PURPOSE:To characterize the clinical spectrum and age-distribution of pseudomelanomas in patients referred for suspected uveal melanoma at the largest ocular-oncology center in South Korea, where uveal melanoma incidence is the lowest worldwide. METHODS:A retrospective review was conducted of consecutive patients referred for suspected uveal melanoma between January 2020 and August 2025. Diagnoses were confirmed using multimodal imaging. Patients were stratified into five groups (0-20, 21-40, 41-60, 61-80, and 81-100 years) to identify age-specific diagnostic patterns. RESULTS:Of 687 patients, 564 (82.1%) had pseudomelanomas and 123 (17.9%) had clinically confirmed melanoma, 81 of which had cytologic/pathologic confirmation. Common pseudomelanomas were choroidal nevus (N=120, 21.3%), congenital hypertrophy of the retinal pigment epithelium (CHRPE, N=70, 12.4%), choroidal hemangioma (N=53, 9.4%), choroidal metastasis (N=39, 6.9%), optic disc melanocytoma (N=35, 6.2%), and retinal capillary hemangioblastoma (N=32, 5.7%). Rare entities included vortex vein varix (N=7, 1.2%), posterior nodular scleritis (N=6, 1.1%), choroidal lymphoma (N=3, 0.5%), degenerative retinoschisis (N=2, 0.4%), RPE adenoma, uveal effusion, ciliary body schwannoma, ciliary body leiomyoma (N=1, 0.2%, respectively), etc. Uveal melanoma was absent in those aged 0-20 years and predominated in adults aged 41-80 years, along with nevus and metastasis, while CHRPE, retinal capillary hemangioblastoma, and choroidal osteoma were more common in ≤40 years. Peripheral exudative hemorrhagic chorioretinopathy was predominant in ≥81 years, while primary vitreoretinal lymphoma occurred in ≥61 years. CONCLUSIONS:Pseudomelanomas accounted for over 80% of suspected uveal melanoma cases in this Korean cohort, with age-specific distribution patterns. Recognizing pseudomelanomas features and these patterns may enhance diagnostic accuracy.

PURPOSE:To compare the outcomes of transscleral four-point fixation using a closed continuous-loop suture and transconjunctival intrascleral haptic fixation (Yamane technique) for intraocular lens (IOL) fixation. METHODS:Patients who underwent scleral fixation of IOL using four-point fixation with a closed continuous-loop suture and the Yamane technique were reviewed. Demographics, pre- and postoperative data, including operation time, complications, and reoperation rates, were reviewed. The cumulative probability of remaining free from IOL redislocation was analyzed using Kaplan-Meier curves, and the factors associated with IOL redislocation were assessed using a Cox proportional hazards model. RESULTS:A total of 179 eyes of 175 patients were included, comprising 120 eyes in the four-point fixation group and 59 eyes in the Yamane group. Visual and refractive outcomes were comparable 6 months postoperatively. Operative time was significantly shorter in the Yamane group (35.6 ± 10.9 vs. 49.5 ± 14.7 min; p < 0.001). Postoperative complication rates, including corneal decompensation, hypotony, and endophthalmitis, did not differ significantly between groups. Cox proportional hazards model showed that the Yamane technique was associated with a significantly higher hazard of IOL redislocation (hazard ratio, 8.68; 95% confidence interval, 1.38-54.46; p = 0.021). CONCLUSION:Both four-point fixation and the Yamane technique yielded comparable visual outcomes and safety profiles. The Yamane technique offered shorter operative time, whereas the four-point fixation was associated with a lower risk of IOL redislocation. These findings highlight the importance of preoperative structural assessments in guiding the selection of fixation methods.

