Investigative ophthalmology & visual science最新文献

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Mathematical Models of Ocular Drug Delivery. 眼部给药数学模型。
IF 4.4 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-09-03 DOI: 10.1167/iovs.65.11.28
Amir Sadeghi,Astrid Subrizi,Eva M Del Amo,Arto Urtti
{"title":"Mathematical Models of Ocular Drug Delivery.","authors":"Amir Sadeghi,Astrid Subrizi,Eva M Del Amo,Arto Urtti","doi":"10.1167/iovs.65.11.28","DOIUrl":"https://doi.org/10.1167/iovs.65.11.28","url":null,"abstract":"Drug delivery is an important factor for the success of ocular drug treatment. However, several physical, biochemical, and flow-related barriers limit drug exposure of anterior and posterior ocular target tissues during drug treatment via topical, subconjunctival, intravitreal, or systemic routes. Mathematical models encompass various barriers so that their joint influence on pharmacokinetics (PKs) can be simulated in an integrated fashion. The models are useful in predicting PKs and even pharmacodynamics (PDs) of administered drugs thereby fostering development of new drug molecules and drug delivery systems. Furthermore, the models are potentially useful in interspecies translation and probing of disease effects on PKs. In this review article, we introduce current modeling methods (noncompartmental analyses, compartmental and physiologically based PK models, and finite element models) in ocular PKs and related drug delivery. The roles of top-down models and bottom-up simulations are discussed. Furthermore, we present some future challenges, such as modeling of intra-tissue distribution, prediction of drug responses, quantitative systems pharmacology, and possibilities of artificial intelligence.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RTP4 Enhances Corneal HSV-1 Infection in Mice With Type 2 Diabetes Mellitus. RTP4 可增强 2 型糖尿病小鼠角膜 HSV-1 感染。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-09-03 DOI: 10.1167/iovs.65.11.36
Yunhai Dai, Shilan Mao, Xinyi Zang, Hongqi Ge, Jing Feng, Yalin Wang, Xia Qi, Lingling Yang, Qingjun Zhou, Xiaolei Wang
{"title":"RTP4 Enhances Corneal HSV-1 Infection in Mice With Type 2 Diabetes Mellitus.","authors":"Yunhai Dai, Shilan Mao, Xinyi Zang, Hongqi Ge, Jing Feng, Yalin Wang, Xia Qi, Lingling Yang, Qingjun Zhou, Xiaolei Wang","doi":"10.1167/iovs.65.11.36","DOIUrl":"10.1167/iovs.65.11.36","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate whether corneal lesions in mice with type 2 diabetes mellitus (T2D) infected with herpes simplex virus (HSV)-1 are more severe, and to elucidate the specific underlying mechanism.</p><p><strong>Methods: </strong>The corneas of control mice and T2D mice induced by a high-fat diet combined with streptozotocin were infected with the HSV-1 Mckrae strain to assess corneal infection, opacity, and HSV-1 replication. RNA sequencing of the corneal epithelium from wild-type and db/db mice (a genetic T2D mouse model) was conducted to identify the key gene affecting T2D infection. Immunofluorescence staining was performed on corneal sections from T2D mice and patients with T2D. The effect of small interfering RNA (siRNA) knockdown on corneal HSV-1 infection was evaluated in both in vitro and in vivo models.</p><p><strong>Results: </strong>T2D mice exhibited a more severe infection phenotype following HSV-1 infection, characterized by augmented corneal opacity scores, elevated viral titers, and transcripts compared to control mice. Transcriptome analysis of corneal epithelium revealed a hyperactive viral response in T2D mice, highlighting the differentially expressed gene Rtp4 (encoding receptor transporter protein 4). Receptor transporter protein 4 (RTP4) expression was enhanced in the corneal epithelium of T2D mice and patients with T2D. Virus binding assays demonstrated that RTP4 facilitated HSV-1 binding to human corneal epithelial cells. Silencing RTP4 alleviated HSV-1 infection in both in vitro and in vivo T2D models.</p><p><strong>Conclusions: </strong>The findings indicate that elevated RTP4 exacerbates HSV-1 infection by enhancing its binding to corneal epithelial cells, whereas Rtp4 knockdown mitigated corneal lesions in T2D mice. This implies RTP4 as a potential target for intervention in diabetic HSV-1 infection.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acute Effects of Oral Caffeine Intake on Human Global-Flash mfERG Responses: A Placebo-Controlled, Double-Masked, Balanced Crossover Study. 口服咖啡因对人体全闪烁 mfERG 反应的急性影响:一项安慰剂对照、双掩蔽、平衡交叉研究。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-09-03 DOI: 10.1167/iovs.65.11.10
