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

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.

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Journal
Journal for ImmunoTherapy of Cancer
Published
2025-04-01
DOI
https://doi.org/10.1136/jitc-2024-011049
Citations
13
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
13.59
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article

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

George N. Papaliodis, Suzanne K. Freitag, Michal Kramer, Fiona Costello et al.
13 citations
Journal for ImmunoTherapy of Cancer
Cancer Immunotherapy and Biomarkers
13.59
article

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

George N. Papaliodis, Suzanne K. Freitag, Michal Kramer, Fiona Costello, Prem S. Subramanian, M. Tariq Bhatti, Edmund Yik Kong Tsui, Ninani Kombo, Renee Liu, Douglas Buckner Johnson, Lynn K. Gordon, Bart K. Chwalisz, Amanda C. Guidon, James Chodosh, Misha Pless, Kerry L. Reynolds, Krista M. Rubin, Marc Dinkin, Afreen Shariff, Lindsey B. De Lott, Sapna S. Gangaputra, Robert A. Egan, Eileen Chang, Katie Huynh, Clare L. Fraser, Lauren A. Dalvin, John Jing-Wei Chen, Meghan Berkenstock, Lucia Sobrin, Andrew G. Lee, Michaël Levy, Dimosthenis Mantopoulos, Michael K. Yoon, Kiandokht Keyhanian, Jon McDunn, Julia S. Pimkina, Johnathan Rine, H. Nida Sen, Anne-Marie Lobo-Chan
article en
13 citations

Abstract

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.

Journal for ImmunoTherapy of CancerVol. 13(4)
Massachusetts Eye and Ear Infirmary (US), Dartmouth–Hitchcock Medical Center (US), Hackensack University Medical Center (US), Mayo Clinic (US), Kaiser Permanente (US), Johns Hopkins University (US), University of California, Los Angeles (US), Tel Aviv University (IL), University of Calgary (CA), University of New Mexico (US), Duke University (US), Cornell University (US), University of Michigan (US), Johns Hopkins Medicine (US), Rabin Medical Center (IL), Yale University (US), University of Illinois Chicago (US), University of Chicago (US), Massachusetts General Hospital (US), Methodist Hospital (US), The George Institute for Global Health (AU), Dana-Farber Cancer Institute (US), National Eye Institute (US), Sphere Institute (US), Hackensack Meridian Health (US), Center for Cancer Research (US), PeaceHealth St. Joseph Medical Center (US), Vanderbilt University Medical Center (US), University of Colorado Denver (US)
Good health and well-being
Openalex Percentile: Top 1%
Cancer Immunotherapy and Biomarkers
13.59
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