Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for neovascular age-related macular degeneration

Vedula SS, Krzystolik M

Published Online:

October 8, 2008

Age-related macular degeneration (AMD) is a common cause of severe vision loss in people 55 years and older. Neovascular AMD, which involves abnormal growth of blood vessels in the back of the eye, accounts for most AMD-related severe vision loss. Medications such as pegaptanib and ranibizumab that block this abnormal growth of blood vessels in the back of the eye are one way to treat this condition. Fewer patients treated with pegaptanib lost 15 or more letters visual acuity at one year. Ranibizumab alone and when combined with verteporfin photodynamic therapy (PDT) resulted in fewer patients losing 15 or more letters visual acuity at one year. Approximately seven patients need to be treated with 0.3 mg or 0.5 mg pegaptanib to prevent loss of 15 or more letters visual acuity in one patient. This number is about 14 for 3 mg pegaptanib. In contrast just over three patients need to be treated with either 0.3 mg or 0.5 mg doses of ranibizumab to prevent loss of 15 or more letters visual acuity. Very few patients treated with pegaptanib gained visual acuity. A greater proportion of patients treated with ranibizumab gained 15 of more letters visual acuity at one year compared with sham or verteporfin PDT. No trial directly compared pegaptanib and ranibizumab. Pegaptanib and ranibizumab are beneficial for treatment of neovascular AMD and their use is associated with few adverse effects. Trials on other agents that block abnormal growth of blood vessels in this condition are ongoing and will be included in updates of the review.

Abstract (click to read)

Background:

Age-related macular degeneration (AMD) is a common cause of severe vision loss in people 55 years and older.

Objectives:

The objective of this review was to investigate the effects of anti-VEGF (vascular endothelial growth factor) modalities for treating neovascular AMD.

Search strategy:

We searched CENTRAL, MEDLINE, EMBASE and LILACS. We handsearched ARVO abstracts for 2006, 2007 for ongoing trials.

Selection criteria:

We included randomized controlled trials (RCTs).

Data collection and analysis:

Two review authors independently extracted data. We contacted trial authors for additional data. We summarized outcomes as relative risks (RR), number needed to treat (NNT) and weighted mean differences.

Main results:

We included five RCTs of good methodological quality. All five trials were conducted by pharmaceutical companies. An intention-to-treat analysis using the last observation carried forward method was done in most trials.

Two trials compared pegaptanib versus sham. One trial compared ranibizumab versus sham, another compared ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and the final trial compared ranibizumab plus verteporfin PDT versus verteporfin PDT alone.

Fewer patients treated with pegaptanib lost 15 or more letters of visual acuity at one year follow-up compared to sham (pooled relative risk (RR) 0.71; 95% confidence interval (CI) 0.61 to 0.84). The NNT was 6.67 (95% CI 4.35 to 14.28) for 0.3 mg pegaptanib, 6.25 (95% CI 4.17 to 12.5) for 1 mg pegaptanib and 14.28 (95% CI 6.67 to 100) for 3 mg pegaptanib. In a trial of ranibizumab versus sham, RR for loss of 15 or more letters visual acuity at one year was 0.14 (95% CI 0.1 to 0.22) in favour of ranibizumab. The NNT was 3.13 (95% CI 2.56 to 3.84) for 0.3 mg ranibizumab and 3.13 (95% CI 2.56 to 3.84) for 0.5 mg ranibizumab. In a trial of ranibizumab versus verteporfin PDT, RR for loss of 15 or more letters at one year was 0.13 (95% CI 0.07 to 0.23) favouring ranibizumab. The NNT was 3.33 (95% CI 2.56 to 4.76) for 0.3 mg ranibizumab and 3.12 (95% CI 2.43 to 4.17) for 0.5 mg ranibizumab. In another trial of combined ranibizumab plus verteporfin PDT versus verteporfin PDT, RR for loss of 15 or more letters at one year favoured combined therapy (RR 0.3 (95% CI 0.15 to 0.60). The NNT was 4.35 (95% CI 2.78 to 11.11).

Pooled RR for gain of 15 or more letters visual acuity at one year was 5.81 (95% CI 3.29 to 10.26) for ranibizumab versus sham, 6.79 (95% CI 3.41 to 13.54) for ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and 4.44 (95% CI 1.40 to 14.08) for ranibizumab plus verteporfin PDT versus verteporfin PDT.

Frequency of endophthalmitis in included studies was between 0.7% to 4.7% with ranibizumab and 1.3% with pegaptanib. Improvement in vision-specific quality of life was reported for both treatments.

Authors' conclusions:

Pegaptanib and ranibizumab reduce the risk of visual acuity loss in patients with neovascular AMD. Ranibizumab causes gains in visual acuity in many eyes. Quality of life and cost will be important for treatment decisions. Other agents blocking VEGF are being tested in ongoing trials.

This record should be cited as:

Vedula SS, Krzystolik M. Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for neovascular age-related macular degeneration. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD005139. DOI: 10.1002/14651858.CD005139.pub2

Assessed as up to date:

February 20, 2008

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Primary Review Group:

Eyes and Vision Group

Health topics:

Eyes & vision > Retinal degeneration > Macular degeneration

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for neovascular age-related macular degeneration

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