Acta Ophthalmologica最新文献

{"title":"Exploring market dynamics of biological including biosimilar treatments for retinal diseases in Europe: An interrupted time-series analysis.","authors":"Elif Car, Isabelle Huys, Steven Simoens, Arnold G Vulto","doi":"10.1111/aos.70148","DOIUrl":"https://doi.org/10.1111/aos.70148","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the impact of biosimilar ranibizumab and on-patent faricimab market entry on pricing and utilization trends and describe national variation in off-label bevacizumab use in Europe.</p><p><strong>Methods: </strong>Interrupted time series analysis of quarterly sales data (Q1 2018-Q2 2024) in 11 European countries evaluated ranibizumab utilization and price after biosimilar entry and aflibercept utilization after faricimab entry. A cross-country survey assessed off-label bevacizumab use.</p><p><strong>Results: </strong>Ranibizumab utilization declined in seven of 11 countries (-1.0% to -29.8%) despite biosimilar entry and associated price reductions. Significant negative trend changes in ranibizumab utilization were observed in France (-0.449; p < 0.001), Germany (-3.935; p = 0.021) and Spain (-8.648; p = 0.002), while Hungary (+33.7; p < 0.001) and the UK (+3.4; p = 0.005) showed increases. Negative trend changes in ranibizumab's weighted average price per TD were observed in four countries ranging from € -0.083 (p < 0.001) in Germany to € -1.309 (p < 0.001) in Hungary. Aflibercept utilization increased across all countries during the study period (+23.6% to +243.3%), but subsequent to faricimab entry, downward utilization trends were observed in several countries, indicating a shift in market dynamics potentially due to extended dosing intervals. Survey results revealed substantial heterogeneity in off-label bevacizumab use, reimbursement status, liability attribution and compounding practises, underscoring fragmented policy environments that influence treatment access.</p><p><strong>Conclusion: </strong>The study found substantial cross-country variation in anti-VEGF utilization in Europe. Coordinated policy action is needed to support a sustainable biosimilar uptake in this evolving market.</p>","PeriodicalId":6915,"journal":{"name":"Acta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of coronary artery bypass grafting on the short- and long-term development and progression of diabetic retinopathy: A Danish national matched cohort study.","authors":"Lukas Greve Maschoreck, Lonny Stokholm, Frederik Nørregaard Pedersen, Nis Andersen, Jens Andresen, Toke Bek, Sebastian Dinesen, Javad Hajari, Steffen Heegaard, Kurt Højlund, Caroline Schmidt Laugesen, Ryo Kawasaki, Sören Möller, Katja Christina Schielke, Yousif Subhi, Anne Suhr Thykjær Petersen, Jakob Grauslund","doi":"10.1111/aos.70147","DOIUrl":"https://doi.org/10.1111/aos.70147","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic retinopathy (DR) is a frequent long-term complication of diabetes. While hemodynamic changes are known risk factors for DR, the effect of coronary artery bypass grafting (CABG) on the development of DR is poorly investigated. We aimed to examine the short- and long-term effects of CABG on DR development or progression in a national cohort.</p><p><strong>Methods: </strong>This longitudinal, register-based matched cohort study included individuals with diabetes aged 18 years or older from the Danish Registry of Diabetic Retinopathy (DiaBase). We included individuals with and without CABG in a 1:2 match, based on sex, year of birth, type of diabetes and level of DR. We then evaluated the effect of CABG on short- (0-12 months) and long-term (above 24 months) development and progression of DR in adjusted Cox proportional hazard regression models.</p><p><strong>Results: </strong>Among 3633 individuals in the two groups (median aged 68 years with 82.4% males), CABG was not associated with short-term development (hazard ratio (HR) 1.14, 95% confidence interval (CI) 0.71-1.82) or progression (HR 1.13, 95% CI 0.75-1.70) of DR. Nor did it result in long-term development (HR 1.06, 95% CI 0.76-1.49) or progression (HR 1.10, 95% CI 0.78-1.55) of DR. However, the individuals from the CABG group had a lower chance of long-term DR-regression (HR 0.56, 95% CI 0.38-0.83).