Chen, John J.

Ophthalmic immune-related adverse events (Eye-irAEs) from immune checkpoint inhibitors can cause visual morbidity. The absence of standardized definitions for Eye-irAEs not only impedes the development of evidence-based treatments but also progress in translational research. The objective of this study was to develop consensus guidance for an approach to Eye-irAEs. Four ophthalmic physicians (uveitis specialists and neuro-ophthalmologists) drafted Eye-irAE consensus guidance and definitions, which were reviewed by the multidisciplinary Eye-irAE definition panel. The panel was divided into Group A (Neuro-ophthalmology/Orbital Disease) and Group B (Uveitis/Ocular Surface Disease). A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. For each disorder, five diagnostic components were evaluated: symptoms, examination findings, laboratory studies/imaging findings, diagnostic criteria, and treatment. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free-text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND Corporation/ University of California Los Angeles Health Services Utilization Study (RAND/UCLA) Appropriateness Method with prespecified definitions. 29 panelists from 25 academic medical centers voted on 114 rating scales (66 neuro-ophthalmic/orbital disease components, 48 uveitis/ocular surface disease components); of these, 86.3% (57/66) in Group A and 89.6% (43/48) in Group B reached first-round consensus. After revisions, all items except 6.1% (4/66) in Group A and 1.6% (1/60) in Group B received second-round consensus. Consensus definitions were achieved for 10/11 neuro-ophthalmic/orbital disorders: optic neuritis, inflammatory optic disc edema, arteritic ischemic optic neuropathy, optic perineuritis, orbital inflammation, thyroid eye disease-like orbital inflammation, cavernous sinus syndrome, oculomotor mononeuritis, trochlear mononeuritis, and abducens mononeuritis. Consensus definitions were achieved for 9/10 uveitis/ocular surface disorders: anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis, Vogt-Koyanagi-Harada-like syndrome, sarcoidosis-like syndrome, acute macular neuroretinopathy, dry eye disease, and scleritis. These disease definitions establish a standardized classification for Eye-irAE, highlighting differences between irAEs and other inflammatory disorders. Importantly, diagnostic certainty does not always align directly with the need to treat as an Eye-irAE. Given the consensus from this representative panel group, it is anticipated the definitions will be used broadly across clinical and research settings.

ImportanceSpecialized ophthalmology terminology limits comprehension for nonophthalmology clinicians and professionals, hindering interdisciplinary communication and patient care. The clinical implementation of large language models (LLMs) into practice has to date been relatively unexplored.ObjectiveTo evaluate LLM–generated plain language summaries (PLSs) integrated into standard ophthalmology notes (SONs) in improving diagnostic understanding, satisfaction, and clarity.Design, Setting, and ParticipantsRandomized quality improvement study conducted from February 1, 2024, to May 31, 2024, including data from inpatient and outpatient encounters in a single tertiary academic center. Participants were nonophthalmology clinicians and professionals and ophthalmologists. The single inclusion criterion was any encounter note generated by an ophthalmologist during the study dates. Exclusion criteria were (1) lack of established nonophthalmology clinicians and professionals for outpatient encounters and (2) procedure-only patient encounters.InterventionAddition of LLM-generated plain language summaries to ophthalmology notes.Main Outcomes and MeasuresThe primary outcome was survey responses from nonophthalmology clinicians and professionals assessing understanding, satisfaction, and clarity of ophthalmology notes. Secondary outcomes were survey responses from ophthalmologists evaluating PLS in terms of clinical workflow and accuracy, objective measures of semantic quality, and safety analysis.ResultsA total of 362 (85%) nonophthalmology clinicians and professionals (33.0% response rate) preferred the PLS to SON. Demographic data on age, race and ethnicity, and sex were not collected. Nonophthalmology clinicians and professionals reported enhanced diagnostic understanding (percentage point increase, 9.0; 95% CI, 0.3-18.2; P = .01), increased note detail satisfaction (percentage point increase, 21.5; 95% CI, 11.4-31.5; P < .001), and improved explanation clarity (percentage point increase, 23.0; 95% CI, 12.0-33.1; P < .001) for notes containing a PLS. The addition of a PLS was associated with reduced comprehension gaps between clinicians who were comfortable and uncomfortable with ophthalmology terminology (from 26.1% [95% CI, 13.7%-38.6%; P < .001] to 14.4% [95% CI, 4.3%-24.6%; P > .06]). PLS semantic analysis found high meaning preservation (bidirectional encoder representations from transformers score mean F1 score: 0.85) with greater readability than SONs (Flesch Reading Ease: 51.8 vs 43.6; Flesch-Kincaid Grade Level: 10.7 vs 11.9). Ophthalmologists (n = 489; 84% response rate) reported high PLS accuracy (90% [320 of 355] a great deal) with minimal review time burden (94.9% [464 of 489] ≤1 minute). PLS error rate on ophthalmologist review was 26% (126 of 489). A total of 83.9% (104 of 126) of errors were deemed low risk for harm and none had a risk of severe harm or death.Conclusions and RelevanceIn this study, use of LLM-generated PLSs was associated with enhanced comprehension and satisfaction among nonophthalmology clinicians and professionals, which might aid interdisciplinary communication. Careful implementation and safety monitoring are recommended for clinical integration given the persistence of errors despite physician review.

