Ophthalmology science最新文献

{"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}

{"title":"Relationship of Inflammatory Mediators (Interleukin and Cortisol Concentrations) with Corneal Epithelial Quantifiable Metrics","authors":"Marcony R. Santhiago MD, PhD ,&nbsp;Larissa R. Stival MD, PhD ,&nbsp;Daniella C. Araujo PhD ,&nbsp;Rosalia Antunes-Foschini MD, PhD ,&nbsp;Marcia C. Toledo MD ,&nbsp;Ianne L.S. Nunes MS ,&nbsp;Claudia R. Morgado MD ,&nbsp;Newton Kara-Junior MD, PhD","doi":"10.1016/j.xops.2024.100624","DOIUrl":"10.1016/j.xops.2024.100624","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To investigate the relationship of inflammatory biomarkers with corneal epithelial quantifiable metrics in patients with keratoconus and in healthy eyes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Prospective observational comparative study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;div&gt;This study included 100 eyes of 100 patients: 48 eyes of 48 patients with keratoconus and 52 healthy eyes of 52 healthy controls.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The concentrations of tear cytokines were investigated in both groups: interleukin (IL) 1B, IL6, IL8, IL10, IL12p70, and tumor necrosis factor α (TNFα) were obtained by capillary flow and measured using flow cytometer. Cortisol concentrations were determined in both groups from the most proximal hair segment as an index of cumulative secretion and measured by liquid chromatography mass spectrometry. Epithelial variables were obtained with OCT. Pearson correlation (r) was used to measure linear dependence between 2 different variables.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Investigating the existence, strength, and significance of any correlation between inflammatory biomarkers (IL1B, IL6, IL8, IL10, IL12p70, TNFα, and hair cortisol concentration) and OCT corneal epithelial quantifiable variables such as minimum and maximum epithelial thickness of the map, difference between the minimum and maximum (Epithelial Min-Max) and standard deviation of the epithelial thickness of the map (Epithelial Std Dev), and average epithelial thickness of the superior and inferior regions of the map.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Eyes with keratoconus presented statistically significantly higher levels of IL1b (&lt;em&gt;P&lt;/em&gt; = 0.02), IL6 (&lt;em&gt;P&lt;/em&gt; &lt; 0.0001), IL8 (&lt;em&gt;P&lt;/em&gt; &lt; 0.0001), and TNFα (&lt;em&gt;P&lt;/em&gt; &lt; 0.0001) and hair cortisol concentration (&lt;em&gt;P&lt;/em&gt; = 0.01) compared with healthy controls.&lt;/div&gt;&lt;div&gt;There was a significant correlation between IL6 and measurement Epithelium Min-Max [Pearson = −0.59 (−0.69, −0.47); &lt;em&gt;P&lt;/em&gt; &lt; 0.0001] and Epithelial Std Dev (Pearson = +0.56 [0.44, 0.67]; &lt;em&gt;P&lt;/em&gt; &lt; 0.0001). There was a significant correlation between hair cortisol concentration and Epithelium Min-Max (Pearson = −0.27 [−0.42, −0.1]; &lt;em&gt;P&lt;/em&gt; &lt; 0.0001]) and Epithelium Std Dev groups (Pearson = +0.2 [0.03, 0.36]; &lt;em&gt;P&lt;/em&gt; = 0.021). There was also a significant correlation between TNFα and Epithelial Max (Pearson = −0.37 [−0.55, 0.17]; &lt;em&gt;P&lt;/em&gt; &lt; 0.0001). We found no significant correlation between the concentration of IL1b, IL8, IL10, and IL2p70 with any epithelium parameters.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The higher concentration of inflammatory markers (IL6 and hair cortisol) in eyes with keratoconus present a significant correlation with OCT metrics identifying epithelial variability, such as Epithelial Min-Max and Std Dev. These findings demonstrate the role of chronic inflammation in eyes with keratoconus, and that these epithelial change","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100624"},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655029","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":"Finite Element Analysis of Mechanical Ocular Sequelae from Badminton Shuttlecock Projectile Impact","authors":"John D. Hong PhD ,&nbsp;Jose A. Colmenarez MS ,&nbsp;Elliot H. Choi MD, PhD ,&nbsp;Alex Suh BS ,&nbsp;Andrew Suh BS ,&nbsp;Matthew Lam MD ,&nbsp;Annette Hoskin PhD ,&nbsp;Don S. Minckler MD, MS ,&nbsp;Ken Y. Lin MD, PhD ,&nbsp;Kourosh Shahraki MD ,&nbsp;Rupesh Agrawal MD ,&nbsp;Pengfei Dong PhD ,&nbsp;Linxia Gu PhD ,&nbsp;Donny W. Suh MD, MBA","doi":"10.1016/j.xops.2024.100625","DOIUrl":"10.1016/j.xops.2024.100625","url":null,"abstract":"<div><h3>Purpose</h3><div>With the growing popularity of badminton worldwide, the incidence of badminton-related ocular injuries is expected to rise. The high velocity of shuttlecocks renders ocular traumas particularly devastating, especially with the possibility of permanent vision loss. This study investigated the mechanism behind ocular complications through simulation analyses of mechanical stresses and pressures upon shuttlecock impact.</div></div><div><h3>Design</h3><div>Computational simulation study.</div></div><div><h3>Participants</h3><div>None.</div></div><div><h3>Methods</h3><div>A 3-dimensional human eye model was reconstructed based on the physiological and biomechanical properties of various ocular tissues. Finite element analysis simulations involved a frontal collision with a shuttlecock projectile at 128.7 km/hour (80 mph). Intraocular pressure (IOP) changes and tissue stress were mapped and quantified in the following ocular structures: the limbus, ciliary body, zonular fibers, ora serrata, retina, and optic nerve head.</div></div><div><h3>Main Outcome Measures</h3><div>Intraocular pressure and tissue stress.</div></div><div><h3>Results</h3><div>Upon shuttlecock impact, compressive force was transferred to the anterior pole of the cornea, propagating posteriorly to the optic nerve head. Deflection of forces anteriorly contributed to refractory oscillations of compressive and tensile stress of ocular tissue. Initial impact led to a momentary (&lt;1 ms) spike in IOP 5.66 MPa (42.5 × 10³ mmHg) that radially distributed for a very brief instance (&lt;1 ms) of pressure at the trabecular meshwork of the iridocorneal angle of 1.25 MPa (9.4 × 10³ mmHg). The lens had a maximal posterior displacement of 1.5 mm with peak zonular fiber tensile strain of 52%. The limbus, ciliary body, and ora serrata had a peak tensile stress of 5.16 MPa, 1.90 MPa, and 0.62 MPa, respectively. Compressive force from the sclera concentrated at the optic nerve head for a peak stress of 5.97 MPa while peak pressure from vitreous humor was 7.99 MPa.</div></div><div><h3>Conclusions</h3><div>Shuttlecock impact led to a very brief, substantial rise in pressure and stress significant for tissue damage and subsequent complications, such as secondary glaucoma, angle recession, lens subluxation, hyphema, or retinal dialysis. Our findings offer valuable mechanistic insights into how ocular structures are affected by shuttlecock projectile impact to inform clinical assessments and treatment strategies, while highlighting the importance of protective eyewear in racket sports.</div></div><div><h3>Financial Disclosures</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 100625"},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655115","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":"Barriers to Extracting and Harmonizing Glaucoma Testing Data: Gaps, Shortcomings, and the Pursuit of FAIRness","authors":"Niloofar Radgoudarzi BS,&nbsp;Shahin Hallaj MD,&nbsp;Michael V. Boland MD, PhD,&nbsp;Brian Stagg MD,&nbsp;Sophia Y. Wang MD, MS,&nbsp;Benjamin Xu MD, PhD,&nbsp;Swarup S. Swaminathan MD,&nbsp;Eric N. Brown MD, PhD,&nbsp;Aiyin Chen MD,&nbsp;Catherine Q. Sun MD,&nbsp;Dilru C. Amarasekera MD,&nbsp;Jonathan S. Myers MD,&nbsp;Murtaza Saifee MD,&nbsp;William Halfpenny MB BChir, MEng,&nbsp;Keri Dirkes MPH,&nbsp;Linda Zangwill PhD,&nbsp;Kerry E. Goetz PhD, MS,&nbsp;Michelle Hribar PhD, MS,&nbsp;Sally L. Baxter MD, MSc","doi":"10.1016/j.xops.2024.100621","DOIUrl":"10.1016/j.xops.2024.100621","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 6","pages":"Article 100621"},"PeriodicalIF":3.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142416753","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":"An Eye on Extracellular Vesicles: Trends and Clinical Translations in Vision Research","authors":"Rahul M. Dhodapkar MD ,&nbsp;Eric Jung MD ,&nbsp;Sun Young Lee MD, PhD","doi":"10.1016/j.xops.2024.100619","DOIUrl":"10.1016/j.xops.2024.100619","url":null,"abstract":"<div><h3>Purpose</h3><div>To perform a review of research, funding, and clinical translation efforts for extracellular vesicles (EVs) within vision science.