Ophthalmology science最新文献

{"title":"Clinical Characteristics and Progression of Pachychoroid and Conventional Geographic Atrophy","authors":"Yukiko Sato MD ,&nbsp;Naoko Ueda-Arakawa MD, PhD ,&nbsp;Ayako Takahashi MD, PhD ,&nbsp;Masahiro Miyake MD, PhD ,&nbsp;Yuki Mori MD, PhD ,&nbsp;Yasunori Miyara MD ,&nbsp;Chikako Hara MD, PhD ,&nbsp;Yoko Kitajima MD ,&nbsp;Ruka Maruko MD, PhD ,&nbsp;Moeko Kawai MD ,&nbsp;Hajime Takahashi MD, PhD ,&nbsp;Hideki Koizumi MD, PhD ,&nbsp;Maiko Maruyama-Inoue MD, PhD ,&nbsp;Yasuo Yanagi MD, PhD ,&nbsp;Tomohiro Iida MD, PhD ,&nbsp;Kanji Takahashi MD, PhD ,&nbsp;Taiji Sakamoto MD, PhD ,&nbsp;Akitaka Tsujikawa MD, PhD","doi":"10.1016/j.xops.2024.100528","DOIUrl":"10.1016/j.xops.2024.100528","url":null,"abstract":"<div><h3>Purpose</h3><p>To elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA).</p></div><div><h3>Design</h3><p>Retrospective, multicenter, observational study.</p></div><div><h3>Participants</h3><p>A total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from 6 university hospitals in Japan were included. All patients were Japanese, aged ≥50 years and with fundus autofluorescence images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group.</p></div><div><h3>Methods</h3><p>The studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semiautomatically measured on fundus autofluorescence images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype.</p></div><div><h3>Main Outcome Measures</h3><p>Clinical characteristics and progression rates of pachychoroid and conventional GA.</p></div><div><h3>Results</h3><p>The pachychoroid GA group was significantly younger (70.3 vs. 78.7 years; <em>P</em> &lt; 0.001), more male-dominant (89.5 vs. 55.6%; <em>P</em> &lt; 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution; <em>P</em> = 0.002), thicker choroid (312.4 vs. 161.6 μm; <em>P</em> &lt; 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%; <em>P</em> &lt; 0.001), and smaller GA area (0.59 vs. 3.76 mm²^; <em>P</em> &lt; 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs. 0.27 mm/year; <em>P</em> &lt; 0.001).</p></div><div><h3>Conclusions</h3><p>Demographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in White populations. Some characteristics of GA in Japanese population differ from those in Waucasian populations, which may be due to the inclusion of pachychoroid GA.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100528"},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000642/pdfft?md5=4f58345dd5be031501cd659ca7700e4f&pid=1-s2.0-S2666914524000642-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140770545","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":"Phase I DAVIO Trial: EYP-1901 Bioerodible, Sustained-Delivery Vorolanib Insert in Patients With Wet Age-Related Macular Degeneration","authors":"Sunil Patel MD, PhD ,&nbsp;Philip P. Storey MD ,&nbsp;Mark R. Barakat MD ,&nbsp;Vrinda Hershberger MD ,&nbsp;William Z. Bridges Jr. MD ,&nbsp;David A. Eichenbaum MD ,&nbsp;David R. Lally MD, PhD ,&nbsp;David S. Boyer MD ,&nbsp;Sophie J. Bakri MD ,&nbsp;Monica Roy OD, MPH ,&nbsp;Dario A. Paggiarino MD","doi":"10.1016/j.xops.2024.100527","DOIUrl":"10.1016/j.xops.2024.100527","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate safety and tolerability of EYP-1901, an intravitreal insert containing vorolanib, a pan–VEGF receptor inhibitor packaged in a bioerodible delivery technology (Durasert E™) for sustained delivery, in patients with wet age-related macular degeneration (wAMD) previously treated with anti-VEGF therapy.</p></div><div><h3>Design</h3><p>Phase I, multicenter, prospective, open-label, dose-escalation trial.</p></div><div><h3>Participants</h3><p>Patients with wAMD and evidence of prior anti-VEGF therapy response.</p></div><div><h3>Methods</h3><p>Patients received a single intravitreal injection of EYP-1901.