Eye drops for retinal disease

Abstract

AbstractUsing topical application to deliver drugs to the posterior segment of the eye remains a challenge. Posterior segment diseases are currently treated by intravitreal injection or implant. Eye drop formulations based on γ‐cyclodextrin (γCD)‐based nanoparticle aggregates were developed and deliver therapeutic concentrations of drugs (dorzolamide and dexamethasone) to both anterior and posterior segments of the eye in animal models and clinical studies. An early study in humans showed dorzolamide/γCD eye drops could achieve comparable intraocular pressure decreases to commercial dorzolamide eye drops, but with less frequent application. Pilot studies with dexamethasone/γCD eye drops showed clinical effect in a range of human conditions, including diabetic macular oedema, cystoid macular oedema and vitritis secondary to uveitis, inflammation after cataract surgery and postoperative treatment in trabeculectomy. A multicentre, double‐masked, parallel‐group, randomized, Phase 2 study was performed to evaluate topical dexamethasone ophthalmic suspension in diabetic macular edema (DME). One hundred and forty four patients aged 18–85 years with DME of <3 years duration, ETDRS central subfield thickness ≥ 310 μm by SD‐OCT and ETDRS letter score ≤ 73 and ≥ 24 in the study eye were randomized 2:1 to OCS‐01 or matching vehicle, 1 drop 3 times/day for 12 weeks. Efficacy was evaluated as change from baseline to Week 12 of ETDRS letter score and central macular thickness (CMT). Mean CMT showed a greater decrease from baseline with OCS‐01 (N = 99) than vehicle (N = 45) at Week 12 (−53.6 vs −16.8 μm, p = 0.0115). Mean change in ETDRS letter score from baseline to Week 12 met the p was +2.6 letters with topical OCS‐01 and 1 letter with vehicle (p = 0.125). In a post‐hoc analysis, there was a greater difference in patients with baseline BCVA ≤65 letters, the OCS‐01 group improved 3.8 letters compared with 0.9 letters with vehicle. OCS‐01 was well‐tolerated, and increased intraocular pressure was the most common adverse event. Cyclodextrin nanoparticle eye drops deliver drugs to the retina in therapeutically relevant concentrations and promise a non‐invasive alternative in drug treatment of retinal diseases.