ESCALÓN: A Prospective Randomized Trial of Corneal Endothelial Cell Therapy in Subjects With Corneal Edema.

PURPOSE: ESCALÓN is a prospective, randomized, double-masked, parallel-group trial designed to evaluate the safety and efficacy of cultured human corneal endothelial cells (CECs) and the Rho-associated protein kinase (ROCK) inhibitor Y-27632 for treating corneal edema secondary to endothelial dysfunction.

METHODS

Eligible eyes with bullous keratopathy (N = 18) or Fuchs dystrophy (N = 4) were randomized to receive endothelial polishing and a single intracameral injection containing 1 x 10 6 CECs and 10, 20, or 100 μM Y-27632. The primary outcome was safety based on incidence and severity of ocular and nonocular treatment-emergent adverse events (TEAEs). Efficacy outcomes included changes from baseline in central corneal thickness (CCT) and best-corrected visual acuity (BCVA) at all time points up to month 12.

RESULTS

Twenty-two eyes received treatment. Data from all study groups were pooled, as no clinically meaningful differences existed between groups. Study eyes experienced no serious TEAEs. Common study eye TEAEs included posterior capsule opacification (72.7%), pupillary disorders/dyscoria (27.3%), and transient intraocular pressure elevations (22.7%). Mean CCT improved from 697.0 μm at baseline to 571.2 μm at month 12. Mean BCVA improved from 0.995 logMAR at baseline to 0.330 logMAR at month 12. The proportion of all subjects with a ≥ 0.3 LogMAR improvement in BCVA was 88.9% at month 12.

CONCLUSIONS

The study demonstrated that transplantation of cultured CECs with Y-27632 was safe and efficacious across all evaluated doses of Y-27632. No clinically meaningful dose response was seen for Y-27632. This innovative therapeutic approach represents a promising option for treating corneal edema arising from corneal endothelial dysfunction.