Subretinal implantation of biodegradable photoreceptor cell delivery scaffolds: surgical tools, procedures and outcomes

Abstract

Purpose : Photoreceptor and RPE cell loss are end stage features of GA from AMD as well as RP and LCA. As scaffolds designed to transplant retinal cells increase cellular survival and integration, we evaluated tools and procedures for reliable delivery of stem cell grafts in the porcine model using novel instruments.

Methods : Eyes of 2-6 month old pigs were allocated into one of 4 groups: un-vitrectomized controls (n=29), pars plana vitrectomy (PPV) surgical controls (n=15), or PPV with implantation of scaffolds with one of two device. Each implantation/surgical control eye received PPV, balanced salt solution (BSS) bleb under the posterior retina, and diathermy creation of a linear retinotomy. Scaffold-implanted eyes received polycaprolactone (PCL) biodegradable polymer placed sub-retinally. Two surgical instrument prototypes were tested, injecting either a 1x5mm strip (n=18 eyes) or 4-5mm diameter discs (n=25 eyes). Of these, 25 eyes (19 disc and 6 strip) were implanted with wells capable of incorporating cells for transplantation. Air-fluid exchange without long acting gas or retinotomy laser was performed. OCT was done at sacrifice (after 1-5 months) followed by histologic characterization. Data was analyzed using Mann-Whitney U test for non-parametric data.

Results : Polymers were successfully inserted in all non-control eyes. At sacrifice, exam, fundus and OCT imaging revealed in eyes with polymer (without polymer in parentheses; all p values were >0.5, i.e. non-significant): retinal reattachment in 93% (98% without); severe uveitis in 0 (0 without); retinal fold in 7% (2% without); RPE atrophic changes 37% (14% without), and subretinal fibrosis in 44% (12% without); collateral retinal vessels were identified near the retinotomy in 17% of eyes with polymer (2% without). Preliminary histologic analysis revealed polymers in the subretinal space with good preservation of overlying retina (n=9); eyes with polymer had mild to moderately increased GFAP staining around the polymer but were negative for immunologic markers IBA1, CD68 and IgG.

Conclusions : Both devices tested demonstrated a high rate of implantation success. Large posterior retinotomies close spontaneously without laser, long-acting tamponade, or prone positioning. These scaffolds appear well tolerated in the subretinal space.

This is a 2020 ARVO Annual Meeting abstract.