Ophthalmology science最新文献

{"title":"Inversion of Asymmetric Vortex Vein Dilatation in Pachychoroid Spectrum Diseases","authors":"Hidetaka Matsumoto MD, PhD,&nbsp;Shoji Kishi MD, PhD,&nbsp;Junki Hoshino MD,&nbsp;Kosuke Nakamura MD,&nbsp;Hideo Akiyama MD, PhD","doi":"10.1016/j.xops.2024.100515","DOIUrl":"10.1016/j.xops.2024.100515","url":null,"abstract":"<div><h3>Purpose</h3><p>Intervortex venous anastomosis is widely recognized as compensating for vortex vein congestion in pachychoroid spectrum diseases. However, determining the blood flow direction within the compensated drainage route is often challenging. Herein, we investigated the morphological patterns of vortex veins in eyes showing retrograde pulsatile vortex venous flow.</p></div><div><h3>Design</h3><p>Retrospective observational case series.</p></div><div><h3>Subjects</h3><p>Six hundred eighty-nine consecutive eyes with treatment-naive central serous chorioretinopathy, pachychoroid neovasculopathy, or polypoidal choroidal vasculopathy.</p></div><div><h3>Methods</h3><p>We reviewed the clinical records of patients with these pachychoroid spectrum diseases. Multimodal images including indocyanine green angiography (ICGA) and en face OCT were analyzed.</p></div><div><h3>Main Outcome Measures</h3><p>Intervortex venous anastomosis between superotemporal and inferotemporal vortex veins and the dominant site of dilated temporal vortex veins were determined in the eyes with retrograde pulsatile vortex venous flow in the temporal vortex veins.</p></div><div><h3>Results</h3><p>Twenty-two eyes with retrograde pulsatile vortex venous flow in the temporal vortex veins were identified utilizing early phase ICGA videos. In 9 eyes, retrograde pulsatile flow was detected in the superotemporal vortex veins, which were connected to the inferotemporal vortex veins via intervortex venous anastomoses. Among these cases, contralateral inferotemporal vortex vein dilatation was dominant in 7 eyes (77.8%), while superotemporal and inferotemporal vortex veins were symmetrically dilated in the other 2 eyes (22.2%). On the other hand, in 13 eyes, the retrograde pulsatile flow was detected in the inferotemporal vortex veins, which were linked to the superotemporal vortex veins via intervortex venous anastomoses. In these eyes, contralateral superotemporal vortex vein dilatation was dominant in 10 eyes (76.9%). Superotemporal and inferotemporal vortex veins were symmetrically dilated in 2 eyes (15.4%), while mainly inferotemporal vortex veins were dilated in 1 eye (7.7%).</p></div><div><h3>Conclusions</h3><p>In pachychoroid spectrum diseases, there are cases wherein congested venous blood might drain into the contralateral vortex veins via intervortex anastomoses. Overloaded contralateral vortex veins may, as a consequence, become more dilated than the primary congested vortex veins. Inversion of asymmetric vortex vein dilatation might thereby develop in pachychoroid spectrum diseases.</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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000514/pdfft?md5=83efe8d3dde33716f5491c45af39f0c0&pid=1-s2.0-S2666914524000514-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140274586","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":"Familial Exudative Vitreoretinopathy With and Without Pathogenic Variants of Norrin/β-Catenin Signaling Genes","authors":"Hiroyuki Kondo MD, PhD ,&nbsp;Tomoko Tsukahara-Kawamura MD, PhD ,&nbsp;Itsuka Matsushita MD, PhD ,&nbsp;Tatsuo Nagata MD, PhD ,&nbsp;Takaaki Hayashi MD, PhD ,&nbsp;Sachiko Nishina MD, PhD ,&nbsp;Koichiro Higasa PhD ,&nbsp;Eiichi Uchio MD, PhD ,&nbsp;Mineo Kondo MD, PhD ,&nbsp;Taiji Sakamoto MD, PhD ,&nbsp;Shunji Kusaka MD, PhD","doi":"10.1016/j.xops.2024.100514","DOIUrl":"10.1016/j.xops.2024.100514","url":null,"abstract":"<div><h3>Purpose</h3><p>To determine the clinical characteristics of familial exudative vitreoretinopathy (FEVR) associated with or without pathogenic variants of the Norrin/β-catenin genes.</p></div><div><h3>Design</h3><p>This was a multicenter, cross-sectional, observational, and genetic study.