Preliminary Analysis Of One-Year Clinical Outcomes In Phase I-Iia Advanced Cellular Therapy For Keratoconus

To report the one-year clinical outcomes of a multicentric Phase I-IIa trial on advanced cellular therapy for corneal stroma regeneration in patients with advanced keratoconus, utilizing autologous adipose-derived adult stem cells (ADASc) with or without decellularized donor human corneal stromal lamina.

This Phase I-IIa, prospective, multicenter, open-label, randomized controlled trial was conducted at Vissum (Miranza Group) in Alicante, Spain.

Eleven patients with advanced keratoconus were selected, with ten multicentric randomly assigned to two experimental groups and one to a control group with cell treatment alone. Group 1: Five patients received 3×10⁶ ADSCs combined with 120-μm-thick decellularized corneal laminas. Group 2: One patient received ADSCs alone. Group 3 : Five patients received a 120-μm-thick decellularized corneal lamina. Autologous ADSCs were obtained via liposuction and implanted into a corneal stromal pocket using a femtosecond-assisted 9.5-mm lamellar dissection. Primary outcomes included uncorrected (UDVA) and best-corrected distance visual acuity (BCVA), while secondary parameters were evaluated preoperatively and at 1, 3, 6, and 12 months postoperatively.

No adverse reactions were observed during the follow-up. Stem cell transformated into keratocyte-shaped cells with new collagen formation, significantly improving corneal transparency. AS-OCT showed well-structured, recellularized lamina. Keratoconus remained stable in 10 of 11 cases. Corneal thickening was achieved in all Group 1 and 3 cases. Visual outcomes were promising: Group 1 (5 patients): Three gained 1–2 Snellen lines (UDVA/BCVA), one lost 1 line in BCVA. Group 2 (1 patient): No significant visual or corneal thickness change, but transparency improved. Group 3 (5 patients): Two gained 1 line in UDVA, two in BCVA; one gained 1 in UDVA but lost 1 in CDVA, and another gained 1 in CDVA. One patient experienced a 1-line CDVA loss.

Advanced therapy using ADSCs, with or without decellularized lamina,  demonstrates to be a safe approach for treating advanced keratoconus, leading to disease stage improvement in most cases.