From the Department of Retina, Ulucanlar Eye Education and Research Hospital, Ankara, Turkey.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Yasemin Ozdamar, MD, Fazilet mah. Açikel sok. 17/6, Postcode: 06110, Diskapi, Ankara, Turkey. E-mail: firstname.lastname@example.org
Ocular tuberculosis is a complex clinical problem owing to various manifestations at presentation and difficulty in diagnosis. Ocular tuberculosis without systemic manifestations has rarely been seen and its incidence has varied widely across time, patient populations, and geography.1–5 Tuberculosis can affect any structure in the eye and typically presents as a granulomatous process. Uveitis is the most common manifestation of ocular tuberculosis, which can present as anterior uveitis, posterior uveitis, and panuveitis. The diagnosis of ocular tuberculosis from clinical and ocular findings can be difficult, and diagnostic criteria for ocular tuberculosis include exclusion of other known etiologies of uveitis, systemic investigations, positive response to anti-tuberculosis treatment, and evidence of Mycobacterium tuberculosis in ocular tissues; however, these investigations cannot be performed routinely. Currently, newer diagnostic methods have been improved for the diagnosis of tuberculosis. The QuantiFERON-tuberculosis gold test is a new assay method that measures the in vitro interferon gamma response of T cells to M. tuberculosis.1,2,4,6
We describe a patient who was diagnosed as having ocular tuberculosis with posterior segment involvement using the QuantiFERON-tuberculosis gold test.
A 14-year-old girl presented to our clinic complaining of progressively decreasing vision for 2 months in the right eye. Her visual acuity was hand motions in the right eye and 20/20 in the left eye. She had no clinically significant systemic or ocular history. Anterior segment findings and intraocular pressures were normal in both eyes. Dilated fundus examination showed 2++ vitreous cells, thick perivascular exudates, and intraretinal exudations in the temporal quadrant in the right eye (Fig. 1). A focal patch of subretinal exudation in the inferotemporal quadrant and an epiretinal membrane formation extending from the optic disc and macular area to the temporal retinal region were also observed in the right eye (Figs. 2 and 3). A widespread peripheral retinal ischemia in the temporal quadrant was a prominent finding in fluorescein angiography of the right eye (Fig. 4). Detailed fundus examination and fluorescein angiography were normal in the left eye. None of these findings were specific for any type of uveitis.
Figure 1. Thick Perivascular Exudates and Intraretinal Exudations in the Temporal Quadrant of the Right Eye.
Figure 2. A Focal Patch of Subretinal Exudation in the Inferotemporal Quadrant of the Right Eye.
Figure 3. An Epiretinal Membrane Formation Extending from the Optic Disc and Macular Area to the Temporal Retinal Region in the Right Eye.
Figure 4. Peripheral Retinal Ischemia in the Temporal Quadrant of the Right Eye.
She had neither a history of tuberculosis nor contact with a patient who had tuberculosis. She had only Bacillus Calmette-Guerin (BCG) vaccination as part of routine health regulation. Complete blood cell counts, chest radiograph, serum angiotensin-converting enzyme assay, anti-nuclear antibodies, syphilis serology, and serum lysozyme levels were unremarkable, whereas the Tuberculin Skin Test (TST) result was positive at 15 mm. General examination was performed by an internist and pulmonologist and no other systemic involvement was detected. The QuantiFERON-tuberculosis gold test was performed and the result was positive at 25.9 IU/mL (normal level: < 1 IU/mL). According to these findings, the diagnosis of ocular tuberculosis was made. The patient received systemic anti-tuberculosis therapy (isoniazid, rifampicin, ethambutol, and pyrazinamide) as recommended by the pulmonologist and posterior sub-Tenon triamcinolone (40 mg/mL) was injected into the right eye. Two months after treatment, visual acuity improved to counting fingers at 3 meters and vitreous cells decreased.
