Tuberculosis-associated Uveitis Research Articles

Current Practices in Ocular Tuberculosis: A Survey of Brazilian Specialists

ABSTRACTPurpose: To describe the approach of Brazilian specialists in the diagnosis and treatment of tuberculosis-associated uveitis (TBU).Methods: Members of the Brazilian Uveitis Society received an electronic invitation to participate in an online questionnaire.Results: Of the 169 invited specialists, 78 answered the questionnaire. Specialists evaluated 5.6 patients with TBU annually. Tuberculin skin test (TST, 81%) was primarily used for diagnosis. Patients with presumed TBU should always be tested for syphilis and HIV according to 51 (88%) and 47 (81%) of respondents, respectively. Chest computed tomography (CT, 72%) was preferable to chest radiography (CXR) for diagnosis. A positive TST (81%) and CXR (60%) were the main indicators of anti-tuberculous therapy, with 34%, 39%, and 14% of specialists treating for 6, 9, and 12 months, respectively.Conclusions: TST remains the preferred method for TBU diagnosis and prompt treatment by Brazilian specialists, though there is no consensus regarding disease treatment and management.

A challenging case of tuberculosis-associated uveitis after corticosteroid treatment for Vogt-Koyanagi-Harada disease.

A challenging case of tuberculosis-associated uveitis after corticosteroid treatment for Vogt-Koyanagi-Harada disease.

Effect of Adjunctive Pars Plana Vitrectomy on Focal Posterior Segment Inflammation: A Case-Control Study in Tuberculosis-Associated Uveitis

Pars plana vitrectomy (PPV) is commonly performed for managing complications of uveitis but the anti-inflammatory potential of PPV has not been extensively investigated beyond aqueous/vitreous inflammation. We studied the effect of PPV on resolution of focal posterior segment lesions in tuberculosis-associated uveitis (TBU). Case control study. Patients with bilateral TBU and active retinal/choroidal lesions in both eyes, and who received PPV in one eye were included. Fellow eyes of same patients, matched for patient characteristics and systemic therapy, were designated as controls. Study eyes received 3-port 23-guage PPV, involving removal of nearly the entire vitreous. Part of vitreous sample was used for quantitative polymerase chain reaction (qPCR) for Mycobacterium tuberculosis. Post-operatively, anti-TB and/or systemic corticosteroid therapy was initiated depending on level of clinical suspicion of tubercular etiology, degree of intraocular inflammation and qPCR results. Focal lesions were documented in preoperative and postoperative fundus diagrams. Clinical photographs were taken whenever adequate media clarity was present. Primary outcome measures were rate of clinical resolution of focal posterior segment lesions and improvement in best-corrected visual acuity (BCVA), at 1 month post-surgery. Thirty-six patients with bilateral posterior segment lesions consistent with TBU were included. Possible and probable TBU (depending on radiographic evidence of TB) were diagnosed in 28 (77.7%) and 4 (11.1%) patients respectively, whereas remaining 4 patients were diagnosed only on basis of qPCR results. Focal posterior segment lesions included retinal vasculitis (n = 27), multifocal-serpigenoid choroiditis (n = 5), multifocal choroiditis (n = 3) and focal choroiditis (n = 1). At one month postvitrectomy, 28 eyes (73.7%) showed complete resolution of focal posterior segment lesions compared to 7 non-vitrectomised eyes (19.4%), while improvement in BCVA was significantly more in study eyes (0.38 logarithm of the minimum angle of resolution [logMAR], P=0.04), compared to controls (0.12 logMAR, P = 0.17). Time to resolution following vitrectomy was unaffected by duration of disease, pre-operative systemic steroids or grade of vitritis. At 3 months, complete resolution was noted in 29 of 30 study eyes (96.7%) and 25 of 30 control eyes (83.3%). PPV facilitates faster resolution of focal posterior segment inflammation and BCVA improvement in TBU.