</div></div><div><h3>Design</h3><div>Retrospective analysis of publication, funding, and clinical trials data.</div></div><div><h3>Methods</h3><div>A pretrained large language model (Jina2) was used to create semantic embeddings for 41 282 abstracts from articles related to EVs archived on EMBASE and published between January 1966 and January 2024. The articles were projected and clustered according to semantic embedding similarity, and research subdomains for EVs were determined through inspection of term frequency-inverse document frequency weighted word clouds. Mann–Kendall trend analysis was performed to identify current areas of growth within EV research. Additionally, National Institutes of Health funding data from RePORT Expenditures and Results and clinical trials data from ClinicalTrials.gov were analyzed to correlate publication trends with funding support and clinical translation efforts.</div></div><div><h3>Results</h3><div>Unsupervised clustering and Mann–Kendall trend analysis identified wound healing/regeneration (<em>P</em> = 0.030) and neurodegenerative disease (<em>P</em> = 0.049) as significantly accelerating in growth of publication over time. Ophthalmology-restricted subset analysis identified that publications in age-related macular degeneration (<em>P</em> = 0.191) and clinical applications (<em>P</em> = 0.086) are no longer growing at a significant rate. Analysis of funding data identified that the National Cancer Institute was the top funding institution overall, but that the National Institute on Aging is rapidly advancing in terms of funding EV research and trials. Analysis of ClinicalTrials.gov data highlights a dearth of clinical trials within ophthalmology despite a growing number of studies in other medical subfields.</div></div><div><h3>Conclusions</h3><div>Extracellular vesicles remain a promising substrate for both the identification and treatment of vision-threatening diseases. A better understanding of the current landscape of research and funding trends should help to inform future funding and translational efforts.</div></div><div><h3>Financial Disclosures</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 100619"},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655081","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":"Association of Hyperautofluorescence Signals with Geographic Atrophy Progression in the METformin for the MINimization of Geographic Atrophy Progression Trial","authors":"Abu Tahir Taha BS ,&nbsp;Liangbo Linus Shen MD ,&nbsp;Antonio Diaz BS ,&nbsp;Noor Chahal BS ,&nbsp;Jasmeet Saroya BS ,&nbsp;Mengyuan Sun PhD ,&nbsp;Michael J. Allingham MD, PhD ,&nbsp;Sina Farsiu PhD ,&nbsp;Glenn Yiu MD, PhD ,&nbsp;Jeremy D. Keenan MD, MPH ,&nbsp;Jay M. Stewart MD","doi":"10.1016/j.xops.2024.100620","DOIUrl":"10.1016/j.xops.2024.100620","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the association between rim area focal hyperautofluorescence (RAFH) signals and geographic atrophy (GA) growth rates, as well as the impact of oral metformin on the longitudinal change of RAFH.</div></div><div><h3>Design</h3><div>Secondary analysis of a randomized controlled trial.</div></div><div><h3>Participants</h3><div>Seventy-one eyes from 44 participants with GA and ≥6 months of follow-up in the METformin for the MINimization of geographic atrophy progression study.</div></div><div><h3>Methods</h3><div>Fundus autofluorescence images were captured using a 488 nm excitation wavelength. Two masked graders identified and measured RAFH lesions using proprietary semiautomatic segmentation software and ImageJ. We calculated RAFH by dividing the areas of hyperautofluorescence within a 450-μm rim circumscribing the GA by the total area enclosed within this rim.</div></div><div><h3>Main Outcome Measures</h3><div>Longitudinal changes in RAFH and GA area.