Topical bevacizumab in the treatment of corneal neovascularization: results of a prospective, open-label, noncomparative study

Abstract

Objective: To study the safety and efficacy of topical bevacizumab in the treatment of corneal neovascularization (NV).

Design: In a prospective, open-label, noncomparative study, 10 eyes from 10 patients with stable corneal NV were treated with topical bevacizumab, 1.0%, for 3 weeks and followed up for up to 24 weeks.

Main outcome measures: The primary safety variables were the occurrence of ocular and systemic adverse events throughout the course of the study. The primary efficacy variables were neovascular area, the area of the corneal vessels themselves; vessel caliber, the mean diameter of the corneal vessels; and invasion area, the fraction of the total corneal area covered by the vessels.

Results: From baseline visit to the last follow-up visit, mean reductions were 47.1% (standard deviation [SD], 36.7%) for neovascular area, 54.1% (SD, 28.1%) for vessel caliber, and 12.2% (SD, 42.0%) for invasion area. The decreases in neovascular area and vessel caliber were statistically significant (P= .001 and P< .001, respectively). However, changes in invasion area did not achieve statistical significance (P= .19). Visual acuity and central corneal thickness showed no significant changes. Topical bevacizumab was well tolerated with no adverse events.

Conclusions: Short-term topical bevacizumab therapy reduces the severity of corneal NV without local or systemic adverse effects.

Application to clinical practice: Topical bevacizumab provides an alternative therapy in the treatment of stable corneal NV.

Trial registration: clinicaltrials.gov Identifier: NCT00559936.

Figures

Figure 1

Quantification of corneal neovascularization. A, Digital slit-lamp corneal pictures were analyzed using graphics editing software (Photoshop) and a mathematical program (Matlab script). After the total corneal area was delineated, the blood vessels were isolated using Photoshop. In order to analyze the efficacy of bevacizumab in treating corneal NV, three metrics were computed using a Matlab script: Neovascular Area (NA), which measures the area of the corneal vessels themselves; Vessel Caliber (VC), which determines an approximate mean diameter of the corneal vessels; Invasion Area (IA), which measures the fraction of corneal area in which vessels are present. B, Changes in corneal vessels (patient 4) at different time points after the treatment.

Figure 2

Summary of changes in: A, Neovascular Area (NA), B, Vessel Caliber (VC), and C, Invasion Area (IA) for all patients at different time points in response to bevacizumab therapy (mean value ± standard deviation). By the last visit, the mean reduction was 47.1% ± 36.7% for NA, 54.1% ± 28.1% for VC, and 12.2% ± 42.0% for IA. The decreases in NA and VC were statistically significant. However, the levels of decrease varied significantly in different patients which were evidenced by high standard deviations in all 3 neovascularization metrics.

Figure 3

The effect of topical bevacizumab in patient 6, a 65-year-old woman with history of herpes zoster ophthalmicus in the left eye complicated by corneal thinning, scarring, and neovascularization. A, Baseline picture shows a main vessel branch emerging from the 9-o’clock position at the limbus and passing into the thin, depressed scar in the corneal mid-periphery where it branched several times into smaller-caliber vessels. B, C, and D, One, 6, and 24 weeks after topical bevacizumab treatment. Note the significant therapeutic response which was evidenced as early as 1 week after initiation of anti-VEGF treatment.

Figure 4

The effect of topical bevacizumab in patient 7, a 39-year-old woman with history of LASIK surgery and partial limbal stem cell deficiency in the left eye complicated by corneal neovascularization. A, Baseline picture shows superficial and deep corneal neovascularization with central lipid keratopathy. B, C, and D, Three, 12 and 24 weeks after topical bevacizumab treatment. Note the significant narrowing of blood vessels in response to anti-VEGF treatment.

Figure 5

The effect of topical bevacizumab in patient 8, a 42-year-old man with failed penetrating keratoplasty in the left eye complicated by corneal neovascularization. A, Baseline picture shows corneal opacity with severe superficial and deep corneal neovascularization. B, C, and D, Three, 12, and 24 weeks after topical bevacizumab treatment. Note the very modest therapeutic response to the anti-VEGF treatment.