Ophthalmology science最新文献

{"title":"Cover","authors":"","doi":"10.1016/S2666-9145(24)00142-8","DOIUrl":"10.1016/S2666-9145(24)00142-8","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001428/pdfft?md5=95d97aa46c724c2dba85eaa459927652&pid=1-s2.0-S2666914524001428-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240448","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":"Analysis of ChatGPT Responses to Ophthalmic Cases: Can ChatGPT Think like an Ophthalmologist?","authors":"","doi":"10.1016/j.xops.2024.100600","DOIUrl":"10.1016/j.xops.2024.100600","url":null,"abstract":"<div><h3>Objective</h3><p>Large language models such as ChatGPT have demonstrated significant potential in question-answering within ophthalmology, but there is a paucity of literature evaluating its ability to generate clinical assessments and discussions. The objectives of this study were to (1) assess the accuracy of assessment and plans generated by ChatGPT and (2) evaluate ophthalmologists’ abilities to distinguish between responses generated by clinicians versus ChatGPT.</p></div><div><h3>Design</h3><p>Cross-sectional mixed-methods study.</p></div><div><h3>Subjects</h3><p>Sixteen ophthalmologists from a single academic center, of which 10 were board-eligible and 6 were board-certified, were recruited to participate in this study.</p></div><div><h3>Methods</h3><p>Prompt engineering was used to ensure ChatGPT output discussions in the style of the ophthalmologist author of the Medical College of Wisconsin Ophthalmic Case Studies. Cases where ChatGPT accurately identified the primary diagnoses were included and then paired. Masked human-generated and ChatGPT-generated discussions were sent to participating ophthalmologists to identify the author of the discussions. Response confidence was assessed using a 5-point Likert scale score, and subjective feedback was manually reviewed.</p></div><div><h3>Main Outcome Measures</h3><p>Accuracy of ophthalmologist identification of discussion author, as well as subjective perceptions of human-generated versus ChatGPT-generated discussions.</p></div><div><h3>Results</h3><p>Overall, ChatGPT correctly identified the primary diagnosis in 15 of 17 (88.2%) cases. Two cases were excluded from the paired comparison due to hallucinations or fabrications of nonuser-provided data. Ophthalmologists correctly identified the author in 77.9% ± 26.6% of the 13 included cases, with a mean Likert scale confidence rating of 3.6 ± 1.0. No significant differences in performance or confidence were found between board-certified and board-eligible ophthalmologists. Subjectively, ophthalmologists found that discussions written by ChatGPT tended to have more generic responses, irrelevant information, hallucinated more frequently, and had distinct syntactic patterns (all <em>P</em> &lt; 0.01).</p></div><div><h3>Conclusions</h3><p>Large language models have the potential to synthesize clinical data and generate ophthalmic discussions. While these findings have exciting implications for artificial intelligence-assisted health care delivery, more rigorous real-world evaluation of these models is necessary before clinical deployment.</p></div><div><h3>Financial Disclosures</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":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001362/pdfft?md5=1fc56cec0e121016c01c38686515b525&pid=1-s2.0-S2666914524001362-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270456","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":"ChatGPT-Assisted Classification of Postoperative Bleeding Following Microinvasive Glaucoma Surgery Using Electronic Health Record Data","authors":"","doi":"10.1016/j.xops.2024.100602","DOIUrl":"10.1016/j.xops.2024.100602","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate the performance of a large language model (LLM) in classifying electronic health record (EHR) text, and to use this classification to evaluate the type and resolution of hemorrhagic events (HEs) after microinvasive glaucoma surgery (MIGS).</p></div><div><h3>Design</h3><p>Retrospective cohort study.</p></div><div><h3>Participants</h3><p>Eyes from the Bascom Palmer Glaucoma Repository.</p></div><div><h3>Methods</h3><p>Eyes that underwent MIGS between July 1, 2014 and February 1, 2022 were analyzed. Chat Generative Pre-trained Transformer (ChatGPT) was used to classify deidentified EHR anterior chamber examination text into HE categories (no hyphema, microhyphema, clot, and hyphema). Agreement between classifications by ChatGPT and a glaucoma specialist was evaluated using Cohen’s Kappa and precision-recall (PR) curve. Time to resolution of HEs was assessed using Cox proportional-hazards models. Goniotomy HE resolution was evaluated by degree of angle treatment (90°–179°, 180°–269°, 270°–360°). Logistic regression was used to identify HE risk factors.</p></div><div><h3>Main Outcome Measures</h3><p>Accuracy of ChatGPT HE classification and incidence and resolution of HEs.