Ophthalmology science最新文献

{"title":"Cover","authors":"","doi":"10.1016/S2666-9145(24)00176-3","DOIUrl":"10.1016/S2666-9145(24)00176-3","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 6","pages":"Article 100640"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721014","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":"Virtual Reality Portable Perimetry and Home Monitoring of Glaucoma: Retention and Compliance over a 2-year Period","authors":"Runjie B. Shi MD, PhD ,&nbsp;Leo Y. Li-Han PhD ,&nbsp;Irfan N. Kherani MD, FRCSC ,&nbsp;Graham E. Trope PhD, FRCSC ,&nbsp;Yvonne M. Buys MD, FRCSC ,&nbsp;Willy Wong PhD ,&nbsp;Moshe Eizenman PhD","doi":"10.1016/j.xops.2024.100639","DOIUrl":"10.1016/j.xops.2024.100639","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate long-term retention, compliance, and performance of glaucoma patients using a virtual reality portable perimeter to monitor visual fields (VFs) at home.</div></div><div><h3>Design</h3><div>Prospective, longitudinal, cohort study.</div></div><div><h3>Subjects</h3><div>Twenty-five glaucoma patients with stable and reliable VFs (average age 67.4 years) were recruited at Toronto Western Hospital, Ontario, Canada.</div></div><div><h3>Methods</h3><div>Participants were instructed to perform bilateral home VF tests fortnightly for 2 years using the Toronto Portable Perimeter (TPP). Based on empirical home monitoring data, simulation analyses were conducted to evaluate the progression detection performance of high-frequency TPP testing.</div></div><div><h3>Main Outcome Measures</h3><div>Retention rates were calculated as the percentage of participants who performed ≥1 home VF test. Compliance rates measured the percentage of participants adhering to the recommended test frequency of every 2-month period. Visual field indices, test reliability, intertest variability, and the precision of estimating progression rate with TPP were compared to those with the Humphrey Field Analyzer (HFA). After 6 months, participants completed a questionnaire to evaluate their experiences and preferences. The years required to detect progression were also compared between HFA and TPP tests.</div></div><div><h3>Results</h3><div>Eighteen of the 25 participants (72%) completed ≥1 unsupervised VF test at home, with an average test frequency of 1.6 tests/month. Compliance decreased as the monitoring duration progressed, dropping from 83% (initial 2 months) to 11% (final 2 months). Unfamiliarity with technology and time constraints were identified as the main barriers to regular testing. Visual field indices of TPP home tests were strongly correlated with clinical results (<em>r</em> &gt; 0.900). Home testing significantly reduced intertest variability (<em>P</em> &lt; 0.001) and improved the precision of progression rate estimates (<em>P</em> &lt; 0.010). Participants overwhelmingly preferred home testing over clinic VF follow-ups (<em>P</em> &lt; 0.001). Simulations showed that TPP tests can significantly shorten the time to detect progression for different progression rates compared with clinical VF follow-up, even with compromised compliance.</div></div><div><h3>Conclusions</h3><div>Despite the small sample size, our study demonstrated that glaucoma patients could reliably perform VF tests at home over a 2-year period. However, issues with retention rate and compliance with long-term VF monitoring were observed in some participants. Nevertheless, high-quality VF data from home tests can provide supplementary information to improve the timely detection of VF progression.</div></div><div><h3>Financial Disclosure(s)</h3><div>The author(s) have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 2","pages":"Article 100639"},"PeriodicalIF":3.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743643","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":"Ocular Adverse Events Following Coronavirus Disease 2019 Infection: A Self-controlled Case Series Study from the Entire Korean Population","authors":"Sungsoon Hwang MD, PhD ,&nbsp;Se Woong Kang MD, PhD ,&nbsp;Jaehwan Choi MD ,&nbsp;Kyung-Ah Park MD, PhD ,&nbsp;Dong Hui Lim MD, PhD ,&nbsp;Ju-Young Shin PhD ,&nbsp;Danbee Kang PhD ,&nbsp;Juhee Cho PhD ,&nbsp;Sang Jin Kim MD, PhD","doi":"10.1016/j.xops.2024.100638","DOIUrl":"10.1016/j.xops.2024.100638","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to assess the risk of ocular adverse events, including retinal artery occlusion (RAO), retinal vein occlusion (RVO), noninfectious uveitis (NIU), noninfectious scleritis (NIS), optic neuritis (ON), ischemic optic neuropathy (ION), and ocular motor cranial nerve palsy (OMCNP), after coronavirus disease 2019 (COVID-19) infection.