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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 60  |  Issue : 4  |  Page : 289-293

A clinical study on ocular tuberculosis in a tertiary care center


Department of Ophthalmology, Tirunelveli Medical College Hospital, Tirunelveli, Tamil Nadu, India

Date of Submission30-Mar-2022
Date of Decision10-Jul-2022
Date of Acceptance20-Jul-2022
Date of Web Publication19-Dec-2022

Correspondence Address:
Savithiri Visvanathan
Department of Ophthalmology, Tirunelveli Medical College Hospital, Tirunelveli, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tjosr.tjosr_34_22

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  Abstract 


Aim: This study is aimed to characterize the various clinical spectrum of ocular Tuberculosis. Methodology: It is a retrospective study of patients presented during January 2020 and January 2021 with tuberculosis and with a follow up period of one year. Results: A total of 676 patients have been included in the study. Pulmonary tuberculosis is 61% (413 patients) and extrapulmonary tuberculosis is 39% (263). Out of 263, 21 patients (8%) had ocular manifestations. The most common ocular presentation is posterior uveitis 43%, followed by panuveitis 24%, intermediate uveitis 19% and anterior uveitis 14%. 70% of the patients were commenced on a standard course of Anti tuberculosis treatment (ATT) as a primary treatment modality, of which two patients were started with ATT empirically given a high index of clinical suspicion, and 30% of the patients were treated with ATT and corticosteroids. Conclusion: Ocular tuberculosis though having a wide spectrum of clinical manifestations and baffling diagnostic methods is still a treatable cause of uveitis. The patient approach should be holistic and integrated with a high index of suspicion in an endemic country like India.

Keywords: ATT, extrapulmonary TB, intraocular tuberculosis, pulmonary TB, tuberculous uveitis


How to cite this article:
Visvanathan S, Velmurugan T, Ramamoorthi A. A clinical study on ocular tuberculosis in a tertiary care center. TNOA J Ophthalmic Sci Res 2022;60:289-93

How to cite this URL:
Visvanathan S, Velmurugan T, Ramamoorthi A. A clinical study on ocular tuberculosis in a tertiary care center. TNOA J Ophthalmic Sci Res [serial online] 2022 [cited 2023 Feb 3];60:289-93. Available from: https://www.tnoajosr.com/text.asp?2022/60/4/289/364243




  Introduction Top


According to the World Health Organization (WHO) Global Report 2021, in 2020 globally, nearly 10 million people fell ill with tuberculosis (TB).[1] India, being named as one of the 30 high-burden countries of TB, is one of the contributors to 86% of the global burden.[1] Tuberculosis is a chronic granulomatous infection caused by the acid-fast bacilli Mycobacterium tuberculosis. Ocular TB poses a diagnostic challenge owing to the wide spectrum of clinical presentation and a lack of universal protocol for management.[2] In a developing country such as India, where TB is customary, the need for early treatment warrants a prompt diagnosis, which can be both vision and lifesaving. This study highlights the diversity of clinical presentation in ocular TB and early effective treatment with ATT.


  Methods Top


It is a retrospective study of 676 patients who presented with TB in a tertiary care centre during the study period of January 2020 to January 2021, and a follow-up period of 1 year was considered. The data regarding the total number of patients who tested positive in 1 year were obtained from the TB cell of the Revised national tuberculosis control program (RNTCP) unit 18.12.2020.

Patients with other causes of ocular inflammation, autoimmune diseases, other ocular infections, and trauma were excluded from the study.

Detailed history regarding the patient demographics, duration of symptoms, contact history, relevant past and treatment history was recorded. Elaborate ocular and systemic examinations were done. Visual acuity was measured using Snellen's chart and converted to logMAR for study purposes. Then, they were classified according to the standardisation of uveitis nomenclature (SUN) workshop classification into anterior, intermediate, and posterior uveitis.[3]

Systemic investigations such as Mantoux, chest X-ray, and interferon-gamma assays including QuantiFERON gold assay were done.

