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Purpose: To present paradoxical reaction (PR) in three cases with ocular tuberculosis (OTB) treated with antitubercular therapy (ATT), highlighting diagnostic challenges and treatment strategies., Methods: We retrospectively reviewed clinical records of three OTB patients presenting with paradoxical worsening after ATT initiation at two Brazilian university hospitals., Results: The patients (2 males, 1 female) experienced worsening clinical presentation (increased inflammation, vision loss) within two to three weeks after initiating ATT. One patient who was HIV-positive with unilateral multifocal choroiditis developed PR soon after starting antiretroviral therapy. The second patient presented with a choroidal tuberculoma in both eyes. The third patient also had multifocal choroiditis and developed a localized choroidal elevation with a double-layer sign as a manifestation of PR. All patients were maintained on ATT therapy in association with corticosteroids and experienced improvement of inflammatory signs., Conclusion: This case series highlights the potential for PR in OTB patients. Close monitoring and prompt therapeutic adjustments are crucial for management success.

Background: Serpiginous-like choroiditis (SLC) denotes ocular tuberculosis (TB), in the presence of positive tuberculin skin test (TST) or interferon gamma release assay (IGRA)., Methods: Retrospective review of SLC patients from a TB-endemic country, with negative TST and IGRA tests, but responsive to anti-TB therapy., Results: Fifteen patients (13 bilateral) with active SLC  were included.   Eleven (73.3%) patients had received corticosteroids ± immunosuppressive therapy prior to presentation. Chest radiographic abnormalities were found in four (26.7%) patients. We treated all patients with a combination of anti-TB therapy (ATT) and corticosteroids. Paradoxical worsening was noted in nine (60%) patients, complete resolution of lesions in 12 (80%), persistent inflammation (post-ATT) in one, while two were yet to complete ATT. None had recurrence after complete resolution of lesions (median follow-up of 71 weeks [range 15-676 weeks])., Conclusions: TB-SLC may present with negative TST and IGRA tests but may still have clinical appearance, and treatment response, like test-positive disease.

Purpose: The aim is to analyze automated quantification of choriocapillaris flow deficit (CCFD) on swept-source (SS)-optical coherence tomography angiography (OCTA) in tubercular serpiginous-like choroiditis (TBSLC)., Methods: In this prospective study, automated CCFD calculations were performed on SS-OCTA and compared with CCFD areas on indocyanine green angiography (ICGA). Patients were divided into two groups based on the occurrence of paradoxical worsening (PW)., Results: Twenty-nine eyes (29 subjects; 18 males; mean age: 33±12 years) were included. The mean CCFD at baseline was 34.9 ± 4.3% on OCTA in eyes without PW and 35.4 ± 5.0% on SS-OCTA with PW (p = .77). At 4 and 12 weeks, CCFD on SS-OCTA improved to 30.6 ± 3.9% and 28.0 ± 4.2% (p < .001) without PW, respectively, and increased to 42.9 ± 4.4% and 48.8 ± 4.1% (p < .001) with PW, respectively. The SS-OCTA CCFD correlated well with ICGA (r = 0.48; p < .001)., Conclusions: Automated quantitative serial assessment of CCFD on SS-OCTA can serve as a useful biomarker of disease activity in eyes with TBSLC.

Competing Interests: Declaration of interests We declare no competing interests.

The diagnosis of OTB (Ocular tuberculosis) is usually difficult to make. Definitive diagnosis requires the identification of M. tuberculosis organisms in ocular tissues or fluids, but samples are often difficult to obtain, and biopsy may be hard to justify. We describe a 50-years-old Maghreb male, who presented a multifocal choroiditis associated with a choroidal tuberculoma on the left eye. Based on positive QuantiFERON-TB-Gold test and suggestive clinical and radiographic findings, a diagnosis of presumed ocular tuberculosis was made. Serial swept-source optical coherence tomography (SS-OCT) and widefield fundus retinographies during subsequent follow-up visits demonstrated the characterization of the atypical tuberculosis presentation and allowed the assessment of response to antitubercular therapy and oral steroids.

Purpose: To assess the ability of wide field Swept Source OCTA (SS-OCTA) imaging to detect morphological variations in Serpiginous Choroiditis (SC) and Serpiginous Like Choroiditis (SLC) in response to treatment and also analyze these findings quantitatively using Image J software., Methods: Retrospective observational case series of nine eyes with clinical diagnosis of active SC and SLC, who underwent SS-OCTA and fundus autofluorescence (FAF) imaging at baseline and each follow up visit till 6 months. Morphological analysis was done by two independent graders and quantitative analysis to measure the size and intensity of lesion was done using publicly available Image J software at baseline and each follow up visit., Design: Retrospective observational case series., Results: Using SS-OCTA, all the active lesions followed a characteristic healing pattern. Active lesions appear well defined hypo flow void patches and as healing progressed, lesion became more ill-defined and iso-hyper- intense. Significant increase in mean intensity of the lesion could be apparent after 1 and 6 month of treatment. There was reduction in the size of lesions during follow up however this difference was not statistically significant., Conclusion: SS-OCTA could be a useful noninvasive tool to study the treatment response in SC/SLC both morphologically as well as quantitatively. Quantitative parameters need to be designed in further research studies to aid in uniform management and follow up of uveitis cases.