</p></div><div><h3>Subjects</h3><p>Two-hundred eighty-one probands with FEVR were studied.</p></div><div><h3>Methods</h3><p>Whole-exome sequence and/or Sanger sequence was performed for the Norrin/β-catenin genes, the <em>FZD4</em>, <em>LRP5</em>, <em>TSPAN12</em>, and <em>NDP</em> genes on blood collected from the probands. The clinical symptoms of the probands with or without the pathogenic variants were assessed as well as differences in the inter Norrin/β-catenin genes.</p></div><div><h3>Main Outcome Measures</h3><p>The phenotype associated with or without pathogenic variants of the Norrin/β-catenin genes.</p></div><div><h3>Results</h3><p>One-hundred eight probands (38.4%) had 88 different pathogenic or likely pathogenic variants in the genes: 24 with the <em>FZD4</em>, 42 with the <em>LRP5</em>, 10 with the <em>TSPAN12</em>, and 12 with the <em>NDP</em> gene. Compared with the 173 probands without pathogenic variants, the 108 variant-positive probands had characteristics of familial predisposition (63.9% vs. 37.6%, <em>P</em> &lt; 0.0001), progression during infancy (75.0% vs. 53.8%, <em>P</em> = 0.0004), asymmetrical severity between the 2 eyes (50.0% vs. 37.6%, <em>P</em> = 0.0472), and nonsyndromic characteristics (10.2% vs. 17.3%, <em>P</em> = 0.1185). The most frequent stage at which the more severe eye conditions was present was at stage 4 in both groups (40.7% vs. 34.7%). However, the advanced stages of 3 to 5 in the more severe eye were found more frequently in probands with variants than in those without variants (83.3% vs. 58.4%, <em>P</em> &lt; 0.0001). Patients with rhegmatogenous retinal detachments progressed from stage 1 or 2 were found less frequently in the variant-positive probands (8.3% vs. 17.3%, <em>P</em> = 0.0346). Nine probands with <em>NDP</em> variants had features different from probands with typical Norrin/β-catenin gene variants including the sporadic, symmetrical, and systemic characteristics consistent with Norrie disease.</p></div><div><h3>Conclusions</h3><p>The results showed that the clinical characteristics of FEVR of patients with variants in the Norrin/β-catenin genes are different from those with other etiologies. We recommend that clinicians who diagnose a child with FEVR perform genetic testing so that the parents can be informed on the prognosis of the vision and general health in the child.</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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000502/pdfft?md5=c8de17d4235869623c274e0b10751bbe&pid=1-s2.0-S2666914524000502-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140273449","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":"Dose-Dependent Progression of Chorioretinal Atrophy at the Injection Site After Subretinal Injection of rAAV2/8 in Nonhuman Primates","authors":"Immanuel P. Seitz MD ,&nbsp;Fabian Wozar MD ,&nbsp;G. Alex Ochakovski ,&nbsp;Felix F. Reichel MD ,&nbsp;Faik Gelisken MD ,&nbsp;K. Ulrich Bartz-Schmidt MD ,&nbsp;Tobias Peters MD ,&nbsp;M. Dominik Fischer MD, PhD","doi":"10.1016/j.xops.2024.100516","DOIUrl":"10.1016/j.xops.2024.100516","url":null,"abstract":"<div><h3>Objective</h3><p>Progressive retinal atrophy has been described after subretinal gene therapy utilizing the adeno-associated virus (AAV) vector platform. To elucidate whether this atrophy is a consequence of inherent properties of AAV, or if it is related to the surgical trauma of subretinal delivery, we analyzed data from an Investigational New Drug–enabling study for PDE6A gene therapy in nonhuman primates.</p></div><div><h3>Design</h3><p>Animal study (nonhuman primates), retrospective data analysis.</p></div><div><h3>Subjects</h3><p>Forty eyes of 30 healthy nonhuman primates (macaca fascicularis) were included in the analysis. Two AAV dose levels (low: 1x10E11, high: 1x10E12) were compared with sham injection (balanced saline solution; BSS). Twenty untreated eyes were not analyzed.</p></div><div><h3>Methods</h3><p>Animals were treated with a sutureless 23G vitrectomy and single subretinal injections of AAV.PDE6A and/or BSS. The follow-up period was 12 weeks. Atrophy development was followed using fundus autofluorescence (AF), OCT, fluorescence angiography, and indocyanine green angiography.