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Cochrane Database of Systematic Reviews

Anti‐vascular endothelial growth factor for proliferative diabetic retinopathy

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Information

DOI:
https://doi.org/10.1002/14651858.CD008721.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 24 November 2014see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Eyes and Vision Group

Copyright:
  1. Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Maria José Martinez‐Zapata

    Correspondence to: Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain

    [email protected]

  • Arturo J Martí‐Carvajal

    Iberoamerican Cochrane Network, Valencia, Venezuela

  • Ivan Solà

    Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain

  • José I Pijoán

    Hospital Universitario Cruces, Barakaldo, Spain

    BioCruces Health Research Institute, CIBER Epidemiología y Salud Pública (CIBERESP), Barakaldo, Spain

  • José A Buil‐Calvo

    Oftalmology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

  • Josep A Cordero

    Blanquerna School of Health Science, Universitat Ramon Llull, Barcelona, Spain

  • Jennifer R Evans

    Cochrane Eyes and Vision Group, ICEH, London School of Hygiene & Tropical Medicine, London, UK

Contributions of authors

Conceiving the review: MJM.
Designing the review: MJM, AM.
Co‐ordinating the review: MJM.
Designing electronic search strategy: Cochrane Eyes and Vision Group editorial base.
Screening search results: MJM, ChF, JAC, JRE.
Obtaining copies of trials: IS, MJM, ChF, JRE.
Appraising quality of papers: MJM, ChF, JAC, JRE.
Abstracting data from papers: MJM, JAC, JRE.
Data management for the review: MJM.
Entering data into Review Manager 5: MJM, JRE.
Analysis of data: MJM.
Interpretation of data: all authors.
Writing the review: MJM, JRE.
Draft the final review: all authors.
Guarantor for the review: MJM.

Sources of support

Internal sources

  • CIBER de Epidemiología y Salud Pública (CIBERESP), Spain.

External sources

  • Grant of the Spanish Ministry of Health (2006‐2008); PI0690322, Spain.

  • National Institute for Health Research (NIHR), UK.

    • Richard Wormald, Co‐ordinating Editor for the Cochrane Eyes and Vision Group (CEVG) acknowledges financial support for his CEVG research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology.

    • The NIHR also funds the CEVG Editorial Base in London.

    • The Cochrane Review Incentive Scheme provided funding for Jennifer Evans to assist with completing this review.

    The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or the Department of Health.

Declarations of interest

None.

Acknowledgements

The Cochrane Eyes and Vision Group (CEVG) created the strategies and ran the searches on the electronic databases. We thank Satyamurthy Anuradha for her comments on the protocol, Nigel Davies for his comments on the review, Catey Bunce and Gianni Virgili for their comments on the protocol and review. We thank Anupa Shah, Managing Editor for CEVG her assistance throughout the editorial process.

We used Covidence (www.covidence.org) to screen the studies. We would like to thank Claire Irving and Clive Adams of the Cochrane Schizophrenia Group for their help in using RevmanHAL (szg.cochrane.org/revman‐hal) to prepare the "effects of interventions" section.

Version history

Published

Title

Stage

Authors

Version

2023 Mar 20

Anti‐vascular endothelial growth factor for proliferative diabetic retinopathy

Review

Maria José Martinez-Zapata, Ignacio Salvador, Arturo J Martí-Carvajal, José I Pijoan, José A Cordero, Dmitry Ponomarev, Ashleigh Kernohan, Ivan Solà, Gianni Virgili

https://doi.org/10.1002/14651858.CD008721.pub3

2014 Nov 24

Anti‐vascular endothelial growth factor for proliferative diabetic retinopathy

Review

Maria José Martinez‐Zapata, Arturo J Martí‐Carvajal, Ivan Solà, José I Pijoán, José A Buil‐Calvo, Josep A Cordero, Jennifer R Evans

https://doi.org/10.1002/14651858.CD008721.pub2

2010 Sep 08

Anti‐vascular endothelial growth factor for proliferative diabetic retinopathy

Protocol

Maria José Martinez‐Zapata, Arturo J Martí‐Carvajal, Ivan Solà, José I Pijoán, José A Buil‐Calvo

https://doi.org/10.1002/14651858.CD008721

Differences between protocol and review

We made the following amendments to the protocol (Martinez‐Zapata 2010).