</p><p><strong>Conclusion: </strong>Although CABG is associated with a 44% lower chance of long-term DR-improvement, it did not increase the short- or long-term risk of DR development or progression. Hence, we did not find evidence that individuals undergoing CABG should receive additional DR screening postoperatively.</p>","PeriodicalId":6915,"journal":{"name":"Acta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The honorary Bjerrum medal lecture of the Danish Ophthalmological Society.","authors":"Anders Ivarsen","doi":"10.1111/aos.70156","DOIUrl":"https://doi.org/10.1111/aos.70156","url":null,"abstract":"","PeriodicalId":6915,"journal":{"name":"Acta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult-onset Coats disease: A systematic review and meta-analysis of imaging biomarkers and targeted therapies.","authors":"Catarina Francisco, Nisa Silva, Camiel J F Boon","doi":"10.1111/aos.70149","DOIUrl":"https://doi.org/10.1111/aos.70149","url":null,"abstract":"<p><p>Coats disease diagnosed in adulthood is a rare idiopathic retinal telangiectatic vasculopathy that may differ in phenotype from childhood-diagnosed cases. This systematic review synthesizes current evidence to characterize its clinical spectrum, imaging features, treatment outcomes and underlying mechanisms, with a focus on immunovascular pathways. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines, PubMed, Scopus and Web of Science were searched through October 2025 for studies including patients ≥18 years with confirmed Coats disease. Clinical and imaging findings, treatment strategies and outcomes were extracted and narratively synthesized. When possible, random-effects meta-analysis was performed. Thirty-five studies comprising 240 patients (250 eyes) were included. Disease presentation was predominantly unilateral and diagnosed at Shields Stage 2 or 3. Laser photocoagulation and anti-vascular endothelial growth factor (VEGF) agents were the most frequently described therapies, with anatomical stabilization or regression of exudation reported in approximately half of treated eyes across heterogeneous studies, and better outcomes in earlier stages. Visual acuity was stabilized or improved in 57.1% of treated eyes, while recurrence occurred in 19.3%. Multimodal imaging consistently identified peripheral telangiectasia, lipid exudation and localized capillary nonperfusion. Aqueous cytokine profiling in small cohorts has reported elevated inflammatory mediators (e.g. interleukin [IL]-6 and IL-1β) in some adults, suggesting that inflammatory signalling may contribute to blood-retina barrier dysfunction and macular oedema alongside VEGF-related permeability. Current evidence supports Coats disease diagnosed in adulthood as a chronic telangiectatic retinal vasculopathy with frequent macular involvement. Therapeutic outcomes appear to favour individualized, imaging-guided combination strategies and prospective studies with standardized endpoints are needed to refine management.</p>","PeriodicalId":6915,"journal":{"name":"Acta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inter-observer variability is unlikely to explain regional differences in retinopathy of prematurity in Norway.","authors":"Dordi Austeng, Kyrre Moljord, Tora Sund Morken, Aaron S Coyner, J Peter Campbell","doi":"10.1111/aos.70146","DOIUrl":"https://doi.org/10.1111/aos.70146","url":null,"abstract":"<p><strong>Purpose: </strong>To test inter-observer variation of plus disease diagnoses among Norwegian ophthalmologists and treatment centres.</p><p><strong>Methods: </strong>All ophthalmologists in Norway who make individual retinopathy of prematurity (ROP) treatment decisions were invited to grade retinal images using a web-based image grading platform. The images (n = 180) were a subset from the US Imaging and Informatics in Retinopathy of Prematurity (i-ROP) study and were either normal, with pre-plus disease, or plus disease. Agreement both between ophthalmologists and between the five different centres in Norway with a reference standard diagnosis (RSD) was measured through weighted kappa (k) and percent agreement (PA). Agreement with the US RSD was also measured. Each image was associated with an artificial intelligence-based Vascular Severity Score (VSS) ranging from 1 to 9, and the VSS agreement rate for each score was compared.