Connor Ross BS , Alexander Ivanov MS , Tobias Elze PhD , Joan W. Miller MD , Flora Lum MD , Alice C. Lorch MD, MPH , Isdin Oke MD, MPH , IRIS® Registry Analytic Center Consortium
{"title":"Factors Associated with Missing Sociodemographic Data in the IRIS® (Intelligent Research in Sight) Registry","authors":"Connor Ross BS , Alexander Ivanov MS , Tobias Elze PhD , Joan W. Miller MD , Flora Lum MD , Alice C. Lorch MD, MPH , Isdin Oke MD, MPH , IRIS® Registry Analytic Center Consortium","doi":"10.1016/j.xops.2024.100542","DOIUrl":"10.1016/j.xops.2024.100542","url":null,"abstract":"<div><h3>Purpose</h3><p>To describe the prevalence of missing sociodemographic data in the IRIS® (Intelligent Research in Sight) Registry and to identify practice-level characteristics associated with missing sociodemographic data.</p></div><div><h3>Design</h3><p>Cross-sectional study.</p></div><div><h3>Participants</h3><p>All patients with clinical encounters at practices participating in the IRIS Registry prior to December 31, 2020.</p></div><div><h3>Methods</h3><p>We describe geographic and temporal trends in the prevalence of missing data for each sociodemographic variable (age, sex, race, ethnicity, geographic location, insurance type, and smoking status). Each practice contributing data to the registry was categorized based on the number of patients, number of physicians, geographic location, patient visit frequency, and patient population demographics.</p></div><div><h3>Main Outcome Measures</h3><p>Multivariable linear regression was used to describe the association of practice-level characteristics with missing patient-level sociodemographic data.</p></div><div><h3>Results</h3><p>This study included the electronic health records of 66 477 365 patients receiving care at 3306 practices participating in the IRIS Registry. The median number of patients per practice was 11 415 (interquartile range: 5849–24 148) and the median number of physicians per practice was 3 (interquartile range: 1–7). The prevalence of missing patient sociodemographic data were 0.1% for birth year, 0.4% for sex, 24.8% for race, 30.2% for ethnicity, 2.3% for 3-digit zip code, 14.8% for state, 5.5% for smoking status, and 17.0% for insurance type. The prevalence of missing data increased over time and varied at the state-level. Missing race data were associated with practices that had fewer visits per patient (<em>P</em> < 0.001), cared for a larger nonprivately insured patient population (<em>P</em> = 0.001), and were located in urban areas (<em>P</em> < 0.001). Frequent patient visits were associated with a lower prevalence of missing race (<em>P</em> < 0.001), ethnicity (<em>P</em> < 0.001), and insurance (<em>P</em> < 0.001), but a higher prevalence of missing smoking status (<em>P</em> < 0.001).</p></div><div><h3>Conclusions</h3><p>There are geographic and temporal trends in missing race, ethnicity, and insurance type data in the IRIS Registry. Several practice-level characteristics, including practice size, geographic location, and patient population, are associated with missing sociodemographic data. While the prevalence and patterns of missing data may change in future versions of the IRIS registry, there will remain a need to develop standardized approaches for minimizing potential sources of bias and ensure reproducibility across research studies.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 6","pages":"Article 100542"},"PeriodicalIF":3.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000782/pdfft?md5=9f01027aeda71e03dab8f257df85f964&pid=1-s2.0-S2666914524000782-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141949711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Is CONNECTDROP®, a Medication Event Monitoring System Add-On Paired with a Smartphone Application, Acceptable to Patients with Glaucoma for Taking Their Daily Medication? The CONDORE Pilot Study","authors":"Jean-Baptiste Dériot MD, Emmanuelle Albertini MD","doi":"10.1016/j.xops.2024.100541","DOIUrl":"10.1016/j.xops.2024.100541","url":null,"abstract":"<div><h3>Objective</h3><p>This pilot study tested the feasibility of a future efficacy trial examining the effect of CONNECTDROP®, a novel Medication Event Monitoring System (MEMS) paired with a mHealth application, on medication adherence in patients with glaucoma.