Ophthalmology science最新文献

{"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}

{"title":"A User-friendly Approach for the Diagnosis of Diabetic Retinopathy Using ChatGPT and Automated Machine Learning","authors":"S. Saeed Mohammadi MD,&nbsp;Quan Dong Nguyen MD, MSc","doi":"10.1016/j.xops.2024.100495","DOIUrl":"10.1016/j.xops.2024.100495","url":null,"abstract":"<div><h3>Purpose</h3><p>To assess the capabilities of Chat Generative Pre-trained Transformer (ChatGPT) and Vertex AI in executing code-free preprocessing, training machine learning (ML) models, and analyzing the data.</p></div><div><h3>Design</h3><p>Evaluation of diagnostic test or technology.</p></div><div><h3>Participants</h3><p>ChatGPT and Vetrex AI as publicly available large language model and ML platform, respectively.</p></div><div><h3>Methods</h3><p>ChatGPT was employed to improve the resolution of fundus photography images from the Methods to Evaluate Segmentation and Indexing Techniques in the field of Retinal Ophthalmology (Messidor-2) open-source dataset using the Contrast Limited Adaptive Histogram Equalization (CLAHE) technique by Fiji software. Subsequently, Vertex AI, an automated ML (AutoML) platform, was utilized to develop 2 classification models. The first model served as a binary classifier for detecting the presence of diabetic retinopathy (DR), while the second determined its severity. Finally, ChatGPT was used to provide scripts for R and Python programming languages for data analysis and was also directly employed in analyzing the data in a code-free method.</p></div><div><h3>Main Outcome Measures</h3><p>Evaluating the utility of ChatGPT in generating scripts for preprocessing images using Fiji and analyzing data across Python and R and assessing its potential in analyzing data through a code-free method. Investigating the capabilities of Vertex AI to train image classification models for detection of DR and its severity.</p></div><div><h3>Results</h3><p>Two ML models were trained using 1740 images from the Messidor-2 database. The first model, designed to detect the severity of DR, achieved an area under the precision-recall curve (AUPRC) of 0.81, with a precision rate of 81.81% and recall of 72.83%. The second model, tailored for the detection of the presence of DR, recorded a precision and recall of 84.48% with an AUPRC of 0.90.</p></div><div><h3>Conclusions</h3><p>ChatGPT and Vertex AI have the potential to enable physicians without coding expertise to preprocess images, analyze data, and train ML models.</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":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000319/pdfft?md5=1f01a32cb89e3c515a76ac3d1f7e962a&pid=1-s2.0-S2666914524000319-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140469931","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":"Artificial Intelligence to Differentiate Pediatric Pseudopapilledema and True Papilledema on Fundus Photographs","authors":"Melinda Y. Chang MD ,&nbsp;Gena Heidary MD, PhD ,&nbsp;Shannon Beres MD ,&nbsp;Stacy L. Pineles MD ,&nbsp;Eric D. Gaier MD, PhD ,&nbsp;Ryan Gise MD ,&nbsp;Mark Reid PhD ,&nbsp;Kleanthis Avramidis MEng ,&nbsp;Mohammad Rostami PhD ,&nbsp;Shrikanth Narayanan PhD ,&nbsp;Pediatric Optic Nerve Investigator Group (PONIG)","doi":"10.1016/j.xops.2024.100496","DOIUrl":"10.1016/j.xops.2024.100496","url":null,"abstract":"<div><h3>Purpose</h3><p>To develop and test an artificial intelligence (AI) model to aid in differentiating pediatric pseudopapilledema from true papilledema on fundus photographs.</p></div><div><h3>Design</h3><p>Multicenter retrospective study.</p></div><div><h3>Subjects</h3><p>A total of 851 fundus photographs from 235 children (age &lt; 18 years) with pseudopapilledema and true papilledema.</p></div><div><h3>Methods</h3><p>Four pediatric neuro-ophthalmologists at 4 different institutions contributed fundus photographs of children with confirmed diagnoses of papilledema or pseudopapilledema. An AI model to classify fundus photographs as papilledema or pseudopapilledema was developed using a DenseNet backbone and a tribranch convolutional neural network. We performed 10-fold cross-validation and separately analyzed an external test set. The AI model’s performance was compared with 2 masked human expert pediatric neuro-ophthalmologists, who performed the same classification task.</p></div><div><h3>Main Outcome Measures</h3><p>Accuracy, sensitivity, and specificity of the AI model compared with human experts.</p></div><div><h3>Results</h3><p>The area under receiver operating curve of the AI model was 0.77 for the cross-validation set and 0.81 for the external test set. The accuracy of the AI model was 70.0% for the cross-validation set and 73.9% for the external test set. The sensitivity of the AI model was 73.4% for the cross-validation set and 90.4% for the external test set. The AI model’s accuracy was significantly higher than human experts on the cross validation set (<em>P</em> &lt; 0.002), and the model’s sensitivity was significantly higher on the external test set (<em>P</em> = 0.0002). The specificity of the AI model and human experts was similar (56.4%–67.3%). Moreover, the AI model was significantly more sensitive at detecting mild papilledema than human experts, whereas AI and humans performed similarly on photographs of moderate-to-severe papilledema. On review of the external test set, only 1 child (with nearly resolved pseudotumor cerebri) had both eyes with papilledema incorrectly classified as pseudopapilledema.</p></div><div><h3>Conclusions</h3><p>When classifying fundus photographs of pediatric papilledema and pseudopapilledema, our AI model achieved &gt; 90% sensitivity at detecting papilledema, superior to human experts. Due to the high sensitivity and low false negative rate, AI may be useful to triage children with suspected papilledema requiring work-up to evaluate for serious underlying neurologic conditions.</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":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524000320/pdfft?md5=a4155e55d0289e14935dfa99b5052346&pid=1-s2.0-S2666914524000320-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140467006","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}