BEVACIZUMAB

Vascular endothelium growth factor (VEGF) stimulates proliferation of vascular endothelial cells resulting in neovascularization and increases the permeability of the capillaries, causing edema. VEGF concentrations increase in the intraocular fluid of patients with CRVO, with the highest levels seen in patients with iris or anterior neovascularization.32 Bevacizumab is a full-length humanized monoclonal antibody against all isomersofVEGFandwasapprovedbytheFoodandDrugAdministration for intravenous administration to treat metastatic colorectal cancer.

Intravitreal injection of bevacizumab was used for macular edema due to CRVO (Figure 20.5). Rosenfeld and associates11 first reported the use of intravitreal bevacizumab to treat macular edema secondary to CRVO. In that study, patients with macular edema due to CRVO were treated with bevacizumab and the VA improved from 20/200 to 20/50. OCT showed resolution of the macular edema within 1 week. The improvements were maintained for 1 month.11 Another study reported on 46 patients with CRVO who underwent repeated intravitreal injections (1.25 mg) of bevacizumab. The mean VA improved from 20/250 to 20/80 at the 6-month follow-up and the mean central retinal thickness decreased from 535 ± 148 m at baseline to 323 ±116 m at the 6-month follow-up visit.12

OTHER MEDICATIONS

Ranimizumab

Coumadin (warfarin)

Coumadin is widely used as an anticoagulant for various systemic diseases such as venous thromboembolism, cardiac arrhythmia, following myocardial infarction, and hematologic abnormalities, among others. However, the efficacy of coumadin for CRVO is not established. It was reported that 13 of 354 patients taking warfarin developed CRVO despite maintaining therapeutic levels of the anticoagulant.34

Urokinase

The effect of systemic administration of urokinase is unclear. One study reported the effectiveness of superselective ophthalmic artery fibrinolytic therapy of urokinase for CRVO. Urokinase was infused through a microcatheter into the ostium of the ophthalmic artery via the femoral artery. Six eyes of 26 patients had a significant improvement in VA 24 hours after the fibrinolysis; eyes with combined central retinal artery occlusion and CRVO with recent visual impairment appeared to be the most responsive.35

Troxerutin

Troxerutin, a derivative of the naturally occurring bioflavonoid rutin, is thought to inhibit red cell and platelet aggregation, improve erythrocyte deformability, and improve plasma viscosity retinal microcirculation. A double-blind randomized clinical trial compared troxerutin with placebo in 27 patients with CRVO. The limitations of the study included a small number of patients and short follow-up time.36

Ticlodipine

Ticlodipine binds to adenosine diphosphate receptors on the platelet surface, resulting in platelet aggregation. A double-blind randomized clinical study that compared the effect of 500 mg/day of ticlodipine with placebo in patients with CRVO found that the treatment group tended to improve compared with placebo, but the results were not significant.37

Pentoxifylline

Pentoxifylline can increase red blood cell deformability, reduce blood viscosity, and decrease platelet aggregation and thrombus formation. Pentoxifylline is an oral agent that improves perfusion of occluded vessels and is used to treat systemic vascular diseases. The retinal flow velocity in patients with RVO treated with pentoxifylline improved compared with placebo, but the study had a small number of patients (n = 8) and short follow-up (4 weeks), and no visual outcome data were reported.38

Hemodilution

In some patients with CRVO, abnormal red cell deformability and increased plasma viscosity and hematocrit and fibrinogen levels were observed. Therefore, reducing hematocrit levels by hemodilution lowers plasma viscosity and may improve retinal microcirculation and perfusion. Several studies have reported significant improvements in VA, arteriovenous passage time, and the clinical appearance by hemodilution.39,40 However, common adverse effects, including letheargy, fainting spells, and exertional dyspnea, were observed.

Laser treatment

The Central Retinal Vein Occlusion Study Group compared the efficacy of immediate prophylactic panretinal photocoagulation in ischemic CRVO with that of observation only. Iris or angle neovascularization developed in 20% of the early treatment group and 34% in the observed group. Greater resolution of iris or angle neovascularization occurred within 1 month after panretinal photocoagulation in 18 of 32 previously untreated eyes compared with four of 18 eyes that had undergone early prophylactic treatment. Panretinal photocoagulation should be applied promptly after the development of iris or angle neovascularization in eyes with ischemic CRVO.41 The Central Retinal Vein Occlusion Study Group reported that grid laser photocoagulation for

A D

B E

C F

Figure 20.4  (A) Fundus photograph of the eye with macular edema secondary to central retinal vein occlusion shows venous dilatation and tortuosity, optic disc edema, widespread intraretinal hemorrhage, and macular edema at baseline before injection of triamcinolone acetonide (TA). (B) Fluorescein angiogram shows marked distention of the retinal vein, optic nerve head swelling, and intraretinal hemorrhage at baseline before intravitreal injection of TA. (C) Optical coherence tomography (OCT) image shows a large area of macular edema with poor visualization of the retinal pigment epithelium due to shadowing at baseline before intravitreal injection of TA. (D) Fundus photograph

1 month after intravitreal injection of TA (4 mg) shows the resorption of the intraretinal hemorrhage and improved venous dilatation and tortuosity. (E) Fluorescein angiogram 1 month after intravitreal injection of TA (4 mg) shows improved distention of the retinal vein and decreased leakage around the optic nerve head. (F) OCT image a month after intravitreal injection of TA (4 mg) shows a marked improvement in the foveal macular thickness.

Pharmacotherapy to Amenable Diseases Retinal • 3 section