  1. In the protocol, we had not considered that anti‐VEGFs would be used in different patient groups with PDR (i.e. people eligible for laser treatment, people eligible for vitrectomy and people undergoing cataract surgery. We felt that clinically it did not make sense to combine these different patient groups and so have presented the results separately.

  2. In the protocol, the primary outcome was regression of proliferative retinopathy and visual acuity was a secondary outcome. On reflection, we felt this was the wrong emphasis and considered that the effect on visual acuity was more relevant for the person than checking if anti‐VEGFs could produce regression of new vessels. We have changed visual acuity to the primary outcome and considered regression of proliferative retinopathy as a secondary outcome.

  3. In the protocol, we planned to exclude from the analysis studies where the fellow eye was used as a control (i.e. the within‐person studies). However, some studies had a parallel group design but included a low percentage of participants with the fellow eye used as a control. We included these studies in the analysis.

  4. We did not calculate the number needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH) due to the low quality of the evidence.

  5. In the protocol, we planned to do a sensitivity analysis by intention‐to‐treat considering the "worst‐case scenario". In the event, we did not do this, partly due to the characteristics of the majority of studies and partly because, on reflection, we felt that this analysis was too extreme and unlikely to be informative.

  6. We planned to do a sensitivity analysis excluding unpublished studies but did not have any data on unpublished studies to do this.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Results from searching for studies for inclusion in the review.
Figures and Tables -
Figure 1

Results from searching for studies for inclusion in the review.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Forest plot of comparison: 1 Anti‐vascular endothelial growth factor (anti‐VEGF) versus photocoagulation, outcome: 1.3 Visual acuity [logMAR].
Figures and Tables -
Figure 4

Forest plot of comparison: 1 Anti‐vascular endothelial growth factor (anti‐VEGF) versus photocoagulation, outcome: 1.3 Visual acuity [logMAR].

Forest plot of comparison: 2 Anti‐vascular endothelial growth factor (anti‐VEGF) plus surgery versus surgery alone or surgery plus sham or placebo, outcome: 2.3 Visual acuity [logMAR].
Figures and Tables -
Figure 5

Forest plot of comparison: 2 Anti‐vascular endothelial growth factor (anti‐VEGF) plus surgery versus surgery alone or surgery plus sham or placebo, outcome: 2.3 Visual acuity [logMAR].

Comparison 1 Anti‐vascular endothelial growth factor (anti‐VEGF) with or without panretinal photocoagulation (PRP) versus PRP alone, Outcome 1 Visual acuity.
Figures and Tables -
Analysis 1.1

Comparison 1 Anti‐vascular endothelial growth factor (anti‐VEGF) with or without panretinal photocoagulation (PRP) versus PRP alone, Outcome 1 Visual acuity.

Comparison 1 Anti‐vascular endothelial growth factor (anti‐VEGF) with or without panretinal photocoagulation (PRP) versus PRP alone, Outcome 2 Regression of proliferative diabetic retinopathy.
Figures and Tables -
Analysis 1.2

Comparison 1 Anti‐vascular endothelial growth factor (anti‐VEGF) with or without panretinal photocoagulation (PRP) versus PRP alone, Outcome 2 Regression of proliferative diabetic retinopathy.

Comparison 1 Anti‐vascular endothelial growth factor (anti‐VEGF) with or without panretinal photocoagulation (PRP) versus PRP alone, Outcome 3 Presence of vitreous or pre‐retinal haemorrhage.
Figures and Tables -
Analysis 1.3

Comparison 1 Anti‐vascular endothelial growth factor (anti‐VEGF) with or without panretinal photocoagulation (PRP) versus PRP alone, Outcome 3 Presence of vitreous or pre‐retinal haemorrhage.