</p></div><div><h3>Design</h3><p>A single-center, single-arm, prospective interventional pilot study (NCT04552964).</p></div><div><h3>Participants</h3><p>Adults with glaucoma managed with at least a fixed combination of timolol/dorzolamide who are adherent to treatment.</p></div><div><h3>Methods</h3><p>Participants (n = 31) were provided with the MEMS device and a smartphone with the application installed. They were required to use the MEMS with their usual timolol/dorzolamide prescription for 9 weeks. The study endpoint was at the end of week 9, when all study materials were returned, and participants completed a 17-item patient satisfaction questionnaire. Data collected continuously by each MEMS for the 9 weeks were analyzed for their suitability to quantify adherence of the individual participant and characterize adherence trends within the study cohort. Clinical data were collected at baseline, week 8, and week 9 for the safety evaluation.</p></div><div><h3>Main Outcome Measures</h3><p>The primary outcome was global patient satisfaction after 9 weeks. Secondary outcome measures included participant feedback on handling the MEMS and its usability, along with that of the connected application. Objective data were used to determine participant medication adherence. The proportion of participants who successfully changed the MEMS to a new bottle at week 8 was reported.</p></div><div><h3>Results</h3><p>The MEMS-connected device achieved a global satisfaction score of 74.1% from study participants after 9 weeks. Furthermore, 70.4% of participants found the MEMS easy to use. However, only 59.2% reported feedback from the mHealth application useful in reminding them to take their treatment. MEMS-derived data showed that 70.4% of participants achieved an \"adherence score\" of 80% or above after 8 weeks and that 40.7% who completed the study had not changed the bottle correctly. No adverse events (AEs) were reported.</p></div><div><h3>Conclusion</h3><p>In this pilot study, the CONNECTDROP device was able to monitor daily intake of anti-glaucomatous medication over 2 months and had high satisfaction amongst this cohort of patients and was easy to use. The objective adherence data obtained appears reliable but must be validated for use in an efficacy trial.</p></div><div><h3>Financial Disclosure(s)</h3><p>The authors have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 6","pages":"Article 100541"},"PeriodicalIF":3.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000770/pdfft?md5=1bdc170bfbfc89972b19e2ec9e55ee84&pid=1-s2.0-S2666914524000770-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142162507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abadh K. Chaurasia MOptom , Connor J. Greatbatch MBBS , Xikun Han PhD , Puya Gharahkhani PhD , David A. Mackey MD, FRANZCO , Stuart MacGregor PhD , Jamie E. Craig MBBS, PhD , Alex W. Hewitt MBBS, FRANZCO, PhD
{"title":"Highly Accurate and Precise Automated Cup-to-Disc Ratio Quantification for Glaucoma Screening","authors":"Abadh K. Chaurasia MOptom , Connor J. Greatbatch MBBS , Xikun Han PhD , Puya Gharahkhani PhD , David A. Mackey MD, FRANZCO , Stuart MacGregor PhD , Jamie E. Craig MBBS, PhD , Alex W. Hewitt MBBS, FRANZCO, PhD","doi":"10.1016/j.xops.2024.100540","DOIUrl":"https://doi.org/10.1016/j.xops.2024.100540","url":null,"abstract":"<div><h3>Objective</h3><p>An enlarged cup-to-disc ratio (CDR) is a hallmark of glaucomatous optic neuropathy. Manual assessment of the CDR may be less accurate and more time-consuming than automated methods. Here, we sought to develop and validate a deep learning–based algorithm to automatically determine the CDR from fundus images.</p></div><div><h3>Design</h3><p>Algorithm development for estimating CDR using fundus data from a population-based observational study.</p></div><div><h3>Participants</h3><p>A total of 181 768 fundus images from the United Kingdom Biobank (UKBB), Drishti_GS, and EyePACS.</p></div><div><h3>Methods</h3><p>FastAI and PyTorch libraries were used to train a convolutional neural network–based model on fundus images from the UKBB. Models were constructed to determine image gradability (classification analysis) as well as to estimate CDR (regression analysis). The best-performing model was then validated for use in glaucoma screening using a multiethnic dataset from EyePACS and Drishti_GS.