Ocular manifestations of STAT3 gain-of-function syndrome: A case of papillitis, retinitis, and retinal vasculitis.

PURPOSE: To report the clinical presentation, multimodal imaging, and management in a patient with signal transducer and activator of transcription-3 (STAT3) gain-of-function (GOF) syndrome presenting with polyendocrinopathy and bilateral posterior uveitis.

OBSERVATIONS: We report a case of bilateral posterior uveitis associated with STAT3-GOF syndrome. A 29-year-old female with type 1 diabetes mellitus, hypothyroidism, and common variable immune deficiency (CVID) presented with bilateral progressive decreased vision. There were no systemic signs and symptoms of infection. Clinical examination showed bilateral mild vitritis, optic disc edema with overlying telangiectasia, and mild non-proliferative diabetic retinopathy. Spectral-domain optical coherence tomography revealed parafoveal outer nuclear layer loss and cystoid macular edema bilaterally. Optic nerve leakage and diffuse capillary leakage in a fern-like pattern were visualized on fluorescein angiography. Fundus autofluorescence showed bilateral hyper-autofluorescence in the posterior poles. Laboratory and imaging workup to rule out occult infection and malignancy were unremarkable. Genetic testing for primary immunodeficiencies revealed a heterozygous germline gain-of function variant in STAT3 (STAT3 c.454C > T), confirming STAT3-GOF syndrome. The patient was treated with subcutaneous immunoglobulin and ruxolitinib, and clinical exam remained stable at 2-year follow up.

CONCLUSIONS AND IMPORTANCE: STAT3-GOF syndrome may present with bilateral optic disc edema, retinitis, and retinal vascular leakage in the setting of recurrent infections and polyendocrinopathy. This case illustrates the role of monogenic mutations in non-neoplastic autoimmune retinopathy and highlights the importance of multidisciplinary management including genetic consultation for accurate diagnosis and targeted immunomodulatory treatment.