</p></div><div><h3>Main Outcome Measures</h3><p>The primary objective was to evaluate safety and tolerability of EYP-1901. Secondary objectives assessed biologic activity of EYP-1901 including best-corrected visual acuity (BCVA) and central subfield thickness (CST). Exploratory analyses included reduction in anti-VEGF treatment burden and supplemental injection-free rates.</p></div><div><h3>Results</h3><p>Seventeen patients enrolled in the 440 μg (3 patients), 1030 μg (1 patient), 2060 μg (8 patients), and 3090 μg (5 patients) dose cohorts. No dose-limiting toxicity, ocular serious adverse events (AEs), or systemic AEs related to EYP-1901 were observed. There was no evidence of ocular or systemic toxicity related to vorolanib or the delivery technology. Moderate ocular treatment-emergent AEs (TEAEs) included reduced visual acuity (2/17) and retinal exudates (3/17). One patient with reduced BCVA had 3 separate reductions of 17, 18, and 16 letters, and another had a single drop of 25 letters. One severe TEAE, neovascular AMD (i.e., worsening/progressive disease activity), was reported in 1 of 17 study eyes but deemed unrelated to treatment. Mean change from baseline in BCVA was −1.8 letters and −5.4 letters at 6 and 12 months. Mean change from baseline in CST was +1.7 μm and +2.4 μm at 6 and 12 months. Reduction in treatment burden was 74% and 71% at 6 and 12 months. Of 16 study eyes, 13, 8, and 5 were injection-free up to 3, 6, and 12 months.</p></div><div><h3>Conclusion</h3><p>In the DAVIO trial (<span>ClinicalTrials.gov</span><svg><path></path></svg> identifier, NCT04747197), EYP-1901 had a favorable safety profile and was well tolerated in previously treated eyes with wAMD. Measures of biologic activity remained relatively stable following a single EYP-1901 injection. These preliminary data support ongoing phase II and planned phase III trials to assess efficacy and safety.</p></div><div><h3>Financial Disclosure(s)</h3><p>The author(s) have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100527"},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000630/pdfft?md5=9d462f7351a608ab1ac261afc7321547&pid=1-s2.0-S2666914524000630-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776026","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":"Visual Function Measurements in Eyes With Diabetic Retinopathy: An Expert Opinion on Available Measures","authors":"Adam R. Glassman MS ,&nbsp;Mohamed Ashraf Elmasry MD, PhD ,&nbsp;Darrell E. Baskin MD ,&nbsp;Mitchell Brigell PhD ,&nbsp;Victor Chong MD ,&nbsp;Quentin Davis PhD ,&nbsp;Luis Lesmes PhD ,&nbsp;Leonard A. Levin MD, PhD ,&nbsp;Ted Maddess PhD, FNAI ,&nbsp;Laura J. Taylor BSc(Hons) ,&nbsp;Andreas Wenzel PhD","doi":"10.1016/j.xops.2024.100519","DOIUrl":"10.1016/j.xops.2024.100519","url":null,"abstract":"<div><h3>Clinical Relevance</h3><p>Visual function impairment from diabetic retinopathy can have a considerable impact on patient’s quality of life. Best-corrected visual acuity (BCVA) is most commonly used to assess visual function and guide clinical trials. However, BCVA is affected late in the disease process, is not affected in early disease, and does not capture some of the visual disturbances described by patients with diabetes. The goal of this report is to evaluate the relationship between diabetic retinal disease (DRD) and visual function parameters to determine which if any of them may be used in a future DRD staging system.</p></div><div><h3>Methods</h3><p>The visual functions working group was 1 of 6 areas of DRD studied as part of the DRD staging system update, a project of the Mary Tyler Moore Vision Initiative. The working group identified 12 variables of possible interest, 7 of which were judged to have sufficient preliminary data to suggest an association with DR to warrant further review: microperimetry, static automated perimetry, electroretinogram (ERG) oscillatory potentials, flicker ERG, low luminance visual acuity (LLVA), contrast sensitivity (CS), and BCVA. The objective field analyzer (OFA) was added after subsequent in-person workshops.