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Year : 2021  |  Volume : 1  |  Issue : 4  |  Page : 683-685

A case report of probable ocular tuberculosis following biologics

Medical Research Foundation, Sankara Nethralaya, 18, College Road, Chennai, Tamil Nadu, India

Date of Submission27-Jan-2021
Date of Acceptance21-Apr-2021
Date of Web Publication09-Oct-2021

Correspondence Address:
Dr. Sudha K Ganesh
Medical Research Foundation, Sankara Nethralaya 18, College Road, Chennai, Tamil Nadu - 600 006
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_227_21

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Biological drugs, especially anti-TNF-α agents, have revolutionized the treatment of chronic immune-inflammatory diseases, however complications include reactivation of tuberculosis and increased incidence of other infections.
We report a 28-year-old male, on biological agents for HLA B27 positive spondyloarthropathy, inflammatory bowel disease and psoriasis, who presented with occlusive retinal perivasculitis. Following a thorough clinical examination and ocular and systemic investigation, a diagnosis of probable ocular tuberculosis (POTB) with tubercular retinal vasculitis (TRV) was made. Biologics were temporarily withdrawn and anti-tubercular therapy (ATT) initiated with good response. Patients on biologics need close monitoring, for ocular and systemic infections especially TB.

Keywords: Biological drugs, HLA B27 related ankylosing spondylitis, infliximab, retinal vasculitis, tuberculosis

How to cite this article:
Ganesh SK, Thatikonda D. A case report of probable ocular tuberculosis following biologics. Indian J Ophthalmol Case Rep 2021;1:683-5

How to cite this URL:
Ganesh SK, Thatikonda D. A case report of probable ocular tuberculosis following biologics. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Oct 18];1:683-5. Available from: https://www.ijoreports.in/text.asp?2021/1/4/683/327726

Biological agents have revolutionized the treatment of chronic immune mediated inflammatory diseases, and recently, uveitis.[1],[2] Tumor necrosis factor (TNF) a pro-inflammatory cytokine is implicated in the pathogenesis of several immune mediated diseases like ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) that respond positively to drugs targeting it, resulting in increased use of anti-TNF agents.[3] Adverse effects of biologics include injection site reactions, risk of opportunistic infections (OI) including tuberculosis (TB), cytopenias, aplastic anemia, risk of malignancy, worsening of congestive cardiac failure, hepatotoxicity and demyelinating disease.[4]

TNF-alpha is a key mediator in controlling tubercular infection.[5] Though development of OIs like systemic TB during anti-TNF therapy is well documented,[3] there are no reports of ocular TB or probable ocular TB (POTB) noted in literature. We report a case of tubercular retinal vasculitis (TRV) in a patient on infliximab for HLA B27 related AS and IBD.

  Case Report Top

A 28-year-old male doctor, with a history of HLA B27 related AS with IBD and psoriasis reported to us with floaters and visual disturbance in the left eye (OS). The patient was investigated at CMC, Vellore. Investigations namely HLA B27 was positive, however bone marrow biopsy, leukemia/lymphoma panel, magnetic resonance imaging (MRI) Brain with multiple sclerosis (MS) protocol, HLA B51 and QuantiFeron TB gold test (QTB) were negative. Computerized tomography (CT) enterography, colonoscopy with biopsy and fecal calprotectin aided in the diagnosis of HLA B27 related AS with IBD and psoriasis. He was initiated on infliximab therapy in 2015 and was maintained on 5 mg/kg every 3-4 monthly along with Sulfasalazine 3 mg.

In October 2019, he had floaters in OS with peripheral vision loss. The local ophthalmologist diagnosed retinal perivasculitis OS and advised a course of oral steroids with increase in Infliximab dose to 6 mg/kg every 2 monthly. Despite this, vasculitis did not resolve and was progressing [Figure 1].
Figure 1: (a-d): Fundus photo of left eye taken by local ophthalmologist in October 2019 shows active vasculitis temporally with vascular cuffing, hemorrhages progressing to occlusive vasculopathy in spite of therapy

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He presented to us in March, 2020 for a second opinion. Best corrected visual acuity (BCVA) was 20/20, N6 in both eyes. Slit lamp examination revealed a normal anterior segment both eyes with a 1+ retrolental vitreous cells in OS. Intra-ocular pressure was 14 mm in both eyes. Fundus examination appeared normal but fluorescein angiography (FFA) showed wedge shaped capillary non-perfusion (CNP) area with active occlusive perivasculitis and staining of the mid peripheral vessels in OS [Figure 2].
Figure 2: 2a- Fundus photo of left eye on presentation to us in March 2020 appeared normal 2b- early phase FA showing a wedge shaped capillary non-perfusion area (CNP) (red arrow) of 2 clock hours in the temporal quadrant. 2c and d- mid and late phases of FA showing vascular staining (2d-red arrow) in the temporal area representing active vasculitis

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On reinvestigation, we found high-resolution computerized tomography (HRCT) chest and abdomen showed calcified granulomas in liver, few small solid nodules in right lung, small ground glass nodule in left lung suggestive of infective aetiology. Mild pleural thickening with enlarged right paratracheal (11 mm) and sub-carinal lymph node (8 mm) with focal calcification was noted. A repeat QTB was positive and absolute CD4 counts were low (335 cells/cmm).