Intraocular tuberculosis has protean clinical manifestations and remains an important etiological differential for uveitis in an endemic region. A 27-year-old male presented with visual acuity of counting fingers close to face in right (OD) and 20/25 in left eye (OS). Examination revealed a choroidal granuloma in OS and healed serpiginous-like choroiditis in OD. Antitubercular therapy was started with systemic corticosteroids. Granuloma resolved completely; however, the patient presented with neuroretinitis and posterior scleritis, as first and second recurrence, respectively, within a oneyear period. These were managed with systemic corticosteroids and immunosuppressive therapy was added, after second recurrence. The patient responded well and maintains remission. This case presented a clinical challenge with distinct recurrence patterns of tubercular posterior uveitis in the same eye, which has not been reported before. Successful management entailed use of antitubercular therapy, corticosteroids, and immunosuppressive therapy in a step-ladder approach, resulting in preservation of vision and achieving long-term remission., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Multifocal choroiditis (MFC) can be associated with ocular tuberculosis (TB). Inflammatory peripapillary choroidal neovascular membrane (PPCNVM) is uncommon in TB MFC. Subretinal pigment epithelial inflammatory lesions are suggestive of acute inflammation or reactivation of inflammation in the setting of MFC. We present a case of MFC, of tubercular aetiology, during course of treatment of PPCNVM developed a subfoveal retinal pigment epithelial lesion. Clinical examination suggested a recurrence of PPCNVM, with the new macular lesions posing a dilemma of new onset inflammatory choroidal neovascular membrane (CNVM) at the macula versus reactivation of choroiditis at the posterior pole. Multimodal imaging helped differentiate the lesion from CNVM and give the appropriate antitubercular treatment to prevent future recurrences., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study presents clinical features and prognosis after long-term (12-18 months) antitubercular therapy (ATT) in patients with ocular tuberculosis (OTB) in East China, an endemic area of tuberculosis. Methods: This retrospective study reviewed data from OTB patients treated at the Eye and ENT Hospital of Fudan University from 2008 to 2018. All the patients completed a minimum follow-up of 6 months after the cessation of ATT. Results: Sixty-six patients with OTB were studied. The ocular manifestations included retinal vasculitis (51.6%), choroiditis (24.2%), panuveitis (23.2%), intermediate uveitis (7.4%), scleritis (5.3%), anterior uveitis (2.1%), and optic neuropathy (1%). Except for two patients (ATT for 6 months), all other patients (64/66, 96.97%) received ATT for at least 12 months (6 patients for 12 months, 30 patients for 15 months, and 28 patients for 18 months). Treatment in conjunction with oral corticosteroids was used in 48 patients (72.7%). The average initial best-corrected visual acuity (BCVA) was 0.8 ± 0.64 (LogMAR), which improved to 0.31 ± 0.35 (LogMAR) at the last follow-up ( P  < 0.05). The final BCVA was significantly associated with the initial BCVA and the duration of clinical symptoms. A complete remission of uveitis was achieved in 97% of the patients. Conclusions: This study observed a favorable prognosis with long-term ATT regimens. Patients with better baseline visual acuity and a shorter duration of clinical symptoms before diagnosis had a better prognosis.

Purpose: To describe a novel case of intraocular tuberculosis (TB) arising in a patient undergoing treatment for Vogt-Koyanagi-Harada disease, and to highlight the use of spectral domain optical coherence tomography for helping confirm the diagnosis and monitor treatment response., Methods: Case report of a patient with Vogt-Koyanagi-Harada disease on prednisone, with acute clinical changes suspicious for bilateral tuberculous choroiditis. Spectral optical coherence tomography, fundus photography, and B-scan ultrasonography were all used to capture the acute lesions, and to monitor their responses after initiation of anti-TB therapy., Results: New subretinal lesions arose bilaterally, as characterized by spectral domain optical coherence tomography, and appeared to regress after a first round of anti-TB therapy, thereby helping confirm the presumed diagnosis of intraocular TB. A new peripheral choroidal lesion arose shortly after temporary cessation of antimicrobial treatment, and again regressed once four-drug therapy was instituted, with no recurrent lesions thereafter., Conclusion: The use of multimodal imaging was instrumental in the management of a rare case of intraocular TB arising in the setting of underlying Vogt-Koyanagi-Harada disease.

Purpose: To describe a case of tubercular serpiginous-like choroiditis that progressed, despite antitubercular medication, corticosteroids, and immunomodulatory treatment, which ultimately quieted after two intravitreal methotrexate injections., Methods: Case report., Results: A 35-year-old woman reported a shadow in the left eye for 2 weeks. She presented with tubercular serpiginous-like choroiditis in the right eye 2 years prior. At that time, she was started on antituberculosis therapy but was noncompliant and lost to follow-up. On re-presentation, there was a new active left-eye serpiginous lesion, with repeat positive QuantiFERON gold testing. Four antituberculosis drugs were started, followed by corticosteroids and azathioprine, with continued progression despite aggressive treatment. She was finally given 2 intravitreal methotrexate injections (400 μg/0.1 cc) 1 month apart, with final arrest of lesion extension. The uveitis remained quiet for over 24 months, and the patient was able to discontinue all systemic therapy., Conclusion: Intravitreal methotrexate injections halted progression of treatment-refractory tubercular serpiginous-like choroiditis.

