Intravenous bevacizumab causes regression of choroidal neovascularization secondary to diseases other than age-related macular degeneration

Abstract

Purpose: To investigate the safety, tolerability, and bioactivity of intravenous infusions of bevacizumab in patients with choroidal neovascularization (CNV) attributable to causes other than age-related macular degeneration.

Design: Nonrandomized clinical trial.

Methods: Ten patients with CNV received infusions of 5 mg/kg of bevacizumab. The primary efficacy outcome measure was change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters read at 4 meters) at 24 weeks and secondary measures were changes from baseline in excess foveal thickness (center subfield thickness), area of fluorescein leakage, and area of CNV.

Results: Infusions were well tolerated and there were no ocular or systemic adverse events. At baseline, median VA was 25.5 letters read at 4 meters (20/80) and median foveal thickness was 346 mum. At the primary endpoint (24 weeks), median VA was 48.5 letters (20/32), representing four lines of improvement from baseline (P = .005), median foveal thickness was 248 mum representing a 72% reduction in excess foveal thickness (P = .007). Four of nine patients had complete elimination of fluorescein leakage, three had near complete elimination (reductions of 91%, 88%, and 87%), two had modest reductions, and one had no reduction. All patients except one showed a reduction in area of CNV with a median reduction of 43%.

Conclusions: Despite the small number of patients studied, the marked improvement in VA accompanied by prominent reductions in foveal thickness, fluorescein leakage, and area of CNV suggest a beneficial effect. It may be worthwhile to consider further evaluation of systemic bevacizumab in young patients with CNV.

Trial registration: ClinicalTrials.gov NCT00407719.

Figures

FIGURE 1

Patient 2, a 50-year-old Caucasian woman with choroidal neovascularization (CNV) attributable to birdshot chorioretinopathy (BCR). Studies obtained at baseline and two, four, and 24 weeks after the first infusion are shown including best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters read at 4 meters and Snellen equivalent, frames from early, mid, and late phases of fluorescein angiograms (FA), and horizontal and vertical cross-sections of optical coherence tomography (OCT) scans labeled T-N (temporal-nasal) and I-S (inferior-superior), respectively. At the primary endpoint of 24 weeks after the first infusion, the patient showed improved BCVA, reduced CNV lesion size, and reduction in leakage and edema, but not complete resolution.

FIGURE 2

Patient 5, a 37-year-old Caucasian woman with CNV attributable to angioid streaks. Studies obtained at baseline and 2, 4, and 24 weeks after the first infusion are shown including BCVA in ETDRS letters read at 4 meters and Snellen equivalent, frames from early, mid, and late phases of FA, and horizontal and vertical cross-sections of OCT scans labeled T-N (temporal-nasal) and I-S (inferior-superior), respectively. At the primary endpoint of 24 weeks after the first infusion, the patient showed improved BCVA, reduced CNV lesion size, resolution of leakage, and resolution of subretinal and intraretinal fluid in the macula.

FIGURE 3

Patient 8, a 58-year-old Caucasian man with CNV attributable to ocular histoplasmosis. Studies obtained at baseline and two, four, and 24 weeks after the first infusion are shown, including BCVA in ETDRS letters read at 4 meters and Snellen equivalent, frames from early, mid, and late phases of FA, and horizontal and vertical cross-sections of OCT scans labeled T-N (temporal-nasal) and I-S (inferior-superior), respectively. At the primary endpoint of 24 weeks after the first infusion (followed by two subsequent infusions of 5 mg/kg bevacizumab), the patient showed improved BCVA, reduced CNV lesion size, resolution of leakage, and resolution of subretinal and intraretinal fluid in the macula.

FIGURE 4

Visual acuity (VA) and excess foveal thickness and subretinal fluid between baseline and the primary endpoint at 24 weeks. Median VA in number of letters read on an ETDRS chart at 4 meters is shown by the line graph. The median VA at baseline was 25.5 letters compared with 48 letters at the primary endpoint, a gain of 23 letters. The median change in excess foveal thickness (EFT)/subretinal fluid (SRF), which is the thickness of the fovea combined with the height of SRF in the fovea – 212 μm, is an indication of the amount of excess fluid within and under the retina is shown by the bar at each time point. The excess fluid present at baseline was reduced by 72%.

FIGURE 5

Median area of CNV and area of leakage at baseline and three time points after start of bevacizumab infusions. Each bar represents the median area of CNV (dark gray) and the median leakage area (light gray) calculated as described in the Methods section from measurements made on FAs obtained in nine patients at four time points. There is a sequential decrease in both parameters (total lesion size) at weeks 2 and 6.