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.

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.

Tuberculosis: A Cunning Disease Presenting with Endopericarditis-Associated Bilateral Uveitis

Mycobacterium tuberculosis can spread through the entire body but rarely involves the eye. We report a patient with endophthalmitis in one eye and simultaneous retinal vasculitis in the fellow eye. Systemic work-up suggested infective endopericarditis. Polymerase chain reaction analyses of the vitreous and pericardial fluid were positive for M. tuberculosis. We initiated a four-drug antituberculous treatment regimen (isoniazid, ethambutol, pyrazinamide, and rifampin). After two weeks, we discontinued all the medications due to drug-induced hepatitis. We restarted isoniazid and rifampin, but hepatitis recurred. Finally, we chose isoniazid/ethambutol combination for 18 months, and also administered short-term systemic corticosteroid. His vision improved considerably with no recurrence of hepatitis or tuberculosis for 3 years after completion of treatment. Ocular tuberculosis can masquerade as other causes of intraocular inflammation, and a medical team consisting of an ophthalmologist and an infectious disease specialist might be needed for the diagnosis and management.

Early treatment of tuberculous uveitis improves visual outcome: a 10-year cohort study.

PURPOSE: Diagnosis of tuberculous uveitis (TBU) is often challenging and is usually made after excluding other causes of uveitis. We analysed the characteristics of TBU and variables associated with visual outcome. METHODS: A retrospective, observational analysis was performed in patients with presumptive TBU who were started on specific TB treatment between January 2006 and June 2016. Demographic, clinical, radiological, analytical and ophthalmic examination variables were studied. After completing TB treatment, a follow-up of at least 9 months was performed. A univariate and logistic regression analysis was applied to identify the variables associated with visual acuity and recurrences of uveitis. RESULTS: Forty affected eyes of 24 individuals were identified; 79% of patients were diagnosed during the last 3 years of the study period. Median delay from onset of symptoms to diagnosis was 12 weeks. Loss of visual acuity was the most frequent symptom (87.5%). Posterior uveitis was the most frequent localization (72.9%); 19 patients (79.2%) presented at least one of the Gupta signs predictive of TBU, but there were no confirmed diagnoses. OUTCOME: There was improvement in visual acuity in 74.4% of the eyes, but a complete response was achieved only in 56.4%. There was recurrence in two patients. The initiation of treatment ≥ 24 weeks after onset of symptoms was significantly associated with no improvement (p = 0.026). CONCLUSION: TBU can cause permanent damage to visual acuity, particularly in patients with delayed diagnosis. A prompt initiation of systemic TB treatment is essential to improve visual prognosis.

Clinical manifestations and treatment outcomes of syphilitic uveitis in HIV-negative patients in China: A retrospective case study.

Syphilitic chorioretinitis should be included in differential diagnosis of any form of ocular inflammation. A significantly higher proportion of human immunodeficiency virus (HIV)-positive patients with ocular syphilis as compared to HIV-negative cases have been reported in published studies. However, the clinical signs and symptoms are more insidious in HIV-negative patients who are easily misdiagnosed. We report a series of cases of ocular syphilis and describe the clinical manifestations and treatment outcomes of syphilitic chorioretinitis in HIV-negative patients in China.This was a retrospective case series study. The clinical records of patients with syphilis chorioretinitis were reviewed. Demographic information and findings of fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and spectral domain optical coherence tomography (SD-OCT) were analyzed. All patients received the standard treatment. Ophthalmology examination and laboratory evaluation were repeated every 3 months. All changes were recorded. The treatment was considered successful if the patients had no inflammation in both eyes and rapid plasma reagin titer was negative after therapy.The study examined 41 eyes of 28 HIV-negative patients. The main complaints were blurry vision, floaters, and visual field defect. Twenty-seven eyes presented with panuveitis, and all had posterior involvement, including uveitis, vasculitis, chorioretinitis, and optic neuritis. The most common manifestations were uveitis and retinal vasculitis. Disc hyperfluorescence and persistent dark spots were the most common findings on FFA and ICGA. The ill-defined inner segment/outer segment junction was the most frequent manifestation on SD-OCT. Patients were diagnosed with syphilitic uveitis based on positive serological tests. Best-corrected visual acuity (BCVA) was improved in 34 eyes after treatment. Eleven patients were misdiagnosed before serological tests were performed. The delay in treatment led to long-standing cystoid macular edema and optic neuropathy, which were associated with poor BCVA (P = .037).The common manifestations of syphilitic chorioretinitis were uveitis, retinal vasculitis, and optic neuritis. Further diagnosis should be prompted by FFA, ICGA, and SD-OCT when ocular manifestation is suspected. The standard treatment for neurosyphilis was effective. If patients are presumed to be in low-risk groups such as HIV-negative, delays in diagnosis, and therapy may be likely. It is necessary to reiterate the importance of including syphilis uveitis as a differential diagnosis for any form of ocular inflammations, especially posterior uveitis and optic neuropathy.

