Management of Retinal Detachment With a Coexistent Macular Hole: Submacular Placement of Retinal Autograft Through a Macular Hole.

PURPOSE: In this article, a submacular autologous neurosensory retinal transplantation technique is presented in patients with large macular hole (MH) accompanying retinal detachment. METHODS: In the surgical procedure, 23-G pars plana vitrectomy and peripheral vitrectomy were performed. An autologous neurosensory retinal patch, which should be larger than the diameter of the MH, was released from a suitable quadrant. The retinal patch was grasped using a 23 gauge microforceps and then passed through the MH and placed under the macula. Liquid perfluorocarbon (PFCL) was injected, and the retina was reattached. A subfoveal autologous neurosensory retinal patch was repositioned in the center of the MH with gentle manipulation under fluid perfluorocarbon, if necessary. Laser retinopexy was applied to peripheral tears under PFCL Subsequently, a 5,000-cSt silicone oil-PFCL exchange was also performed. RESULTS: Four eyes of four patients were operated on using the technique described earlier. Silicone oil was removed from two patients, and the macular holes were closed in all patients at the last follow-up. CONCLUSION: This technique has been beneficial in refractory MHs and can improve the visual potential in eyes with MHs.

Autologous retinal graft for the management of large macular holes associated with retinal detachment.

To present the efficacy of autologous neurosensory retinal transplantation in macular holes surgery with rhegmatogenous retinal detachment. Eleven eyes of 11 patients with rhegmatogenous retinal detachment associated to a large macular hole were enrolled between January 2019 and January 2021 in the Department A of the Hedi Rais Institute of Ophthalmology (Tunis, Tunisia). All patients underwent a 23 G pars plana vitrectomy. An autologous neurosensory retinal patch was placed inside the macular hole. Long-acting silicone tamponade was carried out. Clinical features of the macular area, best-corrected visual acuity (BCVA), fundus examination, and SD-OCT were recorded before surgery, at 1- and 3-month follow-up after surgery. The mean age of our population was 56.6 ± 10.33 years old, ranged from 45 to 76 years old. Final retinal reattachment was achieved clinically in all eyes. The Spectral domain-Optical Coherence Tomography (SD-OCT) follow-up showed the macular hole closure. The retinal patch was demonstrated by OCT at each control. BCVA improved from 1.52 ± 0.23 Logarithm of the Minimum Angle of Resolution (LogMAR) to 0.89 ± 0.16 LogMAR 3 months after surgery (p= 0.014). No adverse events were registered during the study. Autologous neurosensory retinal transplantation has been efficient to treat macular hole associated to rhegmatogenous retinal detachment. Further multicentric studies with a large number of patients are needed to establish the results of this technique in complex cases.

MANAGEMENT OF AUTOLOGUS RETINAL TRANSPLANT COMPLICATIONS: A CASE SERIES.

PURPOSE: To present representative cases of the most common complications associated with an autologous retinal transplant (ART) for macular hole repair. METHODS: A retrospective, consecutive case series on patients who underwent an ART by a single provider (Tamer H. Mahmoud). RESULTS: Four cases were included in this review. Each suffered an ART-specific complication, including graft displacement and dislocation, sub-ART perfluoron, and a delayed proliferative vitreoretinopathy-associated retinal detachment. CONCLUSION: Because more surgeons use ART to treat atypical macular holes, an adequate understanding of surgery-specific complications and techniques to treat those complications is increasingly necessary.

The Role of Retinal Pigment Epithelial Cells in Regulation of Macrophages/Microglial Cells in Retinal Immunobiology.

The ocular tissue microenvironment is immune privileged and uses several mechanisms of immunosuppression to prevent the induction of inflammation. Besides being a blood-barrier and source of photoreceptor nutrients, the retinal pigment epithelial cells (RPE) regulate the activity of immune cells within the retina. These mechanisms involve the expression of immunomodulating molecules that make macrophages and microglial cells suppress inflammation and promote immune tolerance. The RPE have an important role in ocular immune privilege to regulate the behavior of immune cells within the retina. Reviewed is the current understanding of how RPE mediate this regulation and the changes seen under pathological conditions.