Normalised quantitative polymerase chain reaction for diagnosis of tuberculosis-associated uveitis

Normalised quantitative polymerase chain reaction for diagnosis of tuberculosis-associated uveitis

Normalised quantitative polymerase chain reaction for diagnosis of tuberculosis-associated uveitis

Polymerase chain reaction (PCR)-based diagnosis of tuberculosis-associated uveitis (TBU) in TB-endemic countries is challenging due to likelihood of latent mycobacterial infection in both immune and non-immune cells. In this study, we investigated normalised quantitative PCR (nqPCR) in ocular fluids (aqueous/vitreous) for diagnosis of TBU in a TB-endemic population. Mycobacterial copy numbers (mpb64 gene) were normalised to host genome copy numbers (RNAse P RNA component H1 [RPPH1] gene) in TBU (n = 16) and control (n = 13) samples (discovery cohort). The mpb64:RPPH1 ratios (normalised value) from each TBU and control sample were tested against the current reference standard i.e. clinically-diagnosed TBU, to generate Receiver Operating Characteristic (ROC) curves. The optimum cut-off value of mpb64:RPPH1 ratio (0.011) for diagnosing TBU was identified from the highest Youden index. This cut-off value was then tested in a different cohort of TBU and controls (validation cohort, 20 cases and 18 controls), where it yielded specificity, sensitivity and diagnostic accuracy of 94.4%, 85.0%, and 89.4% respectively. The above values for conventional quantitative PCR (≥1 copy of mpb64 per reaction) were 61.1%, 90.0%, and 74.3% respectively. Normalisation markedly improved the specificity and diagnostic accuracy of quantitative PCR for diagnosis of TBU.

Autoreactive T Cells in Immunopathogenesis of TB-Associated Uveitis.

Intraocular inflammation in tuberculosis-associated uveitis (TBU) is usually widespread, and responds unpredictably to treatment. Herein, we analyze the intraocular T-cell response in TBU for its surface phenotype, antigenic specificity, and functional characteristics to explain the above observations. We isolated T cells from vitreous humor samples of patients with TBU and non-TB uveitis (controls). These were directly stained for surface markers CD4, CD8, CD45RO, CD45RA, CCR7, as well as intracellular cytokines IFN-γ, TNF-α, and IL-17 and analyzed on flow cytometry. Antigenic specificity was determined by activating with Mycobacterium tuberculosis-specific antigen Early Secreted Antigenic Target-6 (ESAT-6) or retinal crude extract (RCE). Activation-induced cell death (AICD) characteristics of each T-cell population were analyzed by staining for PI-Annexin V, Fas-FasL, phospho-Akt, and phospho-Erk1/2. Immunophenotyping of vitreous humor samples demonstrated polyfunctional effector and central memory CD4+ T helper cells coexpressing IFN-γ, TNF-α, and IL-17. Both ESAT-6 and RCE (autoreactive) specificity was found in T cells extracted from TBU samples; however, the mycobacterial and autoreactive T-cell populations differed in their sensitivity to AICD. Autoreactive T cells appeared to resist AICD through decreased expression of apoptotic markers, FasL and caspase-3, sustained phosphorylation of Akt, and lowered Erk1/2 activity. Autoreactive T cells are present in TBU eyes and are relatively resistant to AICD. An understanding of this epiphenomenon could be crucial in planning treatment of TBU patients, and interpreting response to anti-TB therapy.

Presumed tuberculosis-associated uveitis: rising incidence and widening criteria for diagnosis in a non-endemic area.