</p></div><div><h3>Results</h3><p>Currently, the only visual function test available for immediate use is BCVA; the remaining tests are either promising (within 5 years) or have potential (&gt;5 years) use. Besides BCVA, most visual function tests had a limited role in current clinical care; however, LLVA, CS, flicker ERG, and OFA demonstrated potential for screening and research purposes.</p></div><div><h3>Conclusions</h3><p>Although current visual function tests are promising, future prospective studies involving patients with early and more advanced retinopathy are necessary to determine if these tests can be used clinically or as endpoints for clinical studies.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100519"},"PeriodicalIF":0.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000551/pdfft?md5=3217947b683f5b6968fe29909225a468&pid=1-s2.0-S2666914524000551-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140788441","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":"Genotype-phenotype Correlations of Ocular Posterior Segment Abnormalities in Marfan Syndrome","authors":"Yan Liu BM ,&nbsp;Yuqiao Ju MM ,&nbsp;Tian-hui Chen MM ,&nbsp;Yong-xiang Jiang MD, PhD","doi":"10.1016/j.xops.2024.100526","DOIUrl":"10.1016/j.xops.2024.100526","url":null,"abstract":"<div><h3>Purpose</h3><p>Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the <em>f</em><em>ibrillin-1</em> ( (<em>FBN1</em>). In addition to typical phenotypes such as ectopia lentis (EL) and aortic dilation, patients with MFS are prone to ocular posterior segment abnormalities, including retinal detachment (RD), maculopathy, and posterior staphyloma (PS). This study aims to investigate the correlations between <em>FBN1</em> genotype and posterior segment abnormalities within a Chinese cohort of MFS.</p></div><div><h3>Design</h3><p>Retrospective study.</p></div><div><h3>Participants</h3><p>One hundred twenty-one eyes of 121 patients with confirmed <em>FBN1</em> mutations between January 2015 and May 2023 were included.</p></div><div><h3>Methods</h3><p>Comprehensive ophthalmic examination findings were reviewed, and the incidence of RD, atrophic, tractional, and neovascular maculopathy (ATN classification system), and PS was analyzed between different genotype groups. Only the more severely affected eye from each patient was included.</p></div><div><h3>Main Outcome Measures</h3><p>Clinical features and risk factors.</p></div><div><h3>Results</h3><p>Of 121 patients, 60 eyes (49.59%) exhibited posterior segment abnormalities, including RD (4, 3.31%), maculopathy (47, 38.84%), and PS (54, 44.63%). The mean age was 11.53 ± 11.66 years, with 79.34% of patients &lt;20 years old. The location and region of mutations were found to be associated with the incidence of maculopathy (<em>P</em> = 0.013, <em>P</em> = 0.033) and PS (<em>P</em> = 0.043, <em>P</em> = 0.036). Mutations in the middle region had a lower incidence of maculopathy and PS (<em>P</em> = 0.028 and <em>P</em> = 0.006, respectively) than those in C-terminal region. Mutations in the transforming growth factor-β (TGF-β) regulating sequence exhibited a higher incidence of maculopathy and PS (<em>P</em> = 0.020, <em>P</em> = 0.040). Importantly, the location and region of mutations were also associated with the incidence of atrophic maculopathy (<em>P</em> = 0.013 and <em>P</em> = 0.033, respectively). Mutations in the middle region had a significantly lower probability of atrophic maculopathy (<em>P</em> = 0.006), while mutations in the TGF-β regulating region had a higher incidence of atrophic maculopathy (<em>P</em> = 0.020).</p></div><div><h3>Conclusions</h3><p>Maculopathy and PS were associated with the location and region of <em>FBN1</em> mutations. Patients with mutations in the TGF-β regulating region faced an increased risk of developing retinopathy.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100526"},"PeriodicalIF":0.