AUTOLOGOUS NEUROSENSORY RETINAL TRANSPLANTATION: Bridging the Gap.

PURPOSE: To review the autologous retinal transplantation surgical technique, indications, rationale, and current outcomes of data published to date. METHODS: Review of surgical technique, preoperative and postoperative best-corrected visual acuity, and macular hole (MH) closure rate in studies with at least five eyes. RESULTS: The weighted average macular hole closure rate is 88%, with a MH closure rate ranging from 66.7% to 100%. The weighted average best-corrected visual acuity improved from mean logarithm of the minimum angle of resolution 1.35 (Snellen equivalent of 20/450) preoperatively to mean logarithm of the minimum angle of resolution 1.02 (Snellen equivalent of 20/210) postoperatively. From the largest autologous retinal transplantation case series, 37% of patients gained 3 or more lines of visual acuity after autologous retinal transplantation for primary or refractory MHs and 74% gained 3 or more lines of visual acuity after autologous retinal transplantation for MH-retinal detachments. Functional improvement including negative Watzke-Allen sign and conversion from positive to negative scotoma was reported in large case series. CONCLUSION: Autologous retinal transplantation is a promising technique for closure of large and refractory MHs otherwise difficult to repair with conventional techniques. This technique may allow for replacement of neural tissue in the macula through cell rehabilitation and regeneration through presumed ectopic synaptogenesis, retinal progenitor cell differentiation and integration, and/or retinal progenitor cell material transfer to host neurons.

Hallazgos por tomografía de coherencia óptica en un caso de agujero macular tratado con trasplante autógeno de retina / Optical coherence tomography findings in a case of macular hole treated with an autologous retinal transplant

Se presenta un caso de una mujer de 56 años de edad con un agujero macular grande, de larga evolución, a quien se le realizó una cirugía de trasplante autógeno de retina neurosensorial. En el seguimiento con retinografías y tomografía de coherencia óptica de dominio espectral, destacó la presencia de edema del injerto con hiperreflectividad de las capas retinianas internas, en las primeras semanas. Después, se observaron puntos hiperreflectivos, predominantemente en las capas internas de la retina, manteniendo la continuidad de las capas externas y la presencia de un material de aspecto lanudo en la superficie del injerto. Al final del seguimiento hubo una integración completa del injerto en la zona receptora del agujero, con la correspondiente mejoría funcional (AU)

A case is presented of a 56-year-old female patient with a long-standing large macular hole who underwent autologous retina transplant surgery. Fundus images and spectral-domain optical coherence tomography images showed the presence of graft oedema with its corresponding hyper-reflectivity of the inner retinal layers in the first weeks of follow-up. Hyper-reflective dots later appeared mainly in the inner retinal layers. The integrity of the outer retinal layers and a woolly-looking material on the surface of the graft were observed. At the end of follow-up, the graft had integrated with the recipient tissue with functional improvement (AU)

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression.

Recent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month. The present study placed hRPESC-RPE monolayers under the macula of a non-human primate model for 3 months. The transplant was able to recover in vivo and maintained healthy photoreceptors. Importantly, there was no evidence that subretinally transplanted monolayers underwent an epithelial-mesenchymal transition. Neither gliosis in adjacent retina nor epiretinal membranes were observed. These findings suggest that hRPESC-RPE monolayers are safe and may be a useful source for RPE cell replacement therapy.

Autologous Retinal Transplantation for Primary and Refractory Macular Holes and Macular Hole Retinal Detachments: The Global Consortium.

