Translational Vision Science & Technology最新文献

{"title":"The Impact of Myopia on Regional Visual Field Loss and Progression in Glaucoma.","authors":"Anagha Lokhande, Luo Song, Yueyin Pang, Yan Luo, Louis R Pasquale, Sarah R Wellik, Carlos Gustavo De Moraes, Jonathan S Myers, Mohammad Eslami, Tobias Elze, Lucy Q Shen, Nazlee Zebardast, David S Friedman, Michael V Boland, Mengyu Wang","doi":"10.1167/tvst.14.9.34","DOIUrl":"10.1167/tvst.14.9.34","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the impact of myopia on regional visual field (VF) loss and progression in glaucoma.</p><p><strong>Methods: </strong>We 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]).</p><p><strong>Results: </strong>More 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).</p><p><strong>Conclusions: </strong>Lower SE values are associated with worse paracentral VF loss. Worse myopia is associated with functional progression, even when excluding patients with high myopia.</p><p><strong>Translational relevance: </strong>We 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.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 9","pages":"34"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained Benefit of Short-Term Levodopa Treatment on Inner Retinal Function in Patients With Diabetes.","authors":"Francesca Moore, Stephen Phillips, Dane Rubenstein, Caleigh Cullinan, Christina Young, Andrew J Feola, Xiaxian Ou, Xiangqin Cui, Risha Patel, Mary Rhee, Andrew Hendrick, Machelle T Pardue","doi":"10.1167/tvst.14.9.5","DOIUrl":"10.1167/tvst.14.9.5","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigated the long-term progression of oscillatory potential (OP) implicit times (ITs) in individuals with preclinical diabetic retinopathy (DR) with and without levodopa (L-DOPA) treatment by quantifying functional and structural retinal changes.</p><p><strong>Methods: </strong>Participants from the Motz et al. (2020) study were re-evaluated after 5 years, including individuals with diabetes mellitus (DM) who received L-DOPA treatment for 2 weeks (the DM + L-DOPA group; n = 14), those who did not (the DM group; n = 6), and non-diabetic healthy controls (the control group; n = 37). Retinal function and structure were assessed using dim-flash electroretinography (ERG) and optical coherence tomography (OCT).</p><p><strong>Results: </strong>After 5 years, OP 1 and OP 2 ITs showed no significant differences among the groups (P > 0.05). The DM + L-DOPA OP IT values remained improved compared to baseline. The outer region thickness of the outer plexus layer (OPL) and ganglion cell layer (GCL) were significantly thinner in the DM + L-DOPA group compared to the DM group (P < 0.05). The DM group showed strong correlations between OP IT and OCT thickness across all retinal regions, whereas the DM + L-DOPA group correlations were similar to the control group.</p><p><strong>Conclusions: </strong>Short-term L-DOPA treatment led to significant functional improvements after 2 weeks, with trends suggesting sustained benefit over 5 years. Inner retinal structural differences suggest potential long-term benefit of L-DOPA on retinal health. These findings support OP IT delays as early biomarkers for preclinical DR and suggest L-DOPA may provide lasting neuroprotective benefits.</p><p><strong>Translational relevance: </strong>Retinal dysfunction and inner retinal structural changes could be potential biomarkers for preclinical DR, and L-DOPA treatment may provide sustained benefits for the diabetic retina.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 9","pages":"5"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of 10-2 Visual Field Using Melbourne Rapid Fields Online Perimetry and Humphrey Field Analyzer.","authors":"Kae Sugihara, Yu Xiang George Kong, Mitsuto Hosokawa, Toshio Okanouchi","doi":"10.1167/tvst.14.9.14","DOIUrl":"10.1167/tvst.14.9.14","url":null,"abstract":"<p><strong>Purpose: </strong>Melbourne rapid fields (MRF) online perimetry is web-based software that allows white-on-white threshold perimetry using any computer. This study assesses the perimetric outcomes of MRF10-2 protocol via laptop computer in comparison to Humphrey field analyzer (HFA).