Effectiveness of early lens extraction for the treatment of primary angle closure glaucoma

1. Effectiveness of early lens extraction for
the treatment of primary angle closure
glaucoma (EAGLE)
Dr. Naggalakshmi, MS,
AEH,PDY
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Augustine azuara-Blanco, Jennifer Burr, Craig Ramsay, David
Cooper, Paul Foster, David Friedman, Graham Scotland, Mehdi
Javanbakht, Claire Cochrane, John Norrie

2. Introduction
• Primary angle closure glaucoma - leading cause of irreversible
blindness worldwide.
• The current standard care for PACG - stepped approach of
combination of medical and surgical (laser or inscisional)
management.
• In early-stage disease, intraocular pressure is raised without
vision loss.
• Since the crystalline lens has a major mechanistic role, lens
extraction might be a useful initial treatment.
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3. Purpose
To assess the efficacy, safety, and cost-effectiveness of clear-lens
extraction compared with laser peripheral iridotomy and
topical medical treatment as first-line therapy in people with
newly diagnosed primary angle closure with raised intraocular
pressure or primary angle-closure glaucoma.
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4. Methods
• A multicenter RCT done in 30 eye hospital across 6 countries
– Australia – 1
– Mainland China – 1
– Hong Kong - 2
– Malaysia – 2
– Singapore – 2
– UK – 22
• Period of study – Jan 2009 to Dec 2011.
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5. Methods
• Randomisation was done web-based application.
• Patients were assigned to undergo
1. Clear lens extraction
2. Laser peripheral iridotomy and topical medical treatment.
• The co-primary endpoints were
1. Patient-reported health status
2. Intraocular pressure
3. Incremental cost-effectiveness ratio per quality-adjusted life-year
gained 36 months after treatment.
• Analysis was by Intention To Treat.
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6. Methods
INCLUSION CRITERIA:
• Diagnosis:
i. PACG
ii. PAC with IOP > 30 mmHg at diagnosis
• Newly diagnosed
i. Untreated
ii. Under medical treatment for six months or less)
• Angle closure of 180 degrees or more
• Patient must be phakic in the affected eye(s)
• Participants will be ≥ 50 years
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7. Methods
EXCLUSION CRITERIA:
• Advanced glaucoma
• Previously diagnosed acute angle closure attack in the
otherwise eligible eye
• Increased surgical risk
• Symptomatic cataract in either eye
• Cataract surgery or laser iridotomy in study eye
• Axial length < 19 mm (nanophthalmos)
• Secondary angle closure glaucoma
• Retinal ischemia, macular edema or wet- AMD
• Medically unfit for surgery or for completion of the trial
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8. 8
Standard medical treatment initiated
Informed consent
Baseline measurements taken
Randomization to Group 1 or 2
1. Intervention Group (Study
visits at 6, 12, 24 & 36 m)
Lens extraction
(phacoemulsification)
Escalation of medical
treatment
FAILED LENS EXTRACTION
2. Standard Management Group
(Study visits at 6, 12, 24 & 36 m)
Laser peripheral iridotomy
Escalation of medical treatment
(+/- peripheral iridoplasty)
FAILED STANDARD CARE
Glaucoma
surgery

9. Methods
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10. 10
OUTCOME MEASURES
PRIMARY SECONDARY
PATIENT CENTERED CLINICAL ECONOMIC
EQ – 5D IOP at the end of 3 years Incremental cost/QALY
gained with QALY based
on response to EQ-5D
1. Mobility
2. Self – care
3. Usual activity
4. Pain / discomfort
5. Anxiety / depression
QALY is calculated from
EQ-5D

11. 11
OUTCOME MEASURES
PRIMARY SECONDARY
PATIENT CENTERED CLINICAL ECONOMIC
• Need for surgery;
best corrected
VA(ETDRS);
progressive visual
field loss.
• Extension of angle
closure clinically;
escalation of
therapy; opening of
AC angle
• No of antiglaucoma
medications; annual
incidence of acute
attacks of angle
closure
Cost to NHS & Patients
•use of health services
for glaucoma related
events or treatments
•Patient costs
•Need for alternate
management
GPI (Glaucoma specific
utility instrument)
1. Central & near vision
2. Lighting & Glare
3. Mobility
4. Activities of daily
living
5. eye discomfort
NEI-VFQ25
A vision specific health
profile measure based on
25 item version of
national eye institute
visual function
questionnaire.
Cost utility analysis
•Incremental cost per QALY
based on response to the
GPI
Cost effectiveness
analysis
•Incremental cost per case
of glaucoma surgery
avoided