This study investigates the effect of epiretinal membrane (ERM) removal in the combined hamartomas of the retina and retinal pigment epithelium (CHRRPE) patients. In this retrospective, comparative case series, 15 CHRRPE patients were included. Six patients received ERM surgery (operation group) and 9 patients were observed (observation group). The differences of age at diagnosis and the severity of ERM were not statistically significant for the operation and observation group at initial diagnosis. The change in central macular thickness (CMT), foveo-papillary distance (FPD) and best corrected visual acuity (BCVA) were analyzed for both groups at initial and final follow-up visits. In the operation group, CMT significantly decreased (initial 480 ± 151 μm VS final 365 ± 59 μm; P = 0.036), while FPD significantly increased (P = 0.031). BCVA significantly improved at the final follow-up in operation group (P = 0.031). In the observation group, FPD decreased significantly (P = 0.012) and BCVA did not change significantly (P = 0.438). Removal of ERM may be beneficial in normalizing macular anatomy and may be effective in preventing visual deterioration in patients with ERM associated with CHRRPE.

The eye's visual function relies on retinal neural cells that are long-lived, post-mitotic, and possess minimal regenerative capacity. These combined properties render them exceptionally vulnerable to the cumulative damage that drives age-related functional decline. Accumulating evidence now implicates epigenetic alterations, such as aberrant DNA methylation and histone modifications, not merely as correlates of aging but as fundamental drivers of aging and disease. These changes disrupt the stable gene expression programs required to maintain cellular identity and function, thereby contributing to the pathogenesis of irreversible blinding diseases like glaucoma and age-related macular degeneration (AMD). Unlike immutable genetic mutations, the reversible nature of these epigenetic marks offers a novel therapeutic paradigm. Epigenetic reprogramming, a strategy involving the transient expression of Yamanaka factors or chemical cocktails, provides a powerful means to reset this dysregulated epigenetic landscape and restore cells to a more youthful state. Compelling preclinical studies have validated this approach by demonstrating vision restoration in models of optic neuropathy through the rejuvenation of damaged and aged neurons. This review provides a comprehensive overview of ocular aging from an epigenetic perspective, examines the promise and potential concerns of epigenetic reprogramming, and discusses the future of rejuvenation therapies in ophthalmology.

Background: The expression levels of the programmed death-ligand 1 (PD-L1) protein serves as a prognostic indicator for patients with colorectal cancer (CRC). Advancement of CRC is facilitated by deubiquitinating enzymes (DUBs), which regulate oncoprotein levels via the ubiquitin-proteasomal pathway. The post-translational regulatory mechanisms governing PD-L1 protein abundance on CRC, in relation to different tumor grades and their clinical relevance, remains unknown. Methods: We analyzed single-cell RNA sequencing (scRNA-seq) data to identify DUB genes associated with PD-L1 expression in CRC. We used a loss-of-function-based CRISPR/Cas9 library to identify putative DUB genes that regulate the PD-L1 protein level. Immunoprecipitation was used to confirm the interaction between the USP32 and PD-L1 along with its ubiquitination status. A series of in vitro and in vivo carcinogenesis-related experiments were conducted to determine the clinical relevance between USP32 and PD-L1 expression in CRC progression. Results: In this study, we analyzed scRNA-seq data from extensive cohorts of human and mice at the single-cell level to identify DUB genes associated with PD-L1 expression in CRC. Our analysis identified multiple putative DUBs, including USP32 and USP12, as prognostic markers associated with PD-L1 expression, which was found to be elevated in T cells, macrophages, and classical monocytes cell types in patients with CRC. A secondary screening using CRISPR/Cas9-mediated loss-of-function analysis for DUBs found that USP32 modulates PD-L1 protein levels in CRC. Furthermore, we demonstrated that USP32 interacts with, stabilizes, and extends the half-life of PD-L1 by preventing its K-48-linked polyubiquitination as an underlying mechanism that contributes for tumorigenesis. Conclusion: A combination of scRNA-seq analysis and wet-lab experimental validation confirmed that USP32 mediates PD-L1 protein stabilization in colon cancer, identifying it as a potential therapeutic target for CRC. CRISPR/Cas9-mediated targeted knockout of the USP32 gene reduced PD-L1 protein levels and significantly mitigated colorectal cell proliferation and tumorigenesis, both in vitro and in vivo, in a xenograft mouse model, underscoring a novel and alternative approach to the treatment of CRC.

