Intervention Review

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Anti-vascular endothelial growth factor for neovascular glaucoma

  1. Arathi Simha1,*,
  2. Andrew Braganza1,
  3. Lekha Abraham1,
  4. Prasanna Samuel2,
  5. Kristina Lindsley3

Editorial Group: Cochrane Eyes and Vision Group

Published Online: 2 OCT 2013

Assessed as up-to-date: 11 JAN 2013

DOI: 10.1002/14651858.CD007920.pub2


How to Cite

Simha A, Braganza A, Abraham L, Samuel P, Lindsley K. Anti-vascular endothelial growth factor for neovascular glaucoma. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD007920. DOI: 10.1002/14651858.CD007920.pub2.

Author Information

  1. 1

    Christian Medical College, Department of Ophthalmology, Vellore, India

  2. 2

    Christian Medical College, Department of Biostatistics, Vellore, Tamil Nadu, India

  3. 3

    Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, Maryland, USA

*Arathi Simha, Department of Ophthalmology, Christian Medical College, Vellore, 632001, India. arathisimha@rediffmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 2 OCT 2013

SEARCH

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Caujolle 2012Retrospective, non-randomized study of ranibizumab injections with or without cryotherapy; 14 participants (14 eyes) previously treated with proton therapy for uveal melanomas with minimum of 4 months follow-up; no control group

Costagliola 2008Prospective pilot study of bevacizumab injections; 23 participants (26 eyes) received injections and were followed for 12 months; no control group

Eid 2009Historical cohort study of bevacizumab injections and aqueous shunting surgery; 20 participants with NVG received injections followed by surgery and were compared to a historical group of 10 participants treated with PRP and surgery without bevacizumab

Gupta 2009RCT of intracameral bevacizumab prior to undergoing MMC trabeculectomy; participants received either 1.25 mg injections (n = 9) or 2.5 mg injections (n = 10) and were followed for six months; there was no control group in which no intracameral bevacizumab was given; participants may have been treated previously with some form of conventional treatment (PRP, anterior retinal cryopexy) or no conventional treatment

Historical cohort of non-randomized participants who did not receive intracameral bevacizumab injections; outcomes from 16 participants/eyes who had MMC trabeculectomy in years prior to the trial were compared with the outcomes from the trial participants

Jonas 2010Retrospective chart review of IVB; 14 participants with iris neovascularization and secondary angle-closure glaucoma treated with between one and three intravitreal injections of bevacizumab and followed for at least 4 months; no control group

Miki 2011Prospective pilot study of bevacizumab injections as an adjunct to trabeculectomy; 15 participants (15 eyes) with previous vitrectomy were treated with trabeculectomy with
MMC plus IVB and were followed for 12 months; no control group

NCT01711879Ongoing RCT of aflibercept in participants with NVG; treatment group 1 consisted of one intravitreal injection of 2 mg (0.05 ml) aflibercept at baseline followed by laser treatment with observation and treatment group 2 consisted of intravitreal injections of 2 mg (0.05 ml) aflibercept at baseline, 4 weeks, and 8 weeks, then every 8 weeks (all study participants received treatment with anti-VEGF therapy)

Sedghipour 2011RCT of IVB augmentation after trabeculectomy versus control group receiving a placebo injection after trabeculectomy; 37 participants with primary or secondary open angle glaucoma (excluded participants with neovascular glaucoma)

Wittstrom 2012RCT of IVB; participants received either IVB prior to PRP (n = 10) or no IVB prior to PRP (n = 9) and were followed for six months; 11 of the 19 participants had pre-existing glaucoma (it was not clear whether these 11 participants had glaucoma before central retinal vein occlusion, in which case this RCT does not address the issue of pure NVG and pre-existing glaucoma can be a major confounder, or only 11 of the 19 participants had NVG with elevated IOPs at baseline); participants additionally received co-interventions (such as IOP-lowering medications, additional PRP, retinal cyclocryotherapy, transscleral diode laser cyclophotocoagulation, and trabeculectomy) determined by individual clinical assessments; the allocation of co-interventions was pragmatic and randomization was not stratified by co-interventions; subgroup analysis according to co-interventions would not be useful since the number of participants in each co-intervention group was small and some participants received multiple co-interventions

Yazdani 2009RCT of IVB; participants received either IVB (n = 14) or saline injections (n = 12) and were followed for six months; participants additionally received co-interventions (such as PRP, filtering procedures, cyclodestructive procedures) determined by individual clinical assessments; the allocation of co-interventions was pragmatic and randomization was not stratified by co-interventions; subgroup analysis according to co-interventions would not be useful since the number of participants in each co-intervention group was small

 
Characteristics of studies awaiting assessment [ordered by study ID]
Arcieri 2010

MethodsRCT
Number randomized: 29 participants

18 months follow-up planned; mean of 8 months

ParticipantsCountry: Brazil
Inclusion criteria: age between 18 and 90 years; NVG with history of PRP; and requiring glaucoma drainage device
Exclusion criteria: learning difficulties, mental illness, or dementia; and unconscious or severely ill

InterventionsTreatment group: implantation of Ahmed valve with intravitreal injections of 1.25 mg (0.05 ml) bevacizumab at end of surgery, and 4 and 8 weeks postoperatively
Control group: implantation of Ahmed valve with pars plana injection of 0.05 ml saline at end of surgery

