Retinal Transplantation Research Articles

Parafoveal retinal massage combined with autologous blood cover in the management of giant, persistent or recurrent macular holes.

To assess the efficacy and safety of parafoveal retinal massage combined with autologous whole blood cover in the treatment of refractory macular holes (MHs) and present the surgical procedure. Patients with giant (minimum diameter ≥800 µm), recurrent or persistent MHs who underwent PPV combined with parafoveal retinal massage and autologous whole blood cover using C3F8 as tamponade agent from February 2018 to May 2019 were enrolled in this retrospective study. After surgery, all patients were informed to maintain a prone position for at least 7d. Preoperative and postoperative best-corrected visual acuities (BCVAs) were compared and MH closure rate was measured as the main outcome. A total of 13 MH patients consisted of 6 giant MHs, 4 persistent holes and 3 recurrent holes (5 men and 8 women; average age was 56.40±11.72y) were enrolled in this study. MH closure was achieved in 11 eyes by this modified surgical technique while 2 eyes failed. Revitrectomy with autologous neurosensory retinal patch transplantations was applied for those 2 patients and then both holes were closed. No intraoperative complications were observed. BCVA improved from 1.73 logMAR to 0.74 logMAR at 6mo postoperation. There was significant difference in BCVA before versus after the surgery (P<0.05). There were no adverse events occurred during the follow-up period. With easier surgical procedure, parafoveal retinal massage combined with autologous whole blood cover is an effective addition to the surgical options for the management of refractory MHs.

Autologous neurosensory free-flap retinal transplantation for refractory chronic macular hole-outcomes evaluated by OCT, microperimetry, and multifocal electroretinography.

To report the safety, anatomical and functional outcomes of autologous neurosensory retinal transplant in patients with a refractory large unclosed macular hole. This is a prospective case series of four patients with large chronic macular hole that underwent vitrectomy and free-flap neurosensory retinal transplantation surgery with silicone oil tamponade. The hole was closed with an autologous retinal transplant of an approximate diameter of 1.5-1.8 mm, harvested outside the vascular arcades. Anatomical and functional outcomes were assessed using best-corrected visual acuity (BCVA-Snellen), optical coherence tomography (OCT), OCT angiography, microperimetry (MP), and multifocal electroretinography (mfERG). There were 2 male and 2 female patients with median age of 73 (60-81) years. The median follow-up period was 17 (13-23) months. The median preoperative size of the macular hole was 1872.5 (868-2591) μm at the widest basal diameter and 828 (556-1099) μm at the minimum diameter. Surgery resulted in the anatomical closure of the macular hole in all cases. The OCT showed structural integration of the transplant and reappearance of the inner segment ellipsoid to different extents. The BCVA improved from preoperative 0.1 (6/60; + 1.0 logMAR), 0.1 (6/60; + 1.0 logMAR), 0.05 (6/120; + 1.3 logMAR), and 0.005 (6/1200; + 2.3 logMAR) to 0.2 (6/30; + 0.7 logMAR) postoperatively in cases 1, 2, and 4, and to 0.1 (6/60; + 1.0 logMAR) in case 3. MP showed retinal function in the region corresponding to the area of the transplant (circle of 1.8 mm in diameter) in all patients after the surgery (median sensitivity in that region was 4.0 dB, range 1.8-12.4 dB). Improvement was noted in the patient that had MP performed before the surgery (mean sensitivity improved from 0 to 1.8 dB). Detectable function was mostly located in the peripheral regions of the transplant. Multifocal ERG showed abnormal function of the central ring and normal function of the second ring in 3 of 4 cases. The OCT angiography showed normal perfusion, without signs of neovascularization. There were no intra- or postoperative complications. Autologous retinal transplantation surgery is a successful technique for closing of large refractory macular holes. The procedure is safe and provides good anatomical results. Visual acuity, microperimetry, and mfERG suggest some gradual functional integration of outer regions of the transplants, but no central functional restitution has been detected as yet.

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

To report the anatomic and functional outcomes of autologous retinal transplantation (ART). Multicenter, retrospective, interventional, consecutive case series. 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 December2019. 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. Macular hole closure rate, visual acuity (VA), external limiting membrane and ellipsoid zone (EZ) band integrity, and alignment of neurosensory layers (ANL) on OCT. 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. 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.

Autologous Retinal Flap Transplantation of a Refractory Giant Macular Hole with Retinal Detachment

Autologous Retinal Flap Transplantation of a Refractory Giant Macular Hole with Retinal Detachment

Recalcitrant Macular Hole Closure by Autologous Retinal Transplant Using the Peripheral Retina.

PurposeThe peripheral adult human retina has been found to contain neuroepithelial stem cells. In this study, we examined the efficacy of an auto-transplant of peripheral retina into refractory macular holes (MH) from both anatomic and physiologic perspectives.MethodsThe population consisted of four female patients aged 72, 82, 65 and 84 years (cases 1–4, respectively) with persistent refractory MH status; internal limiting membrane (ILM) peeling (case 1), ILM transplant (case 2), and inverted ILM (cases 3 and 4 with myopic MH). In all our cases, retinal grafts were harvested beyond the equator from the far retinal periphery using curved horizontal scissors and gently moved toward the MH using a forceps. A 25-G manipulator with a silicone ball tip was used to tuck the trimmed graft into the MH, followed by fluid-air exchange and infusion of silicone oil, which was removed three months later.ResultsPartial restoration and integration of the outer retinal layer were confirmed on an OCT-B scan imaging. The visual acuity (VA) was improved in all cases: 1.2 to 1.0 logMAR (case 1), 2.0 to 1.3 logMAR (case 2), 2.3 to 1.4 logMAR (case 3) and 2.0 to 1.0 logMAR (case 4). Microperimetry showed improved retinal sensitivity in every case. No intra- or post-operative complications were observed.ConclusionUnder pathological conditions, the Müller glia reportedly serves as a source of neuronal progenitor cells in regenerating retina, continuing to divide and migrate to the outer nuclear layer thus replacing lost photo-receptors. Although the histological findings remain unknown, the positive anatomic and physiologic outcomes of the auto-transplanted retinal flap in our series suggest that this technique may offer an effective option for treating recalcitrant MH. Further studies are warranted.

Current management strategies for atypical macular holes.

This review evaluates the current surgical management options for refractory and atypical macular holes (MH) and proposes a treatment paradigm for approaching complex cases. A review of literature was performed to deliver a thorough discussion of the epidemiology and pathophysiology of MH as well as the historic evolution of surgical management strategies. With this context established, an update on recent surgical advances for management of large, chronic, and highly myopic MH is provided. New small MH may be adequately treated with pars plana vitrectomy, while those ≥300 μm should undergo internal limiting membrane (ILM) peel. For MH ≥400 μm with risk factors for failure, primary intervention should involve creation of an ILM flap and various methods of flap creation are discussed. For very large MH ≥700 μm or in refractory cases, autologous retinal transplants and other recently proposed procedures should be considered. While typical MHs enjoy high initial surgical success rates, atypical and refractory MH require additional intraoperative and postoperative considerations to maximize surgical success and optimize vision. With many techniques at the surgeon's disposal, patient selection becomes critical to improving outcomes.

Quantifiable In Vivo Imaging Biomarkers of Retinal Regeneration by Photoreceptor Cell Transplantation.

PurposeShort-term improvements in retinal anatomy are known to occur in preclinical models of photoreceptor transplantation. However, correlative changes over the long term are poorly understood. We aimed to develop a quantifiable imaging biomarker grading scheme, using noninvasive multimodal confocal scanning laser ophthalmoscopy (cSLO) imaging, to enable serial evaluation of photoreceptor transplantation over the long term.MethodsPhotoreceptor cell suspensions or sheets from rhodopsin-green fluorescent protein mice were transplanted subretinally, into either NOD.CB17-Prkdcscid/J or C3H/HeJ-Pde6brd1 mice. Multimodal cSLO imaging was performed serially for up to three months after transplantation. Imaging biomarkers were scored, and a grade was defined for each eye by integrating the scores. Image grades were correlated with immunohistochemistry (IHC) data.ResultsMultimodal imaging enabled the extraction of quantitative imaging biomarkers including graft size, GFP intensity, graft length, on-target graft placement, intra-graft lamination, hemorrhage, retinal atrophy, and periretinal proliferation. Migration of transplanted material was observed. Changes in biomarker scores and grades were detected in 14/16 and 7/16 eyes, respectively. A high correlation was found between image grades and IHC parameters.ConclusionsSerial evaluation of multiple imaging biomarkers, when integrated into a per-eye grading scheme, enabled comprehensive tracking of longitudinal changes in photoreceptor cell grafts over time. The application of systematic multimodal in vivo imaging could be useful in increasing the efficiency of preclinical retinal cell transplantation studies in rodents and other animal models.Translational RelevanceBy allowing longitudinal evaluation of the same animal over time, and providing quantifiable biomarkers, non-invasive multimodal imaging improves the efficiency of retinal transplantation studies in animal models. Such assays will facilitate the development of cell therapy for retinal diseases.

Autologous Retinal Free Flap Transplantation for Recurrent Giant Macular Hole Retinal Detachment in High Myopia

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A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models.

Recently, we successfully transplanted an autograft, or major histocompatibility complex (MHC)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (iPSC-RPE) cells in patients with age-related macular degeneration. However, there was an issue regarding immune rejection after transplantation. In this study, we established a preoperational in vitro “drug–lymphocytes–grafts immune reaction (Drug-LGIR)” test to determine the medication for immune rejection using host immunocompetent cells (lymphocytes) and transplant cells (target iPSC-RPE cells) together with different medications. The adequacy of the test was assessed by in vivo transplantation in monkey models together with medication based on in vitro data. In the results of Drug-LGIR tests, some drugs exhibited significant suppression of RPE cell-related allogeneic reactions, while other drugs did not, and the efficacy of each drug differed among the recipient monkeys. Based on the results of Drug-LGIR, we applied cyclosporine A or local steroid (triamcinolone) therapy to two monkeys, and successfully suppressed RPE-related immune rejections with RPE grafts, which survived without any signs of rejection under drug administration. We propose that our new preoperational in vitro Drug-LGIR test, which specifies the most efficacious medication for each recipient, is useful for controlling immune attacks with personalized treatment for each patient after retinal transplantation.

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

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. 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 3months 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. 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). 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.

Adult-Human Retinal Pigment Epithelial Cell Transplantation Supports Retinal Function in Non-Human Primate Models

While recent trials of retinal pigment epithelium (RPE) transplantation for advanced age-related macular degeneration (AMD) treatment have been promising, the existing strategies still have limitations including the uncertain survival of RPE cells delivered by cell suspension and the risk of uncontrolled cell proliferation in the vitreous cavity. Human cadaveric donor RPE cell (ahRPE) transplants have been shown to rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month, suggesting its suitability as an alternative cell resource. The present study placed an ahRPE monolayer under the macula of a non-human primate model for up to 3 months. It was able to mature in-vivo and support photoreceptor function. Most importantly, transplanted monolayers did not undergo epithelial-mesenchymal transition to form epiretinal membranes. Gliosis was suppressed in adjacent retina. These findings indicate the safety and potential of ahRPE monolayer as a cell replacement source.

LONG-TERM RESULTS OF AUTOLOGOUS RETINAL PIGMENT EPITHELIUM AND CHOROID TRANSPLANTATION FOR THE TREATMENT OF EXUDATIVE AND ATROPHIC MACULOPATHIES.

To evaluate the long-term results of autologous retinal pigment epithelium (RPE) and choroid transplantation (RPE-choroid patch) for exudative and atrophic maculopathies. Consecutive chart review of 120 eyes, which underwent RPE-choroid patch, from 2007 to 2017 for RPE atrophy or choroidal neovascular membrane secondary to exudative and hemorrhagic age-related macular degeneration, myopia, angioid streaks, and laser. Eyes were tested with best-corrected visual acuity (BCVA), reading ability, optical coherence tomography, fluorescein angiography and indocyanine green angiography, autofluorescence, and microperimetry. Eighty-eight eyes of 84 patients had complete data, with 2- to 10-year follow-up. Mean age was 71.9 ± 9.06 years. Mean preoperative and postoperative BCVA was 20/320 (1.2 ± 0.2 logMAR) and 20/200 (0.94 ± 0.36 logMAR), respectively (P = 0.009). Reading ability recovered in 43% of cases. Microperimetry showed central fixation. A gain of at least 15 letters was obtained in 40% of eyes. Integrity (P = 0.009) of external limiting membrane and higher preoperative BCVA (P = 0.001) predicted better final BCVA. Complications were retinal detachment (11.4%), macular atrophy (7%), subretinal hemorrhage (4.5%), epiretinal membrane (4.5%), recurrent choroidal neovascular membrane (4.5%), macular hole (3.4%), and cystoid edema (3%). Autologous RPE-choroid patch achieved long-lasting BCVA improvement and central fixation, in eyes with choroidal neovascular membrane and intact external limiting membrane. Atrophic maculopathies only obtained temporary visual benefit.

Development of a protocol for maintaining viability while shipping organoid-derived retinal tissue.

Retinal organoid technology enables generation of an inexhaustible supply of three-dimensional retinal tissue from human pluripotent stem cells (hPSCs) for regenerative medicine applications. The high similarity of organoid-derived retinal tissue and transplantable human fetal retina provides an opportunity for evaluating and modeling retinal tissue replacement strategies in relevant animal models in the effort to develop a functional retinal patch to restore vision in patients with profound blindness caused by retinal degeneration. Because of the complexity of this very promising approach requiring specialized stem cell and grafting techniques, the tasks of retinal tissue derivation and transplantation are frequently split between geographically distant teams. Delivery of delicate and perishable neural tissue such as retina to the surgical sites requires a reliable shipping protocol and also controlled temperature conditions with damage-reporting mechanisms in place to prevent transplantation of tissue damaged in transit into expensive animal models. We have developed a robust overnight tissue shipping protocol providing reliable temperature control, live monitoring of the shipment conditions and physical location of the package, and damage reporting at the time of delivery. This allows for shipping of viable (transplantation-competent) hPSC-derived retinal tissue over large distances, thus enabling stem cell and surgical teams from different parts of the country to work together and maximize successful engraftment of organoid-derived retinal tissue. Although this protocol was developed for preclinical in vivo studies in animal models, it is potentially translatable for clinical transplantation in the future and will contribute to developing clinical protocols for restoring vision in patients with retinal degeneration.

Long-term clinical outcomes of submacular blood removal with isolated autologous retinal pigment epithelium-choroid patch graft transplantation in long-standing large-sized submacular hematomas: An Indian experience.

Purpose:To study the outcomes of submacular blood removal with isolated autologous full-thickness retinal pigment epithelial (RPE)-choroid patch graft transplantation in long-standing large-sized submacular hematomas in Indian population.Methods:A retrospective study was done on eight consecutive patients of long-standing large-sized submacular hematoma from east India. In all cases, 23G vitrectomy was performed with the induction of retinal detachment (performed with or without 38G or 41G subretinal cannula) and a temporal 180° retinectomy was done. Submacular blood along with choroidal neovascular tissue was removed. A full-thickness RPE-choroid autologous patch graft was taken from a relatively healthy quadrant at the mid periphery and then the graft transferred under perfluorocarbon liquid (PFCL) to place it in the subfoveal area. Then, retina was re-attached using PFCL and laser completed. Silicone oil (5000 cst) was used as a tamponade. Post-operatively, wide-field fundus photographs (Optos), serial optical coherence tomography (OCT), indocyanine green angiography (ICGA), and multifocal electroretinography (ERG) were done.Results:The mean age of the patients at presentation was 67.88 ± 10.03 years. Mean pre-operative best corrected visual acquity (BCVA) was 2.64 ± 0.3 log MAR and mean postoperative BCVA was 1.095 ± 0.27 log MAR (P < 0.05). The mean follow-up was 20 ± 16.57 months. ICG showed re-vascularization of translocated graft in all at 2 months. Multifocal ERG (after 6 months) showed some waveform in all. None of the cases developed re-bleed.Conclusion:Removal of submacular blood and neovascular membrane with autologous RPE-choroid graft is a viable option in cases with long-standing large submacular hematomas.

Autologous retinal graft for closure of large chronic macular hole with old retinal detachment : A report of two cases

Purpose: To report 2 cases of the use of autologous retinal graft for the surgical treatment of traumatic atrophic large macular holes with old retinal detachment.&#x0D; Case report: The patients had pars plana vitrectomy with membrane peeling and flattening of the retina under perfluorocarbon liquid, and autologous retinal graft to close the large atrophic macular holes. Postoperativereviews show closure of the macular holes, attachment of the retina and some improvement of visual acuity.&#x0D; Conclusion: Autologous retinal free patch transplantation may offer a new solution for treatment of large chronic traumatic macular holes with old retinal detachment.

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

To investigate the morphological and functional outcome of refractory large macular hole (MH) with autologous neurosensory retinal free flap transplantation. 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. 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). 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.

Looking into dental pulp stem cells in the therapy of photoreceptors and retinal degenerative disorders

Blindness and vision impairment are caused by irremediable retinal degeneration in affected individuals worldwide. Cell therapy for a retinal replacement can potentially rescue their vision, specifically for those who lost the light sensing photoreceptors in the eye. As such, well-characterized retinal cells are required for the replacement purposes. Stem cell-based therapy in photoreceptor and retinal pigment epithelium transplantation is well received, however, the drawbacks of retinal transplantation is the limited clinical protocols development, insufficient number of transplanted cells for recovery, the selection of potential stem cell sources that can be differentiated into the target cells, and the ability of cells to migrate to the host tissue. Dental pulp stem cells (DPSC) belong to a subset of mesenchymal stem cells, and are recently being studied due to its high capability of differentiating into cells of the neuronal lineage. In this review, we look into the potential uses of DPSC in treating retinal degeneration, and also the current data supporting its application.

Multielectrode Array Recording of Mouse Retinas Transplanted with Stem Cell-Derived Retinal Sheets.

Retinal multielectrode array (MEA) recording allows us to examine the action potentials of retinal ganglion cells and field potentials of photoreceptors and bipolar cells. In addition to studying the retinal circuitry, it has become one of the standard examination tools for the characterization of stem cell-derived retinal transplantation in degenerated retinas. Besides the detection of responses to simple light stimulation, it is also necessary to consider the spatial correlation of the graft and the electrodes, in order to unbiasedly reveal the locally reconstructed retinal circuitry after transplantation. Here, we introduce our newly developed protocol of MEA recording and analysis that may serve as a standard for evaluating transplanted retinas.

Preconditioning the Initial State of Feeder-free Human Pluripotent Stem Cells Promotes Self-formation of Three-dimensional Retinal Tissue

A three-dimensional retinal tissue (3D-retina) is a promising graft source for retinal transplantation therapy. We previously demonstrated that embryonic stem cells (ESCs) can generate 3D-retina in vitro using a self-organizing stem cell culture technique known as SFEBq. Here we show an optimized culture method for 3D-retina generation from feeder-free human pluripotent stem cells (hPSCs). Although feeder-free hPSC-maintenance culture was suitable for cell therapy, feeder-free hPSC-derived aggregates tended to collapse during 3D-differentiation culture. We found that the initial hPSC state was a key factor and that preconditioning of the hPSC state by modulating TGF-beta and Shh signaling improved self-formation of 3D-neuroepithelium. Using the preconditioning method, several feeder-free hPSC lines robustly differentiated into 3D-retina. In addition, changing preconditioning stimuli in undifferentiated hPSCs altered the proportions of neural retina and retinal pigment epithelium, important quality factors for 3D-retina. We demonstrated that the feeder-free hiPSC-derived 3D-retina differentiated into rod and cone photoreceptors in vitro and in vivo. Thus, preconditioning is a useful culture methodology for cell therapy to direct the initial hPSC state toward self-organizing 3D-neuroepithelium.

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

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. Retrospective study, consecutive case series. 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. 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. Autologous retinal transplantation may help rebuild the macular structure resulting in functional improvement for eyes with primary chronic large macular hole.