</div></div><div><h3>Results</h3><div>Baseline RAFH was positively associated with the baseline square root of GA area 0.065/year (<em>P</em> &lt; 0.001). In the entire study cohort, higher baseline RAFH was associated with a faster GA area growth rate in mm²/year (Spearman’s ρ = 0.53; <em>P</em> &lt; 0.001). The association became weaker in square root-transformed GA area growth (ρ = 0.19, <em>P</em> = 0.11) and perimeter-adjusted GA growth rate (ρ = 0.28, <em>P</em> = 0.02), achieving statistical significance only in the latter. When this analysis was stratified into 3 baseline GA tertiles, the first and second tertiles showed weak to moderate association with statistical significance in all 3 modes of GA growth rates. Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (<em>P</em> &lt; 0.01). Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (<em>P</em> &lt; 0.01). The use of oral metformin was not significantly associated with the change in RAFH over time compared with the observation group (0.023/year vs. 0.016/year; <em>P</em> = 0.29).</div></div><div><h3>Conclusions</h3><div>Increased baseline RAFH is associated with faster GA area progression. However, the effect size of this association may depend on the baseline GA lesion size such that small to medium-sized GA lesions display this relationship regardless of the mode of the calculation of GA growth rate.</div></div><div><h3>Financial Disclosures</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 100620"},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655030","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":"Characterization of the Retinal Phenotype Using Multimodal Imaging in Novel Compound Heterozygote Variants of CYP2U1","authors":"Ferenc B. Sallo MD, PhD ,&nbsp;Chantal Dysli MD, PhD ,&nbsp;Franz Josef Holzer MD ,&nbsp;Emmanuelle Ranza MD ,&nbsp;Michel Guipponi MD ,&nbsp;Stylianos E. Antonarakis MD ,&nbsp;Francis L. Munier MD ,&nbsp;Alan C. Bird MD ,&nbsp;Daniel F. Schorderet MD ,&nbsp;Beatrice Rossillion MD ,&nbsp;Veronika Vaclavik MD","doi":"10.1016/j.xops.2024.100618","DOIUrl":"10.1016/j.xops.2024.100618","url":null,"abstract":"<div><h3>Purpose</h3><div>To report the retinal phenotype in 2 patients simulating type 2 macular telangiectasis with new variants in <em>CYP2U1</em> implicated in hereditary spastic paraplegia type 56 (HSP 56).</div></div><div><h3>Design</h3><div>Cross sectional case series study.</div></div><div><h3>Participants</h3><div>Five members of a non-consanguineous family (parents and 3 male children) were investigated.</div></div><div><h3>Methods</h3><div>All family members underwent a full ophthalmic evaluation and multimodal retinal imaging. Two family members demonstrating retinal anomalies underwent additional OCT angiography, dual wavelength autofluorescence and fluorescence lifetime imaging ophthalmoscopy, kinetic perimetry, fundus-correlated microperimetry, electroretinography, and electro-oculography. Whole-exome sequencing was performed in all 5 family members.</div></div><div><h3>Main Outcome Measures</h3><div>To characterize the retinal phenotype in affected patients with variants in <em>CYP2U1</em>, using multimodal imaging: dual-wavelength autofluorescence, fluorescence lifetime, OCT angiography.</div></div><div><h3>Results</h3><div>The 2 siblings with compound heterozygous novel variants c.452C&gt;T; p.(Pro151Leu), c.943C&gt;T; p.(Gln315Ter) in <em>CYP2U1</em> demonstrated parafoveal loss of retinal transparency and hyperreflectivity to blue light, redistribution of macular pigment to the parafoveal edge, photoreceptor loss, and fluorescence lifetime imaging ophthalmoscopy anomalies: a pattern compatible with that seen in macular telangiectasia type 2 (MacTel). One had manifest neurological abnormalities since early childhood; the second had no neurological abnormalities. Each parent and the third sibling were heterozygous for 1 variant and were neurologically and ophthalmically normal.</div></div><div><h3>Conclusions</h3><div>These <em>CYP2U1</em> variants are associated with a retinal phenotype very similar to that otherwise specific for MacTel, suggestive of possible links in the etiology and pathogenesis of these diseases.</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 1","pages":"Article 100618"},"PeriodicalIF":3.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655114","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}