PurposeThe purpose of this study was to investigate the impact of myopia on regional visual field (VF) loss and progression in glaucoma.MethodsWe included 112,633 24-2 VFs; longitudinal analyses comprised patients with at least 5 reliable VFs over 4 years. The degree of myopia was measured by spherical equivalent (SE) extracted from VF testing. Linear and Cox regressions determined the impact of myopia on regional VF loss and progression, respectively. We calculated three VF progression outcomes: (1) mean deviation (MD) progression: MD slope <0; (2) total deviation (TD) pointwise progression: at least 3 TD locations with TD slope ≤−1 decibels (dB)/year; (3) MD fast progression: MD slope ≤−1 dB/year (P value < 0.05). Longitudinal analyses were conducted for all subjects and with exclusion of patients with high myopia (SE ≤−6.00 diopters [D]).ResultsMore negative SE values were associated with worse TD values in the paracentral VF region (up to −0.14 dB/D). A more negative SE is associated MD (odds ratio [OR] = 0.95), TD pointwise (OR = 0.96), and MD fast progression (OR = 0.94; P < 0.001). Results were comparable when excluding patients with high myopia (P < 0.001): MD (OR = 0.95), VFI (OR = 0.95), and MD fast progression (OR = 0.94).ConclusionsLower SE values are associated with worse paracentral VF loss. Worse myopia is associated with functional progression, even when excluding patients with high myopia.Translational RelevanceWe provide evidence for the relationship between SE and VF progression and inform clinical practice by highlighting even mild myopia as a highly prevalent possible risk factor for glaucoma progression.

Noninvasive transcranial electrical stimulation (tES) of the primary visual cortex can reduce crowding in peripheral vision. We investigated the effect of two tES protocols, visual cortex transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS), on reading using peripheral vision, a task that is limited by visual crowding. A double-blind, placebo-controlled experimental design was used. Forty-one heathy adults with normal visual acuity completed one active and one sham tES session. During each session, English sentences were presented one word at a time 10 degrees below fixation. The proportion of words read correctly was assessed before, during, after and 30 minutes after real or sham tDCS (n = 21) or tRNS (n = 20). The tRNS elicited a small but significant performance benefit (P = 0.035), whereas tDCS had no effect. Strong within-session learning effects were observed for all conditions (P = 0.001). These results add to a growing body of evidence indicating that noninvasive stimulation of the visual cortex can enhance visual processing and may have applications in vision rehabilitation. Noninvasive brain stimulation may enhance how the brain processes visual input from a diseased eye, complementing standard eye-based treatments of retinal and macular diseases.

PurposeThe purpose of this study was to predict the vault of implantable collamer lens using artificial intelligence (AI) and interpret the contributions of each parameter.MethodsExtreme Gradient Boosting (XGBoost), a machine learning algorithm, was applied to construct a vault prediction model. The dataset included 247 eyes from Peking University Third Hospital, split into training and test sets (4:1), plus 50 eyes from Beau Care Clinic for external validation. The model was trained and tested by samples with missing and anomalous values to enhance its robustness. Model performance was assessed using mean absolute error (MAE), root mean square error (RMSE), and median absolute error (MedAE). SHapley Additive exPlanations (SHAP) was used to interpret the model’s predictions.ResultsWe found weak linear correlation between preoperative parameters and vaults (all |r| ≤ 0.30). Therefore, a nonlinear model was constructed. It achieved the following performance on the test set: MAE = 117.85 µm, RMSE = 146.92 µm, and MedAE = 108.94 µm. On the external validation set, corresponding metrics were 130.99 µm, 154.24 µm, and 116.51 µm, respectively. SHAP revealed horizontal sulcus-to-sulcus distance (STS), horizontal compression (HC), anterior chamber depth (ACD), and white-to-white distance (WTW) had positive influences on the vault, whereas lens thickness (LT) and crystalline lens rise (CLR) had negative effects. Female subjects also tended to have higher vaults.ConclusionsA low parameter-dependent implantable collamer lens (ICL) vault prediction model which exhibits great robustness was constructed.Translational RelevanceThe use of AI to predict the vault after ICL implantation can reduce the abnormal postoperative vault and improve the safety of ICL implantation.