Human vision relies on photoreceptor cells in the outer retina that are sensitive to visible light. However, many people suffer from blindness due to retinal diseases that cause photoreceptor degeneration. Electrical stimulation of retinal neurons can recreate the action potentials associated with seeing that are generated by these cells. Here we report a thin artificial retina that can be adhered to the epiretinal surface and can convert near-infrared (NIR) light into electrical stimuli that selectively stimulate ganglion cells. The artificial retina consists of a NIR-sensitive phototransistor array and three-dimensional liquid metal micropillar electrodes. The liquid metal electrodes enhance proximity to retinal ganglion cells, providing effective charge injection while minimizing tissue damage, owing to their low Young's modulus. Ex vivo studies demonstrate its biocompatibility, and in vivo studies using healthy and blind mice demonstrate perception of both visible and NIR light, as indicated by cortical recordings and behavioural tests. The retina could, in the future, be used to create a NIR visual channel in patients with photoreceptor degenerative blindness without interfering with their remaining natural vision.

PURPOSE:To evaluate the efficacy of subretinal tissue plasminogen activator (tPA) injection in patients with massive submacular hemorrhage (SMH) with or without vitrectomy. METHODS:This retrospective study included patients with massive SMH treated with subretinal tPA injection (12.5 μg/0.1 mL) using a nanovitreoretinal (NVR) device at a single tertiary referral center between 2020 and 2024. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT); secondary outcomes included SMH thickness reduction and between-group comparison of surgical approaches. RESULTS:Eighteen eyes of 15 patients were analyzed; 11 eyes (61.1%) were from female patients. Twelve eyes underwent vitrectomy (66.7%), while six were treated without vitrectomy (33.3%). Baseline demographic and clinical characteristics were summarized descriptively because of the small and imbalanced subgroup sizes. Neovascular age-related macular degeneration was the leading etiology (17 eyes, 94.4%), comprising typical neovascular age-related macular degeneration (9 eyes, 50.0%), polypoidal choroidal vasculopathy (7 eyes, 38.9%), and retinal angiomatous proliferation (1 eye, 5.6%); the remaining eye (5.6%) had peripheral exudative hemorrhagic chorioretinopathy. BCVA improved significantly from 1.79 ± 0.77 to 1.28 ± 0.83 logMAR (p = 0.010), with 10 eyes (55.6%) achieving ≥3-line improvement. CMT decreased significantly at 6 months (673.8 ± 346.7 to 266.0 ± 327.1 μm, p = 0.019), and 81.3% of eyes achieved ≥20% CMT reduction. SMH thickness decreased significantly postinjection (536.9 ± 345.0 to 221.4 ± 443.4 μm, p = 0.020). No significant differences in final BCVA (1.24 ± 0.77 logMAR vs. 1.37 ± 1.01 logMAR, p = 0.850) or CMT reduction rate (81.8% vs. 80.0%; p > 0.999) were observed between vitrectomy and nonvitrectomy groups. CONCLUSIONS:Subretinal tPA injection via the NVR device was associated with improvements in visual and anatomical outcomes in massive SMH. The nonvitrectomy approach showed no significant difference in outcomes compared with vitrectomy-assisted injection, but this exploratory finding should be interpreted cautiously given the small sample size.

