Consensus Guidelines: Initiating Antitubercular Therapy for Tubercular Uveitis

Antitubercular therapy (ATT) is well established to reduce the recurrence of tubercular uveitis. However, the multinational Collaborative Ocular Tuberculosis Study (COTS), reported in Investigative Ophthalmology & Visual Science, found that variations in management practices around the world lead to differences in treatment outcomes, suggesting the need for uniform guidelines.

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Subsequently, the COTS Consensus Group consolidated the expertise of uveitis specialists from different regions of the world on when to initiate ATT for tubercular uveitis. John H. Kempen, MD, MPH, PhD, MHS, director of epidemiology for Ophthalmology at Mass Eye and Ear and professor of ophthalmology at Harvard Medical School, and colleagues published two consensus reports in Ophthalmology, one about treating tubercular choroiditis and one about treating other subtypes of tubercular uveitis.

Methods

To begin, a COTS subcommittee reviewed the literature and developed statements about possible scenarios for initiating ATT, defined as multidrug therapy according to each country's health policy (typically isoniazid, rifampin, ethambutol and pyrazinamide). Immunologic tests were defined as the tuberculin skin test (TST) and interferon-gamma release assay (IGRA). Chest X-ray and CT were grouped together with no requirement to perform both, as not all countries have access to CT.

81 global experts in ophthalmology, pulmonology and infectious diseases considered the statements in a two-round Delphi process:

• Using an online questionnaire, they rated how likely they would be to start ATT in each scenario
• Statements that received high consensus in the survey were discussed and voted on in person—tubercular choroiditis was considered in November 2018 (Chandigarh, India) and the other phenotypes were discussed in November 2019 (Kaohsiung, Taiwan)

The following sections summarize the final consensus on each phenotype.

Tubercular Choroiditis

Tubercular serpiginous-like choroiditis (TBSLC): A single immunologic test without radiologic evidence is sufficient to initiate ATT. In a non-endemic region, IGRA+ is required; in an endemic region, TST+ is sufficient even with IGRA−.

• Tuberculoma—Consider ATT if there is any immunologic evidence of TB. In endemic areas, positive radiology alone suffices
• Tubercular focal or multifocal choroiditis is relatively weakly associated with TB. ATT must be supported by immunologic evidence plus radiologic signs suggestive of old healed or active pulmonary TB

Adjunctive Therapy for Tubercular Choroiditis

Start oral corticosteroids with or soon after initiation of ATT in patients who have any subtype of tubercular choroiditis (except tuberculoma when active systemic TB is present). If inflammation recurs during tapering of the steroid dose in patients with TBSLC or focal/multifocal choroiditis, systemic corticosteroid-sparing immunosuppressive therapy can be started with careful attention to potential drug interactions.

Tubercular Anterior Uveitis (TAU)

• First episode of TAU—The suggestive phenotype is iris nodules, keratic precipitates and posterior synechiae; insidious onset; and chronicity. Initiate ATT only when both an immunologic test and a radiologic test are positive
• Recurrent TAU in endemic regions—TST+ plus positive radiology suffice for starting ATT, even with IGRA− or IGRA not performed (moderate consensus)
• Recurrent TAU in nonendemic regions—IGRA+ plus positive radiology was needed to reach moderate consensus for starting ATT, regardless of TST results

Tubercular Intermediate Uveitis (TIU)

TIU is characterized by "snowballs," with or without peripheral choroiditis scars, showing diffuse retinal vasculitis, with or without cystoid macular edema.

• Endemic areas—Consider ATT if there is any immunologic evidence of TB plus radiologic signs (moderate consensus)
• Nonendemic areas—ATT requires both IGRA+ and radiologic signs, regardless of TST results (moderate consensus)

Tubercular Panuveitis

Any immunologic evidence of tuberculosis, along with positive radiologic signs, supports ATT regardless of endemicity.

Tubercular Retinal Vasculitis (TRV)

• Active TRV is characterized by occlusive disease and associated perivascular choroiditis patches. In endemic areas, there was consensus to initiate ATT when both an immunologic test and a radiologic test are positive. In non-endemic areas, there was generally weak consensus for starting ATT regardless of test results
• Inactive TRV is characterized by sequelae of occlusive vasculitis (vitreous hemorrhage, retinal neovascularization and capillary nonperfusion without active phlebitis). There was a weak consensus for starting ATT in endemic regions when both an immunologic test and a radiologic test are positive. There was no consensus about ATT in nonendemic regions

A simplified algorithm in the second report aims to guide ophthalmologists, other physicians and regulatory bodies in decision-making about ATT for tubercular uveitis.

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