In the Mantoux test, the intradermal inoculation was done with the help of a tuberculin syringe with 0.1 mL of liquid containing 5 TU of purified protein derivate. The induration was measured after 48 hours in millimeters. If the induration is more than or equal to 15mm, the result is considered positive in individuals with no risk of tuberculosis. In IV drug users and in children less than 4 years, more than or equal to 10mm are considered positive. And if the induration is more than 5 mm, it is considered positive in HIV patients, recent contact with active TB and organ transplanted patients. But due to the diverse endemicity, the sensitivity and specificity of the tuberculin skin test are variable.

Chest X-ray/High resolution computed tomography (HRCT) and radiological investigation revealing consolidations, cavitations, calcifications, and lymphadenitis are crucial in diagnosis.

Interferon-gamma release assay mainly consists of two tests, QuantiFERON gold and T-spot test. It is based on the fact that T lymphocytes release interferon-gamma when exposed to the tuberculous antigen.

Ocular investigations include fundus photography, fundus fluorescein angiography, optical coherence tomography and B-scan.

Fundus photography was used in documenting the clinical signs in posterior, intermediate and pan uveitis. Also, it can be used as a tool to grade the vitreous haze.

Fundus fluorescein angiography was done to delineate the active and inactive lesions, in differentiating tuberculous retinal vasculitis from other forms of vasculitis by showing extensive capillary non-perfusion areas.[4] Optical coherence Tomography (OCT) is a non-invasive investigative tool used to monitor retinal complications and also to monitor the treatment response. B-scan is a non-invasive two-dimensional (2D) tool that was mainly done to look for masquerade syndromes, retinal detachment, T-sign and vitreous pathologies.

The statistical analysis for the collected data was done using the SPSS software (version 28.0.1.1).


  Results Top


Altogether, 676 patients who were diagnosed with pulmonary or extrapulmonary TB in 1 year were included in the study. Of these, pulmonary TB was present in 61% (413 patients) and extrapulmonary TB in 39% (263). Out of 263, 79 patients (30.9%) had pleural involvement, 20 (7.8%) had GI tract involvement, 46 (17.4%) had Central nervous system, (CNS) involvement, 32 (12.1%) patients had bone involvement, 21 patients (8%) had ocular manifestations, and 65 patients (24.7%) had other system involvement. [Chart 1] shows the systemic distribution of TB. The mean age of patients infected with ocular TB was 43 ± 5 years. Males were 33.3% (7 patients) and females were 66.6% (14 patients). [Table 1] demonstrates patient demographics. The mean duration of ocular symptoms was 4 months. Thirty-eight percent (8 patients) of the patients presented with vision loss as the primary symptom, a mixture of pain redness and photophobia as a primary symptom in 19% (4 patients), ocular pain in 14% (3 patients), redness in 14% (3 patients) and floaters in 14% (3 patients).

Table 1: Demonstrates the patient demographics

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Bilateral involvement was seen in 74% of the patients and unilateral in 26%. The most common ocular presentation was posterior uveitis in 43% (9 patients), followed by panuveitis in 24% (5 patients), intermediate uveitis in 19% (4 patients) and anterior uveitis in 14% (3 patients). [Table 2] shows the type of uveitis. In anterior uveitis, the most common presentation was bilateral granulomatous uveitis. In posterior uveitis, the most common presentations were choroidal tubercles and multifocal choroiditis (40%), retinal periphlebitis (27%), macular oedema (20%), vitritis (6.7%) and exudative Retinal detachment (RD) (6.7%).
Table 2: Shows the type of uveitis

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In patients with ocular TB, the percentage of pulmonary TB found was 40%, and other sites of extrapulmonary TB was 14% and 46% of the presented patients had ocular TB as the sole manifestation.

The presenting visual acuity was poorer in patients who presented with symptoms for more than 3 months, compared with patients who presented early with symptoms less than 3 months (P < 0.05).

Forty-eight percent (10 patients) presented with Snellen's visual acuity less than 6/60 (logMAR 1). Also, 19% (4 patients) had visual acuity between 6/36 and 6/60 (logMAR 0.77–1). Further 19% (4 patients) had visual acuity between 6/18 and 6/24 (logMAR 0.4–0.6) and 14% (3 patients) had visual acuity between 6/6 and 6/12 (logMAR 0.3–0). [Chart 2] demonstrates the comparison of visual acuity with the duration of symptoms at presentation.