Jesús Vera, Beatriz Redondo, Fuensanta A Vera-Diaz, Athanasios Panorgias
{"title":"Acute Effects of Oral Caffeine Intake on Human Global-Flash mfERG Responses: A Placebo-Controlled, Double-Masked, Balanced Crossover Study.","authors":"Jesús Vera, Beatriz Redondo, Fuensanta A Vera-Diaz, Athanasios Panorgias","doi":"10.1167/iovs.65.11.10","DOIUrl":"10.1167/iovs.65.11.10","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the acute effect of caffeine intake on the retinal responses as measured with a global-flash multifocal electroretinogram (gfmERG) protocol at different contrast levels.</p><p><strong>Methods: </strong>Twenty-four young adults (age = 23.3 ± 2.4 years) participated in this placebo-controlled, double-masked, balanced crossover study. On two different days, participants orally ingested caffeine (300 mg) or placebo, and retinal responses were recorded 90 minutes later using a gfmERG at three contrast levels (95%, 50%, and 29%). The amplitude response density and peak time of the direct and induced components (direct component [DC] and induced component [IC], respectively) were extracted for five different eccentricities (1.3°, 5.0°, 9.6°, 15.2°, and 21.9°). Axial length, spherical equivalent refraction, habitual caffeine intake, and body weight were considered as continuous covariates.</p><p><strong>Results: </strong>Increased IC amplitude response density was found after caffeine ingestion in comparison to placebo (P = 0.021, ƞp2 = 0.23), specifically for the 95% and 50% stimulus contrasts (P = 0.024 and 0.018, respectively). This effect of caffeine on IC amplitude response density was independent of the retinal eccentricity (P = 0.556). Caffeine had no effect on DC amplitude response density or DC and IC peak times.</p><p><strong>Conclusions: </strong>Our results show that oral caffeine intake increases the inner electro-retinal activity in young adults when viewing stimuli of high- (95%) to medium-contrast (50%). Given the increasing evidence that the inner retinal function is involved in the emmetropization process, these results may suggest that caffeine or its derivatives could potentially play a role in the mechanisms involved in eye growth.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of Ambient Lighting on Intraocular Pressure Rhythms in Rats. 环境照明对大鼠眼压节律的影响
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-08-01 DOI: 10.1167/iovs.65.10.16
Christina M Nicou, Christopher L Passaglia
{"title":"Effect of Ambient Lighting on Intraocular Pressure Rhythms in Rats.","authors":"Christina M Nicou, Christopher L Passaglia","doi":"10.1167/iovs.65.10.16","DOIUrl":"10.1167/iovs.65.10.16","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to determine the effects of ambient lighting on intraocular pressure (IOP) rhythmicity and variability.</p><p><strong>Methods: </strong>IOP was continuously recorded by wireless telemetry from rats under light/dark (LD), dark/light (DL), asymmetric (6L18D and 18D6L), constant dark (DD), and constant light (LL) cycles. In some DD experiments, 1-hour light pulses were presented at varying times. IOP rhythmicity and variability were respectively quantified via cosinor analysis and peak detection algorithms that identified transient and sustained fluctuations.