Safety of Bio-Interventional Uveoscleral Outflow Enhancement: Twelve-Month Post-Operative Results from 395 Eyes in the CREST Study

Purpose: To characterize 12-month ocular safety of bio-interventional uveoscleral outflow enhancement in open-angle glaucoma (OAG). Design: Prospective, multicenter real-world evidence study (CREST; NCT05506423 ). Participants: Adults with OAG treated by bio-interventional uveoscleral outflow enhancement with acellular scleral allograft spacers (AlloFlo™, Iantrek, Inc.), standalone or with phacoemulsification, reaching 12 months of follow-up. Methods: Adverse events were captured prospectively at each protocol-specified visit against pre-defined definitions; data were analyzed at the eye level. Main Outcome Measures: Pre-specified ocular safety endpoints: adverse events, clinically significant hypotony, sustained intraocular pressure (IOP) elevation ≥ 10 mmHg beyond 30 days, allograft migration, corneal endothelial decompensation, secondary incisional glaucoma surgery, and endothelial cell density. Results: Of 395 eyes (mean age 72.8 years; 52% female), 267 were combined with phacoemulsification (Cohort 1) and 128 standalone (Cohort 2). Medicated IOP decreased from 19.1 to 14.5 mmHg (p < 0.001) and medications from 1.9 to 1.2, with 42% medication-free. Sustained IOP elevation occurred in 34 eyes (8.6%), BCVA loss ≥ 2 lines in 15 (3.8%), hyphema > 2 mm in 6 (1.5%) and hypotony in 1 (0.3%). Two allograft spacers entered the anterior chamber in one eye and were successfully repositioned intraoperatively. Serious events occurred in 12 eyes (3.0%). In the N=91 eyes with paired specular microscopy data, endothelial cell density changed -6.5% (-8.7%, -4.4%). There were no reports of endothelial decompensation, endophthalmitis, or sympathetic ophthalmia. Conclusions: Through 12 months no endothelial decompensation, endophthalmitis or sympathetic ophthalmia occurred, and most events were self-limiting or medically managed. Endothelial cell loss tracked concurrent cataract surgery rather than the allograft, though that subgroup is small. Follow-up remains shorter than the interval over which an earlier supraciliary microstent diverged from controls.