The most common cause of severe vision loss (vision less than 6/60) was macular oedema followed by macular scarring and neovascular membranes. Visual acuity improvement was seen in 3 months in 43% (7 patients) and 66% (14 patients) in 6 months of treatment. The reduction in the severity of inflammation and the size of the lesion was seen much earlier.

The Mantoux test was positive in 67%, chest X-ray/CT chest was positive in 20% and QuantiFERON gold test was positive in 30%. For 13% of the patients, a presumptive diagnosis of ocular TB was made.

Patients were commenced on a standard course of ATT as a primary treatment modality in 70%, of which two patients were started with ATT empirically and given a high index of clinical suspicion, and 30% of the patients were treated with ATT and corticosteroids. Oral prednisolone 1 mg/kg body weight under the ATT cover was started and then tapered off according to the response of the treatment.


  Discussion Top


Ocular TB occurs either as a primary infection or secondary infection. In primary infection, the eye is the initial port of entry for tuberculous bacilli, whereas, in secondary disease, the organisms spread to the eye hematogenously from a distant site. The Extra pulmonary Tuberculosis (EPTB) constitutes 15 to 20% of all cases of TB globally. The annual incidence of EPTB has been rising in the last few decades due to the spread of HIV, changing TB control practices, and also because of the cure of TB cases, which might have resulted in a relative rise in annual case detection of EPTB.[5]

There has been a momentous improvement in the diagnosis of pulmonary TB in the last decade. However, the expeditious diagnosis of extrapulmonary TB remains to be addressed. The diagnosis is particularly onerous due to the paucibacillary nature of the disease and diverse clinical presentation, and also to secure an appropriate sample, there is a need for an invasive procedure.

In a study conducted in North India by Singh et al.,[6] out of the total uveitis cases reported, 9.86% were caused by TB.

In a prospective case series, which was reported in Japan, 20.6% of patients with uveitis had a positive TB skin test, and 7.9% were believed to have intraocular TB.[7]

Similarly, in Saudi Arabia, TB was thought to be the cause in 17.8% of uveitis cases.[8]

These studies represent the wide variation in the incidence of ocular TB, which has been reported in different populations and at various periods.

In our study, the most reported ocular involvement was posterior uveitis, because of the rich vascular content of the uveal tract. In posterior uveitis, choroidal tubercles were frequently reported. The attributed pathogenesis of choroidal tubercles is that it results from hematogenous seeding of the tuberculous bacilli.[4]

In a study by Rosen et al.,[9] the most common presentation, 9 out of 12 presented with retinal vasculitis. However, the study by Bouza et al.[10] showed choroidal involvement as the most common. Serpiginous choroiditis occurs from an immunogenic reaction rather than being infective.[11] It classically begins in the peripapillary region as a solitary lesion or multiple lesions, which later coalesce to form a serpiginous-like pattern.[12] Active lesions in fluorescein angiography show initial hypofluorescence with late hyperfluorescence. In retinal vasculitis, it is periphlebitis with thick exudates around the retinal veins resulting in hemorrhages and hemorrhagic infarction.[13] The tuberculous optic neuropathy and optic neuritis can either result from direct inoculation, hematogenous spread or hypersensitivity reaction.[14]

The diagnosis of ocular TB is most troublesome and most commonly it is presumptive. In several studies, patients with ocular TB do not have pulmonary or extrapulmonary TB.[15] The diagnostic criteria for presumptive ocular TB are.[9],[16],[17]

  1. Ocular findings are consistent with possible intraocular TB with no other cause of uveitis suggested by the history of symptoms or ancillary testing.
  2. Strongly positive tuberculin skin test results (≥15 mm area of induration/necrosis).
  3. Response to anti-tuberculous therapy with the absence of recurrences.


