RANDOMIZED CLINICAL TRIALS IN GLAUCOMA- WHAT DO THEY TELL US?

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 < 555 & IOP > 25 CCT < 555 & CD > 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 www.discoveriesinsight.org • 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 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 129 - medical 126 - 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 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

TAT IOP Better for whites ATT failure Better for blacks Results - AGIS 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

RANDOMIZED CLINICAL TRIALS IN GLAUCOMA- WHAT DO THEY TELL US?