Production and Activity of Matrix Metalloproteinase-9 on the Ocular Surface Increase in Dysfunctional Tear Syndrome

Abstract BackgroundStevens-Johnson syndrome (SJS) is an abnormal immune-response causing extensive exfoliation of the mucocutaneous tissue including conjunctiva. While several factors are associated with the alteration of conjunctival microbiota, the conjunctiva of SJS patients are found to harbor a different microbiota compared to healthy subjects. We investigated the conjunctival microbiota of Korean SJS patients, and identified factors associated with the conjunctival microbiota and its positive culture.MethodsMedical records were retrospectively reviewed in 30 SJS patients who had undergone conjunctival swab culture sampling. Chronic ocular surface complications score (COCS), tear break-up time (TBUT), tear matrix metalloproteinase 9 (MMP9), and results of conjunctival swab culture were assessed.Results Positive culture was seen in 58.1%. Gram positive bacteria was most commonly isolated, among which Coagulase-negative Staphylococci (45.5%) and Corynebacterium species (40.9%) were predominantly observed. Tear MMP9 positivity was observed significantly more in the positive culture group (100%) compared to the negative culture group (75%) (P = 0.040). In patients who had repetitive cultures, positive- persistence group had more patients using topical cyclosporine compared to the negative-transition group (90.0% vs 33.3%, respectively, P = 0.041). No significant difference was found between COCS and conjunctival swab culture result, and the same as in TBUT and conjunctival swab culture result.ConclusionOur study suggest that tear MMP9 positivity may reflect the presence of an abnormal ocular surface microbiota and topical cyclosporine may be related to persistent culture positivity in SJS patients.

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Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease

Journal of Ophthalmology ◽

10.1155/2021/9958713 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Luigi Berchicci ◽

Emanuela Aragona ◽

Alessandro Arrigo ◽

Alessandro Marchese ◽

Elisabetta Miserocchi ◽

...

Keyword(s):

T Cell ◽

Matrix Metalloproteinase ◽

Graft Versus Host Disease ◽

Ocular Surface ◽

Matrix Metalloproteinase 9 ◽

Schirmer Test ◽

Host Disease ◽

Graft Versus Host ◽

Early Stages ◽

Metalloproteinase 9

Purpose. Graft versus Host Disease (GVHD) typically affects the ocular surface, with a presentation resembling Dry Eye Disease (DED). Although the etiopathology is not completely known, the conjunctiva might be a key site of T-cell activation. The differential diagnosis might be tricky at early stages, because of the lack of dedicated clinical and laboratory tests. To meet these needs, we evaluated the suitability of ocular surface matrix metalloproteinase-9 (MMP-9) clinical test. Methods. Consecutive GVHD patients, referred to IRCCS San Raffaele Scientific Institute, were recruited. DED patients served as controls. MMP-9 was tested through InflammaDry immunoassay kit in both groups; Ocular Surface Disease Index (OSDI) questionnaire, tear osmolarity, fluorescein Tear Break-up Time (TBUT), corneal and conjunctival staining, and Schirmer test I were also collected. Parametric and nonparametric statistical tests were used to analyze the intergroup differences; Receiver Operating Characteristics (ROC) curve analysis was carried out to perform sensitivity and specificity evaluations. Results. Forty-five GVHD and 40 DED patients were included. MMP-9 expression was significantly higher in GVHD group than in DED (84.4% vs 33%, p ≤ 0.001 ). Corneal and conjunctival staining scores resulted worse in GVHD than in DED (0.95 ± 1.16 vs 0.40 ± 0.63, p = 0.02 ; 0.77 ± 0.42 vs 0.40 ± 0.49, p = 0.0005 , respectively). No significant differences regarded the other collected parameters. GVHD group was characterized by positive correlations between MMP-9 and conjunctival staining (rho = 0.55, p = 0.0002 ) and between MMP-9 and OSDI (rho = 0.3, p = 0.01 ); a faint inverse correlation was found between MMP-9 and Schirmer test (rho = −0.25, p = 0.04 ). Conclusion. MMP-9 has a role in physiologic cellular remodeling; when a proinflammatory stimulus occurs, MMP-9 molecules are overreleased in the extracellular matrix. The positive expression of MMP-9 in GVHD may be interpreted as the consequence of a T-cell aggression against self-antigens and may be considered a reliable biomarker to detect ocular surface inflammation in GVHD, even in early stages of the disease.

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