</p></div><div><h3>Main Outcome Measures</h3><p>The area under the receiver operating characteristic curve and coefficient of determination.</p></div><div><h3>Results</h3><p>Our gradability model vgg19_batch normalization (bn) achieved an accuracy of 97.13% on a validation set of 16 045 images, with 99.26% precision and area under the receiver operating characteristic curve of 96.56%. Using regression analysis, our best-performing model (trained on the vgg19_bn architecture) attained a coefficient of determination of 0.8514 (95% confidence interval [CI]: 0.8459–0.8568), while the mean squared error was 0.0050 (95% CI: 0.0048–0.0051) and mean absolute error was 0.0551 (95% CI: 0.0543–0.0559) on a validation set of 12 183 images for determining CDR. The regression point was converted into classification metrics using a tolerance of 0.2 for 20 classes; the classification metrics achieved an accuracy of 99.20%. The EyePACS dataset (98 172 healthy, 3270 glaucoma) was then used to externally validate the model for glaucoma classification, with an accuracy, sensitivity, and specificity of 82.49%, 72.02%, and 82.83%, respectively.</p></div><div><h3>Conclusions</h3><p>Our models were precise in determining image gradability and estimating CDR. Although our artificial intelligence–derived CDR estimates achieve high accuracy, the CDR threshold for glaucoma screening will vary depending on other clinical parameters.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100540"},"PeriodicalIF":3.2,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000769/pdfft?md5=2051286bae03382c02eff7d1df69d56a&pid=1-s2.0-S2666914524000769-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rachana Haliyur MD, PhD , David H. Parkinson MS , Feiyang Ma PhD , Jing Xu PhD , Qiang Li MD, PhD , Yuanhao Huang , Lam C. Tsoi PhD , Rachael Bogle MS , Jie Liu PhD , Johann E. Gudjonsson MD , Rajesh C. Rao MD
{"title":"Liquid Biopsy for Proliferative Diabetic Retinopathy: Single-Cell Transcriptomics of Human Vitreous Reveals Inflammatory T-Cell Signature","authors":"Rachana Haliyur MD, PhD , David H. Parkinson MS , Feiyang Ma PhD , Jing Xu PhD , Qiang Li MD, PhD , Yuanhao Huang , Lam C. Tsoi PhD , Rachael Bogle MS , Jie Liu PhD , Johann E. Gudjonsson MD , Rajesh C. Rao MD","doi":"10.1016/j.xops.2024.100539","DOIUrl":"10.1016/j.xops.2024.100539","url":null,"abstract":"<div><h3>Purpose</h3><p>Current therapies for proliferative diabetic retinopathy (PDR) do not specifically target VEGF-independent, cell-type–specific processes that lead to vision loss, such as inflammatory pathways. This study aimed to identify targetable cell types and corresponding signaling pathways by elucidating the single-cell landscape of the vitreous of patients with PDR.</p></div><div><h3>Design</h3><p>Case series.</p></div><div><h3>Subjects</h3><p>Vitreous and peripheral blood obtained from 5 adult patients (6 eyes) undergoing pars plana vitrectomy for vision-threatening PDR.</p></div><div><h3>Methods</h3><p>Single-cell RNA sequencing (scRNA-seq) was performed on vitreous cells obtained from diluted cassette washings during vitrectomy from 6 eyes and peripheral blood mononuclear cells (PBMCs, n = 5). Droplet-based scRNA-seq was performed using the Chromium 10x platform to obtain single-cell transcriptomes. Differences in tissue compartments were analyzed with gene ontology enrichment of differentially expressed genes and an unbiased ligand–receptor interaction analysis.</p></div><div><h3>Main Outcome Measures</h3><p>Single-cell transcriptomic profiles of vitreous and peripheral blood.</p></div><div><h3>Results</h3><p>Transcriptomes from 13 675 surgically harvested vitreous cells and 22 636 PBMCs were included. Clustering revealed 4 cell states consistently across all eyes with representative transcripts for T cells (<em>CD2</em>, <em>CD3D</em>, <em>CD3E</em>, and <em>GZMA</em>), B cells (<em>CD79A</em>, <em>IGHM</em>, <em>MS4A1</em> (CD20), and <em>HLA-DRA</em>), myeloid cells (<em>LYZ</em>, <em>CST3</em>, <em>AIF1</em>, and <em>IFI30</em>), and neutrophils (<em>BASP1</em>, <em>CXCR2</em>, <em>S100A8</em>, and <em>S100A9</em>). Most vitreous cells were T cells (91.6%), unlike the peripheral blood (46.2%), whereas neutrophils in the vitreous were essentially absent. The full repertoire of adaptive T cells including CD4+, CD8+ and T regulatory cells (Treg) and innate immune system effectors (i.e., natural killer T cells) was present in the vitreous. Pathway analysis also demonstrated activation of CD4+ and CD8+ memory T cells and ligand–receptor interactions unique to the vitreous.