Comparison 1 Anti‐vascular endothelial growth factor (anti‐VEGF) with or without panretinal photocoagulation (PRP) versus PRP alone, Outcome 4 Adverse effects.
Figures and Tables -
Analysis 1.4

Comparison 1 Anti‐vascular endothelial growth factor (anti‐VEGF) with or without panretinal photocoagulation (PRP) versus PRP alone, Outcome 4 Adverse effects.

Comparison 2 Bevacizumab with vitrectomy compared with vitrectomy alone, Outcome 1 Loss of 3 or more lines of ETDRS visual acuity.
Figures and Tables -
Analysis 2.1

Comparison 2 Bevacizumab with vitrectomy compared with vitrectomy alone, Outcome 1 Loss of 3 or more lines of ETDRS visual acuity.

Comparison 2 Bevacizumab with vitrectomy compared with vitrectomy alone, Outcome 2 Gain of 3 or more lines of ETDRS visual acuity.
Figures and Tables -
Analysis 2.2

Comparison 2 Bevacizumab with vitrectomy compared with vitrectomy alone, Outcome 2 Gain of 3 or more lines of ETDRS visual acuity.

Comparison 2 Bevacizumab with vitrectomy compared with vitrectomy alone, Outcome 3 Visual acuity.
Figures and Tables -
Analysis 2.3

Comparison 2 Bevacizumab with vitrectomy compared with vitrectomy alone, Outcome 3 Visual acuity.

Comparison 2 Bevacizumab with vitrectomy compared with vitrectomy alone, Outcome 4 Presence of vitreous or pre‐retinal haemorrhage.
Figures and Tables -
Analysis 2.4

Comparison 2 Bevacizumab with vitrectomy compared with vitrectomy alone, Outcome 4 Presence of vitreous or pre‐retinal haemorrhage.

Comparison 2 Bevacizumab with vitrectomy compared with vitrectomy alone, Outcome 5 Adverse effects.
Figures and Tables -
Analysis 2.5

Comparison 2 Bevacizumab with vitrectomy compared with vitrectomy alone, Outcome 5 Adverse effects.

Summary of findings for the main comparison. Anti‐VEGF with or without laser (panretinal photocoagulation; PRP) compared with PRP alone for proliferative diabetic retinopathy

Anti‐VEGF with or without laser (panretinal photocoagulation; PRP) compared with PRP alone for proliferative diabetic retinopathy

Patient or population: people with PDR

Settings: hospital

Intervention: anti‐VEGF with or without PRP

Comparison: PRP

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Assumed risk

Corresponding risk

PRP

Anti‐VEGF with or without PRP

Loss of3 lines of ETDRS visual acuity
Follow‐up: 12 months

300 per 1000

57 per 1000 (15 to 243)

RR 0.19 (0.05 to 0.81)

61 (1 study)

⊕⊝⊝⊝
very low1

Gain of3 lines of ETDRS visual acuity
Follow‐up: mean 12 months

10 per 1000

68 per 1000 (4 to 1260)

RR 6.78 (0.37 to 125.95)

61 (1 study)

⊕⊕⊝⊝
very low1

Visual acuity
logMAR

(logMAR scale value of 0 = 6/6 vision, higher score = worse vision)

Follow‐up: 12 months

The mean visual acuity ranged across control groups from
0.08 to 0.72 logMAR

The mean visual acuity in the intervention groups was
0.07 logMAR units lower
(0.12 to 0.02 lower)

373 (5 studies)

⊕⊕⊝⊝
low2

Regression of proliferative diabetic retinopathy (as measured by area of fluorescein leakage)

Follow‐up: 12 months

In 1 trial, people who received bevacizumab in addition to PRP had more regression of PDR, as measured by area of fluorescein leakage at 6 months compared with people who had PRP alone (MD ‐8.13 mm2, 95% CI ‐10.94 mm2 to ‐5.32 mm2, 19 participants). In another trial, people who received ranibizumab in addition to PRP had more regression of PDR, as measured by change in area of fluorescein leakage between baseline and 12 months compared with people who had PRP alone, however, the size of the effect was smaller and the CIs were compatible with no effect, or less regression (MD ‐1.0 mm2, 95% CI ‐5.3 mm2 to 3.3 mm2, 20 participants)

