Pattern recognition is critical in the diagnosis and treatment of any form of uveitis. Here are 10 pearls that will make it easier to recognize patterns of presentation and resolution in tubercular uveitis.
The general approach to diagnosis:
We are all aware of the role of identifying clinical signs of TB in the eye and that of ancillary tests for systemic TB (immunological and radiological). However, we tend to ignore the last part – theexclusion of non-TB entities. These include various infectious and non-infectious conditions that can match a given clinical sign of ocular TB.
Tubercular retinal vasculitis – 1:
TB retinal vasculitis typically causes a periphlebitis, though rarely arterioles can also be affected. The most common clue for a tubercular etiology is the presence of active or healed retinitis lesions underlying the blood vessels (subvascular lesions). These are intraretinal granuloma and are highly predictive of tubercular etiology in TB-endemic countries (Kaza et al., 2020).
Tubercular retinal vasculitis – 2:
The second clue for TB in retinal vasculitis is the presence of focal vascular tortuosities (FVTs), within the active of healed retinitis lesions. These lie away from capillary non-perfusion and do not leak, unlike retinal new vessels. The FVTs probably represent local ischemia within the retinitis lesion and straighten up with a resolution of the lesion.
Tubercular retinal vasculitis – 3:
The third clue is the presence of occlusive retinal vasculitis. Of course, vascular occlusion can be present in many inflammatory conditions. However, in TB-endemic countries, vascular occlusion can help in distinguishing TB from sarcoid, which also presents as periphlebitis.
Serpiginous-like choroiditis (SLC):
As in retinal vasculitis, SLC can also be the end result of several etiologies – infectious and non-infectious (Nazari et al., 2015; Dutta Majumdar et al., 2019). However, in TB-endemic countries, the pattern of serpiginous-like choroiditis – multi-focal, amoeboid lesions in the central or peripheral fundus, should be considered as TB, unless proven otherwise. Fundus autofluorescence is a simple, non-invasive test to track the activity of the SLC lesions from a presentation, till complete resolution.
Do we need evidence of systemic TB for diagnosis of ocular TB:
We need to remember the systemic-ocular paradox in clinical manifestation of TB. Most patients with active pulmonary TB do not have evidence of ocular TB; and many patients (including histologically proven) of ocular TB, may not have any evidence of systemic TB infection. The reasons for the latter include variable sensitivity of the test (e.g. chest X-ray < CT scan < PET-CT), dissemination of infection from sites other than lungs (e.g. bone marrow), and immunological and technical factors affecting results of Mantoux or QuantiFERON TB Gold tests. The bottom line: just as the false positive, beware of the false-negative Mantoux test.
BCG and the Mantoux test:
It is commonly highlighted that the Mantoux test has limited utility in BCG-vaccinated populations. However, the BCG-vaccination in the neonatal period (as practiced in India) has a limited effect on the Mantoux outcome beyond one year of age, and no effect after 10 years – the age group that would include nearly all our tubercular uveitis patients. It must be remembered that neither the Mantoux nor the QuantiFERON TB Gold test distinguishes between latent and active TB. The only real indication for the latter is a strong clinical suspicion of TB with a negative Mantoux test.
Anti-TB monotherapymay suffice in manifestations of tubercular uveitis that are primarily driven by infection. These include TB retinal vasculitis, especially when accompanied by the clinical clues listed above; or the presence of solitary or multifocal choroidal granuloma. It is important to remember that most of these lesions may resolve with corticosteroids alone but will recur at variable intervals of time unless treated with anti-TB therapy (ATT).
Combination therapy of ATT and corticosteroids:
Combination therapy of ATT and corticosteroidsis required if any of the above clinical signs are accompanied by other inflammatory signs threatening visions (e.g. cystoid macular edema, exudative retinal detachment, or dense vitritis), and in cases of TB-SLC. The latter has a high propensity of paradoxical worsening on the initiation of ATT unless supplemented by corticosteroids. The latter also highlights a major challenge of diagnosing TB-SLC. On one hand, there is no definitive evidence of TB in these patients; on the other, the disease worsens on starting anti-TB therapy.
Recurrent inflammation after ‘successful’ completion of ATT:
This is a challenging scenario since there is no microbiological evidence of TB either for diagnosis or for the successful completion of ATT. Such recurrent inflammation may either present as the original lesion (e.g. retinal vasculitis or SLC), or as anterior or intermediate uveitis (irrespective of or the original clinical presentation). In the case of the former, it is important to search for alternate etiology, or for drug resistance (look for MDR-TB in the lungs or contact with such patient). The latter (anterior [non-granulomatous] or intermediate uveitis) is very common and typically responds to local anti-inflammatory therapy. We suspect that these result from bacterial products and do not require a repeat course of ATT.