Purpose: Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) play critical roles in mediating corneal inflammation. In this study, topical blockade of IL-1 and TNF-α, alone or in combination, was compared to conventional corticosteroid anti-inflammatory therapy in suppressing infiltration of the cornea by antigen-presenting Langerhans cells (LCs) and in promoting corneal transplant survival in a mouse model of keratoplasty.

Methods: Study drugs included topical 2% IL-1 receptor antagonist (IL-1Ra), 1.5% soluble TNF-α receptor (sTNFR), and 1% prednisolone phosphate (Pred), all formulated in hyaluronic acid vehicle. Fifty eyes of BALB/c mice were used for LC studies where the numbers of LCs were determined 1 week after electrocautery to the corneal surface or transplantation of C57BL/6 corneas. Additionally, 65 BALB/c mice received corneal allografts and were randomized to receive one of the following for 8 weeks: (1) IL-1Ra, (2) sTNFR, (3) Pred, (4) combined IL-1Ra and Pred, or (5) vehicle alone.

Results: Mean suppression of LC infiltration after electrocautery or transplantation was 67% and 71%, respectively, for IL-1Ra, 40% and 62% for sTNFR, 70% and 72% for sTNFR+IL-1Ra, and 77% and 78% for Pred alone. Rejection rates were 15% for IL-1Ra (P = .01), 38% for sTNFR (P = .1), 17% for Pred (P = .02), and 7% for combined IL-1Ra+Pred (P = .002) as compared to 69% for the vehicle-treated group. IL-1Ra and Pred, but not sTNFR, significantly inhibited post-transplantation neovascularization.

Conclusions: Topical IL-1Ra and prednisolone are comparable in their capacity to promote graft survival. sTNFR therapy, though effective, has much lower efficacy as compared to IL-1Ra or Pred. Combination IL-1Ra and steroid therapy offers only minimal added efficacy over either agent used alone.