Replacement of a subretinal prosthesis with a higher-resolution array improves grating acuity in the same animal

Abstract

Purpose : In patients with atrophic age-related macular degeneration, subretinal photovoltaic implant (PRIMA) provides acuity up to 20/440, closely matching the 100μm pixels size. Next-generation implants with smaller pixels may significantly improve visual acuity. This study in rats evaluates removal of a subretinal implant, replacement with a newer device, and the resulting grating acuity in-vivo. We also assess the effect of immunosuppressing drugs on tissue recovery after surgery.

Methods : Flat photovoltaic implants of 1.5mm in width (PRIMA, Pixium Vision) were implanted beneath the degenerate rat retina (RCS, p180-300), and the retinal integration over time was monitored by OCT imaging. After 6 weeks, the retina was detached, and the devices were gently separated by subretinal BSS injection between the retina and implant. A new device was placed in the same location, with or without subretinal immunosuppressive drugs and allowed to recover for 6 weeks. Grating acuity was monitored in vivo by VEP measurements before eyes were collected for histology and immunohistochemistry analysis.

Results : The inner nuclear layer of the degenerate retina was located in a close proximity to the implants, as observed by OCT after 6 weeks. After the device removal, OCT showed preserved retinal structure with the presence of a subretinal hyper-reflective layer. Immunohistochemistry demonstrated preserved bipolar cells and confirmed the presence of subretinal fibrosis. Subretinal application of dexamethasone during implantation resulted in significant attenuation of such fibrosis. Re-implantation of the new devices into the same location demonstrated de nouveau retinal integration with a new implant. New devices with 20 and 30µm pixels increased the grating acuity from the 100µm capability of PRIMA devices to 30µm, matching the limit of natural visual acuity in rats.

Conclusions : Flat implants can be successfully implanted, explanted and re-implanted in a rodent model of retinal degeneration. The surgical steps are feasible, and the postoperative and histological follow-up showed improved results in the presence of subretinal immunosuppression. In human eyes, such surgery should be easier compared to much smaller (5-6 mm diameter) rat eye. Additionally, since dexamethasone is already approved for ocular treatment, its subretinal use should be easily adapted by regulatory authorities.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.