</p><p><strong>Methods: </strong>This prospective and cross-sectional study included 91 eyes from 91 Japanese glaucoma patients. MRF10-2 visual field (VF) results were compared to HFA10-2 the Swedish Interactive Thresholding Algorithm (SITA)-Standard, including mean deviation (MD), pattern deviation (PD), and reliability indexes. To assess test-retest reliability, patients completed two MRF assessments.</p><p><strong>Results: </strong>MRF demonstrated high level of agreement with HFA in evaluating MD (intraclass correlation coefficient [ICC] = 0.97 [95% confidence interval {CI}, 0.96-0.98]) and pattern standard deviation (PSD; ICC = 0.94 [95% CI, 0.92-0.96]). Bland-Altman analysis revealed a mean bias of -1.31 decibels (dB) (95% limits of agreement [LoA] = -7.21 dB, 4.59 dB) for MD and 0.71 dB (LoA = -3.55 dB, 4.97 dB) for PSD. It also demonstrated good MRF repeatability with a mean bias of 0.39 dB (LoA = -2.34 dB, 3.00 dB) for MD and -0.21 dB (LoA = -2.36 dB, 1.94 dB) for PSD. False-positives and -negatives were not statistically different between the two devices. MRF test time was significantly shorter than HFA (P < 0.001).</p><p><strong>Conclusions: </strong>MRF10-2 online perimetry offers portable approach for central VF assessment, but its measurements are not directly interchangeable with HFA and may exhibit higher variability, warranting caution in clinical interpretation.</p><p><strong>Translational relevance: </strong>The novel protocol of portable online perimetry approach will assess central VF defects when standard equipment is unavailable.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 9","pages":"14"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12429677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macular Optical Coherence Tomography Parameters and Incident Glaucoma Among Myopic Eyes.","authors":"Wei Ma, Xinyi Li, Liqing Xie, Feng Jiang, Mingguang He, Decai Wang, Zhixi Li","doi":"10.1167/tvst.14.9.12","DOIUrl":"10.1167/tvst.14.9.12","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to estimate the correlations between macular optical coherence tomography (OCT)-derived metrics and incident glaucoma risk in myopic eyes.</p><p><strong>Methods: </strong>This longitudinal observational study included 24,181 individuals with myopia (spherical equivalence [SE] ≤ -0.5 diopters [D]) from the UK Biobank study.</p><p><strong>Results: </strong>Participants (mean age = 55.5 ± 8.0 years, 54.5% women) were followed up for 13.2 ± 1.2 years and incident glaucoma was diagnosed in 582 eyes. Those who developed glaucoma were significantly older (P < 0.001), more likely to be male participants (P < 0.001), and had more pronounced myopic refractive error (P < 0.001). Cox regression analyses indicated that participants with thinner retinal nerve fiber layer (RNFL; hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.96-0.99, P < 0.001), thinner ganglion cell-inner plexiform layer (GCIPL; HR = 0.97, 95% CI = 0.96-0.98, P < 0.001), and thinner ganglion cell complex (GCC; HR = 0.98, 95% CI = 0.97-0.99, P < 0.001) had an increasing risk of incident glaucoma after adjustment for age, sex, ethnic group, and SE. Meanwhile, the thicker inner nuclear layer (INL; HR = 1.03, 95% CI = 1.01-1.05, P = 0.002) and photoreceptor segments (PS; HR = 1.03, 95% CI = 1.01-1.06, P = 0.024) were positive for the incidence of glaucoma.</p><p><strong>Conclusions: </strong>This longitudinal study suggested that baseline RNFL, GCIPL, GCC, INL, and PS thickness were significant predictors for the incidence of glaucoma among myopic participants, which indicated a pattern of internal layer thinning (except INL) and outer layer thickening in these pre-glaucoma participants.</p><p><strong>Translational relevance: </strong>Our study highlighted the potential of OCT-derived indicators for early glaucoma risk assessment and clinical monitoring.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 9","pages":"12"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Question-Answering in Ophthalmology With Retrieval-Augmented Generation: Benchmarking Open-Source and Proprietary Large Language Models.","authors":"Quang Nguyen, Duy-Anh Nguyen, Khang Dang, Siyin Liu, Sophia Y Wang, William A Woof, Peter B M Thomas, Praveen J Patel, Konstantinos Balaskas, Johan H Thygesen, Honghan Wu, Nikolas Pontikos","doi":"10.1167/tvst.14.9.18","DOIUrl":"10.1167/tvst.14.9.18","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to evaluate the application of combining information retrieval with text generation using Retrieval-Augmented Generation (RAG) to benchmark the performance of open-source and proprietary generative large language models (LLMs) in question-answering in ophthalmology.