Purpose: To characterize the ophthalmic clinical and multimodal imaging findings of disseminated Mycobacterium chimaera infection after cardiothoracic surgery., Design: Observational case series., Participants: Four patients (8 eyes) with disseminated M. chimaera infection., Methods: Patients were evaluated with biomicroscopy, OCT and OCT angiography, fundus autofluorescence, and fluorescein and indocyanine green angiography., Main Outcome Measures: Clinical and multimodal imaging findings of patients with disseminated M. chimaera infection., Results: All 4 patients were white men with a mean age of 65.5 years (range, 60-75 years) who had aortic valve or root infection, or both, with M. chimaera diagnosed by culture, gene sequencing, or both. All 4 patients demonstrated bilateral choroidal lesions on funduscopy and evidence of osteomyelitis by imaging, culture analysis, or both at the time of ocular diagnosis. Indocyanine green and OCT angiography revealed numerous additional subclinical choroidal lesions and were used to track disease response to therapy. Fluorescein angiography and fundus autofluorescence were useful in determining lesion age and activity. All patients were treated with 3- or 4-drug antimycobacterial therapy. Three underwent revision of cardiothoracic surgery with removal of infected graft. One patient went on to demonstrate progressive ocular disease that was noted before each of his surgical revisions. Two patients showed improvement in ocular and systemic disease, however one of them developed a choroidal neovascular membrane. The final patient was a single encounter whose clinical and imaging findings showed longstanding inactive disease., Conclusions: Ophthalmologists should be aware of the systemic and ocular findings of this rare life-threatening disease. Multimodal imaging is useful in corroborating a diagnosis of ocular M. chimaera and particularly in evaluating patient response to therapy, because choroidal activity seems to mimic systemic activity. Treating physicians should be aware of the co-occurrence of choroiditis and osteomyelitis. Choroidal neovascular membrane can also be a late complication of this disease., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To analyze baseline clinical and imaging risk factors associated with poor outcome in patients with tubercular serpiginous-like choroiditis (TB SLC)., Design: Retrospective clinical study., Methods: Charts and fundus photographs of consecutive patients with active TB SLC seen at a single tertiary referral center with 6 months follow-up after initiation of treatment were reviewed. Logistic mixed models were performed to determine the clinical and imaging factors associated with the response to therapy, including the opacity of choroiditis graded according to a 3-point scale., Results: This study included 203 eyes of 183 patients with active TB SLC. Poor initial best-corrected visual acuity (BCVA) and foveal and optic disc involvement were associated with poor response to therapy at 6 months (odds ratio [OR] 4.489, 95% confidence interval [CI]: 1.92-10.47; P = .001; OR 2.892, 95% CI: 1.23-6.81; P = .015; OR 11.633, 95% CI: 3.17-42.71; P < .001, respectively). The high opacity grades (2 and 3) were also associated with poor outcomes OR 9.541; 95% CI: 2.94-30.91; P = .001). Poor baseline BCVA and high grade of opacity of the lesions were the composite risk factors for paradoxical worsening of TB SLC (OR 7.555, 95% CI: 1.78-32.02; P = 0.006; OR 7.434, 95% CI: 1.34-41.18; P =0.021, respectively)., Conclusions: TB SLC with higher grades of lesion opacity at baseline may be associated with greater risk of poor therapeutic response and paradoxical worsening. Grading of baseline lesion opacity may be used in future prospective studies to predict the biological behavior of the lesions and may serve as a guide to therapeutic interventions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Optic disc neovascularization in uveitis is uncommon, and has been associated with chronic inflammations like Behcet's disease, Vogt-Koyanagi-Harada disease, sarcoidosis, etc. To our knowledge, optic disc neovascularization has not been reported in tubercular serpiginous-like choroiditis. We report three such cases.

Competing Interests: None

Purpose: To describe a novel spectral-domain (SD) OCT finding of a double-layer sign at the site of activity in tubercular serpiginous-like choroiditis (SLC) and how this sign can be used to assess treatment response in these eyes., Design: Retrospective, observational case series., Methods: We retrospectively reviewed simultaneous fundus photographs and SD OCT and fundus autofluorescence (FAF) images of eyes affected with tubercular SLC from the acute stage until resolution of lesions using the Heidelberg Spectralis HRA and OCT system (Heidelberg Engineering, Heidelberg, Germany)., Main Outcome Measures: Occurence of the double layer sign (DLS) during activity; reduction in the double layer sign (DLS) with resolution of choroidal and retinal inflammation; correlation of SD OCT and FAF findings., Results: Five eyes of 5 patients were studied in detail. Spectral-domain OCT findings included choroidal elevation and a double-layer sign (separation of hyperreflective retinal pigment epithelium [RPE] from Bruch's membrane, with the gap between them showing moderate reflectivity) at the site of activity. This correlated with hyperautofluorescence with indistinct borders on FAF imaging. Reduction in the double-layer sign became evident as the lesions began to resolve, and eventually this area was replaced by hyperreflective, irregular, knobbly elevations of the RPE. In eyes with severe inflammation and increased choroidal elevation on OCT, the double-layer sign was very prominent. As the choroidal elevation decreased on OCT, increased reflectance from the choroidal layers was evident. As the lesions resolved, the lesions became predominantly hypoautofluorescent on FAF and loss of RPE, ellipsoid zone, and external limiting membrane on SD OCT scan became evident. Good correlation was found between the resolution of the double-layer sign on SD OCT and FAF findings., Conclusions: The double-layer sign on SD OCT may be a useful finding in monitoring the activity in tubercular SLC. The OCT changes can be correlated with FAF imaging in these eyes., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.