PURPOSE:To evaluate the clinical performance of ultra-widefield swept-source optical coherence tomography (UWF-OCT) in the assessment of choroidal tumors and to compare it with ultrasonography (US), spectral-domain (SD)-OCT, and magnetic resonance imaging (MRI). DESIGN:Retrospective diagnostic comparison. SUBJECTS:Thirty-nine eyes from 39 patients diagnosed with choroidal tumors at a single tertiary referral center. METHODS:This retrospective diagnostic comparison evaluated patients diagnosed with choroidal tumors at a single tertiary referral center between January 2023 and August 2025. All patients underwent UWF-OCT imaging at diagnosis. Tumor measurements obtained with UWF-OCT were compared with US, SD-OCT, and MRI. Comparative analysis among imaging modalities and predictors affecting UWF-OCT applicability was performed. MAIN OUTCOME MEASURES:Tumor thickness (mm) and largest basal diameter (LBD, mm) measurements, and complete measurability rate across different tumor size categories. RESULTS:Thirty-nine eyes from 39 patients (mean age 59.2 ± 16.9 years) were analyzed, including 27 choroidal melanomas (69.2%), 5 metastatic tumors (12.8%), 4 hemangiomas (10.3%), 2 osteomas (5.1%), and 1 (2.6%) indeterminate choroidal melanocytic lesion. UWF-OCT successfully measured both tumor thickness and largest basal diameter (LBD) in 100% (31/31) of small and medium choroidal tumors, substantially outperforming SD-OCT (complete measurement achieved in 63.6% of small tumors, and 0% of medium or large tumors). UWF-OCT measurements were systematically smaller than ultrasonography (thickness: -32.3%, P < .01; LBD: -11.1%, P < .01) and MRI (thickness: -29.2%, P < .01). Mushroom-shaped tumor morphology was the strongest negative predictor of UWF-OCT quality (OR = 0.015, 95% CI 0.001-0.196, P < .01). UWF-OCT's complete measurability was limited in large tumors (12.5%, 1/8). CONCLUSIONS:UWF-OCT provides precise, noninvasive, single-scan assessment of small-to-medium choroidal tumors with detailed structural visualization. It may be particularly useful for dome-shaped tumors, while multimodal imaging with US and MRI remains optimal for complex morphologies. Overall, UWF-OCT represents a valuable tool for diagnosis and treatment planning, with potential utility for longitudinal follow-up in choroidal tumor management.

The accurate and timely diagnosis of inherited retinal diseases (IRDs) represents an unmet clinical need in ophthalmology, as the current pathways rely on resource-intensive phenotyping, multidisciplinary expertise and genetic testing. Here we developed Retina4IRD, an artificial intelligence (AI)-based clinician decision support system (CDSS) that predicts 17 genotype categories from retina images. Retina4IRD uses a Vision Transformer model pretrained with RETFound. We then trained and validated Retina4IRD using multimodal data with color fundus photographs and optical coherence tomography scans from 1,843 genetically confirmed patients (3,376 eyes) across China, South Korea and Poland. The top-5 prediction accuracy was 0.904 (95% confidence interval (CI): 0.896-0.912) and 0.856 (95% CI: 0.850-0.863) for internal and external validation, respectively. We conducted a randomized controlled trial with 300 participants with suspected IRD randomized 1:1 to either Retina4IRD-assisted specialist arm or specialist-only arm. Of these, 295 participants (median age 33 years, 114 (38.6%) females) with available next-generation sequencing reports were included in the final analysis. The primary outcome was met: top-5 genetic accuracy was significantly higher in the Retina4IRD-assisted specialist arm versus the specialist-only arm (88.5% versus 67.3%, P < 0.001). For secondary endpoints, top-1 to top-4 accuracies all favored the Retina4IRD-assisted specialist arm, with top-1 accuracy of 37.8% versus 22.4% and top-4 accuracy of 81.8% versus 53.1%, respectively. Post hoc analyses demonstrated that, with Retina4IRD assistance, clinicians made better management decisions, and the composite downstream management score indicated significantly higher scores relative to the control group (37.7 versus 28.5, P < 0.001). Our study shows that Retina4IRD is a CDSS tool prior to genetic testing and aligns with clinical workflow for patients with suspected IRDs. ClinicalTrials.gov identifier: NCT06839170 .

Background:This prospective, randomized, double-blind clinical trial aimed to evaluate the effects of Korean Red Ginseng (KRG) extract on the retinal microvascular parameters in patients with diabetic retinopathy (DR). Methods:Patients with mild to moderate non-proliferative DR were randomized to receive KRG extract or placebo for 90 days. Outcomes included changes in the best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), and optical coherence tomography angiography (OCTA) parameters, including the foveal avascular zone, vessel length density (VLD), and perfusion index (PI) in the superficial and deep capillary plexuses (SCP and DCP, respectively). The incidence of proliferative DR or diabetic macular edema (DME) was also monitored. Results:Twenty-four patients were enrolled and 23 completed the study. The baseline BCVA, IOP, CMT, and OCTA parameters were comparable between the groups (all p > 0.05). No significant changes were observed in BCVA, CMT, DR severity stage, or incidence of DME over the 3-month follow-up period in either group. Significant group × time interaction effects were observed for inferior DCP VLD (p = 0.011) and for PI in the superior (p = 0.044) and inferior (p = 0.026) DCP regions. No significant interaction effects were identified for SCP parameters or other DCP subfields. No adverse events were reported. Conclusions:KRG extract was associated with short-term, region-specific changes in OCTA-derived DCP perfusion metrics over 3 months. These findings reflect alterations in OCTA-derived microvascular parameters and do not establish modification of clinical outcomes such as DR progression or the development of DME. Trial registration:Clinical Research Information Service, #KCT0010991.

