Clinical trial of autologous cultivated limbal epithelial cell sheet transplantation for patients with limbal stem cell deficiency

• Published in: Ophthalmology
• Main Authors: Oie, Yoshinori, Sugita, Seiichiro, Yokokura, Shunji, Nakazawa, Toru, Tomida, Daisuke, Satake, Yoshiyuki, Shimazaki, Jun, Hara, Yuko, Shiraishi, Atsushi, Quantock, Andrew J., Ogasawara, Takahiro, Inoie, Masukazu, Nishida, Kohji
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier 2023
• Subjects: SCAR
• Online Access: https://orca.cardiff.ac.uk/id/eprint/156536/; https://doi.org/10.1016/j.ophtha.2023.01.016; https://orca.cardiff.ac.uk/id/eprint/156536/1/1-s2.0-S0161642023000611-main.pdf

Objective or Purpose To confirm the efficacy and safety of Good Manufacturing Practice (GMP)-compliant autologous cultivated limbal epithelial cell sheets in government-controlled clinical trials that adhered to Good Clinical Practice stipulations for patients with unilateral limbal stem cell deficiency (LSCD). Design A prospective, multi-center, open-label, uncontrolled, single-arm clinical trial. Subjects, Participants or Controls Ten consecutive eyes of 10 patients with unilateral LSCD were followed for two years after surgery. Preoperative LSCD stage was IIB in four eyes and III in six eyes. Methods A limbal tissue biopsy was obtained from the healthy eye, after which limbal stem cells were dissociated and cultivated on temperature-responsive culture surfaces. All cell sheets were fabricated in a GMP-grade facility under established standard operating procedures. Cell sheets were evaluated using defined shipment criteria before transplantation, and only those that met the criteria were used. The cell sheet was transplanted onto each of the patients' diseased eye after removing the conjunctival scar tissue that covered the corneal surface. The severity of LSCD was determined according to a staging method agreed upon by global consensus, with eyes evaluated as being in stages IA–C representing successful corneal epithelial reconstruction. LSCD diagnosis and staging were determined by the trial's Eligibility Judgment Committee and Effect Assessment Committee using slit-lamp photographs including fluorescein staining. Both committees comprised two or three third-party cornea specialists, who were provided with information anonymously and randomly. Main Outcome Measure Corneal epithelial reconstruction rate was the primary endpoint. Results Corneal epithelial reconstruction was successful in six of 10 eyes (60%) one year postoperatively and was significantly higher than the 15% clinically significant efficacy rate achieved by allogeneic limbal transplantation. The reconstruction rate was 70% of eyes two years ...