RANDOMIZED CLINICAL TRIALS IN GLAUCOMA- WHAT DO THEY TELL US? Dr Jyoti Shetty B.W.Lions superspeciality eye hospital

Randomized clinical trials First major scientific evidence that treatment for glaucoma decreased visual loss Multicentric, prospective studies How do they help us?

NEI clinical trials CNTGS CIGTS AGIS OHTS EMGT Layouts, results, relevance to clinical decision making

Ocular Hypertensive Treatment Study (OHTS) Purpose - Conversion rate to POAG in treated vs untreated groups. - Risk factors for progression to POAG

OHTS Randomized n= 1636 Observation Medication n=819 n=817  Treatment goal –dec IOP by 20%  Prim outcome – dev of POAG ( VF, ONH)

OHTS Summary of results - At 5 yrs dev of POAG * 4.4% in treated eyes * 9% in untreated eyes * 50% of risk * diff with time - Race not predictive (multivariate analysis)

OHTS Summary of results - Conversion 6.4% in treated eyes 4.3 % in untreated eyes - Incidence of POAG higher - Risk factors identified for onset of POAG * Age * Vert CD * PSD * IOP * CCT

OHTS Summary of results CCT 25 CCT 0.5 Risk 36% Risk 22% CCT > 588 &IOP > 25 CCT > 588 & CD >0.5% Risk 6% Risk 8%

Clinical useful points from OHTS OHT – What to do * Treat all * Treat no one * Treat some -- Is treatment effective DOES OHTS HAVE ANSWERS FOR THIS

Clinical useful points from OHTS Absolute risk reduction = 9.5% - 4.5%= 5.1% NNT = 1 / 5.1 = 20 ( To prevent 1 conversion to POAG) 90% of OHT did not convert in 5 yrs Conversion to early POAG - No effect on QOV - Not a sentence to eventual blindness So can afford to wait for evidence of progression

Clinical useful points from OHTS Treat only patients at high risk. Risk factors – risk calculator Importance of CCT ONH & VF monitoring at every FU SWAP,GDx OCT – application not studied in OHTS Study – Rx effective, of the 9.6% that converted half could be prevented by Rx OHTS - ? Conversion after longer FU AgeVertical C/D IOPDM+ CCTPSD If not high risk waiting to treat OHT till conversion- better strategy ( vision related QOL)

Collaborative initial glaucoma treatment study (CIGTS) Objective Is medical or surgical therapy better as an initial treatment of POAG taking into consideration IOP control, VF progression & QOL. 607 PATIENTS MEDICAL SURGICAL(TRAB) FIRST TIME A TARGET IOP ALGORITHM USED

CIGTS RESULTS At 5 yrs both effective Control of IOP lower by surgery (48%), medical (35%) VF loss greater in surgery (cataract) QOL initially better with medical group

Clinical useful points from CIGTS Early POAG – medical Rx effective Our scenario – compliance/cost – deciding factor for either modality Concept of target IOP – must in our management. Drawback – study duration too short for Rx recommendation.

Early manifest glaucoma treatment study (EMGTS) Only glaucoma study where diagnosed early POAG not treated Evaluated effectiveness of IOP reduction in early POAG 255 pts medical126 - control Rx ALT & Betaxolol only

EMGTS – results Progression 62% - control 45% - treated group 25% IOP - risk of progression by 50% Risk of progression less with larger initial IOP drop Risk of progression by 10% / mm Hg IOP from baseline

Clinical useful points from EMGTS 25% IOP - progression from 62 – 45% Regular FU every 3 – 6 months with ONH & VF must – not commonly practiced. Pts with low risk of progression left untreated – no effect on QOL till lifetime Drawbacks – Rx options limited – better drugs now

Advanced glaucoma intervention study (AGIS) Objective – to determine if ALT or surgery is preferred Rx for advanced glaucoma on max tolerated medical Rx. 781 eyes ALT TRAB (ATT) TRAB ALT TRAB (TAT)

AGIS - Results Relationship of IOP & VF progression. Predictive analysis – IOP < 14 mm Hg did better Associative analysis – low IOP & low IOP fluctuation - Decreased progression

Results - AGIS TAT IOP Better for whites ATT failure Better for blacks Risk of cataract after TRAB after 5 years – 78 %

Clinical useful points from AGIS Advanced glaucoma IOP < 14 - VF prog. So lower target IOP aimed for Not only lower IOP but lower fluctuation of IOP Incidence of cataract after glaucoma surgery - high

Collaborative normal tension glaucoma study (CNTG) Objective: To determine if aggressive IOP lowering effective in CNTG. Goal – 30% from baseline IOP

CNTG – results Prog in 12% of Rxed eyes & 35% in untreated group. 30% reduction possible even by medicines. Treated pts that progressed Non IOP related target IOP wrong

Clinical useful points from CNTG IOP lowering beneficial even in NTG IOP should be lowered >30% - low target IOP should be aimed for. Newer medications available now (PG analogues, combination therapy) – easier

Take home message from clinical trials Efficient patient care – practice of evidence based Rx IOP - + risk factor for all glaucomas Recognize threat – lower IOP – lower risk of progression Set a target IOP after asessing risk factors for progression 20%, - OHT 30% - moderate loss, 40% - sever loss If documented risk of progresion - further 15%

Take home message from clinical trials Choice of medical therapy first – change only if target IOP not achieved. Remember QOL – balance efficacy with safety, side effects, economic stress, compliance. Newer PG analogues & combination therapy available – better compliance, flatter diurnal curve.

Take home message from clinical trials Surgical therapy – safe Rx OHT only if high risk (risk calculator) CCT measurements at present unavoidable for correct mgt of glaucoma esp. OHT. All forms of Rx - incidence of cataract Disiease progression with time Newer diagnostics – SWAP/FDT/GDx/OCT – quantification of progression better

Take home message from clinical trials Progression of glaucoma does not necessarily mean threat to QOL. Aim of Rx not no progression at all but reduction to such a level that QOV not endangered during patients lifetime