A 47-year-old female presented with optic disc oedema, peripapillary subretinal fluid and scattered areas of choroiditis. Her ultrasound B-scan showed sclerochoroidal thickening with widening of sub-Tenon space. Subsequent investigations revealed a positive Mantoux test and high-resolution computed tomography of the chest was suggestive of pulmonary involvement. She responded well to antitubercular treatment and systemic corticosteroid. A review of the literature was conducted to identify additional reports on similar cases and discussed. A high index of suspicion and appropriate laboratory work-up can aid in the diagnosis of tuberculous posterior scleritis., Competing Interests: There are no conflicts of interest

Purpose: To analyze the serum cytokines profile in patients with tubercular multifocal serpiginoid choroiditis (TB MSC) receiving anti-tubercular therapy (ATT) and oral corticosteroids., Methods: In this prospective longitudinal study, patients with active TB MSC were included. Serum levels of interferon (IFN)-γ, interleukin (IL)-10, and tumor necrosis factor (TNF)-α were analyzed using bead-based immunoassay. The levels of transforming growth factor (TGF)-β were measured using cytokine bead array. Serial measurement was performed at baseline, 1, 3, and 6 weeks after initiation of therapy. Patients developing paradoxical worsening (PW) of TB MSC were identified and their serum levels of cytokines were compared with those patients who showed healing of lesions. Comparison of cytokine levels with baseline values was also performed., Results: Twelve patients (three females) were included in the study. Four patients showed paradoxical worsening of TB MSC at 3.2 ± 1 weeks after initiation of therapy. Compared to patients who showed healing of lesions, patients with PW showed higher baseline IL-10 (not significant; p = 0.28). Among patients developing PW, levels of IFN-γ peaked at 1 week ((p = 0.01) and levels of TNF-α peaked at 3 weeks (p = 0.02) (coinciding with PW) compared to patients who showed healing. There was no significant difference in TGF-β levels at any time point in either group (p > 0.47)., Conclusions: Baseline and serial levels of inflammatory serum cytokines may help in predicting the response to ATT and corticosteroids in TB MSC. Patients with paradoxical worsening may show rise in pro-inflammatory cytokines after initiation of ATT indicating higher bacillary load.

Serpiginoid multifocal choroiditis is a distinct morphological identity with a reported causal association with Mycobacterium tuberculosis. We report a case of serpiginoid multifocal choroiditis in a 17-year-old boy who was suffering from isolated splenic tuberculosis. He was treated with systemic steroids along with anti-tubercular treatment with good visual recovery. This case was unique as no other organs except spleen and choroid showed tubercular involvement. We hereby emphasize association of extrapulmonary sites with multifocal serpiginoid choroiditis and propose a thorough investigation for primary to be included in routine protocol of choroiditis workup.

Purpose: To analyze the safety and efficacy of sustained-release intravitreal dexamethasone implant (Ozurdex) in management of TB-associated multifocal serpiginoid choroiditis (MSC)., Methods: Retrospective review of TB-associated MSC patients, treated with anti-TB therapy (ATT) and adjunctive intravitreal Ozurdex., Results: Nine eyes of six patients were included. Four patients required Ozurdex implant for progressive or new lesions following ATT and two for additional systemic contraindications to corticosteroids - hyperglycemia and uncontrolled hypertension, respectively. The mean time to resolution was 9.17 ± 7.71 weeks. The mean follow-up post-injection was 13.11 ± 6.05 months (median 12 months [range 6-24.5 months]). Only one of nine eyes developed recurrent MSC lesions and this was attributed to possible autoimmune etiology. Two eyes (22.2%) developed steroid-induced glaucoma - one required implant removal., Conclusions: Sustained-release intravitreal dexamethasone is a safe and efficacious adjunctive anti-inflammatory therapy for TB-associated MSC patients with contraindication for systemic corticosteroids or requiring supplemental anti-inflammatory therapy.

