Glaucoma is a leading cause of irreversible blindness worldwide. One hallmark of glaucoma is the degeneration of retinal ganglion cells (RGCs). In this study, a dual role for growth hormone-releasing hormone receptor (GHRHR) modulation under glaucoma-relevant conditions and complementary injury paradigms involving the RGCs is identified. Using acute IOP elevation (retinal ischemia-reperfusion), chronic ocular hypertension (microbead-induced), and traumatic axonal injury (optic nerve crush) models, we show that GHRHR deficiency preserves RGC survival and uniquely restores visual functions-contrasting with GHRHR activation, which solely promotes cellular survival. Single-cell transcriptomic analysis uncovers RGC-specific alterations in genes associated with ferroptosis, lipid metabolism, oxidative stress, and mitochondrial dynamics. At the mechanistic level, GHRHR deficiency prevents the pathological downregulation of key anti-ferroptotic mediators GPX4 and FTH1 while suppressing pro-ferroptotic factors ACSL4 caused by glaucomatous neurodegeneration. This multifaceted regulation attenuated iron accumulation, lipid peroxidation, and reactive oxygen species (ROS) accumulation, effects that are diminished by the ferroptosis inducer RSL3. Notably, in mitochondria damaged primary RGCs, pharmacological GHRHR inhibition replicates these benefits, reducing lipid peroxidation and mitochondrial ROS to bolster RGC survival. Collectively, these findings establish GHRHR inhibition as a potent therapeutic strategy for glaucomatous neurodegeneration, synergistically rescuing both structural and functional integrity of the retina.

Central serous chorioretinopathy (CSC) is a major cause of vision loss, especially in middle-aged men, and its chronic subtype can lead to legal blindness. Despite its clinical importance, the underlying mechanisms of CSC need further clarification. In this study, we conducted a meta-analysis of three genome-wide association studies (GWASs) for CSC consisting of 8811 Asians and Caucasians, followed by replication in an additional 4338 Asians. We identified four genome-wide hits, including a novel hit (rs12960630 at LINC01924-CDH7, Pmeta = 2.97 × 10-9). A phenome-wide association study for rs12960630 showed a positive correlation between its CSC risk allele with plasma cortisol concentration. Expression/splicing quantitative trait loci (QTL) analyses showed an association of all these hits with the expression and/or splicing of genes in genital organs, which may explain the sex differences in CSC. Protein QTL also suggested the protein-level contribution of the complement factor H pathway to CSC pathogenesis.

BACKGROUND/OBJECTIVE This study aimed to evaluate the accuracy, comprehensiveness, and readability of responses generated by various Large Language Models (LLMs) (ChatGPT-3.5, Gemini, Claude 3, and GPT-4.0) in the clinical context of uveitis, utilizing a meticulous grading methodology. METHODS Twenty-seven clinical uveitis questions were presented individually to four Large Language Models (LLMs): ChatGPT (versions GPT-3.5 and GPT-4.0), Google Gemini, and Claude. Three experienced uveitis specialists independently assessed the responses for accuracy using a three-point scale across three rounds with a 48-hour wash-out interval. The final accuracy rating for each LLM response ('Excellent', 'Marginal', or 'Deficient') was determined through a majority consensus approach. Comprehensiveness was evaluated using a three-point scale for responses rated 'Excellent' in the final accuracy assessment. Readability was determined using the Flesch-Kincaid Grade Level formula. Statistical analyses were conducted to discern significant differences among LLMs, employing a significance threshold of p < 0.05. RESULTS Claude 3 and ChatGPT 4 demonstrated significantly higher accuracy compared to Gemini (p < 0.001). Claude 3 also showed the highest proportion of 'Excellent' ratings (96.3%), followed by ChatGPT 4 (88.9%). ChatGPT 3.5, Claude 3, and ChatGPT 4 had no responses rated as 'Deficient', unlike Gemini (14.8%) (p = 0.014). ChatGPT 4 exhibited greater comprehensiveness compared to Gemini (p = 0.008), and Claude 3 showed higher comprehensiveness compared to Gemini (p = 0.042). Gemini showed significantly better readability compared to ChatGPT 3.5, Claude 3, and ChatGPT 4 (p < 0.001). Gemini also had fewer words, letter characters, and sentences compared to ChatGPT 3.5 and Claude 3. CONCLUSIONS Our study highlights the outstanding performance of Claude 3 and ChatGPT 4 in providing precise and thorough information regarding uveitis, surpassing Gemini. ChatGPT 4 and Claude 3 emerge as pivotal tools in improving patient understanding and involvement in their uveitis healthcare journey.