A case worth mentioning here is a patient, a 14-year-old female who presented with bilateral floaters for 2 weeks. She was diagnosed with a case of optic neuritis 3 months ago, for which she was started on corticosteroids elsewhere. On examination, her visual acuity was 2/60 (logMAR-1.47) in the right eye and 6/60 (logMAR-1) in the left eye. Ocular examination revealed bilateral posterior uveitis with retinal periphlebitis and vitritis. Investigations supporting TB were negative. A diagnosis of presumptive ocular TB was made and she was started on ATT. Corticosteroids were initiated under the cover of ATT. Post-treatment, the ocular inflammation was grossly reduced and the vision improved to 6/24 and 6/18 in the right eye and the left eye, respectively. If the diagnosis of pulmonary TB is clinically non-evident, it does not rule out the possibility of ocular TB, as 60% of patients with extrapulmonary TB do not have evidence of pulmonary TB.[18]

According to Collaborative Ocular Tuberculosis Study-1 (COTS-1), due to lack of standardisation and low sensitivity of the available tests, the presence or absence of positive test results does not influence the management of the disease.[19]

A 24-year-old male patient presented with sudden painless loss of vision for 2 weeks. A history of headache and vomiting was present a month ago and he was diagnosed with a case of TB meningitis with elevated Cerebrospinal fluid (CSF) protein. CT chest showed the tree in bud appearance suggestive of TB. Ocular examination showed a large choroidal tubercle with macular oedema. Visual acuity was 6/36 in the involved eye before treatment. After a month of ATT and with oral corticosteroids, the vision improved to 6/12 and the fundus lesions were reduced in size. [Figure 1] shows positive findings in this case of disseminated TB.
Figure 1: (a)CT chest showing a tree in bud appearance, (b) MRI brain showing restricted diffusion in right corona radiata (c) Fundus photograph showing choroidal tubercles with surrounding oedema (d) Fundus fluorescein angiography showing hyperfluorescence in the late phase

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Hitherto, the difficulty in diagnosis of EPTB has been addressed; however, the presence of HIV further complicates the situation due to the atypical clinical presentation. EPTB constitutes more than 50% of all cases of TB in HIV-positive patients.[20] Even the easily accessible Mantoux test provides false-negative results in EPTB due to a phenomenon called anergy in HIV-positive patients. Not only the conventional tests but also the PCR-based assays such as line probe assay and gene X-pert show a reduction in sensitivity in smear-negative cases. The varied manifestations of ocular TB are shown in [Figure 2].
Figure 2: (a)Slit-lamp photograph showing broken synechiae in granulomatous anterior uveitis (b) Fundus photograph showing multiple choroidal tubercles (c)Fundus photograph showing vasculitis (d) Fundus photograph showing vitreous opacities

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Follow-up should be of prime importance in both active and resolving phases to prevent visual complications and for close monitoring of the recurrence of lesions. Rao et al.[21] demonstrated the presence of TB bacilli in the RPE of the enucleated eye of a patient with panuveitis. It suggests the sequestered location of TB bacilli in RPE, which causes the recurrences in tuberculous choroiditis.

In an endemic country such as India, even the atypical presentations of ocular TB should be picked up with a high index of suspicion. Initiating the treatment with corticosteroids without ATT can be sight-threatening.

Our study was limited by the less number of reported cases of ocular TB in 1 year, probably because of the underreporting of cases during the COVID pandemic.


  Conclusion Top


Ocular TB, though having a wide spectrum of clinical manifestations and baffling diagnostic methods, is still a treatable cause of uveitis. The patient approach should be holistic and integrated with a high index of suspicion in an endemic country such as India. The diagnostic conundrum can be tackled by systemic and multidisciplinary approaches. Discourse with the other specialty physicians such as radiologists, pulmonologists and pathologists is mandatory for prompt diagnosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Global Tuberculosis Report 2020. Geneva: World Health Organization; 2020.Licence: CC BY-NC-SA 3.0 IGO.  Back to cited text no. 1
    
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Bansal R, Basu S, Gupta A, Rao N, Invernizzi A, Kramer M.Imaging in tuberculosis-associated uveitis. Indian JOphthalmol2017;65:264-70.  Back to cited text no. 4
    
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Singh R, Gupta V, Gupta A. Pattern of uveitis in a referral eye clinic in north India.Indian J Ophthalmol2004;52:121-5.  Back to cited text no. 6
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Morimura Y, Okada AA, Kawahara S, Miyamoto Y, Kawai S, Hirakata A, et al. Tuberculin skin testing in uveitis patients and treatment of presumed intraocular tuberculosis in Japan.Ophthalmology2002;109:851-7.  Back to cited text no. 7
    
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