Consensus disease definitions for ophthalmic immune-related adverse events of immune checkpoint inhibitors

Consensus disease definitions for ophthalmic immune-related adverse events of immune checkpoint inhibitors

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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 Animaniacs 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 Bobble Hats 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.