</div></div><div><h3>Design</h3><div>Population-based self-controlled case series (SCCS).</div></div><div><h3>Participants</h3><div>The study included patients from the entire Korean population of 52 million who experienced incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP between January 1, 2021, and October 29, 2022.</div></div><div><h3>Methods</h3><div>This nationwide SCCS utilized data from the Korea National Health Insurance Service and the Korea Disease Control and Prevention Agency. The risk period after infection was defined as up to 24 weeks after COVID-19 infection. Conditional Poisson regression was used to calculate the relative incidence rate ratios (IRRs) for RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP during the designated risk periods.</div></div><div><h3>Main Outcome Measures</h3><div>The IRRs for RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP during the risk periods.</div></div><div><h3>Results</h3><div>The study included 9336, 103 362, 201 010, 25 428, 23 744, 3026, 69 933, and 16 335 cases of incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP, respectively. The IRRs (95% confidence interval) during the early risk period (1–8 weeks) were 0.94 (0.83–1.07), 1.01 (0.97–1.04), 1.00 (0.98–1.03), 0.96 (0.90–1.03), 1.00 (0.94–1.07), 0.97 (0.81–1.17), 0.97 (0.93–1.01), and 1.02 (0.94–1.11), respectively. In the late risk period (9–24 weeks), the IRRs were 1.02 (0.92–1.12), 1.01 (0.98–1.04), 1.01 (0.99–1.03), 1.02 (0.97–1.08), 1.02 (0.97–1.08), 0.99 (0.85–1.15), 1.02 (0.99–1.06), and 0.97 (0.90–1.03), respectively. Stratified analyses showed that in patients with a history of cerebro-cardiovascular disease, the risk of RAO increased during the late risk period, with an IRR (95% confidence interval) of 1.19 (1.02–1.40).</div></div><div><h3>Conclusions</h3><div>The risk of incident RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP did not increase after COVID-19 infection. The risk of incident RAO increased only in individuals with preexisting cardio-cerebrovascular disease.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 2","pages":"Article 100638"},"PeriodicalIF":3.2,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698452","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":"Progression of Capillary Hypoperfusion in Advanced Stages of Nonproliferative Diabetic Retinopathy: 6-month Analysis of RICHARD Study","authors":"Inês Pereira Marques MD, PhD ,&nbsp;Débora Reste-Ferreira MSc ,&nbsp;Torcato Santos ,&nbsp;Luís Mendes PhD ,&nbsp;António Cunha-Vaz Martinho MD ,&nbsp;Taffeta Ching Ning Yamaguchi PhD ,&nbsp;Ana Rita Santos PhD ,&nbsp;Elizabeth Pearce PhD ,&nbsp;José Cunha-Vaz MD, PhD","doi":"10.1016/j.xops.2024.100632","DOIUrl":"10.1016/j.xops.2024.100632","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the 6-month progression of retinal capillary perfusion in eyes with advanced stages of nonproliferative diabetic retinopathy (NPDR).</div></div><div><h3>Design</h3><div>RICHARD (NCT05112445), 2-year prospective longitudinal study.</div></div><div><h3>Participants</h3><div>Sixty eyes with Diabetic Retinopathy Severity Scale (DRSS) levels 43, 47, and 53 from 60 patients with type 2 diabetes. Fifty-one patients completed the 6-month evaluation.</div></div><div><h3>Methods</h3><div>Eyes were evaluated on Optos California (Optos plc) ultrawidefield fundus fluorescein angiography (UWF-FFA), swept-source OCT angiography (SS-OCTA) (PLEX Elite 9000, ZEISS) and spectral-domain OCTA (SD-OCTA) (CIRRUS HD-OCT 5000 Angioplex, ZEISS). DRSS classification was performed based on 7-field color fundus photographs (CFPs) complemented with Optos California UWF-fundus imaging.