Selective Large-Area Retinal Pigment Epithelial Removal by Microsecond Laser in Preparation for Cell Therapy

Abstract

Purpose: Cell therapy is a promising treatment for retinal pigment epithelium (RPE)-associated eye diseases such as age-related macular degeneration. Herein, selective microsecond laser irradiation targeting RPE cells was used for minimally invasive, largearea RPE removal in preparation for delivery of retinal cell therapeutics. Methods: Ten rabbit eyes were exposed to laser pulses 8, 12, 16, and 20 μs in duration (wavelength, 532 nm; top-hat beam profile, 223 × 223 μm2). Post-irradiation retinal changes were assessed with fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). RPE viability was evaluated with an angiographic probit model. Following vitrectomy, a subretinal injection of balanced salt solution was performed over a lasered (maximum 13.6mm2) and untreated control area. Bleb retinal detachment (bRD) morphology was then evaluated by intraoperative OCT. Results: Within 1 hour after irradiation, laser lesions showed FA and ICGA leakage. OCT revealed that large-area laser damage was limited to the RPE. The angiographic median effective dose irradiation thresholds (ED50) were 45 μJ (90mJ/cm2) at 8 μs, 52 μJ (104 mJ/cm2) at 12 μs, 59 μJ (118 mJ/cm2) at 16μs, and71μJ (142mJ/cm2) at 20 μs. Subretinal injection over the lasered area resulted in a controlled, shallowbRD rise,whereas control blebs were convex in shape, with less predictable spread. Conclusions: Large-area, laser-based removal of host RPEwithout visible photoreceptor damage is possible and facilitates surgical retinal detachment. Translational Relevance: Selective microsecond laser-based, large-area RPE removal prior to retinal cell therapy may reduce iatrogenic trauma.