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000629/pdfft?md5=23f4c4d6dcf46bbd8a9c20cbbc318ed9&pid=1-s2.0-S2666914524000629-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776318","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":"Comparison of Methods of Clinical Trial Emulation Utilizing Data From the Comparison of AMD Treatment Trial (CATT) and the IRIS® Registry","authors":"Helene Fevrier MPH ,&nbsp;Andrew LaPrise BS ,&nbsp;Michael Mbagwu MD ,&nbsp;Theodore Leng MD, MS ,&nbsp;Aracelis Z. Torres PhD, MPH ,&nbsp;Durga S. Borkar MD, MMCi","doi":"10.1016/j.xops.2024.100524","DOIUrl":"10.1016/j.xops.2024.100524","url":null,"abstract":"<div><h3>Purpose</h3><p>We used exact matching and inverse propensity score weighting (IPSW) using real-world data (RWD) from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) to emulate the 2 pro re nata (<em>prn</em>) treatment arms from the Comparison of AMD Treatment Trial (CATT) and to compare the outcomes of the RWD arms to the 2 monthly treatment arms from the clinical trial.</p></div><div><h3>Design</h3><p>Retrospective cohort study utilizing deidentified electronic health record registry data and patient-level deidentified clinical trial data.</p></div><div><h3>Subjects</h3><p>All treatment-naive patient eyes with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab only for 1 year from either the CATT or the IRIS Registry.</p></div><div><h3>Methods</h3><p>Patients were identified in the IRIS Registry between October 1, 2015 and December 31, 2019. After all nonimaging-based inclusion and exclusion criteria from the CATT were applied, patient eyes receiving bevacizumab or ranibizumab only on a <em>prn</em> basis were identified as the eligible cohort. Exact matching and ISPW was applied based on age, gender, and baseline visual acuity.</p></div><div><h3>Main Outcome Measures</h3><p>Mean change in visual acuity, in approximated ETDRS letters, between baseline and 1 year for the IRIS Registry prn treatment arms generated by exact matching and IPSW.</p></div><div><h3>Results</h3><p>We identified 427 eyes treated with ranibizumab <em>prn</em> and 771 eyes treated with bevacizumab <em>prn</em>. Using exact matching, 98% (n = 281) of CATT patient eyes in the bevacizumab monthly treatment arm and 87% (n = 261) of CATT patient eyes in the ranibizumab monthly treatment arm were matched to a patient eye in the IRIS Registry. For the ranibizumab <em>prn</em> treatment arm, patient eyes generated using exact matching gained 1.9 letters and those generated using IPSW gained 2.8 letters (exact matching: 1.9 letters ± 14.0 vs. IPSW: 2.8 letters ± 15.0 letters, <em>P</em> = 0.43). For the bevacizumab <em>prn</em> treatment arm, patient eyes generated using exact matching gained 2.4 letters and those generated using IPSW gained 2.1 letters (exact matching: 2.4 letters ± 15.4 vs. IPSW: 2.1 letters ± 16.0 letters, <em>P</em> = 0.79).</p></div><div><h3>Conclusions</h3><p>Both exact matching and IPSW produced similar results in emulating the <em>prn</em> treatment arms of the CATT using IRIS Registry data and patient-level clinical trial data. Similar to prior real-world studies, the clinical outcomes were significantly worse in the IRIS Registry treatment arms compared with the clinical trial.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100524"},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000605/pdfft?md5=83c369ae33ffac7b25cf5beeedbcfd49&pid=1-s2.0-S2666914524000605-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140772763","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 Group Pointwise Spatial Mapping of Structure to Function in Glaucoma","authors":"Zhiqi Chen PhD ,&nbsp;Hiroshi Ishikawa MD ,&nbsp;Yao Wang PhD ,&nbsp;Gadi Wollstein MD ,&nbsp;Joel S. Schuman MD","doi":"10.1016/j.xops.2024.100523","DOIUrl":"https://doi.org/10.1016/j.xops.2024.100523","url":null,"abstract":"<div><h3>Purpose</h3><p>To establish generalizable pointwise spatial relationship between structure and function through occlusion analysis of a deep-learning (DL) model for predicting the visual field (VF) sensitivities from 3-dimensional (3D) OCT scan.