Anti-VEGF therapy for the treatment of glaucoma

April 1, 2013

Early reports on off-label uses for anti-VEGFs are promising

Anti-vascular endothelial growth factor (VEGF) therapy has been widely used in the treatment of ocular neovascular diseases. As a result of their antiangiogenic and anti-fibrotic properties, antiVEGF antibodies have emerged as an adjunctive treatment modality in glaucoma to improve success of conventional treatments.

Bevacizumab is a full-length humanized IgG1 monocolonal antibody against all isoforms of VEGFA,1 and ranibizumab is an antigen-binding fragment (Fab) developed for ocular indications and affinity-matured to bind to all isoforms of VEGF-A. These anti-VEGF antibodies are being used off-label in neovascular glaucoma (NVG) to regress/suppress iris and iridocorneal angle neovascularization and in glaucoma filtration surgery to modulate postoperative wound healing.

In this article, the results of preclinical and clinical studies regarding these off-label uses of bevacizumab and ranibizumab are presented and will guide the use of these agents in clinical practice.

Anti-VEGF antibodies in neovascular glaucoma

Because formation of fibrovascular membrane in the iridocorneal angle and resultant blockage of trabecular aqueous outflow pathway are key pathologies in NVG, human clinical studies on the use of anti-VEGF antibody in the treatment of NVG were performed.

Several case studies reported a regression of iris neovascularization, reduction of intraocular pressure (IOP) or decrease in iris fluorescein angiography leakage after intravitreal bevacizumab injections.2–5 A larger case series was reported on six patients who received 1.25 mg/0.05 mL of bevacizumab followed by panretinal photocoagulation which resulted in complete regression of iris and angle neovascularization.6 Another case series reported complete or partial reduction of leakage in iris fluorescein angiography within 3 weeks after intracameral injection of bevacizumab in 16 of 16 eyes.7 A retrospective review of 41 cases with secondary iris neovascularization or NVG found that initial treatment with intravitreal bevacizumab controlled IOP in patients with iris neovascularization alone or early-stage NVG without angle closure.8 Intravitreal bevacizumab resulted in more rapid decrease in IOP when combined with panretinal photocoagulation.9

Investigations of ranibizumab in the treatment of NVG have been scarce. A case of radiation-induced NVG successfully treated with a single intravitreal injection of 0.5 mg/0.05 mL of ranibizumab was reported.10 In a case series of 14 eyes with NVG after proton therapy for uveal melanoma, Caujolle et al.11 reported promising results using intravitreal ranibizumab either alone or in combination with 180-degree ciliary body cryotherapy as a last-chance treatment before enucleation. All patients suffered from uncontrolled NVG despite maximal medical treatment. Iris neovascularization resolved in all cases and IOP was normalized in 11 out of 14 patients after the treatment.

These early results of bevacizumab and ranibizumab in the treatment of NVG in human eyes are promising, especially for ranibizumab when considering its substantially higher potency on a molar basis and lower possibility of complement-mediated or cell-medicated cytotoxicity than those of bevacizumab.