Presence of vitreous/pre‐retinal haemorrhage

Follow‐up: 12 months

150 per 1000

48 per 1000 (24 to 98)

RR 0.32 (95% CI 0.16 to 0.65)

342 (3 studies)

⊕⊕⊝⊝
low3

Quality of life

No data reported on quality of life

Adverse effects

Adverse effects were reported in 3 studies: 1 study of bevacizumab plus PRP compared with PRP alone and followed up to 3 months (61 participants); 1 study of ranibizumab compared with saline (both groups received PRP if indicated) and followed up to 4 months (261 participants); 1 study of ranibizumab plus PRP compared with PRP alone and followed up to 12 months (31 participants)

  • Neovascular glaucoma: RR 1.09 (95% CI 0.07 to 17.21; 1 RCT, 261 participants)

  • Retinal detachment: RR 0.99 (95% CI 0.44 to 2.25; 1 RCT, 261 participants)

  • Cataract: RR 0.32 (95% CI 0.01 to 7.63; 1 RCT, 61 participants)

  • Raised intraocular pressure: 2 different estimates from 2 trials: RR 0.11 (95% CI 0.01 to 1.92; 1 RCT, 61 participants) and RR 0.92 (95% CI 0.49 to 1.70; 1 RCT, 261 participants)

  • Cerebrovascular accident: RR 3.26 (95% CI 0.13 to 79.34; 2 RCTs, 322 participants)

  • Endophthalmitis: RR 0.36 (95% CI 0.01 to 8.82; 1 RCT, 261 participants) ‐ but unusual trial as control group received injection of saline, only case of endophthalmitis

  • Arterial hypertension: RR 0.47 (95% CI 0.12 to 1.76; 1 RCT, 261 participants)

  • Pain score: MD ‐56.1 (95% CI ‐71.9 to ‐40.3; 1 RCT, 31 participants) in favour of ranibizumab compared with PRP

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; ETDRS: Early Treatment Diabetic Retinopathy Study; MD: mean difference; PDR: proliferative diabetic retinopathy; PRP: panretinal photocoagulation; RR: risk ratio; VEGF: vascular endothelial growth factor.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded for risk of bias (‐1) (study at high risk of selective reporting bias) imprecision (‐1) (wide CIs) and indirectness (‐1) (study reported gain/loss of ≥ 2 lines at 3 months only).
2 Downgraded for risk of bias (‐1) (3 studies at high risk of bias in ≥ 1 domains) and downgraded for indirectness (‐1) (only 1 of the studies followed up to 12 months).

3 Downgraded for risk of bias (‐1) (2 studies at high risk of bias in ≥ 1 domain) and downgraded for indirectness (‐1) (no study reported at 12 months).

Figures and Tables -
Summary of findings for the main comparison. Anti‐VEGF with or without laser (panretinal photocoagulation; PRP) compared with PRP alone for proliferative diabetic retinopathy
Summary of findings 2. Bevacizumab before or during vitrectomy compared with vitrectomy alone

Bevacizumab before or during vitrectomy compared with vitrectomy alone

Patient or population: people undergoing vitrectomy for PDR

Settings: hospital

Intervention: bevacizumab before or during vitrectomy

Comparison: vitrectomy alone or vitrectomy with sham injection

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Assumed risk

Corresponding risk

Surgery

Anti‐VEGF plus surgery

Loss of3 lines of ETDRS visual acuity

Follow‐up: 12 months

60 per 1000

29 per 1000
(5 to 188)

RR 0.49
(0.08 to 3.14)

94
(3 studies)

⊕⊕⊝⊝
low1

Gain of3 lines of ETDRS visual acuity

Follow‐up: 12 months

500 per 1000

810 per 1000
(600 to 1000)

RR 1.62
(1.2 to 2.17)

94
(3 studies)