</p></div><div><h3>Design</h3><p>Retrospective cross-sectional study.</p></div><div><h3>Participants</h3><p>A total of 2151 eyes from 1129 patients.</p></div><div><h3>Methods</h3><p>A DL model was trained to predict 52 VF sensitivities of 24-2 standard automated perimetry from 3D spectral-domain OCT images of the optic nerve head (ONH) with 12 915 OCT-VF pairs. Using occlusion analysis, the contribution of each individual cube covering a 240 × 240 × 31.25 μm region of the ONH to the model's prediction was systematically evaluated for each OCT-VF pair in a separate test set that consisted of 996 OCT-VF pairs. After simple translation (shifting in x- and y-axes to match the ONH center), group t-statistic maps were derived to visualize statistically significant ONH regions for each VF test point within a group. This analysis allowed for understanding the importance of each super voxel (240 × 240 × 31.25 μm covering the entire 4.32 × 4.32 × 1.125 mm ONH cube) in predicting VF test points for specific patient groups.</p></div><div><h3>Main Outcome Measures</h3><p>The region at the ONH corresponding to each VF test point and the effect of the former on the latter.</p></div><div><h3>Results</h3><p>The test set was divided to 2 groups, the healthy-to-early-glaucoma group (792 OCT-VF pairs, VF mean deviation [MD]: −1.32 ± 1.90 decibels [dB]) and the moderate-to-advanced-glaucoma group (204 OCT-VF pairs, VF MD: −17.93 ± 7.68 dB). Two-dimensional group t-statistic maps (x, y projection) were generated for both groups, assigning related ONH regions to visual field test points. The identified influential structural locations for VF sensitivity prediction at each test point aligned well with existing knowledge and understanding of structure-function spatial relationships.</p></div><div><h3>Conclusions</h3><p>This study successfully visualized the global trend of point-by-point spatial relationships between OCT-based structure and VF-based function without the need for prior knowledge or segmentation of OCTs. The revealed spatial correlations were consistent with previously published mappings. This presents possibilities of learning from trained machine learning models without applying any prior knowledge, potentially robust, and free from bias.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100523"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000599/pdfft?md5=65047abf0529d3473597b4e65c7cb8ae&pid=1-s2.0-S2666914524000599-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141242476","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":"Development and Clinical Evaluation of a CRISPR/Cas12a-Based Nucleic Acid Detection Platform for the Diagnosis of Keratomycoses","authors":"Hanith Raj Deivarajan MSc ,&nbsp;Vignesh Elamurugan MBBS ,&nbsp;Padmapriya Sivashanmugam MSc ,&nbsp;Jaishree Pandian PhD ,&nbsp;Karvannan Sevugamurthi MSc ,&nbsp;Gunasekaran Rameshkumar MSc ,&nbsp;Swagata Ghosh PhD ,&nbsp;Daipayan Banerjee PhD ,&nbsp;Anitha Venugopal MBBS ,&nbsp;Anju Jose MBBS, DNB ,&nbsp;Ram Rammohan PhD ,&nbsp;Anita Raghavan FRCOphth ,&nbsp;Revathi Rajaraman MBBS ,&nbsp;Dharmalingam Kuppamuthu PhD ,&nbsp;Lalitha Prajna MBBS ,&nbsp;Venkatesh N. Prajna FRCOphth ,&nbsp;Siddharth Narendran MBBS","doi":"10.1016/j.xops.2024.100522","DOIUrl":"10.1016/j.xops.2024.100522","url":null,"abstract":"<div><h3>Objective</h3><p>The objective of this study was to develop a rapid and accurate clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a-based molecular diagnostic assay (Rapid Identification of Mycoses using CRISPR, RID-MyC assay) to detect fungal nucleic acids and to compare it with existing conventional mycologic methods for the diagnosis of fungal keratitis (FK).