</p><p><strong>Methods: </strong>Our dataset comprised 260 multiple-choice questions sourced from two question-answer banks designed to assess ophthalmic knowledge: the American Academy of Ophthalmology's (AAO) Basic and Clinical Science Course (BCSC) Self-Assessment program and OphthoQuestions. Our RAG pipeline retrieves documents in the BCSC companion textbook using ChromaDB, followed by reranking with Cohere to refine the context provided to the LLMs. Generative Pretrained Transformer (GPT)-4-turbo and 3 open-source models (Llama-3-70B, Gemma-2-27B, and Mixtral-8 × 7B) are benchmarked using zero-shot, zero-shot with Chain-of-Thought (zero-shot-CoT), and RAG. Model performance is evaluated using accuracy on the two datasets. Quantization is applied to improve the efficiency of the open-source models. Effects of quantization level are also measured.</p><p><strong>Results: </strong>Using RAG, GPT-4-turbo's accuracy increased by 11.54% on BCSC and by 10.96% on OphthoQuestions. Importantly, the RAG pipeline greatly enhances overall performance of Llama-3 by 23.85%, Gemma-2 by 17.11%, and Mixtral-8 × 7B by 22.11%. Zero-shot-CoT had overall no significant improvement on the models' performance. Quantization using 4 bit was shown to be as effective as using 8 bits while requiring half the resources.</p><p><strong>Conclusions: </strong>Our work demonstrates that integrating RAG significantly enhances LLM accuracy especially for smaller LLMs.</p><p><strong>Translation relevance: </strong>Using our RAG, smaller privacy-preserving open-source LLMs can be run in sensitive and resource-constrained environments, such as within hospitals, offering a viable alternative to cloud-based LLMs like GPT-4-turbo.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 9","pages":"18"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Subconjunctivally Applied Everolimus- and Sirolimus-Pretreated MSCs in Preventing Diabetic Retinopathy.","authors":"Ji Seung Jung, Hyo Youn Jo, Jiyi Hwang, Donghee Kim, Myeongjee Kwon, Jungyeon Yong, Haerin Yoon, Hyun Jik Lee, Kyung-Mee Park","doi":"10.1167/tvst.14.9.19","DOIUrl":"10.1167/tvst.14.9.19","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic retinopathy (DR) is a leading cause of vision impairment in diabetic patients. This study investigates the preventive effects of subconjunctivally applied mesenchymal stem cells (MSCs) pretreated with mammalian target of rapamycin (mTOR) inhibitors on DR.</p><p><strong>Methods: </strong>Thirty-six male Sprague-Dawley rats were used, with diabetes induced by a single intraperitoneal injection of streptozotocin (STZ) at 55 mg/kg. Four groups were established: diabetic control, MSC-treated, everolimus-pretreated MSC-treated (MSC-E), and sirolimus-pretreated MSC-treated (MSC-S). Each treated group received subconjunctival injections of 1 × 106 MSCs in 30 µL phosphate-buffered saline at 3, 5, and 7 weeks post-STZ. Electroretinography (ERG) was performed at 2 and 8 weeks post-STZ. At 11 weeks, cataract formation, uveitis grading, and retinal histology were assessed.</p><p><strong>Results: </strong>mTOR inhibitor-pretreated MSCs significantly prevented the decline in retinal function compared to untreated MSCs and diabetic controls. Everolimus-pretreated MSCs tended to show higher ERG flicker amplitudes than sirolimus-pretreated MSCs, although the difference was not statistically significant. Histologically, both pretreated groups showed preserved thickness in the outer plexiform and nuclear layers, suggesting protection against retinal damage.</p><p><strong>Conclusions: </strong>Subconjunctival application of MSCs pretreated with mTOR inhibitors may help prevent DR progression, with everolimus showing a potential advantage in preserving retinal function.</p><p><strong>Translational relevance: </strong>These findings suggest that mTOR inhibitor-pretreated MSCs could be a viable therapeutic strategy for DR, warranting further clinical trials to confirm efficacy and safety in humans.