OutcomesPrimary outcome specified as: IOP control at 6 months

Secondary outcome specified as: safety of intravitreal bevacizumab at 6 months

Outcomes reported in conference abstract: mean change in IOP, visual acuity, mean number of anti-glaucoma medications, extension of goniosynechiae, reduction of new vessels in the anterior chamber angle, regression of rubeosis iridis

NotesThis study was presented at the 2010 Association for Research in Vision and Ophthalmology (ARVO) conference. Details of study methods and participants were not provided in the conference abstract. The clinical trial registration for this study did not yield additional information to assist with determining eligibility

Chakrabarti 2008

Methods"prospective, randomized, interventional study"
Number randomized: 38 eyes

One year follow-up

ParticipantsCountry: not reported
Inclusion criteria: eyes with NVG

InterventionsTreatment group 1 (n = 15): PRP
Treatment group 2 (n = 12): intravitreal bevacizumab monotherapy

Treatment group 3 (n = 11): intravitreal bevacizumab plus PRP

OutcomesOutcomes reported at 12 months:

IOP reduction of 50% from baseline

Regression of NVI

Reduced NVI regression time, in days

Decrease NVI recurrence

Reduced repeat injections of intravitreal bevacizumab

NotesThis study was presented at the 2008 American Academy of Ophthalmology (AAO) conference. Details of study methods and participants were not provided in the conference abstract. We have not identified complementary reports of this study to assist with determining eligibility

NCT01128699

MethodsRCT
Number randomized: 40 (one study eye per participant)

One year follow-up

ParticipantsCountry: Iran
Inclusion criteria: age between 20 and 80 years; and refractory glaucoma (IOP > 21 mmHg with maximum medication, previous surgical failure, or both)
Exclusion criteria: visual acuity of no light perception or worse; elevated IOP associated with silicone oil; history of glaucoma drainage device in study eye; history of cyclodestructive treatment; and increased risk of endophthalmitis, posterior segment disorders, or ocular comorbidities

InterventionsTreatment group: one intraoperative subconjunctival injection of 1.25 mg bevacizumab and implantation of Ahmed valve (Model FP7, New World Medical Inc.)
Control group: implantation of Ahmed valve (Model FP7, New World Medical Inc.)

OutcomesPrimary outcome specified as: change in IOP at 12 months

Secondary outcomes specified as:

Surgical failure at 12 months

Change in IOP at day 1, week 1, and months 1, 3, 6, and 9

NotesThe study investigators included participants with refractory glaucoma, which may include participants with NVG. It was not clear whether any study participants had NVG or how many. Study dates were May 2010 to May 2011. No study results were provided

 
Table 1. Characteristics of Yazdani 2009 study

MethodsRandomized controlled trial
Number of participants randomized: 26

Six months follow-up

ParticipantsCountry: Iran
Baseline characteristics, including age, sex, intraocular pressure (IOP), iris neovascularization, and causes of neovascular glaucoma (NVG) were comparable between groups
Follow up: 3 participants were lost to follow-up at six months (1 participant in the treatment group and 2 participants in the control group)

Intervention

Co-interventions
Treatment group (n = 14): 3 intravitreal injections of 2.5 milligrams (mg) (0.1 milliliters (ml)) bevacizumab at monthly intervals for six months
Control group (n = 12) : 3 subconjunctival injections of 0.1 ml normal saline at monthly intervals for six months

All participants received conventional treatment for NVG including medications, retinal ablation, glaucoma shunt, and/or cyclodestructive procedures to achieve target IOP of high teens to low 20s

The allotment of participants to specific co-interventions was not uniform or randomized. Some participants received multiple co-interventions

OutcomesPrimary outcomes: change in IOP and change in the extent of iris neovascularization

Secondary outcomes: change in visual acuity and change in glaucoma medication requirement

 
Table 2. Additional conventional procedures* in the Yazdani 2009 study

InterventionIVB groupSham group

Panretinal photocoagulation89

Glaucoma shunt procedures42

Cyclodestructive procedures21

Cataract surgery34

Deep vitrectomy11

 *35 additional procedures were performed in 23 eyes which included 18 procedures in 12 eyes in the IVB group and 17 procedures in 11 eyes in the sham group
IVB: intraocular bevacizumab
 
Table 3. IOP and NVI at baseline and follow up for Yazdani 2009 study

IVB group
Mean ± SD
PSham group
Mean ± SD
P

IOP baseline33.4 ± 14.532.3 ± 14.3

IOP at 1 month21.8 ± 13.70.00734.9 ± 15.20.046

IOP at 3 months25.1 ± 20.00.05835.2 ± 10.70.29

IOP at 6 months23.9 ±1 8.70.04732.2 ± 7.30.92

NVI at baseline347 ± 48270 ± 138

NVI at 1 month206 ± 1850.01277 ± 1300.34

NVI at 3 months180 ± 1870.004300 ± 1170.22

NVI at 6 months180 ± 1800.004324 ± 1140.34

 IOP: intraocular pressure (mmHg)
IVB: intravitreal bevacizumab
NVI: neovascularization of iris (degrees)
P: P-value compared with baseline
SD: standard deviation