</p></div><div><h3>Results</h3><p>The study included 434 goniotomy eyes (368 patients) and 528 Schlemm’s canal stent (SCS) eyes (390 patients). Chat Generative Pre-trained Transformer facilitated excellent HE classification (Cohen’s kappa 0.93, area under PR curve 0.968). Using ChatGPT classifications, at postoperative day 1, HEs occurred in 67.8% of goniotomy and 25.2% of SCS eyes (<em>P</em> &lt; 0.001). The 270° to 360° goniotomy group had the highest HE rate (84.0%, <em>P</em> &lt; 0.001). At postoperative week 1, HEs were observed in 43.4% and 11.3% of goniotomy and SCS eyes, respectively (<em>P</em> &lt; 0.001). By postoperative month 1, HE rates were 13.3% and 1.3% among goniotomy and SCS eyes, respectively (<em>P</em> &lt; 0.001). Time to HE resolution differed between the goniotomy angle groups (log-rank <em>P</em> = 0.034); median time to resolution was 10, 10, and 15 days for the 90° to 179°, 180° to 269°, and 270° to 360° groups, respectively. Risk factor analysis demonstrated greater goniotomy angle was the only significant predictor of HEs (odds ratio for 270°–360°: 4.08, <em>P</em> &lt; 0.001).</p></div><div><h3>Conclusions</h3><p>Large language models can be effectively used to classify longitudinal EHR free-text examination data with high accuracy, highlighting a promising direction for future LLM-assisted research and clinical decision support. Hemorrhagic events are relatively common self-resolving complications that occur more often in goniotomy cases and with larger goniotomy treatments. Time to HE resolution differs significantly between goniotomy groups.</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":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001386/pdfft?md5=6a7c056392e56a9af8bd6168c9dd77cb&pid=1-s2.0-S2666914524001386-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270369","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":"Diagnosing Glaucoma Based on the Ocular Hypertension Treatment Study Dataset Using Chat Generative Pre-Trained Transformer as a Large Language Model","authors":"","doi":"10.1016/j.xops.2024.100599","DOIUrl":"10.1016/j.xops.2024.100599","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate the capabilities of Chat Generative Pre-Trained Transformer (ChatGPT), as a large language model (LLM), for diagnosing glaucoma using the Ocular Hypertension Treatment Study (OHTS) dataset, and comparing the diagnostic capability of ChatGPT 3.5 and ChatGPT 4.0.</p></div><div><h3>Design</h3><p>Prospective data collection study.</p></div><div><h3>Participants</h3><p>A total of 3170 eyes of 1585 subjects from the OHTS were included in this study.</p></div><div><h3>Methods</h3><p>We selected demographic, clinical, ocular, visual field, optic nerve head photo, and history of disease parameters of each participant and developed case reports by converting tabular data into textual format based on information from both eyes of all subjects. We then developed a procedure using the application programming interface of ChatGPT, a LLM-based chatbot, to automatically input prompts into a chat box. This was followed by querying 2 different generations of ChatGPT (versions 3.5 and 4.0) regarding the underlying diagnosis of each subject. We then evaluated the output responses based on several objective metrics.</p></div><div><h3>Main Outcome Measures</h3><p>Area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, and F1 score.</p></div><div><h3>Results</h3><p>Chat Generative Pre-Trained Transformer 3.5 achieved AUC of 0.74, accuracy of 66%, specificity of 64%, sensitivity of 85%, and F1 score of 0.72. Chat Generative Pre-Trained Transformer 4.0 obtained AUC of 0.76, accuracy of 87%, specificity of 90%, sensitivity of 61%, and F1 score of 0.92.</p></div><div><h3>Conclusions</h3><p>The accuracy of ChatGPT 4.0 in diagnosing glaucoma based on input data from OHTS was promising. The overall accuracy of ChatGPT 4.0 was higher than ChatGPT 3.5. However, ChatGPT 3.5 was found to be more sensitive than ChatGPT 4.0. In its current forms, ChatGPT may serve as a useful tool in exploring disease status of ocular hypertensive eyes when specific data are available for analysis. In the future, leveraging LLMs with multimodal capabilities, allowing for integration of imaging and diagnostic testing as part of the analyses, could further enhance diagnostic capabilities and enhance diagnostic accuracy.</p></div><div><h3>Financial Disclosures</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":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001350/pdfft?md5=9446852d5e50ba948a58b4ce06421174&pid=1-s2.0-S2666914524001350-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between Neighborhood-Level Social Risk Factor Measures and Presenting Glaucoma Severity Utilizing Multilevel Modeling","authors":"","doi":"10.1016/j.xops.2024.100598","DOIUrl":"10.1016/j.xops.2024.100598","url":null,"abstract":"<div><h3>Purpose</h3><p>The neighborhood and built environment social determinant of health domain has several social risk factors (SRFs) that are modifiable through policy efforts. We investigated the impact of neighborhood-level SRFs on presenting glaucoma severity at a tertiary eye care center.