⊕⊕⊝⊝
low 1

Visual acuity

logMAR
(logMAR scale value of 0 = 6/6 vision, higher score = worse vision)

Follow‐up: 12 months

The mean visual acuity ranged across control groups from
0.51 to 1.46 logMAR units

The mean visual acuity in the intervention groups was
0.24 logMAR units lower
(0.50 lower to 0.01 higher)

335
(6 studies)

⊕⊕⊝⊝
low3

Regression of PDR (as measured by area of fluorescein leakage)

Follow‐up: 12 months

No data reported on regression of PDR

Presence of vitreous/pre‐retinal haemorrhage

Follow‐up: 12 months

500 per 1000

150 per 1000 (90 to 260)

RR 0.30 (0.18 to 0.52)

393 (7 studies)

⊕⊕⊝⊝
low4

Quality of life

No data reported on quality of life

Adverse effects

Neovascular glaucoma: RR 2.33 (95% CI 0.28 to 19.17; 1 RCT, 368 participants)

Retinal detachment: RR 0.56 (95% CI 0.11 to 2.86; 3 RCTs, 182 participants)

Cataract: RR 0.68 (95% CI 0.38 to 1.23; 2 RCTs, 137 participants)

Raised intraocular pressure: RR 0.31 (95% CI 0.01 to 7.47; 1 RCT, 68 participants)

Myocardial infarction: no events in 2 trials (175 participants)

Cerebrovascular accident: no events in 2 trials (175 participants)

Endophthalmitis: none of the studies reported endophthalmitis

Arterial hypertension: none of the studies reported arterial hypertension

Pain: none of the studies reported pain

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; ETDRS: Early Treatment Diabetic Retinopathy Study; PDR: proliferative diabetic retinopathy; RR: risk ratio; VEGF: vascular endothelial growth factor.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded for imprecision (‐1) (wide CIs) and downgraded for indirectness (‐1) (only 1 trial reported at 12 months and only 1 (other) trial reported loss of ≥ 3 lines).
2 Downgraded for indirectness (‐1) (only 1 trial reported at 12 months and only 1 (other) trial reported gain of ≥ 3 lines) and downgraded for inconsistency (‐1) (I2 = 73%).

3Downgraded for risk of bias (‐1) (2 studies at high risk of bias in ≥ 1 domains) and downgraded for inconsistency (‐1) (I2 = 66%).

4 Downgraded for risk of bias (‐1) (2 studies at high risk of bias in ≥ 1 domains, 3 studies at unclear risk of bias in ≥ 3 domains) and downgraded for indirectness (‐1) (only 1 study reported at 12 months).

Figures and Tables -
Summary of findings 2. Bevacizumab before or during vitrectomy compared with vitrectomy alone
Table 1. ETDRS classification of diabetic retinopathy

Mild

Presence of at least 1 microaneurysm

Moderate

Haemorrhages or microaneurysms (or both) more than standard photo 2A, presence of soft exudates, venous beading, IRMA definitively present

Severe

Haemorrhages or microaneurysms (or both) more than standard photo 2A in all 4 quadrants, or venous beading in ≥ 2 quadrants, or IRMA more than standard photo 8A in at least 1 quadrant

Very severe

Any ≥ 2 of the changes seen in severe NPDR

Early PDR

Presence of new vessels

High‐risk PDR

Any of the following: NVD more than one‐third to one‐quarter disc diameter, NVD less than one‐third to one‐quarter disc diameter with vitreous or pre‐retinal haemorrhage, new vessels elsewhere with vitreous or pre‐retinal haemorrhage

ETDRS: Early Treatment Diabetic Retinopathy Study; IRMA: intraretinal microaneurysm; NPDR: non‐proliferative diabetic retinopathy; NVD: new vessels at optic disc; PDR: proliferative diabetic retinopathy.

