American Journal of Ophthalmology最新文献

{"title":"Corrigendum to “Baseline Visual Field Findings in the RUSH2A Study: Associated Factors and Correlation With Other Measures of Disease Severity” [Am J Ophthalmol 2020;219:87-100]","authors":"Jacque L. Duncan , Wendi Liang , Maureen G. Maguire , Isabelle Audo , Allison R. Ayala , David G. Birch , Joseph Carroll , Janet K. Cheetham , Simona Degli Esposti , Todd A. Durham , Laura Erker , Sina Farsiu , Frederick L. Ferris III , Elise Heon , Robert B. Hufnagel , Alessandro Iannaccone , Glenn J. Jaffe , Christine N. Kay , Michel Michaelides , Mark E. Pennesi , José-Alain Sahel","doi":"10.1016/j.ajo.2025.02.024","DOIUrl":"10.1016/j.ajo.2025.02.024","url":null,"abstract":"","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"273 ","pages":"Pages 265-266"},"PeriodicalIF":4.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Errors and Delays in Diagnosing Keratitis Fugax Hereditaria","authors":"ANNAMARI T. IMMONEN ,&nbsp;SABITA KAWAN ,&nbsp;MICHAEL P. BACKLUND ,&nbsp;HEIKKI SAAREN-SEPPÄLÄ ,&nbsp;TERO T. KIVELÄ ,&nbsp;JONI A. TURUNEN","doi":"10.1016/j.ajo.2025.03.004","DOIUrl":"10.1016/j.ajo.2025.03.004","url":null,"abstract":"<div><h3>Purpose</h3><div>To study errors and delays in diagnosing keratitis fugax hereditaria (KFH), an autosomal-dominant periodic corneal autoinflammatory disease caused by the <em>NLRP3</em> variant c.61G&gt;C, by reviewing the medical records of genetically confirmed Finnish patients with KFH and by determining the frequency of the c.61G&gt;C variant in selected biobank samples.</div></div><div><h3>Design</h3><div>A retrospective cohort and a cross-sectional biobank study.</div></div><div><h3>Participants and subjects</h3><div>Medical records of 96 clinically diagnosed, genetically confirmed patients with KFH, and 2010 DNA samples from patients with anterior uveitis, herpes keratitis, nonulcerative keratitis, or corneal opacity in the 2 largest Finnish biobanks.</div></div><div><h3>Methods</h3><div>The age, sex, ocular and other diagnoses, and laboratory results were reviewed in the retrospective cohort. The c. 61G&gt;C variant was genotyped from the biobank samples using restriction fragment length polymorphism analysis. Sanger sequencing was used for validation. The most common causes of anterior uveitis, such as rheumatoid arthritis, or infectious keratitis were exclusion criteria.</div></div><div><h3>Main outcome measures</h3><div>Misdiagnoses and differential diagnoses of KFH, diagnostic delays, and the frequency of the c. 61G&gt;C variant in biobank samples.</div></div><div><h3>Results</h3><div>The most common misdiagnoses in the retrospective cohort were anterior uveitis or anterior chamber cell reaction (40% of patients and 79% of misdiagnoses), conjunctivitis (14% and 27%, respectively), and recurrent corneal erosion (13% and 25%, respectively). Time from the onset of symptoms to KFH diagnosis ranged from 0 to 62 years (median, 19; interquartile range, 8-44). Of the 2010 biobank samples from patients with anterior uveitis, herpes keratitis, nonulcerative keratitis, or corneal opacity without an obvious cause, 12 (0.6%) carried the c.61G&gt;C variant: 11 were diagnosed with anterior uveitis, 1 with unspecified keratitis, and 3 correctly with KFH.</div></div><div><h3>Conclusions</h3><div>KFH in Finland is most likely misdiagnosed as anterior uveitis. We suggest prospectively evaluating the addition of the <em>NLRP3</em> variant c.61G&gt;C to laboratory test packages for differential diagnosis of anterior uveitis. KFH should be considered in the differential diagnosis of anterior uveitis, especially in the Nordic countries and populations originating from them. Symptoms similar to those of KFH may also occur in other <em>NLRP3</em>-linked autoinflammatory syndromes.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"274 ","pages":"Pages 122-130"},"PeriodicalIF":4.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial Mapping Efficacy for Subclinical Keratoconus Identification","authors":"BARBARA A. L. DUTRA ,&nbsp;BASSEL HAMMOUD ,&nbsp;BIANCA N. SUSANNA ,&nbsp;LARA ASROUI ,&nbsp;GIULIANO SCARCELLI ,&nbsp;WILLIAM J. DUPPS JR ,&nbsp;J. BRADLEY RANDLEMAN","doi":"10.1016/j.ajo.2025.02.042","DOIUrl":"10.1016/j.ajo.2025.02.042","url":null,"abstract":"<div><h3>PURPOSE</h3><div>To evaluate the utility of automated epithelial thickness metrics to identify subclinical keratoconus (SKC) through epithelial thickness pattern comparisons between normal controls, (SKC), and manifest keratoconus (KC).