PURPOSE:To evaluate the treatment response and long-term prognosis of foveal serous retinal detachment (SRD) associated with inferior staphyloma to anti-vascular endothelial growth factor (anti-VEGF) treatment and photodynamic therapy (PDT). MATERIALS AND METHODS:Treatment-naïve patients who underwent >24 months of follow-up were included. We analyzed inter-visit changes in the foveal subretinal fluid (SRF) height after anti-VEGF treatment or PDT compared to no treatment and long-term prognosis of best-corrected visual acuity in choroidal neovascularization (CNV)-free patients. RESULTS:Nineteen patients were enrolled, and the mean follow-up duration was 4.81 years. In 14 CNV-free patients, 11 received anti-VEGF injections, three patients underwent PDT, and two patients had both treatments. During the follow-up period, there were a total of 243 inter-visit events (88 injections and 155 observations without treatment). At the last visit of patients who received the treatment, complete resolution was more significantly achieved in the CNV group than in the CNV-free group (p=0.028). In CNV-free patients, visual acuity improved when complete resolution was achieved; otherwise, it generally decreased. After adjusting for confounding factors, analyses showed no statistically significant differences in inter-visit changes of foveal SRF height between the anti-VEGF treatment and no treatment cases (absolute value, rate, subgroup categorized as ±20% of change; p=0.733, p=0.916, p=0.277; respectively). All patients who underwent PDT did not show complete resolution or maintained improvement of SRF. CONCLUSION:Treatment with anti-VEGF and PDT do not seem to be effective for foveal SRD of CNV-free inferior staphyloma.

BACKGROUND:Aggressive retinopathy of prematurity (A-ROP) poses a significant risk for visual impairment in preterm neonates, including those considered at low risk for ROP. Nonetheless, factors influencing A-ROP occurrence in low-risk preterm neonates remain underexplored. We aimed to identify oxygen therapy-related factors associated with A-ROP in this population. METHODS:This retrospective case-control study included low-risk preterm neonates (gestational age ≥30 weeks and birth weight ≥1 kg) treated for ROP between January 2005 and May 2023 at two Korean hospitals. Patients were divided into A-ROP and staged ROP groups, and oxygen therapy-related factors were analyzed using logistic regression. RESULTS:Of the 99 neonates included, 72% were diagnosed with A-ROP. No significant between-group differences were observed in the total duration of oxygen therapy or its delivery methods, except for non-invasive positive ventilation. Mean partial pressure of oxygen (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89-0.99) and its fluctuation (OR, 1.09; 95% CI, 1.03-1.15) were significant risk factors for A-ROP, with cutoff values of <52.8% and >82.3%, respectively. CONCLUSION:Maintaining stable oxygen levels while avoiding hypoxia may help reduce the risk for A-ROP in low-risk neonates requiring ROP treatment. These findings may help refine oxygen therapy guidelines in neonatal care to improve A-ROP prevention in this population. IMPACT STATEMENT:Aggressive retinopathy of prematurity (A-ROP) can significantly threaten vision, even in preterm neonates considered at low risk for ROP. The contributing factors to A-ROP in this low-risk population have been insufficiently investigated. This study is the first to identify peripheral oxygen levels and their fluctuations as significant factors associated with A-ROP development in low-risk preterm neonates requiring treatment. These findings highlight the importance of maintaining stable oxygenation and preventing hypoxia to reduce the risk of A-ROP in this population.

