Abstract
BackgroundAs intravitreal anti-VEGF injections became the mainstay of treatment for many retinal diseases, the cause of a secondary sustained elevated intraocular pressure is still unclear. The aim of our study was to study the clearance of Aflibercept from the anterior chamber angle, in a rat model, to test if an aggregation exists.MethodsChoroidal neovascular lesions (CNV) were induced in the right eye of 12 brown Norway rats, using indirect laser ophthalmoscope. Intravitreal Aflibercept injection (0.12 mg/3 µl) was performed 3 days after CNV induction. Rats were euthanized at predetermine time intervals of 3, 6, 24 and 48 h post injection, with immediate enucleation for histological analysis with H&E and immunofluorescence staining. Aflibercept molecules were stained with red fluorescence thanks to the formation of the immune complex Aflibercept-Rabbit anti human IgG-Anti rabbit antibodies-Cy3.ResultsImmediately after the injection, a strong fluorescence signal was detected, indicating the presence of Aflibercept in the iridocorneal angle. At 3- and 6-h interval a strong signal of Aflibercept was still seen. Six hours post injection, the signal was highly concentrated in Schlemm’s canal. In the 2 eyes harvested 24 h post Aflibercept injection, red fluorescence signal intensity was decreased in one eye, occupying mainly intra scleral venous plexuses, and absent in the other eye. At 48 h there was no fluorescence signal, confirming complete clearance of Aflibercept.ConclusionsIn our rat model, a complete clearance of Aflibercept from the anterior chamber angle, was seen 48 h after the injection. This finding refutes the theory of possible connection between IOP elevation and mechanical obstruction. Evacuation time of Aflibercept through the angle is of the same magnitude as that of Bevacizumab in the same rat model.
Highlights
The employment of intravitreal injections to inhibit vascular endothelial growth factor (VEGF) has grown tremendously in recent years
The findings in this study suggest that following a single injection, Bevacizumab does not accumulate in the trabecular meshwork (TM)
Choroidal neovascular lesions (CNV) induction On day 0, choroidal neovascularization was induced in the eyes of the test group by indirect diode laser photocoagulation (Iris Medical Oculight SLX System©, Iridex, Mountain View, CA, USA), with the treatment beam set at 810 nm and the aiming beam at 650–670 nm, 450 mW power, 100 ms duration, as described previously [14]
Summary
The employment of intravitreal injections to inhibit vascular endothelial growth factor (VEGF) has grown tremendously in recent years. Evidence from several clinical studies in the past decade have demonstrated that receiving multiple intravitreal anti-VEGF injections may cause a sustained intraocular. Sustained IOP elevation has been described after the administration of either Bevacizumab, Ranibizumab or Aflibercept. While the rate of increased IOP after Bevacizumab and Ranibizumab injections was found to be similar, the incidence after Aflibercept injections has been described as significantly lower in different studies [4,5,6,7,8,9,10]. As intravitreal anti-VEGF injections became the mainstay of treatment for many retinal diseases, the cause of a secondary sustained elevated intraocular pressure is still unclear. The aim of our study was to study the clearance of Aflibercept from the anterior chamber angle, in a rat model, to test if an aggregation exists
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