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Aim: To compare the efficacy of aflibercept (Eylea®), a potent antivascular endothelial growth factor (VEGF) agent, with betamethasone (Celestone®) and placebo for the treatment of formed corneal neovascularization in a rabbit model., Methods: A central corneal chemical burn was created in the right eye of 24 New Zealand albino rabbits. Four weeks later, the rabbits were randomly divided into 4 equal groups for subconjunctival injection of aflibercept, betamethasone, aflibercept+ betamethasone, or saline (control). Digital photographs taken at weekly intervals were rated by 2 masked observers for extent, centricity, and density of corneal neovascularization according to a predefined scale. The percentage of corneal surface involved by neovascularization was quantified by image analysis software (Fiji-J). The change in corneal neovascularization from treatment administration (4 weeks after injury) to 4 weeks later (8 weeks after injury) was assessed. The rabbits were then euthanized, and their eyes were enucleated and processed for histopathological and immunofluorescence studies., Results: There was no significant difference in the change in corneal neovascularization after treatment among the 4 groups according to the digital images (p > 0.15) or histological evaluation with hematoxylin and eosin (p > 0.08). On immunofluorescence assay, a lower VEGF concentration was observed in all treatment groups compared to the control group., Conclusions: In this rabbit model, corneal neovascularization induced by chemical burn failed to regress with treatment with aflibercept, betamethasone, or their combination., (© 2019 S. Karger AG, Basel.)

Background: To investigate the long-term visual and optical coherence tomography (OCT) anatomical outcomes of type 3 neovascularisation (NV) and to identify any baseline predictors of poor outcomes., Methods: In this retrospective study, patients diagnosed with treatment naïve type 3 NV were identified and categorised into two groups: good or poor vision based on final vision at 1 year. Baseline demographic features and visual acuity (VA) and baseline and 1-year spectral domain OCT (SD-OCT) anatomical findings were studied and correlated with good versus poor visual outcomes., Results: Ten of 25 eyes were classified as having a poor visual outcome (20/50 or worse) at 1 year. Increased age (P=0.049), male gender (p=0.041) and worse baseline VA (ρs=0.61, p=0.001) were associated with poor vision at 1 year. Greater foveal atrophy was noted at 1 year in the poor visual outcome group (p=0.030). Subretinal hyper-reflective material and choroidal thinning were additional features noted more commonly in this group., Conclusion: Increased age, male gender and lower baseline vision may be important baseline predictors of poor visual outcomes in eyes with type 3 NV. The development of central outer retinal atrophy and fibrosis, as identified with SD-OCT, may limit long-term vision in eyes with type 3 NV., Competing Interests: Competing interests: KBF is a consultant for Genentech, Optovue, Optos, Spark Therapeutics and Heidelberg Engineering. He receives research support from Genentech/Roche. D Sarraf is a consultant for Amgen, Bayer, Novartis, Genentech and Optovue and receives research funding from Allergan, Genentech, Heidelberg, Optovue and Regeneron. BS, D Su, OG-O: none declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: We aimed to evaluate the efficacy of subconjunctival aflibercept, a vascular endothelial growth factor trap compound, for the treatment of corneal neovascularization in a rat model., Methods: Chemical burn was produced in the central cornea of 31 male Sprague-Dawley rats. Animals were randomized to receive treatment with subconjunctival injection of 0.08 mL aflibercept (25 mg/mL), 0.05 mL bevacizumab (25 mg/mL), or 0.05 mL physiologic saline. Corneal neovascularization was evaluated on postinjury days 1, 3, 7, 9, and 13 by corneal photographs. The rats were killed on day 21 and samples were collected for histological and flat-mount immunofluorescence analyses., Results: In all rats, vascular sprouting began on day 3, reached maximum density on days 7-9, and spontaneously regressed thereafter. Mean burn area in the central cornea comprised ∼15% of the total corneal area. The aflibercept group had a significantly smaller relative area of neovascularization than both control group (P < 0.05, 12.27 ± 9.91, 29.66 ± 9.96 days 7) and bevacizumab group (P < 0.05, 12.27 ± 9.91, 21.27 ± 8.19 days 7 and 15.5 ± 10.25, 32.38 ± 9.44 days 9; Mann-Whitney test). On histological study, hematoxylin and eosin staining revealed blood vessels extending to the central cornea in the control and bevacizumab groups and limited to the periphery in the aflibercept group. Immunofluorescence study with an endothelial marker revealed a smaller area of staining in the aflibercept group., Conclusions: Aflibercept effectively inhibits corneal neovascularization in a rat model of chemical burn-induced neovascularization and warrants further study for potential use in humans.