PurposeTo assess the incidence, clinical ocular involvement and effectiveness of anti-tuberculous treatment in patients with chronic uveitis presumed to be associated with tuberculosis in a non-endemic community.Patients and methodsRetrospective case series of patients with uveitis and evidence of tuberculosis, with no other identified cause of uveitis, who underwent a 6-month course of standard anti-tuberculosis treatment between 2008 and 2015. The response to treatment was assessed at 6 and 12 months after initiation of treatment.ResultsForty-eight patients were included of whom 36 (75%) were born outside the United Kingdom. Only five had concurrent active pulmonary or nodal tuberculosis. There were 85 affected eyes, including 25 with granulomatous anterior uveitis, 32 with retinal vasculitis (occlusive in 21), and 20 with multifocal choroiditis or serpiginous-like retinochoroiditis. Gamma-interferon testing was positive in 95%. Complete resolution at end point was seen in only 60%, but a further 19% were inflammation-free on topical steroid only. Resolution was lower (50%) in those with panuveitis compared to other anatomical types (75%). Sixty-four eyes (75%) had a LogMAR visual acuity of 0.1 or better at the end of the study.ConclusionsThe incidence of presumed tuberculosis-associated uveitis (TBU) has almost quadrupled in this region. The efficacy of treatment has not been enhanced by the introduction of gamma-interferon testing to support diagnosis. Some patients may require more prolonged antibiotic therapy to ensure quiescence, but chronic non-infective anterior uveitis may in any case follow treated TBU.

Imaging in tuberculosis-associated uveitis.

Intraocular tuberculosis (TB) can have several clinical presentations, affecting nearly every tissue of the eye. These clinical signs have specific imaging characteristics which help in associating them with tuberculous etiology. This review enumerates the conventional and emerging imaging techniques for intraocular TB and highlights their clinical application for diagnosis and management of specific clinical presentations.

Advances in tuberculosis-associated uveitis.

Advances in tuberculosis-associated uveitis.

The spectrum of presumed tubercular uveitis in Tunisia, North Africa.

The purpose of this study was to analyze the spectrum of presumed tubercular uveitis in Tunisia, North Africa. We retrospectively reviewed the clinical records of 38 patients (65 eyes) diagnosed with presumed tubercular uveitis at two referral centers in Tunisia, between January 2009 and December 2011. Mean age at presentation was 42.7 years. Twenty-four patients were women (63.2%) and 14 (36.8%) were men. Twenty-three eyes (35.4%) had posterior uveitis, 21 eyes (32.3%) had intermediate uveitis, 13 eyes (20%) had panuveitis, and 8 eyes (12.3%) had anterior uveitis. Ocular findings included vitritis in 67.7% of eyes, posterior synechiae in 47.7%, multifocal non-serpiginoid choroiditis in 23.1%, multifocal serpiginoid choroiditis in 21.5%, periphlebitis in 21.5%, and mutton-fat keratic precipitates in 20%. Anti-tubercular treatment was prescribed in 33 patients (86.8%) and was associated with systemic corticosteroids in 20 patients (52.6%) and periocular injections of corticosteroids in four patients (10.5%). After a mean follow-up of 14.2 months (range, 10-58), inflammation was controlled, with a significant improvement in visual acuity (VA) (p = 0.028). However, recurrences developed in two patients (5.3%). Final VA was better than 20/40 in 27 eyes (41.5%) and less than 20/200 in five eyes (7.7%). In Tunisia, all anatomic types are possible in tuberculosis-associated uveitis, but posterior and intermediate uveitis are more frequent. Vitritis, posterior synechiae, multifocal serpiginoid or non-serpiginoid choroiditis, and periphlebitis are the most common manifestations.

The Manchester Uveitis Clinic: The First 3000 Patients—Epidemiology and Casemix

Purpose: To demonstrate the demography, anatomical, and diagnostic classification of patients with uveitis attending the Manchester Uveitis Clinic (MUC), a specialist uveitis clinic in the northwest of England, UK.Methods: Retrospective retrieval of data on a computerized database incorporating all new referrals to MUC from 1991 to 2013.Results: A total of 3000 new patients with uveitis were seen during a 22-year period. The anatomical types seen were anterior 46%; intermediate 11.1%; posterior 21.8%; and panuveitis 21.1%. The most common diagnoses were Fuchs heterochromic uveitis (11.5% of total), sarcoidosis-related uveitis (9.7%), idiopathic intermediate uveitis (7.9%), idiopathic acute anterior uveitis (7.0%), and toxoplasmosis (6.9%). Syphilis and tuberculosis-associated uveitis increased markedly in frequency during the study period.Conclusions: The uveitis casemix in this region reflects a predominantly white Caucasian population in a temperate country, but with changing characteristics owing to increasing immigration, enhanced diagnostic techniques, changes in referral pattern, and some real changes in disease incidence.