PURPOSE: To report the anatomic and functional outcomes of autologous retinal transplantation (ART). DESIGN: Multicenter, retrospective, interventional, consecutive case series. PARTICIPANTS: One hundred thirty eyes of 130 patients undergoing ART for the repair of primary and refractory macular holes (MHs), as well as combined MH-rhegmatogenous retinal detachment (MH-RRD), between January 2017 and December 2019. METHODS: All patients underwent pars plana vitrectomy and ART, with surgeon modification of intraoperative variables. A large array of preoperative, intraoperative, and postoperative data was collected. Two masked reviewers graded OCT images. Multivariate statistical analysis and subgroup analysis were performed. MAIN OUTCOME MEASURES: Macular hole closure rate, visual acuity (VA), external limiting membrane and ellipsoid zone (EZ) band integrity, and alignment of neurosensory layers (ANL) on OCT. RESULTS: One hundred thirty ART surgeries were performed by 33 vitreoretinal surgeons worldwide. Patient demographics were: mean age of 63 ± 6.3 years, 58% female, 41% White, 23% Black, 19% Asian, and 17% Latino. Preoperative VA was 1.37 ± 0.12 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, approximately 20/500), which improved significantly to 1.05 ± 0.09 logMAR (Snellen equivalent, approximately 20/225; P < 0.001) after surgery (mean follow-up, 8.6 ± 0.8 months). Autologous retinal transplantation was performed for primary MH repair in 27% of patients (n = 35), for refractory MH in 58% of patients (n = 76; mean number of previous surgeries, 1.6 ± 0.2), and for MH-RRD in 15% of patients (n = 19). Mean maximum MH diameter was 1470 ± 160 µm, mean minimum diameter was 840 ± 94 µm, and mean axial length was 24.6 ± 3.2 mm. Overall, 89% of MHs closed (78.5% complete; 10% small eccentric defect), with a 95% closure rate in MH-RRD (68.4% complete; 26.3% small eccentric defect). Visual acuity improved by at least 3 lines in 43% of eyes and by at least 5 lines in 29% of eyes. Reconstitution of the EZ (P = 0.02) and ANL (P = 0.01) on OCT were associated with better final VA. Five cases of ART graft dislocation (3.8%), 5 cases of postoperative retinal detachment (3.8%), and 1 case of endophthalmitis (0.77%) occurred. CONCLUSIONS: In this global experience, patients undergoing ART for large primary and refractory MHs and MH-RRDs achieved good anatomic and functional outcomes, with low complication rates despite complex surgical pathologic features.

INTRAOPERATIVE AND POSTOPERATIVE MONITORING OF AUTOLOGOUS NEUROSENSORY RETINAL FLAP TRANSPLANTATION FOR A REFRACTORY MACULAR HOLE ASSOCIATED WITH HIGH MYOPIA.

PURPOSE: To describe the intraoperative and postoperative morphological and functional outcomes after autologous neurosensory retinal flap transplantation (ART) for a high myopia-related refractory macular hole (MH). METHODS: This prospective interventional study enrolled five eyes of five patients (age range 54-84 years) with highly myopic refractory MHs who underwent ART. All cases were evaluated with intraoperative optical coherence tomography and postoperative optical coherence tomography, optical coherence tomography angiography, and microperimetry for at least 6 months postoperatively. RESULTS: Intraoperatively, the MH was covered by an ART flap with a persistent small subretinal space that was filled with the ART flap after 4 days to 6 days. Optical coherence tomography discriminated the original from the transplanted retina. The mean basal diameter of the original MH decreased from 1,504 ± 684 µm preoperatively to 1,111 ± 356 µm postoperatively. The best-corrected visual acuity improved in two cases, was stable in two cases, and deteriorated in one case. Microperimetry demonstrated no obvious postoperative changes in the fixation points and the absolute scotoma corresponding to the base of MHs with chorioretinal atrophy. In two eyes, choroidal neovascularization developed beneath the transplanted retinas. CONCLUSION: Transplanted tissue was in a fixed position by 1 week postoperatively with a decreased diameter of the original MH. Postoperative fixation points were on the original retina at the MH edge. Because choroidal neovascularization may develop, detailed monitoring is required.

[Photoreceptor cell transplantation for future treatment of retinitis pigmentosa]. / Nouvelle approche thérapeutique pour les rétinites pigmentaires - La transplantation de photorécepteurs dérivés de cellules souches.

