The Fate Of Collagen-based Hydrogels As Corneal Substitutes In "High Risk" Graft Recipients

Abstract

Purpose: : To compare the fate of collagen-based hydrogel implants as corneal substitutes in naïve vs. herpes simplex virus-1 (HSV-1)-infected opaque corneas.

Methods: : Implants (150-200μm in thickness) were prepared as 18% type III recombinant human collagen (RHC) cross-linked with (1) 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and its co-reactant N-hydroxysuccinimide (NHS); (2) (N-Cyclohexyl-N’-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate (CMC) and NHS and (3) EDC/NHS with phosphorylcholine (MPC) as an interpenetrating network. They were implanted into 1.5mm diameter graft beds of "high-risk" (HSV-infected) and "low-risk" (naïve) recipients. HSV-1 infection of the cornea was induced 6 weeks before the implant surgery. Hydrogels were secured with a single continuous suture. Implant "survival" time was graded clinically as corneal opacity and corneas evaluated immunohistochemically.

Results: : All three hydrogels were sufficiently strong to withstand the surgical procedure and were securely attached to the graft bed without clinically visible leak and with a well formed anterior chamber. The mean survival time (MST) of RHC-MPC hydrogel in naïve animals was 21.1d. The overall MSTs in HSK recipients as assessed by the opacity score was 13.5d/12.5d/14.4d (RHC-EDC vs. RHC-CMC vs. RHC-MPC respectively) post graft (no significant difference among groups). The MST in HSV-infected vascularised graft beds was significantly lower compared to HSV-infected graft beds without vessels (11.1d vs. 21.6d in RHC-EDC group; 7.25d vs. 23d in RHC-CMC group and 10.3d vs. 22.6d in RHC-MPC group). The main complication was wound necrosis and extrusion of implant. Immunohistology showed severe infiltration of myeloid cells with less infiltration of lymphoid cells in the recipient cornea but also around the implanted hydrogel. A thick retro-hydrogel membrane was detectable in some eyes which had extruded the implant.

Conclusions: : Collagen-based hydrogels are an attractive possibility as corneal substitutes for use in "high risk" opaque corneas such as those due to the previous HSV infection because of the potential to incorporate agents into the hydrogel to overcome the considerable immune and non-immune factors preventing graft acceptance.

Keywords: keratoprostheses • inflammation • herpes simplex virus