Uveitis of undifferentiated etiology: insights into diagnosis and evolution from a cohort of 338 patients

Despite considerable advances in diagnostic work-up, approximately one-third of uveitis remains of undifferentiated etiology. Few studies have evaluated the proportion of etiological diagnoses made during follow-up in patients initially classified as undifferentiated uveitis. The study aimed to assess the achievement of a diagnosis during the follow-up and to describe how the diagnosis was reached for these patients. We conducted a retrospective study of patients with uveitis referred to our tertiary center between 2002 and 2023. Uveitis was classified as undifferentiated after an exhaustive diagnostic work-up and at least one year of follow-up. An etiological diagnosis can be established through new clinical signs, ophthalmologic examinations, or additional tests. 338 patients with uveitis were initially classified as undifferentiated. During a median follow-up of 58.4 months, an etiological diagnosis was established in 52 patients (15.4%), mainly by the appearance of new clinical symptoms in twenty-two patients. Specifically, ten patients presented with neurological symptoms, five with mucocutaneous involvement, and five with rheumatological symptoms. In nineteen patients, an etiology was diagnosed by the contribution of complementary investigations, mainly by next-generation sequencing in 7 patients and a PET (Positron Emission Tomography) scan in 3 patients. In eleven patients, new specific ocular signs were identified during ophthalmological examinations, leading to the establishment of a new diagnosis. In patients with initially undifferentiated uveitis, an etiology was identified during follow-up in about one-sixth of the patients, primarily through repeated physical examinations and the performance of new complementary tests.