Retinal pigment epithelial and outer retinal atrophy (RORA) and complete RORA (cRORA) are major determinants of long-term vision in neovascular age-related macular degeneration (nAMD), but their development across subtypes is poorly defined, especially in Asian populations, in whom pachychoroid-driven disease is common. We compared long-term visual outcomes and atrophy burden between the conventional and novel nAMD classifications. One hundred twenty eyes of 120 treatment-naïve patients with nAMD followed at least six years were classified by conventional (typical nAMD [tAMD], polypoidal choroidal vasculopathy [PCV], retinal angiomatous proliferation [RAP]) and novel (drusen type, pachychoroid type, mixed type, other type) schemes. All eyes received three loading anti-VEGF injections followed by a pro re nata regimen. RORA within the central 1 mm was graded on optical coherence tomography; lesions ≥ 250 μm were defined as cRORA. Visual acuity (VA) retention, atrophy prevalence, and VA around atrophy onset were assessed. Mean age was 78.0 ± 9.2 years and overall VA retention was 71

Purpose To report a rare case of a full-thickness macular hole (FTMH) that underwent spontaneous closure on two separate occasions following vitrectomy and intraocular lens (IOL) scleral fixation. Observations A 58-year-old man, who had undergone IOL scleral fixation and vitrectomy for a dislocated IOL, developed an FTMH (minimum diameter: 21 μm) in the left eye approximately one year post-surgery. While awaiting surgical intervention, the macular hole closed spontaneously two months after its discovery. Two years and nine months later, the FTMH recurred (minimum diameter: 180 μm) and closed spontaneously again within four weeks. Optical coherence tomography (OCT) confirmed the presence of epiretinal proliferation (EP) at the macular surface during both occurrences. Conclusions and Importance: Small-diameter FTMHs that form after vitrectomy, particularly those with associated EP, may have the potential for spontaneous closure. This case indicates that short-term observation may be a reasonable management option for select cases of small post-vitrectomy macular holes before proceeding with further surgery.