</p></div><div><h3>Design</h3><p>A cross-sectional study from August 2012 to May 2022 in the University of Michigan electronic health record (EHR).</p></div><div><h3>Participants</h3><p>Patients with a diagnosis of any open-angle glaucoma with ≥1 eye care visit at the University of Michigan Kellogg Eye Center and ≥1 reliable visual field (VF).</p></div><div><h3>Methods</h3><p>Participants who met inclusion criteria were identified by International Classification of Diseases ninth and tenth revision codes (365.x/H40.x). Data extracted from the EHR included patient demographics, address, presenting mean deviation (MD), and VF reliability. Addresses were mapped to SRF measures at the census tract, block group, and county levels. Multilevel linear regression models were used to estimate the fixed effects of each SRF on MD, after adjusting for patient-level demographic factors and a random effect for neighborhood. Interactions between each SRF measure with patient-level race and Medicaid status were tested for an additive effect on MD.</p></div><div><h3>Main Outcome Measures</h3><p>The main outcome measure was the effect of SRF on presenting MD.</p></div><div><h3>Results</h3><p>In total, 4428 patients were included in the analysis who were, on average, 70.3 years old (standard deviation = 11.9), 52.6% self-identified as female, 75.8% self-identified as White race, and 8.9% had Medicaid. The median value of presenting MD was −4.94 decibels (dB) (interquartile range = −11.45 to −2.07 dB). Neighborhood differences accounted for 4.4% of the variability in presenting MD. Neighborhood-level measures, including worse area deprivation (estimate, β = −0.31 per 1-unit increase; <em>P</em> &lt; 0.001), increased segregation (β = −0.92 per 0.1-unit increase in Theil’s H index; <em>P</em> &lt; 0.001), and increased neighborhood Medicaid (β = −0.68; <em>P</em> &lt; 0.001) were associated with worse presenting MD. Significant interaction effects with race and Medicaid status were found in several neighborhood-level SRF measures.</p></div><div><h3>Conclusions</h3><p>Although patients’ neighborhood SRF measures accounted for a minority of the variability in presenting MD, most neighborhood-level SRFs are modifiable and were associated with clinically meaningful differences in presenting MD. Policies that aim to reduce neighborhood inequities by addressing allocation of resources could have lasting impacts on vision outcomes.</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":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001349/pdfft?md5=241edf796058dadff7c3bb9a45c9e13d&pid=1-s2.0-S2666914524001349-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270455","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 between Spectral-Domain and Swept-Source OCT Angiography for the Measurement of Persistent Hypertransmission Defects in Age-Related Macular Degeneration","authors":"","doi":"10.1016/j.xops.2024.100593","DOIUrl":"10.1016/j.xops.2024.100593","url":null,"abstract":"<div><h3>Purpose</h3><p>Spectral-domain OCT angiography (SD-OCTA) scans were tested in an algorithm developed for use with swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the detection and measurement of persistent choroidal hypertransmission defects (hyperTDs).</p></div><div><h3>Design</h3><p>Retrospective study.</p></div><div><h3>Participants</h3><p>Forty pairs of scans from 32 patients with late-stage nonexudative age-related macular degeneration (AMD).</p></div><div><h3>Methods</h3><p>Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 × 6 mm OCTA scan patterns. Using a semiautomatic algorithm that helped with outlining the hyperTDs, 2 graders independently validated persistent hyperTDs, which are defined as having a greatest linear dimension ≥250 μm on the en face images generated using a slab extending from 64 to 400 μm beneath Bruch’s membrane. The number of lesions and square root (sqrt) total area of the hyperTDs were obtained from the algorithm using each imaging method.</p></div><div><h3>Main Outcome Measures</h3><p>The mean sqrt area measurements and the number of hyperTDs were compared.</p></div><div><h3>Results</h3><p>The number of lesions and sqrt total area of the hyperTDs were highly concordant between the 2 instruments (r_c = 0.969 and r_c = 0.999, respectively). The mean number of hyperTDs was 4.3 ± 3.1 for SD-OCTA scans and 4.5 ± 3.3 for SS-OCTA scans (<em>P</em> = 0.06). The mean sqrt total area measurements were 1.16 ± 0.64 mm for the SD-OCTA scans and 1.17 ± 0.65 mm for the SS-OCTA scans (<em>P</em> &lt; 0.001). Because of the small standard error of the differences, the mean difference between the scans was statistically significant but not clinically significant.