</div></div><div><h3>Main Outcome Measures</h3><div>Ischemic index was obtained from Optos. Vascular quantification metrics, namely foveal avascular zone, skeletonized vessel density (SVD), and perfusion density (PD) metrics, were acquired on OCTA in the superficial and deep capillary plexuses (SCP and DCP). Microaneurysm assessment was automatically performed based on CFP images using the RetmarkerDR (Retmarker SA, Meteda Group).</div></div><div><h3>Results</h3><div>Swept-source-OCTA metrics showed statistically significant differences between the advanced stages of NPDR. Differences between DRSS levels 47 and 53 were found at baseline in the inner ring (SVD, SCP: <em>P</em> = 0.005 and DCP: <em>P</em> = 0.042 and PD, SCP: <em>P</em> = 0.003) and outer ring (SVD, SCP: <em>P</em> = 0.007 and DCP: <em>P</em> = 0.030 and PD, SCP: <em>P</em> = 0.020 and DCP: <em>P</em> = 0.025). No significant differences were observed at baseline between DRSS levels 43 and 47. In SD-OCTA, the differences were similar but did not reach statistical significance. The total ischemic index showed an increase in association with diabetic retinopathy (DR) severity, but the differences between DRSS levels did not reach statistical significance. The number of microaneurysms also increased significantly with DR severity (<em>P</em> = 0.033). Statistically significant 6-month progression was detected with SS-OCTA in eyes with DRSS levels 47 and 53 but not in DRSS level 43. In eyes with DRSS level 53, 6-month progression was identified using a combination of metrics of capillary nonperfusion and microaneurysm counts.</div></div><div><h3>Conclusions</h3><div>In a 6-month period, significant microvascular disease progression can be identified in eyes with DRSS levels 47 and 53 by performing OCTA examinations and microaneurysm counting using CFP.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 2","pages":"Article 100632"},"PeriodicalIF":3.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698451","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":"Automated Detection of Central Retinal Artery Occlusion Using OCT Imaging via Explainable Deep Learning","authors":"Ansgar Beuse ,&nbsp;Daniel Alexander Wenzel MD ,&nbsp;Martin Stephan Spitzer MD ,&nbsp;Karl Ulrich Bartz-Schmidt MD ,&nbsp;Maximilian Schultheiss MD ,&nbsp;Sven Poli MD ,&nbsp;Carsten Grohmann PhD, MD","doi":"10.1016/j.xops.2024.100630","DOIUrl":"10.1016/j.xops.2024.100630","url":null,"abstract":"<div><h3>Objective</h3><div>To demonstrate the capability of a deep learning model to detect central retinal artery occlusion (CRAO), a retinal pathology with significant clinical urgency, using OCT data.</div></div><div><h3>Design</h3><div>Retrospective, external validation study analyzing OCT and clinical baseline data of 2 institutions via deep learning classification analysis.</div></div><div><h3>Subjects</h3><div>Patients presenting to the University Medical Center Tübingen and the University Medical Center Hamburg-Eppendorf in Germany.</div></div><div><h3>Methods</h3><div>OCT data of patients suffering from CRAO, differential diagnosis with (sub) acute visual loss (central retinal vein occlusion, diabetic macular edema, nonarteritic ischemic optic neuropathy), and from controls were expertly graded and distinguished into 3 groups. Our methodological approach involved a nested multiclass five fold cross-validation classification scheme.</div></div><div><h3>Main Outcome Measures</h3><div>Area under the curve (AUC).</div></div><div><h3>Results</h3><div>The optimal performance of our algorithm was observed using 30 epochs, complemented by an early stopping mechanism to prevent overfitting. Our model followed a multiclass approach, distinguishing among the 3 different classes: control, CRAO, and differential diagnoses. The evaluation was conducted by the “one vs. all” area under the receiver operating characteristics curve (AUC) method. The results demonstrated AUC of 0.96 (95% confidence interval [CI], ± 0.01); 0.99 (95% CI, ± 0.00); and 0.90 (95% CI, ± 0.03) for each class, respectively.</div></div><div><h3>Conclusions</h3><div>Our machine learning algorithm (MLA) exhibited a high AUC, as well as sensitivity and specificity in detecting CRAO and the differential classes, respectively. These findings underscore the potential for deploying MLAs in the identification of less common etiologies within an acute emergency clinical setting.