Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) for neovascular age-related macular degeneration.
OBJECTIVE
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).


METHODS
Open-label, 2-center, uncontrolled, randomized clinical study of 3 different dose-escalating regimens of ranibizumab.


METHODS
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.


METHODS
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.
Rosenfeld
Philip J
PJ
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, Florida 33136, USA. prosenfeld@med.miami.edu
Heier
Jeffrey S
JS
Hantsbarger
Gary
G
Shams
Naveed
N
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D007267:Injections; D007429:Intraocular Pressure; D008268:Macular Degeneration / Q000150:complications / Q000188:drug therapy*; D008297:Male; D000069579:Ranibizumab; D012008:Recurrence; D016896:Treatment Outcome; D014792:Visual Acuity; D014822:Vitreous Body
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069579:Ranibizumab