Prognostic significance of matrix metalloproteinase 9 in COMET operated chronic ocular Stevens-Johnson syndrome

2021 ◽  
pp. bjophthalmol-2021-319302
Author(s):  
Renu Venugopal ◽  
Namrata Sharma ◽  
Seema Sen ◽  
Sujata Mohanty ◽  
Seema Kashyap ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Ocular Surface ◽  
Prognostic Significance ◽  
Matrix Metalloproteinase 2 ◽  
Clinicopathological Parameters ◽  
Stevens Johnson Syndrome ◽  
Matrix Metalloproteinase 1 ◽  
Johnson Syndrome ◽  
Surface Inflammation ◽  
Ocular Surface Inflammation

PurposeMolecular pathogenesis underlying persistent ocular surface inflammation in chronic Stevens-Johnson syndrome (SJS) still remains largely unexplored. The present study investigates the expression of matrix metalloproteinase 2 (MMP2), MMP3, MMP9, MMP11 and TIMP1 (tissue inhibittor of matrix metalloproteinase 1) in pannus tissues of chronic ocular SJS undergoing cultivated oral mucosal epithelial transplantation (COMET) and their prognostic relevance.MethodsIn this prospective study, 45 eyes with chronic SJS underwent COMET for visual and anatomical rehabilitation. Preoperative and postoperative clinical parameters were documented. MMP2, MMP3, MMP9, MMP11 and TIMP1 expression were assessed using immunohistochemistry and quantitative real time PCR. Inflammadry MMP9 assay was performed at 1-year follow-up. Kaplan-Meier curves and Cox proportional hazard models were used to correlate protein expression with clinicopathological parameters and COMET graft survival outcomes.ResultsMMP9 and MMP11 positivity was seen in both pannus epithelia (48% and 55%, respectively) and in stromal layer (57% and 33%, respectively) while MMP2 and MMP3 showed only pannus epithelial positivity in 35% and 51% cases, respectively. High MMP9 stromal expression was significantly associated with preoperative corneal keratinisation (p=0.011), conjunctival hyperaemia (p=0.014), symblepharon (p=0.028). High MMP9 and MMP3 epithelial expression were found to be independent risk factors for poor best-corrected visual acuity (BCVA) outcomes post-COMET (p=0.022 and p=0.048). Multivariate analysis revealed MMP9 to be the best prognostic marker (p=0.050).ConclusionOur findings suggest that differential expression of MMPs and TIMP1 is seen in SJS in chronic stage. Emergence of MMP9 as a poor prognostic predictor of BCVA post COMET and postoperative MMP9 immunoassay positivity could be a useful tool in further studies to understand the unresolved ocular surface inflammation seen in SJS.

scholarly journals Japan: Diagnosis and Management of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis With Severe Ocular Complications

2021 ◽  
Vol 8 ◽  
Author(s):  
Chie Sotozono ◽  
Mayumi Ueta ◽  
Shigeru Kinoshita
Keyword(s):  
Stem Cell ◽  
Contact Lens ◽  
Ocular Surface ◽  
Disease Onset ◽  
Stevens Johnson Syndrome ◽  
Ocular Involvement ◽  
Chronic Stage ◽  
Rigid Contact ◽  
Surface Inflammation ◽  
Ocular Surface Inflammation

In 2005, the “Japanese Research Committee on Severe Cutaneous Adverse Reaction” (J-SCAR) presented the official “Diagnostic Criteria” for SJS/TEN, and the specific ocular findings are included in these very important criteria. In SJS/TEN cases involving ocular disorder, conjunctivitis often occurs prior to the onset of the high fever. In a Japanese survey, ocular involvement was observed in 77% of the cases, and the incidence of ocular sequelae increased depending on the score of the acute ocular severity findings. Pseudo-membrane formation and epithelial defects are considered to be high-risk signs of ocular sequelae. At the chronic stage, limbal stem cell deficiency, visual disturbance, and severe dryness of the ocular surface are the primary disease characteristics. In 2002, we started performing Cultivated Oral Mucosal Epithelial Transplantation (COMET) for the treatment of severe ocular disorders, including SJS/TEN. As an additional treatment method, we developed a new type of rigid contact lens (CL) that is 13 to 14.0-mm in diameter, known as the “Limbal Rigid Contact Lens (Limbal CL).” Our Limbal Rigid CL greatly enhances the postoperative outcome of COMET. The detection rate of ocular surface bacteria is high in SJS/TEN cases. Thus, appropriate use of topical antibiotics reduces the risk of ocular surface inflammation. Moreover, rebamipide is an ophthalmic solution for dry eye that was developed in Japan, and it also has the effect of suppressing ocular surface inflammation. From disease onset until the chronic stage, the control of inflammation and stem cell loss is key to successfully treating eyes afflicted with SJS/TEN.

scholarly journals Matrix Metalloproteinase-9 and Topical Cyclosporine Are Associated with Conjunctival Microbiota Culture Positivity in Korean Patients with Stevens-Johnson Syndrome

2021 ◽  
Author(s):  
Jayoon Moon ◽  
Yunjin Lee ◽  
Mee Kum Kim
Keyword(s):  
Matrix Metalloproteinase ◽  
Ocular Surface ◽  
Positive Culture ◽  
Matrix Metalloproteinase 9 ◽  
Stevens Johnson Syndrome ◽  
Culture Result ◽  
Culture Positivity ◽  
Johnson Syndrome ◽  
Conjunctival Swab ◽  
Metalloproteinase 9

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.

Long-term Progression of Ocular Surface Disease in Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis

Cornea ◽  
2020 ◽  
Vol 39 (6) ◽  
pp. 745-753
Author(s):  
Yamato Yoshikawa ◽  
Mayumi Ueta ◽  
Hideki Fukuoka ◽  
Tsutomu Inatomi ◽  
Isao Yokota ◽  
...  
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Ocular Surface ◽  
Ocular Surface Disease ◽  
Stevens Johnson Syndrome ◽  
Johnson Syndrome

scholarly journals Autologous Blood Products: When, Where, and How?

2021 ◽  
Vol 8 (1) ◽  
pp. 1-9
Author(s):  
Alfonso L Sabater ◽  
Keyword(s):  
Ocular Surface ◽  
Keratoconjunctivitis Sicca ◽  
Therapeutic Option ◽  
Autologous Blood ◽  
Stevens Johnson Syndrome ◽  
Eye Drops ◽  
Corneal Epithelial ◽  
Johnson Syndrome ◽  
Ocular Surface Diseases ◽  
Persistent Epithelial Defects

Autologous blood eye drops have become an interesting, well-known, and widely used therapeutic option for many ocular surface diseases since their introduction into the ophthalmologic field forty-six years ago. The foundation for their use in the treatment of pathologies such as severe keratoconjunctivitis sicca, persistent epithelial defects, ocular chemical burns, recurrent epithelial erosions, Stevens-Johnson syndrome, ocular graft versus host disease, and, lately, in many other ocular surface conditions, relies on the fact that they contain proteins, vitamins, cytokines, and growth factors that participate in the signaling pathways of corneal epithelial healing in similar amounts to those found in normal, healthy tear films

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