Tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment: a case report.

BACKGROUND: Ocular tuberculosis is a relatively rare extrapulmonary manifestation of tuberculosis. This vision-threatening disease is extremely challenging to diagnose, particularly because it can mimic other diseases. We report a case of tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment. CASE REPORT: A 52-year-old female presented with bullous retinal detachment in her left eye, and ultrasound biomicroscopy (UBM) verified the presence of a lesion with ciliary body granulomatous inflammation. The T-SPOT was positive, and the purified protein derivative (PPD) test was strongly positive (diameter of 20 mm). Following the administration of oral anti-tuberculosis regimen combined with prednisone, the retina gradually became reattached, the ciliary body granuloma became significantly reduced in size, and the visual acuity of the patient noticeably improved. CONCLUSIONS: Tuberculous ciliary body granulomas can cause bullous exudative retinal detachment and can be diagnosed with UBM. Early and full-course anti-tuberculosis treatment (ATT) combined with corticosteroid therapy can improve the patient prognosis.

Correlation of angiogenic growth factors and inflammatory cytokines with the clinical phenotype of ocular tuberculosis.

PURPOSE: To determine the correlation of angiogenic growth factors and inflammatory cytokines with the clinical phenotype of ocular tuberculosis (OTB). METHODS: Vitreous fluid was analysed for cytokines in patients with OTB and non-OTB uveitis using multiplex fluorescent bead-based flow cytometric assay. The clinical phenotypes were recorded and correlated with vitreous biomarkers. RESULTS: Vitreous humour from OTB patients had elevated levels of interleukin-10 (IL-10), IL-17-A, interferon-gamma (IFN-γ), and tumour necrosis factor-alpha (TNF-α). Angiopoietin (Ang-2) levels were higher in the panuveitis phenotype. OTB posterior uveitis phenotype had relatively higher vascular endothelial growth factor (VEGF) levels and lower fibroblast growth factor (FGF) levels. Additionally, eyes with choroiditis and vasculitis had elevated levels of VEGF and Ang-2 with FGF downregulation. Both IFN-γ and IL-10 were upregulated in the choroiditis phenotype of OTB. CONCLUSION: Angiogenic growth factors and inflammatory cytokines were altered in the vitreous humour of OTB patients. IFN-γ, VEGF, and IL-10 levels are increased in choroiditis and vasculitis phenotypes. Receiver operating characteristic (ROC) curve analysis further emphasized the importance of the IFN-γ assay in the diagnosis of OTB.

Could different aqueous humor and plasma cytokine profiles help differentiate between ocular sarcoidosis and ocular tuberculosis?

OBJECTIVE AND DESIGN: A cross-sectional single-center study was conducted to assess cytokine levels in aqueous humor (AH) and plasma of three different uveitis entities: definite ocular sarcoidosis (OS), definite OS associated with QuantiFERON®-TB Gold test positivity (Q + OS) and presumed tubercular uveitis (TBU). SUBJECTS: Thirty-two patients (15 OS, 5 Q + OS, 12 TBU) were included. METHODS: Quantification of selected cytokines was performed on blood and AH samples collected before starting any treatment. Statistical analysis was conducted using the Kruskal-Wallis test, the Mann-Whitney or Fisher test and the Principal Component Analysis (PCA). RESULTS: IL-6, IL-8 and IP-10 levels were higher in AH samples than in peripheral blood. In AH samples, BLC, IL-8 and IP-10 were significantly higher in definite OS than in presumptive TBU. There were no statistically significant differences in terms of cytokine levels between Q + OS and presumptive TBU. PCA showed a similar cytokine pattern in the latter two groups (IFNγ, IL-15, IL-2, IP-10, MIG), while the prevalent expression of BLC, IL-10 and MIP-3 α was seen in definite OS. CONCLUSIONS: The different AH and plasma cytokine profiles observed in OS compared to Q + OS and TBU may help to differentiate OS from TBU in overlapping clinical phenotypes of granulomatous uveitis (Q + OS).

Dysregulated expression of microRNAs in aqueous humor from intraocular tuberculosis patients.

