucoma
• Use 10-2 strategy in advanced glaucoma

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Regarding Visual Fields

• Are they more better for early glaucoma?
• OR
• Are they more better in established

glaucomas?

Treatment Paradigm Summary

• Mean IOP in study populations

 Early treatment to lower IOP reduces and delays progression  NEI trials show better outcomes at lowest IOP

• IOP in individual patient

 To preserve vision, every mm Hg matters  Individualized, low target IOP recommended

• New predictors of progression

 Diurnal fluctuation and long-term variation in IOP within

individual patients can cause glaucomatous damage

• Treatment goal: get IOP low, and keep it low

Heijl et al. Arch Ophthalmol. 2002; Kass et al. Arch Ophthalmol. 2002; Lichter et al. Ophthalmology. 2001; AGIS Investigators:

• 7. Am J Ophthalmol. 2000.

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Primary Medical Therapy

• Building block approach
• Start with the STRONGEST FOUNDATION
• Efficacy Goals of Primary Therapy

 Achieve lowest IOP on single agent

 High response rate – every mm Hg matters  Maintain consistent long term and diurnal

pressure lowering

MSOffice1

Eric’s 7 Simple Rules For Treatment

• 1. Choose 30% IOP decrease as initial

target

• 2. Squash the diurnal curve (Keep IOP peak

<18mm)

• 3. Assess risk factors for progression and

rate of progression (CT<555, IOP >26,C/D 0.5)

Slide 77 MSOffice1 , 10/21/2004

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Eric’s Rules cont.

• 4. If you are going to treat; treat aggressively
• 5. KISS
• 6. Be mindful of perfusion issues
• 7. Above all, do no harm

The Glaucoma Treatment Universe 2018

• Prostaglandins
• Alpha –agonist
• ROC -Inhibitors
• CAI
• Combo drugs
• Ginkgo , etc
• Beta-blockers
• Cardioselective beta-

blockers

• SLT
• Trabeculectomy
• Nutrition issues

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Prostaglandins

• All decrease IOP by increasing

uveoscleral outflow

• All are effective at squashing the diurnal

curve

• They have either no effect or a positive

effect on retinal perfusion

• But does 1 work better than the others?

XLT Study: Mean IOP at Week 12

• Study population: previously treated patients



Approximately 50% on latanoprost at screening

• Consistently lower mean IOP with bimatoprost*

*Statistical analysis not reported

8 AM 12 PM 4 PM 8 PM

Parrish et al. Am J Ophthalmol. 2003.

Mean IOP + SEM (mm Hg) Time of Day at Week 12

15 16 17 18 Bimatoprost Latanoprost Travoprost

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Bimatoprost vs Travoprost

• Three clinical comparison studies in patients with elevated

IOP

Parrish et al,

2003*

Noecker et al,

2003†

Cantor et al,

2005

Sponsor

Pharmacia

Allergan Allergan Length 12 weeks 3 months 6 months Bimatoprost n=136 n=16 n=77 Travoprost (0.004%) n=138 n=15 n=81 Latanoprost n=136 Outcome‡ Favored:

Bimatoprost Bimatoprost Bimatoprost§

Parrish et al. Am J Ophthalmol. 2003; Noecker et al. Am J Ophthalmol. 2003; Cantor et al. ARVO. 2005. *Study included latanoprost treatment arm, n=136 (see earlier slides).

†Study population comprised African-American patients. ‡Mean IOP reduction. §Significant difference between treatment groups.

Patients Consistently Achieving a Mean Diurnal IOP <18 mm Hg At Every Visit Through 6 Months

Choplin et al. IGS. 2005.

% of Patients

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Circadian IOP

Walters et al. Surv Ophthalmol. 2004. P ≤ .037 vs timolol

Mean IOP ± SEM (mm Hg)

Majority of Patients on More Than One IOP-Lowering Medication

• Schappert. National Center for Health Statistics. 1995.

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Why Are so Many Patients on Multiple Medications?