</p></div><div><h3>Main Outcome Measures</h3><p>Area [mm²] of retinal pigment epithelium atrophy on AF. Presence of outer retinal atrophy on optical coherence tomography. Area [mm²] of hyperfluorescence in fluorescence angiography and hypofluorescence in indocyanine green angiography.</p></div><div><h3>Results</h3><p>Progressive atrophy at the injection site developed in 54% of high-dose-treated, 27% of low-dose-treated, and 0% of sham-treated eyes. At the end of observation, the mean ± SD area of atrophy in AF was 1.19 ± 1.75 mm², 0.25 ± 0.50 mm², and 0.0 ± 0.0 mm², respectively (sham × high dose: <em>P</em> = 0.01). Atrophic lesions in AF (<em>P</em> = 0.01) and fluorescence angiography (<em>P</em> = 0.02) were significantly larger in high-dose-treated eyes, compared with sham-treated eyes. Rate of progression in high-dose-treated eyes was 4.1× higher compared with low-dose-treated eyes.</p></div><div><h3>Conclusion</h3><p>Subretinal injection of AAV.PDE6A induced dose-dependent, progressive retinal atrophy at the site of injection. Findings from multimodal imaging were in line with focal, transient inflammation within the retina and choroid and secondary atrophy. Atrophic changes after gene therapy with AAV-based vector systems are not primarily due to surgical trauma and increase with the dose given.</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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000526/pdfft?md5=983a8d5bd59a693a12c3dda3d080bb5c&pid=1-s2.0-S2666914524000526-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140274963","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":"Prosthetic Visual Acuity with the PRIMA Subretinal Microchip in Patients with Atrophic Age-Related Macular Degeneration at 4 Years Follow-up","authors":"Mahiul Muhammed Khan Muqit MD, FRCOphth ,&nbsp;Yannick Le Mer MD ,&nbsp;Lisa Olmos de Koo MD ,&nbsp;Frank G. Holz MD ,&nbsp;Jose A. Sahel MD ,&nbsp;Daniel Palanker PhD","doi":"10.1016/j.xops.2024.100510","DOIUrl":"10.1016/j.xops.2024.100510","url":null,"abstract":"<div><h3>Objective</h3><p>To assess the efficacy and safety of the PRIMA neurostimulation system with a subretinal microchip for improving visual acuity (VA) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) at 48-months postimplantation.</p></div><div><h3>Design</h3><p>Feasibility clinical trial of the PRIMA subretinal prosthesis in patients with atrophic AMD, measuring best-corrected ETDRS VA (<span>Clinicaltrials.gov</span><svg><path></path></svg> <span>NCT03333954</span><svg><path></path></svg>).</p></div><div><h3>Subjects</h3><p>Five patients with GA, no foveal light perception, and VA of logarithm of the minimum angle of resolution (logMAR) 1.3 to 1.7 (20/400-20/1000) in their worse-seeing “study” eye.</p></div><div><h3>Methods</h3><p>In patients subretinally implanted with a photovoltaic neurostimulation array containing 378 pixels of 100 μm in size, the VA was measured with and without the PRIMA system using ETDRS charts at 1 m. The system’s external components, augmented reality glasses, and pocket computer provide image processing capabilities, including zoom.</p></div><div><h3>Main Outcome Measures</h3><p>Visual acuity using ETDRS charts with and without the system, as well as light sensitivity in the central visual field, measured by Octopus perimetry. Anatomical outcomes demonstrated by fundus photography and OCT up to 48 months postimplantation.</p></div><div><h3>Results</h3><p>All 5 subjects met the primary end point of light perception elicited by the implant in the scotoma area. In 1 patient, the implant was incorrectly inserted into the choroid. One subject died 18 months postimplantation due to study-unrelated reasons. ETDRS VA results for the remaining 3 subjects are reported here. Without zoom, VA closely matched the pixel size of the implant: 1.17 ± 0.13 pixels, corresponding to a mean logMAR of 1.39, or Snellen of 20/500, ranging from 20/438 to 20/565. Using zoom at 48 months, subjects improved their VA by 32 ETDRS letters versus baseline (standard error 5.1) 95% confidence intervals (13.4, 49.9; <em>P</em> &lt; 0.0001). Natural peripheral visual function in the treated eye did not decline after surgery or during the 48-month follow-up period (<em>P</em> = 0.08).