BACKGROUND: Systemic Mycobacterium tuberculosis (Mtb) infection alters microRNA's expression that controls cellular processes and modulates host defense mechanisms. However, the role of miRNAs in intraocular tuberculosis (IOTB) remains unknown. Therefore, this study aims to identify dysregulated miRNAs in the aqueous humor (AH) of patients with IOTB. METHODS: AH from intraocular tuberculosis patients (n = 2) and cataract controls (n = 2) were used for small RNA deep sequencing using HiSeq Illumina sequencing platform. Differentially expressed miRNAs and their targets were identified by the bioinformatics approach, and their regulatory functions were predicted by pathway enrichment analysis. The expression of selected miRNAs and their binding targets were further validated by real-time quantitative PCR (RT-qPCR). RESULTS: In total, we identified 56 differentially expressed miRNAs in the AH of intraocular tuberculosis (IOTB) patients compared to controls. We selected four significantly dysregulated miRNAs (miR-423-5p, miR-328-3p, miR-21-5p, and miR-16-5p) based on the RT-qPCR validation and predicted their gene targets. We developed a miRNA-targets regulatory network by combining pathways of interest and genes associated with TB. We identified that these four miRNAs might play an important role in IOTB pathogenesis via tuberculosis-associated pathways; PI3K-Akt signaling, autophagy and MAPK pathway. CONCLUSIONS: For the first time, this study identifies the dysregulation of four miRNAs in the AH of IOTB patients using the ultra-low input small-RNA sequencing approach. Further target prediction and validation identify the role of these miRNAs in tuberculosis pathogenesis via tuberculosis-related pathways. This study identifies miRNAs as potentially ideal biomarkers in the aqueous humor of IOTB patients.

Clinical features and long-term treatment outcomes in choroidal tuberculoma.

PURPOSE: To investigate the clinical features and treatment outcomes of patients with choroidal tuberculoma. METHODS: In this retrospective, observational case series, the medical records of five patients with choroidal tuberculoma who were followed up at a university hospital for at least 6 months were analyzed. RESULTS: Of five patients, one was male and four were female. The overall mean age was 38.0 ± 9.4 years (mean follow-up: 41.2 ± 33.8 months). Tuberculin skin test was performed in three patients, and it was positive in two of them. Interferon-gamma assay was performed in two patients and was positive in all two. Three patients had systemic tuberculosis involving the lung or other organs. Five patients were treated with antitubercular therapy for a period of 9.6 ± 8.6 months. Systemic corticosteroid treatment was performed in 3 patients, with a period of 3.5 ± 0.7 months. One patient with a recurrent vascularized tuberculoma was successfully treated with single intravitreal bevacizumab injection. CONCLUSION: Choroidal tuberculoma can develop without evidence of systemic tuberculosis and can recur despite antitubercular treatment. High index of suspicion is important in early detection, and management of choroidal tuberculoma. In cases of suspected choroidal tuberculoma, positive results on immunological tests would be sufficient to initiate antitubercular therapy even if radiological evidence of systemic tuberculosis is not found. Antitubercular therapy combined with systemic corticosteroids provided favorable results. Intravitreal injection of anti-vascular endothelial growth factor may be considered for highly vascularized choroidal tuberculoma.

Histological Diagnosis of Ocular and Periocular Tuberculosis 1945 - 2020. / Histologisch diagnostizierte okuläre und periokuläre Tuberkulose von 1945 bis 2020.

BACKGROUND: Ocular tuberculosis is a rare but important differential diagnosis for inflammatory conditions of all eye tissues, including the ocular surface and adnexa. Tissue diagnostics may prove challenging as some ocular tissues are difficult to biopsy and the detection of pathogens may be insensitive. We were interested in how many cases in the archive of the ophthalmopathological laboratory had been diagnosed with (peri)ocular tuberculosis since 1945. MATERIALS AND METHODS: Retrospective analysis of historical records and specimens of the ophthalmopathology laboratory of the eye department at Freiburg university hospital. Systematic re-evaluation of available slides for presence of granuloma, necrosis, giant cells, acid fast bacteria, and chronic as well as acute inflammation, plus comparison of current and historic evaluations. In addition, we describe a recent case with tuberculoma of the iris. RESULTS: There were 50,418 records archived since 1945, of which 23 specimens taken from 22 patients had been diagnosed as (peri)ocular tuberculosis. Of these, 22 (96%) were archived and available for re-interpretation. Four specimens (17%) had been excised from children. The most common tissues were enucleated eye globes (10/23, 44%), followed by the lacrimal sac (5/23, 22%) and conjunctiva (2/23, 9%). The most frequent histopathological findings were granulomas (23/23, 100%), chronic inflammation (22/23, 96%), giant cells (21/23, 91%), and necrosis (14/23, 61%). An acute inflammatory response was found in 4/23 specimens (17%). Ziehl-Neelsen stains for acid-fast bacteria had been performed in five cases, of which three were positive (60%). The greatest discrepancy between current and historical findings related to the presence of necrosis (59% consensus). In other findings, the consensus was high (78 - 96%). In a recent case of a patient with wasting syndrome attributed to lymphoma, histopathological workup of an iris tumour led to the diagnosis of tuberculosis. CONCLUSION: Ocular tuberculosis is a rare but important histopathological differential diagnosis. In the available specimens, the classic finding of necrotizing inflammation was rarest and showed least consensus on histological re-evaluation. Other typical findings, such as giant cells and a predominantly lymphocytic infiltrate, are sometimes not found even with proven presence of Mycobacterium tuberculosis. They should not be considered essential in cases where there is strong clinical suspicion.

