Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for neovascular age-related macular degeneration.
BACKGROUND
Age-related macular degeneration (AMD) is a common cause of severe vision loss in people 55 years and older.


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


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


METHODS
We included randomized controlled trials (RCTs).


METHODS
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.


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.


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.
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D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide / Q000627:therapeutic use; D020256:Choroidal Neovascularization; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy*; D008875:Middle Aged; D011166:Porphyrins / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000069579:Ranibizumab; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D000077362:Verteporfin
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide; D011166:Porphyrins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077362:Verteporfin; C495058:pegaptanib; D000069579:Ranibizumab