Syphilitic Scleritis.

A 47-year-old man developed a painful right red eye for 72 hours with a 20/25 decreased visual acuity. He had no medical history. Slit-lamp examination revealed a painful nodular scleritis at the equator of the globe in the infero-temporal quadrant. There was a moderate intraocular inflammation in the anterior segment. Fundus examination revealed a grade 1 hyalitis and a focal retinitis with vasculitis and arterio-veinous occlusion toward the scleritis zone. Syphilis and HIV serology were positive and the scleritis resolved 5 days after a penicillin G medication. Syphilitic scleritis are relatively uncommon.

Klebsiella Endophthalmitis as Retinal Vasculitis with Prostatic Abscess.

PURPOSE: To describe an unusual case of endogenous Klebsiella endophthalmitis associated with prostatic abscess in an immunocompetent patient. CASE REPORT: A 59-year-old previously healthy man presented with rapidly progressive retinal vasculitis in the left eye. He received an empirical antibiotic and antiviral agent intravenously followed by oral prednisolone until the etiology was identified; however, intraocular inflammation in the left eye continued to worsen, followed by the development of subretinal abscess in the contralateral eye. Finally, a diagnosis of endogenous Klebsiella endophthalmitis associated with prostatic abscess was made through a culture of the vitreous acquired by diagnostic vitrectomy. However, we could not save the vision of the left eye despite the intensive treatment with intravenous and intravitreal injections of antibiotics. CONCLUSIONS: Rapidly progressive retinal vasculitis could be an initial sign of endogenous Klebsiella endophthalmitis even in an immunocompetent patient.

Association of Mycobacterium tuberculosis in the causation of Eales' disease: an institutional experience.

BACKGROUND: Eales' disease is an idiopathic retinal vasculitis characterized by retinal inflammation, ischemia, and neo-vascularisation. It frequently causes massive vitreous haemorrhage and retinal detachment leading to blindness. Although the exact etiology is unknown, this condition is considered to be a consequence of hypersensitivity reaction to tubercular protein due to previous Mycobacterium tuberculosis (M. tuberculosis) infection. This study is aimed at the detection of association of M. tuberculosis in patients with Eales' disease. MATERIALS AND METHODS: A prospective case-control study was undertaken in 65 clinically diagnosed cases of Eales' disease. Patients with proliferative diabetic retinopathy, neo-vascular proliferation, macular oedema, premacular fibrosis and tractional retinal detachment were taken as controls. M. tuberculosis DNA was detected (MPT64 gene by polymerase chain reaction, PCR) in patients with Eales' disease. Clinical symptoms along with tuberculin skin test (TST) and erythrocyte sedimentation rate (ESR) were used as gold standard for comparing results of PCR. RESULT: PCR positivity was found in 12 (38.7%) patients with Eales' disease. The PCR positivity was significantly associated with the patients with high TST reading and high ESR values. CONCLUSION: Patients with a high TST reading and ESR value and a positive PCR in vitreous samples have a high likelihood of having M. tuberculosis as an etiology.

Recurrent bilateral retinal vasculitis as a manifestation of post-streptococcal uveitis syndrome.