</p></div><div><h3>Conclusions</h3><p>In the first single-cell transcriptomic characterization of human vitreous in a disease state, we show PDR vitreous is primarily composed of T cells, a critical component of adaptive immunity, with activity and proportions distinct from T cells within the peripheral blood, and neutrophils are essentially absent. These results demonstrate the feasibility of liquid vitreous biopsies via collection of otherwise discarded, diluted cassette washings during vitrectomy to gain mechanistic and therapeutic insights into human vitreoretinal disease.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 6","pages":"Article 100539"},"PeriodicalIF":3.2,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000757/pdfft?md5=b0564bad17268d31be2faeea5ce8b098&pid=1-s2.0-S2666914524000757-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141963046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simon Nusinovici PhD , Lei Zhou PhD , Xinyue Wang MS , Yih Chung Tham PhD , Xiaomeng Wang PhD , Tien Yin Wong MD, PhD , Usha Chakravarthy MD, PhD , Ching-Yu Cheng MD, PhD
{"title":"Contributions of Lipid-Related Metabolites and Complement Proteins to Early and Intermediate Age-Related Macular Degeneration","authors":"Simon Nusinovici PhD , Lei Zhou PhD , Xinyue Wang MS , Yih Chung Tham PhD , Xiaomeng Wang PhD , Tien Yin Wong MD, PhD , Usha Chakravarthy MD, PhD , Ching-Yu Cheng MD, PhD","doi":"10.1016/j.xops.2024.100538","DOIUrl":"https://doi.org/10.1016/j.xops.2024.100538","url":null,"abstract":"<div><h3>Objective</h3><p>Our objective was to determine the effects of lipids and complement proteins on early and intermediate age-related macular degeneration (AMD) stages using machine learning models by integrating metabolomics and proteomic data.</p></div><div><h3>Design</h3><p>Nested case–control study.</p></div><div><h3>Subjects and Controls</h3><p>The analyses were performed in a subset of the Singapore Indian Chinese Cohort (SICC) Eye Study. Among the 6753 participants, we randomly selected 155 Indian and 155 Chinese cases of AMD and matched them with 310 controls on age, sex, and ethnicity.</p></div><div><h3>Methods</h3><p>We measured 35 complement proteins and 56 lipids using mass spectrometry and nuclear magnetic resonance, respectively. We first selected the most contributing lipids and complement proteins to early and intermediate AMD using random forest models. Then, we estimated their effects using a multinomial model adjusted for potential confounders.</p></div><div><h3>Main Outcome Measures</h3><p>Age-related macular degeneration was classified using the Beckman classification system.</p></div><div><h3>Results</h3><p>Among the 310 individuals with AMD, 166 (53.5%) had early AMD, and 144 (46.5%) had intermediate AMD. First, high-density lipoprotein (HDL) particle diameter was positively associated with both early and intermediate AMD (odds ratio [OR]<sub>early</sub> = 1.69; 95% confidence interval [CI],1.11–2.55 and OR<sub>intermediate</sub> = 1.72; 95% CI, 1.11–2.66 per 1-standard deviation increase in HDL diameter). Second, complement protein 2 (C2), complement C1 inhibitor (IC1), complement protein 6 (C6), complement protein 1QC (C1QC) and complement factor H-related protein 1 (FHR1), were associated with AMD. C2 was positively associated with both early and intermediate AMD (OR<sub>early</sub> = 1.58; 95% CI, 1.08–2.30 and OR<sub>intermediate</sub> = 1.56; 95% CI, 1.04–2.34). C6 was positively (OR<sub>early</sub> = 1.41; 95% CI, 1.03–1.93) associated with early AMD. However, IC1 was negatively associated with early AMD (OR<sub>early</sub> = 0.62; 95% CI, 0.38–0.99), whereas C1QC (OR<sub>intermediate</sub> = 0.63; 95% CI, 0.42–0.93) and FHR1 (OR<sub>intermediate</sub> = 0.73; 95% CI, 0.54–0.98) were both negatively associated with intermediate AMD.