</p><p><strong>Results: </strong>All invited ophthalmologists (n = 15, of which six from the largest centre and two to three from each of the other four centres) agreed to participate. Agreement between ophthalmologists and the Norwegian RSD ranged from moderate (k = 0.458) to near perfect (k = 0.844), and from substantial (k = 0.679) to near perfect (k = 0.802) between consensus diagnosis at each centre and the Norwegian RSD. The agreement between centres and the US RSD ranged from moderate to substantial (κ = 0.561-0.729).</p><p><strong>Conclusion: </strong>Overall inter-observer variability in Norway was low. Such variability is therefore unlikely to explain regional differences in the frequency of treated ROP in Norway.</p>","PeriodicalId":6915,"journal":{"name":"Acta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-modal large language models for paediatric tele-ophthalmology: A blinded real-world evaluation of diagnostic accuracy and safety.","authors":"Daohuan Kang, Lu Yuan, Jia Feng, Andrzej Grzybowski, Kai Jin","doi":"10.1111/aos.70136","DOIUrl":"https://doi.org/10.1111/aos.70136","url":null,"abstract":"<p><strong>Background: </strong>The rapid integration of large language models (LLMs) into online medical consultations demands rigorous evaluation, particularly in specialized fields like paediatric ophthalmology. This study systematically assessed the diagnostic accuracy, safety and communication quality of advanced LLMs in real-world paediatric ophthalmology tele-consultations, with a focus on comparing text-only inputs to multi-modal inputs (text paired with parent-taken mobile photographs).</p><p><strong>Methods: </strong>A prospective, blinded, multi-model study was conducted using 50 authentic paediatric ophthalmology cases from an internet-based hospital platform. Four leading LLMs-Grok 4.1, GPT 5.1 Thinking, Gemini 2.5 Pro (advanced models) and GPT-4o (baseline)-were tested in multi-modal and text-only scenarios. Responses were evaluated by three blinded senior paediatric ophthalmologists using composite scoring system (maximum 19 points), encompassing diagnostic accuracy (up to six points), guideline adherence and safety (up to four points) and parent communication quality (up to nine points).</p><p><strong>Results: </strong>Advanced LLMs consistently outperformed GPT-4o, driven by superior Safety and Communication efficacy. Grok 4.1 led with the highest overall score in the multi-modal arm (15.06 ± 0.68), followed by GPT 5.1 Thinking (14.52 ± 1.19) and Gemini 2.5 Pro (14.30 ± 1.08), while GPT-4o lagged significantly at 11.20 ± 0.72. In the text-only arm, advanced models again excelled: Grok 4.1 (14.08 ± 1.18), GPT 5.1 Thinking (13.62 ± 1.77) and Gemini 2.5 Pro (13.42 ± 1.50). Multi-modal inputs significantly boosted scores (e.g., Grok 4.1: Δ = 0.98, p < 0.001), with gains specifically attributable to improvements in Safety and Communication rather than diagnostics. Regarding safety, advanced models exhibited markedly fewer major harmful responses (Grok 4.1: 4%; GPT 5.1 Thinking: 8%; Gemini 2.5 Pro: 10%) compared to GPT-4o (16%). Parent preferences favoured advanced LLMs, with Grok 4.1 receiving 23% of votes, reflecting higher perceived clarity, empathy and trustworthiness.</p><p><strong>Conclusion: </strong>Advanced LLMs demonstrate markedly superior capabilities over GPT-4o in handling paediatric ophthalmology tele-consultations, especially with multi-modal data, offering enhanced safety, communication and parent trust. However, persistent variations in safety across models and residual risks of harmful advice underscore the need for condition-specific validation and stringent safety guardrails prior to deployment. Multi-modal integration is essential for optimizing LLM reliability in this high-stakes domain.