In inherited retinal diseases such retinitis pigmentosa, characterized by progressive loss of light sensitive neurons (photoreceptors), cell therapy is now considered as an attractive strategy. Photoreceptor cell replacement would be valuable for restoring function to retinas in a way that is independent from the cause of the disease. With advances in stem cell biology, considerable strides have been made towards the generation of retinal cells, in particular with the development of 3D culture systems allowing the generation of retinal organoids from pluripotent stem cells. In this review, we present a state-of-the art of preclinical strategies conducted in animal models for photoreceptor replacement from stem cell-derived photoreceptors and we discuss the important obstacles to overcome in the future.

TITLE: Nouvelle approche thérapeutique pour les rétinites pigmentaires - La transplantation de photorécepteurs dérivés de cellules souches. ABSTRACT: Dans les maladies dégénératives de la rétine affectant les photorécepteurs, la transplantation de cellules permettant la restauration de la vision est aujourd'hui envisagée. La dernière décennie a vu des progrès remarquables dans la génération de cellules de rétine à partir de cellules souches pluripotentes humaines avec, en particulier, le développement de systèmes de culture en trois dimensions (3D) permettant la génération d'organoïdes de rétine. Dans cette revue, nous faisons un état des lieux sur les stratégies précliniques menées dans des modèles animaux pour le remplacement des photorécepteurs par des photorécepteurs dérivés de cellules souches et présentons les obstacles importants qui restent à être surmontés.

Autologous neurosensory retinal transplantation for recurrent macular hole retinal detachment in highly myopic eyes.

PURPOSE: To investigate the morphological and functional reconstruction of the macular fovea after autologous neurosensory retinal transplantation for recurrent macular hole retinal detachment (MHRD) in highly myopic eyes. METHODS: Ten consecutive cases of recurrent MHRD with high myopia were retrospectively reviewed. All eyes underwent pars plana vitrectomy combined with autologous neurosensory retinal transplantation and were followed up for at least 3 months after silicone oil extraction. The main outcomes were whether or not the retina was reattached and the macular hole (MH) was closed, morphological changes in the retinal graft, best-corrected visual acuity (BCVA), the sensitivity threshold and blood flow signal in the macula. RESULTS: At the one month postoperative visit, there was an obvious boundary between the graft and the surrounding retinal tissue, and some retinal structural layers could be seen in the graft on optical coherence tomography scans. At the final follow-up, eight eyes (80%) showed retinal reattachment and closure of the MH. Optical coherence tomography revealed blurring of the boundary between the graft and surrounding retinal tissue and that the retinal structure in the graft was disordered. The MH was not closed in two eyes (20%), in one case because of partial displacement of the graft and in the other because of incomplete coverage of the MH as a result of a smaller graft. The post-BCVA was significantly better than the pre-BCVA (1.32 ± 0.33 versus 2.01 ± 0.29 logMAR; p = 0.000, paired t-test). CONCLUSION: Autologous neurosensory retinal transplantation can be an effective treatment for recurrent MHRD in highly myopic eyes. 'Fusion' between the neurosensory retinal graft and the original retinal tissue may be the mechanism involved in the closure of the MH and reconstruction of the macular fovea.

Vascularization and Reperfusion of Autologous Retinal Transplant for Giant Macular Holes.

Importance: Autologous retinal transplant is a recently described treatment modality for myopic and other refractory macular holes (MH). Establishment of blood supply may influence survival of a transplanted tissue. However, there are currently no reports on the vascular status of a transplanted retinal graft. Objective: To report on vascularization and reperfusion of autologous retinal graft after transplant for giant MHs demonstrated by multimodal imaging. Design, Setting, Participants: Two patients with giant MH (basal diameter ≥2000 µm) who underwent autologous retinal transplant at Retina-Vitreous Associates Medical Group in Los Angeles, California, in June 2018 and February 2019, respectively, were included. Main Outcomes and Measures: Status of MH, Snellen visual acuity, optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography findings. Results: Two eyes of 2 female patients were included. The mean age was 68.5 years. Baseline visual acuity was counting fingers and 20/200, and MHs measured 3441 µm and 2387 µm, respectively. Six weeks postoperatively, MHs were closed and the superficial inner retina blood vessels within the graft appeared perfused. Optical coherence tomography and optical coherence tomography angiography demonstrated early integration of the graft into the surrounding retina and perfused graft vasculature in both patients. Fluorescein angiography confirmed perfusion of retinal graft. At the last follow-up, visual acuity was 20/200 and 20/150, respectively, the MH was closed, and the retinal grafts were perfused. Conclusions and Relevance: Autologous neurosensory retinal transplant may be used for the treatment of giant MHs. Vascularization and reperfusion of the retinal graft is observed within 6 weeks of transplant. It is hypothesized that visual improvement occurs as a result of flattening of the MH rim, partial centripetal migration of MH edges during the early healing phase, and further centripetal migration in the later phase associated with the shrinkage of the retinal graft.