</p></div><div><h3>Conclusions</h3><p>Although both HDL diameter and C2 levels show associations with both early and intermediate AMD, dysregulations of IC1, C6, C1QC, and FHR1 are only observed at specific stages of AMD. These findings underscore the complexity of complement system dysregulation in AMD, which appears to vary depending on the disease severity.</p></div><div><h3>Financial Disclosure(s)</h3><p>The authors have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100538"},"PeriodicalIF":3.2,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000745/pdfft?md5=e3bd3d3b0fc07ddd1b2067bcad6b08f0&pid=1-s2.0-S2666914524000745-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emmanuel K. Addo OD , Joanna E. Gorka BS , Susan J. Allman CCRC , Deborah Y. Harrison MSc , Mohsen Sharifzadeh PhD , Robert O. Hoffman MD , M. Elizabeth Hartnett MD , Michael W. Varner MD , Paul S. Bernstein MD, PhD
{"title":"Ocular Effects of Prenatal Carotenoid Supplementation in the Mother and Her Child: The Lutein and Zeaxanthin in Pregnancy (L-ZIP) Randomized Trial - Report Number 2","authors":"Emmanuel K. Addo OD , Joanna E. Gorka BS , Susan J. Allman CCRC , Deborah Y. Harrison MSc , Mohsen Sharifzadeh PhD , Robert O. Hoffman MD , M. Elizabeth Hartnett MD , Michael W. Varner MD , Paul S. Bernstein MD, PhD","doi":"10.1016/j.xops.2024.100537","DOIUrl":"10.1016/j.xops.2024.100537","url":null,"abstract":"<div><h3>Purpose</h3><p>Lutein (L) and zeaxanthin (Z) are xanthophyll carotenoids that have been promoted to enhance maternal health and infant visual and neurodevelopment. In this study, we determined the effects of prenatal L and Z supplementation on systemic and ocular carotenoid status in the mother and her newborn infant (NCT03750968). This report focuses on the ocular effects of prenatal carotenoid supplementation.</p></div><div><h3>Design</h3><p>A prospective randomized clinical trial with 47 subjects randomly assigned by 1:1 allocation to receive standard-of-care prenatal vitamins along with 10 mg L and 2 mg Z softgel (Carotenoid Group) or standard-of-care prenatal vitamins with a placebo softgel (Control Group) starting in the first trimester.</p></div><div><h3>Subjects</h3><p>We enrolled low-risk pregnancy subjects aged ≥18 years from the obstetrics and gynecology clinic of the University of Utah Hospital.</p></div><div><h3>Methods</h3><p>Maternal macular, skin, and serum carotenoid concentrations were measured using autofluorescence imaging, resonance Raman spectroscopy, and high-performance liquid chromatography, respectively. Infants’ ocular carotenoids and retinal architecture were measured by blue light reflectance imaging and spectral-domain OCT, respectively.</p></div><div><h3>Main Outcome Measures</h3><p>Changes in maternal and infant macular pigment, skin, and serum carotenoid status over the study period. Differences in infants’ retinal maturity indicators between the 2 study groups.</p></div><div><h3>Results</h3><p>Following supplementation, there was a statistically significant increase in maternal macular pigment optical volume (<em>P</em> < 0.001) in the Carotenoid Group relative to the Control Group at all study time points, and there was no detectable maternal ocular carotenoid depletion. Infant skin and serum carotenoids increased significantly in the Carotenoid Group compared with the Control Group. As exploratory endpoints, infants in the Carotenoid Group had a 20% increase in macular pigment optical density (<em>P</em> = 0.242) and more mature foveal parameters compared with those in the Control Group.</p></div><div><h3>Conclusion</h3><p>Prenatal carotenoid supplementation significantly increased maternal and infant systemic carotenoids and caused a pattern of increased infant ocular carotenoid status, which may benefit both mothers and their infants’ ocular development and function. This study provides important data to design and power a future multicenter study of prenatal carotenoid supplementation in higher-risk pregnancies.</p></div><div><h3>Financial Disclosure(s)</h3><p>The author(s) have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100537"},"PeriodicalIF":3.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000733/pdfft?md5=00e617c27d3ef6e20fa85d7a1b992d27&pid=1-s2.0-S2666914524000733-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140761423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samaneh Farashi PhD , Roberto Bonelli PhD , Victoria E. Jackson PhD , Brendan R.E. Ansell PhD , Robyn H. Guymer MBBS, PhD , Melanie Bahlo PhD