Posterior segment involvement is common in patients with ocular tuberculosis. The retina and choroid are frequently involved. Posterior segment manifestations can be seen as choroidal tubercules, choroidal granulomas or subretinal abscess, endophthalmitis, neuroretinitis, and vasculitis.1–4
Ocular tuberculosis results from the hematogenous/lymphomatous seeding from the primary complex or from the reactivation of dormant lesions, where the bacilli may remain latent for years before reactivation. Additionally, immune-mediated ocular tuberculosis can occur due to hypersensitivity to M. tuberculosis antigens from a distant focus such as lungs. The absence of pulmonary tuberculosis does not preclude ocular tuberculosis, because approximately 60% of patients with extrapulmonary involvement have no signs of pulmonary tuberculosis.1–5
Classically, the diagnosis of ocular tuberculosis has mainly depended on the clinical appearance of the eye, if present, evidence of tuberculosis elsewhere in the body, the TST, histologic evidence of tuberculosis, recognition of the bacilli themselves, or response to anti-tubercular therapy. The TST, practical application, has been widely used for many years for the diagnosis of tuberculosis. The interpretation of the TST can be difficult and it has many drawbacks, including a high rate of false-positive and false-negative results, requiring a second visit to read results, and subjectivity and interpersonal variability among health care professionals. Also, the TST has the potential disadvantage of boosting an anamnestic response with successive tests. The laboratory diagnosis of tuberculosis is largely based on direct microscopy, isolation, and culture for mycobacterium; all of these investigations cannot usually be performed, they are time-consuming, their interpretation can be difficult, and some of them are invasive, especially in cases of extrapulmonary tuberculosis.1–4,7
Recently, interferon gamma release assay tests have been developed to aid in the diagnosis of tuberculosis. The QuantiFERON-tuberculosis gold test is one of the new assay methods that measures the release of interferon gamma after stimulation in vitro by M. tuberculosis. The QuantiFERON-tuberculosis gold test specifically detects responses of interferon gamma released by the patient’s sensitized T cells to two antigens (early secretory antigenic target-6 and culture filtrate protein-10). These antigens are found in M. tuberculosis but not in BCG or most atypical mycobacteria.
In contrast to the TST, the QuantiFERON-tuberculosis gold test is an objective in vitro laboratory-based assay that is not affected by previous BCG vaccination and a result can be obtained within 24 hours without a second visit. The assay does not expose the patient to antigen and therefore does not lead to the boosting response that affects repeated TST results.1,2,4,6 The QuantiFERON-tuberculosis gold test is more specific than the TST in identifying infections by M. tuberculosis, especially in immunocompromised and pediatric patients. In addition, the QuantiFERON-tuberculosis gold test has advantages such as convenience of administration and lack of subjective interpretation, and therefore it has more reproducible results. The specificity and sensitivity of the QuantiFERON-tuberculosis gold test are 89% to 100% and 72% to 90%, respectively.8,9
The clinical appearance of our case was suggestive of ocular tuberculosis, but none of the ophthalmic findings were pathognomic for the diagnosis of tuberculosis. She had no active focus of tuberculosis anywhere in the body. Our patient had tuberculin skin reaction at 15 mm. The presence of tuberculosis infection was supported by the QuantiFERON-tuberculosis gold test after ruling out other etiologies. A few reports are available in the literature regarding the use of the QuantiFERON-tuberculosis gold test in the determination of ocular tuberculosis and uveitis.10–13
There are results regarding the use of various drug regimens for the treatment of tuberculosis in the literature. The use of steroid concomitant with multidrug anti-tuberculosis chemotherapy may limit damage to ocular tissues from delayed type of hypersensitivity.1–4,14 Our patient was locally treated with posterior sub-Tenon triamcinolone injection and covered with systemic treatment.
The diagnosis of ocular tuberculosis without systemic involvement can be difficult and the QuantiFERON-tuberculosis gold test has added a valuable alternative for the diagnosis of ocular tuberculosis and initiating appropriate therapy.
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