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 2","pages":"Article 100630"},"PeriodicalIF":3.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142722496","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":"The Optical Nature of Myopic Changes in Retinal Vessel Caliber","authors":"Fabian Yii BSc ,&nbsp;Niall Strang MCOptom, PhD ,&nbsp;Colin Moulson BSc, MCOptom ,&nbsp;Baljean Dhillon FRCPS, FRCOphth ,&nbsp;Miguel O. Bernabeu PhD ,&nbsp;Tom MacGillivray PhD","doi":"10.1016/j.xops.2024.100631","DOIUrl":"10.1016/j.xops.2024.100631","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;Dimensional measures of retinal features are subject to the optical influence of ocular magnification. We examined the impact of ocular magnification on the association between axial length (AL) and measurements of retinal vessel caliber in fundus photographs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Cross-sectional study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;div&gt;Eighty-two normal right eyes from healthy participants aged 16 to 31 years.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Central retinal arteriolar and venular equivalents (CRAE and CRVE) were derived from color fundus photographs using semiautomated software. Ordinary least squares linear regression was used to assess the influence of AL (independent variable) on CRAE and CRVE, controlling for age, sex, and ethnicity, both before and after magnification correction using different formulae. These formulae estimate magnification based on different ocular parameters: AL only (Bennnett’s formula), refractive error only (Bengtsson’s formula), and refractive error combined with keratometry (Littmann’s formula). Previous research has primarily relied on Bengtsson’s formula, which is less accurate than Bennett’s formula. We also examined the impact of treating the nontelecentric fundus camera used in this study as telecentric when applying these magnification correction formulae.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Central retinal arteriolar and venular equivalents (in pixels).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Before magnification correction, increasing AL was associated with decreasing CRAE (β: −0.49, 95% confidence intervals: −0.89 to −0.09, &lt;em&gt;P&lt;/em&gt; = 0.02) and CRVE (β: −0.91, 95% confidence intervals: −1.62 to −0.20, &lt;em&gt;P&lt;/em&gt; = 0.01). After magnification correction, this observation was no longer evident, regardless of the correction formula applied. When inappropriately assuming the fundus camera to be telecentric, we observed a bias toward increasing magnification-corrected CRAE and CRVE with increasing AL (β coefficients were positive or became more positive), reaching statistical significance (&lt;em&gt;P&lt;/em&gt; &lt; 0.05) for CRAE corrected using Bennett’s or Littmann’s formula, and for CRVE corrected using Bennett’s formula.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Failing to correct for ocular magnification results in apparent narrowing of vessels in longer eyes, while inappropriate assumptions about telecentricity during magnification correction introduce an optical artifact that causes apparent widening of vessels. These findings suggest that myopic changes in retinal vessel caliber are optical (not biological) in nature. Proper correction of this effect to accurately derive dimensional measures is a crucial—yet often overlooked—methodological consideration in “oculomics” research investigating retinal biomarkers of systemic conditions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Financial Disclosure(s)&lt;/h3&gt;&lt;div&gt;Proprietary or commercial disclosure may be found in the Footnote","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100631"},"PeriodicalIF":3.