Anti-vascular endothelial growth factor for neovascular age-related macular degeneration (Review)

Objective: To evaluate the safety and efficacy of intravitreal injections of an antigen-binding fragment of a recombinant humanized monoclonal antibody directed toward vascular endothelial growth factor (rhuFab VEGF) in a monkey model of choroidal neovascularization (CNV). Methods: In phase 1 of the study, each animal received intravitreal injections, 500 µg per eye, of rhuFab VEGF in one eye (prevention eye), while the contralateral eye received rhuFab VEGF vehicle (control eye) at 2-week intervals. On day 21, laser photocoagulation was performed to induce CNV. In phase 2, the vehicletreated eye was crossed over and both eyes received 500 µg of rhuFab VEGF beginning 21 days following laserinduced injury at days 42 and 56. The eyes were monitored by ophthalmic examinations, color photographs, and fluorescein angiography. Results: rhuFab VEGF did not cause any ocular hemorrhages. All eyes treated with rhuFab VEGF developed acute anterior chamber inflammation within 24 hours of the first injection that resolved within 1 week, and this inflammation was less severe with subsequent injections. The incidence of CNV, defined angiographically, was significantly lower in the prevention eyes than the control eyes (PϽ.001). Subsequent treatments were associated with less leakage in eyes with established CNV that were crossed over from the control eyes to the treatment eyes (P =.001). Conclusions: Intravitreal rhuFab VEGF injections prevented formation of clinically significant CNV in cynomolgus monkeys and decreased leakage of already formed CNV with no significant toxic effects. Clinical Relevance: This study provides the nonclinical proof of principle for ongoing clinical studies of intravitreally injected rhuFab VEGF in patients with neovascular age-related macular degeneration.

Mice express S and M opsins that form visual pigments for the detection of light and visual signaling in cones. Here, we show that S opsin transcription is higher than that of M opsin, which supports ultraviolet (UV) sensitivity greater than midwavelength sensitivity. Surprisingly, most cones coexpress both S and M opsins in a common cone cell type throughout the retina. All cones express M opsin, but the levels are graded from dorsal to ventral. The levels of S opsin are relatively constant. However, in the far dorsal retina, S opsin is repressed stochastically, such that some cones express M opsin only. These observations indicate that two different mechanisms control M and S opsin expression. We suggest that a common cone type is patterned across the retinal surface to produce phenotypic cone subtypes.

Analysis 1.17. Comparison 1 Anti-VEGF treatment versus control, Outcome 17 Mean change in quality of life scores at 1 year...... Analysis 1.18. Comparison 1 Anti-VEGF treatment versus control, Outcome 18 Mean change in quality of life scores at 2 years..... Analysis 2.1. Comparison 2 Bevacizumab versus ranibizumab, Outcome 1 Gain of 15 or more letters visual acuity at 1 year........ Analysis 2.2. Comparison 2 Bevacizumab versus ranibizumab, Outcome 2 Gain of 15 or more letters visual acuity at 2 years....... Analysis 2.3. Comparison 2 Bevacizumab versus ranibizumab, Outcome 3 Loss of fewer than 15 letters visual acuity at 1 year...... Analysis 2.4. Comparison 2 Bevacizumab versus ranibizumab, Outcome 4 Loss of fewer than 15 letters visual acuity at 2 years..... Analysis 2.5. Comparison 2 Bevacizumab versus ranibizumab, Outcome 5 Visual acuity better than 20/200