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 1: Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis.

TOPIC: An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. CLINICAL RELEVANCE: The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. METHODS: An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. RESULTS: Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. DISCUSSION: Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis.

TOPIC: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). CLINICAL RELEVANCE: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. METHODS: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. RESULTS: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. DISCUSSION: The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.

Ocular tuberculosis in a calf.

BACKGROUND: Bovine tuberculosis is a chronic inflammatory disease that causes granuloma formation mainly in retropharyngeal, tracheobronchial, mediastinal lymph nodes and lungs of bovines. The presence of these lesions in other tissues such as the eyeball is very rare and difficult to diagnose. This study describes macroscopic and microscopic pathological findings in a calf with ocular and meningeal tuberculosis. CASE PRESENTATION: March 2019, an eight-month-old Holstein Friesian calf was identified in a dairy farm located in central Mexico with a clinical cough, anorexia, incoordination, corneal opacity and vision loss. At necropsy, pneumonia, lymphadenitis, meningitis, and granulomatous iridocyclitis were observed. The histopathological examination revealed granulomatous lesions in lung tissue, lymph nodes, meninges and eyes with the presence of acid-fast bacilli associated with Mycobacterium spp. CONCLUSION: To the best of our knowledge, this is the first report that describes macroscopic and microscopic pathological findings of ocular tuberculosis in cattle. This report highlights the importance of considering bovine tuberculosis in the differential diagnosis of corneal opacity and loss of vision in cattle.

CLINICAL PREDICTORS OF TUBERCULAR RETINAL VASCULITIS IN A HIGH-ENDEMIC COUNTRY.

PURPOSE: To determine clinical signs suggestive of tubercular etiology in retinal vasculitis. METHODS: A retrospective comparative study of patients who presented with retinal vasculitis at three tertiary care centers in India. All patients underwent detailed clinical evaluation and tailored laboratory investigations for etiological diagnosis. Tubercular etiology was diagnosed on basis on the presence of retinal periphlebitis in association with ancillary evidence of systemic tuberculosis and exclusion of nontuberculosis entities. Patients with tubercular (Group A) and nontubercular (Group B) etiology were compared for demographic characteristics, supportive diagnostic evidence, and specific ocular signs. Statistical analysis was performed at 5% confidence levels. RESULTS: Of the 114 patients diagnosed with retinal vasculitis, Group A had 69 patients (100 eyes) and Group B had 45 patients (75 eyes). Active or healed subvascular lesions (P ≤ 0.0001), focal vascular tortuosity (P ≤ 0.0001), and occlusive vasculitis (P = 0.002) were significantly more common in Group A patients than in Group B patients. All three were independent predictors of tubercular etiology on multivariate regression analysis. CONCLUSION: The presence of healed or active subvascular lesions, focal vascular tortuosity, and occlusive vasculitis could be predictive of tubercular etiology in retinal vasculitis.

LONGITUDINAL FOLLOW-UP OF TUBERCULAR SERPIGINOUS-LIKE CHOROIDITIS USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To analyze and describe serial follow-up of choriocapillaris alterations in tubercular serpiginouslike choroiditis (SLC) using optical coherence tomography angiography (OCTA) and to compare it with multimodal imaging. METHODS: In this prospective cohort study, patients with active tubercular SLC underwent OCTA using Optovue RTVue XR Avanti and other imaging techniques including enhanced-depth imaging OCT (EDI-OCT) (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany), fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. Serial imaging was performed for a total follow-up of 3 months. Choriocapillaris alterations at the site of lesions were analyzed on OCTA imaging, and their mean lesion areas were calculated. RESULTS: Twenty-six eyes (26 patients; 20 males; mean age: 32.68 ± 10.56 years) were included. Fourteen eyes had active multifocal lesions (n = 39), whereas 12 eyes had active placoid lesions (n = 12). At baseline, OCTA showed hyporeflective flow deficit lesions corresponding to the hypofluorescent lesions on indocyanine green angiography in all eyes. In the multifocal type of SLC, the mean lesion area decreased in all eyes compared with baseline, and lesions with a lesion area less than 0.1 mm2 on OCTA showed near-complete resolution with minimal choriocapillaris atrophy. In comparison, all eyes with a placoid type of SLC showed no significant reduction in the lesion area and showed extensive choriocapillaris atrophy. CONCLUSION: Optical coherence tomography angiography has the unique ability to demonstrate pathological flow impairment at the level of choriocapillaris in active tubercular SLC. Serial OCTA analysis reveals that large tubercular SLC lesions result in choriocapillaris atrophy as the lesions heal, whereas smaller multifocal lesions show resolution of choriocapillaris hypoperfusion with minimal atrophy.