We report a case of post-streptococcal uveitis mainly presenting with bilateral recurrent retinal vasculitis in Korea. A 14-year-old Asian female presented with decreased visual acuity of 20 / 30 in the right eye and 20 / 25 in the left eye. The patient had a history of glomerulonephritis nine months before onset of uveitis. The manifestation of uveitis was predominantly retinal vasculitis. We presumed post-streptococcal uveitis because probable streptococcal infection was confirmed by anti-streptolysin O titer elevation. With topical and oral steroid treatments, the patient experienced complete vision recovery. Post-streptococcal uveitis occurs rarely and mostly involves young patients in the form of non-granulomatous anterior uveitis. However, as this case shows, it may primarily involve the posterior uvea without anterior inflammation and may recur.

Quantitative polymerase chain reaction for Mycobacterium tuberculosis in so-called Eales' disease.

PURPOSE: To report mycobacterial load in the vitreous of patients labeled as having Eales' disease. METHODS: Eighty-eight patients were prospectively enrolled into 3 groups: 28 patients with so-called Eales' disease (group A); 30 positive controls with specific uveitis syndromes (group B), and 30 negative controls (group C). The undiluted vitreous humor samples were collected and subjected to real-time PCR assay for MPB64 gene of Mycobacterium tuberculosis (MTB) and load quantified. RESULTS: Sixteen (57.14%) vitreous fluid samples in group A; 1 sample in group B, and none of the samples in group C were positive for MTB genome from the vitreous. The copies of MTB genomes in the positive samples in group A were 1.52 × 10(4) to 1.01 × 10(6). CONCLUSION: MTB genome was demonstrated in more than 50% of vitreous fluid samples with significant bacillary load, indicating that half of patients with so-called Eales' disease are indeed cases of tubercular vasculitis.

Frosted branch angiitis in a woman with Mycobacterium tuberculosis infection.

PURPOSE: To describe a case of frosted branch angiitis in a patient with tuberculous meningitis. METHODS: Case report. RESULTS: A 27-year-old woman of tuberculous meningitis was referred to us complaining of blurred vision for 2 days. Prominent white sheathing of the retinal venules and, to a much lesser extent, arterioles, consistent with frosted branch angiitis were also observed in both eyes. And after treatment with systemic anti-tuberculosis medications and steroid, frosted branch angiitis showed resolution. CONCLUSIONS: Frosted branch angiitis can be caused by Mycobacterium tuberculosis. Systemic anti-tubercular therapy and steroids were effective.

Profile of retinal vasculitis in a tertiary eye care center in Eastern India.

AIMS: To provide a fact file on the etiology, clinical presentations and management of retinal vasculitis in Eastern India. MATERIALS AND METHODS: Retrospective, record based analysis of retinal vasculitis cases in a tertiary care center in Eastern India from January 2007 to December 2009 . RESULTS: One hundred and thirteen eyes of 70 patients of retinal vasculitis were included in this study. Sixty (85.7%) patients were male (mean age 33± 11.1 years) and 10 (14.3%) were female (mean age 32.4 ± 13.6 years). Vasculitis was bilateral in 43 (61.4%) and unilateral in 27 (38.6%) patients. Commonest symptoms were dimness of vision (73; 64.6%) and floaters (36; 31.9%). Vascular sheathing (82; 72.6%) and vitritis (51; 45.1%) were commonest signs. Mantoux test was positive in 21 (30%) patients but tuberculosis was confirmed in only four (5.71%) patients. Raised serum angiotensin-converting enzyme level and positive antinuclear antibody level were reported in four (5.71%) patients each. Human leukocyte antigen B5 (HLA B5) marker was present in one (1.4%) patient. However, none of the total 70 patients were found to have a conclusively proven systemic disease attributable as the cause of retinal vasculitis. Oral corticosteroid (60; 85.7%) was the mainstay of treatment. Forty-eight (42.5%) eyes maintained their initial visual acuity and 43 (38%) gained one or more line at mean follow-up of 16.6± 6.3 months. CONCLUSION: Retinal vasculitis cases had similar clinical presentations and common treatment plan. There was no systemic disease association with vasculitis warranting a careful approach in prescribing investigations.

Retinal vasculitis as an early indicator of systemic candidal abscesses in a premature infant.

