Relapse in ocular tuberculosis: Study reveals one-third of cases resurface after treatment

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An international study conducted by researchers in Indonesia, The Netherlands, the UK, and Singapore reported that about one-third of patients with ocular tuberculosis (OTB) in a low tuberculosis (TB)-endemic area had a relapse of uveitis after achieving clinical inactivity, which is predicted by the disease course and an initial poor treatment response,¹ according to first author Ikhwanuliman Putera, MD, and PhD candidate.

He is from the Department of Ophthalmology, Faculty of Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia; and the Department of Ophthalmology, Laboratory Medical Immunology, Department of Immunology, and the Department of Internal Medicine Section Allergy and Clinical Immunology, Erasmus University Medical Centre, Rotterdam, The Netherlands.

The lungs are the primary site affected by TB, but the eye is an extrapulmonary site that can be affected, the authors explained. “The prevalence of OTB among patients with uveitis can range from between 3% in non-high-burden settings to 7% to 11% in high-burden settings,”² they said.

Treating these patients is challenging. The recommendation is to begin antitubercular treatment (ATT) in patients with tubercular choroiditis, serpiginous-like choroiditis), or tuberculoma, who also have signs of systemic TB based on positive interferon-gamma release assay (IGRA) or tuberculin skin test or chest radiologic features suggesting TB.³

However, the decision becomes more complicated in the presence of uveitic manifestations rather than the other phenotypes. Dr. Putera and colleagues explained that relapse and chronic uveitis can occur after infectious uveitis was treated successfully, for instance, in the case of streptococcal infections.⁴ Uveitic relapse after treatment for Mycobacterium tuberculosis, the cause of TB, has received limited attention to date.

In their recent small case series study, they showed that during long-term follow-up, despite a successful full course of ATT, three of five patients had a recurrence.⁵

In light of that, they undertook a retrospective analysis of patients with OTB over a 10-year period. The time-to-relapse of uveitis and the risk factors were evaluated.

Results of retrospective analysis

In the 93 cases of OTB identified, 75 patients achieved clinical inactivity following treatment, the median time to which was 3.97 months.

Putera and colleagues reported, “During a median follow-up of 20.7 months after clinical inactivity, uveitis relapse occurred in 25 of the 75 patients (33.3%). Patients who were considered poor treatment responders during their initial uveitis episode had a significantly higher risk of relapse after achieving clinical inactivity than good responders (adjusted hazard ratio, 3.84, 95% confidence interval, 1.28-11.51). Thirteen of the 25 relapsed patients experienced multiple uveitis relapse episodes, accounting for 78 eye-relapse episodes during the entire observation period. Over half (46 of 78, 59.0%) of these episodes were anterior uveitis. A significant number of uveitis relapse episodes (31 episodes, 39.7%) were managed effectively with topical corticosteroids.”

The authors concluded that uveitic relapses, primarily manifesting as anterior uveitis and effectively treated with corticosteroids, are common, occurring in one-third of cases within a median follow-up period of 20.7 months after inactivity was achieved for the initial presenting uveitis. About half of patients re-tested for IGRA still had IGRA positivity during the first relapse episode, most of these relapse episodes were effectively managed using immunosuppressive drugs without restarting ATT.

“The intraocular inflammation status at 6 months following treatment initiation for the initial uveitis appeared to be a significant predictor of relapse prognosis. Poor responders for the treatment of the initial uveitis episode were at a significantly higher risk of experiencing a relapse after achieving clinical inactivity,” they concluded.

References

1. Putera I, ten Berge JCEM, Thiadens AAHJ, et al. Relapse in ocular tuberculosis: relapse rate, risk factors and clinical management in a non-endemic country. Br J Ophthalmol. 2024;108:1642-1651.

2. AlliHD, Ally N, Mayet I, et al. Global prevalence and clinical outcomes of Tubercular uveitis: a systematic review and meta-analysis. Surv Ophthalmol. 2022;67:770–92:S0039-6257(21)00189-2. doi:10.1016/j.survophthal.2021.10.001

3. AgrawalR, Testi I, BodaghiB, et al. Collaborative ocular tuberculosis study consensus guidelines on the management of Tubercular uveitis-report 2: guidelines for initiating Antitubercular therapy in anterior uveitis, intermediate uveitis, Panuveitis, and retinal vasculitis. Ophthalmology. 2021;128:277–87:S0161-6420(20)30598-4. doi:10.1016/j.ophtha.2020.06.0

4. CunninghamET, ForresterJV, RaoNA, et al. Post-infectious uveitis. Ocul Immunol Inflamm. 2016;24:603–6. doi:10.1080/09273948.2016.1253983

5. PuteraI,van DaelePLA, ten BergeJCEM, et al. Long-term follow-up after treatment of Tubercular uveitis: case series and review of the literature. Front Ophthalmol. 2023;3. doi:10.3389/fopht.2023.1270948