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Clinical Trials |

Topical Bevacizumab in the Treatment of Corneal Neovascularization:  Results of a Prospective, Open-Label, Noncomparative Study

Mohammad H. Dastjerdi, MD; Khalid M. Al-Arfaj, MD; Nambi Nallasamy, BA; Pedram Hamrah, MD; Ula V. Jurkunas, MD; Roberto Pineda II, MD; Deborah Pavan-Langston, MD; Reza Dana, MD, MSc, MPH
Arch Ophthalmol. 2009;127(4):381-389. doi:10.1001/archophthalmol.2009.18.
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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

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Figure 1.

Quantification of corneal neovascularization. A, Digital slitlamp corneal photographs were analyzed using graphics editing software (Photoshop CS2; Adobe Systems Inc, Berkeley, California) and a mathematical program (Matlab; MathWorks Inc, Natick, Massachusetts). After the total corneal area was delineated, the blood vessels were isolated using Photoshop. To analyze the efficacy of bevacizumab in treating corneal neovascularization, 3 metrics were computed using a Matlab script: neovascular area, which measures the area of the corneal vessels themselves; vessel caliber, which determines an approximate mean diameter of the corneal vessels; and invasion area, which measures the fraction of corneal area in which vessels are present. B, Changes in corneal vessels (patient 4) at different points after treatment.

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Figure 2.

Summary of changes in neovascular area (A), vessel caliber (B), and invasion area (C) in response to bevacizumab therapy for all patients at different points. By the last visit, the mean reduction was 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. However, the levels of decrease varied significantly in different patients, evidenced by high SDs in all 3 neovascularization metrics.

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Figure 3.

The effect of topical bevacizumab in patient 6, a 65-year-old woman with a history of herpes zoster ophthalmicus in the left eye complicated by corneal thinning, scarring, and neovascularization. A, The baseline photograph 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 midperiphery, where it branches several times into smaller-caliber vessels. One (B), 6 (C), and 24 (D) weeks after topical bevacizumab treatment. Note the significant therapeutic response, evidenced as early as 1 week after initiation of anti–vascular endothelial growth factor treatment.

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Figure 4.

The effect of topical bevacizumab in patient 7, a 39-year-old woman with a history of laser in situ keratomileusis and partial limbal stem cell deficiency in the left eye complicated by corneal neovascularization. A, The baseline photograph shows superficial and deep corneal neovascularization with central lipid keratopathy. Three (B), 12 (C), and 24 (D) weeks after topical bevacizumab treatment. Note the significant narrowing of blood vessels in response to anti–vascular endothelial growth factor treatment.

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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, The baseline photograph shows corneal opacity with severe superficial and deep corneal neovascularization. Three (B), 12 (C), and 24 (D) weeks after topical bevacizumab treatment. Note the very modest therapeutic response to the anti–vascular endothelial growth factor treatment.

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