</p></div><div><h3>Design</h3><p>This study was structured as a development and validation study focusing on the creation and assessment of the RID-MyC assay as a novel diagnostic modality for FK.</p></div><div><h3>Subjects</h3><p>Participants comprised 142 individuals presenting with suspected microbial keratitis at 3 tertiary care institutions in South India.</p></div><div><h3>Methods</h3><p>The RID-MyC assay utilized recombinase polymerase amplification targeting the 18S ribosomal RNA gene for isothermal amplification, followed by a CRISPR/Cas12a reaction. This was benchmarked against microscopy, culture, and polymerase chain reaction for the diagnosis of FK.</p></div><div><h3>Main Outcome Measures</h3><p>The primary outcome measures focused on the analytical sensitivity and specificity of the RID-MyC assay in detecting fungal nucleic acids. Secondary outcomes measured the assay's diagnostic sensitivity and specificity for FK, including its concordance with conventional diagnostic methods.</p></div><div><h3>Results</h3><p>The RID-MyC assay exhibited a detection limit ranging from 13.3 to 16.6 genomic copies across 4 common fungal species. In patients with microbial keratitis, the RID-MyC assay showed substantial agreement with microscopy (kappa = 0.714) and fair agreement with culture (kappa = 0.399). The assay demonstrated a sensitivity of 93.27% (95% confidence interval [CI], 86.62%–97.25%) and a specificity of 89.47% (95% CI, 66.86%–98.70%) for FK diagnosis, with a median diagnostic time of 50 minutes (range, 35–124 minutes).</p></div><div><h3>Conclusions</h3><p>The RID-MyC assay, utilizing CRISPR-Cas12a technology, offers high diagnostic accuracy for FK. Its potential for point-of-care use could expedite and enhance the precision of fungal diagnostics, presenting a promising solution to current diagnostic challenges.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100522"},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000587/pdfft?md5=c299eca26f092f6d329935f2953783f2&pid=1-s2.0-S2666914524000587-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140403930","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":"Rationale of Basic and Cellular Mechanisms Considered in Updating the Staging System for Diabetic Retinal Disease","authors":"M. Elizabeth Hartnett MD ,&nbsp;Ward Fickweiler MD, PhD ,&nbsp;Anthony P. Adamis MD ,&nbsp;Michael Brownlee MD ,&nbsp;Arup Das MD, PhD ,&nbsp;Elia J. Duh MD ,&nbsp;Edward P. Feener PhD ,&nbsp;George King MD ,&nbsp;Renu Kowluru PhD ,&nbsp;Ulrich F.O. Luhmann PhD ,&nbsp;Federica Storti PhD ,&nbsp;Charles C. Wykoff MD, PhD ,&nbsp;Lloyd Paul Aiello MD, PhD ,&nbsp;Basic and Cellular Mechanisms Working Group of the Mary Tyler Moore Vision Initiative","doi":"10.1016/j.xops.2024.100521","DOIUrl":"10.1016/j.xops.2024.100521","url":null,"abstract":"<div><h3>Purpose</h3><p>Hyperglycemia is a major risk factor for early lesions of diabetic retinal disease (DRD). Updating the DRD staging system to incorporate relevant basic and cellular mechanisms pertinent to DRD is necessary to better address early disease, disease progression, the use of therapeutic interventions, and treatment effectiveness.</p></div><div><h3>Design</h3><p>We sought to review preclinical and clinical evidence on basic and cellular mechanisms potentially pertinent to DRD that might eventually be relevant to update the DRD staging system.</p></div><div><h3>Participants</h3><p>Not applicable.</p></div><div><h3>Methods</h3><p>The Basic and Cellular Mechanisms Working Group (BCM-WG) of the Mary Tyler Moore Vision Initiative carefully and extensively reviewed available preclinical and clinical evidence through multiple iterations and classified these.</p></div><div><h3>Main Outcome Measures</h3><p>Classification was made into evidence grids, level of supporting evidence, and anticipated future relevance to DRD.