Purpose: Assessing visual function in patients with ultra–low vision (ULV), particularly those with retinitis pigmentosa (RP), remains a significant challenge in therapeutic development. Full–field stimulus test (FST) provides a quantitative measure of retinal light sensitivity and may serve as a valuable clinical endpoint. We investigated FST in ULV RP by examining its associations with functional measures and daily activity–based tasks. Design: Observational, cross–sectional study. Participants: Patients with RP and visual acuity in the worse–seeing eye below counting fingers (CF) were enrolled. Methods: After dilation and 45–minute dark adaptation, FST was performed monocularly with brief full–field white–light flashes across three visits. Visual acuity was classified into four groups: no light perception (NLP), light perception (LP), hand motion (HM), and CF or better. We assessed functional vision using two tabletop object–recognition and exploration tasks, two mobility tasks, and three vision–related questionnaires. FST thresholds were compared across visual acuity groups, and associations with functional outcomes were analyzed. Main Outcome Measures: FST thresholds and their associations with functional vision outcomes. Results: Thirty–five patients (70 eyes; median age, 62 years, range 39–84) were included. Median FST thresholds (log cd·s/m2) by visual acuity group were as follows: NLP, 1.13 (–0.63 to 2.54); LP, –0.27 (–2.70 to 2.91); HM, –1.13 (–6.24 to 0.51); CF or better, –2.82 (–5.67 to 1.73) (p < 0.001). Measurable FST thresholds were obtained in 9 of 14 NLP eyes (64.3%). FST thresholds showed significant correlations with tabletop performance (r = –0.70 to –0.46) and mobility performance (r = –0.65), whereas no significant association was observed with questionnaire scores. Test–retest variability across three visits showed no systematic bias, with a coefficient of repeatability of ±0.66 to ±0.82 log cd·s/m2. ROC analyses identified FST cutoffs of –1.75 to –0.87 log cd·s/m2 at which patients first achieved nonzero functional task performance. Conclusions: FST quantifies residual visual function in ULV RP and correlates strongly with performance-based measures of functional vision in daily life. These findings support FST as a clinically meaningful endpoint for therapeutic trials in advanced RP and other severe visual impairments and highlight the value of anchoring FST thresholds to functional task performance. ### Competing Interest Statement All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. This study was sponsored by Restore Vision Inc. Y. Katada and T. Kurihara are co-founders of Restore Vision Inc. Individual investigators participating in the sponsored project were not directly compensated by the sponsor; any salary support was provided through their institution. Restore Vision Inc. provided financial support and supported study operations, but had no role in data collection, data analysis or interpretation, manuscript preparation, or the decision to submit for publication. ### Funding Statement This study was sponsored by Restore Vision Inc. and partially supported by the Japan Agency for Medical Research and Development (AMED) under Grant Number 23be0904005j0003 and 23qfb127003j0001. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board of Keio University School of Medicine gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Purpose:To evaluate the therapeutic potential of nicotinamide mononucleotide (NMN) for modulating the neurovascular inflammatory microenvironment and blunting tissue remodeling in neovascular age-related macular degeneration (nAMD). Methods:A laser-induced choroidal neovascularization (CNV) model was established in C57BL/6J mice, and CNV lesion size was quantified on RPE/choroid flat mounts. Immunostaining evaluated myeloid cell accumulation and fibrosis-associated remodeling. Quantitative RT-PCR and Western blotting assessed inflammatory/angiogenic gene expression and signaling activation in the retina and RPE/choroid. In vitro, lipopolysaccharide (LPS)-stimulated bEnd.3 and primary mouse RPE cells and TGF-β-stimulated THP-1-derived macrophage cells were used to model inflammatory and profibrotic responses. Results:NMN treatment significantly reduced CNV size in the laser-induced CNV model. This was accompanied by decreased myeloid cell accumulation within CNV lesions. NMN attenuated inflammatory and angiogenesis-related gene expression in the RPE/choroid and neural retina and reduced downstream signaling activation. In vitro, NMN suppressed LPS-induced inflammatory and proangiogenic responses in primary RPE cells and bEnd.3 endothelial cells and inhibited NF-κB activation. NMN further attenuated tissue remodeling, as shown by reduced collagen I-positive area under prolonged and delayed dosing regimens, together with decreased F4/80-positive area and α-smooth muscle actin-positive area within CNV lesions. In TGF-β-induced THP-1-derived macrophage cells, NMN suppressed profibrotic responses. Conclusions:Our findings indicate that NMN reduces inflammatory signaling and alleviates the inflammatory microenvironment in CNV, accompanied by decreased angiogenesis-related gene expression and fibrosis-related remodeling. By attenuating inflammatory activation and tissue remodeling processes, NMN warrants further evaluation as an adjunctive approach to limit CNV progression and late-stage tissue remodeling in nAMD.

Purpose We report a case of ocular siderosis caused by a subretinal iron foreign body. Observations A 30-year-old male construction worker injured by a small piece of shrapnel while working visited an eye clinic for decreased vision in left eye on day X, and was subsequently referred to our hospital with a diagnosis of vitreous hemorrhage on day X+1. Although a penetrating foreign body was suspected, no obvious wound or intraocular foreign body was found even after the hemorrhage subsided. On X+3 months, a rhegmatogenous retinal detachment was found and a lens-sparing vitrectomy was performed. A black elevated subretinal lesion was noted intraoperatively but not removed because it was considered to be a blood clot. The postoperative course was stable with best corrected visual acuity (BCVA) recovering to 20/16. However, the BCVA decreased to 20/30 on X+11 months with the subretinal lesion turning reddish brown. The electroretinogram also showed a significant attenuation of all stimuli. Siderosis was considered to have developed due to the subretinal foreign body. On X+14 months, we performed a combined phaco-vitrectomy to remove the foreign body. Analysis revealed iron as the main component of the foreign body. However, the postoperative electroretinogram remained unchanged, and the BCVA was 20/63 without improvement. Conclusions and importance We experienced a case of a subretinal iron foreign body being mistaken for a blood clot. Even if the vision stays stable, ocular siderosis may occur over the long term if a subretinal iron foreign body remains. Therefore, surgical removal should be actively considered when a subretinal iron foreign body is suspected.