</div></div><div><h3>DESIGN</h3><div>Retrospective cross-sectional study.</div></div><div><h3>METHODS</h3><div>There were 200 eyes from 200 patients evaluated, including: (1) 100 control eyes from 100 patients with bilaterally normal corneal topography/tomography and slit-lamp examination (controls); (2) 50 eyes from 50 patients with SKC; (3) 50 eyes from 50 patients with KC. Epithelial mapping was performed using anterior segment optical coherence tomography (AS-OCT) imaging (Avanti RTVue XR, Optovue). Area under the receiver operating characteristic (AUROC) curves were used to determine the overall discriminative accuracy of the significant test parameters as described by the area under the curve (AUC) and to calculate the sensitivity and specificity of each parameter.</div></div><div><h3>RESULTS</h3><div>There were no differences between control and SKC groups in any regional OCT epithelial thickness parameter. Among relational epithelial thickness metrics, only superonasal - inferotemporal (SN-IT) value differences reached statistical significance between control and SKC groups (–0.81 μm versus 0.41 μm), but this metric still showed limited performance in differentiating groups (AUROC = 0.68). Most stromal thickness values were significantly different between SKC and controls.</div></div><div><h3>CONCLUSION</h3><div>Epithelial thickness patterns were not effective as a primary metric to identify subclinical keratoconus. Scheimpflug metrics and regional stromal thickness values significantly outperformed epithelial metrics in differentiating both SKC and KC eyes from controls. Epithelial mapping metrics thus appear significantly less sensitive than predicted for subclinical keratoconus detection in early disease manifestations.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"274 ","pages":"Pages 209-220"},"PeriodicalIF":4.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinitis Pigmentosa GTPase Regulator-Associated X-Linked Retinitis Pigmentosa: Molecular Genetics and Clinical Characteristics","authors":"Sungsoon Hwang ,&nbsp;Sohee Jeon ,&nbsp;Je Moon Yoon ,&nbsp;Se Joon Woo ,&nbsp;Kwangsic Joo ,&nbsp;Yong Je Choi ,&nbsp;Chang Ki Yoon ,&nbsp;Minjeong Kim ,&nbsp;Hyuk Jun Lee ,&nbsp;Suk Ho Byeon ,&nbsp;Christopher Seungkyu Lee ,&nbsp;Jehwi Jeon ,&nbsp;Jin Yeong Kim ,&nbsp;Jinu Han ,&nbsp;Dongheon Surl ,&nbsp;Min Sagong ,&nbsp;Areum Jeong ,&nbsp;Tae Kwann Park ,&nbsp;Hyo Song Park ,&nbsp;Mirinae Kim ,&nbsp;Sang Jin Kim","doi":"10.1016/j.ajo.2025.03.001","DOIUrl":"10.1016/j.ajo.2025.03.001","url":null,"abstract":"<div><h3>Purpose</h3><div>To describe in detail the genetic profile, clinical features, and genotype-phenotype correlation of retinitis pigmentosa GTPase regulator (<em>RPGR</em>)-associated X-linked retinitis pigmentosa (RP) in Koreans.</div></div><div><h3>Design</h3><div>A retrospective multicenter case series.</div></div><div><h3>Methods</h3><div>This study recruited genetically confirmed <em>RPGR</em>-associated X-linked RP patients from nine tertiary hospitals and clinics across Korea. Genetic profiles, age at night blindness onset, visual acuity (VA), visual field radius, ellipsoid zone (EZ) bandwidth, bone spicule pigmentation, fundus autofluorescence (AF) pattern, and genotype-phenotype correlation were analyzed.</div></div><div><h3>Results</h3><div>A total of 133 patients (104 males and 29 females from 107 families) with pathogenic or likely pathogenic <em>RPGR</em> variants were included. The majority of patients (86.5%) had truncating mutations and 72.9% of variants located in the open reading frame 15 regions. In male patients, night blindness onset occurred before the age of 20 in most patients (85%). Worse VA was associated with older age, with the estimated mean best-corrected VA reaching 20/200 by the age of 40 in male. More than half of the male patients in their 30s had the widest visual field diameter of less than 20°, and more than three-quarters of patients over 40 were classified in this category. Complete loss of the EZ band was rare before the age of 