To evaluate the clinical applicability of three generic Vision-Large-Language Models (VLLMs) — OpenAI’s GPT-4omni, GPT-4V(ision) and Google’s Gemini in detecting and diagnosing inherited retinal diseases (IRDs), using fundus photographs. The head-to-head comparative study curated 60 ultra-widefield (UWF) fundus images of 30 IRD patients from the National University Hospital, Singapore. Additionally, ten normal, open-sourced UWF fundus images were included for comparison. The 70 fundus images were analysed by the three VLLMs using standardised prompts to generate descriptions of 10 specified retinal features and provide clinical insights. Each VLLM received 2100 scores for descriptions across ten features, rated by three blinded consultant-level graders using three-point scale (0 = poor, 1 = borderline, 2 = good). Clinical insights including disease detection, diagnosis and pathological gene inference evaluated against clinical ground-truth. GPT-4o achieved the highest mean quality score in feature description (1.64 [0.697], mean [SEM]), outperforming GPT-4V (1.57 [0.738]) and Gemini (1.46 [0.800]; both p < 0.001). All models demonstrated high detection accuracy ( ≥ 81.4 ≤ 20.3 ≥ 97.1

Large language models (LLMs) show promise as clinical consultation tools and may assist optic neuritis patients, though research on their performance in this area is limited. Our study aims to assess and compare the performance of four commonly used LLM-Chatbots-Claude-2, ChatGPT-3.5, ChatGPT-4.0, and Google Bard-in addressing questions related to optic neuritis. We curated 24 optic neuritis-related questions and had three ophthalmologists rate the responses on two three-point scales for accuracy and comprehensiveness. We also assessed readability using four scales. The final results showed performance differences among the four LLM-Chatbots. The average total accuracy scores (out of 9): ChatGPT-4.0 (7.62 ± 0.86), Google Bard (7.42 ± 1.20), ChatGPT-3.5 (7.21 ± 0.70), Claude-2 (6.44 ± 1.07). ChatGPT-4.0 (p = 0.0006) and Google Bard (p = 0.0015) were significantly more accurate than Claude-2. Also, 62.5% of ChatGPT-4.0's responses were rated "Excellent," followed by 58.3% for Google Bard, both higher than Claude-2's 29.2% (all p ≤ 0.042) and ChatGPT-3.5's 41.7%. Both Claude-2 and Google Bard had 8.3% "Deficient" responses. The comprehensiveness scores were similar among the four LLMs (p = 0.1531). Note that all responses require at least a university-level reading proficiency. Large language models-Chatbots hold immense potential as clinical consultation tools for optic neuritis, but they require further refinement and proper evaluation strategies before deployment to ensure reliable and accurate performance.

Autosomal dominant optic atrophy (ADOA) caused by mutations in the nuclear-encoded OPA1 gene result in the preferential loss of retinal ganglion cells (RGCs) and progressive optic nerve degeneration. The severity of ADOA can be highly variable. This study compared the pathophysiological consequences of the c.1034 G > A OPA1 missense mutation and the c.1305+2delGT OPA1 deletion. There was a significant correlation between the severity of visual loss and the extent of macular RGC loss as determined by optical coherence tomography imaging. In cells transfected with the c.1034 G > A mutant, the percentage of fragmented mitochondria was greater than 60% with cytochrome c (cyt c) overflow, and significantly elevated levels of reactive oxygen species (ROS) and apoptosis. In contrast, the c.1305+2delGT mutant caused mitochondrial fragmentation in ~ 20% of HeLa cells, resulting in less cyt c overflow and apoptosis. The extent of mitochondrial network fragmentation and apoptosis increased with decreasing WT OPA1 mRNA expression levels. The c.1034 G > A OPA1 missense mutation is likely to induce a dominant-negative effect compared with haploinsufficiency with the c.1305+2delGT OPA1 deletion. These contrasting pathophysiological mechanisms could influence disease severity in ADOA through their differential consequences on mitochondrial structure and function. The small drug molecule Paromomycin was able to rescue the mitochondrial fragmentation induced by the c.1034 G > A mutation, providing proof-of-concept for further therapeutic validation in ADOA.