PURPOSE. This study aimed to evaluate the efficacy of photoimmunotherapy (PIT) targeting VEGFR2 for the treatment of neovascular AMD and to investigate its potential as a novel therapeutic strategy. METHODS. DC101-IR700, a conjugate of the anti-mouse VEGFR2 monoclonal antibody DC101 and the photosensitizer IR700, was investigated both in vitro and in vivo. VEGFR2 expression in endothelial cells was confirmed via qPCR and immunocytochemistry. Laser-induced choroidal neovascularization (CNV) was established in C57BL/6J mice. Localization of DC101-IR700 within CNV lesions was assessed by immunofluorescence. After PIT was performed using either a 690 nm near-infrared manual laser or a slit lamp laser, CNV volumes were quantified through confocal microscopy. Cell viability post PIT was measured using MTT assay and cell death in CNV lesions was evaluated using TUNEL staining. RESULTS. DC101-IR700 localized specifically to VEGFR2-positive cells in CNV lesions, and PIT induced significant VEGFR2-dependent cytotoxicity in vitro. In vivo, both PIT and directional PIT using slit lamp laser significantly reduced CNV volumes compared with controls. TUNEL staining confirmed VEGFR2-specific cell death in treated CNV lesions. Directional PIT achieved similar efficacy to PIT, demonstrating its potential as a clinically viable alternative. CONCLUSIONS. PIT targeting VEGFR2 selectively induced cell death in pathological neovascular tissues, significantly reducing CNV volume in an AMD model. These findings suggest that VEGFR2-specific PIT represents a promising and targeted approach for treating neovascular AMD, offering advantages over conventional anti-VEGF therapies by potentially decreasing treatment frequency and improving efficacy.

Intraocular lenses (IOLs) have evolved significantly with the development of cataract surgery. Today multifocal intraocular lenses (MFIOLs) are increasingly used due to their ability to reduce dependence on glasses and improve patient satisfaction. However, late complications, such as IOL dislocation, pose challenges, especially for patients wishing to retain MFIOLs. The belt loop technique (BLT), a sutureless scleral fixation method, has been proposed as a simple and minimally invasive solution for IOL repositioning. Despite its potential, clinical evidence supporting BLT, particularly its needle externalization approach, remains limited. This report describes a 64-year-old male with MFIOL dislocation. Following a history of macular-off rhegmatogenous retinal detachment (RRD) repair by vitrectomy with gas tamponade, the patient experienced vision decline due to IOL displacement. Using the BLT needle externalization approach, both haptics of the MFIOL were successfully repositioned. Postoperatively, the patient achieved stable and improved near and distance visual acuity without significant glare or halos, maintaining these outcomes over a half year. This case demonstrates the clinical efficacy of the BLT needle externalization approach for MFIOL repositioning. The technique offers a minimally invasive, effective alternative for managing dislocated IOLs, even in complex cases involving MFIOLs. This method holds promise as a valuable addition to the repertoire of IOL fixation techniques, while the long-term stability requires further study.

PURPOSE:To demonstrate the novel use of a 31-gauge needle for flanged intrascleral intraocular lens (IOL) fixation using the double-needle technique. METHODS:Flanged intrascleral IOL fixation was performed using the ZELOSTAT 31G (ASTI, Shizuoka, Japan) needle in a 73-year-old male with right IOL subluxation. RESULTS:The IOL was successfully fixated with smooth intraoperative handling, excellent postoperative outcomes, no complications, and minimal refractive error. CONCLUSION:The 31-gauge needle has a larger inner diameter compared to the conventional 30-gauge thin-wall needle, which may facilitate intrascleral IOL fixation procedures.