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 9","pages":"19"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Artificial Intelligence to Predict Implantable Collamer Lens Vault: A Low Parameter-Dependent Model for Better Surgical Outcomes.","authors":"Peien Sheng, Yinan Liu, Mingyue Shen, Yuxi Shi, Bowei Yuan, Zhan Shen, Xiaoyong Chen","doi":"10.1167/tvst.14.9.32","DOIUrl":"10.1167/tvst.14.9.32","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to predict the vault of implantable collamer lens using artificial intelligence (AI) and interpret the contributions of each parameter.</p><p><strong>Methods: </strong>Extreme 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.</p><p><strong>Results: </strong>We 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.</p><p><strong>Conclusions: </strong>A low parameter-dependent implantable collamer lens (ICL) vault prediction model which exhibits great robustness was constructed.</p><p><strong>Translational relevance: </strong>The use of AI to predict the vault after ICL implantation can reduce the abnormal postoperative vault and improve the safety of ICL implantation.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 9","pages":"32"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Action Spectrum of Visible Light for Human Lens Epithelial Cell Migration In Vitro.","authors":"Hiromi Miyoshi, Masafumi Otomo, Aki Nishida, Takuto Suzuki, Masashi Yamazaki, Yuki Tani","doi":"10.1167/tvst.14.9.30","DOIUrl":"10.1167/tvst.14.9.30","url":null,"abstract":"<p><strong>Purpose: </strong>The action spectrum for lens epithelial cell (LEC) migration was quantified using an in vitro wound healing assay to provide a basis for preventing posterior capsule opacification (PCO) by optimizing light exposure after cataract surgery.</p><p><strong>Methods: </strong>This study evaluated the effects of narrowband light in the 400- to 800-nm range with irradiances equal to or lower than those of sunlight (2-10 W/m2) on LEC morphological changes and migration to close a monolayer wound with a 500-µm width.</p><p><strong>Results: </strong>Under no irradiation (dark) conditions as a negative control, LECs migrated to close the wound in 30 hours. The migration speed in the 400- to 480-nm blue light was lower than that in the dark negative control but was equivalent in the 490- to 540-nm range. The degree of speed reduction was greater for shorter wavelengths and higher irradiances. At wavelengths ≤ 430 nm, cells shrank into dendritic or rounded shapes, with marker staining confirming both as apoptotic. At 570 to 800 nm, the speed was higher in the first 15 hours than that in the dark, after which it decreased.</p><p><strong>Conclusions: </strong>To the best of our knowledge, this is the first reported action spectrum based on a systematic analysis of LEC migration. Visible light from the blue to far-red region either suppressed or enhanced the LEC migration speed depending on the wavelength and irradiance; that is, including both components potentially decreases and increases PCO risk.</p><p><strong>Translational relevance: </strong>Our findings can guide light management strategies by optimizing harmful and beneficial light exposure to minimize PCO risk.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 9","pages":"30"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent Proinflammatory Cytokine Profile in the Tear Fluid of Stable Keratoconus: Rethinking Clinical Quiescence.","authors":"Pedro Gil, João Quadrado Gil, Nuno Cruz, Celso Costa, Paulo Rodrigues-Santos, Luana Madalena Sousa, Jani Sofia Almeida, Rosa Fernandes, Nuno Alves, Andreia Rosa, Joaquim Murta","doi":"10.1167/tvst.14.9.31","DOIUrl":"10.1167/tvst.14.9.31","url":null,"abstract":"<p><strong>Purpose: </strong>Keratoconus is traditionally classified as a noninflammatory corneal ectasia, despite growing evidence suggesting an underlying inflammatory component. This study evaluates whether patients with stable keratoconus exhibit persistent inflammatory activity in tear fluid compared to healthy controls.</p><p><strong>Methods: </strong>Cross-sectional case-control study. Keratoconus progression was evaluated using tomographic and clinical criteria. Tear fluid samples were collected under standardized conditions and concentrations of nine cytokines (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, and TNF-α) were quantified using a multiplex assay. Group comparisons, correlation analyses, and receiver operating characteristic (ROC) curves were performed to evaluate cytokine expression and network behavior.