</p>","PeriodicalId":6915,"journal":{"name":"Acta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive factors for injection interval extension after switching to faricimab in neovascular AMD: The FAR WEST multicentre study.","authors":"Antoine Posnic, Sami Yagoub, Chloé Lebastard, Mathilde Vaast, Alexandra Poinas, Estelle Le Pabic, Jean-Paul Bellamy, Christian Delhay, Samy Faure, Jean-François Le Rouic, Adrien Henry, Olivier Lebreton, Helene Masse, Francois Susini, Tremeur Guillaumie, Isabelle Fournier, Adam Mainguy, Marie-Laure Le Lez, Raoul Kanav Khanna, Geoffroy Mortemousque, Arnaud George, Valentin Pipelart, Yan Bernard, Pierre Grimbert, Driss Mazhar, Mounir Benzerroug, Bénédicte Briend, Manon Clement, Henry-Pierre Jammes-Veaux, Marie-Pascale Posnic, Alexandre Bonissent, Charlène Guyot, Nicolas Rousseau, Benoît Trinh Van Dam, Lucas Bellot, Raphaëlle Ferron, Guylène Le Meur, Frédéric Mouriaux, Michel Weber, Yann Maucourant, Jean-Baptiste Ducloyer","doi":"10.1111/aos.70134","DOIUrl":"https://doi.org/10.1111/aos.70134","url":null,"abstract":"<p><strong>Purpose: </strong>To assess whether switching to faricimab allowed extending injection intervals after 12 months (M12) in patients with neovascular age-related macular degeneration (nAMD) and to identify predictive factors for interval extension.</p><p><strong>Design: </strong>FAR WEST was a multicentre, observational, retrospective cohort study.</p><p><strong>Participants: </strong>Patients with nAMD treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections for at least 1 year before switching to faricimab.</p><p><strong>Methods: </strong>The reason for switching (clinician's intent to extend the interval in the absence or presence of a recurrence or refractory status), and the switch strategy (whether an induction phase comprising 2, 3 or 4 injections was performed using the same or a shorter interval, or whether the interval was immediately extended from the second injection without induction) were left to the physician's discretion.</p><p><strong>Main outcome measures: </strong>The following data were collected from the medical records at the time of the decision to switch to faricimab (M0) and at the M12 follow-up visit: recurrence-free interval, last injection interval, best-corrected visual acuity (BCVA), central macular thickness (CMT), exudation status and intraocular inflammation events.</p><p><strong>Results: </strong>A total of 845 eyes of 718 patients were included in 23 centres. The recurrence-free injection interval increased significantly from 5.7 weeks at M0 to 8.6 weeks at M12 (difference: +2.9 weeks, p < 0.001). The proportion of exudative patients decreased from 571 (68%) to 337 (42%) (- 41%, p < 0.001). BCVA decreased from 0.33 (20/40) to 0.35 logMAR (20/40) (p = 0.0038). Among 238 refractory cases at M0, 84 (35%) achieved a dry macula at M12. In multivariable analysis, absence of an induction phase was associated with greater injection interval gain. (p < 0.001). There were no differences according to time since the first injection, type of neovascularization. The number of injections per year decreased from 8.7 at M0 to 6.1 at M12 (-2.6, p < 0.001), and the number of consultations decreased from 6.1 at M0 to 5.2 at M12 (-0.9, p < 0.001). The intraocular inflammation rate was 1.6% (n = 14).</p><p><strong>Conclusion: </strong>Switching to faricimab allowed significantly extending the recurrence-free injection interval, decreasing the proportion of exudative patients and reducing the therapeutic burden in nAMD patients. Further studies are needed to determine the most appropriate switching modalities and which patients actually require an induction phase.</p>","PeriodicalId":6915,"journal":{"name":"Acta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced rates of intraocular surgeries in anterior uveitis.","authors":"Sanna Leinonen, Rita Palviainen","doi":"10.1111/aos.70129","DOIUrl":"https://doi.org/10.1111/aos.70129","url":null,"abstract":"","PeriodicalId":6915,"journal":{"name":"Acta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The long-term impact of neovascular age-related macular degeneration undergoing routine treatment in first and second eyes on vision-related quality-of-life: FASBAT Report 3.","authors":"Archana Airody, Rachel L W Hanson, Isabel Bunola-Hadfield, Sobha Sivaprasad, Antony B Morland, Usha Chakravarthy, Richard P Gale","doi":"10.1111/aos.70150","DOIUrl":"https://doi.org/10.1111/aos.70150","url":null,"abstract":"<p><strong>Purpose: </strong>The study evaluated the long-term effect on vision-related quality-of-life (VRQoL) of routinely treated neovascular age-related macular degeneration (nAMD) in first and second eyes.