Objective or Purpose To investigate the effect of anti-VEGF therapy on wide-field retinal and choroidal thickness in patients with macular edema secondary to RVO, and to identify how these effects vary based on clinical characteristics such as occlusion location and patient sex. Design Retrospective observational study. Subjects, Participants, and/or Controls Thirty-eight patients (38 eyes) with RVO treated at Keio University Hospital (26 males, 12 females; mean age, 67.7 ± 8.5 years). Seventeen fellow eyes without injection served as internal controls. Methods, Intervention, or Testing We analyzed 38 eyes with RVO who received intravitreal injections of aflibercept (n=31) or ranibizumab (n=7). Wide-field optical coherence tomography (OCT) was performed at baseline (within 7 days) and at the follow-up visit (30±14 days after the injection) . Changes in retinal and choroidal thickness were analyzed across nine predefined regions: a central 5-mm subfield (C0) and eight surrounding peripheral sectors: temporal (L1), superior-temporal (L2), superior (L3), superior-nasal (L4), nasal (L5), inferior-nasal (L6), inferior (L7), and inferior-temporal (L8). Statistical analysis was performed the Wilcoxon signed-rank test and Bonferroni correction for nine regions. Main Outcome Measures Changes in partial retinal and choroidal thickness Results Post-injection, retinal thickness significantly decreased in all regions except L4 and L6 (p < 0.0056). Choroidal thickness showed a significant reduction in L2, L5, and L8 (p < 0.0056). Subgroup analyses revealed no significant changes in choroidal thickness in either eyes with superior RVO (n = 9) or those with inferior RVO (n = 17). A clear sex-based difference was also observed: male patients (n = 26) exhibited choroidal thinning in L4, L5, L6, and L8 (p < 0.0056), whereas female patients (n = 12) showed no significant changes in any region. Conclusion Anti-VEGF therapy reduced retinal and choroidal thickness in partial regions in eyes with RVO. No significant differences were observed between eyes with superior and inferior occlusions. In male patients, significant thinning was observed in partial regions, whereas no significant changes were noted in female patients. These findings suggest that the choroidal response to anti-VEGF therapy is complex and warrants further investigation.

AMP -activated protein kinase (AMPK) plays a crucial role in maintaining ATP homeostasis in photoreceptor neurons. AMPK is a heterotrimeric protein consisting of alpha, beta, and gamma subunits. The independent functions of the 2 isoforms of the catalytic alpha subunit, PRKAA1 and PRKAA2, are uncharacterized in specialized neurons, such as photoreceptors. Here, we demonstrate in mice that rod photoreceptors lacking PRKAA2, but not PRKAA1, showed altered levels of cGMP, GTP, and ATP, suggesting isoform-specific regulation of photoreceptor metabolism. Furthermore, PRKAA2deficient mice displayed visual functional deficits on electroretinography and photoreceptor outer segment structural abnormalities on transmission electron microscopy consistent with neuronal dysfunction, but not neurodegeneration. Phosphoproteomics identified inosine monophosphate dehydrogenase (IMPDH) as a molecular driver of PRKAA2-specific photoreceptor dysfunction, and inhibition of IMPDH improved visual function in Prkaa2 rod photoreceptor-knockout mice. These findings highlight a therapeutically targetable PRKAA2 isoform-specific function of AMPK in regulating photoreceptor metabolism and function through a potentially previously uncharacterized mechanism affecting IMPDH activity.

Drusen are one of the most characteristic pathologies of precursor lesion of age-related macular degeneration (AMD). Drusen comprise a yellowish white substance that accumulates typically under the retinal pigment epithelium (RPE), and their constituents are lipids, complement, amyloid, crystallin, and others. In the past, many researchers have focused on drusen and tried to elucidate the pathophysiology of AMD because they believed that disease progression from early AMD to advanced AMD might be based on drusen or drusen might cause AMD. In fact, it is well established that drusen are the hallmark of precursor lesion of AMD and a major risk factor for AMD progression mainly based on their size and number. However, the existence of advanced AMD without drusen has long been recognized. For example, polypoidal choroidal vasculopathy (PCV), which comprises the majority of AMD cases in Asians, often lacks drusen. Thus, there is the possibility that drusen might be no more than a biomarker of AMD and not a cause of AMD. Now is the time to reconsider the relationship between AMD and drusen. In this review, we focus on early AMD pathogenesis based on basic research from the perspective of cholesterol metabolism and hypoxic response in the retina, and we discuss the role of drusen.

Purpose The burden of ocular diseases has been gradually increasing worldwide. Various factors are suggested for the development and progression of ocular diseases, such as ocular inflammation, oxidative stress, and complex metabolic dysregulation. Thus, managing ocular diseases requires the modulation of pathologic signaling pathways through many mechanisms. Nicotinamide mononucleotide (NMN) is a bioactive molecule naturally found in life forms. NMN is a direct precursor of the important molecule nicotinamide adenine dinucleotide (NAD + ), an essential co-enzyme required for enormous cellular functions in most life forms. While the recent experimental evidence of NMN treatment in various metabolic diseases has been well-reviewed, NMN treatment in ocular diseases has not been comprehensively summarized yet. In this regard, we aimed to focus on the therapeutic roles of NMN treatment in various ocular diseases with recent advances. Methods How we came to our current opinion with a recent summary was described based on our own recent reports as well as a search of the related literature. Results We found that NMN treatment might be available for the prevention of and protection from various experimental ocular diseases, as NMN treatment modulated ocular inflammation, oxidative stress, and complex metabolic dysregulation in murine models for eye diseases such as ischemic retinopathy, corneal defect, glaucoma, and age-related macular degeneration. Conclusion Our current review suggests and discusses new modes of actions of NMN for the prevention of and protection from various ocular diseases and can urge future research to obtain more solid evidence on a potential future NMN treatment in ocular diseases at the preclinical stages.