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704140","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":"ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation","authors":"Justis P. Ehlers MD ,&nbsp;Allen Hu MD ,&nbsp;David Boyer MD ,&nbsp;Scott W. Cousins MD ,&nbsp;Nadia K. Waheed MD ,&nbsp;Philip J. Rosenfeld MD, PhD ,&nbsp;David Brown MD ,&nbsp;Peter K. Kaiser MD ,&nbsp;Anthony Abbruscato PharmD ,&nbsp;Gui Gao PhD ,&nbsp;Jeffrey Heier MD","doi":"10.1016/j.xops.2024.100628","DOIUrl":"10.1016/j.xops.2024.100628","url":null,"abstract":"<div><h3>Objective</h3><div>This study evaluated the safety and efficacy of elamipretide in dry age-related macular degeneration (AMD) with noncentral geographic atrophy (GA).</div></div><div><h3>Design</h3><div>ReCLAIM-2 was a prospective, phase II, randomized, placebo-controlled, double-masked, multicenter trial (NCT03891875).</div></div><div><h3>Subjects</h3><div>Patients aged ≥55 years with ≥1 eye with dry AMD with GA were enrolled.</div></div><div><h3>Methods</h3><div>Administration of daily subcutaneous elamipretide 40 mg was investigated in subjects for 48 weeks followed by a 4-week follow-up period.</div></div><div><h3>Main Outcome Measures</h3><div>The primary efficacy end points were the mean change from baseline (BL) in low-luminance best-corrected visual acuity (LL BCVA) and the change in square root (Sqrt) converted GA area from BL as measured by OCT. Additional predefined end points included ellipsoid zone (EZ) integrity preservation assessment and categorical changes in LL BCVA. The primary safety end point was the incidence and severity of adverse events.</div></div><div><h3>Results</h3><div>Of the 176 patients randomized, there were 117 and 59 patients in the elamipretide and placebo groups, respectively. Although elamipretide did not meet statistical significance for the primary end points (mean change in LL BCVA and mean change in Sqrt converted GA area), elamipretide produced a 43% reduction in the mean progression from BL in the macular percentage of total EZ attenuation/loss (i.e., complete loss of EZ band; nominal <em>P</em> = 0.0034) and 47% reduction in the mean progression of macular percentage of partial EZ attenuation/degradation (i.e., EZ-retinal pigment endothelium thickness of ≤20 microns; nominal <em>P</em> = 0.0040) versus placebo at week 48. Elamipretide treatment was also associated with significantly more patients experiencing a ≥10 letter gain in LL BCVA versus placebo (14.6% vs. 2.1%; nominal <em>P</em> = 0.0404). Adverse events were reported in 86% of those receiving elamipretide and 71% of the placebo group with the most common events being injection site reactions (e.g., pruritus, injection site pain, bruising, and erythema).</div></div><div><h3>Conclusions</h3><div>While the primary end points were not met in this phase II study, elamipretide treatment was associated with a slowing of progressive EZ degradation/loss, a surrogate for photoreceptor damage. These findings have important clinical relevance since EZ attenuation/photoreceptor loss precedes and predicts the progressive pathological changes associated with vision loss and AMD. The EZ attenuation/loss end point will serve as the regulatory approved primary end point in the elamipretide phase III clinical development program.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100628"},"PeriodicalIF":3.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655033","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":"Interplay between Lipids and Complement Proteins—How Multiomics Data Integration Can Help Unravel Age-related Macular Degeneration Pathophysiology: A Proof-of-concept Study","authors":"Simon Nusinovici PhD ,&nbsp;Lei Zhou PhD ,&nbsp;Lavanya Raghavan MD ,&nbsp;Yih Chung Tham PhD ,&nbsp;Hengtong Li MS ,&nbsp;Danny Cheung MD ,&nbsp;Xiaomeng Wang PhD ,&nbsp;Chui Ming Gemmy Cheung MD, PhD ,&nbsp;Tien Yin Wong MD, PhD ,&nbsp;Usha Chakravarthy MD, PhD ,&nbsp;Ching-Yu Cheng MD, PhD","doi":"10.1016/j.xops.2024.100629","DOIUrl":"10.1016/j.xops.2024.100629","url":null,"abstract":"<div><h3>Objective</h3><div>Our objectives were to identify correlation patterns between complement and lipid pathways using a multiomics data integration approach and to determine how these interconnections affect age-related macular degeneration (AMD).</div></div><div><h3>Design</h3><div>Nested case-control study.</div></div><div><h3>Subjects and Controls</h3><div>The analyses were performed in a subset of the Singapore Indian Eye Study. We randomly selected 155 AMD cases and age- and sex-matched them with 155 controls.