Int Ophthalmol (2015) 35:445–450 DOI 10.1007/s10792-015-0061-y
CASE REPORT
Spectral domain optical coherence tomography imaging of tubercular chorioretinitis and intraretinal granuloma. Intraretinal tuberculosis: a case report Maria P. Pirraglia • Paolo Tortorella • Alessandro Abbouda • Fabrizio Toccaceli Maurizio La Cava
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Received: 12 October 2014 / Accepted: 16 March 2015 / Published online: 27 March 2015 Ó Springer Science+Business Media Dordrecht 2015
Abstract The aim of this study is to report the clinical and spectral domain optical coherence tomography (SD-OCT) findings in a patient suffering from ulcerative colitis with bilateral tubercular chorioretinitis and intraretinal granuloma regressed with systemic antitubercular therapy (ATT). This study is a case report of a 33-year-old Bangladeshi male with ulcerative colitis treated with oral corticosteroids and azathioprine who was referred to our department with a diagnosis of central serous chorioretinopathy. Serological tests, the Mantoux skin test, complete ophthalmologic examination, ocular fundus photography, fundus fluorescein angiography, and SD-OCT scans were performed. The ophthalmological inflammatory pattern and serological investigations provided an early diagnosis of ocular tuberculosis. Systemic ATT led to significant improvement and resolution of the ocular inflammation. SD-OCT was a useful noncontact imaging technique in the follow-up of tubercular choroiditis. The excellent response to systemic ATT confirmed the clinical diagnosis. This is an unusual case of tubercular chorioretinitis with M. P. Pirraglia P. Tortorella (&) A. Abbouda Diagnostic Chorioretinal Service, Department of Ophthalmology, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy e-mail:
[email protected] F. Toccaceli M. La Cava Departement of Clinical Medicine, Sapienza University of Rome, Rome, Italy
intraretinal granuloma and is the first such SD-OCT description reported in the ophthalmological literature. Keywords Antitubercular treatment Chorioretinitis Intraretinal granuloma Ocular tuberculosis Spectral domain optical coherence tomography (SD-OCT)
Introduction In recent years, tuberculosis (TB) has re-emerged as a serious health problem in the US and European countries. The World Health Organization (WHO) estimated that TB affects one-third of the global population and is considered a global emergency [1]. An increased incidence of ocular TB was associated with the TB recurrence, which was considered to be uncommon and difficult to diagnose [2]. TB has a range of ocular manifestations and may therefore mimic other ocular inflammatory diseases. The choroid is the most commonly affected structure in ocular TB [2, 3]. Choroidal involvement can have three different clinical presentations: choroidal tuberculoma, multifocal choroiditis, and serpiginous-like choroiditis [2]. A definitive diagnosis of ocular TB is established by the combination of clinical ocular inflammatory signs and the demonstration of the mycobacterium
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using culture or DNA amplification of ocular samples. Presumptive diagnosis can be proved by the combination of the ophthalmological inflammatory pattern of ocular TB and confirmatory tests for TB infection [4]. Moreover, ocular TB may occur in patients with no systemic disease. Therefore, most cases of ocular TB remain undiagnosed because of the absence of ocular biopsies [2]. Spectral domain optical coherence tomography (SDOCT) enables high-resolution visualisation of the retina and choroid [3]. The ability of SD-OCT to image tissue morphology in situ and in real-time is termed ‘‘optical biopsy’’ [5]. Therefore, high-resolution, cross-sectional OCT scans can be applied to the detailed analysis and evaluation of choroidal and retinal lesions. We report a rare tubercular chorioretinitis and intraretinal granuloma pattern using singular SD-OCT imaging. A definitive diagnosis of ocular TB was confirmed by the significant response to systemic antitubercular therapy (ATT) supported by SD-OCT.
Materials and methods A 33-year-old Bangladeshi male with ulcerative colitis treated with oral corticosteroids and azathioprine was referred to our department with a potential diagnosis of bilateral central serous chorioretinopathy. The purified protein derivative skin test and the QuantiFERON–TBGOLD test yielded negative results prior to immunosuppressive treatment. Complete ophthalmologic examination included best-corrected visual acuity (BCVA) using Snellen charts, intraocular pressure (IOP) assessment using the Goldmann applanation tonometer, slit-lamp biomicroscopy, and fundus examination using a bilateral indirect ophthalmoscope. Ocular fundus photography and fundus fluorescein angiography (FFA) (FF450 Plus Fundus Camera, Carl Zeiss Meditec, Germany) and SD-OCT (Heidelberg Engineering, Heidelberg, Germany) were performed during the initial and follow-up visits. The patient underwent routine laboratory examinations (full blood count, erythrocyte sedimentation rate, C-reactive protein, serum angiotensin converting enzyme, and serological tests for syphilis (venereal disease research laboratory) and human immunodeficiency virus). In addition, the patient underwent a chest X-ray, a TB skin test, and the QuantiFERON– TBGOLD test.
