Ocular tuberculosis is a specific systemic presentation of mycobacterial infection generally caused by direct invasion of the TB bacilli or an immunogenic reaction secondary to an extraocular infection. Tuberculosis has a proclivity for causing caseating granulomatous inflammation primarily in the lungs, but it can also affect the gamut of organs in the human body.
Ocular TB can present clinically in a myriad of ways both extraocularly and intraocularly. These presentations are both nonspecific and mercurial. Primary ocular TB describes focal disease, while secondary ocular TB arises with hematogenous dissemination or contiguous spread from a local insult. Primary TB infections predominantly affect the external aspects of the eye including the conjunctiva and cornea and commonly present as keratitis, scleritis, ulceration, or phlyctenulosis. Intraocular TB manifestations are mainly secondary to systemic seeding, primarily from a pulmonary focus. While studies indicate that choroiditis is the most common intraocular presentation of TB, anterior uveitis, retinal vasculitis, vitritis, and papillitis can also be found in patients with ocular TB [5–9]. In our sample of nine patients, each of these manifestations presented in at least one patient. Thus, it is imperative for physicians to consider ocular TB in their differential diagnosis, especially given that ocular TB can present in a nonspecific manner similar to more common conditions that lead to ocular inflammation.
TB is often recognized in medicine to be “the great imitator” and can therefore present with diverse clinical pictures. Given its ability to often masquerade as an ocular inflammatory reaction without obvious tuberculoid correlation, as well as the fact that testing for ocular TB is generally limited to invasive, expensive, and less available definitive diagnostic tests such as polymerase chain reaction (PCR) with ocular fluid samples, early diagnosis of ocular TB is exceptionally difficult. Therefore, diagnosis of ocular TB is often made presumptively in concert with tuberculin skin tests and interferon gamma release assays after other possible etiologies have been excluded [10–15]. Favorable response to anti-tuberculosis therapy (ATT) may also indirectly serve as evidence further elucidating the potential diagnosis.
The nine cases included in this study presented with a variety of ocular involvement including anterior uveitis, panuveitis, optic nerve edema, sequential papillitis, granulomatous uveitis, peripheral vasculitis, and possible choroidal granuloma. The predominant clinical presentation in our group of patients was anterior uveitis (44%) rather than posterior uveitis, which has been the most common presentation in prior reports [15, 16]. Of note, the two patients who had a history of immunosuppression (cases 1 and 2) both experienced bilateral anterior uveitis. Additionally, extraocular TB manifestations were only seen in 44% of patients, and known history of TB exposure was only obtained in 22% of our patients. This presents critical evidence that patient reported history of TB exposure or presence of symptomatic systemic TB disease are unreliable criteria for the diagnosis of ocular TB.
It is critical to note this exceedingly low proportion of patients with a known history of TB exposure and manifestations of ocular TB. This highlights the general lack of presumption of diagnosis amongst our population as well as the critical nature of obtaining TB testing even in patients with no reported history of exposure or symptomatic systemic manifestations. Those patients without known exposure and without extraocular manifestations are most at risk for being misdiagnosed and therefore being left untreated for TB.
Within our study of nine patients, we were able to identify potential, but unconfirmed, mechanisms of TB exposure in three of our cases. The patient in Case 1 was born in a high-risk country and currently works as a postal carrier. The patient in Case 3 works as a manager at a local pizza restaurant. The patient in Case 9 presented shortly after arriving in the United States as a refugee from a high-risk country.
Laboratory confirmation of ocular TB is often limited due to the invasive, expensive, and logistic difficulty with obtaining ocular samples for PCR testing. In each of the cases presented here, the diagnosis of ocular TB was a presumptive diagnosis based on chronological correlation of clinical presentation and response to both topical ocular medications and systemic anti-tuberculoid treatment without flare up during the follow up period. Accordingly, a subset of patients who had both ocular inflammatory disease and positive TB testing but lacked either a chronological or clinical response correlation between the two diseases were excluded from this study.
A concern that this report raises is the duration of time between most patients’ presentation with ocular disease and the investigation into TB as the potential cause. Barring the cases where a positive TB test was taken prior to eye manifestations, this time ranged from 3 days to 13 years from first reported ocular manifestation to testing for TB. In these cases, there was significant clinical improvement of ocular disease after the administration of ATT. In our study group, a favorable response to complete ATT was noted in 89% of patients. One patient (case 8) has refused systemic anti-TB treatment, cancelled all infectious disease appointments, and continues to experience recurrent anterior uveitis despite topical corticosteroid use. Given the relative efficacy and cost efficiency of TB treatment, it is crucial to establish the diagnosis and initiate treatment early in these patients with ocular TB with the objective of providing optimal chances of preserving sight [5, 17, 18]. In addition, proper diagnosis of ocular TB is crucial to avoid the use of systemic corticosteroids, which would likely aggravate the underlying TB infection and could put the patient at potential risk of permanent visual damage.
While this is a relatively large study compared to current literature on ocular TB, a limitation of this study is the fairly small sample size of nine patients as well as the retrospective nature of the study. In addition, the lack of PCR testing or confirmed microbiologic diagnosis of ocular TB, as well as the various systemic TB treatments used amongst the cases, are limitations of this series. Lastly, there are many inherent limitations with the use of electronic medical records (EMR) as well as the fact that it was implemented at our institution during our study period. Some patient information was found on scanned paper documents from prior to the EMR implementation, however, there were likely patients that fit our inclusion criteria and were missed in our search due to the difficulty in obtaining this data via a search through a large amount of paper charts. The use of the EMR, especially as more integration occurs across hospital systems and specialties, will likely assist in identifying more patients with ocular TB in the future. As younger patients continue to have more and more of their medical history in one central EMR, rather than partially on paper and partially electronic, data will be easier to follow and disease correlations easier to detect. This will allow for better evaluation of a rare cause of intraocular inflammation in the future. Finally, future prospective studies with more definitive diagnostic criteria for ocular TB including PCR and sequencing for Mycobacteria tuberculosis from samples of intraocular fluid will be of value and advance the understanding of disease prevalence, manifestations, and ultimately treatment, as well as help establish a standard treatment protocol for patients with ocular tuberculosis.