Cardiovascular abnormality-mediated retinal ischemia causes severe visual impairment. Retinal ischemia is involved in enormous pathological processes including oxidative stress, reactive gliosis, and retinal functional deficits. Thus, maintaining retinal function by modulating those pathological processes may prevent or protect against vision loss. Over the decades, nicotinamide mononucleotide (NMN), a crucial nicotinamide adenine dinucleotide (NAD+) intermediate, has been nominated as a promising therapeutic target in retinal diseases. Nonetheless, a protective effect of NMN has not been examined in cardiovascular diseases-induced retinal ischemia. In our study, we aimed to investigate its promising effect of NMN in the ischemic retina of a murine model of carotid artery occlusion. After surgical unilateral common carotid artery occlusion (UCCAO) in adult male C57BL/6 mice, NMN (500 mg/kg/day) was intraperitoneally injected to mice every day until the end of experiments. Electroretinography and biomolecular assays were utilized to measure ocular functional and further molecular alterations in the retina. We found that UCCAO-induced retinal dysfunction was suppressed, pathological gliosis was reduced, retinal NAD+ levels were preserved, and the expression of an antioxidant molecule (nuclear factor erythroid-2-related factor 2; Nrf2) was upregulated by consecutive administration of NMN. Our present outcomes first suggest a promising NMN therapy for the suppression of cardiovascular diseases-mediated retinal ischemic dysfunction.

Retinal ischemia/reperfusion (I/R) injury can cause severe vision impairment. Retinal I/R injury is associated with pathological increases in reactive oxygen species and inflammation, resulting in retinal neuronal cell death. To date, effective therapies have not been developed. Nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD+) intermediate, has been shown to exert neuroprotection for retinal diseases. However, it remains unclear whether NMN can prevent retinal I/R injury. Thus, we aimed to determine whether NMN therapy is useful for retinal I/R injury-induced retinal degeneration. One day after NMN intraperitoneal (IP) injection, adult mice were subjected to retinal I/R injury. Then, the mice were injected with NMN once every day for three days. Electroretinography and immunohistochemistry were used to measure retinal functional alterations and retinal inflammation, respectively. The protective effect of NMN administration was further examined using a retinal cell line, 661W, under CoCl2-induced oxidative stress conditions. NMN IP injection significantly suppressed retinal functional damage, as well as inflammation. NMN treatment showed protective effects against oxidative stress-induced cell death. The antioxidant pathway (Nrf2 and Hmox-1) was activated by NMN treatment. In conclusion, NMN could be a promising preventive neuroprotective drug for ischemic retinopathy.

PURPOSE:To investigate the risk factors for the development of proliferative vitreoretinopathy grade C (PVR-C), independent of prior surgical invasion.METHODS:Patients who underwent surgery for rhegmatogenous retinal detachment were prospectively registered with the Japan-Retinal Detachment Registry, organized by the Japanese Retina and Vitreous Society, between February 2016 and March 2017. Data obtained from general ophthalmic examinations performed before and at 1, 3, and 6 months after surgery were analyzed.RESULTS:We included 2013 eyes of 2013 patients (men, 1326 (65.9%); mean age, 55.2 ± 15.2 years) from amongst 3446 registered patients. Preoperative PVR-C was observed in 3.6% of patients. Propensity score matching revealed that a shorter axial length (AL) was a risk factor for preoperative PVR-C (OR (Odds Ratio), 0.81; 95% CI (Confidence Interval), 0.69 to 0.96; p = 0.015), which was a risk factor for surgical failure (OR, 4.22; 95% CI, 1.12 to 15.93; p = 0.034); the association was particularly significant for eyes with an AL < 25.0 mm (p = 0.016), while it was insignificant for eyes with an AL ≥ 25.0 mm.CONCLUSIONS:A shorter AL was related to the development of PVR-C before surgical invasion. Our results will help elucidate the fundamental pathogenesis of PVR and caution clinicians to meticulously examine eyes with a shorter AL to detect retinal detachment before PVR development.