</p><p><strong>Results: </strong>A total of 23 stable keratoconus patients and 25 age-matched healthy controls were included. The stable keratoconus group exhibited significantly elevated levels of tear fluid inflammatory cytokines compared to controls (all P < 0.05, except IL-2). Spearman correlation heatmaps revealed a coordinated cytokine network in the keratoconus group, suggesting persistent immunological activation despite clinical quiescence. No significant correlations were observed between cytokine levels and keratoconus staging indices. ROC analysis indicated moderate discriminatory performance of IL-6 (area under the curve = 0.68).</p><p><strong>Conclusions: </strong>Even clinically stable keratoconus is associated with a distinct proinflammatory tear fluid cytokine profile, challenging the traditional paradigm of keratoconus as a noninflammatory disease. These findings highlight the potential utility of tear fluid-based inflammatory biomarkers in keratoconus and suggest inflammation may persist independently of clinical progression.</p><p><strong>Translational relevance: </strong>This study highlights the potential role of tear-based inflammatory biomarkers for monitoring disease activity, understanding keratoconus pathophysiology and guiding adjunctive anti-inflammatory therapies in keratoconus beyond structural stabilization.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 9","pages":"31"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Structural Phenotype and Polygenic Risk Scores in Intermediate Age-Related Macular Degeneration - A MACUSTAR Report.","authors":"Lukas Schloesser, Jan H Terheyden, Charlotte Behning, Hannah Klinkhammer, Davide Garzone, Marlene Saßmannshausen, Sarah Thiele, Steffen Schmitz-Valckenberg, Carel Hoyng, Clara I Sánchez, Matthias Schmid, Ulrich F O Luhmann, Heather Floyd, Sergio Leal, Frank G Holz, Robert P Finger","doi":"10.1167/tvst.14.9.37","DOIUrl":"10.1167/tvst.14.9.37","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to analyze genotype-phenotype associations in intermediate age-related macular degeneration (iAMD) based on global and pathway-specific polygenic risk scores (psPRS) in participants of the prospective European multicenter cohort study MACUSTAR.</p><p><strong>Methods: </strong>Assessed structural biomarkers included reticular pseudodrusen (RPD), pigmentary abnormalities, hyper-reflective foci (HRF), and incomplete or complete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA and cRORA). Blood samples were genotyped and imputed via a local pipeline. Global and pathway-specific PRS (complement PRS [C-PRS], with and without ARMS2/HTRA1 variants [C+AH-PRS and AH-PRS]; extracellular matrix PRS [E-PRS]; and lipid PRS [L-PRS]) were calculated. The associations between global and pathway-specific PRS and structural iAMD biomarkers were assessed with multivariable models, controlling for age and sex.</p><p><strong>Results: </strong>In total, 404 participants (263 women, 65.1%; mean age = 71.5 ± 7.0 years, mean ± standard deviation [SD]) were included in the analysis. Multivariable regression models revealed that RPD was associated with a higher AH-PRS (estimate = 7.11 × 10-2, P = 9.0 × 10-3), C+AH-PRS (estimate = 9.96 × 10-2, P = 5.0 × 10-3), and E-PRS (estimate = 3.28 × 10-2, P = 3.1 × 10-2). The presence of cRORA was associated with a higher AH-PRS (estimate = 1.34 × 10-1, P = 2 × 10-3) and a higher C+AH-PRS (estimate = 1.59 × 10-1, P = 6 × 10-3).</p><p><strong>Conclusions: </strong>Structural risk biomarkers are associated with psPRS in iAMD. These findings further underscore the heterogeneity of pathogenic pathways in AMD and indicate differential risk characteristics across the broad spectrum of iAMD.</p><p><strong>Translational relevance: </strong>Our findings reveal subgroups in iAMD based on genotype-phenotype associations which can help identifying patients at high risk for iAMD and establish new endpoints for clinical trials in iAMD.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 9","pages":"37"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}