</p></div><div><h3>Conclusions</h3><p>Subretinal implantation of PRIMA in subjects with GA experiencing profound vision loss due to AMD is feasible and well tolerated, with no reduction of natural peripheral vision up to 48 months. Prosthetic central vision provided by photovoltaic neurostimulation enabled patients to reliably recognize letters and sequences of letters, and with zoom, it improved VA of up to 8 ETDRS lines.</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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000460/pdfft?md5=1ab9d0dd84f5ae65da17ee9fd952f926&pid=1-s2.0-S2666914524000460-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140091670","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":"Clinical Profile and Ocular Morbidities in Patients with Both Diabetic Retinopathy and Uveitis","authors":"","doi":"10.1016/j.xops.2024.100511","DOIUrl":"10.1016/j.xops.2024.100511","url":null,"abstract":"<div><h3>Purpose</h3><p>To describe the clinical profile and complications of diabetic retinopathy (DR) and uveitis in patients with coexisting conditions and to derive associations based on site of primary inflammation, stage of DR, and complications of each.</p></div><div><h3>Design</h3><p>Single-center, cross-sectional observational study.</p></div><div><h3>Participants</h3><p>Sixty-six patients with coexisting DR and uveitis.</p></div><div><h3>Methods</h3><p>Electronic medical records of 66 such cases were evaluated. The demographic data, diabetic status, clinical characteristics, and complications of DR and uveitis on the final follow-up were recorded.</p></div><div><h3>Main Outcome Measures</h3><p>Associations between best corrected visual acuity (BCVA), prevalence of various stages, and complications of DR among eyes with and without uveitis, and correlation between the intensity and primary sites of inflammation among eyes with proliferative and nonproliferative changes.</p></div><div><h3>Results</h3><p>Of the 132 eyes, all had DR and 97 eyes had uveitis (35 unilateral and 31 bilateral cases). Mean age of patients was 53.4 ± 8.7 years, duration of diabetes was 10.5 ± 6.9 years, and duration of uveitis was 61.3 ± 68.8 months. Of uveitis patients, 54.6% had anterior uveitis (AU), 20.6% had intermediate, 10.3% posterior, and 14.4% panuveitis. Forty-nine point five percent of eyes had proliferative DR (PDR) changes. There was a higher proportion PDR cases among anterior (56.6%), posterior (70%), and panuveitis (64.3%), with difference in AU cases approaching statistical significance (<em>P</em> = 0.067). Conversely, significant (<em>P</em> &lt; 0.001) intermediate uveitis cases had nonproliferative changes (80%). Final BCVA was significantly poorer in the group with uveitis (<em>P</em> = 0.045). The proportion of fibrovascular proliferations, tractional detachments. and iris neovascularization among proliferative retinopathy eyes with uveitis (14.6%, 18.8%, and 12.5% respectively) was higher than those without uveitis (5.3%, 10.5%, and 5.3%). Among uveitis cases, 58.5% eyes developed cataracts, 44.3% had posterior synechiae, 12.3% developed secondary glaucoma, 4.1% had epiretinal membrane, 4.1% had band-shaped keratopathy, and 1.0% developed macular neovascularization.</p></div><div><h3>Conclusions</h3><p>Eyes with coexisting DR and uveitis have a higher prevalence of neovascular and uveitis complications along with a risk of poorer visual outcomes. Treatment should aim at limiting the duration and intensity of inflammation. Strict glycemic control is essential for inflammation control and preventing the progression of DR to more advanced stages.