Transcript randomised clinical trials (2)

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
OHTS
CIGTS
AGIS
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
n=819
Medication
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
Risk 36%
CCT > 588 &IOP > 25
Risk 6%
CCT < 555 & CD > 0.5
Risk 22%
CCT > 588 & CD >0.5%
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
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
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
ALT
TRAB
TRAB
(ATT)
(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