Restoration of Corneal Stiffness in Rabbits Following Withdrawal of Travoprost.

Abstract

Purpose: To evaluate if the effect of travoprost on corneal material stiffness could be restored after drug withdrawal.

Methods: Seventy-two rabbits were randomly allocated into three groups: medicine (M), medicine withdrawal (MW), and blank (B). Within the M and MW groups, treatment with travoprost was administered to the right eyes (MT and MWT) over a period of 12 weeks. Subsequently, the M group was killed, but the MW group underwent an additional 12-week period for treatment withdrawal. No treatment was given to the contralateral eyes (MC and MWC) in the M and MW groups. A separate blank control (BC) group remained untreated for the entire 24-week duration. In each group, corneas from 18 rabbits were tested mechanically under inflation conditions to estimate their tangent modulus (Et). The corneas of the remaining six rabbits underwent electron microscopy analysis, which focused on fibril diameter and interfibrillar spacing.

Results: Central corneal thickness (CCT) of the treated eyes (MT and MWT groups) decreased with 12 weeks of travoprost treatment (P < 0.05). The CCT in the MWT group increased after 12 weeks of withdrawal but was still lower than that in the BC group (P < 0.05). The Et of the MT group was significantly lower than that of the MC group at mean tissue stresses of 2, 4, and 6 kPa (P < 0.05). Conversely, no significant difference in Et values was observed between the MWT, MWC, and BC groups, indicating recovery after treatment cessation. Furthermore, the stromal interfibrillar spacing of the treated MT group was significantly larger (P < 0.05) than that of the control MC group, but no disparity was noted among the MWT, MWC, and BC groups following treatment withdrawal. Additionally, there were no significant differences in the mean diameter of collagen fibrils among all groups (all P > 0.05).

Conclusions: Travoprost treatment appears to soften corneal tissue, decrease tissue thickness, and reduce the density of stromal collagen fibers by increasing the interfibrillar spacing. These changes were partially reversed after treatment cessation. Travoprost could further inhibit corneal growth, so its use in childhood and adolescence should be carefully considered. Additionally, the effect of travoprost in reducing corneal stiffness may lead to underestimations of intraocular pressure (IOP) measurement and hence overestimations in the effect of treatment in lowering IOP.