</p></div><div><h3>Results</h3><p>A total of 40 identified targets based on pathophysiology and other parameters for DRD were grouped into concepts or evaluated as specific candidates. VEGFA, peroxisome proliferator-activated receptor-alpha related pathways, plasma kallikrein, and angiopoietin 2 had strong agreement as promising for use as biomarkers in diagnostic, monitoring, predictive, prognostic, and pharmacodynamic responses as well as for susceptibility/risk biomarkers that could underlie new assessments and eventually be considered within an updated DRD staging system or treatment, based on the evidence and need for research that would fit within a 2-year timeline. The BCM-WG found there was strong reason also to pursue the following important concepts regarding scientific research of DRD acknowledging their regulation by hyperglycemia: inflammatory/cytokines, oxidative signaling, vasoprotection, neuroprotection, mitophagy, and nutrients/microbiome.</p></div><div><h3>Conclusion</h3><p>Promising targets that might eventually be considered within an updated DRD staging system or treatment were identified. Although the BCM-WG recognizes that at this stage little can be incorporated into a new DRD staging system, numerous potential targets and important concepts deserve continued support and research, as they may eventually serve as biomarkers and/or therapeutic targets with measurable benefits to patients with diabetes.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100521"},"PeriodicalIF":3.2,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000575/pdfft?md5=a87b97073173e329ffa4a4eea0d25dc3&pid=1-s2.0-S2666914524000575-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140406208","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":"Foveal Retinal Ganglion Cells Develop Altered Calcium Dynamics Weeks After Photoreceptor Ablation","authors":"Zhengyang Xu BSc ,&nbsp;Karteek Kunala PhD ,&nbsp;Peter Murphy BSc ,&nbsp;Laura Patak BSc ,&nbsp;Teresa Puthussery OD, PhD ,&nbsp;Juliette McGregor PhD","doi":"10.1016/j.xops.2024.100520","DOIUrl":"https://doi.org/10.1016/j.xops.2024.100520","url":null,"abstract":"<div><h3>Purpose</h3><p>Physiological changes in retinal ganglion cells (RGCs) have been reported in rodent models of photoreceptor (PR) loss, but this has not been investigated in primates. By expressing both a calcium indicator (GCaMP6s) and an optogenetic actuator (ChrimsonR) in foveal RGCs of the macaque, we reactivated RGCs <em>in vivo</em> and assessed their response in the weeks and years after PR loss.</p></div><div><h3>Design</h3><p>We used an <em>in vivo</em> calcium imaging approach to record optogenetically evoked activity in deafferented RGCs in primate fovea. Cellular scale recordings were made longitudinally over a 10-week period after PR ablation and compared with responses from RGCs that had lost PR input &gt;2 years prior.</p></div><div><h3>Participants</h3><p>Three eyes received PR ablation, the right eye of a male <em>Macaca mulatta</em> (M1), the left eye of a female <em>Macaca fascicularis</em> (M2), and the right eye of a male <em>Macaca fascicularis</em> (M3). Two animals were used for <em>in vivo</em> recording, 1 for histological assessment.</p></div><div><h3>Methods</h3><p>Cones were ablated with an ultrafast laser delivered through an adaptive optics scanning light ophthalmoscope (AOSLO). A 0.5 second pulse of 25 Hz 660 nm light optogenetically stimulated RGCs, and the resulting GCaMP fluorescence signal was recorded using an AOSLO. Measurements were repeated over 10 weeks immediately after PR ablation, at 2.3 years and in control RGCs.</p></div><div><h3>Main Outcome Measures</h3><p>The calcium rise time, decay constant, and sensitivity index of optogenetic-mediated RGC were derived from GCaMP fluorescence recordings from 221 RGCs (animal M1) and 218 RGCs (animal M2) <em>in vivo</em>.</p></div><div><h3>Results</h3><p>After PR ablation, the mean decay constant of the calcium response in RGCs decreased 1.5-fold (standard deviation 1.6 ± 0.5 seconds to 0.6 ± 0.3 seconds) over the 10-week observation period in subject 1 and 2.1-fold (standard deviation 2.5 ± 0.5 seconds to 1.2 ± 0.2 seconds) within 8 weeks in subject 2. Calcium rise time and sensitivity index were stable. Optogenetic reactivation remained possible 2.3 years after PR ablation.