</div></div><div><h3>Methods</h3><div>Firstly, a multiomics data integration method was used to identify correlation patterns between the omics data. Then, we tested possible interactions between the lipids and complement proteins using logistic regression models.</div></div><div><h3>Main Outcome Measures</h3><div>Age-related macular degeneration was determined according to the Beckman classification system. We measured in serum samples 35 complement proteins and 66 lipids, and used 9 genetic variants.</div></div><div><h3>Results</h3><div>Among the 155 AMD cases, 93 (60.0%) had early and 62 (40.0%) intermediate AMD. Firstly, we identified 2 clusters between complement proteins and lipids involving (1) mannan-binding lectin serine protease 1 and several different high-density lipoprotein particles, and (2) complement factor H-related protein 1, carboxypeptidase N subunit 2 and complement component C8 gamma chain, and sphingomyelin and different cholesterol. Secondly, we identified 1 interaction between complement protein 1R and sphingomyelin with an odds of AMD 2 times higher for individuals with low levels of sphingomyelin and complement protein 1R (odds ratio = 2.13 [1.09, 4.17]).</div></div><div><h3>Conclusions</h3><div>We report here, using a cutting-edge multiomics integration approach, the complex interconnections between genetic, metabolomics, and proteomic data. This method permitted us to obtain a holistic picture and identify multiomics signature of AMD pathophysiology. These results advocate for a personalized therapeutic approach that accounts for multiple pathways. However, these results need to be validated in larger studies with different ethnic groups.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100629"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655031","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":"Systemic Treatment with the Janus Kinase Inhibitor Baricitinib in Ocular Chronic Graft-versus-Host Disease","authors":"Taylor McManus BS, MS ,&nbsp;Noa G. Holtzman MD ,&nbsp;Aaron Zhao BS ,&nbsp;Chantal Cousineau-Krieger MD ,&nbsp;Susan Vitale PhD, MHS ,&nbsp;Edmond J. FitzGibbon MD ,&nbsp;Debbie Payne BS, MBA ,&nbsp;Janine Newgen COT ,&nbsp;Celestina Igbinosun BSN, RN ,&nbsp;Annie P. Im MD ,&nbsp;Cody Peer MS, PhD ,&nbsp;William Douglas Figg Sr. Pharm D ,&nbsp;Edward W. Cowen MD ,&nbsp;Jacqueline W. Mays DDS, PhD ,&nbsp;Steven Pavletic MD, PhD ,&nbsp;M.Teresa Magone MD","doi":"10.1016/j.xops.2024.100627","DOIUrl":"10.1016/j.xops.2024.100627","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the effects of oral baricitinib on ocular surface disease (OSD) in patients with chronic graft-versus-host disease (cGVHD).</div></div><div><h3>Design</h3><div>Prospective phase 1 to 2 single institution trial.</div></div><div><h3>Subjects</h3><div>Eighteen patients with ocular graft-versus-host-disease (oGVHD) and systemic steroid-refractory cGVHD.</div></div><div><h3>Methods</h3><div>Oral baricitinib (2 mg and 4 mg) was administered daily for up to 12 months in an intrapatient dose-escalation design. National Institutes of Health (NIH) oGVHD score, vision, corneal Oxford staining (COS), tear break-up time (TBUT), Schirmer I test (ST) without anesthesia, and microliter tear equivalent conversion were assessed at baseline, 6 months (primary efficacy end point), and 12 months if patients remained on the drug.</div></div><div><h3>Main Outcome Measures</h3><div>Improvement in NIH oGVHD score, COS, TBUT, and ST results in patients with and without conjunctival fibrosis at 6 months.</div></div><div><h3>Results</h3><div>At 6 months, the NIH oGVHD score significantly improved (<em>P</em> = 0.014) with all OSD parameters also showing improvement, though not statistically significant. COS baseline, 2.17 to 0.95; TBUT baseline, 6.66 to 8.18 seconds, Schirmer I baseline, 3.86 mm (2.6 μl) to 5.56 mm (3.9 μl). For patients continuing treatment at 12 months improvements persisted compared with the baseline but remained statistically nonsignificant. Corneal Oxford staining decreased to 0.94; TBUT increased to 8.95 seconds, and ST improved to 10.19 mm (7.2 μL). Conjunctival fibrosis was present in 39% (n = 7) of the patients