Figures and Tables -
Table 1. ETDRS classification of diabetic retinopathy
Table 2. ICDRDS scale

Non‐apparent retinopathy

No abnormalities

Mild NPDR

Microaneurysms only

Moderate NPDR

More than just microaneurysms but less than severe NPDR

Severe NPDR

Any of the following: > 20 intraretinal haemorrhages in each of 4 quadrants; definite venous beading in 2 quadrants; prominent intraretinal microvascular abnormalities in 1 quadrant and no signs of proliferative retinopathy

Proliferative diabetic retinopathy

≥ 1 of the following: neovascularisation, vitreous or pre‐retinal haemorrhage

ICDRDS: International Clinical Diabetic Retinopathy Disease Severity scale; NPDR: non‐proliferative diabetic retinopathy.

Figures and Tables -
Table 2. ICDRDS scale
Comparison 1. Anti‐vascular endothelial growth factor (anti‐VEGF) with or without panretinal photocoagulation (PRP) versus PRP alone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Visual acuity Show forest plot

5

373

Mean Difference (IV, Random, 95% CI)

‐0.07 [‐0.12, ‐0.02]

1.1 Pegaptanib

1

16

Mean Difference (IV, Random, 95% CI)

‐0.06 [‐0.22, 0.10]

1.2 Bevacizumab

2

80

Mean Difference (IV, Random, 95% CI)

‐0.01 [‐0.11, 0.09]

1.3 Ranibizumab

2

277

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐0.16, ‐0.03]

2 Regression of proliferative diabetic retinopathy Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

3 Presence of vitreous or pre‐retinal haemorrhage Show forest plot

3

342

Risk Ratio (M‐H, Fixed, 95% CI)

0.32 [0.16, 0.65]

3.1 Bevacizumab

1

61

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 1.92]

3.2 Pegaptanib

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.2 [0.01, 3.70]

3.3 Ranibizumab versus control

1

261

Risk Ratio (M‐H, Fixed, 95% CI)

0.38 [0.18, 0.81]

4 Adverse effects Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Neovascular glaucoma

1

261

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.07, 17.21]

4.2 Retinal detachment

1

261

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.44, 2.25]

4.3 Cataract

1

61

Risk Ratio (M‐H, Fixed, 95% CI)

0.32 [0.01, 7.63]

4.4 Raised intraocular pressure

2

322

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.42, 1.36]

4.5 Cerebrovascular accident

2

322

Risk Ratio (M‐H, Fixed, 95% CI)

3.26 [0.13, 79.34]

4.6 Endophalmitis

1

261

Risk Ratio (M‐H, Fixed, 95% CI)

0.36 [0.01, 8.82]

4.7 Arterial hypertension

1

261

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.12, 1.76]

Figures and Tables -
Comparison 1. Anti‐vascular endothelial growth factor (anti‐VEGF) with or without panretinal photocoagulation (PRP) versus PRP alone
Comparison 2. Bevacizumab with vitrectomy compared with vitrectomy alone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Loss of 3 or more lines of ETDRS visual acuity Show forest plot

3

94

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.08, 3.14]

2 Gain of 3 or more lines of ETDRS visual acuity Show forest plot

3

94

Risk Ratio (M‐H, Fixed, 95% CI)

1.62 [1.20, 2.17]

3 Visual acuity Show forest plot

6

335

Mean Difference (IV, Random, 95% CI)

‐0.24 [‐0.50, 0.01]

4 Presence of vitreous or pre‐retinal haemorrhage Show forest plot

7

393

Risk Ratio (M‐H, Random, 95% CI)

0.30 [0.18, 0.52]

5 Adverse effects Show forest plot

5

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Neovascular glaucoma

1

107

Risk Ratio (M‐H, Random, 95% CI)

2.33 [0.28, 19.17]

5.2 Retinal detachment

3

182

Risk Ratio (M‐H, Random, 95% CI)

0.56 [0.11, 2.86]

5.3 Cataract

2

137

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.38, 1.23]

5.4 Raised intraocular pressure

1

68

Risk Ratio (M‐H, Random, 95% CI)

0.31 [0.01, 7.47]

5.5 Myocardial infarction

2

175

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.6 Cerebrovascular accident

2

175

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.7 Arterial hypertension

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 2. Bevacizumab with vitrectomy compared with vitrectomy alone