Seeing The Invisible With Intraoperative OCT In Surgical Vitreoretinal Animal Research For Upcoming Clinical Applications.

Abstract

Purpose : The subretinal space is an attractive target for cell and gene therapies. Here we explore the use of the Zeiss RESCAN intraoperative optical coherence tomography (iOCT), which is integrated into an operating microscope for translational preclinical animal work for stem cell based retinal pigment epithelium (RPE) replacement.

Methods : Pluripotent stem cell derived RPE were transplanted on translucent cell carriers. Rabbits (n=10), pigs (n=6) and monkeys (n= 6) underwent vitrectomy with removal of posterior cortical vitreous with subsequent subretinal BSS injection to induce a bleb retinal detachment (bRD) at the posterior pole. A 25g chandelier endoillumination (Alcon) was the sole intraocular light source in most procedures. The RPE was removed surgically in some animals. The RPE monolayer transplant was maneuvered into the subretinal space using custom instrumentation. A fluid air exchange flattened the retina. All surgical steps were monitored and/or guided with the iOCT.

Results : All key surgical steps could be imaged in all species. Imaging was most reproducible in rabbits. In pigs and macaques the default iOCT laser settings did not provide enough contrast, particularly for subretinal structures. Upon a manufacturer-adjusted increase in OCT laser power, contrast levels became satisfactory. The b-scan infused into the microscope-integrated HUD allowed real-time feedback for critical maneuvers like RPE scraping and subretinal implantation. The iOCT proved especially useful in identifying the implant’s subretinal position under detached retina or in air-filled eyes. In 2 of 6 monkeys, small full thickness macular holes incurred as a complication of excessive retinal stretching during bRD, were only detectable by iOCT. Objective visualization of subretinal fluid drainage by iOCT after fluid air exchange improved RPE graft integration at early follow up. Limitations in the iOCT depth of focus sometimes precluded fine resolution of the RPE interface under bleb retinal detachment in pigs and monkeys.

Conclusions : iOCT-based visualization of subretinal maneuvering and implants adds powerful novel possibilities to improve surgical aspects for cell replacement strategies. Further work aims to correlate intraoperative iOCT findings with postoperative SD-OCT.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.