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Introduction: The purpose of this study was to evaluate the effect of intravitreal injection of tissue plasminogen activator (tPA) on proliferative vitreoretinopathy (PVR)., Methods: PVR was induced in a rabbit model by intraocular injection of dispase (0.05 U/0.1 mL). Progression of PVR was followed by indirect ophthalmic examination. Following 6 weeks, 5 animals received intravitreal injection of 25 µg/0.1 mL tPA and four were injected with balanced salt solution (BSS). Animals were euthanized at 48 h following tPA/BSS injection, and eyes were enucleated for histological evaluation and staining with α-smooth muscle actin (αSMA) and Sirius Red., Results: Following tPA injection, one eye had a reduction in PVR from grade 2 to 1 and three eyes remained stable. Following BSS, PVR grade was unchanged in three eyes. In one eye in each group, the severity of PVR could not be assessed due to limited view. Staining with αSMA showed reduced presence of fibroblasts in eyes injected with tPA compared with those injected with BSS. Collagen type I and III, demonstrated by Sirius Red staining, was reduced in the tPA group in comparison with controls., Conclusion: Our results suggest that intravitreally injected tPA may show an inhibitory effect on PVR progression. Further exploration in clinical trials is desired., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

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.)

Purpose: To determine whether intravitreal unconjugated tissue plasminogen activator (tPA) (alteplase) can penetrate the intact neural retina and reach the subretinal space in an experimental model., Methods: This study was performed in 24 Sprague-Dawley rats aged 12 weeks. Under general anesthesia, the right eye was injected with either 0.75 μg of 3 μL tPA (14 rats; study group) or saline (10 rats, control group) into the vitreous. Animals were euthanized at 3, 24, and 48 h. The eyes were enucleated, and cryosections were prepared for immunofluorescence staining. Goat anti-tPA antibody was used to detect tPA., Results: In the study group, staining for tPA was detected in the deep retinal layers in all eyes. The staining was deeper and more intense at 3 and 24 h than at 48 h. There was no tPA staining in the retina of eyes injected with saline., Conclusions: This experimental study shows that unconjugated tPA administered into the vitreous is capable of penetrating the deep retinal layers and the subretinal space. These findings suggest that further clinical research is warranted on the benefits of intravitreal tPA in the treatment of submacular hemorrhage., (© 2017 S. Karger AG, Basel.)