Purpose: To assess choroidal vascular changes among patients with tubercular multifocal serpiginoid choroiditis (TB MSC) using previously validated techniques., Methods: Patients with TB MSC (n = 18) and healthy controls (n = 30) underwent enhanced-depth imaging optical coherence tomography (EDI-OCT) imaging. Using previously validated algorithm of image binarization, EDI-OCT scans were segmented to derive total choroidal area, luminal area, stromal area, and choroidal vascularity index (CVI)., Results: There was a statistically significant difference in the CVI between controls (66.90 ± 1.77%) and TB MSC patients (65.46 ± 2.53%; p < 0.001). There was significant reduction in CVI at follow-up (3 months) (63.77 ± 3.91%; p = 0.05). The choroidal thickness was higher in TB MSC compared to controls (278.90 ± 57.84 µm versus 329.33 ± 27.69 µm; p = 0.001)., Conclusions: CVI provides insight into structural changes in choroid in TB MSC. During the active disease, there is relative decrease in choroidal vascularity. As the lesions heal, choriocapillaris atrophy occurs with remodeling of choroid.

A 37-year-old immunocompetent male patient presented with the blurring of vision, both eyes for the past1 year. Fundus examination revealed bilateral multiple subretinal abscesses with areas of healed serpiginous-like choroiditis. Laboratory investigations showed positive tuberculin skin test, positive QuantiFERON TB-Gold Test, and high resolution computed tomography chest showed enlarged mediastinal lymph nodes. The aqueous sample revealed polymerase chain reaction (PCR) positive for Mycobacterium tuberculosis (MTB) (MPB64 genome). He was treated antitubercular therapy (ATT) along with oral steroids. Although he responded well initially, he had recurrent inflammation and paradoxical worsening. This was managed with a high dose of intravenous corticosteroids, immune suppressive and ATT. He also had a diagnostic vitreous biopsy which was also PCR positive for MTB (IS6110 gene). He subsequently continued ATT along with corticosteroids and immune suppressive and responded well. We present this case report for its unusual presentation.

Objective: To describe the clinical spectrum and outcome of patients with presumed tubercular uveitis and choroidal involvement., Methods: A retrospective case series nested in a cohort study was enrolled at a tertiary referral eye care center in the UK. Failure was defined as recurrence of lesion within 6 months of completion of antitubercular therapy (ATT) or corticosteroid therapy., Results: Seventy-seven patients with presumed ocular tuberculosis and choroidal involvement were included in the study. Mean age was 45.5 ± 15.7 years, 44 (57.1%) patients were male, and 51 (66.2%) presented with bilateral disease. Choroidal granuloma was the most frequent clinical presentation (n = 27, 35.07%), followed by multifocal choroiditis (n = 24, 31.17%) and serpiginous-like choroiditis (n = 18, 23.38%). Quantiferon Gold in Tube Test (QFT) was positive in 64 (83.11%) patients. Fifty (64.94%) patients received ATT., Conclusions: Choroidal involvement in presumed ocular tuberculosis can present with a variable spectrum. Treatment failure rates were equivalent between ATT and non-ATT treated groups.

Aims: The aim of this study was to detect Mycobacterium tuberculosis (MTB) DNA with polymerase chain reaction (PCR) in aqueous or vitreous samples of patients suffering from choroiditis presumed to be infectious origin., Settings and Design: Hospital-based, retrospective case-control study., Subjects and Methods: In all, forty eyes of forty patients with choroiditis divided into two groups - Group A (serpiginous-like choroiditis, ampiginous choroiditis, multifocal choroiditis) and Group B (choroidal abscess, miliary tuberculosis (TB), choroidal tubercle) were analyzed retrospectively. In 27 controls (patients without uveitis undergoing phacoemulsification), anterior chamber aspirate was done and sample subjected to real-time PCR. Patients underwent nested PCR for MTB using IS6110 and MPB64 primers from aqueous (n = 39) or vitreous (n = 1). All patients underwent detailed ophthalmological examination by slit-lamp biomicroscopy, fundus examination by indirect ophthalmoscopy, and fundus photograph and fundus fluorescein angiography if required., Statistical Analysis: Positive results of PCR for MTB within the group and between two groups were statistically analyzed using Chi-square test., Results: There were 25 males and 15 females. Mean age at presentation was 34.66 years (range, 14-62). PCR positivity rates were 41.3% (n = 12/29) and 81.82% (n = 9/11) in Groups A and B, respectively. No controls had PCR-positive result. Comparison of PCR positivity rates showed statistically significant difference between Groups A and B (P = 0.028). Systemic TB was detected in 57.14% (n = 12/21) of all PCR-positive cases (Group A - 33.3%, n = 4/12; Group B - 88.9%, n = 8/9). Systemic antitubercular treatment (ATT) for 9 months and oral steroids were successful in resolution of choroiditis in all PCR-positive patients (n = 21) without disease recurrence., Conclusions: Eyes with choroiditis of suspected/presumed tubercular origin should be subjected to PCR for diagnosis of TB and subjected to ATT for prevention of recurrences.