</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":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000472/pdfft?md5=607385eaac94d8bfae3d6c33ee79807b&pid=1-s2.0-S2666914524000472-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140270662","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":"Deep Learning-Based Identification of Intraocular Pressure-Associated Genes Influencing Trabecular Meshwork Cell Morphology","authors":"Connor J. Greatbatch MBBS ,&nbsp;Qinyi Lu MD, PhD ,&nbsp;Sandy Hung PhD ,&nbsp;Son N. Tran PhD ,&nbsp;Kristof Wing MBBS ,&nbsp;Helena Liang MD, PhD ,&nbsp;Xikun Han PhD ,&nbsp;Tiger Zhou FRANZCO, PhD ,&nbsp;Owen M. Siggs MD, PhD ,&nbsp;David A. Mackey FRANZCO, MD ,&nbsp;Guei-Sheung Liu PhD ,&nbsp;Anthony L. Cook PhD ,&nbsp;Joseph E. Powell PhD ,&nbsp;Jamie E. Craig FRANZCO, DPhil ,&nbsp;Stuart MacGregor PhD ,&nbsp;Alex W. Hewitt FRANZCO, PhD","doi":"10.1016/j.xops.2024.100504","DOIUrl":"10.1016/j.xops.2024.100504","url":null,"abstract":"<div><h3>Purpose</h3><p>Genome-wide association studies have recently uncovered many loci associated with variation in intraocular pressure (IOP). Artificial intelligence (AI) can be used to interrogate the effect of specific genetic knockouts on the morphology of trabecular meshwork cells (TMCs) and thus, IOP regulation.</p></div><div><h3>Design</h3><p>Experimental study.</p></div><div><h3>Subjects</h3><p>Primary TMCs collected from human donors.</p></div><div><h3>Methods</h3><p>Sixty-two genes at 55 loci associated with IOP variation were knocked out in primary TMC lines. All cells underwent high-throughput microscopy imaging after being stained with a 5-channel fluorescent cell staining protocol. A convolutional neural network was trained to distinguish between gene knockout and normal control cell images. The area under the receiver operator curve (AUC) metric was used to quantify morphological variation in gene knockouts to identify potential pathological perturbations.</p></div><div><h3>Main Outcome Measures</h3><p>Degree of morphological variation as measured by deep learning algorithm accuracy of differentiation from normal controls.</p></div><div><h3>Results</h3><p>Cells where <em>LTBP2</em> or <em>BCAS3</em> had been perturbed demonstrated the greatest morphological variation from normal TMCs (AUC 0.851, standard deviation [SD] 0.030; and AUC 0.845, SD 0.020, respectively). Of 7 multigene loci, 5 had statistically significant differences in AUC (<em>P</em> &lt; 0.05) between genes, allowing for pathological gene prioritization. The mitochondrial channel most frequently showed the greatest degree of morphological variation (33.9% of cell lines).</p></div><div><h3>Conclusions</h3><p>We demonstrate a robust method for functionally interrogating genome-wide association signals using high-throughput microscopy and AI. Genetic variations inducing marked morphological variation can be readily identified, allowing for the gene-based dissection of loci associated with complex traits.</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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266691452400040X/pdfft?md5=71fbd2bf0bb8c3ea8a492f2781609685&pid=1-s2.0-S266691452400040X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140084950","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":"A Phase IIa Multicenter, Randomized, Vehicle-Controlled, Dose Escalating Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of CBT-001 Ophthalmic Solution in Patients With Primary or Recurrent Pterygium","authors":"Scott M. Whitcup MD ,&nbsp;Kenneth N. Sall MD ,&nbsp;John A. Hovanesian MD ,&nbsp;Damien F. Goldberg MD ,&nbsp;Olivia L. Lee MD ,&nbsp;Rong Yang PhD ,&nbsp;Jinsong Ni PhD","doi":"10.1016/j.xops.2024.100502","DOIUrl":"10.1016/j.xops.2024.100502","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate the safety and efficacy of CBT-001, a multitarget tyrosine kinase inhibitor eyedrop, for pterygia.</p></div><div><h3>Design</h3><p>Phase II clinical trial. Stage 1 was a single center, open-labeled, vehicle-controlled study. Stage 2 was a multicenter, randomized, double-masked, vehicle-controlled trial.</p></div><div><h3>Participants</h3><p>Patients with primary or recurrent pterygia.