Convolutional Neural Networks (CNNs) have rapidly transformed the landscape of medical image analysis, particularly in the detection and management of diabetic retinopathy (DR), a leading cause of irreversible vision loss worldwide. Since their inception in early architectures such as LeNet and AlexNet, CNNs have evolved into advanced designs including VGGNet, Inception, ResNet, U‑Net, DenseNet, EfficientNet, and ConvNeXt, enabling increasingly precise classification, detection, and segmentation of retinal lesions. This systematic review synthesizes current evidence on CNN applications across diverse DR tasks, including disease classification, lesion localization, vessel segmentation, diabetic macular edema detection, ischemia assessment, and disease monitoring. Comparative analyses highlight the performance of CNNs relative to traditional machine learning methods, as well as the benefits of ensemble strategies and customized architectures tailored to multimodal imaging. Despite remarkable progress, real‑world deployment faces persistent challenges related to data quality, computational demands, interpretability, clinical reliability, and ethical considerations. Emerging solutions such as lightweight CNNs, hybrid models, and ensemble learning approaches aim to enhance scalability, efficiency, and clinical integration. The findings reveal both the transformative potential and the limitations of CNNs in DR management, underscoring the need for future research on robust, interpretable, and ethically aligned systems. This review provides ophthalmologists, data scientists, and healthcare practitioners with the latest insights into CNN‑based diabetic retinopathy analysis, fostering the advancement of accessible and clinically reliable diagnostic technologies poised to transform patient care and outcomes.

Purpose This study aims to evaluate and compare the diagnostic reasoning of five large language models (LLMs) in complex neuro-ophthalmological cases. We assessed the performance of GPT-o1 Pro, GPT-4o, Google Gemini, Grok 2 and DeepSeek in handling clinical scenarios related to neuro-ophthalmology.Method 18 clinical scenarios, derived from six complex neuro-ophthalmological cases, were presented to five LLMs: GPT-o1 Pro, GPT-4o, Google Gemini, Grok 2 and DeepSeek. The responses generated by these models were evaluated using the Revised-IDEA (R-IDEA) assessment tool. R-IDEA scores for high-quality responses ranged from 6 to 10, with ‘Excellent’ responses defined as those scoring between 8 and 10. In addition, the simplicity of each response was evaluated based on word count using a readability tool.Result GPT-o1 Pro (8.80) significantly outperformed GPT-4o (6.80) and Grok 2 (6.94) in the R-IDEA scores (p=0.001). It achieved 100% high-quality responses, compared with 72.2% for GPT-4o, 77.8% for Grok 2 and 83.3% for both Gemini and DeepSeek (p=0.175). Regarding ‘Excellent’ responses, GPT-o1 Pro achieved 88.9% of its responses rated as Excellent, significantly outperforming the other models: 27.8% for GPT-4o, 38.9% for Grok 2 and 55.6% for both Gemini and DeepSeek (p=0.003). GPT-o1 Pro used the fewest words, showing significant differences compared with GPT-4o (p<0.001) and Gemini (p=0.032).Conclusion The study underscores the superior clinical reasoning capabilities of ChatGPT-o1 Pro in neuro-ophthalmology compared with other LLMs, highlighting its potential for enhancing diagnostic processes in this complex field.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, disabling inflammatory disease of the central nervous system (CNS). Aquaporin-4 (AQP4)-specific T cells play a key role in the pathogenesis of NMOSD. In addition to immune factors, T cells recognizing the AQP4 epitope showed cross-reactivity with homologous peptide sequences in C. perfringens proteins, suggesting that the gut microbiota plays an integral role in the pathogenicity of NMOSD. In this review, we summarize research on the involvement of the gut microbiota in the pathophysiology of NMOSD and its possible pathogenic mechanisms. Among them, Clostridium perfringens and Streptococcus have been confirmed to play a role by multiple studies. Based on this evidence, metabolites produced by gut microbes, such as short-chain fatty acids (SCFAs), tryptophan (Trp), and bile acid (BA) metabolites, have also been found to affect immune cell metabolism. Therefore, the role of the gut microbiota in the pathophysiology of NMOSD is very important. Alterations in the composition of the gut microbiota can lead to pathological changes and alter the formation of microbiota-derived components and metabolites. It can serve as a biomarker for disease onset and progression and as a potential disease-modifying therapy.

