Development of Novel Corneal Storage Solution With Rho Kinase Inhibitor (ROCKi) HA-1077

We propose supplementing a novel hypothermic corneal storage solution (CSS), Eversol, with the Rho kinase inhibitor HA-1077 (EversolPlus) to better nurture corneal endothelial cells (CEC) during storage, ultimately, to improve transplantation success. The goal of this study is to evaluate the ex vivo stability, safety, and efficacy of HA-1077-supplemented hypothermic CSS over a 14-day period.

Corneal endothelium was injured by brushing, then corneas were cultured, and wound healing was assessed (n = 7). Two independent studies compared corneas stored at 2 to 8°C for 14 days recovered into EversolPlus or Eversol (n = 8), and into Optisol-GS or EversolPlus (n = 11). Central corneal thickness (CCT), CEC density, and morphology were assessed on days 1, 3, 7, 10, and 14.

After endothelial brushing, corneas stored in HA-1077-supplemented media demonstrated markedly improved healing compared with the control group (P = 0.0402), confirming the compound's beneficial effect for endothelial health under physiological conditions. During hypothermic storage, corneas stored in EversolPlus demonstrated reduced CCT on day 1 (P = 0.0028) and day 3 (P = 0.0090) compared with the Eversol group. Corneas stored in EversolPlus displayed reduced CCT on day 1 (P = 0.0024) and day 3 (P = 0.0048) compared with the Optisol-GS group. CEC density and morphometric parameters were within acceptable ranges for all study groups over 14 days.

Supplementing CSS with HA-1077 results in overall thinner corneas during the first 7 days of hypothermic storage, likely because of improved nurturing of CECs. We postulate that ROCKi containing CSS, such as EversolPlus, could improve clinical outcomes after endothelial keratoplasty procedures.