Clinics of ocular tuberculosis: A review.

Ocular tuberculosis (OTB) is an extrapulmonary mycobacterial infection, which still sees variations in incidence, manifestations, diagnostic and therapeutic approaches. While the disease is gaining more recognition as a differential in ocular inflammation, it remains a difficult entity to detect and treat. Global efforts to synthesize and standardize the approach to OTB could prove useful in delivering quicker, more effective care. We summarize recent insights in appropriate nomenclature, clinical presentations, diagnostic modalities and courses of treatment.

Further evidence of the association of latent Mycobacterium tuberculosis in Eales' disease.

PURPOSE: To find out association of Eales' disease with Mycobacterium tuberculosis. METHODS: A retrospective study was done recruiting patients visiting the uvea clinic with diagnosis of Eales' disease from 2015-2019. Seventy-nine eyes of 50 patients diagnosed as Eales' disease underwent Mantoux test, QuantiFERON-TB Gold test, high resolution computed tomography (HRCT) of the chest and anterior chamber or vitreous tap for TB genome polymerase chain reaction(PCR). RESULTS: The study included 41 males and 9 females. The mean age of the patient was 35.62 ± 11.49 y. Out of 50 patients, 42% (n = 21) patients had unilateral involvement. Mantoux test was positive in 73% patients. QuantiFERON-TB Gold test was positive in 56% patients. HRCT chest was suggestive of pulmonary tuberculosis in 34% patients. Out of 6 patients, PCR from anterior chamber tap showed TB genome positive in 2 (33.3%) patients. Out of 9 patients, vitreous tap PCR was positive for TB genome in 2 (22.2%) patients. CONCLUSIONS: Our study showed that one or more tests were positive for TB in Eales' disease suggesting a pivotal role of TB as a primary etiology for this disease. We conclude that Eales' disease is associated with Mycobacterium tuberculosis infection.

The clinical presentation and treatment outcomes of ocular tuberculosis: a 5-year experience in an endemic area.

PURPOSE: To report the clinical presentations of ocular tuberculosis infection (OTB) and the treatment regimen and outcome in an endemic area. METHODS: This is a retrospective case series of patients with presumed OTB treated in a tertiary teaching hospital in Hong Kong in 2014-2019. RESULTS: Among the nineteen patients recruited, the most common clinical presentation of OTB was retinal vasculitis (42.1%), followed by scleritis, intermediate uveitis, and choroidal tuberculoma (15.8% respectively). 94.7% and 94.4% of the subjects were treated with ATT and steroid, respectively, and 31.6% were put on systemic immunosuppressant prior to the initiation of ATT. Apart from those suffering from intermediate uveitis, most demonstrated good clinical response within 8 weeks of ATT initiation. CONCLUSION: Ocular involvement of TB has been increasingly recognized, especially in endemic regions like Hong Kong. High index of suspicion is recommended for OTB in typical clinical phenotypes or recurrent/resistant ocular inflammation unresponsive to conventional therapy. TB retinal vasculitis was the most common presentation of OTB in this study and OTB generally requires treatment with either regional or systemic steroid together with ATT.

Incidence of ocular inflammation among patients with active tuberculosis or nontuberculous mycobacterial infections in a tertiary hospital in Japan.