</p></div><div><h3>Main Outcome Measures</h3><p>The primary efficacy end point was lesion vascularity based on masked grading of photographs by an independent reading center. Other end points included dimensions of pterygia and safety.</p></div><div><h3>Methods</h3><p>In stage 1, 24 eyes of 24 patients received 1 drop of CBT-001 in a dose escalation fashion (0.02%, 0.05%, and 0.2%) to determine the maximally tolerated dose based on adverse events (AEs) and blood drug levels. In stage 2, subjects were randomly assigned to receive the maximally tolerated dose of CBT-001 or vehicle dosed 3 times a day for 4 weeks with a 20-week follow-up.</p></div><div><h3>Results</h3><p>In stage 1, the plasma maximum concentration values for all doses of CBT-001 were at or below the limit of detection (0.01 ng/ml). The most commonly reported AEs were mild foreign body sensation and irritation. CBT-001 0.2% was evaluated in stage 2. Baseline demographic characteristics were similar between patients receiving CBT-001 (n = 25) and vehicle (n = 23). After 4 weeks of dosing, the mean change from baseline in pterygium vascularity scores was −0.8 ± 0.7 (mean ± standard deviation) in subjects receiving CBT-001 0.2% and 0.0 ± 0.5 in subjects receiving vehicle (<em>P</em> &lt; 0.001; 95% confidence interval: −1.12, −0.40). Pterygium vascularity scores remained significantly decreased, after the 4-week dosing period, at weeks 8 and 16, but not at week 24. The mean changes from baseline in the length of the pterygia were also significantly lower in subjects receiving CBT-001 compared with vehicle at weeks 2, 4, and 8 (<em>P</em> ≤ 0.014). The most commonly reported AEs were ocular, mild in severity, resolved after therapy, and did not result in discontinuation.</p></div><div><h3>Conclusions</h3><p>CBT-001 0.2% decreased pterygia vascularity and lesion length after 4 weeks of dosing with a prolonged effect after dosing. The drug was well tolerated with minimal detected systemic drug levels.</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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000381/pdfft?md5=974290352b8c6e60b846833b465ba559&pid=1-s2.0-S2666914524000381-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140274965","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 Signs and Testing Most Compatible with Sarcoidosis-Associated Uveitis: A Latent Class Analysis","authors":"Fanxiu Xiong MAS ,&nbsp;Nisha Acharya MD, MS ,&nbsp;Narsing Rao MD ,&nbsp;Manabu Mochizuki MD, PhD ,&nbsp;Thomas M. Lietman MD ,&nbsp;John A. Gonzales MD","doi":"10.1016/j.xops.2024.100503","DOIUrl":"10.1016/j.xops.2024.100503","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aims to explore the potential subgroups of sarcoidosis-associated uveitis (SAU) within a multicenter cohort of uveitis participants.</p></div><div><h3>Design</h3><p>Cross-sectional study.</p></div><div><h3>Participants</h3><p>A cohort of 826 uveitis patients from a uveitis registry from 19 clinical centers in 12 countries between January 2011 and April 2015.</p></div><div><h3>Methods</h3><p>We employed a latent class analysis (LCA) incorporating recommended tests and clinical signs from the revised International Workshop on Ocular Sarcoidosis (IWOS) to identify potential SAU subgroups within the multicenter uveitis cohort. Additionally, we assessed the performance of the individual tests and clinical signs in classifying the potential subclasses.</p></div><div><h3>Main Outcome Measures</h3><p>Latent subtypes of SAU.</p></div><div><h3>Results</h3><p>Among 826 participants included in this analysis, the 2-class LCA model provided a best fit, with the lowest Bayesian information criteria of 7218.7 and an entropy of 0.715. One class, consisting of 548 participants, represented the non-SAU, whereas the second class, comprised of 278 participants, was most representative of SAU. Snowballs/string of pearls vitreous opacities had the best test performance for classification, followed by bilaterality and bilateral hilar lymphadenopathy (BHL). The combination of 4 tests with the highest classification importance, including snowballs/string of pearls vitreous opacities, periphlebitis and/or macroaneurysm, bilaterality, and BHL, demonstrated a sensitivity of 84.8% and a specificity of 95.4% in classifying the SAU subtypes. In the exploratory analysis of the 3-class LCA model, which had comparable fit indices as the 2-class model, we identified a candidate non-SAU subtype, candidate SAU subtype with pulmonary involvement, and a candidate SAU with less pulmonary involvement.