Improvement and stabilization of vision for 18 months after Human Embryonic Stem-cell (hESC) derived, RPE-sheet transplantation on a synthetic basement membrane for trestment of severe, wet Age-Related Macular Degeneration

Abstract

Purpose : To report clinical outcomes from the first 2 patients in a prospectice phase 1 trial of hESC derived sheet-RPE transplantation as a possible treatment for severe, wet Age-related Macular Degeneration (Clinical Trials.gov: NCT01691261).

Methods : Surgical delivery of hESC-derived RPE, on a human vitronectin-coated artificial basement membrane, into the submacular space, was carried out within 6 weeks of sudden vision loss from severe wet age-related macular degeneration. Immunosuppression consisted of short-course perioperative oral prednislone and long-term local depot administration of fluoqinolone. Visual function assessments pre and post surgery were completed by masked optometrists and consisted of best corrected, Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (BCVA), Minnesota MN Read, Pelli-Robson contrast sensitivity and Nidek Microperimeter based fixation and retinal sensitivity over the transplanted RPE sheet.

Results : The ETDRS BCVA improved from 10 to 39 and from 8 to 27 letters over 18 months in cases 1 and 2 respectively. Fixation in case 1 was stable at year 1 (83% within 2° and 100% within 4°) but became unstable at month 18 (17% within 2° and 70% within 4°). In case 2 however, fixation was stable at both year 1 (98% within 2° and 100% within 4°) and month 18 (81% within 2° and 100% within 4°). Fixation remained at the geometric centre of the patch (pre-op fovea) in case 2 but moved from the centre to the edge of the patch in case 1. Micro-perimetry showed visual sensitivity over the patch in both cases. Reading speed improved from 1.7 to 82.8 and 0 to 47.8 words/min in case 1 and 2 respectively at 12 months. Pelli-Robson contrast sensitivity scores (Log) improved from 0.45 to 1.35 in case 1 and 0 to 1.05 in case 2 at 12 months.

Conclusions : The hESC-derived-RPE therapeutic element was delivered successfully and continued to function with evidence of sustained visual recovery for 18 months in 2 patients. Sustained survival and function of the RPE was achieved using intra-ocular steroid implants with no long-term, systemic immunosuppression. This work supports the feasibility and safety of hESC-derived RPE transplantation as a regenerative strategy for AMD and as a broader treatment paradigm for hESC-derived tissue transplantation.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.