An Open Label, Pilot Study of Intravenous Bevacizumab in Subjects with Choroidal Neovascularization Secondary to Diseases Other Than Age-Related Macular Degeneration (nonAMD CNV)

Abstract

Purpose:: To investigate the safety, tolerability, and bioactivity of intravenous infusions of Bevacizumab in patients with nonAMD CNV.

Methods:: Ten patients (4, pathologic myopia; 2 ocular histoplasmosis;3 PIC; 1 angioid streaks;7 with bilateral CNV) with mean age of 44 years were given an infusion of 5mg/kg of Bevacizumab at baseline and Day 14. Patients were evaluated every two weeks up to 12 weeks and given up to 2 more infusions for persistent leakage by fluorescein angiography (FA). Patients were followed up at 16, 24, 36 and 48 weeks. The primary efficacy outcome measure was change in visual acuity (VA, ETDRS letters) at 24 weeks and secondary measures were foveal thickness (FT) and macular volume (MV) measured by optical coherence tomography and absence of leakage by FA.

Results:: Infusions were well-tolerated and there were no ocular or systemic adverse events, including no significant elevation in blood pressure. Eight patients received 4 infusions and two received 3 infusions. At baseline, median VA was 27 ETDRS letters, median FT was 346 µm, and median MV was 7.25 mm³. Four weeks after the second infusion, median VA increased to 41 ETDRS letters (p=0.008), FT was reduced to 268 µm (p=0.01), and MV was 7.1 mm³(p=0.03). At the primary endpoint, 24 weeks, median VA was 48 ETDRS letters, which represents 4 lines of improvement (p= 0.005), median FT was 249 µm representing 79% reduction in excess FT compared to baseline (p= 0.007) and mean MV was 6.92 mm³, a reduction of 42% compared to baseline. One patient could not have FAs due to allergy; the other 9 patients showed complete resolution of fluorescein leakage.

Conclusions:: Intravenous Bevacizumab was well-tolerated in patients with nonAMD CNV with no significant changes in blood pressure or urinary protein levels. Despite the small number of patients studied, the complete resolution of fluorescein leakage in all patients, accompanied by striking improvement in VA, FT, and MV suggest a beneficial effect. Further evaluation of systemic Bevacizumab should be considered since it could provide a useful alternative to intraocular injections in patients with bilateral disease.

Clinical Trial:: www.clinicaltrials.gov pending

Keywords: choroid: neovascularization • myopia • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials