Assessment of histological and immunohistochemical features of retinal tissues using a novel tissue submission procedure.

We introduce a novel tissue submission procedure without additional equipment or storage facilities for assessing the histological and immunohistochemical features of retinal tissues. In total, 150 specimens were collected from patients who underwent vitrectomy or macular surgery from January to December 2020. Ninety-eight specimens were submitted using the new procedure, and 58 specimens were submitted as flat-mount slides to compare specimen adequacy. The tissues submitted using the new procedure were subjected to paraffin-embedding and sectioning for hematoxylin & eosin staining. Additional immunohistochemical analysis was performed to assess the cellular composition in retinal tissues with diverse etiologies. The new submission procedure had an adequacy ratio of 75.51%, which was comparable to that of the flat-mount method (p = 0.1397). The new method could produce high-quality images of histological features of tissues and facilitated immunohistochemical analysis to demonstrate cell origins. More glial cells (p = 0.000) and myofibroblasts (p = 0.012) were detected in the epiretinal membranes (ERMs) than in the internal limiting membranes (ILMs). Subgroup analysis revealed that secondary ERMs contained more macrophage-like cells (p = 0.001) and retinal pigment epithelial cells (p = 0.000) than did idiopathic ERMs. Our novel tissue submission procedure can be applied to routine clinical practice. Our study provides additional histological and immunohistochemical evidence of cellular components in retinal tissues based on a large number of human tissue samples. Moreover, tissues submitted using the new method can be permanently preserved, enabling future investigation for potential prognostic or therapeutic targets.

A Simple New Technique to Peel Epiretinal Membrane Without Removing Silicone Oil.

PURPOSE: To introduce a new surgical technique that can keep constant intraocular pressure of the eyeball during peeling epiretinal membrane under silicone oil status. METHODS: A viscoelastic agent was injected into the air pump of the constellation system via the metal tip. This procedure offers a buffer zone to keep constant pressure within the eyeball without disturbing the surgical field by an air bubble. RESULTS: Three cases were performed efficiently (15 ± 5 minutes) under this technique with improvement in anatomical feature and visual function after the surgery. CONCLUSION: Using this simple yet important technique can provide us the constant intraocular pressure without hypotony and avoid the traditional complicated procedures.

Same-Day Bilateral Intravitreal Dexamethasone Implants for the Treatment of Diabetic Macular Edema.

INTRODUCTION: The aim of this study was to evaluate the outcomes and complications associated with the use of same-day bilateral intravitreal dexamethasone (DEX) implants for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 130 eyes of 65 patients with bilateral DME who were treated with intravitreal DEX implants. The patients were divided into two groups: a control group (comprising 40 eyes treated with an alternating unilateral regimen) and a study group (comprising 90 eyes treated with concomitant bilateral DEX implants). All patients were followed up monthly after implantation. The changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to sixth month after implantation, and ocular adverse effects such as intraocular pressure, cataract, and tolerability of bilateral implantation were reviewed. The primary endpoint was to assess the safety of the same-day bilateral treatment protocol. The secondary endpoints focused on evaluating the functional and anatomical changes associated with bilateral simultaneous or alternating implantations. RESULTS: At 6 months after implantation, mean BCVA increased and CRT decreased in both groups. Moreover, no serious ocular adverse effects were observed. In addition, no differences were observed between the two groups in the number of patients who required extra follow-up visits or the number of extra visits made in addition to the treatment schedule. CONCLUSIONS: Same-day bilateral intravitreal DEX implants are associated with a low complication rate and are well tolerated by patients. This safe practice may optimize efficiency and reduce the burden on both the health-care system and patients, when used to treat bilateral DME.

Mitochondrial transport mediates survival of retinal ganglion cells in affected LHON patients.

The mutations in the genes encoding the subunits of complex I of the mitochondrial electron transport chain are the most common cause of Leber's hereditary optic neuropathy (LHON), a maternal hereditary disease characterized by retinal ganglion cell (RGC) degeneration. The characteristics of incomplete penetrance indicate that nuclear genetic and environmental factors also determine phenotypic expression of LHON. Therefore, further understanding of the role of mutant mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit proteins and nuclear genetic factors/environmental effects in the etiology of LHON is needed. In this study, we generated human-induced pluripotent stem cells (hiPSCs) from healthy control, unaffected LHON mutation carrier, and affected LHON patient. hiPSC-derived RGCs were used to study the differences between affected and unaffected carriers of mitochondrial DNA point mutation m.11778G > A in the MT-ND4 gene. We found that both mutated cell lines were characterized by increase in reactive oxygen species production, however, only affected cell line had increased levels of apoptotic cells. We found a significant increase in retrograde mitochondria and a decrease in stationary mitochondria in the affected RGC axons. In addition, the messenger RNA and protein levels of KIF5A in the LHON-affected RGCs were significantly reduced. Antioxidant N-acetyl-L-cysteine could restore the expression of KIF5A and the normal pattern of mitochondrial movement in the affected RGCs. To conclude, we found essential differences in the mutually dependent processes of oxidative stress, mitochondrial transport and apoptosis between two LHON-specific mutation carrier RGC cell lines, asymptomatic carrier and disease-affected, and identified KIF5A as a central modulator of these differences.

Correlations between Clinical and Histopathologic Characteristics in Idiopathic Epiretinal Membrane.

PURPOSE: To investigate correlations between clinical and histopathologic characteristics of idiopathic epiretinal membrane (ERM). DESIGN: Retrospective interventional case series. PARTICIPANTS: In total, 87 eyes from 87 patients with idiopathic ERM who underwent pars plana vitrectomy with peeling of the ERM from 2019 to 2020 were included. METHODS: The outcomes of clinical ophthalmic examination, including measurement of best-corrected visual acuity (BCVA) and spectral-domain OCT (SD-OCT), before and after surgery were reviewed. Surgical specimens were fixed in formalin and embedded in paraffin for histologic and immunohistochemical analysis. MAIN OUTCOMES MEASURES: The association between morphological characteristics revealed on SD-OCT images and the cellular composition of the surgically excised ERM demonstrated with immunohistochemical staining were the main outcome measures. Changes in the BCVA and central macular thickness (CMT) were assessed through a comparison of preoperative and postoperative measurements. RESULTS: Based on SD-OCT morphological characteristics in the foveal area, 15 cases were classified into group 1A (mainly outer retinal thickening), 39 into group 1B (more tenting of the outer retina and distorted inner retina), and 33 into group 1C (prominent inner retina thickening). Overall, postoperative final BCVA and CMT at 1 year improved in all groups. Patients who presented with a better initial BCVA exhibited a more favorable final BCVA. Epiretinal membranes in group 1C demonstrated the greatest decrease in CMT compared with those in groups 1B and 1A, but the final CMT did not differ among the groups. A negative correlation between the density of hyalocytes (P = 0.003) and myofibroblasts (P = 0.047) was noted between the 3 groups. Total cell density and glial cell density of the ERMs were strongly associated with poor final BCVA and BCVA improvement. CONCLUSIONS: The present study provides new histopathologic information regarding the formation and progression of idiopathic ERM. Glial cell proliferation plays a predominant role in these processes. Epiretinal membranes with high cellularity and glial cell density may cause damage to the retina structure, resulting in poor postoperative visual outcomes. These findings provide additional evidence supporting early surgical intervention in patients with idiopathic ERM reported with visual disturbance.

Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities.

Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

Pluripotent Stem Cells in Clinical Cell Transplantation: Focusing on Induced Pluripotent Stem Cell-Derived RPE Cell Therapy in Age-Related Macular Degeneration.

Human pluripotent stem cells (PSCs), including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), represent valuable cell sources to replace diseased or injured tissues in regenerative medicine. iPSCs exhibit the potential for indefinite self-renewal and differentiation into various cell types and can be reprogrammed from somatic tissue that can be easily obtained, paving the way for cell therapy, regenerative medicine, and personalized medicine. Cell therapies using various iPSC-derived cell types are now evolving rapidly for the treatment of clinical diseases, including Parkinson's disease, hematological diseases, cardiomyopathy, osteoarthritis, and retinal diseases. Since the first interventional clinical trial with autologous iPSC-derived retinal pigment epithelial cells (RPEs) for the treatment of age-related macular degeneration (AMD) was accomplished in Japan, several preclinical trials using iPSC suspensions or monolayers have been launched, or are ongoing or completed. The evolution and generation of human leukocyte antigen (HLA)-universal iPSCs may facilitate the clinical application of iPSC-based therapies. Thus, iPSCs hold great promise in the treatment of multiple retinal diseases. The efficacy and adverse effects of iPSC-based retinal therapies should be carefully assessed in ongoing and further clinical trials.

Expression of Endogenous Angiotensin-Converting Enzyme 2 in Human Induced Pluripotent Stem Cell-Derived Retinal Organoids.

Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal organoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.

Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing.

Inherited retinal dystrophies (IRDs) are rare but highly heterogeneous genetic disorders that affect individuals and families worldwide. However, given its wide variability, its analysis of the driver genes for over 50% of the cases remains unexplored. The present study aims to identify novel driver genes, disease-causing variants, and retinitis pigmentosa (RP)-associated pathways. Using family-based whole-exome sequencing (WES) to identify putative RP-causing rare variants, we identified a total of five potentially pathogenic variants located in genes OR56A5, OR52L1, CTSD, PRF1, KBTBD13, and ATP2B4. Of the variants present in all affected individuals, genes OR56A5, OR52L1, CTSD, KBTBD13, and ATP2B4 present as missense mutations, while PRF1 and CTSD present as frameshift variants. Sanger sequencing confirmed the presence of the novel pathogenic variant PRF1 (c.124_128del) that has not been reported previously. More causal-effect or evidence-based studies will be required to elucidate the precise roles of these SNPs in the RP pathogenesis. Taken together, our findings may allow us to explore the risk variants based on the sequencing data and upgrade the existing variant annotation database in Taiwan. It may help detect specific eye diseases such as retinitis pigmentosa in East Asia.

An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials.

Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye's accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.

A new immunodeficient retinal dystrophic rat model for transplantation studies using human-derived cells.

PURPOSE: To create new immunodeficient Royal College of Surgeons (RCS) rats by introducing the defective MerTK gene into athymic nude rats. METHODS: Female homozygous RCS (RCS-p+/RCS-p+) and male nude rats (Hsd:RH-Foxn1mu, mutation in the foxn1 gene; no T cells) were crossed to produce heterozygous F1 progeny. Double homozygous F2 progeny obtained by crossing the F1 heterozygotes was identified phenotypically (hair loss) and genotypically (RCS-p+ gene determined by PCR). Retinal degenerative status was confirmed by optical coherence tomography (OCT) imaging, electroretinography (ERG), optokinetic (OKN) testing, superior colliculus (SC) electrophysiology, and by histology. The effect of xenografts was assessed by transplantation of human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) and human-induced pluripotent stem cell-derived RPE (iPS-RPE) into the eye. Morphological analysis was conducted based on hematoxylin and eosin (H&E) and immunostaining. Age-matched pigmented athymic nude rats were used as control. RESULTS: Approximately 6% of the F2 pups (11/172) were homozygous for RCS-p+ gene and Foxn1mu gene. Homozygous males crossed with heterozygous females resulted in 50% homozygous progeny for experimentation. OCT imaging demonstrated significant loss of retinal thickness in homozygous rats. H&E staining showed photoreceptor thickness reduced to 1-3 layers at 12 weeks of age. Progressive loss of visual function was evidenced by OKN testing, ERG, and SC electrophysiology. Transplantation experiments demonstrated survival of human-derived cells and absence of apparent immune rejection. CONCLUSIONS: This new rat animal model developed by crossing RCS rats and athymic nude rats is suitable for conducting retinal transplantation experiments involving xenografts.

POSTOPERATIVE INNER NUCLEAR LAYER MICROCYSTS AFFECTING LONG-TERM VISUAL OUTCOMES AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To investigate the risk factors and long-term visual impact of microcysts in the inner nuclear layer developed after epiretinal membrane (ERM) surgery. METHODS: This study used a retrospective review of medical records, operative video and images of patients who had undergone idiopathic ERM surgery with more than 12 months of follow-up. RESULTS: This study enrolled 44 patients (44 eyes) with ERM and a mean follow-up period of 30.2 months. The visual acuity improved from a mean of 6/22.8 to 6/12 (P < 0.001). Results indicated that a final visual acuity greater than 0.5 was associated with younger age, better preoperative visual acuity, a complete postoperative inner segment and outer segment line, and absence of inner nuclear layer microcysts. The visual acuity difference between patients with and without inner nuclear layer microcysts emerged in the first month and continued throughout the entire study period. Shorter duration of visual symptoms, more severe grade of ERM with paravascular abnormalities, and retinal petechiae immediately after the peeling of the ERM are risk factors of microcysts. CONCLUSION: This study suggests that inner nuclear layer microcysts are induced shortly after surgery and have long-term visual effects. Factors associated with this side effect suggest that severity, acuteness, and adhesiveness of ERM may play a significant role in visual outcomes.

CT of globe rupture: analysis and frequency of findings.

OBJECTIVE: The objective of our study was to evaluate the CT characteristics of globe rupture. MATERIALS AND METHODS: The medical records of patients seen in the emergency department with blunt, penetrating, or explosive orbit injury were retrospectively reviewed. A total of 75 patients (76 injured globes) were included (56 males and 19 females; average age, 45.1 years; age range, 5-95 years). CT examinations were reviewed by two experienced radiologists without knowledge of ophthalmologic findings, original orbital CT images, or surgical outcomes. RESULTS: Of the 76 globe injuries, 33 (43%) were ruptured and 43 (57%) were nonruptured. There were significant differences between the ruptured and nonruptured globes with respect to intraocular hemorrhage, lens dislocation and destruction, an intraocular foreign body, intraocular gas, anterior chamber depth (ACD), and globe deformity and wall irregularity (p < 0.05). There was good interrater agreement between the two radiologists (kappa value range, 0.63-0.96). The average sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CT for the detection of globe rupture based on readings by two radiologists were 76%, 85%, 80%, 82%, and 81%, respectively. CONCLUSION: Although CT is extremely useful in the evaluation of ocular trauma, it should not be solely relied on for the diagnosis of globe rupture because of the potentially catastrophic consequences of an undiagnosed injury. A difference in ACD can be diagnostic of globe rupture.

Brolucizumab in recalcitrant neovascular age-related macular degeneration-real-world data in Chinese population.

This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.

Exome sequencing and genome-wide association analyses unveils the genetic predisposition in hydroxychloroquine retinopathy.

OBJECTIVES: To unveil the candidate susceptibility genes in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy using whole exome sequencing (WES) and genome-wide association study (GWAS). METHODS: Patients with a diagnosis of CQ/HCQ retinopathy based on the comprehensive demographic and ocular examination were included. The peripheral blood was extracted for WES and GWAS analyses. The Chinese Han Southern database from 1000 genomes was used as control group to compare the affected percentage. Multivariate logistic regression analysis adjusted for age, HCQ dose, duration and renal disease were used to analyze the correlation between genetic variants and visual outcome. A poor vision outcome was defined as visual acuity <6/12. An abnormal anatomical outcome was defined as disruption of ellipsoid zone in the fovea. RESULTS: Twenty-nine patients with an average age of 60.9 ± 13.4 years, treatment duration of 12.1 ± 6.2 years, daily dose of 8.5 ± 4.1 mg/kg, and the cumulative dose of 1637.5 ± 772.5 g, were genotyped. Several candidate genes associated with CQ/HCQ retinopathy were found, including RP1L1, RPGR and RPE65, with a difference of affected percentage over 50% in mutation between the case and control groups. New foci in CCDC66: rs56616026 (OR = 63.43, p = 1.63 × 10-8) and rs56616023 (OR = 104.7, p = 5.02 × 10-10) were identified significantly associated with HCQ retinopathy. Multivariate analysis revealed increased genetic variants were significantly associated with poor functional (OR = 1.600, p = 0.004) and structural outcome (OR = 1.318, p = 0.043). CONCLUSIONS: Several candidate susceptibility genes including RP1L1, RPGR, RPE65 and CCDC66 were identified to be associated with CQ/HCQ retinopathy. In addition to disease susceptibility, patients with increased genetic variants are more vulnerable to poor visual outcomes.

TMEM132D and VIPR2 Polymorphisms as Genetic Risk Loci for Retinal Detachment: A Genome-Wide Association Study and Polygenic Risk Score Analysis.

Purpose: Retinal detachment (RD) is a sight-threatening ocular disease caused by separation of the neurosensory retina from the underlying retinal pigment epithelium layer. Its genetic basis is unclear because of a limited amount of data. In this study, we aimed to identify genetic risk loci associated with RD in participants without diabetes mellitus and to construct a polygenic risk score (PRS) to predict the risk of RD. Methods: A genome-wide association study was conducted using data from the Taiwan Biobank to identify RD risk loci. A total of 1533 RD cases and 106,270 controls were recruited, all of whom were Han Chinese. Replication studies were performed using data from the UK Biobank and Biobank Japan. To construct the PRS, a traditional clumping and thresholding method was performed and validated by fivefold cross-validation. Results: Two novel loci with significant associations were identified. These two genes were TMEM132D (lead single nucleotide polymorphism [SNP]: rs264498, adjusted-P = 7.18 × 10-9) and VIPR2 (lead SNP: rs3812305, adjusted-P = 8.38 × 10-9). The developed PRS was effective in discriminating individuals at high risk of RD with a dose-response relationship. The quartile with the highest risk had an odds ratio of 1244.748 compared to the lowest risk group (95% confidence interval, 175.174-8844.892). Conclusions: TMEM132D and VIPR2 polymorphisms are genetic candidates linked to RD in Han Chinese populations. Our proposed PRS was effective at discriminating high-risk from low-risk individuals.

HLA-Homozygous iPSC-Derived Mesenchymal Stem Cells Rescue Rotenone-Induced Experimental Leber's Hereditary Optic Neuropathy-like Models In Vitro and In Vivo.

BACKGROUND: Mesenchymal stem cells (MSCs) hold promise for cell-based therapy, yet the sourcing, quality, and invasive methods of MSCs impede their mass production and quality control. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) can be infinitely expanded, providing advantages over conventional MSCs in terms of meeting unmet clinical demands. METHODS: The potential of MSC therapy for Leber's hereditary optic neuropathy (LHON) remains uncertain. In this study, we used HLA-homozygous induced pluripotent stem cells to generate iMSCs using a defined protocol, and we examined their therapeutic potential in rotenone-induced LHON-like models in vitro and in vivo. RESULTS: The iMSCs did not cause any tumorigenic incidence or inflammation-related lesions after intravitreal transplantation, and they remained viable for at least nine days in the mouse recipient's eyes. In addition, iMSCs exhibited significant efficacy in safeguarding retinal ganglion cells (RGCs) from rotenone-induced cytotoxicity in vitro, and they ameliorated CGL+IPL layer thinning and RGC loss in vivo. Optical coherence tomography (OCT) and an electroretinogram demonstrated that iMSCs not only prevented RGC loss and impairments to the retinal architecture, but they also improved retinal electrophysiology performance. CONCLUSION: The generation of iMSCs via the HLA homozygosity of iPSCs offers a compelling avenue for overcoming the current limitations of MSC-based therapies. The results underscore the potential of iMSCs when addressing retinal disorders, and they highlight their clinical significance, offering renewed hope for individuals affected by LHON and other inherited retinal conditions.

Three-Year Outcomes of Intravitreal Aflibercept Injections for Retinal Angiomatous Proliferation According to Disease Stage.

INTRODUCTION: To evaluate the outcomes of intravitreal aflibercept injections for retinal angiomatous proliferation (RAP) according to disease stage. METHODS: This retrospective chart review included 68 eyes of 53 individuals diagnosed as having RAP and 109 neovascular age-related macular degeneration (nAMD) eyes of 109 patients as controls. All patients received intravitreal injections of aflibercept in a real-world setting. The main outcome measures were the changes in the mean of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) as well as the total number of injections received during the 3-year follow-up period. RESULTS: The average BCVA and CRT changes in eyes affected by RAP and the controls at 3 years were non-significant. Both populations received a similar number of injections. After 3 years of treatment, patients with RAP had visual decline despite stable anatomical outcomes. Approximately 50% of the eyes with stage II RAP exhibited significant BCVA decline at the end of the third year. Among those eyes that had deteriorated BCVA, persistently worsening BCVA and thinning CRT were observed from year 2 to year 3. CONCLUSION: Similar to treating nAMD, intensive injections or aggressive treatment strategies are required to treat RAP to achieve optimal visual outcomes in a real-world setting. The response to aflibercept treatment at the second year is associated with the final visual outcome of eyes with stage II RAP lesions.

Evaluation of a remote telemedicine platform using a novel handheld fundus camera: Physician and patient perceptions from real-world experience.

BACKGROUND: Although teleophthalmology has gained traction in recent years, it is at the center of the coronavirus disease pandemic. However, most hospitals are not ready owing to a severe lack of real-world experience. Furthermore, a limited number of studies have evaluated telemedicine applications on remote islands. This study aimed to evaluate real-world clinical and referral accuracy, image quality, physician-perceived diagnostic certainty, and patient satisfaction with telemedicine eye screening using a novel handheld fundus camera in a rural and medically underserved population. METHODS: This prospective study included 176 eyes from a remote island. All participants underwent a comprehensive ophthalmic examination. Nonmydriatic retinal images obtained using a handheld fundus camera were reviewed by two retinal specialists to determine image quality, diagnosis, and need for referrals. The agreement of diagnosis between image-based assessments was compared with that of binocular indirect ophthalmoscopic assessments. RESULTS: Image quality of fundus photographs was considered acceptable or ideal in 97.7% and 95.5% of eyes assessed by two reviewers, respectively. There was considerable agreement in diagnosis between the indirect ophthalmoscopic assessment and image-based assessment by two reviewers (Cohen's kappa = 0.80 and 0.78, respectively). Likewise, substantial agreement was achieved in the referrals. The sensitivity for referable retinopathy from the two reviewers was 78% (95% confidence interval [CI], 57%-91%) and 78% (95% CI, 57%-91%), whereas specificity was 99% (95% CI, 95%-99%] and 98% (95% CI, 93%-99%), respectively. For physicians' perceived certainty of diagnosis, 93.8% and 90.3% were considered either certain or reliable. Overall, 97.4% of participants were satisfied with their experiences and greatly valued the telemedicine services. CONCLUSION: Novel fundus camera-based telemedicine screening demonstrated high accuracy in detecting clinically significant retinopathy in real-world settings. It achieved high patient satisfaction and physician-perceived certainty in diagnosis with reliable image quality, which may be scaled internationally to overcome geographical barriers under the global pandemic.

Pseudophakic pupillary block after phacoemulsification and posterior chamber intraocular lens implantation: Cause identification and treatment refinement.

BACKGROUND: Pseudophakic pupillary block (PPB) was rare in patients who undergo phacoemulsification and posterior chamber intraocular lens (PCIOL) implantation. Laser peripheral iridotomy was the most reported but ineffective treatment in the literature. METHODS: Retrospective, interventional case series of patients who developed PPB in Taipei Veterans General Hospital from 2017 to 2021. Clinical course, diagnostic methods, treatment and outcomes were recorded and discussed. RESULTS: Four eyes of three patients were documented. All of them had diabetes and diabetic retinopathy. Anterior segment Optical coherence tomography (OCT) of these patients showed an exudative membrane at the peripapillary area while slit lamp image could not provide a clear view due to the severely edematous corneal condition. Laser peripheral iridotomy and yttrium aluminum garnet (YAG) laser aiming to the peripapillary exudation were applied to break the PPB successfully. CONCLUSION: Diabetes mellitus, intravitreal injection and inflammation are crucial risk factors for PPB. Anterior segment OCT can be a useful diagnostic tool for the detection of the peripapillary exudative membrane while corneal clarity is compromised due to high intraocular pressure. In addition to peripheral laser iridotomy, an effective approach to resolve PPB may be the use of the YAG laser to break the exudative membrane.