BackgroundChina exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China’s pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks.MethodsRetrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny.ResultsVarious diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation.ConclusionThis investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19’s disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.

Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma, the leading cause of irreversible blindness. We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury. To investigate the underlying mechanism, in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor (4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole) by intravitreal injection. We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages. Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors. Furthermore, casein kinase-2 inhibition downregulated the expression of genes (Cck, Htrsa, Nef1, Htrlb, Prph, Chat, Slc18a3, Slc5a7, Scn1b, Crybb2, Tsga10ip, and Vstm21) involved in intraocular pressure elevation. Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.

OBJECTIVE:To identify the risk factors for the development of diabetic retinopathy (DR), diabetic macular edema (DME), and sight-threatening DR (STDR) based on a city-wide diabetes screening program.RESEARCH DESIGN AND METHODS:Diabetic patients were prospectively recruited between June 2016 and December 2022. All patients underwent dilated fundus photography centered on the disc and macula or macular spectral domain optical coherence tomography (SD-OCT) scan. Complete medical history was documented. Systematic examination, blood analysis, and urinalysis were performed. Multivariate logistic regression analysis adjusting for age and sex was conducted.RESULTS:Out of 7274 diabetic patients, 6840 had gradable images, among which 3054 (42.0%) were graded as DR, 1153 (15.9%) as DME, and 1500 (20.6%) as STDR. The factors associated with DR, DME, and STDR included younger age (odds ratio [OR]: 0.96, 0.97, and 0.96 respectively), lower BMI (OR: 0.97, 0.95, and 0.95 respectively), longer duration of diabetes (OR: 1.07, 1.03, and 1.05 respectively) and positive of urinary albumin (OR: 2.22, 2.56, and 2.88 respectively). Other associated factors included elevated blood urea nitrogen (OR: 1.22, 1.28, and 1.27 respectively), higher LDL-cholesterol, lower blood hemoglobin (OR: 0.98, 0.98, and 0.98), insulin intake, presence of diabetic foot pathologies and diabetic peripheral neuropathy. We also identified novel risk factors, including high serum potassium (OR: 1.37, 1.46, and 1.55 respectively), high-serum sodium (OR: 1.02, 1.02, and 1.04 respectively). Better family income was a protective factor for DR, DME, and STDR. Alcohol consumption once a week was also identified as a protective factor for DR.CONCLUSIONS:Similar risk factors for DR, DME, and STDR were found in this study. Our data also indicates high serum sodium, high serum potassium, low blood hemoglobin, and level of family income as novel associated factors for DR, DME, and STDR, which can help with DR monitoring and management.

Background and purpose The objective of this investigation was to assess the therapeutic efficacy of distinct glucocorticoid therapy dosages in the management of acute nonarteritic anterior ischemic optic neuropathy (NAION). Materials and methods This retrospective, unmasked, and non-randomized study included a total of 85 patients. The patients were categorized into four groups: Group 1 (control) consisted of 15 patients who did not receive glucocorticoids, Group 2 included 16 patients administered with oral prednisone at a dosage of 1 mg/kg/d for 14 days, Group 3 comprised 30 patients who received 250 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days, and Group 4 encompassed 24 patients who received 500 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days. The best-corrected visual acuity (BCVA) was assessed at baseline and the final follow-up (> 7 days post-treatment). The changes in visual acuity between baseline and the 7–14 day follow-up, as well as between baseline and the concluding appraisal, were employed as metrics for assessing the extent of visual enhancement. Results No significant differences were noted in the final visual outcomes or in the changes between final visual acuity and baseline across the four groups. In Group 1 (control), the best-corrected visual acuity (BCVA) remained unchanged during final follow-ups compared to baseline. Conversely, the intervention groups exhibited statistically significant enhancements in BCVA during final follow-up ( p = 0.012, p = 0.03, and p = 0.009 for Group 2, Group 3, and Group 4, respectively) when compared to baseline. During the 7–14 day follow-up, there was a significant difference in the changes between baseline BCVA and follow-up BCVA across the groups ( p = 0.035). Go a step further by Bonferroni correction for multiple comparisons, group 4 showed a greater change in vision compared with group1 ( p = 0.045). Conclusion Our study on acute nonarteritic anterior ischemic optic neuropathy (NAION) showed no significant final visual outcome differences. Nevertheless, Groups 2, 3, and 4 demonstrated improved best-corrected visual acuity (BCVA) during the final follow-up. Notably, a 500-unit dose of methylprednisolone resulted in short-term BCVA enhancement. This suggests potential consideration of 500 units of methylprednisolone for short-term NAION vision improvement, despite its limited long-term impact.