Purpose: To compare 3 different molecular techniques to detect the Mycobacterium tuberculosis genome in vitreous fluid of eyes with multifocal serpiginoid choroiditis (MSC)., Design: Prospective, interventional case series., Participants: Eleven patients (11 eyes) with active MSC in at least 1 eye underwent diagnostic pars plana vitrectomy (PPV) between October 2012 and December 2013., Methods: Vitreous fluid samples were subjected to multitargeted polymerase chain reaction (PCR) for a M. tuberculosis assay, the Gene Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA), and a line probe assay (GenoType MTBDRplus; Hain Lifescience, GmbH, Nehren, Germany). The samples with positive results were subjected to rpoB gene sequencing to demonstrate rifampicin resistance. The clinical details, digital fundus imaging, and treatment details and outcomes also were noted., Main Outcome Measures: Detection of the M. tuberculosis genome and rifampicin resistance in the vitreous samples., Results: Of the 11 eyes subjected to PPV, the multitargeted PCR results for tuberculosis were positive for 10 eyes, the MTBDRplus assay results were positive in 6 eyes, and the Gene Xpert MTB/RIF assay results were positive in 4 eyes. Rifampicin resistance was detected in 3 eyes by rpoB gene sequencing, in 3 eyes by the MTBDRplus assay, and in 1 eye by the Gene Xpert MTB/RIF assay., Conclusions: We detected the M. tuberculosis genome in the vitreous fluid of eyes with MSC using 3 different molecular techniques. Rifampicin resistance was detected for the first time in eyes with MSC., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To present a case of tubercular serpiginous-like choroiditis (SLC) with previously unreported choroidal findings on enhanced depth imaging OCT (EDI-OCT)., Design: Case report., Methods: A 60-year-old female presented with decreased vision. Serpiginous choroidopathy was diagnosed. Laboratory workup revealed an infectious etiology. EDI-OCT revealed previously unreported choroidal findings., Results: Laboratory workup revealed nonreactive Treponema pallidum antibodies and positive QuantiFERON Gold. CT chest showed scars of prior granulomatous disease. OCT with EDI of active lesions demonstrated infiltration of the choroid, elevation of the RPE-Bruch's membrane complex and focal increase of choroidal thickness., Conclusions: Choroidal infiltration with elevation of the RPE was demonstrated on EDI-OCT in active areas of tuberculous serpiginous-like choroiditis in this patient. This finding has not been described in imaging of patients with noninfectious serpiginous choroidopathy and may be a useful tool to differentiate serpiginous choroidopathy (SC) from serpiginous-like choroiditis (SLC). EDI-OCT may provide characterization of choroidal involvement.

Purpose: To assess tuberculous uveitis in Chinese patients., Methods: The hospital-based observational case series study included patients who attended a third-referral hospital and presented with chronic and recurrent uveitis without primarily detected aetiology. The patients underwent the tuberculin skin test (TST) and/or interferon gamma release test (IGRA). Patients with positive test results received standard antituberculous therapy. Patients who responded to the therapy and did not show recurrence of uveitis in the follow-up period were diagnosed as tuberculous uveitis and formed the study group. The remaining patients were diagnosed as non-tuberculous uveitis and formed the control group. The clinical characteristics were compared between both groups., Results: The study group with tuberculous uveitis included 46 patients and the non-tuberculous group 38 patients. Multifocal choroiditis [n = 9 (20%) versus n = 1(3%); p = 0.04] and retinal vasculitis [n = 25(54%) versus 8 = (21.1%); p = 0.002] were significantly more common in the study group. Of 25 patients with retinal vasculitis in the study group, 11 patients (44%) additionally showed choroiditis lesions, compared with only one (13%) of eight patients in the control group (p = 0.01). In multivariate regression analysis, multifocal choroiditis [odds ratio (OR): 32.1], choroidal granuloma (OR: 21.4) and retinal vasculitis (OR: 11.2) were independent predictors of tubercular uveitis., Conclusions: About 50% of a group of 84 patients with primarily unexplained chronic posterior uveitis had tuberculosis and showed multifocal choroiditis, choroidal granuloma and retinal vasculitis. These features had a high predictive value for the diagnosis of tuberculous uveitis. Tuberculosis is an important part in the differential diagnosis of unexplained uveitis., (© 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate clinical manifestations of patients with uveitis and scleritis of unknown origin and positive QuantiFERON-TB Gold In-Tube test (quantiferon) in a country not endemic for tuberculosis., Design: Multicenter retrospective cohort study., Methods: Retrospective review of the clinical, laboratory, and imaging data of 77 patients. Main outcome measures consisted of ocular and systemic features as well as results of laboratory examinations., Results: Out of all, 60 of 71 (85%) were living for at least 6 months in tuberculosis-endemic regions. Location of uveitis was variable; posterior uveitis (29/77; 38%) was the most frequent. Two clinical entities were commonly noted: retinal occlusive vasculitis (21/77; 27%) and serpiginoid choroiditis (11/77; 14%). Antituberculosis treatment was completed in 32 patients; 29 of them (91%) achieved complete remission. Mean quantiferon level was 7.5 U/mL; 71% had values above 2 U/mL and 41% above 10 U/mL. We observed no associations between quantiferon levels and clinical and/or imaging features. Previous tuberculosis infection was diagnosed in 5 of 77 patients (6.5%), while hilar/mediastinal lymphadenopathy was found in 25 of 76 patients (33%). Of these, 12 were consistent with the diagnosis of sarcoidosis, 9 were typical for (prior) tuberculosis, and 4 were compatible with both diagnoses., Conclusions: Ocular features of patients with idiopathic uveitis and positive quantiferon were diverse, but retinal occlusive vasculitis and serpiginoid choroiditis were common. The quantiferon levels were usually highly elevated and 33% of patients exhibited lymphadenopathy, suggesting frequently the diagnosis of sarcoidosis. Ocular inflammation reacted favorably to antituberculosis treatment, although only a small minority had documented (prior) tuberculosis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To report on the use of intravitreal methotrexate (IVT MTX) as part of treatment of presumed tuberculous serpiginous-like choroiditis progressing despite the use of tuberculostatics., Methods: Case series of patients suffering from serpiginous-like choroiditis with positive tuberculin skin test who received IVT injections of MTX as part of treatment. Ocular disease was active despite the use of systemic tuberculostatic (isoniazid, rifampicin, pyrazinamide, and ethambutol), and choroidal lesions showed signs of progression. A single injection of IVT MTX (400 μg/0.1 mL) was administered in the eye with macular-threatening features. Change in visual acuity, appearance of the lesion, and staining patterns on angiography were among the main outcome measurements., Results: Three eyes from two patients were included. Both cases presented bilateral involvement with mild vitritis. In all three eyes, choroidal lesions healed within the first month after an IVT MTX injection with visual acuity improvement in two. No adverse reaction was related to the medication or to the procedure. Patients were followed for a mean of 13.5 months after being injected., Conclusion: The use of IVT MTX seems effective in the management of the inflammatory component of tuberculous serpiginous-like choroiditis, whereas systemic tuberculostatics are aimed at controlling the infectious one.

