Macular Degeneration: Hantsbarger G

Rosenfeld PJ, Heier JS, Hantsbarger G, Shams N. · Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, Florida 33136, USA. · Ophthalmology. · Pubmed #16581423 No free full text.

Abstract: PURPOSE: To investigate whether multiple intravitreal doses of up to 2 mg of an antigen-binding fragment known as ranibizumab, derived from a humanized anti-vascular endothelial growth factor antibody, can be tolerated and are biologically active when injected using a dose-escalating strategy in eyes of patients with neovascular age-related macular degeneration (AMD). DESIGN: Open-label, 2-center, uncontrolled, randomized clinical study of 3 different dose-escalating regimens of ranibizumab. PARTICIPANTS: Thirty-two patients with primary or recurrent subfoveal choroidal neovascularization secondary to AMD were enrolled. Baseline best-corrected visual acuity (VA) in the study eye was from 20/40 to 20/640 (Snellen equivalent). METHODS: Treatment regimens consisted of 5, 7, or 9 intravitreal injections of ranibizumab at 2- or 4-week intervals for 16 weeks, with escalating doses ranging from 0.3 to 2.0 mg. Patients were evaluated through day 140, 4 weeks after their last injection. MAIN OUTCOME MEASURES: Safety was assessed based on ocular and nonocular adverse events, changes in VA, changes in intraocular pressure (IOP), slit-lamp ocular examination, changes in lesion characteristics based on fluorescein angiography and color fundus photography, and the presence of anti-ranibizumab antibodies. RESULTS: Twenty-nine patients received an injection at baseline, and 27 patients completed the study through day 140. Results were similar across the 3 treatment groups. All patients experienced ocular adverse events, most of which were mild. The most common ocular adverse events were iridocyclitis (83%) and injection-site reactions (72%). Inflammation did not increase with repeated injections, despite the increasing ranibizumab doses. Transient mild IOP elevations were common after ranibizumab injection. No serum anti-ranibizumab antibodies were detected. Overall, median and mean VAs in the study eyes improved by day 140 in all 3 groups. Only 3 of the 27 patients lost significant vision. There was no significant lesion growth, and a decrease in area of leakage from choroidal neovascularization was detected through day 140. CONCLUSIONS: Multiple intravitreal injections of ranibizumab at escalating doses ranging from 0.3 to 2.0 mg were well tolerated and biologically active in eyes with neovascular AMD through 20 weeks. Mild transient ocular inflammation was the most common postinjection adverse event.

Heier JS, Antoszyk AN, Pavan PR, Leff SR, Rosenfeld PJ, Ciulla TA, Dreyer RF, Gentile RC, Sy JP, Hantsbarger G, Shams N. · Ophthalmic Consultants of Boston, Boston, Massachusetts 02114, USA. · Ophthalmology. · Pubmed #16483659 No free full text.

Abstract: 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 > or =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 > or =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.