30; however, more than half of the patients in their 30s exhibited complete EZ band loss. Bone spicule pigmentation was uncommon before the age of 20 (10% of those under 10 and 35% in their teens), whereas peripheral hypoAF pattern was commonly observed after the age of 10 (22% of those under 10 and 81% in their teens). Female carriers generally exhibited a milder phenotype and showed significantly greater interocular asymmetry compared to males (all <em>P</em> &lt; .001). Truncating variants were associated with worse VA and a higher risk of complete EZ band loss compared to nontruncating variants (<em>P</em> &lt; .001 and <em>P</em> = .031, respectively).</div></div><div><h3>Conclusions</h3><div>This study provides a detailed genetic and age-specific clinical profile of <em>RPGR</em>-related X-linked RP, demonstrating significant differences in phenotypic severity based on the genotype. Our findings provide insights for estimating potential RPGR gene therapy candidate populations, supporting future clinical applications.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"274 ","pages":"Pages 171-183"},"PeriodicalIF":4.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increasing Incidence of Posterior Uveal Melanoma in Scandinavia 1960-2022: A Tri-National Study","authors":"KRISTOFFER NISSEN ,&nbsp;JENS FOLKE KIILGAARD ,&nbsp;MARIA FILI ,&nbsp;STEFAN SEREGARD ,&nbsp;JESINTHA NAVARATNAM ,&nbsp;JØRGEN KROHN ,&nbsp;THOMAS PEDERSEN BÆRLAND ,&nbsp;TRUDE EID ROBSAHM ,&nbsp;NILS EIDE ,&nbsp;GUSTAV STÅLHAMMAR","doi":"10.1016/j.ajo.2025.03.002","DOIUrl":"10.1016/j.ajo.2025.03.002","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate temporal trends in the incidence of posterior uveal melanoma in Scandinavia (Sweden, Denmark, and Norway) between 1960 and 2022 and explore potential associations with changes in tumor size and patient age at diagnosis.</div></div><div><h3>Design</h3><div>Retrospective, registry‐based cohort study utilizing nationwide data from the 3 Scandinavian countries.</div></div><div><h3>Participants</h3><div>All patients diagnosed with posterior uveal melanoma (choroid or ciliary body) in Sweden (1960-2022), Denmark (1960-2022), and Norway (1993-2022), totaling 10,154 cases. Iris melanomas were excluded.</div></div><div><h3>Methods</h3><div>Crude, age-standardized, and log-transformed age-standardized incidence rates were calculated using direct standardization (1970-1974 population). Linear regression was applied to assess trends in incidence, largest basal diameter (LBD), tumor thickness, and patient age at diagnosis. A multivariate linear regression model tested whether tumor size or patient age accounted for the time-dependent increase in incidence. <em>P</em> values were Bonferroni-adjusted for multiple comparisons.</div></div><div><h3>Main Outcome Measures</h3><div>Crude, age-standardized, and log-transformed age-standardized incidence rates of posterior uveal melanoma.</div></div><div><h3>Results</h3><div>Crude, age-standardized, and log-transformed age-standardized incidence rates increased significantly in all 3 countries. Combined Scandinavian age-standardized rates rose from 5.2 to 6.8 per million inhabitants and year in the 1960s to 6.1-8.7 in the 2010s (slope 0.033; 95% CI: 0.022-0.044). Log-transformed rates showed a similar upward trend (slope 0.002; 95% CI: 0.002-0.003). Tumor size (diameter and thickness) decreased, while patient age at diagnosis increased over time. Multivariate analysis confirmed a time-dependent increase in incidence, independent of tumor size or patient age.</div></div><div><h3>Conclusions</h3><div>Posterior uveal melanoma incidence in Scandinavia has increased since 1960. The linear trend is independent of changes in tumor size or patient age.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"274 ","pages":"Pages 131-141"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Vascularization Rate Predicts Retinopathy of Prematurity and Remains Unaffected by Low-Dose Bevacizumab Treatment","authors":"Emer Chang ,&nbsp;Amandeep Josan ,&nbsp;Ravi Purohit ,&nbsp;Sher A. Aslam ,&nbsp;Caroline Hartley ,&nbsp;Chetan K. Patel ,&nbsp;Kanmin Xue","doi":"10.1016/j.ajo.2025.02.040","DOIUrl":"10.1016/j.ajo.2025.02.040","url":null,"abstract":"<div><h3>PURPOSE</h3><div>To assess the rate of retinal vascularization derived from ultra-widefield (UWF) imaging-based retinopathy of prematurity (ROP) screening as predictor of type 1 ROP and characterize the effect of anti–vascular endothelial growth factor (anti-VEGF) therapy on vascularization rate.