Objective This retrospective study aimed to investigate the clinical features of optic neuritis associated with COVID-19 (COVID-19 ON), comparing them with neuromyelitis optica-associated optic neuritis (NMO-ON), myelin oligodendrocyte glycoprotein-associated optic neuritis (MOG-ON), and antibody-negative optic neuritis (antibody-negative ON). Methods Data from 117 patients (145 eyes) with optic neuritis at the Shantou International Eye Center (March 2020-June 2023) were categorized into four groups based on etiology: Group 1 (neuromyelitis optica-related optic neuritis, NMO-ON), Group 2 (myelin oligodendrocyte glycoprotein optic neuritis, MOG-ON), Group 3 (antibody-negative optic neuritis, antibody-negative ON), and Group 4 (optic neuritis associated with COVID-19, COVID-19 ON). Characteristics of T2 and enhancement in orbital magnetic resonance imaging (MRI) were assessed. Best-corrected visual acuity (BCVA) was compared before treatment, at a short-term follow-up (14 days), and at the last follow-up after treatment. Results The COVID-19-associated optic neuritis (COVID-19 ON) group exhibited 100% bilateral involvement, significantly surpassing other groups (P < 0.001). Optic disk edema was observed in 100% of COVID-19 ON cases, markedly differing from neuromyelitis optica-related optic neuritis (NMO-ON) (P = 0.023). Orbital magnetic resonance imaging (MRI) revealed distinctive long-segment lesions without intracranial involvement in T1-enhanced sequences for the COVID-19 ON group compared to the other three groups (P < 0.001). Discrepancies in optic nerve sheath involvement were noted between the COVID-19 ON group and both NMO-ON and antibody-negative optic neuritis (antibody-negative ON) groups (P = 0.028). Before treatment, no significant difference in best-corrected visual acuity (BCVA) existed between the COVID-19 ON group and other groups. At the 14-day follow-up, BCVA in the COVID-19 ON group outperformed the NMO-ON (P < 0.001) and antibody-negative ON (P = 0.028) groups, with no significant difference observed compared to the myelin oligodendrocyte glycoprotein optic neuritis (MOG-ON) group. At the last follow-up after treatment, BCVA in the COVID-19 ON group significantly differed from the NMO-ON group (P < 0.001). Conclusion Optic neuritis associated with COVID-19 (COVID-19 ON) predominantly presents with bilateral onset and optic disk edema. Orbital magnetic resonance imaging (MRI) demonstrates that COVID-19 ON presents as long-segment enhancement without the involvement of the intracranial segment of the optic nerve in T1-enhanced images. Glucocorticoid therapy showed positive outcomes.

BACKGROUND:In this paper, we present a 9-year-old boy who demonstrates a complex interplay between myopia progression, axial length (AL) extension, and retinal nerve fiber layer (RNFL) thickness loss in both eyes. Additionally, concurrent optic neuritis has directly impacted RNFL thickness in his right eye, and its potential indirect influence on RNFL and macular ganglion cell layer (mGCL) thickness in his left eye is also noteworthy.CASE SUMMARY:A 9-year-old boy with bilateral myopia presented with diminished vision and pain in his right eye due to optic neuritis, while his left eye showed pseudopapilledema. Steroid therapy improved his vision in the right eye, and 16-mo follow-up revealed recovery without recurrence despite myopia progression. Follow-up optical coherence tomography conducted 16 mo later revealed a notable thinning of the RNFL in both eyes, especially along with a reduction in mGCL thickness in the left eye. This intricate interaction between optic neuritis, myopia, and retinal changes underscores the need for comprehensive management, highlighting potential long-term visual implications in young patients.CONCLUSION:The progression of myopia and AL extension led to the loss of RNFL thickness in both eyes in a 9-year-old boy. Concurrently, optic neuritis directly affected RNFL thickness in his right eye and may indirectly play a role in the thickness of RNFL and mGCL in his left eye.

