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