</div></div><div><h3>DESIGN</h3><div>Retrospective, consecutive cohort study.</div></div><div><h3>SUBJECTS</h3><div>The study included 132 eyes of 76 premature infants with a mean gestational age (GA) of 26.0 (±2.0 SD) weeks and birthweight (BW) of 815 (±264) g, who underwent longitudinal UWF imaging for ROP screening, at a level 3 neonatal unit in Oxford, United Kingdom.</div></div><div><h3>METHODS</h3><div>The extent of retinal vascularization on each UWF image was measured as the ratio between “disc-to-temporal vascular front” and “disc-to-fovea” distance along a straight line bisecting the vascular arcades. Measurements from ≥3 time points plotted against post-menstrual age (PMA) enabled calculation of temporal vascularization rate (TVR) for each eye. Using TVR, GA, and BW as predictors, a machine learning model was created to classify eyes as either group AB (no ROP and type 2 ROP) or group C (type 1 ROP). The model was validated in a withheld cohort of 32 eyes (19 infants), of which 8 eyes (5 infants) required treatment. TVR in 37 eyes (20 infants) was compared before and after ultra-low-dose (0.16 mg) intravitreal bevacizumab treatment.</div></div><div><h3>MAIN OUTCOME MEASURES</h3><div>The rate of retinal vascularization was determined.</div></div><div><h3>RESULTS</h3><div>Slower retinal vascularization correlated with increasing ROP severity, with TVR being 29% slower in group C eyes (n=50) than group AB eyes (n=33 no ROP and n=49 type 2 ROP) (<em>P</em> = .04). Our model correctly predicted ROP outcomes of 30/32 eyes, achieving a balanced accuracy of 95.8%. No significant change in TVR was found before and after bevacizumab treatment with mean posttreatment imaging follow-up of 7.7 (±7.9) weeks (<em>P</em> = .60 right eyes, <em>P</em> = .71 left eyes).</div></div><div><h3>CONCLUSIONS</h3><div>UWF imaging-based ROP screening enables quantification of retinal vascularization rate, which can provide early prediction of type 1 ROP independent of BW and GA. Rate of physiological retinal vascularization does not appear to be significantly affected by ultra-low-dose anti-VEGF treatment, which has significant implications for the development of peripheral avascular retina and timing of anti-VEGF intervention to prevent disease progression in high-risk infants.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"275 ","pages":"Pages 74-87"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visual Impairment and Cognitive Function in Aging Adults: Sex and Age Differences in Mediating Effect of Social Isolation and Depression","authors":"D. DIANE ZHENG ,&nbsp;DAVID J. LEE ,&nbsp;TATJANA RUNDEK ,&nbsp;BYRON L. LAM ,&nbsp;NINEL Z GREGORI ,&nbsp;ROSIE E. CURIEL ,&nbsp;DAVID A. LOEWENSTEIN","doi":"10.1016/j.ajo.2025.02.043","DOIUrl":"10.1016/j.ajo.2025.02.043","url":null,"abstract":"<div><h3>Purpose</h3><div>Visual impairment (VI) is prevalent in older adults and associated with cognitive decline. However, the mechanisms through which visual impairment affects cognitive functioning during the aging process are poorly understood. Our study aims to estimate the direct effect of visual acuity on cognitive function and its indirect effect through social isolation and depressive symptoms by sex and age.</div></div><div><h3>Design</h3><div>Cross-sectional study.</div></div><div><h3>Participants</h3><div>117,231 individuals aged 40-70 participated in the UK Biobank baseline and ocular assessment. Of these, 81% were white, 54% were female, and 45.6% were aged 60-70. The mean age was 56.8 (SD 8.1) years.</div></div><div><h3>Methods</h3><div>Path analyses with multiple equations were conducted to examine the direct and indirect effects of visual acuity (VA). Stratified analyses by gender and age were performed.</div></div><div><h3>Main Outcome Measures</h3><div>LogMAR VA was the exposure, with social isolation and depressive symptoms as mediators. Cognitive functions, including visual memory, verbal-numerical reasoning, processing speed, and prospective memory, were the outcomes.