Exposure to excessive visible light causes retinal degeneration and may influence the progression of retinal blinding diseases. However, there are currently no applied treatments. Here, we focused on endoplasmic reticulum (ER) stress, which can cause cellular degeneration and apoptosis in response to stress. We analyzed functional, histological, and molecular changes in the light-exposed retina and the effects of administering an ER-stress inhibitor, 4-phenylbutyric acid (4-PBA), in mice. We found that light-induced visual function impairment related to photoreceptor cell loss and outer segment degeneration were substantially suppressed by 4-PBA administration, following attenuated photoreceptor apoptosis. Induction of retinal ER stress soon after light exposure, represented by upregulation of the immunoglobulin heavy chain binding protein (BiP) and C/EBP-Homologous Protein (CHOP), were suppressed by 4-PBA. Concurrently, light-induced oxidative stress markers, Nuclear factor erythroid 2–related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1), and mitochondrial apoptotic markers, B-cell lymphoma 2 apoptosis regulator (Bcl-2)-associated death promoter (Bad), and Bcl-2-associated X protein (Bax), were suppressed by 4-PBA administration. Increased expression of glial fibrillary acidic protein denoted retinal neuroinflammation, and inflammatory cytokines were induced after light exposure; however, 4-PBA acted as an anti-inflammatory. Suppression of ER stress by 4-PBA may be a new therapeutic approach to suppress the progression of retinal neurodegeneration and protect visual function against photo-stress.

Background/AimsPars plana vitrectomy (PPV) is widely performed in patients with idiopathic epiretinal membrane (iERM) to improve vision. Postoperative visual field defects (VFDs) have been previously reported. However, whether they occur when using the most recent PPV system, and the frequency of VFDs as measured by standard automated perimetry, remain poorly documented and were examined in this study.MethodsData of 30 eyes (30 patients; mean age, 66.1 years; 15 men) who underwent PPV for iERM during February 2016–June 2019 and had preoperative and postoperative visual field measurements using standard automated perimetry (Humphrey visual field analyser 30-2 program) were retrospectively analysed. Eyes with diseases other than iERM, including moderate-to-severe cataract or preoperative VFDs were excluded.ResultsVFD, defined by the Anderson and Patella’s criteria, was found in 73.3% of the eyes 1 month after PPV. After age adjustment, internal limiting membrane (ILM) peeling was identified as a risk factor for postoperative VFD (p=0.035; 95% CI 1.173 to 92.8). Postoperative VFD was frequently observed nasally (86.4%, p=0.002), and on optical coherence tomography measurements, ganglion cell layer (GCL) thinning was found temporal to the fovea (p=0.008). Thinning of the superior and inferior retinal nerve fibre layers and of the GCL temporal to the fovea were significant in eyes after ILM peeling (all p<0.05).ConclusionILM peeling may cause inner retinal degeneration and lead to the development of VFDs after PPV, which should be further examined.

Leber congenital amaurosis type nine is an autosomal recessive retinopathy caused by mutations of the NAD+ synthesis enzyme NMNAT1. Despite the ubiquitous expression of NMNAT1, patients do not manifest pathologies other than retinal degeneration. Here we demonstrate that widespread NMNAT1 depletion in adult mice mirrors the human pathology, with selective loss of photoreceptors highlighting the exquisite vulnerability of these cells to NMNAT1 loss. Conditional deletion demonstrates that NMNAT1 is required within the photoreceptor. Mechanistically, loss of NMNAT1 activates the NADase SARM1, the central executioner of axon degeneration, to trigger photoreceptor death and vision loss. Hence, the essential function of NMNAT1 in photoreceptors is to inhibit SARM1, highlighting an unexpected shared mechanism between axonal degeneration and photoreceptor neurodegeneration. These results define a novel SARM1-dependent photoreceptor cell death pathway and identifies SARM1 as a therapeutic candidate for retinopathies.