To characterize the acute phase clinical manifestations and visual outcomes of the patients with Vogt-Koyanagi Harada (VKH) disease in southern China. In total, 186 patients with acute-onset VKH disease were recruited. The demographic data, clinical signs, ophthalmic examinations, and visual outcomes were analyzed. Among the 186 VKH patients, 3 were diagnosed as complete VKH, 125 as incomplete VKH, and 58 as probable VKH. All patients visited the hospital within 3 months of onset and complained of decreased vision. For the extraocular manifestations, 121 patients (65

Purpose. The aim of this study was to analyze choroidal vascular density alteration in high myopia with or without choroidal neovascularization by using optical coherence tomography angiography (OCTA). Methods. This was a cross-sectional, observational study that included 60 high-myopia eyes. All the participants had comprehensive ophthalmic assessments with visual acuity, intraocular pressure, slit lamp-assisted biomicroscopy, color fundus photography, axial length, optometry, and OCTA. Age, sex, and comorbidities were collected from their medical charts. Univariate and multiple analyses were made to compare the age, spherical equivalent, choroidal vascular density, gender, and choroidal thickness between normal and patients with choroidal neovascularization. Results. 60 eyes with high myopia were included in our study, including 30 eyes with choroidal neovascularization and 30 eyes without choroidal neovascularization or other fundus pathology. The mean age of high myopic patients was older in the choroidal neovascularization group than in the normal group (48.43 ± 19.06 years vs. 28.83 ± 9.92 years, p < 0.01). The mean choroidal thickness of high myopic patients was thinner in the neovascularization group than in the normal group (68.81 ± 48.81 μm vs. 137.80 ± 66.33 μm, p < 0.01). The mean choroidal vascular density in the normal group was greater than in the choroidal neovascularization group (82.43 ± 8.73 vs. 67.54 ± 12.56, p < 0.01). There was no significant difference in spherical equivalent between the choroidal neovascularization group and the normal group (−10.56 ± 2.97D vs. −11.93 ± 3.38D, p = 0.11). Multivariate analysis showed that after adjusting for covariates, less choroidal vascular density and older age were independent factors associated with choroidal neovascularization in the high myopic eye. Conclusion. Decreased choroidal vascular density and older age played an important role in the development of choroidal neovascularization in high myopic eyes. OCTA may help us to identify the highly myopic patients that need to intervene.

Deep neural network-based programs can be applied to protein structure modeling by inputting amino acid sequences. Here, we aimed to evaluate the AlphaFold2-modeled myocilin wild-type and variant protein structures and compare to the experimentally determined protein structures. Molecular dynamic and ligand binding properties of the experimentally determined and AlphaFold2-modeled protein structures were also analyzed. AlphaFold2-modeled myocilin variant protein structures showed high similarities in overall structure to the experimentally determined mutant protein structures, but the orientations and geometries of amino acid side chains were slightly different. The olfactomedin-like domain of the modeled missense variant protein structures showed fewer folding changes than the nonsense variant when compared to the predicted wild-type protein structure. Differences were also observed in molecular dynamics and ligand binding sites between the AlphaFold2-modeled and experimentally determined structures as well as between the wild-type and variant structures. In summary, the folding of the AlphaFold2-modeled MYOC variant protein structures could be similar to that determined by the experiments but with differences in amino acid side chain orientations and geometries. Careful comparisons with experimentally determined structures are needed before the applications of the in silico modeled variant protein structures.

The retinal ganglion cells (RGCs) are the sole output neurons that connect information from the retina to the brain. Optic neuropathies such as glaucoma, trauma, inflammation, ischemia and hereditary optic neuropathy can cause RGC loss and axon damage, and lead to partial or total loss of vision, which is an irreversible process in mammals. The accurate diagnoses of optic neuropathies are crucial for timely treatments to prevent irrevocable RGCs loss. After severe ON damage in optic neuropathies, promoting RGC axon regeneration is vital for restoring vision. Clearance of neuronal debris, decreased intrinsic growth capacity, and the presence of inhibitory factors have been shown to contribute to the failure of post-traumatic CNS regeneration. Here, we review the current understanding of manifestations and treatments of various common optic neuropathies. We also summarise the current known mechanisms of RGC survival and axon regeneration in mammals, including specific intrinsic signalling pathways, key transcription factors, reprogramming genes, inflammation-related regeneration factors, stem cell therapy, and combination therapies. Significant differences in RGC subtypes in survival and regenerative capacity after injury have also been found. Finally, we highlight the developmental states and non-mammalian species that are capable of regenerating RGC axons after injury, and cellular state reprogramming for neural repair.