Tubercular uveitis (TB-uveitis) is a general term for inflammation caused by Mycobacterium tuberculosis (Mtb) within the eye 1). However, direct detection of tubercle bacilli from the eye is nearly impossible, and clinically, diagnosis relies on immunological tests and response to antitubercular therapy.
Tuberculosis is a major cause of infectious uveitis, especially in high-burden countries, accounting for 22.9–48.0% of infectious uveitis cases in India and Indonesia 1). The prevalence among all uveitis patients is reported to be 0.2–10.5% in tertiary care centers worldwide 2). In Japan, the tuberculosis incidence rate is significantly higher than in Western developed countries, particularly in large cities. Additionally, with the increase in travelers from high-burden countries, this disease should always be considered in the differential diagnosis of uveitis.
Visual impairment due to tuberculous uveitis can be severe. It has been reported that in about one-third of patients, best visual acuity is less than 3/601). Uveal macular edema and secondary glaucoma occur in about 30% of patients1).
QCan ocular tuberculosis develop without pulmonary tuberculosis?
A
Ocular tuberculosis can develop even without active pulmonary lesions. Pulmonary findings are often absent or limited5). If there are immunological findings indicating tuberculosis infection, such as a positive IGRA, ocular tuberculosis should be suspected regardless of the presence of pulmonary lesions.
This is the most common clinical type, with the following representative findings.
Choroidal Tuberculosis
Miliary choroidal tuberculosis: Yellow-white small exudative spots scattered beneath the retina. Nodules of 1/2 to 1/6 disc diameter present a multifocal choroiditis appearance. Usually bilateral, and commonly occurs when cellular immunity is compromised, such as in AIDS.
Choroidal tuberculoma: A yellow-white mass larger than one disc diameter formed near the posterior pole. It is a granuloma composed of epithelioid cells and Langhans giant cells, with caseous necrosis. Extremely rare.
Choroiditis
Serpiginous-like choroiditis: Typically spares the fovea and presents with serpiginous lesions accompanied by vitreous inflammation. Even a single positive interferon-gamma release assay result is recommended to initiate anti-tuberculosis therapy 2).
Geographic choroiditis: Recognized as irregular choroidal atrophic lesions.
Retinal vasculitis: Caused by an immune response to constituent proteins of Mycobacterium tuberculosis. It presents as retinal periphlebitis or occlusive vasculitis, with retinal hemorrhages and venous sheathing. Non-perfusion areas expand relatively rapidly, potentially leading to neovascularization and vitreous hemorrhage. Recurrent vitreous hemorrhage is also called Eales disease.
The pathogenesis of tuberculous uveitis is not fully understood. The following three mechanisms have been proposed1).
Direct infection by Mycobacterium tuberculosis: Bacteria that reach ocular tissues via the bloodstream directly cause inflammation. The choroid has abundant blood flow and high oxygen partial pressure, making it a favorable environment for the bacteria.
Immune response (in the absence of bacteria): An excessive immune response to extraocular tuberculosis antigens triggers intraocular inflammation. It can occur even without live bacteria in the eye.
Autoimmune response: Cross-reactivity (antigen mimicry) between tuberculosis antigens and retinal antigens may induce anti-retinal autoimmunity1). In active and latent tuberculous uveitis, serum anti-retinal antibodies (ARA) have been reported to be more frequently positive than in healthy individuals1).
Clinically distinguishing these mechanisms is currently difficult, and further pathophysiological research is needed to optimize treatment approaches1).
The definitive diagnosis of tuberculous uveitis is the detection of Mycobacterium tuberculosis in intraocular fluid or ocular tissue 2). However, because the bacterial load is extremely low and biopsy specimens are very small, it is rare to demonstrate the bacteria by culture or smear 1)2). Therefore, in most cases, treatment is based on a presumptive diagnosis.
Type IV allergic reaction to Mycobacterium tuberculosis
Affected by BCG vaccination
Interferon-gamma release assay
Measures interferon-gamma. Not affected by BCG
Also positive in latent infection
T-SPOT
ELISPOT method. Useful for detecting prior tuberculosis infection.
Has similar limitations as the interferon-gamma release assay.
Tuberculin skin test: A strongly positive result provides an important clue for differentiating from sarcoidosis. However, it may be negative in cases of impaired cell-mediated immunity such as miliary tuberculosis or AIDS.
Interferon-gamma release assay (QuantiFERON-TB Gold Plus, etc.): Measures interferon-gamma production by Mycobacterium tuberculosis-specific CD4/CD8-positive T lymphocytes. It has the advantage of not being affected by BCG vaccination. In non-endemic countries, the proportion of uveitis patients with a positive interferon-gamma release test who have an unknown cause is significantly higher than those with a negative test (59% vs 39%)1).