Importance Semaglutide, a glucagonlike peptide-1 receptor agonist (GLP-1RA), has recently been implicated in cases of nonarteritic anterior ischemic optic neuropathy (NAION), raising safety concerns in the treatment of type 2 diabetes (T2D). Objective To investigate the potential association between semaglutide and NAION in the Observational Health Data Sciences and Informatics (OHDSI) network. Design, Setting, and Participants This was a retrospective study across 14 databases (6 administrative claims and 8 electronic health records). Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non–GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023. The incidence proportion and rate of NAION were calculated. Association between semaglutide and NAION was assessed using 2 approaches: an active-comparator cohort design comparing new users of semaglutide with those taking other GLP-1RAs and non–GLP-1RA drugs, and a self-controlled case-series (SCCS) analysis to compare individuals’ risks during exposure and nonexposure periods for each drug. The cohort design used propensity score–adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). Network-wide HR and IRR estimates were generated using a random-effects meta-analysis model. Exposures GLP-1RA and non–GLP-1RAs. Main Outcomes and Measures NAION under 2 alternative definitions based on diagnosis codes: one more inclusive and sensitive, the other more restrictive and specific. Results The study included 37.1 million individuals with T2D, including 810 390 new semaglutide users. Of the 43 620 new users of semaglutide in the Optum’s deidentified Clinformatics Data Mart Database, 24 473 (56%) were aged 50 to 69 years, and 26 699 (61%) were female. The incidence rate of NAION was 14.5 per 100 000 person-years among semaglutide users. The HR for NAION among new users of semaglutide was not different compared with that of the non–GLP-1RAs using the sensitive NAION definition—empagliflozin (HR, 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR, 1.30; 95% CI, 0.56-3.01; P = .27), and glipizide (HR, 1.23; 95% CI, 0.66-2.28; P = .25). The risk was higher only compared with patients taking empagliflozin (HR, 2.27; 95% CI, 1.16-4.46; P = .02) using the specific definition. SCCS analysis of semaglutide exposure showed an increased risk of NAION (meta-analysis IRR, 1.32; 95% CI, 1.14-1.54; P < .001). Conclusions and Relevance Results of this study suggest a modest increase in the risk of NAION among individuals with T2D associated with semaglutide use, smaller than that previously reported, and warranting further investigation into the clinical implications of this association.

AbstractCases of myelin oligodendrocyte glycoprotein (MOG) antibody‐associated disease (MOGAD) co‐occurring with neoplasms have been reported. In this international, retrospective cohort study in South Korea and the USA, 16 of 445 (3.6%) patients with MOGAD had concurrent neoplasm within 2 years of MOGAD onset, resulting in a standardized incidence ratio for neoplasm of 3.10 (95% confidence interval [CI], 1.77–4.81; P < 0.001) when compared to the age‐ and country‐adjusted incidence of neoplasm in the general population. However, none of the nine tumor tissues obtained demonstrated MOG immunostaining. The slightly increased frequency without immunohistopathological evidence suggest with true paraneoplastic MOGAD is extremely rare.