Gene editing prospects for treating inherited retinal diseases.

Retinal diseases (RD) include inherited retinal dystrophy (IRD), for example, retinitis pigmentosa and Leber's congenital amaurosis, or multifactorial forms, for example, age-related macular degeneration (AMD). IRDs are clinically and genetically heterogeneous in nature. To date, more than 200 genes are known to cause IRDs, which perturb the development, function and survival of rod and cone photoreceptors or retinal pigment epithelial cells. Conversely, AMD, the most common cause of blindness in the developed world, is an acquired disease of the macula characterised by progressive visual impairment. To date, available therapeutic approaches for RD include nutritional supplements, neurotrophic factors, antiangiogenic drugs for wet AMD and gene augmentation/interference strategy for IRDs. However, these therapies do not aim at correcting the genetic defect and result in inefficient and expensive treatments. The genome editing technology based on clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (Cas) and an RNA that guides the Cas protein to a predetermined region of the genome, represents an attractive strategy to tackle IRDs without available cure. Indeed, CRISPR/Cas system can permanently and precisely replace or remove genetic mutations causative of a disease, representing a molecular tool to cure a genetic disorder. In this review, we will introduce the mechanism of CRISPR/Cas system, presenting an updated panel of Cas variants and delivery systems, then we will focus on applications of CRISPR/Cas genome editing in the retina, and, as emerging treatment options, in patient-derived induced pluripotent stem cells followed by transplantation of retinal progenitor cells into the eye.

AUTOLOGOUS RETINAL TRANSPLANTATION AS A PRIMARY TREATMENT FOR LARGE CHRONIC MACULAR HOLES.

PURPOSE: To report the outcomes of autologous neurosensory retinal transplant as a primary treatment for patients with large chronic macular holes and evaluate the safety and feasibility of the procedure. DESIGN: Retrospective study, consecutive case series. METHODS: We reviewed seven patients with a primary chronic large macular hole, who underwent autologous neurosensory retinal transplant. Mean preoperative minimum and maximum hole diameters were 643 µm and 1214 µm, respectively. Changes in visual acuity were measured postsurgery, and optical coherence tomography, fluorescein angiography, and microperimetry-3 were analyzed after the procedure. RESULTS: Closure of the macular hole was achieved in all seven eyes in the study. At 1 year post-surgery, there was significant improvement in mean visual acuity (LogMAR 1.10 vs. 0.68, P = 0.001). Optical coherence tomography showed that all grafts had formed attachments to the retinal epithelial cells of the recipient retina. Mean preoperative ellipsoid zone defect was 1,089 ± 403.8 µm (range, 918-1,329 µm) which further decreased to 921 ± 129.1 µm (range, 670-1,201 µm) at final follow up (P = 0.09). Microperimetry-3 testing indicated retinal sensitivity in the graft in five eyes. CONCLUSION: Autologous retinal transplantation may help rebuild the macular structure resulting in functional improvement for eyes with primary chronic large macular hole.

MANAGEMENT OF REFRACTORY LARGE MACULAR HOLE WITH AUTOLOGOUS NEUROSENSORY RETINAL FREE FLAP TRANSPLANTATION.