• Target IOPs set lower than in the past
• As disease progresses, patients need

even lower IOP

• Even the most effective IOP-lowering

medications, the lipids, do not get all patients to low target IOPs

Choosing Therapy: Switch or Add?

• Target IOP should be reached with minimal number of

medications

• Build strongest foundation prior to adjunctive therapy
• Switching to a more effective medication may be best

course of action

• Differences within medication classes exist
• Potential benefits of monotherapy

 Improved patient compliance  Decreased cost  Reduced cumulative exposure to benzalkonium chloride

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What If:

• A patient failed on Xalatan?
• If switched to Lumigan, 57% achieved

target IOP

• If switched to Travatan, 45.5% achieved

target IOP

• SO?

Latanoprost Non-Responders: Switch to Bimatoprost

Gandolfi, Cimino. Ophthalmology. 2003.

Mean 16-Hour Diurnal IOP

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Regarding Prostaglandins:

• Generally the 1st line of treatment
• There are interindividual differences in

efficacy

• Are there racial differences?
• If at first one fails; try, try , try again (with

another prostaglandin)

• Why wouldn’t you use a prostaglandin 1st?

Prostaglandin Side Effects

• Conjunctival hyperemia: Severe

hyperemia

 Lumigan 3.5%  Travatan 1.5%  Xalatan <1%  Rescula 1%

• Is this a transient phenomenon?
• Is it an allergic conjunctivitis?
• Is it worth stopping the drop?

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Prostaglandin Side Effects

• Iris pigmentation

 Is it reversible?  Is it pre-cancerous?

• Xalatan – 6.7% @ 6mths

16% @ 12mths

• Travatan – 3% @ 12 mths
• Lumigan – 1.9% @ 12mths
• Rescula – 1 patient
• SO?

Other Prostaglandin side effects

• CME
• Uveitis
• Reactivation of HSK
• Hypertrichosis
• One must take into consideration the

benefits of low IOP with the risks of the side effects

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Final prostaglandin thoughts

• They are additive to other G drugs but not

with each other

• Travatan and Lumigan maintain target IOP

36hrs after instillation and significant IOP drop up to 84 hrs after instillation

What if Target Pressure Is Not Reached With Even the Most Powerful Monotherapy?

• Add a second medication!

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Primary Considerations in Choosing Adjunctive Therapy

• Efficacy when used with the first-line medication

 IOP should be reduced by at least an additional

15% to a level as low as possible

 A medication that is effective monotherapy, or when

added to one medication, may not be effective when added to a different medication!

• Safety

 Safety concerns increase with each additional

medication: add the safest medication possible

Brimonidine vs Dorzolamide Added to Topical Beta-Blocker

• Only patients who met target 15% IOP reduction were continued

beyond 1 month

* P < .007

Patients Achieving Target  15% IOP Reduction (%) Month 1 Month 3

86% 62% 78% 44%

Brimonidine BID Dorzolamide TID

Simmons, Alphagan/Trusopt Study Group. Clin Ther. 2001.

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Treatment paradigm – Step 2

• Prostaglandins 1st
• If not successful – try another agent by

itself: Brimonidine bid or timolol QAM

• If neither of these get IOP to desired level

then add

Treatment Paradigm, Part III

1.Prostaglandins alone

• 2. Brimonidine or beta-blocker alone
• 3. Prostaglandin + beta-blocker or

brimonidine (unless 1 of these absolutely sucked!)

• 4. Consider CAI or Cosopt if (3) is not

successful

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Treatment paradigm, part IV

• If on 2 meds and target IOP not met…

 1. Consider 3rd drop (Betoptic S or CAI)  2. Substitute combination drop for least

successful drop

 3. Consider SLT  4. Surgical intervention

• What is maximum medical therapy

nowadays?

• SLT and trabeculectomy should not be

considered weapons of last choice or last chance

Remember The Diurnal Curve!!!

• PGAs
• Trabeculectomy
• Brimonidine -TID
• CAI – TID
• What about beta-blockers?