{"title":"Decreased Circulating Very Small Low-Density Lipoprotein is Likely Causal for Age-Related Macular Degeneration","authors":"Samaneh Farashi PhD , Roberto Bonelli PhD , Victoria E. Jackson PhD , Brendan R.E. Ansell PhD , Robyn H. Guymer MBBS, PhD , Melanie Bahlo PhD","doi":"10.1016/j.xops.2024.100535","DOIUrl":"10.1016/j.xops.2024.100535","url":null,"abstract":"<div><h3>Objective</h3><p>Abnormal changes in metabolite levels in serum or plasma have been highlighted in several studies in age-related macular degeneration (AMD), the leading cause of irreversible vision loss. Specific changes in lipid profiles are associated with an increased risk of AMD. Metabolites could thus be used to investigate AMD disease mechanisms or incorporated into AMD risk prediction models. However, whether particular metabolites causally affect the disease has yet to be established.</p></div><div><h3>Design</h3><p>A 3-tiered analysis of blood metabolites in the United Kingdom (UK) Biobank cohort to identify metabolites that differ in AMD patients with evidence for a putatively causal role in AMD.</p></div><div><h3>Participants</h3><p>A total of 72 376 donors from the UK Biobank cohort including participants with AMD (N = 1353) and non-AMD controls (N = 71 023).</p></div><div><h3>Methods</h3><p>We analyzed 325 directly measured or derived blood metabolites from the UK Biobank for 72 376 donors to identify AMD-associated metabolites. Genome-wide association studies for 325 metabolites in 98 316 European participants from the UK Biobank were performed. The causal effects of these metabolites in AMD were tested using a 2-sample Mendelian randomization approach. The predictive value of these measurements together with sex and age was assessed by developing a machine learning classifier.</p></div><div><h3>Main Outcome Measures</h3><p>Evaluating metabolic biomarkers associated with AMD susceptibility and investigating their potential causal contribution to the development of the disease.</p></div><div><h3>Results</h3><p>This study noted age to be the prominent risk factor associated with AMD development. While accounting for age and sex, we identified 84 metabolic markers as significantly (false discovery rate-adjusted <em>P</em> value < 0.05) associated with AMD. Lipoprotein subclasses comprised the majority of the AMD-associated metabolites (39%) followed by several lipoprotein to lipid ratios. Nineteen metabolites showed a likely causative role in AMD etiology. Of these, 6 lipoproteins contain very small, very low-density lipoprotein (VLDL), and phospholipids to total lipid ratio in medium VLDL. Based on this we postulate that depletion of circulating very small VLDLs is likely causal for AMD. The risk prediction model constructed from the metabolites, age and sex, identified age as the primary predictive factor with a much smaller contribution by metabolites to AMD risk prediction.</p></div><div><h3>Conclusions</h3><p>This study underscores the pronounced role of lipids in AMD susceptibility and the likely causal contribution of particular subclasses of lipoproteins to AMD. Our study provides valuable insights into the metabopathological mechanisms of AMD disease development and progression.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100535"},"PeriodicalIF":3.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266691452400071X/pdfft?md5=dd59b7a474641d6246898e35d7a7604b&pid=1-s2.0-S266691452400071X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140779863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cellular Determinants of Visual Outcomes in Eyes with Epiretinal Membrane: Insights from Adaptive Optics OCT","authors":"Masaharu Ishikura MD, PhD, Yuki Muraoka MD, PhD, Naomi Nishigori MD, Takahiro Kogo MD, Yuki Akiyama MD, Shogo Numa MD, PhD, Masayuki Hata MD, PhD, Kenji Ishihara MD, PhD, Sotaro Ooto MD, PhD, Akitaka Tsujikawa MD, PhD","doi":"10.1016/j.xops.2024.100536","DOIUrl":"10.1016/j.xops.2024.100536","url":null,"abstract":"<div><h3>Objective</h3><p>In this study, we aimed to evaluate cellular alterations in the foveal neuroglia of eyes with idiopathic epiretinal membrane (ERM) and examine their correlation with visual function. We also aimed to identify prognostic markers for visual outcomes postvitrectomy.