Post on 02-Feb-2016
description
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)
OHTSSummary 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)
OHTSSummary 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 OHTSAbsolute 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 OHTSTreat 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
Age Vertical C/D
IOP DM+
CCT PSD
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
CIGTSRESULTS 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 dropRisk 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
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 progressedNon 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 RxIOP - + risk factor for all glaucomasRecognize threat – lower IOP – lower risk of progressionSet 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