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Marie-Claude Robert, Samer N Arafat, Sandra Spurr-Michaud, James Chodosh, Claes H Dohlman, Ilene K Gipson; Tear Matrix Metalloproteinases and Myeloperoxidase Levels Following Boston Keratoprosthesis Type I surgery.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4685. doi: https://doi.org/.
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To investigate the levels and activity of matrix metalloproteinases (MMPs), myeloperoxidase (MPO) and tissue inhibitor of metalloproteinase-a (TIMP-1) in tears of eyes with Boston Keratoprosthesis type I (KPro) and to correlate these markers with the well-established prognostic hierarchy for KPro surgery. Indeed, eyes with non-cicatricial disease, chemical burns and autoimmune disease have, in this order, an increasing risk of failure following KPro implantation.
In this prospective, non-interventional cohort study, bilateral tear washes were collected from patients with KPro. Tear fluid analysis for levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 was performed using a multianalyte bead-based enzyme-linked immunosorbent assay. Total MMP activity was determined using a fluorometric assay. Correlation studies were performed between the various analytes and the underlying diagnoses leading to KPro. In eyes with unilateral KPro, MMP and MPO levels were compared between the operated and non-operated eye.
Of the fourteen patients participating in this study, two had an underlying diagnosis of autoimmune disease, two had chemical burn and ten had non-cicatricial diagnoses. Tear collection was performed an average of 8 years (range 1 month to 17 years) after initial KPro surgery. MMP-9 and MPO levels were elevated in all KPro tears. When compared to eyes with non-cicatricial diseases, eyes with autoimmune disease had higher tear levels MMP-8, MMP-9 and MPO while eyes with chemical burn had higher tear levels of MMP-9 and MPO only. The MMP-8 to TIMP-1 and MMP-9 to TIMP-1 ratios were 2.4 and 1.3 times higher in eyes with KPro when compared to the contralateral eyes without KPro.
Our study shows that the tears of eyes with KPro have constitutively high levels of MMPs even years after the initial insult and KPro surgery. This is particularly true for those eyes with autoimmune disease or chemical burn. In the presence of bilateral pathology, eyes with KPro seem to have higher MMP and MPO levels when compared to that of the contralateral non-KPro eye. The introduction of MMP inhibitors and/or additional anti-inflammatory prophylaxis may be warranted to suppress MMP activity and therefore, protect high-risk KPro eyes from corneal tissue melt.
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