</p></div><div><h3>Conclusions</h3><p>Spectral-domain OCTA scans provide similar results to SS-OCTA scans when used to obtain the number and area measurements of persistent hyperTDs through a semiautomated algorithm previously developed for SS-OCTA. This facilitates the detection of atrophy with a more widely available scan pattern and the longitudinal study of early to late-stage AMD.</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":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001295/pdfft?md5=1d219e52f1d3cce12729e047e485c32e&pid=1-s2.0-S2666914524001295-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232580","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 Evidence of a Photoreceptor Origin in Diabetic Retinal Disease","authors":"","doi":"10.1016/j.xops.2024.100591","DOIUrl":"10.1016/j.xops.2024.100591","url":null,"abstract":"<div><h3>Clinical Relevance</h3><p>Although diabetes is associated with a classic microvascular disease of the retina, it is also increasingly being recognized as a cause of retinal neuropathy. Preclinical evidence suggests that retinal neuropathy in diabetes manifests in part as photoreceptor dysfunction, preceding the development of vascular features in experimental models. It remains unknown whether such findings are relevant to patients with diabetes.</p></div><div><h3>Methods</h3><p>Here, we review 4 lines of clinical evidence suggesting that diabetes-associated photoreceptor pathology is linked to the development of retinal microvascular disease.</p></div><div><h3>Results</h3><p>First, a major population-based investigation of susceptibility loci for diabetic retinopathy (DR) implicated a photoreceptor protein product as a protective factor. Next, electroretinography and other studies of visual function collectively show that rod and/or cone-derived abnormalities occur decades before the development of vascular features of DR. Third, protection from DR seemingly develops in patients with coincident retinitis pigmentosa, as suggested by several case series. Finally, based on anatomic features, we propose that the beneficial effect of macular laser in DR occurs via ablation of diseased photoreceptors.</p></div><div><h3>Conclusions</h3><p>The evidence we present is limited due to the small patient populations used in the studies we cite and due to the lack of methodologies that allow causative relationships to be inferred. Collectively, however, these clinical observations suggest that photoreceptors are involved in early diabetic retinal disease and may in fact give rise to the classic features of DR.</p></div><div><h3>Financial Disclosure(s)</h3><p>Proprietary or commercial disclosures 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":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001271/pdfft?md5=03b8c3f460842b579f490019dd45ab72&pid=1-s2.0-S2666914524001271-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239014","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 Study of Intravitreal Injection of Autologous CD34+ Stem Cells from Bone Marrow in Eyes with Vision Loss from Retinitis Pigmentosa","authors":"","doi":"10.1016/j.xops.2024.100589","DOIUrl":"10.1016/j.xops.2024.100589","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate the feasibility and safety of intravitreal injection of autologous CD34+ stem cells from bone marrow (BMSCs) in eyes with vision loss from retinitis pigmentosa (RP).</p></div><div><h3>Design</h3><p>Phase I prospective, open-label, single-center study.</p></div><div><h3>Participants</h3><p>Seven eyes (7 patients) with RP with best-corrected visual acuity (BCVA) of 20/60 to 20/400 or visual field constriction to within 10°.</p></div><div><h3>Methods</h3><p>A comprehensive examination with ETDRS BCVA, macular OCT, perimetry, and fluorescein angiography was performed at baseline, 1 to 3 months, and 6 months after study treatment. Bone marrow aspiration, isolation of CD34+ BMSCs under good manufacturing practice conditions, and intravitreal cell injection were performed on the same day. The CD34+ cells were isolated from bone marrow using a Ficoll gradient and the Miltenyi CliniMACS system. Isolated CD34+ cells were released for clinical use if viability, sterility, and purity met the release criteria accepted by the United States Food and Drug Administration for this clinical study.</p></div><div><h3>Main Outcome Measures</h3><p>Number of CD34+ cells isolated for injection and adverse events associated with study treatment during follow-up. Secondary outcome measures are changes in BCVA and perimetry.</p></div><div><h3>Results</h3><p>All isolated CD34+ cells passed the release criteria. A mean of 3.26 ± 0.66 million viable CD34+ cells (range 1.6 to 7.05 million) were injected intravitreally per eye. No adverse event was noted during the study follow-up except for 1 participant who was noted with transient cells in the anterior chamber with mild elevation in intraocular pressure at 18 hours after study injection which normalized by 24 hours. Best-corrected visual acuity remained within 2 lines of baseline or improved in all participants at 6 months follow-up. Perimetry was stable or improved in all eyes during study follow-up except 1 eye with transient improvement at 1 month and worsening of both eyes at 6 months.