Secondary choriocapillaritis in infectious chorioretinitis

To analyse the indocyanine green angiography (ICGA) patterns of hypofluorescence that are compatible with choriocapillaritis that occur secondarily to toxoplasmic retinochoroiditis (ToRC), ocular tuberculosis (including tuberculous choroiditis, TuCR and multifocal serpiginoid choroiditis, TMSC) and syphilitic chorioretinitis (SyCR). This was a single centre, retrospective case review study. Patients with a diagnosis of ToRC, TuCR, TMSC or SyCR were identified, their charts were reviewed and fundus photographs, fluorescein angiography (FA) and ICGA pictures were assessed. Indocyanine green angiography was performed at the initial presentation in 63 of the 105 patients with ToRC, in 37 of the 38 patients with TuCR, in six of six patients with TMSC and in two of four patients with SyCR. The following four ICGA patterns indicated choriocapillaritis: extension of hypofluorescence beyond the hypofluorescence of the actual infectious focus as seen on fundus photography or FA (seen only in ToRC and TuCR); small dark dots around the infectious focus (seen only in ToRC); multiple 'confetti-like' hypofluorescent areas or hypofluorescent geographical confluent areas (seen only in TMSC); and widespread areas of nonperfusion visible only in ICGA (seen only in SyCR). Patients with secondary choriocapillaritis have distinct typical ICGA findings. ICGA is thus an important diagnostic tool that can provide an explanation for otherwise obscure visual loss and that might have diagnostic value for specific conditions like ToRC and SyCR.

Interferon-gamma release assay as a diagnostic test for tuberculosis-associated uveitis

BackgroundTo study the use of interferon-gamma release assay (IFN-γ) (IGRAs) as a diagnostic test for tuberculosis (TB)-associated uveitis (TAU).DesignProspective cohort study.ParticipantsConsecutive new patients (n=162) with clinical ocular signs suggestive of TAU, seen >1 year period at a single tertiary center.MethodsAll subjects underwent investigations to rule out underlying disease, including T-SPOT.TB and tuberculin skin test (TST). Twenty-one subjects with underlying disease and three with interdeterminate T-SPOT.TB results were excluded. Those with T-SPOT.TB- or TST-positive results were referred to infectious diseases physician for evaluation. Anti-TB therapy (ATT) was prescribed if required. Patients' treatment response and recurrence were monitored for six months after completion of ATT, if given; or 1 year if no ATT was given.Main outcome measureDiagnosis of TAU.ResultsMean age of study cohort (n=138) was 46.8±15.3 years. Majority were Chinese (n=80, 58.0%) and female (n=75, 54.3%). TST was more sensitive than T-SPOT.TB (72.0% vs36.0%); but T-SPOT.TB was more specific (75.0% vs51.1%) for diagnosing TAU. Patients with either a T-SPOT.TB (1.44; 95% confidence intervals (CI), 0.86–2.42) or TST (1.47; 95% CI, 1.12–1.94)-positive result are more likely to have TAU. The accuracy of diagnosing TAU increases when both tests are used in combination (area under the receiver operator curve=0.665; 95% CI, 0.533–0.795). Patients with both tests positive are 2.16 (95% CI, 1.23–3.80) times more likely to have TAU. Negative T-SPOT.TB or TST results do not exclude TAU (negative likelihood ratios <1.0).ConclusionsWe recommend using a combination of clinical signs, IGRA, and TST to diagnose TAU.

Clinical significance of an equivocal interferon γ release assay result

AimTo identify clinical risk factors for obtaining an ‘equivocal’ T-SPOT.TB result in patients consistent with tuberculosis (TB)-associated uveitis (TAU).MethodsProspective cohort study of consecutive new patients, with ocular signs consistent with...

The use of positron emission tomography/CT in the diagnosis of tuberculosis-associated uveitis

BackgroundDetection of tuberculosis as the underlying disease in uveitis can be problematic because of the limited sensitivity of conventional diagnostic methods, especially in the case of latent infection. The aim...