PURPOSE: This study aimed to elucidate the incidence of ocular involvement among patients with active tuberculosis (TB) or nontuberculous mycobacterial (NTM) infection in a hospital in Japan. METHODS: Patients with active TB or NTM infection at Yoshijima Hospital from April 2017 to July 2018 were included in this retrospective study. All patients underwent ophthalmic examinations, including fundus evaluation under pupil dilation, before initiation of antibiotic therapy. Patients with ocular inflammation were regularly followed up by ophthalmologists. RESULTS: In total, 101 patients with active TB and 27 patients with active NTM infection underwent ophthalmic examinations during the study period. Seven patients with TB (6.9%) had ocular inflammation; four had bilateral involvement. In these seven patients, ocular inflammation comprised anterior uveitis (n = 2), intermediate uveitis (n = 1), posterior uveitis (n = 4). Choroidal tubercles were observed in two patients with posterior uveitis. Female sex was associated with higher incidence of ocular inflammation among patients with TB. Conversely, no patients with NTM infection had ocular inflammation. CONCLUSION: Ocular inflammation was present in approximately 7% of patients with active TB. Although TB choroiditis is presumed to be rare in Japan, approximately 30% of the patients with ocular inflammation exhibited choroidal lesions in this study. In contrast, no ocular inflammation was observed among patients with systemic NTM infection.

Concurrent tuberculous chorioretinitis with choroidal neovascularization and tuberculous meningitis: a case report.

BACKGROUND: Tuberculosis (TB) remains a severe health burden worldwide. The manifestation of concurrent tuberculous cerebral and ocular involvements associated with TB is uncommon. CASE PRESENTATION: We report a 17-year-old girl with concurrent tuberculous cerebral and ocular involvements and visual impairment due to choroidal neovascularization. This study emphasizes the definite diagnosis with the combination of ophthalmological examination, multimodal imaging and routine tuberculosis testing, and the proper management with intravitreal anti-VEGF injection accompanied by systemic anti-tuberculosis therapy. CONCLUSION: Combined applications of routine TB tests, fundus multimodal imaging and diagnostic therapy greatly help the clinician to establish a precise diagnosis and in monitoring the therapeutic response.

Mycobacterium tuberculosis does not show evidence of molecular DNA in human cadaveric ocular tissues in an endemic setting.

BACKGROUND: Mycobacterium tuberculosis (MTB) in latent infection has been demonstrated in pulmonary/extra-pulmonary locations (lung, spleen, liver, kidney, adipose tissue) in autopsy studies, but its presence in ocular tissues in the latent state is not known. METHODS: We conducted molecular and histopathological study of 100 cadaver eyes (50 humans) who died from causes other than tuberculosis (TB) (and were potential candidates for corneal transplantation) to detect MTB in ocular tissues in an endemic setting. After removal of the corneal button, an 8 to 10 mm block of tissue (choroid, retina and part of the vitreous) was excised from the remaining globe for DNA isolation. Gel-based IS6110 and devR3 polymerase chain reaction (PCR) assays were done, followed by real-time PCR using beta actin gene as an internal control. Sixteen randomly selected DNA samples were double checked using a commercial kit for MTB and non-tuberculous mycobacteria (NTM) DNA. The remaining larger part of the globe was subjected to histopathology. RESULTS: The mean age was 65.14 ± 18 years. All 100 samples were negative for both IS6110 and devR, and all 16 samples were negative with NTM MTB commercial kit. All samples were negative with Ziehl-Neelsen stain for acid fast bacilli and none showed any inflammation or granulomatous pathology. CONCLUSIONS: MTB could not be detected in human ocular tissues in latent state in India, a TB-endemic country. This may suggest the inability of MTB to seed ocular tissues in the latent state, unlike other organs which serve as reservoirs for the bacilli in the absence of manifest disease.

Program-wide review and follow-up of erythema Induratum of Bazin and tuberculosis-associated ocular inflammation management in a TB low-incidence setting: need for improved treatment candidate selection, therapy standardization, and care collaboration.

BACKGROUND: Erythema induratum of Bazin (EIB) - nodular vasculitis associated with Mycobacterium tuberculosis (TB) - and Tuberculosis-Associated Ocular Inflammation (TB-AOI) represent uncommon manifestations of TB. There is limited data and a lack of diagnostic and treatment standards for these conditions. METHODS: Eleven-year retrospective review of EIB and TB-AOI cases managed in a provincial TB program with prospective phone-based follow-up of anti-tubercular therapy (ATT) recipients. Presumptive TB-AOI and EIB diagnoses were determined by ophthalmologist or dermatologist assessments correlated with positive tuberculin skin test and/or QuantiFERON-TB Gold, along with pathologic criteria in EIB cases. RESULTS: Of 21 EIB and 20 TB-AOI cases that received ATT, 13 and 11, respectively, were reached for follow-up. The majority of EIB and TB-AOI cases were female and immigrated from TB high-burden countries. Median durations of pre-diagnosis symptoms were 2 and 0.8 years (IQR 2.5 & 1.1) for EIB and TB-AOI cases, respectively. Overall, 14 different ATT regimens were used for a median duration of 6 months (range 5-9). ATT related adverse events resulting in treatment discontinuation occurred in 14% of EIB and 10% of TB-AOI cases. On last follow-up, 76% of EIB and 42% of TB-AOI had improvement or resolution of disease. CONCLUSION: EIB and TB-AOI were uncommon presentations receiving variable therapy. While treatment response was modest for EIB cases, TB-AOI cases had sub-optimal treatment outcomes. The unique diagnostic and management challenges presented by these conditions in TB low-incidence settings highlight a need for improved treatment candidate selection, therapy standardization, and cross-specialty medical collaboration.

