Ranibizumab for Treatment of Neovascular Age-Related Macular Degeneration. A Phase I/II Multicenter, Controlled, Multidose Study

Jeffrey S. Heier, Andrew N. Antoszyk, Peter Reed Pavan, Steven R. Leff, Philip J. Rosenfeld, Thomas A. Ciulla, Richard F. Dreyer, Ronald C. Gentile, Judy P. Sy, Gary Hantsbarger, Naveed Shams

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365 Scopus citations


Objective: To assess safety of repeated intravitreal injections of ranibizumab in treating neovascular age-related macular degeneration (AMD), and to assess changes in visual acuity (VA) and AMD lesion characteristics. Design: Multicenter, controlled, open-label, clinical trial. Participants: Sixty-four patients with subfoveal predominantly or minimally classic AMD-related choroidal neovascularization. Methods: In part 1, subjects were randomized to monthly intravitreal ranibizumab for 3 months (4 injections of 0.3 mg or 1 injection of 0.3 mg followed by 3 injections of 0.5 mg; n = 53) or usual care (UC; n = 11). In part 2, subjects could continue their regimen for 3 additional months or cross over to the alternative treatment. Main Outcome Measures: Adverse events (AEs), intraocular pressure (IOP), VA, and lesion characteristics assessed by fluorescein angiography and fundus photography. Results: Of the 64 randomized subjects, 62 completed the 6-month study. Twenty of 25 subjects (80%) randomized to 0.3 mg, and 22 of 28 subjects (79%) randomized to 0.5-mg ranibizumab in part 1 continued on that treatment in part 2; 9 of 11 (82%) subjects randomized to UC in part 1 crossed over to ranibizumab treatment in part 2. The most common AEs with ranibizumab were reversible inflammation and minor injection-site hemorrhages. Serious AEs were iridocyclitis, endophthalmitis, and central retinal vein occlusion (1 subject each). Postinjection, IOP increased transiently in 22.6% of ranibizumab-treated eyes in parts 1 and 2. After 4 ranibizumab injections (day 98), mean (± standard deviation) VA had increased 9.4±13.3 and 9.1±17.2 letters in the 0.3- and 0.5-mg groups, respectively, but had decreased 5.1±9.6 letters with UC. In part 2 (day 210), VA increased from baseline 12.8±14.7 and 15.0±14.2 letters in subjects continuing on 0.3 and 0.5 mg, respectively. Visual acuity improved from baseline ≥15 letters in 26% (day 98) and 45% (day 210) of subjects initially randomized to and continuing on ranibizumab, respectively, and areas of leakage and subretinal fluid decreased. No UC subject had a ≥15-letter improvement at day 98. Conclusions: Repeated intravitreal injections of ranibizumab had a good safety profile and were associated with improved VA and decreased leakage from choroidal neovascularization in subjects with neovascular AMD.

Original languageEnglish
Pages (from-to)633-642.e4
Issue number4
StatePublished - Apr 2006
Externally publishedYes


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