</p></div><div><h3>Design</h3><p>A prospective longitudinal study.</p></div><div><h3>Subjects</h3><p>The study comprised 84 subjects, including 50 eyes diagnosed with idiopathic ERM and 34 healthy eyes serving as controls.</p></div><div><h3>Methods</h3><p>The foveal neuroglial changes in eyes with idiopathic ERM were determined using adaptive optics OCT (AO-OCT) by comparing them with healthy eyes. For patients with ERM, the ERM and inner limiting membrane were removed during vitrectomy in all eyes.</p></div><div><h3>Main Outcome Measures</h3><p>Foveal microstructures on AO-OCT images, best-corrected visual acuity (BCVA) and M-CHARTS scores, evaluated preoperatively and at 1, 3, and 6 months postoperatively, and associations between foveal neuroglial changes and these parameters.</p></div><div><h3>Results</h3><p>Adaptive optics OCT revealed discernible differences in the foveal cones of the eyes with ERM and their healthy counterparts. The thickness of the ellipsoid zone (EZ) band was augmented in eyes with ERM. The alignment of the Müller cells was more vertical and the density of the foveal cone cell nuclei was higher in eyes with ERM than in healthy eyes. Within the AO-OCT parameters, the higher cone nuclei count correlated with worse M-CHARTS scores, both preoperatively and 6 months postoperatively (<em>P</em> = 0.004, 0.010, respectively). Greater EZ thickness was significantly associated with poorer 6-month postoperative BCVA (<em>P</em> = 0.005).</p></div><div><h3>Conclusions</h3><p>Adaptive optics OCT can be used to precisely identify cellular alterations in eyes with ERM that are closely related to visual function impairments. These cellular insights enhance our understanding of ERM pathology and offer promising prognostic indicators of visual outcome after vitrectomy.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100536"},"PeriodicalIF":3.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000721/pdfft?md5=6ebe20c52a43697fdfeed1142f227e4b&pid=1-s2.0-S2666914524000721-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140779420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Special Commentary: My Perspective on Vision and Vision Rehabilitation","authors":"","doi":"10.1016/j.xops.2024.100532","DOIUrl":"10.1016/j.xops.2024.100532","url":null,"abstract":"<div><p>Vision is the most powerful sense guiding our interaction with the environment. Its process starts with the retinal image as input and results in visually guided behaviors as output. This paper summarizes insights I gained over >40 years dealing with clinical ophthalmology, visual science, and vision rehabilitation, disciplines that all involve vision, but from different points of view. The retinal image contains 2-dimensional forms that have no inherent meaning. The brain matches this input to stored concepts, to create a Mental Model that is filled with 3-dimensional objects that are meaningful and linked to other senses. Ultimately this leads to the output of goal-directed visually guided behavior. The processes involved are too complex to be covered by a single practitioner. Optimal vision rehabilitation requires teamwork that includes contributions from various professions. It also requires an understanding, as well as possible, of the cerebral processes involved. The visual sciences study mostly the input-driven process from retinal image to visual percepts. Their studies deal mostly with groups and group averages and only occasionally with individual disease conditions. Clinical ophthalmology deals mostly with individuals, rather than group averages. The motto of the American Academy of Ophthalmology reminds us that the end point of patient care goes beyond “preserving sight.” It also includes “empowering lives” by creating the conditions for goal-directed interaction with the environment through visually directed behavior. Traditionally, the study of vision has mainly involved the conscious part of vision, handled mostly in the ventral stream. However, the