The aim of this experimental study was to compare the efficacy of topical aflibercept and topical bevacizumab in preventing corneal neovascularization. A chemical burn was created in the right central cornea of male Sprague-Dawley rats, followed immediately by instillation of one drop (25 mg/ml, 20 μl volume) of aflibercept (15 eyes), bevacizumab (14 eyes), or saline (15 eyes). Treatment was repeated twice daily for 7 days. Corneal neovascularization was determined using corneal photographs (ImageJ) on days 1, 4, 7, 10, and histological and immunofluorescence studies, on day 10. Stromal immunoreactivity was evaluated 2 days after injury in 6 rats treated singly with bevacizumab or aflibercept. Corneal neovascularization was observed clinically on day 4 in all groups. In the aflibercept group, the area of neovascularization increased from 7.38 ± 2.23% on day 4 to 21.73 ± 14.59% on day 7 and 31.0 ± 23.61% on day 10. Corresponding values in the bevacizumab group were 6.04% ± 1.81%, 51.27 ± 15.50%, and 54.4 ± 11.33%, and in the control group, 8.99 ± 1.93%, 42.6 ± 19.59%, and 55.15 ± 11.54%. The area of neovascularization was significantly smaller on days 7 and 10 in the aflibercept group than in the control and bevacizumab groups (P < 0.001, all analyses), with no significant differences between the latter two groups (day 7, P = 0.868; day 10, P = 0.213). Clinical findings were compatible with the histological data and supported by immunofluorescence and corneal flat-mount staining. Both drugs demonstrated variable penetration into the corneal stroma. Topical aflibercept effectively inhibits corneal neovascularization in a rat model of chemical burn. These findings may have important therapeutic implications for humans., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Antivascular endothelial growth factor (Anti-VEGF) agents have been widely used for a variety of ocular disorders. The etiology of sustained ocular hypertension following intravitreal administration of anti-VEGF agents is yet to be unraveled. Our study investigates and characterizes the presence of intravitreally injected bevacizumab in the aqueous outflow channels of a rat model. Choroidal neovascularization (CNV) was induced by diode laser photocoagulation to the right eye of twelve Brown Norway rats. Bevacizumab (25 mg/ml) was injected intravitreally after 3 days. Immediately after bevacizumab injection, and 3, 6, 24 and 48 h later, animals were euthanized for immunofluorescence staining. Donkey anti-human IgG labeled with Alexa Fluor(®) 488 was used for bevacizumab immunoreactivity detection. Anti-CD31 antibody was used as a marker for Schlemm's canal endothelial cells. Untreated eyes were used as negative controls. The intensity of the immunostaining was analyzed qualitatively. Bevacizumab immunoreactivity was found in the aqueous outflow channels including the trabecular meshwork and Schlemm's canal immediately after injection, and declined incrementally within the following hours. Forty-eight hours after the injection, no bevacizumab staining was detected in the aqueous outflow channel structures. Our manuscript demonstrates the presence of bevacizumab in the trabecular meshwork and Schlemm's canal structures after intravitreal injection in a CNV induced rat model. Bevacizumab molecules passed through the aqueous outflow channels within 48 h after intravitreal bevacizumab injection., (Copyright © 2016 Elsevier Ltd. All rights reserved.)