Classification of Histologically Proven Inflammation in Clinically Inactive Corneal Scars: Implications for Graft...

Background/Objectives: Clinically inactive corneal scars have repeatedly been shown to exhibit histological inflammation. This study aimed to evaluate the degree of histological inflammation in clinically inactive corneal scars of different origins and its correlation with graft rejection and failure following penetrating keratoplasty. Methods: The study included 205 primary corneal explants with clinically inactive central scars resulting from herpes simplex virus keratitis (HSV, n = 55), keratoconus (n = 39), mechanical trauma (n = 27), scrophulosa (n = 22) or other/unknown causes (n = 62). Central histological sections were categorized by the degree of inflammation, and an overall inflammation score (IS) was calculated. Results: HSV-associated scars exhibited a trend towards more graft rejection with higher IS (p = 0.074). Keratoconus-associated scars showed no IS-dependent differences in graft rejection or failure. The rejection rate in this group was 13/39. Scars resulting from mechanical trauma, such as perforating injuries, demonstrated a trend towards higher graft rejection (p = 0.15) and failure rates (p = 0.089) with increasing IS. The rejection rate in this group was 11/27. Scrophulosa-associated scars had significantly higher graft rejection rates (p = 0.041) at a lower cut-off of 0.06 compared to the cut-off of 0.36 for the other groups. Scars of other or unknown causes showed no IS-dependent differences in graft rejection or failure. Conclusions: Histological inflammation in HSV scars and scars resulting from mechanical trauma appeared to contribute to graft rejection. Despite low IS, the rejection rate in keratoconus scars and scars following mechanical trauma was unexpectedly high, indicating the presence of other influencing factors. While some correlations did not reach statistical significance due to small sample sizes in the subgroups, the observed trends should be considered clinically relevant. The study may have been "underpowered", as histopathologically inflamed specimens with clinically inactive corneal scars are relatively rare.