</p><p><strong>Methods: </strong>The FASBAT (Observing Fibrosis, macular Atrophy and Subretinal highly reflective material Before and After Treatment with anti-VEGF treatment) study followed individuals with new unilateral nAMD (first eye) undergoing routine treatment for up to 4.5 years. Visual acuity (VA) was measured as part of routine care and VRQoL was assessed using the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25).</p><p><strong>Results: </strong>Of the 424 participants, 307 had only the first eye affected by nAMD (mean age = 76.5, SD = 8.4 years). The mean VA was 58.1 (SD = 15.5) and 79.4 (SD = 5.6) letters at baseline, and 58.4 (SD = 20.9)/78.5 (SD = 7.8) letters at 36-months in the affected and unaffected eyes, respectively. The mean composite NEI-VFQ-25 score was 87.1 (SD = 11.9) at baseline and 85.2 (SD = 13.5) at 36-months. One hundred and seventeen participants (mean age = 77.6, SD = 7.3 years) developed second eye nAMD, with a mean of 18.9 (SD = 10.2) months following the first eye. Mean VA in first and second eye was 56.3 (SD = 19.3)/74.1 (SD = 9.9) letters at the time of second eye development, and 51.1 (SD = 22.5)/73.6 (SD = 8.9) letters after 24-months. Mean composite NEI-VFQ-25 score was 81.4 (SD = 14.6) and 79.1 (SD = 17.2) at these time points.</p><p><strong>Conclusions: </strong>Long-term VRQoL remains stable in unilateral treated nAMD. However, a clinically meaningful reduction in VRQoL occurs following development and treatment in the second eye which does not recover. It is important to offer appropriate support when the first and then second eye develop nAMD.</p>","PeriodicalId":6915,"journal":{"name":"Acta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic risk factors in Finnish patients with Fuchs endothelial corneal dystrophy.","authors":"Inka-Tuulevi Vähämäki, Annamari T Immonen, Joel T Rämö, Aino M Jaakkola, Kari Krootila, Maria Kaukonen, Aarno Palotie, Hannes Lohi, Tero T Kivelä, Joni A Turunen","doi":"10.1111/aos.70144","DOIUrl":"https://doi.org/10.1111/aos.70144","url":null,"abstract":"<p><strong>Purpose: </strong>To study the genetic risk factors of Fuchs endothelial corneal dystrophy (FECD) in the Finnish population using hospital-based and large biobank cohorts.</p><p><strong>Methods: </strong>We genotyped a cohort of 107 Finnish patients with FECD for the primary associated genetic risk factor, the TCF4 (CTG)_>50 expansion, and studied their clinical phenotype. For 18 TCF4 (CTG)_≤50 patients, we performed exome-based candidate gene analysis. We also utilised FinnGen biobank-based samples to perform a genome-wide association study (GWAS).</p><p><strong>Results: </strong>In the cohort, 83% (89/107) carried one allele with the TCF4 (CTG)_>50 expansion. Those without the expansion were younger at enrolment and at the time of first keratoplasty (p = 0.011, p = 0.044, respectively). A genome-wide association study of 892 patients and 497 827 controls identified a lead variant rs11659764 (AF = 2.3%, OR = 8.2, p = 2.9 × 10^-195). Genotyping showed that 89% of TCF4 (CTG)_>50 carriers had the associated TA genotype rather than the TT genotype, whereas none of the TCF4 (CTG)_≤50 carriers did. Exome-based analyses of the 18 TCF4 (CTG)_≤50 carriers identified a candidate gene variant, AGBL1 c.901 + 2 T>G in one patient.</p><p><strong>Conclusion: </strong>In Finland, the TCF4 (CTG)_>50 expansion is a significant risk factor for FECD. A nearby single-nucleotide polymorphism (SNP) was found to perform well as a surrogate for genotyping. However, not all patients carried the expanded repeat, and a variant in a previously associated gene was observed in a single patient. Further research is needed to investigate the origins of FECD in individuals without the repeat expansion.</p>","PeriodicalId":6915,"journal":{"name":"Acta Ophthalmologica","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}