</p><p><strong>Results: </strong>Rat IOP peaked at night and troughed during the day with LD amplitude of 8.7 ± 3.4 mm Hg. Rhythmicity persisted in DD and LL with a free-running period of 24.1 ± 0.3 and 25.2 ± 0.4 hours, respectively. Peak-to-trough amplitude was approximately 60% smaller in LL, often disappeared after 1 to 2 weeks as daytime IOP drifted 2.6 ± 1.5 mm Hg higher, and returned to approximately 60% larger in LD. Rhythmicity was similarly impacted but resynchronized to DL over 4 to 6 days. Rhythmicity was unaltered by short photoperiods (6L18D), but the nocturnal IOP elevation was markedly shortened by long photoperiods (18L6D) and temporarily lowered to daytime levels by light pulses during the subjective night. Transient and sustained event rate, amplitude, interval, and energy content were nearly identical in LD, DD, and LL.</p><p><strong>Conclusions: </strong>Aqueous humor dynamics of rat eyes are intrinsically configured to set IOP at daytime levels. Circadian clock input modulates these dynamics to elevate IOP at night. Light at night blocks this input, sending IOP back to daytime levels. Effects of abnormal lighting on IOP rhythmicity may contribute to pressure-related ocular neuropathies.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11314632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fabry Disease Rat Model Develops Age- and Sex-Dependent Anterior Segment Ocular Abnormalities. 法布里病大鼠模型出现与年龄和性别相关的眼球前段异常。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-08-01 DOI: 10.1167/iovs.65.10.14
Madelyn E Erdman, Sanjay Ch, Amer Mohiuddin, Khalid Al-Kirwi, Molly R Rasper, Sibabalo Sokupa, Shermaine W Y Low, Christine M B Skumatz, Vinicius De Stefano, Iris S Kassem, Shyam S Chaurasia
{"title":"Fabry Disease Rat Model Develops Age- and Sex-Dependent Anterior Segment Ocular Abnormalities.","authors":"Madelyn E Erdman, Sanjay Ch, Amer Mohiuddin, Khalid Al-Kirwi, Molly R Rasper, Sibabalo Sokupa, Shermaine W Y Low, Christine M B Skumatz, Vinicius De Stefano, Iris S Kassem, Shyam S Chaurasia","doi":"10.1167/iovs.65.10.14","DOIUrl":"10.1167/iovs.65.10.14","url":null,"abstract":"<p><strong>Purpose: </strong>Fabry disease is an X-linked lysosomal storage disorder that results in multi-systemic renal, cardiovascular, and neuropathological damage, including in the eyes. We evaluated anterior segment ocular abnormalities based on age, sex (male and female), and genotype (wild-type, knockout [KO] male, heterozygous [HET] female, and KO female) in a rat model of Fabry disease.</p><p><strong>Methods: </strong>The α-Gal A KO and WT rats were divided into young (6-24 weeks), adult (25-60 weeks), and aged (61+ weeks) groups. Intraocular pressure (IOP) was measured. Eyes were clinically scored for corneal and lens opacity as well as evaluated for corneal epithelial integrity and tear break-up time (TBUT). Anterior chamber depth (ACD) and central corneal thickness (CCT) using anterior segment-optical coherence tomography (AS-OCT).</p><p><strong>Results: </strong>The Fabry rats showed an age-dependent increase in IOP, predominantly in the male genotype. TBUT was decreased in both male and female groups with aging. Epithelial integrity was defective in KO males and HET females with age. However, it was highly compromised in KO females irrespective of age. Corneal and lens opacities were severely affected irrespective of sex or genotype in the aging Fabry rats. AS-OCT quantification of CCT and ACD also demonstrated age-dependent increases but were more pronounced in Fabry versus WT genotypes.</p><p><strong>Conclusions: </strong>Epithelial integrity, corneal, and lens opacities worsened in Fabry rats, whereas IOP and TBUT changes were age-dependent. Similarly, CCT and ACD were age-related but more pronounced in Fabry rats, providing newer insights into the anterior segment ocular abnormalities with age, sex, and genotype in a rat model of Fabry disease.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11314710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Localized Evaporative Cooling Explains Observed Ocular Surface-Temperature Patterns. 局部蒸发冷却解释了观察到的眼表温度模式。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-08-01 DOI: 10.1167/iovs.65.10.15
Young Hyun Kim, Joshua Lee, Sarah M Yi, Meng C Lin, Clayton J Radke