12. Statistical analysis
• A single main analysis will be performed at the end of trial –
with interim analysis during DMC ( Data Monitoring
Committee ) meeting.
• Analysis based on all participants – randomised, irrespective
of compliance.
• The outcomes will be compared between test & control
groups, using analysis of covariance method.
• Statistical significance of 5% (2P < 0.05 ), with 90% power of
study.
• Analysis of covariance also measured in sub-group analysis of
IOP based on ethnicity & diagnosis. (PAC or PACG).
• Subgroup analysis is done with stricter p value of <0.01, with
99% statistical significance.
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13. Sample size
• A study with 170 participants in each group would have 90%
power at 5% significance level to detect a difference in means
of 0.35 of SD.
• Assuming a dropout rate of 15% , due to the patients needing
immediate intervention, a sample size of 400, with 200
assigned to each group was chosen.
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14. RESULTS
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18. Results
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23. DISCUSSION
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24. DISCUSSION
• VISUAL ACUITY
– Was better in CLE by 3 ETDRS chart
– Though clinically irrelevant, this points to overall improvement in
visual function.
• IOP
– Better in CLE by 1mm hg after 3 years.
– Difference in small (1mm), maybe clinically irrelevant.
– 61% patients required further management in Std group, whereas a
mere 21% did so in CLE group.
– This points towards the more efficacy in the CLE protocol.
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25. DISCUSSION
• VISUAL FIELD
– No statistically significant difference btw groups.
– The study was not specifically powered to detect this difference. So
finding it is unlikely.
• SUB-GROUP ANALYSIS
– No significant difference in outcome
• COMPLICATIONS
– CLE – intra-op/post-op complications
• 2 cases had PCR
– Std Grp – may require further cataract extraction in future
• 12 such cases need it in this study
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26. DISCUSSION
• COST EFFECTIVENESS
– CLE – increased mean cost to NHS & increased mean QALY (0.069 ) at 3
years.
– This is due to increased early procedure costs.
– However, this is offset on the long term due to reduced no of further
visit / procedures. (the probability of CLE being cost-effective was
0.885 at ceiling ratio of £20,000 per QALY and 0.940 at £30,000 per
QALY)
– Conclusion - Cost effectiveness of CLE, improves on the long term.
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27. STRENGTH OF THE STUDY
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28. STRENGTH Vs LIMITATIONS
STRENGTH
• Pragmatic design
• Large sample with low
attrition
• Diversity – involvement of
UK and Asian population
• Randomization
• Masking of the outcomes
• Double blind study
LIMITATIONS
• Limitation of masking
– Sx, complications, cant be
masked
• Loss of data – gonioscopy
• Poor detention of
complications
• Generalization – possible
difference in outcomes
between Asian & non-Asian
population
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29. TAKE HOME MESSAGE
One good quality trial may not be enough to change policy.
HOWEVER
1. The superiority of CLE in terms of pt reported and clinical
benefits
2. The absence of serious safety issues
3. The consistency of the results with relation to previous studies
in this regard
Makes CLE a strong consideration as the first line treatment for
POCG and primary angle closure with raised IOP.
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30. Reference
• Azuare-Blanco et al. The effectiveness of early lens extraction
with intraocular lens implantation for the treatment of
primary angle-closure glaucoma (EAGLE): study protocol for a
randomized controlled trial. Trials 2011 12:133
• Javanbakht M, Azuara-Blacnco A, Burr JM, et al. Early lens
extraction with intraocular lens implantation for the
treatment of primary angle closure glaucoma: an economic
evaluation based on data from the EAGLE trial. BMJ Open
2017;6:e013254.doi10.1136/bmjopen-2016-013254
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31. Thank you
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