Combination of tuberculin skin test and interferon-gamma release assay: Using both together improves the sensitivity of diagnosing ocular tuberculosis3).
However, tuberculin reaction and interferon-gamma release assays may yield false-negative results during administration of corticosteroids or immunosuppressive drugs. If possible, testing should be performed before starting immunosuppression 8).
Bruzzone et al. (2024) reported a case in which QuantiFERON-TB Gold Plus became positive after two negative tuberculin reactions, leading to a diagnosis of tuberculous multifocal choroiditis8). This report highlights the importance of the timing of interferon-gamma release assay testing.
PCR testing using intraocular fluid (aqueous humor or vitreous fluid) is performed. Real-time PCR methods (e.g., targeting the IS6110 sequence) are useful, but a systematic review found that PCR positivity is only 55%, and specificity is also insufficient 1). In high-prevalence countries like India, positivity rates can reach up to 70% when using MPB64 primers 1).
The Standardization of Uveitis Nomenclature (SUN) Working Group established classification criteria for tuberculous uveitis1). The following clinical types are recognized as having a strong association:
Although a definitive diagnosis cannot be made based on ocular findings alone, organizing the phenotypes suggestive of tuberculous uveitis is useful for presumptive diagnosis7).
The Collaborative Ocular Tuberculosis Study (COTS) group has proposed guidelines that are easy to use in clinical practice and applicable to a wider range of clinical situations1)2).
Sarcoidosis: This is the most important differential diagnosis clinically. Since both conditions present with granulomatous inflammation, the tuberculin skin test and IGRA are important for differentiation.
Behçet’s disease: Requires differentiation when retinal vasculitis is present.
Toxoplasmosis: When presenting with retinitis or vitritis, tuberculosis can show similar clinical features3)6).
VKH (Vogt-Koyanagi-Harada) disease: Differentiation is necessary when accompanied by bilateral serous retinal detachment or choroidal thickening4).
QDoes a positive QuantiFERON test not necessarily indicate ocular tuberculosis?
A
A positive IGRA indicates an immune response to Mycobacterium tuberculosis, but it can also be positive in latent infection, so it does not confirm ocular tuberculosis. Diagnosis is made by combining typical ocular findings, exclusion of other diseases, and treatment response 1)2).
The mainstay of treatment for tuberculous uveitis is multidrug antituberculosis therapy (ATT) 1). ATT has been reported to reduce the recurrence rate by approximately 75% 2).
The standard RIPE therapy regimen is as follows:
Initial intensive phase (2 months): Combination of four drugs: isoniazid (INH) + rifampicin (RFP) + pyrazinamide (PZA) + ethambutol (EB)
Maintenance phase (4 months): Combination of INH + RFP
The standard treatment duration is 6 to 9 months5).
The therapeutic trial of isoniazid is emphasized. If inflammation subsides or worsens (drug reaction) within about one week after starting isoniazid, it is considered effective. If there is no effect after one month, it is deemed ineffective and discontinued. If effective, additional drugs such as rifampicin are added.
For serpiginous choroiditis and choroidal tuberculoma, if one immunological test (TST/IGRA) is positive, ATT initiation is recommended even without chest imaging findings suggestive of tuberculosis2). For other clinical types, clinical presentation, immunological tests, and imaging findings are comprehensively assessed.
When used in combination with ATT, it is effective for controlling posterior inflammation 5). It is usually started at the same time as or immediately after ATT initiation and tapered over 4 to 6 weeks. The COTS guidelines also support the usefulness of steroid adjuvant therapy for tuberculous uveitis5).
Mycobacterium tuberculosis disseminates hematogenously from the primary lung infection site to ocular tissues. The choroid, with its high blood flow and oxygen tension, provides a favorable environment for bacterial colonization. Granulomas with caseous necrosis in ocular tissues have been reported 1). The formation of granulomas composed of epithelioid cells and Langhans giant cells involves a cell-mediated immune response centered on macrophages.
Even when no viable bacteria are present in the eye, an excessive immune response to tuberculosis antigens can cause intraocular inflammation.
In a review by Putera et al. (2023), an animal experiment is described in which chronic uveitis developed only in mice pre-sensitized with Mycobacterium tuberculosis antigens 1). This suggests that immune memory to Mycobacterium tuberculosis antigens plays an important role in the development of ocular inflammation.
The involvement of autoimmune reactions due to molecular mimicry between Mycobacterium tuberculosis antigens and retinal antigens has been proposed 1). Cases of granulomatous anterior uveitis resembling tuberculous uveitis have been reported after intravesical BCG instillation, with peripheral T lymphocytes producing high levels of IL-2 and IFN-γ 1). In active and latent tuberculous uveitis, the serum positivity rate for anti-retinal antibodies (ARA) is higher than in healthy controls 1).