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Results The patient came to our department complaining of blurred vision in both eyes. The BCVA was 8/10 and 6/10 in the right and left eyes, respectively. Using previously published test procedures [6, 7], we found that the anterior chamber flare was zero in both eyes, and the binocular indirect ophthalmoscopic scores were also zero (no vitreous haze). On examination, the IOP was 14 mmHg. Fundoscopy in the right eye showed macular oedema (Fig. 1a). In the left eye, one yellowish-white elevated subretinal lesion with distinct borders measuring overall half of the optic disc diameter surrounded by macular oedema was found at the posterior pole (Fig. 1b). FFA showed hyperfluorescence in the right eye in the early arteriovenous phase, with progressive staining of one lesion, while staining of two lesions was found in the left eye in the late phase (Fig. 2). In the right eye, SD-OCT scans revealed wide, serous, neurosensory retinal detachment involving the fovea. In the left eye, SD-OCT imaging revealed a single rounded hyperreflective intraretinal lesion in the neurosensory retina, featuring a partially hyporeflective core surrounded by a hyporeflective area. Neurosensory retinal detachment was evident around this lesion. In the same region, we noted proliferating retinal pigment epithelium (RPE) that was granular in appearance (the hyperreflective spot) in the outer retinal layers. The RPE/choriocapillaris complex under the retinal lesion exhibited inhomogeneous localised thickening. The choroidal appearance was modified by a blocking effect attributable to the choroidal granuloma (Fig. 3a). Temporally to the fovea, EPR detachment was found (Fig. 3b). No dome-shaped retinal elevation specific to granuloma was noted [3]. Systemic therapy using oral corticosteroids and azathioprine was ceased. The chest X-ray was negative, whereas the TB skin test showed a positive reaction of 16 mm on the second day of the test. A positive QuantiFERON test confirmed the presumed ocular TB diagnosis. The four-drug regimen (quadritherapy) consisted of daily 300-mg isoniazid, 600-mg rifampicin, 800-mg ethambutol, and 1500-mg pyrazinamide doses for 2 months. This was followed by isoniazid and rifampicin alone for 4 months, all according to the guidelines for the therapy of extrapulmonary TB
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Fig. 1 a Fundus photograph showing in the right eye macular oedema at the posterior pole. b In the left eye, a retinal granuloma at the posterior pole. One yellowish-white elevated subretinal lesion with surrounding retinal fluid is observed
The patient preferred to avoid further FFA control examination, and the good response to therapy, highlighted by SD-OCT imaging, permitted us to comply with the request. A marked decrease in chorioretinitis activity was observed, as indicated by a total remission of the retinal lesions. Ocular inflammation responded well to ATT without corticosteroid use, confirming the diagnosis of ocular TB.
Discussion
Fig. 2 Fundus fluorescein angiography of the left eye shows staining of two lesions in the late phase (black arrow)
of the WHO and Centres for Disease Control and Prevention [2]. No drug toxicity or side effects were observed during the follow-up period. The BCVA after 6 months was 10/10 in both eyes. Fundus examination demonstrated bilateral macular oedema resolution (Fig. 4a, b). In SD-OCT, total resolution of subretinal fluid in both eyes was found. Altered reflectivity of the RPE and choriocapillaris was noted in the regions of resolved retinal lesions. In the left eye, the RPE/choriocapillaris complex under the retinal lesion shows inhomogeneous localised thickening superiorly to the fovea (Fig. 5).
