IDH2-Mutated Clonal Hematopoiesis Associated Uveitis

Somatic hematopoietic mutations are increasingly recognized as drivers of acquired hemato-inflammatory diseases. This study aimed to characterize ocular inflammation associated with IDH2-mutant clonal hematopoiesis.

We describe a retrospective case series of three male patients evaluated at IRCCS San Raffaele Scientific Institute between 2022 and 2026. All patients underwent comprehensive ophthalmic, infectious, immunologic, hematologic, and molecular evaluation, including next-generation sequencing of peripheral blood or bone marrow samples and targeted UBA1 testing.

Three unrelated men developed noninfectious uveitis in the setting of distinct hematologic phenotypes: acute myeloid leukemia, chronic myelomonocytic leukemia, and clonal cytopenia of undetermined significance. Ocular manifestations included unilateral recurrent granulomatous anterior uveitis with papillitis, bilateral panuveitis with necrotizing nodular scleritis, and bilateral multifocal choroiditis with panuveitis. All patients harbored the same somatic oncogenic IDH2 p.R140Q variant, whereas UBA1 testing was negative. Local glucocorticoid therapy, including topical and intravitreal treatment, was administered in two patients and achieved control of ocular inflammation.

IDH2 p.R140Q-mutant clonal hematopoiesis may be associated with noninfectious uveitis in older adults with unexplained cytopenias or myeloid disease. Recognition of this association may prompt earlier hematologic and molecular evaluation and support multidisciplinary management of otherwise unexplained ocular inflammation.