</p></div><div><h3>Conclusions</h3><p>Latent class modeling, incorporating tests and clinical signs from the revised IWOS criteria, effectively identified a subset of participants with clinical features indicative of SAU. Though the sensitivity of individual ocular signs or tests was not perfect, using a combination of tests provided a satisfactory performance in classifying the SAU subclasses identified by the 2-class LCA model. Notably, the classes identified by the 3-class LCA model, including a non-SAU subtype, an SAU subtype with pulmonary involvement, and an SAU subtype with less pulmonary involvement, may have potential implication for clinical practice, and hence should be validated in further research.</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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000393/pdfft?md5=96749eb9a601b611c2d8349150459dae&pid=1-s2.0-S2666914524000393-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140087392","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 Relationship Between Artificial Intelligence–Assisted OCT Angiography–Derived Foveal Avascular Zone Parameters and Visual-Field Defect Progression in Eyes with Open-Angle Glaucoma","authors":"Takahiro Ninomiya MD ,&nbsp;Naoki Kiyota MD, PhD ,&nbsp;Parmanand Sharma PhD ,&nbsp;Kazuko Omodaka MD, PhD ,&nbsp;Noriko Himori MD, PhD ,&nbsp;Masayuki Yasuda MD, PhD ,&nbsp;Hiroshi Kunikata MD, PhD ,&nbsp;Toru Nakazawa MD, PhD","doi":"10.1016/j.xops.2023.100387","DOIUrl":"10.1016/j.xops.2023.100387","url":null,"abstract":"<div><h3>Purpose</h3><p>To investigate clinical factors associated with foveal avascular zone (FAZ) parameters obtained using OCT angiography (OCTA) with assistance from a previously developed artificial intelligence (AI) platform in eyes with open-angle glaucoma (OAG).</p></div><div><h3>Design</h3><p>Retrospective longitudinal.</p></div><div><h3>Participants</h3><p>This study followed up 885 eyes of 558 patients with OAG for ≥ 2 years; all eyes underwent ≥ 5 Humphrey visual-field (VF) tests and had 3.0 × 3.0 mm macular OCTA scans available.</p></div><div><h3>Methods</h3><p>Average total deviation (TD) in the superior, superocentral, inferocentral, and inferior sectors of the Humphrey 24-2 program was calculated. We collected 3.0 × 3.0 mm macular OCTA images from each patient and used a previously developed AI platform with these images to obtain FAZ parameters, including FAZ area, FAZ circularity index (CI), and FAZ perimeter. Multivariable linear mixed-effects models were used to analyze the relationship between FAZ parameters, TD or TD slope in each quadrant, and systemic factors, adjusting for potential confounding factors, including axial length.</p></div><div><h3>Main Outcome Measures</h3><p>Ophthalmic and systemic variables, FAZ parameters, and TD or TD slope in each quadrant.</p></div><div><h3>Results</h3><p>The multivariable model showed that FAZ parameters were correlated with both TD and TD slope in the inferocentral quadrant (β = −0.244 - 0.168, <em>P</em> &lt; 0.001). Both upper-half and lower-half FAZ parameters were better associated with TD-inferocentral and TD-inferocentral slope than TD-superocentral or TD-superocentral slope in terms of β size and statistical significance, indicating that there was no evident vertical anatomical correspondence between TD in the central quadrant and FAZ parameters. Foveal avascular zone area enlargement was associated with female gender (β = 0.242, <em>P</em> = 0.003). Loss of FAZ circularity was associated with both aging and comorbid sleep apnea syndrome (SAS) (yes: 1, no: 0) (β = −0.188, <em>P</em> &lt; 0.001; β = −0.261, <em>P</em> = 0.031, respectively). Foveal avascular zone perimeter elongation was associated with aging and female gender (β = 0.084, <em>P</em> = 0.040; β = 0.168, <em>P</em> = 0.042, respectively).