PurposeTo develop an in vitro model that mimics aspects of corneal healing in humans for uncovering key mechanisms involved in the mechanisms involved in the healing and scarring processes.MethodsAs part of the healing matrix, TGF-β1–induced and corneal-derived myofibroblasts were cultured in fibrin hydrogels with configurations that recapitulate the healthy (aligned) and wounded (random) microenvironment of the cornea.ResultsEvaluation of cellular alpha smooth muscle actin (α-SMA) and collagen hybridizing peptide (CHP) showed cell and matrix alignment, respectively. The aligned compared to the random constructs demonstrated an increased ability to synthesize total soluble proteins, including collagen type V, but collagen type I levels were reduced. This finding reveals a differential pattern for these proteins. Additionally, the collagen fibril diameters were larger in the aligned tissue constructs compared to the random constructs. Fibronectin and CHP colocalization patterns did not differ between groups; however, fibronectin and decorin were increased in the aligned group in contrast to tenascin C, which showed no difference.ConclusionsThese findings suggest that the alignment of the healing microenvironment plays a crucial role in modulating the structural properties of the extracellular matrix (ECM) and regulates the synthesis of key proteins that are closely involved in fibrillogenesis and are indicative of the quality of the deposited ECM.Translational RelevanceWe developed a three-dimensional in vitro model that closely mimics in vivo conditions to investigate the role of corneal myofibroblasts in healing and regeneration. Ultimately, this model can help develop targeted antifibrotic therapies to prevent corneal scarring.

To investigate adaptive changes in retinal and choroidal vasculature with increasing retinal surface area in myopia. Widefield optical coherence tomographyangiographyand enhanced depth imaging (EDI)-OCT images of the retina were used to acquire digital images of the choroidal and retinal vasculature in 32 eyes with axial myopia and 14 emmetropic control population eyes. Retinal vessel density was calculated using Otsu's method and used for quantitative comparison of retinal vascular architecture and perfusion ability with increasing retinal surface area. The choroidal vascularity index was also calculated from skeletonized 15 × 9 mm swept-source EDI-OCT images. Correlations were sought between increasing myopia and the retinal vessel density and choroidal vascularity index. Increased axial myopia was negatively correlated with retinal vessel density (r2 = 0.35, P < 0.001) and positively correlated with choroidal vascularity index (r2 = 0.31, P < 0.001). Increased retinal surface area in myopia results in decreased retinal vascular surface coverage. The inadequacy of retinal vascular coverage is compensated for by increased choroidal vascularity index in high myopes. This adaptive change may enable oxygen diffusion from choroidal vessels to the relatively thinner retina, thereby supplementing the oxygen needs of the inner retinal neurons. Adaptive changes in the choroidal vessels to supply more oxygen to the inner retina can explain why myopic patients exhibit a decreased risk of diabetic retinopathy and its vision-threatening complications despite being vulnerable due to inadequate retinal vascular coverage.

The purpose of this study was to investigate aqueous humor total antioxidant capacity (TAC) and ascorbic acid (AA) levels of patients with diabetic retinopathy (DR), and their correlation with serum glycated hemoglobin (HbA1c) levels. This case-control study enrolled 177 eyes from 177 patients that underwent cataract surgery between April 2019 and November 2022 in Chang Gung Memorial Hospital. Group 1 comprised 103 eyes from patients without diabetes; group 2 comprised 40 eyes from patients with diabetes but without DR; and group 3 comprised 34 eyes from patients with DR. Aqueous humor samples were collected and analyzed for TAC and AA levels using the ferric reducing/antioxidant AA assay. Aqueous humor TAC and AA levels were decreased in group 3 compared with group 2 and group 1 (P < 0.001 and P < 0.001). Aqueous humor TAC and AA levels were independent protective factors against DR in the diabetes population, with adjusted odds ratios of 0.109 (95% confidence interval [CI] = 0.017-0.719, P = 0.021) and 0.095 (95% CI = 0.012-0.726, P = 0.023), respectively. Aqueous humor TAC and AA concentrations were weakly negatively correlated with serum HbA1c levels, with Pearson's correlation coefficients of -0.339 (P = 0.013) and -0.341 (P = 0.012), respectively. TAC and AA had protective effects against DR. Decreased aqueous humor TAC and AA levels may serve as potential biomarkers for DR among the diabetes population. This study highlights the role of antioxidants in DR and provides foundation for future research on AA supplementation's potential for the prophylaxis and treatment of DR.

The purpose of this study was to assess large language models (LLMs) for enhancing the readability of online patient education materials (PEMs) on pediatric cataracts through multilingual adaptation, content retrieval, and prompt engineering. This study included 103 PEMs presented in different languages and retrieved from diverse resources. Three LLMs (ChatGPT-4o, Gemini 2.0, and DeepSeek-R1) were used for content improvement. Readability was assessed for both the original and converted PEMs with multiple formulas. Different prompt engineering strategies for LLMs were also tested in this study. The PEMs directly generated by LLMs exceeded a 10th grade reading level. Compared to a traditional Google search, LLMs' web browsing feature provided online PEMs with better characteristics and a higher reading level. Original PEMs from Google showed significantly improved readability after LLM conversion, with DeepSeek-R1 achieving the greatest reduction in reading level from 10.59 ± 2.20 to 7.01 ± 0.91 (P < 0.001). Prompt engineering also showed statistically significant results in their effects on LLM conversion, and Zero-shot-Cot (APE) successfully achieving target readability below the sixth grade reading level. Besides, the LLMs' simplified Chinese conversion, as well as the LLMs conversion of other original Chinese PEMs, both showed that they meet the recommended standards for reading levels in multiple dimensions. LLMs can significantly enhance the readability of multilingual online PEMs on pediatric cataract. Combining it with web browsing and prompt engineering can further optimize outcomes and advance patient education. This study links LLMs with patient education and demonstrates their potential to significantly improve the readability of online PEMs.

