Immune checkpoint inhibitor-associated Vogt-Koyanagi-Harada-like syndrome: A descriptive systematic review

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TOPIC: Vogt-Koyanagi-Harada (VKH)-like uveitis is uniquely reported with immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors. This article aims to provide a comprehensive portrait of the comorbidities, ocular presentations, treatments, and visual outcomes of patients with VKH-like uveitis following ICI therapy. CLINICAL RELEVANCE: ICIs are increasingly used in cancer therapy, but poorly understood ocular immune-related adverse events (irAEs) can lead to suspension of treatment and be vision-threatening. METHODS: We conducted a systematic review (PROSPERO #CRD42024558269) according to PRISMA guidelines. MEDLINE, Embase, CENTRAL, and Web of Science were searched for English articles published up to June 28, 2024. All study designs reporting on incident VKH-like uveitis following ICI were included. Risk of Bias was assessed using a tool modified from Murad et al. (2018). RESULTS: Of 865 articles, we included 42 articles (4 observational studies, 28 case reports, 6 case series, 3 letters, and 1 editorial) from 12 countries, comprising 52 patients. The mean age was 60.0 ± 11.9 years, and 32 (61.5%) were females. Thirty-six (69.2%) had melanoma, and most were undergoing treatment with a PD-1 inhibitor alone (n = 33, 63.5%) or in combination with a CTLA-4 inhibitor (n = 10, 19.2%). The mean duration of ICI treatment before VKH-like uveitis symptoms was 22.2 ± 29.6 weeks, and the mean duration of ocular symptoms was 16.7 ± 18.6 weeks, with wide variation. Overall, 43 patients (73.1%) had imaging or exams suggesting bilateral involvement and 21 cases (40.4%) suggesting panuveitis. Only 31 cases (59.6%) met the acute initial-onset uveitis criteria, and 15 (28.8%) met the chronic phase criteria. Most (n = 47, 90.4%) required systemic or intravitreal steroids, termination of ICI (n = 31, 59.6%), and experienced full resolution or remission of visual symptoms (n = 43, 82.7%). Most articles (n = 40, 95.2%) were judged to be at medium risk of bias. CONCLUSION: This descriptive systematic review consisted mostly of case reports, but it confirmed that a high proportion of VKH-like uveitis occur with PD-1 inhibitors and melanoma patients. VKH-like uveitis can lead to suspension of treatment. Further collaboration between oncologists and ophthalmologists is needed in the continuum of cancer care.