PURPOSE: To investigate the morphological and functional outcome of refractory large macular hole (MH) with autologous neurosensory retinal free flap transplantation. METHODS: This case series enrolled 10 patients suffering from refractory large MH at Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. All eyes underwent pars plana vitrectomy, a neurosensory retinal free flap with a 1.5 to 2-MH diameter was harvested. We used an adhesive agent such as whole blood or Viscoat to assist the stabilization of the retinal free flap and then use tamponade silicone oil to tamponade the vitreous cavity. Silicone oil was removed 6 months postoperatively. Main outcome measures including closure of MH and change in best-corrected visual acuity change were recorded. RESULTS: The mean age was 64.9 ± 11.5 years. Before presentation, all cases had received at least two vitreoretinal procedures including vitrectomy, internal limiting membrane peeling, and fluid-gas exchange. At last visit, closure of the MH was achieved in 9 of 10 (90%) cases. The mean preoperative best-corrected visual acuity and that after 12 months of surgery improved from 1.65 ± 0.43 logarithm of minimum angle of resolution to 0.88 ± 0.49 logarithm of minimum angle of resolution (P < 0.001). CONCLUSION: For eyes with refractory or large MH, autologous neurosensory retinal free flap under silicone oil tamponade may provide a new option to improve the anatomical and function outcome, especially in cases where insufficient internal limiting membrane is left.

Functional and morphological evaluation of autologous retinal graft in large traumatic macular hole.

A 7-year-old boy presented with history of blunt trauma 1 month back. Best corrected visual acuity (BCVA) was 20/200 with optical coherence tomography (OCT) showing a large macular hole. Spontaneous closure of the macular hole seemed unlikely following a month of observation. Pars plana vitrectomy along with autologous retinal graft was performed. At subsequent follow up, hole appeared closed with nasal shrinkage of graft and BCVA improved to 20/100. OCT showed mechanical integration of the graft with adjoining retina. Autologous retinal graft is a feasible option in cases where conventional internal limiting membrane peeling shows lower anatomical success.

Perfluorocarbon Liquid-Assisted Neurosensory Retinal Free Flap for Complicated Macular Hole Coexisting with Retinal Detachment.

PURPOSE: To report the surgical results and technique of perfluorocarbon-assisted neurosensory retinal flap transplantation into macular hole for concomitant macular hole and complicated retinal detachment. METHOD: This is a retrospective, consecutive case series of 7 cases with concomitant macular hole and complicated retinal detachment with proliferative vitreoretinopathy. All eyes had previous vitrectomy and internal limiting membrane peeling, or very large (>1,000 µm) macular holes. Perfluorocarbon liquid-assisted free neurosensory retinal flap transplantation into the macular hole, and subretinal fluid drainage through iatrogenic retinectomy/retinotomy were performed, followed by air-fluid exchange with gas or silicone oil tamponade. RESULTS: All eyes had retina reattached. Macular hole was closed in all eyes, with the graft visualized by optical coherence tomography. The best corrected visual acuity in logarithm of minimal angle of resolution improved from 2.80 ± 0.45 preoperatively to 1.40 ± 0.51 postoperatively (p < 0.01). CONCLUSIONS: Neurosensory retinal flap may be a good option in closing macular holes in eyes with concomitant macular hole and complicated retinal detachment. Because of its specific properties, the flap is easy to handle during the operation. Retinectomy or retinotomy serves to release traction, drain subretinal fluid, and provide retinal flap tissue.

Vascular and Neuronal Protection in the Developing Retina: Potential Therapeutic Targets for Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a common retinal disease in preterm babies. To prolong the lives of preterm babies, high oxygen is provided to mimic the oxygen level in the intrauterine environment for postnatal organ development. However, hyperoxia-hypoxia induced pathological events occur when babies return to room air, leading to ROP with neuronal degeneration and vascular abnormality that affects retinal functions. With advances in neonatal intensive care, it is no longer uncommon for increased survival of very-low-birth-weight preterm infants, which, therefore, increased the incidence of ROP. ROP is now a major cause of preventable childhood blindness worldwide. Current proven treatment for ROP is limited to invasive retinal ablation, inherently destructive to the retina. The lack of pharmacological treatment for ROP creates a great need for effective and safe therapies in these developing infants. Therefore, it is essential to identify potential therapeutic agents that may have positive ROP outcomes, especially in preserving retinal functions. This review gives an overview of various agents in their efficacy in reducing retinal damages in cell culture tests, animal experiments and clinical studies. New perspectives along the neuroprotective pathways in the developing retina are also reviewed.