{"title":"Localized Evaporative Cooling Explains Observed Ocular Surface-Temperature Patterns.","authors":"Young Hyun Kim, Joshua Lee, Sarah M Yi, Meng C Lin, Clayton J Radke","doi":"10.1167/iovs.65.10.15","DOIUrl":"10.1167/iovs.65.10.15","url":null,"abstract":"<p><strong>Purpose: </strong>We determined interblink corneal surface-temperature decline and tear-film evaporation rates of localized tear breakup cold regions (LCRs) and localized tear unbroken warm regions (LWRs) of the corneal surface, as well as that of the overall average corneal surface.</p><p><strong>Methods: </strong>Each subject underwent 4 inter-day visits where the interblink corneal surface-temperature history of the right eye was measured using a FLIR A655sc infrared thermographer. Corneal surface temperature history was analyzed to determine the overall, LCR, and LWR temperature-decline rates. Evaporation rates of LCR and LWR regions were determined from the measured LCR and LWR temperature data using the physical model of Dursch et al.</p><p><strong>Results: </strong>Twenty subjects completed the study. Mean (SD) difference of LCR temperature-decline rate was -0.08 (0.07)°C/s faster than LWR (P < 0.0001). Similarly, evaporation rates of LCR and LWR were statistically different (P < 0.0001). At ambient temperature, mean LCR and LWR evaporation rates were 76% and 27% of pure water evaporation flux, respectively. There was no statistically significant difference between the inter-day measured temperature-decline rates and the interblink starting temperature.</p><p><strong>Conclusions: </strong>Significant differences in corneal temperature-decline rate and evaporation rate between LCR and LWR were quantified using infrared thermography. In agreement with literature, LCRs and LWRs correlate directly with fluorescein break-up areas and unbroken tear areas, respectively. Because lipid-evaporation protection is diminished in breakup areas, higher local evaporation rates and faster local cooling rates occur in LCRs relative to LWRs. Our results confirm this phenomenon clinically for the first time.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11314627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cholesterol Accumulation Promotes Photoreceptor Senescence and Retinal Degeneration. 胆固醇积累促进光感受器衰老和视网膜退化
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-08-01 DOI: 10.1167/iovs.65.10.29
Ryo Terao, Brian S Sohn, Taku Yamamoto, Tae Jun Lee, Jason Colasanti, Charles W Pfeifer, Joseph B Lin, Andrea Santeford, Shinobu Yamaguchi, Mitsukuni Yoshida, Rajendra S Apte
{"title":"Cholesterol Accumulation Promotes Photoreceptor Senescence and Retinal Degeneration.","authors":"Ryo Terao, Brian S Sohn, Taku Yamamoto, Tae Jun Lee, Jason Colasanti, Charles W Pfeifer, Joseph B Lin, Andrea Santeford, Shinobu Yamaguchi, Mitsukuni Yoshida, Rajendra S Apte","doi":"10.1167/iovs.65.10.29","DOIUrl":"10.1167/iovs.65.10.29","url":null,"abstract":"<p><strong>Purpose: </strong>Dysregulated cholesterol metabolism is critical in the pathogenesis of AMD. Cellular senescence contributes to the development of numerous age-associated diseases. In this study, we investigated the link between cholesterol burden and the cellular senescence of photoreceptors.</p><p><strong>Methods: </strong>Retinas from rod-specific ATP binding cassette subfamily A member 1 (Abca1) and G member 1 (Abcg1) (Abca1/g1-rod/-rod) knockout mice fed with a high-fat diet were analyzed for the signs of cellular senescence. Real-time quantitative PCR and immunofluorescence were used to characterize the senescence profile of the retina and cholesterol-treated photoreceptor cell line (661W). Inducible elimination of p16(Ink4a)-positive senescent cells (INK-ATTAC) mice or the administration of senolytic drugs (dasatinib and quercetin: D&Q) were used to examine the impact of senolytics on AMD-like phenotypes in Abca1/g1-rod/-rod retina.</p><p><strong>Results: </strong>Increased accumulation of senescent cells as measured by markers of cellular senescence was found in Abca1/g1-rod/-rod retina. Exogenous cholesterol also induced cellular senescence in 661W cells. Selective elimination of senescent cells in Abca1/g1-rod/-rod;INK-ATTAC mice or by administration of D&Q improved visual function, lipid accumulation in retinal pigment epithelium, and Bruch's membrane thickening.</p><p><strong>Conclusions: </strong>Cholesterol accumulation promotes cellular senescence in photoreceptors. Eliminating senescent photoreceptors improves visual function in a model of retinal neurodegeneration, and senotherapy offers a novel therapeutic avenue for further investigation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of Age of Menopause and Glaucoma Diagnosis in Female Veterans. 女性退伍军人绝经年龄与青光眼诊断的关系。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-08-01 DOI: 10.1167/iovs.65.10.32