MYCN amplification without concurrent RB1 mutations characterizes a rare yet highly aggressive subtype of retinoblastoma; however, its precise developmental origins and therapeutic vulnerabilities remain incompletely understood. Here, we modeled this subtype by lentiviral-mediated MYCN overexpression in human pluripotent stem cell-derived retinal organoids, revealing a discrete developmental window (days 70-120) during which retinal progenitors showed heightened susceptibility to transformation. Tumors arising in this period exhibited robust proliferation, expressed SOX2, and lacked CRX, consistent with origin from primitive retinal progenitors. MYCN-overexpressing organoids generated stable cell lines that reproducibly gave rise to MYCN-driven tumors when xenografted into immunodeficient mice. Transcriptomic profiling demonstrated that MYCN-overexpressing organoids closely recapitulated molecular features of patient-derived MYCN-amplified retinoblastomas, particularly through activation of MYC/E2F and mTORC1 signaling pathways. Pharmacological screening further identified distinct therapeutic vulnerabilities, demonstrating distinct subtype-specific sensitivity of MYCN-driven cells to transcriptional inhibitors (THZ1, Flavopiridol) and the cell-cycle inhibitor Volasertib, indicative of a unique oncogene-addicted state compared to RB1-deficient retinoblastoma cells. Collectively, our study elucidates the developmental and molecular mechanisms underpinning MYCN-driven retinoblastoma, establishes a robust and clinically relevant human retinal organoid platform, and highlights targeted transcriptional inhibition as a promising therapeutic approach for this aggressive pediatric cancer subtype.

Few studies have comprehensively examined the clinical features of peripheral exudative hemorrhagic chorioretinopathy (PEHCR) due to its low prevalence. This study analyzed the clinical characteristics of patients diagnosed with PEHCR at a single center in Korea. We conducted a retrospective review of patient records from November 2005 to December 2020. The cohort included 36 patients (43 eyes), with a mean age of 70 years, and 67% were female. The mean initial best-corrected visual acuity was 0.95 logMAR (Snellen equivalent, 0.11). The most common initial symptom was decreased visual acuity, followed by floaters and visual field defects, while 26% of patients reported no ocular symptoms. Lesions were predominantly located in the inferotemporal (58%) and superotemporal quadrants (51%), with exudations being the most prevalent finding (65%). More than half of the patients (56%) were initially misdiagnosed with choroidal melanoma, while only 8% received the correct diagnosis of PEHCR. Of the 37 eyes (86%) that received treatment, 57% received anti-vascular endothelial growth factor injections, and 19% underwent vitrectomy. PEHCR is a rare degenerative condition with varied presentations in the peripheral retina, often leading to misdiagnosis and delayed treatment. Thus, careful monitoring and appropriate management are essential to minimize the risk of vision-threatening complications.

Abstract Background Posterior chamber intraocular lens (IOL) dislocation is a common complication of cataract surgery. Dislocated IOLs often require surgical intervention due to the potentially severe risks of leaving this condition untreated. If a patient with extremely low corneal endothelial cell density (ECD) presents with IOL dislocation, the surgeon faces a crucial dilemma of choosing the most optimal surgical treatment option. We sought to investigate the efficacy and safety of retropupillary iris claw intraocular lens (R-IOL) implantation in patients with IOL dislocation and extremely low (< 1000 cells/mm2) ECD. Methods We retrospectively reviewed the medical records of nine patients (all men) whose pre-operative ECD was < 1000 cells/mm2 and who underwent R-IOL implantation due to intraocular subluxation or total dislocation into the vitreous cavity between 2014 and 2020. We evaluated corneal endothelial function and visual outcomes after surgery. Results Nine patients were included in this study. The mean age at diagnosis was 64.89 ± 7.15 years (range 57–76 years), and the follow-up duration was 37.93 ± 23.72 months (range 18.07–89.07 months). No patients developed bullous keratopathy during follow-up. Compared to the initial ECD, corneal thickness (CT), coefficient variation of cell area (CV) and percentage of hexagonal cells (HEX), there was no statistically significant decrease in the ECD, CV, and HEX at last follow-up (P = 0.944, 0.778, 0.445, 0.443). There was significant improvement in the mean uncorrected distance visual acuity (UDVA) at the last follow-up (average 0.13 logMAR, 20/27 Snellen) compared to the pre-operative mean UDVA (average 1.09 logMAR, 20/250 Snellen) (P < 0.01). Conclusions R-IOL implantation did not result in a statistically significant decline in corneal endothelial function in patients with preoperatively low ECD, and it significantly improved the mean UDVA postoperatively. R-IOL implantation appears to be a safe and effective treatment modality for intraocular lens dislocation in patients with low ECD (< 1000 cells/mm²); however, long-term follow-up studies are warranted to corroborate these findings.