</p></div><div><h3>Conclusions</h3><p>Altered calcium dynamics developed in primate foveal RGCs in the weeks after PR ablation. The mean decay constant of optogenetic-mediated calcium responses decreased 1.5- to twofold. This is the first report of this phenomenon in primate retina and further work is required to understand the role these changes play in cell survival and activity.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100520"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000563/pdfft?md5=b3f87fb6329877d175bd350d0f97c34c&pid=1-s2.0-S2666914524000563-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141242477","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":"Automatic Measurement and Comparison of Normal Eyelid Contour by Age and Gender Using Image-Based Deep Learning","authors":"Ji Shao MD ,&nbsp;Jing Cao MD ,&nbsp;Changjun Wang MD,&nbsp;Peifang Xu MD,&nbsp;Lixia Lou MD, PhD,&nbsp;Juan Ye MD, PhD","doi":"10.1016/j.xops.2024.100518","DOIUrl":"https://doi.org/10.1016/j.xops.2024.100518","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aimed to propose a fully automatic eyelid measurement system and compare the contours of both the upper and lower eyelids of normal individuals according to age and gender.</p></div><div><h3>Design</h3><p>Prospective study.</p></div><div><h3>Participants</h3><p>Five hundred and forty healthy Chinese aged 0 to 79 years in a tertiary hospital were included.</p></div><div><h3>Methods</h3><p>Facial images in the primary gazing position were used to train and test the proposed automatic system for eye recognition and eye segmentation. According to the 10-millimeter diameter circular marker, measurements were transformed from pixel sizes into factual distances.</p></div><div><h3>Main Outcome Measures</h3><p>Midpupil lid distances (MPLDs) every 15° of all participants were automatically measured in both genders (30 males and 30 females in each age group) by the proposed deep learning (DL)-based system. Intraclass correlation coefficients (ICCs) were performed to assess the agreement between the automatic and manual margin reflex distances (MRDs). The eyelid contour, eyelid asymmetry, and palpebral fissure obliquity were analyzed using MPLD, temporal-versus-nasal MPLD ratio, and the angle between the inner and outer canthi, respectively.</p></div><div><h3>Results</h3><p>The measurement of MRDs by the automatic system excellently agreed with that of the expert, with ICCs ranging from 0.863 to 0.886. As the age of the participants increased, the values of MPLDs reached a peak in those in their 20s or 30s and then gradually decreased at all angles. The temporal sector showed greater changes in MPLDs than the nasal sector, and the changes were more significant in females than in males. The maximum value of palpebral fissure obliquity appeared before 10 years in both genders and remained relatively stable after the 20s (<em>P</em> &gt; 0.05).</p></div><div><h3>Conclusions</h3><p>The proposed DL-based eyelid analysis system allowed automatic, accurate, and comprehensive measurement of the eyelid contour. The refinement of eyelid shape quantification could be beneficial for future objective assessment preocular and postocular plastic surgery.</p></div><div><h3>Financial Disclosure(s)</h3><p>The authors have no proprietary or commercial interest in any materials discussed in this article.</p></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 5","pages":"Article 100518"},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266691452400054X/pdfft?md5=9730a55c2b126e3bf82150b0b43a576e&pid=1-s2.0-S266691452400054X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141240379","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}