Kelleigh Hogan, Xiangqin Cui, Annette Giangiacomo, Andrew J Feola
{"title":"Association of Age of Menopause and Glaucoma Diagnosis in Female Veterans.","authors":"Kelleigh Hogan, Xiangqin Cui, Annette Giangiacomo, Andrew J Feola","doi":"10.1167/iovs.65.10.32","DOIUrl":"10.1167/iovs.65.10.32","url":null,"abstract":"<p><strong>Purpose: </strong>Age of menopause has been associated with the risk of developing glaucoma; however, it is unclear if the onset of menopause is directly associated with the development of glaucoma. Our objective was to determine if there is an association between the age at diagnosis of menopause and glaucoma.</p><p><strong>Methods: </strong>This retrospective, case-only analysis was performed using the Veterans Affairs (VA) Corporate Data Warehouse of female veterans from 2000 to 2019. Women with both menopause and glaucoma diagnoses were matched based on covariates. The two matched cohorts were early menopause-early comparative (EM-EC; n = 1075) and late menopause-late comparative (LM-LC; n = 1050) women. We used a Pearson correlation to examine the linear relationship between age at diagnosis of menopause and glaucoma. Afterward, we used a multivariate linear regression model with age at diagnosis of glaucoma serving as the outcome variable to account for the covariates.</p><p><strong>Results: </strong>We found that EM women developed glaucoma 6.0 years (interquartile range [IQR], 5.1-6.5) earlier than the EC group (P < 0.001), and LM women developed glaucoma an average of 5.2 years (IQR, 4.8-5.7) later than the LC group (P < 0.001). There was a modest linear relationship between the age of menopause and glaucoma diagnoses in the EM-EC (r = 0.40) and LM-LC (r = 0.46) cohorts. In our multivariate analysis, age at diagnosis of menopause was the largest factor related to age at diagnosis of glaucoma while accounting for our covariates. Our models predicted a 0.67-year delay in age at diagnosis of glaucoma with each additional premenopausal year.</p><p><strong>Conclusions: </strong>This case-only analysis elucidates a temporal association between menopause and glaucoma, highlighting the need to characterize the role of menopause in the onset of glaucoma for women.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Landolt C-Tests With "Fixed" Arcmin Separations Detect Amblyopia But Underestimate Crowding in Moderate-to-Severe Amblyopic Children and Adults. 具有 "固定 "弧分间隔的兰多尔特 C 测试可检测中度至重度弱视儿童和成人的弱视,但低估了拥挤程度。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-08-01 DOI: 10.1167/iovs.65.10.33
Sarah J Waugh, Maria Fronius
{"title":"Landolt C-Tests With \"Fixed\" Arcmin Separations Detect Amblyopia But Underestimate Crowding in Moderate-to-Severe Amblyopic Children and Adults.","authors":"Sarah J Waugh, Maria Fronius","doi":"10.1167/iovs.65.10.33","DOIUrl":"10.1167/iovs.65.10.33","url":null,"abstract":"<p><strong>Purpose: </strong>Crowding is exaggerated in central vision of strabismic amblyopia, impacting on reading ability. Crowding magnitude and interocular differences (IODs) in acuity are indicators for detection, assessment, and monitoring of treatment. Lateral masking (including contour interaction) also affects acuity and can mimic or ameliorate crowding. We investigated lateral masking/contour interaction and crowding impact on crowding magnitude and IOD measures in healthy and amblyopic pediatric and juvenile/adult groups using two Landolt C-tests with \"fixed\" arcmin separations.