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Thomas Dohlman, Jia Yin, Zala Luznik, William Foulsham, Tomas Blanco, Sunil Chauhan, Reza Dana; Graft Opacity in Corneal Transplant Failure is Characterized by Stromal Fibrosis: a Confocal Microscopy Analysis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6306.
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The relative contributions of stromal fibrosis, edema and immune cell infiltration to graft opacity in corneal transplant failure are unknown. The purpose of this study was to evaluate the contribution of fibrosis to graft opacity using confocal microscopy.
Standard low-risk allogeneic murine corneal transplants were performed and followed for 8 weeks. Graft opacity was graded on slit-lamp examination according to a standardized clinical scoring system. Grafts that were clear at post-operative week 2 and then subsequently developed opacity were considered failures and included for analysis (n=10). Confocal microscopy volume sequencing was used to evaluate grafts for the presence of stromal fibrosis, which was graded according to a novel scoring system (0-3) based on the degree and extent of fibrosis (0=no fibrosis, 1=minimal, 2=moderate, 3=advanced fibrosis). Syngeneic transplants served as controls (n=5).
Stromal fibrosis was identified on confocal microscopy in 8 out of 10 failed grafts but was not identified in any syngeneic control grafts (p=0.007). The 8 failed grafts with fibrosis were noted to contain multiple hyperreflective fan-like bands running anterior-posterior in the anterior stroma. Fibrosis was first noted at week 5 (4 grafts), week 6 (1 graft) and week 7 (3 grafts). By week 8, 4 grafts were graded as having advanced fibrosis, 2 had moderate fibrosis and 2 had minimal fibrosis. In contrast, the 2 failed grafts without fibrosis as well as the syngeneic controls displayed homogenous hyperreflectivity on confocal microscopy and did not display fibrotic bands.
In a murine model of corneal transplantation, we identified stromal fibrosis in a majority (80%) of failed corneal grafts, a previously unreported finding. Further investigation into the mechanisms of corneal fibrosis and its contributions to graft opacity are warranted.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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