This study aims to understand the differences in cellular and molecular patterns between the Main and Accessory (Acc) regions of pterygium tissue, with a focus on inflammation and mitochondrial energy metabolism. We collected bulk RNA sequencing (RNA-seq) data from six pterygium patients and single-cell RNA-seq data from two pterygium patients. Subsequently, we investigated pathway enrichment, pathway correlation, differential gene expression, protein-protein interactions, and cell-cell communication in pterygium. Bulk RNA-seq analysis revealed distinct expression patterns in the Acc group compared to the Main and control groups. This finding suggested the need to separate the Main and Acc regions within pterygium samples and use single-cell data to understand differences between the Main and control groups that bulk data could not capture. The single-cell data identified a cluster of epithelial cells containing only pterygium samples, which contributed significantly to the ANGPTL, IL1, and KLK signaling networks. Cells involved in inflammatory pathways associated with the integrated stress response and the renin-angiotensin-aldosterone system, both of which exhibited high correlations with energy metabolism-associated pathways, were significantly upregulated. Additionally, expression changes in multiple proinflammatory, antioxidant, and immune-associated genes were identified. The distinctions between the Main and Acc groups suggest the necessity of distinguishing anatomical regions in future pterygium studies. Additionally, the pivotal role of epithelial cells from the Main group in the inflammation of pterygium indicates a potential clinical approach for managing the disease. This study aims to identify apex-specific biomarkers of pterygium for a more efficient diagnosis and treatment.

To propose a new parameter for evaluating lamina cribrosa (LC) morphology in myopic eyes with optic nerve head (ONH) distortion. This study included 169 eyes with normal-tension glaucoma (NTG) and myopic ONH distortion from the Myopic NTG Treatment Study. The LC curvature index (LCCI) and the LC steepness index (LCSI) were assessed in optical coherence tomography B-scan images obtained using an enhanced-depth imaging technique. These were measured as the curvature of the anterior LC surface within Bruch's membrane opening and as the slant of the temporal anterior LC surface relative to the plane of the anterior scleral opening, respectively. The LCSI was strongly correlated with the LCCI (R2 = 0.594, P < 0.001). A larger LCSI was associated with a thinner LC (P = 0.021) and narrower peripapillary γ-zone (P < 0.001). Neither the LCCI nor the LCSI was associated with the severity of visual field (VF) damage. A thinner LC (P = 0.009), and thinner retinal nerve fiber layer (P < 0.001) were significantly associated with worse VF mean deviation. The strong correlation between the LCCI and LCSI indicates that the latter may substitute the former for evaluating LC morphology in myopic eyes where ONH distortion blocks the visibility of the whole LC. The LCSI may serve as a reliable biomarker for assessing LC deformation in myopic eyes with optic nerve head distortion, enhancing evaluations when visibility is limited.

PurposeActivating pyruvate kinase M2 (PKM2) has been shown to be neuroprotective in preclinical models of photoreceptor degeneration. We recently developed novel, small molecule activators for ocular delivery. Here, we sought to characterize the ocular pharmacology, toxicity, and efficacy of MCTI-566, a novel PKM2 activator, to translate this therapeutic strategy to the clinic.MethodsX-ray protein crystallography and isothermal titration calorimetry assessed the interaction of MCTI-566 with PKM2. PKM2 activation and tissue pharmacokinetics were examined after intravitreal or systemic administration of MCTI-566. Retinal toxicity was evaluated in rats after intravitreal injection. The effect of MCTI-566 on photoreceptor death was assessed using in vitro and in vivo models of outer retinal stress and on the inflammatory response in the rd10 retina using flow cytometry and quantitative real-time polymerase chain reaction.ResultsThe PKM2-MCTI-566 co-crystal structure demonstrated a binding pocket distinct from endogenous activators. MCTI-566 increases retinal PK activity 200% following intravitreal or systemic administration. MCTI-566 distributed to the retina after intravitreal or systemic administration, activated the target for ≥90 days and was specific for photoreceptor PKM2. No retinal toxicity was observed after repeated intravitreal administration. MCTI-566 reduced photoreceptor apoptosis in a model of retinal detachment, and delayed photoreceptor degeneration and altered the inflammatory response in the rd10 retina.ConclusionsMCTI-566 is a small molecule drug candidate for photoreceptor neuroprotection.Translational RelevanceMCTI-566, a long-acting and well-tolerated ocular PKM2 activator, may be a potential therapeutic to combat currently untreatable retinal degenerations.