TB infection is again of great interest because of its increased incidence. Human immunodeficiency, mostly virus or therapy induced, is an important risk factor for the spread of TB infection. Ocular TB should always be considered in choroidal inflammatory diseases because of its wide presentation spectrum. There is an absence of evidence for pulmonary TB in up to 60 % of patients with extrapulmonary TB, leading to a difficult and delayed diagnosis of the infection. The most affected initial site of ocular TB is the choroid, with focal, multifocal, or serpiginous-like choroiditis, solitary choroidal tuberculoma, or multiple choroidal tubercles [2]. The SD-OCT pattern for choroidal TB has been described previously [3, 4]. Salman et al. described the characteristic but not the pathognomonic features of tuberculous choroidal granulomas [3]. They found a
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Fig. 3 a An SD-OCT vertical scan of the left eye taken through the area of the granuloma prior to initiation of therapy reveals single rounded hyperreflective intraretinal lesion apparently divided into two segments by a posterior shadow effect of the arteriole. A partial hyporeflective core (asterisk), surrounded by oedema, with distortion of the normal retinal architecture, is apparent. Serous retinal detachment (SRD) around the lesion involves the fovea, and proliferating retinal pigment epithelium (RPE) exhibiting granularity (a hyperreflective spot) is apparent
in the outer retinal layers (white arrows). The RPE/choriocapillaris complex under the retinal lesion exhibits inhomogeneous localised thickening (white arrowheads). The choroidal appearance was modified by a blocking effect attributable to the choroidal granuloma. b SD-OCT cross-sectional macular B-scan of left eye demonstrate the rounded hyperreflective intraretinal lesion (asterisk) surrounded by SRD (white arrow). RPE detachment is noted (white arrowhead)
localised area of adhesion between the RPE– choriocapillaris layer and the overlying neurosensory retina, termed the ‘‘contact sign’’, surrounded by an area of exudative retinal detachment. In our patient, there were no classical ophthalmoscopy or SD-OCT features of tuberculous choroiditis, making it more difficult to diagnose. The SD-OCT imaging showed a singular pattern of TB chorioretinitis with intraretinal granuloma, never described previously. Fundus ophthalmoscopy indicated that the lesion could be a choroidal tuberculoma or a subretinal abscess [8–10]. As both haemorrhage and a cellular vitreous reaction were absent, a subretinal abscess was excluded. In addition, the SD-OCT scans did not reveal dome-shaped retinal elevation [3].
Basu et al. histologically described isolated retinal TB in the non-enucleated eye [11]. Retinal TB generally occurs because of choroidal extension and includes granulomas and retinal vasculitis. The presence of Mycobacterium tuberculosis in the retina can activate retinal microglia and blood-derived macrophages, inducing intraretinal granuloma [11]. Saini et al. described a microscopic examination of tubercular granulomas in the retina, where the tubercles consisted of a central caseous necrosis surrounded by epithelioid cells, lymphocytes, and giant cells [12]. In the present case, SD-OCT imaging demonstrated retinal granuloma. Granuloma with a portion being abscess could be indicated by the hyporeflective core within the hyperreflective rounded intraretinal lesion
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Fig. 4 a, b Fundus photography of right eye (a) and left eye (b) showing the complete resolution of the lesions with a bilateral mottled hypoepithelial areas after 6 months with systemic antitubercular therapy
Fig. 5 SD-OCT imaging of left eye at the end of therapy shows a persistent inhomogeneous localised thickening of the RPE/choriocapillaris complex (white arrowheads)
representing the inflammatory response. This lesion was surrounded by an area of exudative retinal detachment, indicating blood–retinal barrier breakdown. Therefore, activated microglia as well as bloodderived macrophages and lymphocytes can induce a granuloma in the neurosensory retina. In our patient, FFA showed no significant difference in permeability between the hyporeflective core and hyperreflective portion of the inflammatory infiltrate. SD-OCT also demonstrated chorioretinitis regression, neurosensory detachment resolution, and healing of the intraretinal granuloma. The use of SD-OCT allowed us to confirm healing without further FFA. The SD-OCT scans demonstrated choroidal inflammatory infiltration, which causes compression of the
choroidal vessels in the choriocapillaris. A reduction in the hyperreflective dots, corresponding to the crosssectional views of parallel-lying pericapillary arterioles and venules, described previously in the literature [5], was observed. This feature decreased following ATT. The results of SD-OCT indicate that it may be an excellent diagnostic tool in the management of ocular TB-associated retinal lesions. Furthermore, SD-OCT could play a role in the follow-up of tuberculous retinal granulomas, supporting more rapid diagnosis and treatment of ocular TB. Conflict of Interest conflict of interest.
The authors declare that they have no
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