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使用市售即时免疫检测法在干燥性眼病中检测基质金属蛋白酶 9。

Matrix Metalloproteinase 9 Testing in Dry Eye Disease Using a Commercially Available Point-of-Care Immunoassay.

机构信息

Department of Ophthalmology, Ludwig-Maximilians-Universität, München, Germany.

Department of Ophthalmology, Ludwig-Maximilians-Universität, München, Germany.

出版信息

Ophthalmology. 2016 Nov;123(11):2300-2308. doi: 10.1016/j.ophtha.2016.07.028. Epub 2016 Sep 21.

Abstract

PURPOSE

To measure matrix metalloproteinase 9 (MMP-9) in the tear film of patients with dry eye disease (DED) compared with controls and to correlate clinical findings.

DESIGN

In a prospective study, 101 patients and controls underwent MMP-9 testing of the tear film. Thereafter, they were evaluated for symptoms and signs of DED.

PARTICIPANTS

Included patients were those who showed 3 of the following 4 dry eye criteria: ocular surface disease index (OSDI) score of more than 12, tear film break-up time (TBUT) of 10 seconds or less, Schirmer test results without anesthesia of less than 10 mm/5 minutes, and corneal staining results of 1 or more. Fifty-four healthy eyes and 47 eyes fulfilling diagnostic criteria for DED of various levels of severity were included in this study.

METHODS

The tear film was analyzed for MMP-9 by a commercially available test (InflammaDry; Rapid Pathogen Screening, Inc, Sarasota, FL) detecting MMP-9 levels of more than 40 ng/ml. Symptoms and signs of DED were evaluated using the OSDI questionnaire, TBUT, conjunctival and corneal staining, Schirmer test results without anesthesia, and meibomian gland examination. These findings were correlated to results of the MMP-9 test in tears.

MAIN OUTCOME MEASURES

Positive MMP-9 results in tears.

RESULTS

In 19 of 47 patients confirmed with dry eye (40.4%) and in 3 of 54 controls (5.6%), the MMP-9 results were positive. This difference was statistically significant (P < 0.001). Thus, the MMP-9 results indicated a clinically significant inflammation in 40% of dry eye patients. Positive results correlated well with subjective symptoms of DED evaluated by OSDI (P = 0.001), TBUT of less than 5 seconds (P < 0.013), Schirmer test results (P < 0.001), conjunctival staining (P < 0.001), and corneal staining (P = 0.007). Moreover, MMP-9 results correlated with the number of obstructed meibomian ducts (P = 0.005) and a pathologic meibomian gland secretion (P = 0.001). The MMP-9 results were increased significantly in women (P < 0.001) and in patients with autoimmune disease (P = 0.005), especially Sjögren's syndrome (P = 0.001) and thyroid disease (P = 0.012).

CONCLUSIONS

Matrix metalloproteinase 9 testing in DED is a valuable new diagnostic tool. It correlated well with other dry eye tests and identified the presence of ocular surface inflammation in 40% of confirmed dry eye patients. It may be especially helpful to identify patients with ocular surface inflammation and autoimmune disease and may facilitate the decision to institute anti-inflammatory treatment in these patients.

摘要

目的

与对照组相比,测量干眼症(DED)患者泪膜中的基质金属蛋白酶 9(MMP-9),并进行相关性临床研究。

设计

在一项前瞻性研究中,对 101 名患者和对照组进行了泪膜 MMP-9 检测。此后,对他们的眼部干燥症状和体征进行了评估。

参与者

纳入的患者符合以下 4 项干眼症标准中的 3 项:眼表疾病指数(OSDI)评分大于 12 分,泪膜破裂时间(TBUT)小于 10 秒,无麻醉情况下的 Schirmer 测试结果小于 10mm/5 分钟,角膜染色结果为 1 或更多。本研究共纳入 54 只健康眼和 47 只符合不同严重程度 DED 诊断标准的眼。

方法

采用一种商业上可获得的检测方法(InflammaDry;Rapid Pathogen Screening,Inc,佛罗里达州萨拉索塔)检测 MMP-9 水平,当 MMP-9 水平大于 40ng/ml 时,检测结果为阳性。通过 OSDI 问卷、TBUT、结膜和角膜染色、无麻醉情况下的 Schirmer 测试结果以及睑板腺检查评估 DED 的症状和体征。将这些发现与泪膜中的 MMP-9 检测结果相关联。

主要观察指标

泪膜中 MMP-9 阳性检测结果。

结果

在 47 名确诊为干眼症的患者中有 19 例(40.4%)和 54 名对照组中有 3 例(5.6%)的 MMP-9 检测结果为阳性。这一差异具有统计学意义(P<0.001)。因此,MMP-9 检测结果表明 40%的干眼症患者存在临床显著的炎症。阳性结果与干眼症患者的主观症状(OSDI,P=0.001)、TBUT 小于 5 秒(P<0.013)、Schirmer 测试结果(P<0.001)、结膜染色(P<0.001)和角膜染色(P=0.007)相关性良好。此外,MMP-9 检测结果与阻塞性睑板腺数量(P=0.005)和病理性睑板腺分泌(P=0.001)相关。MMP-9 检测结果在女性(P<0.001)和自身免疫性疾病患者中(P=0.005)显著增加,尤其是干燥综合征(P=0.001)和甲状腺疾病(P=0.012)患者。

结论

在 DED 中进行 MMP-9 检测是一种有价值的新诊断工具。它与其他干眼症检测方法相关性良好,并在 40%确诊的干眼症患者中识别出眼表炎症的存在。它可能特别有助于识别眼表炎症和自身免疫性疾病患者,并可能有助于决定对这些患者进行抗炎治疗。

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