Safety and Efficacy of Intravitreal Injection of Ranibizumab in Combination With Verteporfin PDT on Experimental Choroidal Neovascularization in the Monkey

Abstract

To study the safety and efficacy of intravitreal injections of anti-vascular endothelial growth factor antibody fragment (ranibizumab [formerly known as rhuFabV2], Lucentis; Genentech, South San Francisco, Calif) in combination with intravenous verteporfin (Visudyne; Novartis, East Hanover, NJ) photodynamic therapy (PDT) on experimental choroidal neovascularization in the monkey eye. Methods: Choroidal neovascularization was induced by laser injury in both eyes of cynomolgus monkeys and followed with weekly fundus photography and fluorescein angiography. Two weeks after induction, weekly treatments were initiated. These treatments included using either an intravitreal injection of ranibizumab (previously known as rhuFabV2) in combination with verteporfin PDT or a ranibizumab vehicle (placebo) in combination with verteporfin PDT (PDT only). Six animals (group 1) initially received intravitreal injections followed 1 week later by PDT. Four animals (group 2) initially received PDT followed 1 week later by intravitreal injection. Two animals (group 3) received injections and PDT on the same day at 2-week intervals. Photodynamic therapy was applied in all 3 groups every 2 weeks for 3 treatments with follow-up through 2 weeks after the last PDT treatment. Fluorescein angiograms were graded using a masked standardized protocol. The data were analyzed using the McNemar 2 test for matched pairs. Results: No choroidal neovascularization leakage was observed in the eyes of animals treated with ranibizumab and PDT at day 21 or 42 after the start of the first treatment. Leakage persisted in eyes treated with PDT alone at 21 days (3 of 12 eyes) and 42 days (2 of 12 eyes). At all time points studied, the ranibizumab and PDT-treated eyes experienced bet-terangiographicoutcomesthantheeyesreceivingPDTalone. Conclusion: These preliminary data indicate that an intravitreal ranibizumab injection in combination with verteporfin PDT (ranibizumab and PDT) causes a greater reduction in angiographic leakage than PDT and intravitreal vehicle injection (PDT only) in experimental choroidal neovascularization. Clinical Relevance: This combination therapy can potentially offer a new treatment modality for choroidal neovascularization in patients with macular degeneration and other diseases.

<p>Comparing The Efficacy Of An Anti-Human VEGF-A Neutralizing Antibody Versus Bevacizumab On A Laser-Induced Choroidal Neovascularization (CNV) Rhesus Monkey Model</p>

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<p>Comparing The Efficacy Of An Anti-Human VEGF-A Neutralizing Antibody Versus Bevacizumab On A Laser-Induced Choroidal Neovascularization (CNV) Rhesus Monkey Model</p>

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Prevention of the Angiogenic Switch in Human Breast

“…In ~90-95% of patients, the disease was arrested, and there was no further loss of sight. By contrast, patients who were treated with a placebo continually lost visual acuity over a 12-month period, as was expected [35][36][37][38][39][40] (FIG. 3a).…”

Follow-up after intravitreal triamcinolone acetonide for exudative age-related macular degeneration

“…[37][38][39][40] In the present study, a drop in visual acuity of at least three lines occurred in 34% of the eyes at 6 months after the injection, while 11% of the eyes showed an increase in visual acuity by three or more lines at the same time. At 12 months after the injection, 49% of the eyes had experienced a decrease in visual acuity by at least three lines, and 11% of the eyes showed an increase in visual acuity by three or more lines ( Table 1).…”

<p>Comparing The Efficacy Of An Anti-Human VEGF-A Neutralizing Antibody Versus Bevacizumab On A Laser-Induced Choroidal Neovascularization (CNV) Rhesus Monkey Model</p>

“……”

“……”

“……”

Prevention of the Angiogenic Switch in Human Breast

“…In ~90-95% of patients, the disease was arrested, and there was no further loss of sight. By contrast, patients who were treated with a placebo continually lost visual acuity over a 12-month period, as was expected [35][36][37][38][39][40] (FIG. 3a).…”

Follow-up after intravitreal triamcinolone acetonide for exudative age-related macular degeneration

“…[37][38][39][40] In the present study, a drop in visual acuity of at least three lines occurred in 34% of the eyes at 6 months after the injection, while 11% of the eyes showed an increase in visual acuity by three or more lines at the same time. At 12 months after the injection, 49% of the eyes had experienced a decrease in visual acuity by at least three lines, and 11% of the eyes showed an increase in visual acuity by three or more lines ( Table 1).…”

<p>Comparing The Efficacy Of An Anti-Human VEGF-A Neutralizing Antibody Versus Bevacizumab On A Laser-Induced Choroidal Neovascularization (CNV) Rhesus Monkey Model</p>

“……”

“……”

“……”

Prevention of the Angiogenic Switch in Human Breast

“…In ~90-95% of patients, the disease was arrested, and there was no further loss of sight. By contrast, patients who were treated with a placebo continually lost visual acuity over a 12-month period, as was expected [35][36][37][38][39][40] (FIG. 3a).…”

Follow-up after intravitreal triamcinolone acetonide for exudative age-related macular degeneration

“…[37][38][39][40] In the present study, a drop in visual acuity of at least three lines occurred in 34% of the eyes at 6 months after the injection, while 11% of the eyes showed an increase in visual acuity by three or more lines at the same time. At 12 months after the injection, 49% of the eyes had experienced a decrease in visual acuity by at least three lines, and 11% of the eyes showed an increase in visual acuity by three or more lines ( Table 1).…”