Matrix metalloproteinase 9 is associated with conjunctival microbiota culture positivity in Korean patients with chronic Stevens-Johnson syndrome

Abstract

Background: Stevens-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.

Methods: Medical records were retrospectively reviewed in 30 chronic SJS patients who had undergone conjunctival swab culture sampling. Demographic factors, chronic ocular surface complications score (COCS), tear break-up time (TBUT), tear secretion, 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 (70%) (P = 0.041). Topical cyclosporine and corticosteroid were not associated with repetitive positive cultures. No significant differences in COCS, TBUT, and tear secretion were found between culture-positive and culture-negative groups.

Conclusion: Our study suggests that tear MMP9 positivity may be related with the presence of an abnormal ocular surface microbiota in chronic SJS patients.

Keywords: Conjunctiva; Matrix metalloproteinase 9; Microbiota; Stevens-Johnson syndrome.

Fig. 1

The representative photos of low (0–7) and high (≥ 8) COCS. Figures A and B represents low (0–7) COCS and are photos of a female subject’s left eye with a COCS score of 3 who had been diagnosed with sulfasalazine-related SJS at the age of 49. Her left eye exhibited 12 clock hours of corneal neovascularization and nasal corneal opacity but without severe meibomian gland dysfunctions, chronic conjunctival hyperemia nor symblepharon (A). Under cobalt blue filter examination after fluorescein application, superficial punctate epithelial erosions were observed in the inferior 2/3 of the cornea (B). Figures C and D represents high (≥ 8) COCS and are photos of a female subject’s left eye with a COCS score of 10 who had an onset of SJS at age 44 after taking cold medications. Her left eye had conjunctivalization at the upper 2/3 of the cornea due to limbal stem cell deficiency with diffuse corneal haze, chronic conjunctival hyperemia, severe eyelid meibomian gland dysfunctions with trichiasis and symblepharon at both upper and lower lateral portions (C). Under cobalt blue filter examination after fluorescein application, diffuse superficial punctate epithelial erosions were observed (D). COCS: Chronic Ocular Surface Complications Score, SJS: Stevens-Johnson syndrome.

Fig. 2

Analysis of demographic characteristics or clinical factors to affect positive culture group. A-C No significant differences were observed in the average age (A), disease duration (B) and history of prior infectious keratitis (C) between positive-culture and negative-culture groups (Mann-Whitney test, Fisher’s exact test, P > 0.05). D-E The COCS (D) and tear secretion by Schirmer test (E) were not different between those groups (Mann-Whitney test, P > 0.05). F Tear MMP9 positivity was higher in positive-culture group than in negative-culture group (Fisher’s exact test, P = 0.041) (G-I). There were no differences in the use of topical medications, such as corticosteroids (G), cyclosporine (H) or antibiotics (I) (Fisher’s exact test, P > 0.05). COCS: Chronic Ocular Surface Complications Score, TBUT: Tear break up time, MMP9: Matrix metalloproteinase 9, vs: Versus