at baseline. The greatest improvement was observed in the 11 patients without prior conjunctival fibrosis compared with the baseline: COS 1.84, TBUT 6.32 seconds, ST 4.07 mm (2.1 μl); 6 months: COS 0.25 (<em>P</em> = 0.018), TBUT 8.62 seconds, ST 9.12 mm (5.4 μl); 12 months: COS 0, TBUT 10.29 seconds, ST 16.88 mm (10.6 μl). Vision was stable in all groups. Two patients developed asymptomatic, self-limited conjunctival papillomas, and 1 patient developed uncomplicated bacterial conjunctivitis twice. No dose limiting toxicity was observed. Severe adverse events with hospitalizations for possible drug-related systemic infections occurred in 5 patients.</div></div><div><h3>Conclusions</h3><div>Systemic baricitinib was well-tolerated, improved NIH oGVHD scores and OSD parameters in patients with oGVHD, with the greatest benefits observed in patients without pre-existing conjunctival fibrosis. Conjunctival fibrosis may affect outcomes and should be considered in patient selection for clinical trials.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100627"},"PeriodicalIF":3.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655032","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":"Intraretinal Retinal Pigment Epithelium Cells in Age-Related Macular Degeneration","authors":"Songhomitra Panda-Jonas MD ,&nbsp;Rahul A. Jonas MD ,&nbsp;Jie Xu MD ,&nbsp;Ya Xing Wang MD ,&nbsp;Jost B. Jonas MD","doi":"10.1016/j.xops.2024.100626","DOIUrl":"10.1016/j.xops.2024.100626","url":null,"abstract":"<div><h3>Purpose</h3><div>To examine intraretinally migrated retinal pigment epithelium cells (iRPECs) in enucleated human eyes with various retinal conditions and corresponding intraretinal hyperreflective bodies (iHRBs) in a large cohort of patients with age-related macular degeneration (AMD) in China.</div></div><div><h3>Design</h3><div>Population-based study and histomorphometric investigation.</div></div><div><h3>Participants</h3><div>Participants of the population-based Beijing Eye Study and enucleated human eyes.</div></div><div><h3>Methods</h3><div>OCT-based and fundus photography-based examination of the macula of the Beijing Eye Study participants and light-microscopical histomorphometry of enucleated human eyes.</div></div><div><h3>Main Outcome Measures</h3><div>Presence and location of iRPECs and iHRBs.</div></div><div><h3>Results</h3><div>In the Beijing Eye Study (6551 eyes; 3301 participants), the prevalence of intermediate AMD and late AMD was 331 (5.1%) and 44 (0.6%), respectively. All 42 eyes with intermediate AMD and macular hyperpigmentation had iHRBs at locations corresponding spatially with macular hyperpigmentation on the fundus photographs. Among all eyes with intermediate AMD (n = 331), iHRBs were detected in 262 (79.2%) eyes. The most internal location of the iHRBs was at the ellipsoid zone in 46 (13.9%) eyes, at the external limiting membrane (ELM) in 45 (13.6%) eyes, and in the outer nuclear layer in 145 (43.8%) eyes. Out of the 262 eyes with iHRBs, 186 (71.0%) eyes showed a corresponding defect in the ellipsoid zone, and 128 (48.9%) eyes showed a defect in the ELM. The eyes with an iHRB located beneath the ELM did not show an ELM defect. The iHRBs were associated with a plume-like appearance and with a smoke-like appearance in 20 (7.6%) eyes and 137 (52.3%) eyes, respectively. All iHRBs did not have a shadow on the OCT images. Similar findings were obtained in the eyes with late AMD. Among 237 eyes examined histologically, 21 globes showed iRPECs: 8 eyes in parapapillary α zone/β zone; 5 eyes with myopic patchy atrophies, and 3 eyes with AMD. The iRPECs were spatially associated with an ELM defect and were not surrounded by a basal membrane.</div></div><div><h3>Conclusions</h3><div>Intraretinal hyperreflective bodies can be found in 3 out of 4 eyes with intermediate AMD, correlate histologically with intraretinally located (migrated) retinal pigment epithelium cells, and correspond spatially with localized defects of the ellipsoid zone and ELM.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 2","pages":"Article 100626"},"PeriodicalIF":3.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660969","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}