Treatment of Retinal/Choroidal Vascular Diseases by Sustained Delivery of VEGF Receptor Tyrosine Kinase Inhibitors.

Purpose: To review current investigational strategies utilizing sustained delivery of VEGF receptor tyrosine kinase inhibitors (TKIs) for the treatment of retinal and choroidal vascular diseases.

Design: Narrative review.

Methods: A comprehensive review of preclinical and clinical studies evaluating the safety, efficacy, and durability of VEGF receptor TKIs delivered via sustained-release platforms, including intravitreal hydrogel implants, suprachoroidal injections, subcutaneous delivery systems, and oral formulations.

Results: Multiple VEGF receptor TKIs, including axitinib, sunitinib, vorolanib, and dendranib, are under evaluation for sustained treatment of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and diabetic retinopathy (DR). Delivery platforms such as bioerodible implants (OTX-TKI/axitinib, EYP-1901/vorolanib), suprachoroidal injections (CLS-AX/axitinib), microparticle suspensions (GB-102/sunitinib), and oral or subcutaneous therapies (X-82, D-4517.2) have demonstrated variable degrees of treatment durability, reduction in anti-VEGF injection burden, and maintenance of anatomic and functional outcomes in early phase studies. Safety profiles have generally been favorable, though certain formulations showed dose-dependent adverse effects.

Conclusions: Sustained delivery of VEGF receptor TKIs represents a promising therapeutic paradigm for retinal and choroidal vascular diseases, potentially reducing treatment burden while maintaining efficacy. Continued evaluation through larger, controlled clinical trials is essential to validate these early findings and define the role of these agents in clinical practice.