</p><p><strong>Methods: </strong>Acuity (logMAR) was measured with Landolt C-tests with specified 2.6' (\"crowded\") and 35' (\"uncrowded\") separations. Crowding magnitudes (crowded - uncrowded acuities) and IODs were calculated. Participants were 69 subjects with strabismic amblyopia (n = 39 pediatric, i.e. children ≤8 years of age), 31 subjects with anisometropic amblyopia (n = 14 pediatric), and 76 healthy controls (n = 36 pediatric). Subjects with amblyopia were subgrouped by acuity as low severity (<0.4 logMAR) or high severity (≥0.4 logMAR) using the 35' separation C-test.</p><p><strong>Results: </strong>Crowding magnitudes were greater in strabismic than in anisometropic amblyopia and control/fellow eyes. They were higher in pediatric control/fellow eyes than in juvenile/adult eyes. In high severity strabismic amblyopia, crowding magnitudes progressively and significantly reduced (slope = -0.17 ± 0.07, P < 0.05) with worsening acuity. IODs for this group were higher on the 2.6' C-test, but lower than expected. In high severity pediatric subjects with anisometropic amblyopia, seven of eight had lower IODs measured with the \"crowded\" than the \"uncrowded\" C-tests.</p><p><strong>Conclusions: </strong>These C-tests detect amblyopia but underestimate crowding in children and adults with high severity strabismic amblyopia. Separate isolated optotype acuity and crowding distance tests may better target specific functions, while minimizing the impact of masking.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Systemic Genotype-Phenotype Characterization of PAX6-Related Eye Disease in 164 Chinese Families. 164个中国家庭中与PAX6相关眼病的系统基因型表型特征分析
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-08-01 DOI: 10.1167/iovs.65.10.46
Yi Jiang, Zhen Yi, Yuxi Zheng, Jiamin Ouyang, Dongwei Guo, Shiqiang Li, Xueshan Xiao, Panfeng Wang, Wenmin Sun, Qingjiong Zhang
{"title":"The Systemic Genotype-Phenotype Characterization of PAX6-Related Eye Disease in 164 Chinese Families.","authors":"Yi Jiang, Zhen Yi, Yuxi Zheng, Jiamin Ouyang, Dongwei Guo, Shiqiang Li, Xueshan Xiao, Panfeng Wang, Wenmin Sun, Qingjiong Zhang","doi":"10.1167/iovs.65.10.46","DOIUrl":"10.1167/iovs.65.10.46","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to evaluate the genetic and phenotypic characteristics and elucidate the genotype-phenotype correlations of a large Chinese cohort with PAX6-related disorders.</p><p><strong>Methods: </strong>Variants detected with exome sequencing were filtered through multistep bioinformatic and co-segregation analyses, and validated by Sanger sequencing. The related clinical data were collected, and cluster analysis and statistical analysis of the PAX6-related phenotypes across different variant groups were carried out. Parental mosaicism was investigated using cloning analysis and Droplet digital PCR.</p><p><strong>Results: </strong>A total of 119 pathogenic or likely pathogenic PAX6 variants, including 74 truncation, 31 missense, and 14 others, were identified in 228 patients from 164 unrelated families. The most common phenotypes were foveal hypoplasia (97.8%), nystagmus (92.6%), aniridia (76.7%), cataract (36.8%), and iris hypoplasia (22.4%). Mosaicism ranging from 13.9% to 18.8% was identified in 3 unrelated patients' parents with relatively mild phenotypes. Missense variants in the linker region of the paired domain were associated with high myopia, whereas truncation variants in the homeodomain and proline-serine-threonine-rich domain were associated with hyperopia. Similarly, the degree of iris defects, visual acuity, and associated ocular comorbidity varied among the different types and locations of PAX6 variants.</p><p><strong>Conclusions: </strong>Our data indicate that foveal hypoplasia but not aniridia is the most common sign of PAX6-related disorders, contributing to subtle iris changes that might easily be overlooked in clinical practice. Recognition of mosaicism in atypical cases or parents with very mild phenotypes is important in genetic counseling as their offspring are at increased risk of typical aniridia. Recognition of the genotype-phenotype relationship emphasizes involvement of PAX6 regulation in shaping complex ocular phenotypes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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