 BID vs QAM  ½% vs ¼%  Effect on diurnal curve

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Safety Issues With Beta-Blockers

• For many years, timolol was the most effective IOP-

lowering agent available

• Widespread use revealed serious systemic adverse

effects

 Exacerbation of reactive airway disease (asthma),

exercise intolerance, impotence, depression, cardiopulmonary adverse events, etc

• Beta-blockers contraindicated or should be used with

caution in many patients

• Up to 22% of patients may be unable to use

nonselective beta-blockers due to contraindications or inability to tolerate side effects

Kolker et al. Invest Ophthalmol Vis Sci. 1999.

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• Systemic Adverse Effects of Beta-adrenergic

Blockers: An Evidence-based Assessment (Lama, AJO Nov 2002)

 Many of the claimed adverse side effects of beta-

blockers are not supported by clinical trials

 Most anectodal claims  More patients may be eligible for beta-blockers  Careful medical hx and checking pulse rate and

rhythm should be sufficient

What About Imaging Units?

• Are they essential?
• What do they do ?
• What do they don’t do?
• Are they the standard of care?

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Risk Factors For Conversion

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3 Questions For The Audience:

• 1. What is your definition of glaucoma?
• 2. What is the pathology of glaucoma?
• 3. Is retinal imaging the standard of care

for treating glaucoma?

RNFL defects precede ONH changes1

1Quigley HA, et al Ophthalmology. 1992; 99:19-28.

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RNFL and Glaucoma

• Axons of retinal ganglion cells form the

retinal nerve fiber layer (RNFL)

• Glaucoma is characterized by loss of

ganglion cells leading to loss of retinal nerve fibers

Glaucoma is a disease of the RNFL

RNFL and Glaucoma

• RNFL changes are early to occur in glaucoma
• Up to 50% of the retinal nerve fibers may be lost

before a visual field defect is detectable

• Early detection of glaucoma by RNFL imaging

and analysis leads to early treatment, improving the chance to delay or halt the disease progression

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Glaucoma Early Detection – The Macula

Central 10 ° contains 23% of retinal ganglion cells Central 30 ° contains 58% of retinal ganglion cells GCC scan area Macula = central 20° Contains 50% of retinal ganglion cells

Glaucoma: Where we scan

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Imaging Overlay of the pRNFL and GCC Related to OS 30-2 Visual Field

pRNFL GCC

Ganglion Cell Complex Analysis

for earliest detection of structural change associated with glaucoma

Inner retinal layer provides Ganglion cell assessment:

• Axons = nerve fiber layer
• Cell Body = ganglion cell layer
• Dendrites = inner plexiform layer

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Imaging the GCC

ILM NFL GCL IPL INL OPL ONL PR IS/OS RPE Choriocapillaris and choroid

Blood vessel

GCC Full Retina Thickness

GCC is inner retinal layers

• Nerve Fiber Layer – Ganglion cell axons
• Ganglion cell layer – Cell bodies
• Inner-Plexiform Layer - Dendrites

Normal Glaucoma with thinner GCC GCC GCC

GCC Thinning in Glaucoma

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DIAGNOSE: Early is Better

Disc change precedes VF loss in most cases

GCC Analysis may detect damage before RNFL

GCC and RNFL analysis will be correlated, however GCC analysis may be more sensitive for detecting early damage in some patients

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Comparing RNFL, GCC, and VF

24-2 Visual Field shows early superior VF defect Inferior RNFL defect Inferior GCC defect larger than RNFL and VF

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Overlay of the RNFL and GCC (OS) with RTVue FD OCT

pRNFL GCC

MANAGE: Looking for Progression

• Change is not always clear or certain
• The HRT does the math for you, pixel by pixel
• Significant change is marked and tracked

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MANAGE: Topographic Change Analysis

• Images automatically aligned
• Areas with statistically significant change are highlighted
• Validated against a 10-year database of glaucoma

progression cases