It is difficult to clearly distinguish clinical cases of punctate inner choroidopathy from multifocal choroiditis and panuveitis, even with the aid of diagnostic criteria. Reevaluating existing criteria and considering additional characteristics could improve diagnostic accuracy. Purpose:This retrospective case series aimed to assess the concordance between clinical diagnoses of punctate inner choroidopathy and multifocal choroiditis and panuveitis (MCP) using the 2021 Standardization of Uveitis Nomenclature Working Group criteria.Methods:Using the medical records of the patients, the authors reevaluated 100 eyes of 75 patients with idiopathic multifocal chorioretinal inflammatory lesions based on Standardization of Uveitis Nomenclature criteria and compared the result with the clinical diagnosis.Results:Of 100 eyes, 29 eyes (29%) were diagnosed as punctate inner choroidopathy and 15 eyes (15%) were diagnosed as MCP using Standardization of Uveitis Nomenclature criteria, and 56 (56%) eyes could not be diagnosed as either. Clinically diagnosed punctate inner choroidopathy eyes were significantly more myopic than the clinically diagnosed MCP eyes (mean spherical equivalent -6.65 +/- 4.63 vs. -3.85 +/- 2.31, P = 0.01). Sixteen eyes with vitreous inflammation were all clinically diagnosed as MCP, but four (25%) could not be diagnosed as MCP using Standardization of Uveitis Nomenclature criteria.Conclusion:The existing diagnostic criteria showed limitations in capturing all clinical cases of punctate inner choroidopathy or MCP, and adding or revising criteria on features such as vitreous inflammation or myopia could be considered to enhance diagnostic accuracy.

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.

BACKGROUND: Remnant cholesterol (remnant-C) levels during lipid-lowering therapy (LLT) may indicate residual risk. OBJECTIVE: We aimed to investigate the clinical outcomes based on on-treatment remnant-C distribution in patients with atherosclerotic cardiovascular disease (ASCVD) under statin-based LLT. METHODS: In this post hoc analysis of the RACING trial, 3,348 patients with ASCVD lipid profiles 1 year after randomization were investigated. Remnant-C was calculated as total cholesterol minus low- density lipoprotein cholesterol (LDL-C) minus high-density lipoprotein cholesterol. The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. RESULTS: The study population was grouped into tertiles according to on-treatment remnant-C: high ( > 20.5 mg/dL; n = 1,116), intermediate (14-20.5 mg/dL; n = 1,031), and low ( <= 14.0 mg/dL; n = 1,201) remnant-C groups. The high remnant-C group showed the highest incidence of the primary endpoint at 3 years (11.0%, 10.3%, and 7.5% in the high, intermediate, and low remnant-C groups, respectively; p = 0.009). The high remnant-C levels at 1 year were independently associated with an increased risk of the primary outcome, whereas achieving LDL-C < 55 or 70 mg/dL was not associated with the incidence of the primary endpoint. The on-treatment remnant-C cut-off of 17 mg/dL (median) demonstrated the ability to discriminate between patients at higher and lower risks for the primary endpoints (hazard ratio: 1.42; 95% confidence interval: 1.14-1.78; p = 0.002). CONCLUSIONS: In patients with ASCVD undergoing statin-based LLT, high on-treatment remnant-C values were associated with unfavorable clinical outcomes. On-treatment remnant-C levels may serve as an additional means of assessing residual cardiovascular risk. Clinical trial registration: ClinicalTrials. gov ID: NCT03044665. (c) 2024 National Lipid Association. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.