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

Background

To study the use of interferon-gamma release assay (IFN-γ) (IGRAs) as a diagnostic test for tuberculosis (TB)-associated uveitis (TAU).

Design

Prospective cohort study.

Participants

Consecutive new patients (n=162) with clinical ocular signs suggestive of TAU, seen >1 year period at a single tertiary center.

Methods

All 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 measure

Diagnosis of TAU.

Results

Mean 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).

Conclusions

We recommend using a combination of clinical signs, IGRA, and TST to diagnose TAU.     

结核性葡萄膜炎的研究进展

伴随着结核病的新发病例数逐年增加,结核性葡萄膜炎的发病率也呈不断上升趋势.结核性葡萄膜炎的临床表现多种多样,可表现为前葡萄膜炎、脉络膜结节、多灶性脉络膜炎,少见的有匐行性脉络膜炎、视网膜下脓肿等,也可表现为疑似眼内肿瘤,甚至以黄斑囊样水肿为惟一表现.由于目前尚缺乏合适的诊断标准,临床上极易漏诊、误诊及延迟诊断,常造成患者视力丧失、盲,甚至眼球摘除的严重后果.聚合酶链反应及γ干扰素释放试验等新技术有助于结核性葡萄膜炎的诊断.结核性葡萄膜炎的早期诊断和正确治疗亟需加强.     

Hypopyon in the context of tuberculous uveitis

An 86-year-old man presented with blurred vision and pain in the left eye. A slitlamp examination revealed anterior uveitis with hypopyon. During the investigation of the uveitis, the diagnosis of tuberculosis was confirmed. Hypopyon is a rare manifestation of uveitis due to tuberculosis.     

玻璃体切割治疗结核性葡萄膜炎1例

患者,女,17岁,因左眼视力下降8个多月于2 0 0 2年12月2日入院。8个月前因“高烧、盗汗、咳嗽2 0余天”被当地医院拟以“血型播散性肺结核”收住入院。入院后第三天双眼视力骤降至视物不见,当地医院诊断为“急性虹膜炎”。予以结膜下注射和眼药水治疗(具体不详) ,视力稍有好转但仍然视物不清,后多次就诊外院,予以结膜下注射和眼药水及口服药物治疗,右眼视力恢复,左眼无明显好转。有低热及咳嗽史,无卡介苗接种史。其家族有结核病史。现“肺结核”已痊愈。查体:心、肺、腹部检查未见明显异常。专科检查:视力,右眼0 .15 ,矫正0 .8;左眼0 .0 2 ,…     

Clinical application of an in-house ELISPOT assay in patients with suspicious tuberculous uveitis and no signs of active tuberculosis

Purpose. The purpose of this study is to evaluate the rate of Mycobacterium tuberculosis infection in uveitis patients using an ELISPOT-IFN-gamma (ELISPOT-MTP) assay and a tuberculin skin test (TST). Methods. Fifty-three patients with suspicious tuberculous uveitis, seen at the Ocular Immunology and Uveitis Service, Scientific Institute San Raffaele, Milan, Italy, were compared with 233 healthy control subjects. All uveitis patients, together with healthy control subjects, underwent in-house ELISPOT-MTP assay and then the TST. Results. None of the patients had signs of active tuberculosis. A total of 75.5% of uveitis patients showed positive TST reaction while 58.5% responded positively to ELISPOT-MTP. In healthy individuals, these responses were 30.5% and 25.3%, respectively (p<0.0001). In a different diagnosis subset, TST and ELISPOT positivity were, respectively, 80% and 50% in anterior uveitis; 75% and 50% in intermediate uveitis; 100% and 87.5% in serpiginous-like choroiditis; 90% and 80% in posterior uveitis; and 57.1% and 42.9% in panuveitis. Serpiginous-like choroiditis and posterior uveitis patients had a higher number of ELISPOT-MTP positive results and a higher grade of intensity of ELISPOT-MTP responses compared to healthy control subjects (p=0.0098). Conclusions. Our uveitis patients had higher M tuberculosis infection rate and grade of intensity response than healthy control subjects detected by ELISPOT-MTP. This response is statistically significant and higher in patients with serpiginous-like choroiditis and posterior uveitis.     

A case of tuberculous uveitis complicated by myelodysplastic syndrome

BACKGROUND: Recently, the incidence of tuberculosis in compromised hosts has increased. CASE: A 52-year-old man suffering from myelodysplastic syndrome (MDS) had pulmonary tuberculosis. On June 22, 1996, we found a disc-sized choroidal lesion with milky appearance on the paramacular in his right eye. After 1 month, a similar choroidal lesion was found near the disc in the same eye. In spite of chemotherapy for MDS and antituberculosis medications, those choroidal lesions gradually enlarged. In November, satellite lesions were found around them. Some retinal exudates and hemorrhage were also detected in both eyes. He died on April 6, 1997. We found Langhans' giant cells in the choroid on the specimen of his eyes. So we judged the choroidal lesions to be tuberculous uveitis. CONCLUSION: This case showed choroidal tuberculosis and choroidal miliary tuberculosis in the same eye that were resistant to medications. We thought resistance to medication was due to destruction of the immune system by MDS.     

