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Prognostic significance of matrix metalloproteinase 9 in COMET operated chronic ocular Stevens-Johnson syndrome
  1. Renu Venugopal1,
  2. Namrata Sharma1,
  3. Seema Sen2,
  4. Sujata Mohanty3,
  5. Seema Kashyap2,
  6. Tushar Agarwal1,
  7. Jasbir Kaur4,
  8. Rasik B Vajpayee5
  1. 1Ophthalmology, Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
  2. 2Ocular Pathology, Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
  3. 3Stem Cell Facility, All India Institute of Medical Sciences, New Delhi, Delhi, India
  4. 4Ocular Biochemistry, Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, Delhi, India
  5. 5Vision Eye Institute, Melbourne, Victoria, Australia
  1. Correspondence to Dr Namrata Sharma, Ophthalmology, All India Institute of Medical Sciences, New Delhi, Delhi, India; namrata.sharma{at}gmail.com

Abstract

Purpose Molecular 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.

Methods In 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.

Results MMP9 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).

Conclusion Our 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.

  • ocular surface
  • pathology
  • tears

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Footnotes

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  • Contributors RV contributed to the study protocol, conducted the experiment, analysed and interpreted the data, wrote, proofed and revised the article. NS and SS designed the study protocol, analysed and interpreted the data, wrote, proofed and revised the article. SM, TA, SK and JK provided materials, designed the study protocol, analysed and interpreted the data, proofed and revised the article. RBV proofed and revised the article.

  • Funding This study was funded by UGC-CSIR JRF fellowship no 20-06/2010(I)EU-IV.

  • Disclaimer The sponsor or funding organisation had no role in the design or conduct of this research.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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