Abstract
Purpose :
Topical treatments inhibiting the carbonic anhydrase enzyme are commonly employed in reducing intraocular pressure in glaucoma cases. Nonetheless, their effectiveness in clinical settings is often constrained by the necessity of frequent daily applications. Sustained-release drugs represent a promising therapeutic strategy to address this issue. This study aims to investigate the efficacy of a single intravitreal injection of dorzolamide-loaded polyethylene glycol (PEG) microspheres in maintaining reduced intraocular pressure (IOP) in normotensive rabbits.
Methods :
Two types of releasable dorzolamide-conjugated tetra-PEG microspheres were synthesized using different Prolynx linkers (www.Prolynxinc.com) that control the release profile of the drug (medium-term release group, half-life ~20 d; long-term release group, half-life ~100 d). In normotensive rabbits (n=3 for each group), 0.05 mL of these microspheres were intravitreally injected into the unilateral eye. IOP measurements and clinical examinations were performed for both eyes until 8 weeks post-injection. The IOP-lowering effect was assessed by comparing it with that of the contralateral non-treated eyes.
Results :
Intravitreal injection of dorzolamide-conjugated PEG microspheres resulted in a reduction of IOP by as much as 3.0 ± 0.4 mmHg in the medium-term release group and 2.0 ± 0.4 mmHg in the long-term release group compared to untreated fellow eyes for up to 4 weeks (P < 0.0001, Linear mixed model). In the medium-term release group, the IOP-lowering effect gradually decreased over time. Conversely, in the long-term release group, a sustained IOP reduction of 1.4 ± 0.4 mmHg (P = 0.0004) compared to the fellow eyes was observed from 4 to 8 weeks post-injection. No apparent ocular inflammatory response was observed in any of the injected eyes throughout the observation period.
Conclusions :
Intravitreal injection of dorzolamide-conjugated PEG microspheres demonstrated a favorable sustained IOP-lowering effect, showing promise as a drug delivery platform for glaucoma treatment.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.