</div></div><div><h3>Results</h3><div>VA had a direct effect on cognitive function (β = -0.979 for reasoning and OR = 0.67 for prospective memory). VA also influenced cognition indirectly through social isolation and depressive symptoms. The direct effect of VA on cognitive function was similar in men vs. women and middle-aged vs. older. However, there is a marked difference in the mediating effect via social isolation and depressive symptoms by age and sex. The mediating effect of VI on cognition via social isolation was stronger in older adults than middle-aged and in men than women; while the mediating effect via depressive symptoms was stronger in women and middle-aged individuals. VI had the largest mediating effect via social isolation in older males.</div></div><div><h3>Conclusion and Relevance</h3><div>Vision, social isolation, and depressive symptoms are modifiable factors and can be treated to preserve cognition. Encouraging social engagement among male and older adults with VI and promoting mental health awareness in women and middle-aged individuals with VI will reduce the negative impact of VI on cognition, lower dementia risk, and improve the well-being of aging adults.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"274 ","pages":"Pages 196-208"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Lamina Parameters in Nonglaucomatous Eyes With and Without Pseudoexfoliation Syndrome","authors":"YOUNG HOON JUNG ,&nbsp;JOON MO KIM ,&nbsp;EUN JI LEE ,&nbsp;TEA-WOO KIM ,&nbsp;SO YOUNG HAN ,&nbsp;YONGWOO LEE ,&nbsp;JI EUN SONG","doi":"10.1016/j.ajo.2025.02.041","DOIUrl":"10.1016/j.ajo.2025.02.041","url":null,"abstract":"<div><h3>Objective</h3><div>To compare lamina cribrosa (LC) parameters in nonglaucomatous eyes with pseudoexfoliation syndrome (PXFS) and healthy control eyes to assess structural alterations that may contribute to early glaucoma pathophysiology.</div></div><div><h3>Design</h3><div>Retrospective, cross-sectional study.</div></div><div><h3>Participants</h3><div>Fifty eyes with non-glaucomatous PXFS and 50 healthy, age-matched control eyes.</div></div><div><h3>Methods</h3><div>All participants underwent spectral-domain optical coherence tomography with enhanced-depth imaging. LC parameters were measured at the superior mid-peripheral, central, and inferior mid-peripheral regions. Comparisons between groups were assessed with paired <em>t</em>-tests for continuous data and the McNemar test for categorical data. Mixed effects model analysis was utilized to identify factors associated with lamina cribrosa thickness (LCT).</div></div><div><h3>Main Outcome Measures</h3><div>Measurements of LCT, lamina cribrosa curvature depth (LCCD), curvature index (LCCI), and prelaminar tissue thickness (PLTT).</div></div><div><h3>Results</h3><div>Eyes with PXFS exhibited significantly thinner LCT than controls across all regions: superior mid-peripheral (163.85 ± 39.13 µm vs. 222.18 ± 38.03 µm), central (172.95 ± 40.63 µm vs. 220.17 ± 51.77 µm), and inferior mid-peripheral (165.58 ± 35.18 µm vs. 217.73 ± 44.00 µm). No significant differences were observed in PLTT, LCCD and LCCI between the 2 groups. Multivariable mixed effects model analysis identified the presence of PXFS (β = -50.687) as an independent factor associated with LCT.</div></div><div><h3>Conclusion</h3><div>PXFS eyes show significant LC thinning, potentially representing early structural changes preceding glaucoma. Monitoring LC parameters in PXFS eyes may facilitate early detection of patients at risk of disease progression.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"274 ","pages":"Pages 163-170"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurofibromatosis Type 1 (NF1)–Related Ocular Signs: New Insights on Their Prevalence, Incidence, and Genotype-Phenotype Correlation in NF1 Children","authors":"Edoardo Midena ,&nbsp;Eleonora Cosmo","doi":"10.1016/j.ajo.2025.02.044","DOIUrl":"10.1016/j.ajo.2025.02.044","url":null,"abstract":"<div><h3>PURPOSE</h3><div>To assess, in a large pediatric population affected by neurofibromatosis type 1 (NF1), the prevalence, incidence, age of onset, and genotype correlation of the main NF1-related ocular signs, including optic pathway glioma (OPG), Lisch nodules (LNs), choroidal abnormalities (CAs), and retinal vascular abnormalities (RVAs).