Safety of Long-Acting Intravitreal Hydrogels: A Comprehensive Evaluation of Intraocular Pressure and Retinal Integrity across Rabbit and Non-Human Primate Models.

Injectable hydrogels have emerged as promising platforms for sustained drug delivery to the posterior segment of the eye, with the potential to reduce treatment burden and improve patient adherence in chronic disease management. Although numerous preclinical studies report favorable biocompatibility and biodegradability, the effects of intravitreal (IVT) hydrogels on the ocular environment have yet to be comprehensively evaluated. In this study, we conducted a meta-analysis of preclinical investigations evaluating IVT, drug-loaded hydrogels in rabbit and nonhuman primate models. Primary safety end points included longitudinal changes in intraocular pressure (IOP) and total retinal thickness (TRT). Across all included studies, no significant or sustained elevations in IOP were observed relative to baseline or untreated controls. TRT remained stable for 14 days up to two months postadministration, with no evidence of clinically meaningful thinning, degeneration, or retinal toxicity. These outcomes were consistent across diverse hydrogel compositions, therapeutic payloads, gelation mechanisms, and animal models, indicating a broadly favorable intraocular safety profile. Collectively, this analysis provides quantitative evidence supporting the ocular safety of IVT hydrogel-based drug delivery systems based on IOP and TRT measurements in preclinical models. These findings reinforce the translational potential of injectable hydrogels as biocompatible, long-acting alternatives to conventional IVT injection-based therapies and support their continued development for intraocular applications.