Multimodal imaging after subretinal hESC-RPE xenografting into monkeys

Session Details

Session Title: Free Paper Session 25: Imaging IV

Session Date/Time: Sunday 10/09/2017 | 10:00-11:30

Paper Time: 11:12

Venue: Room 113

First Author: : E.Wong SINGAPORE

Co Author(s): :    G. Tan   Z. Liu   V. Barathi   H. Skottman   B. Stanzel                 

Abstract Details


The macula is an attractive target for cell and gene therapies. However, the effect of surgical protocols on submacular retinal pigment epithelium (RPE) graft integration remain less understood. Here we present the postoperative imaging outcomes following several implantation strategies in a monkey model for RPE replacement with monolayer grafts.


The primary outcome measure was the appearance of the macula and xenograft in multimodal imaging, secondary outcomes were positional stability of the implant and safety.


Human embryonic stem cell (hESC) derived RPE were transplanted on translucent cell carriers. The macaques were immunosuppressed prior to surgery. Fourteen eyes of monkeys (n= 14) underwent vitrectomy with removal of posterior cortical vitreous. Several modes to create a bleb retinal detachment (bRD) with subretinal BSS injection throughout the posterior pole were explored. A retinotomy was created to allow subretinal access. The RPE under the bRD was removed surgically. The RPE monolayer transplant was maneuvered underneath the macula using custom instrumentation. A fluid air exchange flattened the bRD. All key surgical maneuvers were guided with intraoperative OCT (iOCT). The animals were imaged with a combined SLO/ OCT device before and at 3, 7, 14 and 28 days postoperatively.


Baseline imaging characteristics revealed no anatomical abnormalities in all animals. All key surgical steps could be imaged with iOCT. The subretinal BSS injection resulted into either formation of full thickness foveal tear, BSS-induced cystoid macular edema with or without foveal de-roofing and complete foveal detachment. Complete submacular resorption of SRF at postop days 3-5 was observed in 9 of 12 implanted eyes, 1 eye had sham surgery and 1 eye developed iatrogenic cataract. iOCT visualization of the extent of subretinal fluid drainage after fluid air exchange enabled correlation with the extent of retinal reattachment on SD-OCT postOP. In preliminary data, foveal atrophy on SD-OCT was observed at postOP day 28 in 3/8 eyes evaluated and seemed correlated to the degree of surgical trauma. Implant position stability was confirmed in 12 of 12 eyes on multimodal images. Blue fundus autofluorescence (BAF) revealed progressive hyperfluorescent changes at the posterior pole beyond the original bRD area with larger volume subretinal BSS injections, while in controlled smaller volume subretinal BSS injections the hyperfluorescent BAF changes remained confined and nonprogressive; the implant appeared hypofluorescent throughout the observation period. On fluorescein angiography the implant site showed no leakage in all eyes in the late phase.


Correlation of iOCT and multimodal imaging suggested a strong influence of surgical protocol on postoperative outcome in submacular hESC-RPE xenografts. Further work is necessary to minimize iatrogenic damage to the neural retina for subfoveal RPE monolayer transplants.

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