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, large-area 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 13.6 mm2) 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 (90 mJ/cm2) at 8 µs, 52 µJ (104 mJ/cm2) at 12 µs, 59 µJ (118 mJ/cm2) at 16 µs, and 71 µJ (142 mJ/cm2) at 20 µs. Subretinal injection over the lasered area resulted in a controlled, shallow bRD rise, whereas control blebs were convex in shape, with less predictable spread.
Conclusions: Large-area, laser-based removal of host RPE without 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.