</p></div><div><h3>Conclusions</h3><p>Artificial intelligence-assisted OCTA-measured FAZ enlargement and irregular shape might be good markers of ocular hypoperfusion and associated inferocentral VF defect progression in eyes with OAG. <strong><em>Financial Disclosure(s):</em></strong> 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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914523001197/pdfft?md5=9e95440f596191c5ad829b1f6980f00d&pid=1-s2.0-S2666914523001197-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43029513","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 Epigenome-Wide Association Study of DNA Methylation and Proliferative Retinopathy over 28 Years in Type 1 Diabetes","authors":"Rachel G. Miller PhD ,&nbsp;Josyf C. Mychaleckyj DPhil ,&nbsp;Suna Onengut-Gumuscu PhD ,&nbsp;Trevor J. Orchard MD, MMedSci ,&nbsp;Tina Costacou PhD","doi":"10.1016/j.xops.2024.100497","DOIUrl":"10.1016/j.xops.2024.100497","url":null,"abstract":"<div><h3>Purpose</h3><p>To perform a prospective epigenome-wide association study of DNA methylation (DNAm) and 28-year proliferative diabetic retinopathy (PDR) incidence in type 1 diabetes (T1D).</p></div><div><h3>Design</h3><p>Prospective observational cohort study.</p></div><div><h3>Participants</h3><p>The Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood-onset (&lt; 17 years) T1D.</p></div><div><h3>Methods</h3><p>Stereoscopic fundus photographs were taken in fields 1, 2, and 4 at baseline, 2, 4, 6, 8, 16, 23, and 28 years after DNAm measurements. The photos were graded using the modified Airlie House System. In those free of PDR at baseline (n = 265; mean T1D duration of 18 years at baseline), whole blood DNAm (EPIC array) at 683 597 CpGs was analyzed in Cox models for time to event. Associations between significant CpGs and clinical risk factors were assessed; genetic variants associated with DNAm were identified (methylation quantitative trait loci [meQTLs]). Mendelian randomization was used to examine evidence of causal associations between DNAm and PDR. Post hoc regional and functional analyses were performed.</p></div><div><h3>Main Outcome Measures</h3><p>Proliferative diabetic retinopathy was defined as the first instance of a grade of ≥ 60 in at least 1 eye or pan-retinal photocoagulation for PDR. Follow-up time was calculated from the study visit at which DNAm data were available (baseline) until PDR incidence or censoring (December 31, 2018 or last follow-up).</p></div><div><h3>Results</h3><p>PDR incidence was 53% over 28-years’ follow-up. Greater DNAm of cg27512687 (<em>KIF16B</em>) was associated with reduced PDR incidence (<em>P</em> = 6.3 × 10⁻⁹; false discovery rate [FDR]: &lt; 0.01); 113 cis-meQTLs (<em>P</em> &lt; 5 × 10⁻⁸) were identified. Mendelian randomization analysis using the sentinel meQTL as the instrumental variable supported a potentially causal association between cg27512687 and PDR. Cg27512687 was also associated with lower pulse rate and albumin excretion rate and higher estimated glomerular filtration rate, but its association with PDR remained independently significant after adjustment for those factors. In regional analyses, DNAm of <em>FUT4</em>, <em>FKBP1A</em>, and <em>RIN2</em> was also associated with PDR incidence.</p></div><div><h3>Conclusions</h3><p>DNA methylation of <em>KIF16B, FUT4, FKBP1A</em>, and <em>RIN2</em> was associated with PDR incidence, supporting roles for epigenetic regulation of iron clearance, developmental pathways, and autophagy in PDR pathogenesis. Further study of those loci may provide insight into novel targets for interventions to prevent or delay PDR in T1D.</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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000332/pdfft?md5=85f2c517d7229ffc540ff6dfe60ed7be&pid=1-s2.0-S2666914524000332-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140467907","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}