Based on the clinical picture of occlusive retinal vasculitis, HRCT findings and QTB a diagnosis of POTB was made. Infliximab was temporarily stopped by rheumatologist and pulmonologist started on ATT with oral Prednisolone 1 mg/kg/day. After 4 months of ATT and steroids the TRV resolved and sectoral laser photocoagulation was done in the CNP areas. Last follow-up after 8 months showed stable fundus with resolution of ocular symptoms [Figure 3].
Figure 3: (a) Fundus photo of left eye in July 2020 after treatment and laser photocoagulation to CNP areas. Laser scars are seen in the involved area (red arrow). (b) Fundus photo of left eye in November 2020 showing a stable fundus with laser scars in temporal area

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  Discussion Top

Though anti-TNF agents have emerged as a major evolution in the treatment of immune-mediated diseases, infections like pulmonary, extra pulmonary and disseminated TB have been reported following therapy with anti TNF agents.[2],[3]

Wang et al., showed that pooled odds ratio of developing TB was significantly higher in infliximab group in patients with Rheumatoid arthritis (RA), IBD and AS.[6] Dixon et al., noted that risk of TB in RA patients on anti TNF therapy, was six-fold higher in those with non-white ethnicity.[7] Jung et al., found the incidence of TB with anti-TNF therapy in South Korea, was higher in patients with IBD and RA on infliximab therapy.[8] Agarwal et al., assessed the risk of TB reactivation following infliximab in Indian patients with IBD and concluded that the risk of TB is extremely high.[3] However there are no reports of ocular TB or POTB during anti TNF therapy noted in literature.

Our patient was on infliximab therapy 5 mg/kg every 3-4 monthly since 2015 and presented with retinal perivasculitis. A diagnosis of IBD related vasculitis was considered and the dose and frequency of infliximab was increased with no response. However, a review of previous fundus pictures and repeat FFA revealed primary occlusive perivasculitis with hemorrhages and CNP areas, typical of TRV.[9] Further, recent HRCT chest and abdomen were suggestive of TB infection. The repeat QTB was positive, with a prior negative report, suggestive of an immunological evidence of TB infection. CD4 counts, were low, suggestive of an immune-compromised state and a risk for TB. Based on these findings and classification of intraocular tuberculosis by Gupta et al., a diagnosis of POTB with TRV was made.[10] In consultation with the treating pulmonologist and rheumatologist, we advised a course of ATT and steroid therapy with temporary withdrawal of anti TNF agents, which resulted in a complete resolution of TRV. Krishnan VS et al., reported a similar case of pleural TB in a patient with AS after initiation of infliximab therapy in spite of prior negative TB screening.[2]

  Conclusion Top

Clinicians should be aware of potential side effects of anti-TNF agents and closely monitor the ocular and systemic status of these patients, especially in a TB endemic country, where immunological and radiological tests for TB, could be repeated when there is the slightest suspicion.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

LaMattina KC, Goldstein DA. Adalimumab for the treatment of uveitis. Expert Rev Clin Immunol 2017;13:181-8.  Back to cited text no. 1
Krishnan VS, Madhyastha S, Ramamoorthi K, Acharya RV, Gopalaswamy V. Pleural tuberculosis following infliximab therapy for ankylosing spondylitis. J Pharmacol Pharmacother 2017;8:41-3.  Back to cited text no. 2
Agarwal A, Kedia S, Jain S, Gupta V, Bopanna S, Yadav DP, et al. High risk of tuberculosis during infliximab therapy despite tuberculosis screening in inflammatory bowel disease patients in India. Intest Res 2018;16:588-98.  Back to cited text no. 3
Connor V. Anti-TNF therapies: A comprehensive analysis of adverse effects associated with immunosuppression. Rheumatol Int 2011;31:327-37.  Back to cited text no. 4
Mootoo A, Stylianou E, Arias MA, Reljic R. TNF-alpha in tuberculosis: A cytokine with a split personality. Inflamm Allergy Drug Targets 2009;8:53-62.  Back to cited text no. 5
Wang Q, Wen Z, Cao Q. Risk of tuberculosis during infliximab therapy for inflammatory bowel disease, rheumatoid arthritis, and spondyloarthropathy: A meta-analysis. Exp Ther Med 2016;12:1693-704.  Back to cited text no. 6
Dixon WG, Hyrich KL, Watson KD, Lunt M, Galloway J, Ustianowski A; B S R B R Control Centre Consortium; D P M Symmons, BSR Biologics Register. Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: Results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis 2010;69:522-8.  Back to cited text no. 7
Jung SM, Ju JH, Park MS, Kwok SK, Park KS, Kim HY, et al. Risk of tuberculosis in patients treated with anti-tumor necrosis factor therapy: A nationwide study in South Korea, a country with an intermediate tuberculosis burden. Int J Rheum Dis 2015;18:323-30.  Back to cited text no. 8
Testi I, Agrawal R, Mehta S, Basu S, Nguyen Q, Pavesio C, et al. Ocular tuberculosis: Where are we today? Indian J Ophthalmol 2020;68:1808-17.  Back to cited text no. 9
[PUBMED]  [Full text]  
Gupta A, Sharma A, Bansal R, Sharma K. Classification of intraocular tuberculosis. Ocul Immunol Inflamm 2015;23:7-13.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]


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