After three monthly injections of either dose, substantial improvements in foveal thickness and visual acuity (VA) were apparent. The median improvement in letters read at 4 m (ETDRS protocol) was 17 in the patients with CRVO who received 0.3 mg of ranibizumab and 14 in the patients who received the 0.5-mg dose. In the patients with BRVO, the respective increases were 10 and 18 letters.
Optical coherence tomography showed that the 0.5-mg dose resulted in a more rapid decrease in central retinal thickness compared with the 0.3-mg dose, and the decreases in the central retinal thickness on average lasted somewhat longer between injections; however, by the end of the study, the excess central retinal thickening had been reduced by roughly 90% in all four treatment groups.
No correlation existed between the amount of improvement in VA and duration of disease or patient age at baseline, but a negative correlation did exist between the aqueous vascular endothelial growth factor (VEGF) level at baseline and the amount of improvement. The mean level of VEGF in the aqueous was significantly greater in patients with CRVO compared with patients with BRVO. The results at the primary endpoint have been published in Molecular Therapy (2008;16:791-799).
Dr. Campochiaro said that the study data indicated that excess production of VEGF in the retinas of patients with CRVO or BRVO is a major contributor to ME and may influence the outcome of treatment with ranibizumab. These data support further investigation of both doses of ranibizumab in patients with ME due to vein occlusions, which is being done in the CRUISE and BRAVO phase III studies that are sponsored by the marketer of the drug.
Follow-up of patients beyond the primary endpoint has demonstrated that edema recurred in most of them. An amendment to the study allows treatment of recurrent edema with injections of ranibizumab. A major objective of the follow-up study was to determine if and when patients have prolonged resolution of edema and no longer require ranibizumab injections. The most important goal is to determine the level of VA (and the change in VA from baseline) when such stabilization is achieved, Dr. Campochiaro said.
Other investigators include Gulnar Hafiz, MD; Syed M. Shah, MD; Quan Dong Nguyen, MD; Howard Ying, MD; Diana V. Do, MD; Edward Quinlan, MD; Ingrid Zimmer-Galler, MD; Julia A. Haller, MD; Sharon D. Solomon, MD; Jennifer U. Sung, MD; Yasmin Hadi, BS; Kashif A. Janjua, MD; Nida Jawed, BS; David F. Choy, PhD; and Joseph Arron, PhD.