</div></div><div><h3>METHODS</h3><div>NF1 patients ≤16 years old followed at our institution between 2010 and 2022 were included. Presence of NF1-related ocular signs was assessed at baseline and during follow-up evaluations through slit lamp observation (LNs), near-infrared imaging (CAs and RVAs), and neuroimaging revision (OPG). Patients were categorized according to their genetic variant.</div></div><div><h3>RESULTS</h3><div>A total of 237 patients were enrolled. Among those, 204 underwent at least 1 follow-up and genetic test was available for 210. Prevalence of OPG, LNs, CAs, and RVAs at baseline was, respectively, 20.7%, 43.5%, 46.8%, and 6.8%. Their incidence during follow-up was 6.4%, 22.4%, 21.4%, and 5.4%, respectively, and the mean age at onset was 6.3±3.6, 7.1±3.0, 6.4±3.0, and 6.6±2.9 years. Patients with truncating mutations presented a higher number of ocular signs than those with non-truncating mutations (1.7±1.0 vs 0.9±0.9, <em>P</em> = .0019).</div></div><div><h3>CONCLUSIONS</h3><div>Data on prevalence and incidence of NF1-related ocular signs in pediatric patients evidences that the development of these signs seems negligible after the age of 7. LNs and CAs seem to develop independently and, therefore, can be considered as two separate diagnostic criteria. Truncating mutations correlate with a higher number of NF1-related ocular signs phenotype. Note: Publication of this article is sponsored by the American Ophthalmological Society.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"275 ","pages":"Pages 58-73"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Structural Characterization of a Novel TGFBI Mutation Linked to a Lattice Corneal Dystrophy Variant in a Greek Family","authors":"Margarita Zacharogianni ,&nbsp;Nikos C. Papandreou ,&nbsp;Nikolaos M. Marinakis ,&nbsp;Faidon-Nikolaos Tilemis ,&nbsp;Joanne Traeger-Synodinos ,&nbsp;Sotiria Palioura","doi":"10.1016/j.ajo.2025.03.003","DOIUrl":"10.1016/j.ajo.2025.03.003","url":null,"abstract":"<div><h3>Purpose</h3><div>To describe a novel pathogenic <em>TGFBI</em> variant identified in a Greek family and investigate its structural impact on the TGFBI protein, focusing on clinical significance and genotype-phenotype correlations.</div></div><div><h3>Design</h3><div>Single-family case-control study with computational structural analysis.</div></div><div><h3>Methods</h3><div>Three generations of a Greek family, including the proband, her brother, and their mother were clinically evaluated using slit-lamp examination and anterior segment optical coherence tomography. Whole exome sequencing was performed on the proband, followed by targeted sequencing of family members. Bioinformatics tools, including DynaMut2, PROVEAN, and AlphaFold2, were used to predict the mutation's impact on protein structure and stability.</div></div><div><h3>Results</h3><div>A novel heterozygous variant, c.1517_1518insCCCCCCCAAGGG, was identified. This 12-nucleotide insertion replaces methionine at position 506 with isoleucine, proline, proline, lysine, and glycine (p.M506delinsIPPKG). Clinically, this mutation was associated with geographic subepithelial and anterior stromal opacities without discernible lattice lines and presented as recurrent corneal erosions in the second decade. Structural analysis revealed disruption of the first α-helix of the FAS1-4 domain, destabilizing the protein and potentially exposing amyloidogenic regions. Previously reported mutations within this α-helix consistently produce a phenotype of geographic subepithelial opacities and a similar age of onset.</div></div><div><h3>Conclusions</h3><div>M506delinsIPPKG represents a novel pathogenic <em>TGFBI</em> variant associated with an autosomal dominant lattice corneal dystrophies variant. The structural disruption of the FAS1-4 domain's α-helix likely underlies the disease mechanism and links structural changes to specific phenotypic traits. These findings contribute to our understanding of genotype-phenotype correlations in <em>TGFBI</em>-related corneal dystrophies and highlight the importance of structural analysis in such cases.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"274 ","pages":"Pages 112-121"},"PeriodicalIF":4.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}