Protein therapeutics, owing to their high specificity and potent activity, have demonstrated significant efficacy in the treatment of various ocular diseases, particularly playing a central role in posterior segment disorders such as macular degeneration, diabetic retinopathy, and uveitis.However, effective ocular delivery remains challenging because of anatomical barriers and rapid clearance mechanisms.Topical eye drops are convenient but suffer from low bioavailability and poor stability, while intravitreal injections are effective but invasive and require frequent administration.This expert commentary outlines current applications of protein drugs in the eye, evaluates key delivery challenges, and discusses the physiological barriers encountered in ocular protein delivery via eye drops, along with strategies to enhance drug stability and penetration on the ocular surface, as well as the metabolic clearance pathways following intraocular injection and approaches to prolong intraocular drug residence time.By highlighting both limitations and potential solutions, this article aims to enlighten the development of more effective ocular protein therapies.

Protein therapeutics, owing to their high specificity and potent activity, have demonstrated significant efficacy in the treatment of various ocular diseases, particularly playing a central role in posterior segment disorders such as macular degeneration, diabetic retinopathy, and uveitis.However, effective ocular delivery remains challenging because of anatomical barriers and rapid clearance mechanisms.Topical eye drops are convenient but suffer from low bioavailability and poor stability, while intravitreal injections are effective but invasive and require frequent administration.This expert commentary outlines current applications of protein drugs in the eye, evaluates key delivery challenges, and discusses the physiological barriers encountered in ocular protein delivery via eye drops, along with strategies to enhance drug stability and penetration on the ocular surface, as well as the metabolic clearance pathways following intraocular injection and approaches to prolong intraocular drug residence time.By highlighting both limitations and potential solutions, this article aims to enlighten the development of more effective ocular protein therapies.