Retinal vasculitis is thought to result from an immune response to constituent proteins of Mycobacterium tuberculosis. Occlusive vasculitis leads to rapid expansion of retinal nonperfusion areas, causing neovascularization and vitreous hemorrhage. An association with Eales disease has been noted, and positive PCR for Mycobacterium tuberculosis has been reported.
7. Latest Research and Future Perspectives (Investigational Reports)
In addition to conventional ATT, approaches that enhance the host immune response to improve the efficacy of ATT are being studied1). Against the backdrop of increasing drug-resistant tuberculosis, several HDT candidate drugs are being investigated in the field of pulmonary tuberculosis.
Putera et al. (2023) suggested that HDT may be applicable to tuberculous uveitis1). When an excessive immune response to Mycobacterium tuberculosis causes tissue damage, an immunomodulatory approach may be useful. However, preclinical evidence in ocular tuberculosis is still limited.
Association between Tuberculous Uveitis and Vogt-Koyanagi-Harada Disease
Amjad et al. (2024) reported a case of a 55-year-old woman with positive IGRA who developed bilateral VKH-like serous retinal detachment4). Although she responded markedly to steroid pulse therapy, atypical findings of peripheral retinal perivasculitis were present. It has been suggested that a hypersensitivity reaction to tuberculosis may have induced a VKH-like clinical picture.
Such mixed cases indicate that distinguishing VKH from ocular tuberculosis is extremely important in tuberculosis-endemic areas4).
Diverse Clinical Presentations of Posterior Ocular Tuberculosis
Faneli et al. (2026) reported six cases of posterior ocular tuberculosis 5). The cases included diverse clinical forms such as choroidal granuloma, multifocal choroiditis, serpiginous choroiditis, and occlusive retinal vasculitis. In all cases, inflammation was controlled with RIPE therapy plus corticosteroids. Four patients had a history of incarceration, and pulmonary findings were observed in only three cases. Anti-VEGF therapy was added in one case complicated by choroidal neovascularization.
Atypical Cases and Autoimmune Retinopathy-Like Conditions
Hou et al. (2025) reported a case of a 36-year-old man with presumed ocular tuberculosis mimicking autoimmune retinopathy 9). After worsening with corticosteroid therapy, vision and macular structure markedly improved with one month of ATT monotherapy.
Babalola (2025) reported an atypical case of ocular tuberculosis in a 15-year-old boy with bilateral optic atrophy and epiretinal membrane10). A family history of tuberculosis and the presence of choroidal nodules provided clues for the presumptive diagnosis.
Putera I, Schrijver B, ten Berge JCEM, et al. The immune response in tubercular uveitis and its implications for treatment: From anti-tubercular treatment to host-directed therapies. Prog Retin Eye Res. 2023;95:101189. doi:10.1016/j.preteyeres.2023.101189.
Agrawal R, Testi I, Mahajan S, et al. Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis—Report 1: Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis. Ophthalmology. 2021;128:266-276.
Bromeo AJ, Lerit SJ, Arcinue C. Ocular tuberculosis masquerading as atypical ocular toxoplasmosis. GMS Ophthalmol Cases. 2023;13:Doc19.
Amjad M, Zafar A. A Case of Vogt-Koyanagi-Harada Disease and Retinal Peri-Phlebitis in a Patient With Presumed Ocular Tuberculosis. Cureus. 2024;16(7):e64200.
Faneli AC, Souza GM, Neto PFS, et al. Chasing shadows: case series of six posterior segment manifestations of ocular tuberculosis. AME Case Rep. 2026;10:50.
Chong WK, Khoo Kah Kuen K, Mun-Wei L, et al. Infectious Sclerouveitis in an Immunocompetent Patient: A Probable Case of Simultaneous Ocular Tuberculosis and Toxoplasmosis. Cureus. 2022;14(11):e31726.
Gupta A, Bansal R, Gupta V, et al. Ocular signs predictive of tubercular uveitis. Am J Ophthalmol. 2020;205:72-80.
Bruzzone F, Plebani M, Koryllou A, et al. The importance of QuantiFERON Gold Plus test for the diagnosis of presumed ocular tuberculosis. Klin Monatsbl Augenheilkd. 2024;241:432-434.
Hou SM, Liu Q, Zhang XH, et al. Presumed ocular tuberculosis masquerading as autoimmune retinopathy. Am J Ophthalmol Case Rep. 2025;38:102296.
Babalola YO. Bilateral optic atrophy and epiretinal membranes: an atypical presentation of ocular tuberculosis. Niger Med J. 2025;66(1):389-393.
Copy the article text and paste it into your preferred AI assistant.
Article copied to clipboard
Open an AI assistant below and paste the copied text into the chat box.
