Anti-VEGF Agents Clearance Through the Aqueous Outflow Pathway in a Rat Model

Area of Science:

• Ophthalmology
• Pharmacology
• Retinal Diseases

Background:

• Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are standard for retinal diseases.
• Sustained intraocular pressure (IOP) increases post-injection are theoretically linked to anti-VEGF aggregation in the iridocorneal angle.
• Previous studies indicated complete clearance of specific anti-VEGF agents.

Purpose of the Study:

• To analyze and compare the clearance rates of bevacizumab, aflibercept, and ranibizumab from the eye after a single intravitreal injection.
• To investigate the theoretical attribution of IOP increase to anti-VEGF aggregation in the iridocorneal angle.

Main Methods:

• Intravitreal injections of anti-VEGF agents were administered to Brown Norway rats.
• Eyes were analyzed at various time points (0-48 hours) using immunofluorescence and confocal microscopy.
• Drug clearance rates were quantified via signal concentration analysis and validated with control groups.

Main Results:

• All tested anti-VEGF agents showed positive immunofluorescent signals in the iridocorneal angle structures.
• Anti-VEGF immunostaining peaked immediately post-injection and significantly decreased by 48 hours (P < 0.05).
• Clearance rates from the iridocorneal angle ranged from 98.68% to 99.87% at 48 hours, with no significant differences between agents (P > 0.05).

Conclusions:

• Bevacizumab, aflibercept, and ranibizumab demonstrated complete and rapid clearance from the iridocorneal angle within 48 hours in rats.
• The clearance rates were similar for all three agents.
• These findings refute the hypothesis that anti-VEGF aggregation in the iridocorneal angle causes sustained IOP increases.