The primary therapeutic goal in management of patients with uveitis is to ascertain a specific diagnosis, facilitating targeted intervention. However, the diagnostic process is often complex, leading many cases to be classified as idiopathic. The absence of a definitive diagnosis, and subsequent lack of specific therapy, predisposes patients to recurrent intraocular inflammation episodes, escalating the risk of progressive vision loss. Timely diagnosis is imperative not only for preserving visual function but also to prevent the downstream socioeconomic consequences. Delays or inaccuracies in diagnosis can have profound implications on patient outcomes and broader societal health economics.
In idiopathic uveitis, the designation 'idiopathic' frequently becomes synonymous with 'non-infectious' or 'autoimmune' uveitis. Consequently, many patients with this diagnosis are treated with corticosteroids, sometimes complemented by immunosuppressive therapy. Currently, no standardized guidelines advise the repetition of laboratory tests for this patient group. Yet, in clinical practice, specialists often re-evaluate those initially diagnosed as 'idiopathic,' striving to pinpoint a specific etiology. Choi et al7 embarked on such a reassessment, examining 179 patients who were referred to them with a diagnosis of idiopathic uveitis. Their findings indicated approximately 29.0% of these patients, a majority being females (67.6%), were later identified with a specific underlying condition after undergoing a thorough evaluation based on the SUN criteria. Notably, sarcoidosis (36.5%) and HLA-B27 associated uveitis (21.1%) were among the most frequently diagnosed conditions, followed by other diseases like infectious etiologies, tubulo-interstitial nephritis with uveitis, juvenile idiopathic arthritis-associated uveitis, Behcet’s disease, and Crohn’s disease. Nonetheless, the benefits of re-assessing patients who consistently exhibit recurrent symptoms, even while under ongoing care at the same center, remain unclear.
In the present study, we analyzed 123 patients who had been under our care and followed up for a decade. Notably, a significant number of these patients (96/123) returned regularly due to the recurrent nature of their disease. The majority were females, and the predominant age group was between 17–40 years. This suggests that younger patients tend to have a more prolonged and recurrent course of the disease.11–15
Over a 10-year follow-up, 30 (50.85%) out of 59 patients with idiopathic uveitis received a revised definitive etiological diagnosis. This finding is significant, indicating that the same experts (AG, VG, RB) who initially diagnosed these patients as idiopathic persisted in seeking a specific etiology. Consequently, nearly 50% of patients initially labelled as idiopathic were diagnosed with specific causes, including infectious etiologies. The shift in diagnosis from idiopathic (non-infectious) to infectious can be attributed to various factors. These include the availability of newer tests like multi-targeted polymerase chain reaction, QuantiFERON TB Gold, CECT chest, or changing phenotypes/recurrent episodes influencing the test selection. By the last follow-up, infectious etiologies increased by 15.44% and immune-mediated etiologies by 9.94%, due to improved diagnostic tools and disease classification.
Out of 30 patients with revised diagnosis, 19 were identified with an infectious etiology at follow-up. Specifically, 17 were diagnosed with OTB, with one each diagnosed with syphilis and HSV. The evolving diagnostic criteria also influenced the identification of etiology. For instance, a positive Mantoux test was previously defined by an induration measurement of 20 mm or more but is now marked by a cut-off value of 10 mm. Over the decade, 40 patients tested positive for Mantoux. IGRA was positive in 7 patients at varied times during follow-up, with TB-PCR positive in one patient and CECT chest helping diagnose patients in subsequent visits4. Notably, these patients tested negative for these infections initially. The conversion of TB tests from negative to positive may have been influenced by the administration of systemic corticosteroids and immunosuppressive therapy. Similarly, tests for non-infective etiologies, like ANA, Rheumatoid factor, and HLA typing, were employed alongside radiological investigations like CECT and MRI. At follow-up, 10 patients received a revised diagnosis for non-infective etiology: five were diagnosed with HLA-B27 associated-uveitis, three with sarcoidosis, and two with Vogt-Koyanagi-Harada disease.
In an earlier epidemiological study, infectious causes were identified as the predominant issues in our tertiary centre.16 Yet, at the 10-year follow-up, the majority of patients (64%) were diagnosed with non-infectious uveitis, encompassing both immune-mediated (40%) and idiopathic cases (24%). One potential reason for this shift might be the administration of specific anti-infective therapy to those with infectious uveitis. This treatment not only reduces recurrences but can also effectively cure the disease, leading to the possibility that patients don't return for follow-ups once recovered. 17–19
To better understand the factors associated with diagnostic changes, we divided patients into three categories: 1) those with a diagnosis change within the first year of follow-up; 2) those with a diagnosis change after the first year; and 3) those whose diagnosis remained unchanged throughout the follow-up. Multiple factors contributed to these diagnostic shifts. Predominantly, they included clinical aspects tied to the disease's progression, such as its recurrent nature, and paraclinical elements like a positive HLA-B27 result. Notably, patients with a diagnostic revision after the first year showed a higher recurrence rate. Moreover, those whose diagnosis shifted after the initial year were more inclined to be prescribed ATT over immunosuppressants. This highlights the significance of monitoring for immunoconversion in TB and underscores the value of repeating tests for infectious causes, especially in recurrent disease cases where other potential etiologies have been excluded. It suggests that patients who initially test negative via the Mantoux test and chest X-ray but show recurring symptoms despite undergoing immunosuppressant treatment might be prime candidates for diagnostic re-evaluation. The overarching aim is to accurately determine the root cause of the uveitis and implement the most appropriate treatment.