THE COLLABORATIVE OCULAR TUBERCULOSIS STUDY (COTS)-1: A Multinational Review of 251 Patients With Tubercular Retinal Vasculitis.

PURPOSE: Tubercular retinal vasculitis (TRV) is a heterogeneous disease that can be difficult to manage because of nonspecific presentation and limitations of confirmatory tests for tuberculosis. This is a big data analysis on phenotypes and treatment outcomes for TRV. METHODS: Multicentre retrospective study of patients with TRV between January 2004 and December 2014 and a minimum follow-up of 1 year. RESULTS: Two hundred and fifty-one patients with TRV with a mean age of 38.9 ± 14.4 years (range, 9-86 years) were included. The patients were predominantly males (n = 167/251; 66.5%) of Asian ethnicity (n = 174/246; 70.7%), and geographical origin (n = 137/251; 54.6%). Most patients had features of occlusive type of RV (n = 113/185; 61.1%) except Caucasians (n = 11; 28.2%). There was no significant difference in treatment failure whether patients received antitubercular therapy (ATT) (P = 0.29), although treatment failure was less frequent in patients who received ATT (13.6%; n = 31/228) compared with those who did not (21.7%, n = 5/23). Less treatment failures were observed in patients with occlusive type RV who received ATT; however, this was not significant on survival analysis (P = 0.09). Treatment with ATT was associated with higher failure rates in patients of Hispanic and African American race and those with TRV associated with panuveitis (compared with posterior uveitis). CONCLUSION: In this multinational study of TRV, there was no significant therapeutic effect of ATT. However, a definitive conclusion about the role of ATT could not be made because of a few patients who did not receive ATT. Because this is a retrospective study with a limited 1-year follow-up, the effect of ATT may have been overestimated (or underestimated) in the duration of follow-up.

DETECTION OF TYPE 1 CHOROIDAL NEOVASCULAR MEMBRANES USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN TUBERCULAR POSTERIOR UVEITIS.

PURPOSE: To study optical coherence tomography angiography (OCTA) and multimodal imaging features of Type 1 inflammatory choroidal neovascularization (CNV) in tubercular serpiginous-like choroiditis and response to anti-vascular endothelial growth factor therapy. METHODS: In this study, multimodal imaging was performed using OCTA, enhanced-depth imaging optical coherence tomography, fluorescein angiography, and indocyanine green angiography. Correlation of OCTA with other imaging modalities in the detection of CNV was performed. The changes in CNV configuration after anti-vascular endothelial growth factor therapy were assessed. RESULTS: In this study, nine eyes (8 patients; 5 females; mean age: 32.5 ± 11.57 years) with diagnosis of tubercular serpiginous-like choroiditis were included. All the eyes had presence of low-lying pigment epithelial detachments on enhanced-depth imaging optical coherence tomography. Using OCTA, it was possible to detect Type 1 CNV in all eyes. Type 1 CNV networks comprised fine anastomotic network of vessels, some of which had a hairpin loop configuration. After anti-vascular endothelial growth factor therapy, there was a decrease in branching and anastomosis. The visual acuity significantly improved from 0.49 ± 0.26 (20/60 Snellen equivalent) at baseline to 0.26 ± 0.17 (20/36 Snellen equivalent) (P = 0.03) in all eyes. CONCLUSION: Type 1 CNV can occur among patients with tubercular serpiginous-like choroiditis, leading to significant visual loss even in the healed stages of the disease. Optical coherence tomography angiography can help in the detection of Type 1 CNV where conventional multimodal imaging, including fluorescein angiography and OCT, fails to make a definitive diagnosis and thereby guide the initiation of anti-vascular endothelial growth factor therapy.