Autologous translocation of the choroid and retina pigment epitelial cells(RPE) in age-related macular degeneration: Monitoring the viability of choroid and RPE patch with indocyanine green angiography(ICGA) and fundus autofluorescence(FAF).

PURPOSE: To investigate the functional and anatomical results of autologous retinal pigment epithelial(RPE) cells and choroidal translocation after removal of the subfoveal choroidal neovascular membrane(CNVM) in patients with exudative age-related macular degeneration(AMD). To monitor the viability of choroidal patch with indocyanine green angiography(ICGA) and fundus autofluorescence(FAF) METHODS: This study was conducted as a retrospective, interventional case series, and evaluation of 8 patients ;4 patients had large (> 1 disk diameter) subfoveal choroidal membranes, 3 with massive subretinal hemorrhage and 1 case with suprachoroidal hemorrhage(SCH) + rhegmatogenous retinal detachment(RRD). After removal of the CNVM, the autologous full-thickness patch of the RPE, bruch's membrane, choriocapillaris, and choroid was excised from the midperiphery and placed under the macula. At the 1 st month, 3rd month, 6th month and final examination, color fundus pictures and optical coherence tomography (OCT) were performed by preferred fixation of the OCT-light. Visual test with the early treatment of diabetic retinopathy study(ETDRS), OCT imaging with fixation, scanning with laser ophthalmoscopy autofluorescence, and ICGA were performed to evaluate the viability of choroidal patch at each visits. RESULTS: This study was carried out in 8 patients with a mean follow-up of 14.12 ±â€¯8.16 (range 7-30 months) months. The mean age was 73 ±â€¯7.17(range, 60-80 years) years. Pre-operative visual acuity ranged from hand motion (HM) (20/2000) to light perception (LP)(20/20000). Post-operative vision ranged from HM (20/2000) to 0.15(20/125). In 6 patients, autofluorescence was reflected in FAF imaging and lipofuscin activity was evaluated as viable. Post-operative subretinal hemorrhage was encountered in 1 (12.5%) patient and it also resolved spontaneously. There was a statistically significant increase in visual acuity at the postoperative final visit compared to baseline. (p = 0.027) CONCLUSIONS: After removal of the CNVM, translocation of a full-thickness patch with the autologous peripheral RPE and choroid can be performed at the macula, resulted in survival and functional graft for 6 months and moreover, hereby viability of the choroid and RPE patch were monitored by imaging methods such as FAF and ICGA.

Transplantation of Human Embryonic Stem Cell-Derived Retinal Tissue in the Subretinal Space of the Cat Eye.

To develop biological approaches to restore vision, we developed a method of transplanting stem cell-derived retinal tissue into the subretinal space of a large-eye animal model (cat). Human embryonic stem cells (hESC) were differentiated to retinal organoids in a dish. hESC-derived retinal tissue was introduced into the subretinal space of wild-type cats following a pars plana vitrectomy. The cats were systemically immunosuppressed with either prednisolone or prednisolone plus cyclosporine A. The eyes were examined by fundoscopy and spectral-domain optical coherence tomography imaging for adverse effects due to the presence of the subretinal grafts. Immunohistochemistry was done with antibodies to retinal and human markers to delineate graft survival, differentiation, and integration into cat retina. We successfully delivered hESC-derived retinal tissue into the subretinal space of the cat eye. We observed strong infiltration of immune cells in the graft and surrounding tissue in the cats treated with prednisolone. In contrast, we showed better survival and low immune response to the graft in cats treated with prednisolone plus cyclosporine A. Immunohistochemistry with antibodies (STEM121, CALB2, DCX, and SMI-312) revealed large number of graft-derived fibers connecting the graft and the host. We also show presence of human-specific synaptophysin puncta in the cat retina. This work demonstrates feasibility of engrafting hESC-derived retinal tissue into the subretinal space of large-eye animal models. Transplanting retinal tissue in degenerating cat retina will enable rapid development of preclinical in vivo work focused on vision restoration.