Aim: To describe the increasing incidence of multifocal outer retinal and inner choroidal inflammation as a marker for intraocular tuberculosis in the UK, a non-endemic area., Patients and Methods: Retrospective case series., Results: 14 patients presented with serpiginous-like choroiditis over 10 years (seven within the last 2 years). Seven of 14 patients showed evidence of exposure to tuberculosis and received antituberculous treatment. 17 of 23 eyes showed stable or improved visual acuity. All with decreased acuity had direct macular involvement at presentation., Conclusions: Multifocal outer retinal and inner choroidal inflammation is a marker for intraocular tuberculosis of increasing importance, even in a non-endemic area. Originally described as 'serpiginous-like choroiditis', the lesions are multifocal, irregular in shape, very numerous, widespread, often asymmetrical and often demonstrating both active and resolved lesions simultaneously. Active lesions show contiguous extension. We recommend that every patient with SLC should undergo testing for previous exposure to tuberculosis, and undergo antituberculous treatment if lesions are progressive and sight-threatening.

Purpose: To describe the clinical features, course, and outcome in tubercular serpiginous-like choroiditis., Design: Retrospective cohort study., Participants: A total of 105 patients (141 eyes) between May 2002 and July 2010., Methods: Patients had the following inclusion criteria: (1) complete clinical records and digital fundus images at baseline and follow-up visits, (2) positive tuberculin skin test or QuantiFERON-TB Gold (Cellestis International Pty Ltd. Chadstone, Victoria, Australia) test result, (3) active serpiginous-like choroiditis in at least 1 eye, (4) all known causes of infectious (except tuberculosis) and noninfectious uveitis ruled out, and (5) a minimum of 9 months of follow-up from initiation of treatment that included antitubercular therapy (ATT) with oral corticosteroids (93 patients) or corticosteroids alone (12 patients)., Main Outcome Measures: Clinical characteristics and evolution of choroiditis lesions from the acute to healed stage, recurrence, visual outcome, and complications., Results: Mean age was 33 ± 9.3 years (range, 12-54 years; 75 male and 30 female patients). Serpiginous-like choroiditis was bilateral (at least 1 eye active) in 66 patients (62.9%). Of 171 affected eyes, 141 (82.45%) had active lesions at presentation. Of 141 eyes, 115 (81.56%) showed vitreous inflammation. Lesions were multifocal in 133 eyes (94.3%), were noncontiguous to optic disc in 122 eyes (86.52%), and involved the macula in 125 eyes (88.65%). Of patients receiving ATT, all showed resolution of lesions and 9 (9.7%) developed recurrences (median follow-up, 21 months). In addition, 12 patients (12.9%) showed continued progression over a median 3.5 weeks after initiation of therapy. Of 12 patients treated with corticosteroids alone, none showed progression but 9 (75%) developed recurrence (median, 26.5 months). Final visual acuity of ≥ 6/12 was achieved in 108 eyes (76.60%) versus 72 eyes (51.06%) before treatment. Fovea was spared in 95 of 125 eyes (76%) with macular involvement. Five eyes (3.5%) developed choroidal neovascular membrane., Conclusions: Tubercular serpiginous-like choroiditis presented as multifocal serpiginoid choroiditis affecting predominantly young to middle-aged men. It was frequently bilateral with vitreous inflammation and characterized by multifocal lesions that were noncontiguous to the optic disc and showed serpiginoid spread. Antitubercular therapy significantly reduced recurrences. Lesions responded to combined antitubercular and steroid therapy, usually spared fovea, and had a good final visual acuity., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the long-term outcome (up to 7 years) of presumed ocular tuberculosis (TB) when the therapeutic decision was based on WHO guidelines., Methods: Twelve out of 654 new uveitic patients (1998-2004) presented with choroiditis and positive tuberculosis skin test (TST) (skin lesion diameter >15 mm). Therapy was administered according to WHO recommendations after ophthalmic and systemic investigation. The area size of ocular lesions at presentation and after therapy, measured on fluorescein and indocyanine green angiographies, was considered the primary outcome. Relapse of choroiditis was considered a secondary outcome. The T-SPOT TB test was performed when it became available., Results: Visual acuity significantly improved after therapy (p=0.0357). The mean total surface of fluorescein lesions at entry was 44.8 ± 20.9 (arbitrary units) and decreased to 32.5 ± 16.9 after therapy (p=0.0165). The mean total surface of indocyanine green lesions at entry was 24.5 ± 13.3 and decreased to 10.8 ± 5.4 after therapy (p=0.0631). The T-SPOT TB revealed 2 false TST-positive results. The mean follow-up was 4.5 ± 1.5 years. Two relapses out of 10 confirmed ocular TB was observed after complete lesion healing, 2.5 years and 4.5 years after therapy, respectively., Conclusions: A decrease of ocular lesion mean size and a mean improvement of VA were observed after antituberculous therapy. Our long-term follow-up of chorioretinal lesions demonstrated relapse of ocular tuberculosis in 10% of patients with confirmed ocular TB, despite complete initial retinal scarring.

