An unusual presentation of intraocular tuberculosis in a monocular patient: clinicopathological correlation
- Kanika Aggarwal†1,
- Aniruddha Agarwal†1,
- Shobha Sehgal2,
- Suryaprakash Sharma1,
- Nirbhai Singh1,
- Kusum Sharma3,
- Ramanuj Samanta1,
- Alessandro Invernizzi4,
- Aman Sharma5 and
- Vishali Gupta1Email author
© The Author(s). 2016
Received: 13 October 2016
Accepted: 23 November 2016
Published: 25 November 2016
Lack of uniform diagnostic criteria often poses a challenge in the diagnosis and management of tubercular uveitis. The index case describes an unusual presentation of tubercular panuveitis initially misdiagnosed as sympathetic ophthalmia, where the appropriate diagnosis was made using various imaging and laboratory investigations.
A 52-year-old Indian woman underwent multimodal imaging, extensive clinical and laboratory work-up, and analysis of microbiological and histopathological specimens. At presentation, her best-corrected visual acuity (BCVA) was 20/30 in OD and no perception of light in OS. Ocular examination revealed multiple grayish-yellow choroiditis lesions resembling Dalen-Fuch’s nodules, vitritis, and disc edema. Diagnosis of sympathetic ophthalmia was made and patient treated with intravenous and oral corticosteroids and immunosuppressive therapy. After an initial favorable response, the lesions progressively increased with worsening of vitritis. Due to worsening of chorioretinal lesions which were atypical for sympathetic ophthalmia, further investigations were performed that revealed positive tuberculin skin test and contrast-enhanced computerized tomography chest showed calcified mediastinal lymph nodes. Enucleation of OS confirmed acid-fast bacilli on Ziehl-Neelsen staining, tubercular granulomas on histopathology, and positive polymerase chain reaction. Anti-tubercular therapy and oral steroids were started with good healing response.
Tubercular uveitis may have protean clinical manifestations. Thorough clinical evaluation and molecular/histopathological evaluation helps in establishing the diagnosis and the institution of appropriate therapy.
KeywordsIntraocular tuberculosis Enhanced depth imaging optical coherence tomography Mycobacteria Histopathology Dalen Fuchs spots Autofluorescence Enucleation
Intraocular tuberculosis (IOTB) is a form of extrapulmonary TB and has been reported to be the most common etiology of infectious uveitis in TB-endemic regions [1–3]. It can present with protean clinical manifestations with varied anatomic, morphological, and imaging characteristics. However, the paucibacillary nature of disease in the eye makes the confirmation of diagnosis by standard microbiological methods such as demonstration of Mycobacterium tuberculosis organisms on smear microscopy or culture from ocular samples difficult. Nucleic acid amplification techniques such as multi-targeted polymerase chain reaction (PCR) have greatly enhanced the sensitivity and specificity of detection from ocular tissues [4–6].
Accurate diagnosis of IOTB often needs a multimodal approach with a combination of a comprehensive clinical evaluation and targeted laboratory investigations. The index study describes an unusual case where the diagnosis of IOTB was confirmed with the help of microbiological and histopathological evaluation of the enucleated specimen from the fellow non-seeing eye.
Laboratory tests revealed a positive tuberculin skin test (18 × 18 mm) and QuantiFERON TB Gold® test. Contrast-enhanced computerized tomography of the chest revealed multiple calcified lesions in both the upper lobes of the lung with small mediastinal lymph nodes (not amenable to endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA). Whole body positron emission tomography (PET) scan revealed fluorodeoxyglucose (FDG) avid subcentimetric mediastinal lymph nodes and FDG avid patchy consolidatory changes in both lung upper lobes likely to be post-granulomatous changes. An FDG avid lesion was present in the left orbit.
The index case presented as a diagnostic challenge since granulomatous panuveitis in a monocular patient with a history of trauma in the fellow eye was highly suggestive of sympathetic ophthamia. Our patient demonstrated interval improvement in vitritis and optic disc edema, and the choroidal lesions seemed to heal during the initial follow-up after initiation of intravenous methylprednisolone, oral corticosteroids, and azathioprine (Fig. 2a). However, as the patient was on continued immunosupression, her choroidal lesions increased in number and size, and the disease continued to progress. Thus, at this stage, an alternate diagnosis was considered. Multimodal imaging analyses were performed which revealed presence of distinct hypo-autofluorescent lesions with hyper-autofluorescent borders in the retinal periphery (Fig. 2e, f). The appearance of these lesions was not a characteristic of sympathetic ophthalmia . Moreover, careful analysis of EDI-OCT scans passing through these peripheral choroidal lesions revealed presence of multiple, large choroidal granulomas which were different from those observed in sympathetic ophthalmia (Fig. 3) . Since the fellow eye was non-seeing, the patient was given an option of enucleation to confirm an alternate diagnosis and conclusively rule out sympathetic ophthalmia.
An important learning point in our case was the detection of choroidal granulomas on EDI-OCT and identification of FAF lesions (Figs. 2 and 3). We hypothesize that immunosuppression in our patient led to development of a IOTB with multifocal disease in the form of multiple choroidal granulomas. Such a form of IOTB is rarely reported in literature. Due to the paucibacillary nature of the disease in a majority of the patients, nucleic acid amplication techniques are more commonly applied to confirm the diagnosis of IOTB. Only a handful of cases with histopathological detection of acid-fast bacilli from choroidal biopsies have been reported in the literature [9–11]. However, these were patients with large choroidal masses, subretinal abscesses, or those undergoing an unrelated retinal surgery. Thus, previous reports have highlighted the paucity of mycobacteria on histology in eyes with ocular TB . The index case is unique because in our patient, the diagnosis of IOTB was possible from the histopathological analysis of the fellow non-seeing eye, and comprehensive multimodal imaging analysis of the affected eye. In addition, PCR analysis of the aspirate from the enucleated globe agreed with the histopathology, imaging, and laboratory evaluation (Fig. 4).
Thus, the diagnosis of IOTB is often challenging due to its protean clinical manifestations. However, once the diagnosis is confirmed, treatment with ATT and corticosteroids may result in resolution of the choroiditis lesions with progressive hypo-autofluorescence on FAF imaging. The limitations of our case were the non-availability of indocyanine green angiography to detect the choroidal granulomas. However, choroidal granulomas can be well demonstrated on EDI-OCT. [12, 13] Our patient demonstrated adequate response to ATT with gradual healing response of the choroiditis lesions, vitritis, and optic disc edema (Fig. 5).
The index case report demonstrates challenges encountered in diagnosing and managing IOTB. Our patient presented with granulomatous panuveitis that was initially misdiagnosed as sympathetic ophthalmia. Techniques such as histopathology, multimodal imaging including FAF and EDI-OCT, as well as PCR analysis greatly aid in arriving at the accurate diagnosis in such challenging cases.
VG, KA, and AA conceived the manuscript, performed the literature review, and participated in the clinical management of the case. RS and AS participated in the clinical management of the case, acquisition of data, and drafting the manuscript. SS, SS, NS, and KS participated in the laboratory work-up, acquisition of data and drafting the manuscript. AI participated in drafting the manuscript. VG provided the concept and design, was involved in the management of the case, provided intellectual content, and revised the manuscript. All authors read and approved the final manuscript.
All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interests (such as honoraria; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interests; and expert testimony or patent-licensing arrangements), or non-financial interests (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript. The authors declare that they have no competing interests.
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The consent to publish has been obtained from the participant to report individual patient data.
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