</p></div><div><h3>Conclusions</h3><p>Intravitreal injection of autologous CD34+ BMSCs is feasible and appears to be well tolerated in eyes with vision loss from RP. A larger randomized prospective study would be needed to evaluate further the safety and potential efficacy of this cell therapy for vision loss associated with RP.</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":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001258/pdfft?md5=26ee261925521bae1e4cb8e10d7ee52b&pid=1-s2.0-S2666914524001258-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239013","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":"Subconjunctival Administration of an Adeno-Associated Virus Expressing Stanniocalcin-1 Provides Sustained Intraocular Pressure Reduction in Mice","authors":"","doi":"10.1016/j.xops.2024.100590","DOIUrl":"10.1016/j.xops.2024.100590","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;p&gt;To investigate subconjunctival administration of a single-stranded, adeno-associated virus, serotype 2, engineered to express stanniocalcin-1 with a FLAG tag (ssAAV2-STC-1-FLAG) as a novel sustained (IOP) lowering agent with a reduced ocular surface side effect profile.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;p&gt;In vivo preclinical investigation in mice.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;p&gt;C57BL/6J, DBA/2J, prostaglandin F (FP) receptor knockout mice.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Normotensive C57BL/6J mice were treated with a subconjunctival injection of ssAAV2-STC-1-FLAG (2 μL; 6 × 10&lt;sup&gt;9&lt;/sup&gt; viral genomes [VGs]) in 1 eye and the same volume and concentration of ssAAV2-green fluorescent protein (GFP) or the same volume of phosphate-buffered saline in the fellow eye. Ocular hypertensive DBA/2J mice were subconjunctivally injected with 6 × 10&lt;sup&gt;9&lt;/sup&gt; VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Steroid-mediated ocular hypertension was induced in C57BL/6J mice with weekly injections of dexamethasone into the conjunctival fornix, and mice were then injected subconjunctivally with 6 × 10&lt;sup&gt;9&lt;/sup&gt; VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Prostaglandin F receptor knockout mice were injected subconjunctivally with 6 × 10&lt;sup&gt;9&lt;/sup&gt; VGs of ssAAV2-STC-1-FLAG or phosphate-buffered saline. An identical vector was constructed without the FLAG tag (ssAAV2-STC-1) and evaluated in normotensive C57BL/6J mice. Intraocular pressure was assessed using the Tonolab tonometer for all experiments. Tumor necrosis factor alpha (TNFα), a marker of ocular surface inflammation, was compared between subconjunctivally delivered ssAAV2-STC-1-FLAG and other treatments including daily topical latanoprost.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;p&gt;Intraocular pressure assessment.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Subconjunctival delivery of ssAAV2-STC-1-FLAG significantly reduced IOP for 10 weeks post injection in normotensive mice. Maximal IOP reduction was seen at week 3 postinjection (17.4%; 17.1 ± 0.8 vs. 14.1 ± 0.8 mmHg, &lt;em&gt;P&lt;/em&gt; &lt; 0.001). After the IOP-lowering effect had waned, a second injection restored the ocular hypotensive effect. Subconjunctivally delivered ssAAV2-STC-1-FLAG lowered IOP in DBA/2J mice (16.9%; 17.8 ± 2.0 vs. 14.8 ± 0.9 mmHg, &lt;em&gt;P&lt;/em&gt; &lt; 0.001) and steroid-mediated ocular hypertensive mice (20.0%; 19.0 ± 0.6 vs. 15.2 ± 0.7 mmHg, &lt;em&gt;P&lt;/em&gt; &lt; 0.001) over the experimental period. This construct also reduced IOP to a similar extent in wild-type (15.9%) and FP receptor knockout (15.7%) mice compared with the fellow eye. A related construct also lowered IOP without the FLAG tag in a similar manner. Reduction in conjunctival TNFα was seen when comparing subconjunctivally delivered ssAAV2-STC-1-FLAG to daily topical latanoprost.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;Subconjunctival delivery of the STC-1 transgene with a vector system may represent a novel treatment strategy for sustained IOP reduction and improved ocular to","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266691452400126X/pdfft?md5=923846108f994b5e9af7245756c01095&pid=1-s2.0-S266691452400126X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239012","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":"Re: Angela S Li et al Gradeability and Reproducibility of Geographic Atrophy Measurement in GATHER-1, a Phase II/III Randomized Interventional Trial","authors":"","doi":"10.1016/j.xops.2024.100567","DOIUrl":"10.1016/j.xops.2024.100567","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001039/pdfft?md5=610b539237d19b6d55b4f8213cb752b4&pid=1-s2.0-S2666914524001039-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141961194","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}