We report a case of fungal retinal vasculitis in a 32 week gestational age, 1200 g premature infant detected during routine screening for retinopathy of prematurity at 78 days of age. The patient subsequently developed sepsis with perinephric abscess but responded rapidly to systemic therapy. Fortuitous detection of retinal vasculitis as the first evidence of a systemic fungal infection in an immunocompetent and asymptomatic infant has not, to our knowledge, been previously reported.

Pulmonary tuberculosis associated retinal vasculitis presenting as xanthopsia.

PURPOSE: To report a patient presenting with unilateral xanthopsia who was diagnosed as having retinal vasculitis with pulmonary tuberculosis. DESIGN: A case report. METHODS: A 20-year-old man presented with xanthopsia in the right eye. Fundus examination revealed multiple retinal hemorrhages, vascular sheathing, and a yellowish retina. RESULTS: He was diagnosed as having retinal phlebitis with pulmonary tuberculosis by chest x-ray and computerized tomography scans and treated with anti-tuberculosis medications. After treatment, he described clearance of xanthopsia, and fundus examination also showed normal coloration. CONCLUSIONS: Xanthopsia may be a sign of retinal vasculitis associated with tuberculosis. Ophthalmologists should suspect retinal vasculitis when patient complains of xanthopsia.

Unusual retinal manifestations of cat scratch disease.

We report on 2 patients with unusual retinal manifestations of cat scratch disease (CSD), caused by Bartonella henselae. Case 1. A 42-year-old farmer presented with a 5-day history of blurred vision in his right eye. Right visual acuity was 20/25. Fundus examination of the right eye revealed mild vitreous hemorrhage and diffuse retinal hemorrhages in the mid-peripheral retina. Fluorescein angiography showed multiple vasculitic occlusions in the same area. A blood sample taken on the day of examination revealed the presence of immunoglobulin (Ig)M and IgG to B. henselae. Oral azithromycin was given for 8 days. One month later, right visual acuity was 20/20, the vitreous and retinal hemorrhages resolved, and arteriolar attenuation and sclerosis was observed in the peripheral temporal retina. Case 2. A 66-year-old craftsman with systemic hypertension and hypercholesterolemia complained of sudden visual loss (light perception) in his left eye. Fundus evaluation and fluorescein angiography revealed central retinal artery occlusion (CRAO) in the affected eye. About 2 weeks earlier, he had been bitten and scratched on his right hand by a stray cat. Serologic testing detected the presence of IgM to B. henselae. Oral azithromycin was given for 6 days. One month later, left visual acuity was hand motion. Ophthalmologists should be aware that unusual ocular complications associated with CSD include vitreous hemorrhage with retinal vasculitis and isolated CRAO. Vitreous hemorrhage and retinal vasculitis may be the only clinical manifestation of CSD.

Presumed tuberculosis-induced retinal vasculitis, diagnosed with positron emission tomography (18F-FDG-PET/CT), aspiration biopsy, and culture.

PURPOSE: The diagnosis of tuberculosis as an etiological factor in patients with uveitis is difficult because of lack of specific diagnostic tests. The authors report 2 cases of occlusive retinal vasculitis, in which (18)F-FDG-PET/CT was helpful for the diagnosis of tuberculosis as a presumptive cause of intraocular inflammation. METHODS: In 2 patients with severe occlusive retinal vasculitis and positive QuantiFERON TB-Gold test, (18)F-FDG-PET/CT, transbronchial needle-aspiration biopsy, and microbiological investigation were performed. RESULTS: (18)F-FDG-PET/CT showed increased fluorodeoxyglucose uptake in some mediastinal and hilar lymph nodes. After needle-aspiration biopsy of PET-positive lymph nodes, M. tuberculosis was recovered in culture in both cases. Remission of uveitis was achieved only after a combination therapy with 3 anti-tubercular agents and systemic steroids. CONCLUSION: The authors favor the use of (18)F-FDG-PET/CT in patients with sight-threatening intraocular inflammation and positive interferon-gamma release assay. Anti-tubercular therapy, together with anti-inflammatory treatment, may lead to a remission in such patients.