Managing the Patient with POAG Vision Institute Annual Fall Conference Mitchell W. Dul, OD, MS, FAAO mdul@sunyopt.edu Richard J. Madonna, MA, OD, FAAO rmadonna@sunyopt.edu Ocular Hypertension (OHT) Most important element is to determine who should be treated and who should be watched. OHTS 5 Year Results Overall Control: 9.5% convert Treated: 4.4% convert African Americans Control: 16.1% convert Treated: 8.4% convert 1
Risk Analysis Ocular Hypertension Treatment Study (OHTS) IOP Central Corneal Thickness Older Age Vertical C/D PSD 2
Risk Calculator Outcomes: Guide to Patient Management 5-Year Risk for Progression of OHTN Glaucoma Risk Level Range Recommendations Low 5% Monitor Moderate 5%-15% Consider treatment High 15% Treatment The predictions derived using these methods are designed to aid, but not to replace clinical judgment. Other Factors to Consider When Deciding To Treat Younger Age Family history Myopia Systemic Health Perfusion Pressure? Race? Other Patient perceptions and personality Cost benefit ratio Follow Up Decision to treat Establish a target pressure OHTS: IOP < 24 and a minimum of a 20% reduction from baseline (using any available medication) Decision to monitor Periodic structural and functional testing 3
Baseline Pre treatment IOP An adequate number of IOPs should be measured to reduce the effects of fluctuation Three? Gonioscopy Disc Stereoscopic examination Photography RNFL Fundus exam Photography Imaging Disc Circumpapillary RNFL Macula Visual field An adequate number of VFs should be performed to reduce the effects of fluctuation Beginning Treatment Target IOP Least number of drops (therapies) to reach target Consider contraindications and potential adr s Educate PGA most common first line Prostaglandin Analogs TRAVATAN Z Lumigan Latanoprost generic (Xalatan) 4
Prostaglandin Analogs Achieved new gold standard beyond beta blockers for total IOP reductions 30% IOP reduction with once per day dosing Excellent safety profile but several tolerability concerns Contraindications of Prostaglandins Uveitis /Ocular Inflammation Cystoid Macular Edema Herpes Simplex Keratitis Cost Prostaglandins Ocular Tolerability Conjunctival hyperemia Lumigan > Travatan> Xalatan Worst at day one, diminishes over 2 3 weeks Iris pigmentation 3 15%; cosmetic, no pathology association Periorbital pigmentation 2% at six months; some pts may reverse Deepening of lid sulcus Effect is on adipocytes CME ( 2%) & uveitis ( 5%) Almost all pt s had prior hx = minimal to low risk Eyelash changes ( 10% 15%) growth, thickness, number 5
PGA Preservatives LATANOPROST LUMIGAN 0.01% 0.02% BAK 0.02% BAK LUMIGAN 0.03% TRAVATAN Z ZIOPTAN 0.0015% 0.005% BAK BAK Free sofzia Preservative Free 26 What about generics? Monocular Trial? 6
Assumptions we rely on for the Monocular Trial to hold true: 1. IOP fluctuation is the same between right and left eyes 2. Diurnal curve is the same over time 3. Medication has no crossover effect 4. Each eye responds the same to a medication 5. Patients have good compliance What is the concern about using the Monocular Trial? Determine that the drug works when it doesn t. Start ineffective medication in fellow eye Determine that the drug does not work when it actually does. Patient is deprived of safe and effective medication Adjunctive Therapy 7
Products: Options for Adjunctive Therapy Fixed Combinations Additional Mean IOP Reduction when Added to a PGA (at 3 months) Combigan 6.9 mm Hg 1 Cosopt 5.2 mm Hg 1 Alpha agonists ALPHAGAN P 3.3 mm Hg 2 Carbonic anhydrase inhibitors (CAIs) Azopt 3.1 mm Hg 2 Trusopt 2.7 mm Hg 3 Beta blockers Timolol 2.5 mm Hg 4 1. Nixon et al. Curr Med Res Opin. 2009; 2. Day. Curr Med Res Opin. 2008; 3. Maruyama and Shirato. J Glaucoma 2006; 4. Miura et al. J Glaucoma 2008. Criteria for the Choice of Adjunctive Therapy Incremental efficacy The main reason for changing initial monotherapy is the need for additional IOP lowering The purpose of adjunctive therapy is to obtain target IOP Other considerations Compliance Tolerability Safety 1 Rouland JF et al. Eur J Ophthalmol. 2003;13(suppl 4):S5-S20; 2 European Glaucoma Society. Terminology and Guidelines for Glaucoma. Savona, Italy: DOGMA Srl; 2003. Beta Blockers Traditional first line option for IOP Long track record of success Reduce aqueous production 0.25% vs. 0.5% options qd vs. bid dosing 20 25% IOP expected ~ 15% of patients will show no response Systemic Beta blocker tx will topical effect Tenormin, Lopressor, Corgard, Inderal, Normodyne Potential Side Effects: Depression, impotence, bronchospasm 8
Beta Blockers Avoid in patients on systemic beta blockers Small IOP effect, decreased heart rate/ BP Important contraindications Asthma, congestive heart failure, second and third degree heart block, bradycardia, active young patients Topical CAIs Currently available: Brinzolamide 1% (Azopt) Dorzolamide 2% (Trusopt) Generic availability MOA = decrease aqueous production 15 20% as stand alone FDA Labeled as TID agents Used BID when in combination! Alpha Agonists Alphagan P 0.1% (Allergan) P = Purite Less ocular allergy because of decreased amt of active agent Aqueous suppressant and uveoscleral outflow? Neuroprotection? animal models Bid vs. Tid dosing Generic brimonidine (BAK): 0.2%, 0.15% 9
Brimonidine Tartrate Relatively safe systemically Reported: Fatigue, Dry Mouth Watch with systemic MAO inhibitors Can cause significant ocular allergy Which is best to add to a PGA? Beta blocker? CAI? Alpha agonist? Fixed Combinations with PGA 10
Fixed Combination Dorzolamide hydrochloride/timolol maleate ophthalmic solution (Cosopt ) Generic dorzolamide / timolol maleate ophthalmic solution Also branded Cosopt PF Fixed Combination Combigan (Allergan) Brimonidine 0.2% and timolol 0.5% BID dosing Less allergy than brimonidine alone Fixed Combination Azarga (Alcon) Brinzolamide 1% + timolol 0.5% susp. 11
Simbrinza (Alcon) Brimonidine 0.2% + brinzolamide 1% susp. BAK 21% 35% IOP lowering as stand alone Side effect profile as individual agents Fixed Combination Rescula (unoprostone 0.15%) Prostone NOT a prostaglandin Does it have a role? 52 LTP ALT or SLT IOP lowering similar to one medication when used adjunctively What is appropriate timing for LTP? First line? 12
SLT vs. ALT SLT is effective as treatment for patients with OAG and appears to be equivalent to ALT in IOP lowering at 12 months only in patients without a prior treatment. In case of retreatment SLT appears to be better than ALT in IOP lowering. Russo V, et al. Eur J Ophthalmol, 2009. Adjunctive Therapy Individualize for each patient Consider Target IOP Adherence ADR Systemic and ocular comorbities Cost 13