subconscious part of vision, handled mostly in the dorsal stream must also be considered. This is further stimulated by the demands of computer vision, image processing, and artificial intelligence. Vision rehabilitation traditionally deals with the input side through better illumination and various magnification devices. This is the domain of low vision aids. Increasingly, however, it must also address the output side, and the involvement of other senses (braille, long cane, and talking books). This requires better understanding of the goal-directed higher visual processes. The supplemental material covers the development of numerical scales to quantify not only visual acuity but also visual abilities, and the use of different tests.</p></div><div><h3>Financial Disclosure(s)</h3><p>The author(s) have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 6","pages":"Article 100532"},"PeriodicalIF":3.2,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266691452400068X/pdfft?md5=d5104c64a7e060424da850daee9e5403&pid=1-s2.0-S266691452400068X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140759946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Kim , Victoria Chen MD , Jessica Pottenburgh MS, PA , Marvin Cruz , Gillian Cooper , Catherine Sun , Lily Im MD , Laurence Magder MPH, PhD , Osamah J. Saeedi MD, MS
{"title":"Netarsudil 0.02% Alters Episcleral Venous Flowrates: A Clinical Trial Using Erythrocyte-Mediated Angiography","authors":"Sarah Kim , Victoria Chen MD , Jessica Pottenburgh MS, PA , Marvin Cruz , Gillian Cooper , Catherine Sun , Lily Im MD , Laurence Magder MPH, PhD , Osamah J. Saeedi MD, MS","doi":"10.1016/j.xops.2024.100533","DOIUrl":"10.1016/j.xops.2024.100533","url":null,"abstract":"<div><h3>Objective</h3><p>To characterize the effect of netarsudil 0.02% on episcleral blood flow in treatment-naive glaucoma suspect or ocular hypertension subjects.</p></div><div><h3>Design</h3><p>Prospective, unmasked, single-arm cohort study.</p></div><div><h3>Participants</h3><p>Ten treatment-naive patients with a diagnosis of glaucoma suspect or ocular hypertension.</p></div><div><h3>Methods</h3><p>Erythrocyte-mediated angiography (EMA) was used to measure episcleral erythrocyte velocity, vessel diameter, and blood flow at baseline before treatment, 1 hour after drop instillation (T1), 1 to 2 weeks after daily netarsudil 0.02% drop use (T2), and 1 hour after drop instillation at the 1-to-2-week time point (T3). Intraocular pressure (IOP) and blood pressure were measured at each visit.</p></div><div><h3>Main Outcome Measures</h3><p>Change in episcleral venous erythrocyte velocity, diameter, and blood flow between time points analyzed using generalized estimating equation models.</p></div><div><h3>Results</h3><p>Of the 18 eligible study eyes of 10 enrolled treatment-naive subjects, baseline IOP was 16.8 ± 3.6 mmHg (mean ± standard deviation), which significantly decreased to 13.9 ± 4.2 mmHg at T1, 12.6 ± 4.1 mmHg at T2, and 11.8 ± 4.7 mmHg at T3 (<em>P</em> < 0.05 at each time point compared with baseline). Episcleral vessels averaged 61.3 ± 5.3 μm in diameter at baseline which increased significantly at all posttreatment time points (78.0 ± 6.6, 74.0 ± 5.2, 76.9 ± 6.9 μm, respectively; mean ± standard deviation, <em>P</em> < 0.05 for each time point). Episcleral venous flowrates were 0.40 ± 0.22 uL/minute (mean ± standard deviation) at baseline, which increased significantly to 0.69 ± 0.45 uL/min at T1 (<em>P</em> = 0.01), did not significantly differ at T2 (0.38 ± 0.30 uL/minute), and increased significantly to 0.54 ± 0.32 uL/minute at T3 (<em>P</em> < 0.05 compared with baseline and T2).</p></div><div><h3>Conclusions</h3><p>Netarsudil causes episcleral venous dilation at all time points and resulting increases in episcleral venous flowrates 1 hour after drop instillation. Increased episcleral venous flow, associated with decreased episcleral venous pressure, may result in lowered IOP.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100533"},"PeriodicalIF":3.2,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000691/pdfft?md5=2000ff2ff496c4d4e2f76b3c4d6876cb&pid=1-s2.0-S2666914524000691-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140796061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}