A 17-year old boy, with decreased vision in right eye for 15 days, presented with retinal periphlebitis in multiple quadrants of the right eye and partially active serpiginous-like choroiditis in the left eye. Tuberculin test was positive (16 mm induration), and chest X-ray showed hilar lymphadenopathy. The patient was treated with a 9-month course of anti-tubercular therapy and a tapering dose of oral corticosteroids. Both retinal vasculitis and choroiditis lesions resolved over 3-4 months. Retinal neovascularization in the right eye was treated with laser photocoagulation. There was no recurrence over an 18-month follow-up. The probable pathogenic mechanism for such a presentation is discussed.

To investigate the efficacy of anti-tuberculous therapy and systemic corticosteroids in patients suffering from active presumed tuberculous choroiditis by the assessment of central retinal sensitivity and fixation characteristics. Six patients (six eyes) with active presumed tuberculous choroiditis were treated with anti-tuberculous therapy and systemic corticosteroids. Mean central retinal sensitivities and fixation stability and location were investigated with MP-1 microperimetry before and after treatment. After a mean follow-up of 11.33 ± 7.53 months (range 6-24 months), all eyes showed resolution of inflammation, with no recurrences, associated with a significant improvement in visual acuity (P = 0.003). At the baseline, mean central retinal sensitivities were 2.03 ± 2.46 dB (range 0.0-6.6 dB). Fixation was stable and predominantly central in three eyes, and unstable and predominantly eccentric in three eyes. After treatment at a mean of 9.33 ± 6.56 months (range 4-20 months), mean central retinal sensitivities improved to 9.65 ± 5.35 dB (range 2.4-15.2 dB) (P = 0.004) and fixation became predominantly central and stable in all eyes. Anti-tuberculous therapy combined with systemic corticosteroids improves central retinal sensitivity and fixation characteristics in patients with presumed tuberculous choroiditis.

Objective: To compare distinctive clinical features of presumed tuberculous serpiginouslike choroiditis (Tb-SLC) with classic serpiginous choroiditis (SC) in patients living in a region that is nonendemic for tuberculosis., Methods: Retrospective comparative analysis of clinical features of 5 patients with recurrent Tb-SLC and 5 with SC., Results: All patients with recurrent Tb-SLC primarily emigrated from areas highly endemic for tuberculosis and had been unsuccessfully treated with steroids/immunosuppressive agents. Results of uveitis investigations were negative except for positive tuberculin skin test results. These patients received oral tuberculostatic drugs, without recurrences (follow-up, 6-91 months). The ocular involvement in Tb-SLC was mostly unilateral, with multiple irregular serpiginoid lesions involving the posterior pole and periphery but usually sparing the juxtapapillary area. All 5 cases had inflammatory cells in the vitreous. Patients with SC were from areas nonendemic for tuberculosis, had negative uveitis workup findings (including tuberculin skin test results), and were successfully managed with steroids/immunosuppressive agents (follow-up, 6-72 months) with no recurrence. Ocular involvement in SC was usually bilateral, rarely multifocal, and primarily involved the posterior pole, especially around the optic disc and extending contiguously to the macula. No patient with SC presented with vitritis., Conclusion: In areas nonendemic for tuberculosis, SC can be clinically differentiated from Tb-SLC. Patients with Tb-SLC come from highly endemic regions, show significant vitritis, and often present with multifocal lesions in the posterior pole and periphery. Cases of SC, in contrast, reveal minimal or no vitritis and frequently show bilateral involvement with larger solitary lesions extending primarily from the juxtapapillary area and sparing the periphery.