Aging eye is focus of ARVO meeting in 2007

Key Points

Retina

Vascular endothelial growth factor (VEGF) is a signaling protein for angiogenesis; anti-VEGF agents, such as the monoclonal antibody bevacizumab (Avastin, Genentech), and its fragment ranibizumab (Lucentis, Genentech), are the two primary anti-VEGF agents for the treatment of neovascular (wet) AMD. Although ranibizumab is FDA-approved for ophthalmic use, bevacizumab still awaits formal approval. Bevacizumab is reported to have an efficacy comparable with that of ranibizumab, but it costs significantly less. ARVO posters reflected the ophthalmic community's enthusiasm for bevacizumab; noticeably more abstracts mentioned bevacizumab than ranibizumab.

Individuals with branch retinal vein occlusion (BRVO) also may benefit from intravitreal bevacizumab. A retrospective study of 36 patients with BRVO found that nine eyes remained within 3 lines of baseline visual acuity, and vision in 27 eyes improved 2 or more lines, after a mean of 1.4 doses.²

Bevacizumab also may be useful for treating childhood blindness. In a study involving 27 children with retinopathy of prematurity, neovascular regression was observed in all patients (mean follow-up, 6 months).³

Also in development for the treatment of wet AMD is a potent fusion protein anti-VEGF agent (VEGF Trap-Eye, Regeneron Pharmaceuticals Inc.). Interim phase II data showed that, at the 12-week endpoint, the agent delivered intravitreally significantly reduced retinal thickness by an average of 135 µm and significantly improved visual acuity by an average of 5.9 letters. The dose regimen of the agent also may be appealing: no significantly different outcomes have been noted between monthly and quarterly dosing schedules.⁴

Photodynamic therapy (PDT) currently is one of the primary methods of treating AMD. Although PDT can seal neovascular membranes permanently, it also can stimulate inflammation and VEGF release. Anti-VEGF agents, therefore, may be useful co-therapies for AMD; however, the order in which the treatments are administered may affect efficacy. After conducting a chart review of 20 patients who received PDT along with an anti-VEGF agent (pegaptanib, bevacizumab, or both), it was noted that patients who received PDT first were more likely (75%) to have improved acuity compared with patients who first received an anti-VEGF agent (33%).⁵ PDT and anti-VEGF combination therapy also is being investigated for the treatment of wet AMD.⁶

Other viable methods of inhibiting ocular angiogenesis may exist. The bioactive lysolipid sphingosine 1-phosphate (S1P) mediates pro-angiogenic signaling in non-ocular diseases. A mouse model of choroidal neovascularization (CNV) was used to test the efficacy of intravitreal shingozumab, a monoclonal antibody that binds to S1P. Neovascular lesion formation was inhibited 98.5% by volume compared with the vehicle.⁷ Antioxidants may have similar inhibitory effects on angiogenesis; the antioxidant OT-551/OT674 significantly inhibited the effects of pro-angiogenic stimulators.⁸

Another signaling molecule involved in the pathogenesis of CNV is JAK2. TG101095 is a dual VEGF receptor and JAK2 inhibitor; when dosed topically b.i.d. for 2 weeks in a CNV mouse model, it significantly reduced CNV area. It, therefore, may have clinical efficacy for both diabetic retinopathy and AMD.⁹