Laser iridectomy in tuberculous uveitis complicated by glaucoma and ophthalmic hypertension

By means of an ophthalmological device "Iatagan", laser iridectomy, in personal modification, was made in 54 patients with chronic (in 40 cases--tuberculosis) uveitis in 67 eyes with predominantly organic changes in the anterior chamber angle. Before operation, ophthalmic hypertension was recorded in 55 eyes, of them glaucoma of different stages--in 43 (in 12 eyes intraocular pressure was normal). In immediate and remote terms, normalization of intraocular pressure was achieved in more than 60% of cases. Complications were rare and, as a rule, easily removed. There were no essential differences in effectiveness of laser iridectomy used in tuberculous and nontuberculous uveitis. The results obtained speak about the expediency of wide usage of laser iridectomy in chronic uveitis for both therapeutic and prophylactic purposes.     

结核性葡萄膜炎初始抗结核治疗矛盾反应的临床特征

目的 总结结核性葡萄膜炎矛盾反应的临床特点。设计回顾性病例系列。研究对象2012-2020年北京同仁医院眼科结核性葡萄膜炎初始抗结核治疗后出现矛盾反应者8例(10眼)。方法 回顾患者的病历资料。平均随访(10.0±5.6)个月。主要指标眼前节、及眼底表现,治疗情况。结果 患者平均年龄(45.0±10.8)岁。8例患者中1例(12.5%)患活动性肺结核,6例(75.0%)可疑既往肺结核感染,1例(12.5%)无明确结核病史。矛盾反应发生于初始抗结核治疗后平均(0.9±0.3)个月(0.5～1.5个月)。其中脉络膜结核瘤2眼(20.0%),表现为瘤体扩大,表面视网膜脱离;全葡萄膜炎3眼(30%),表现为前房、玻璃体炎性反应加重,黄斑水肿加重;中间型葡萄膜炎2眼(20%),表现为玻璃体混浊加重;匐行样脉络膜炎3眼(30%),表现为眼底黄白色病灶增多、高自发荧光区域增多。所有患者在矛盾反应出现后在抗结核同时全身或局部加用糖皮质激素,炎性反应均得到有效控制。结论 结核性葡萄膜炎患者矛盾反应多发生于肺结核非活动期初始抗结核治疗1个月左右,规范抗结核和糖皮质激素联合应用可明显减轻矛盾反应。(眼科,2...     

PCR检测在结核性葡萄膜炎诊断中的应用

结核性葡萄膜炎因难以获得病原学诊断依据,至今仍很难明确诊断。聚合酶链式反应（polymerase chain reaction,PCR）技术可扩增痕量级核酸的特点对少菌性感染的结核性葡萄膜炎而言是一大优势。在临床实际应用中,PCR技术的类别、靶基因序列的选用、眼内液样本类型及患者的选择等在一定程度上可能影响PCR检测的敏感度。对结核性葡萄膜炎致病机理及抗结核药物治疗反应等的深入剖析有助于临床医生从不同角度更好地分析PCR检测结果及治疗结局。（国际眼科纵览,2022, 46：66-70）     

Clinical and optical coherence tomographic findings and outcome of treatment in patients with presumed tuberculous uveitis

Purpose To define the clinical characteristics and optical coherence tomographic (OCT) features, and to assess the outcome of treatment, in patients with presumed tuberculous uveitis (PTU). Methods All patients diagnosed with PTU at King Abdulaziz University Hospital between January 1998 and May 2006 were reviewed. The diagnosis was made when findings were consistent with possible intraocular tuberculosis with no other cause of uveitis suggested by history, symptoms, or ancillary testing, strongly positive tuberculin skin-test results, and response to antituberculous therapy. Results Fifty-one patients (73 eyes) were identified. There were 34 males (66.7%) and 17 females (33.3%) with a mean age of 40.1 ± 11.0 years (range 16–68 years). Fifty-eight eyes (79.5%) had panuveitis and 15 eyes (20.5%) had posterior uveitis at presentation. Clinical manifestations included vitritis (71.2%), macular edema (63%), retinal periphlebitis (35.6%), multifocal choroiditis (20.5%), and granulomatous anterior uveitis (17.9%). All patients received antituberculous therapy and systemic corticosteroids. After a mean follow-up of 18.9 ± 21.9 months (range 6–96 months), all eyes showed resolution of inflammation, with no recurrences, associated with significant improvement in visual acuity (VA) (P = 0.007). There was a significant positive correlation between initial and final VAs (r = 0.7856, P < 0.001). Thirty-one eyes with macular edema were examined at baseline and at follow-up with OCT. There were three patterns of macular edema: diffuse (DME) (28.5%), cystoid (29%), and serous retinal detachment (45.2%). Initial VA of 20/40 or better was significantly associated with central macular thickness (CMT) of 300 μm or less (P = 0.0065) and DME (0.0484). At final follow-up, there was a significant reduction in CMT (P < 0.001) associated with a significant improvement in VA (P = 0.0091). Conclusions Antituberculous therapy combined with systemic corticosteroids leads to resolution of inflammation and elimination of recurrences of PTU. OCT is useful in monitoring the efficacy of treatment in patients with macular edema.