Sodium hydroxymethylglycinate via eyedrop for corneal cross-linking in Dutch-belted rabbits: a comparison of 40mM (0.5%) vs 80mM (1%) concentrations

Abstract

Purpose : Using an eyedrop, to develop a safe and effective way to increase corneal tissue strength where the effect can be modulated based on the patients response. This also avoids the use of UV light and painful epithelial debridement. For use as a replacement or adjunct to the current UV-riboflavin photochemical method (i.e. CXL)

Methods : Corneal therapeutic tissue cross-linking (cTXL) using sodium hydroxymethylglycinate (SMG) at 40 or 80mM was carried out on Dutch-belted rabbits (n=8). SMG eyedrops (right eye) and vehicle control (left eye) were applied to the corneal surface 1-3 times/day for up to 3 months. Intermittent bolus dosing (every 15 min for 1 or 3.5 hours followed by Draize testing) was also carried out on two animals. The animals were evaluated in real-time using ultrasound pachymetry, applanation tonometry, confocal microscopy (HRT3-RCM), corneal topography, and fluorescein epithelial staining. Post-mortem cross-linking effects were evaluated by mechanical inflation testing and thermal denaturation temperature, and routine histology was also included

Results : The higher 80mM concentration caused some irritation and drying of the eyelid during 3 months dosing. The 40mM eyes were normal. Corneal thickness, intraocular pressure, endothelial cell density, and epithelial defect changes were not significantly affected by either concentration tested over 3 months. Tissue stiffening by mechanical inflation testing was noted in 4 of 4 animals [avg △apex displacement between treated and paired control eye (at 2kPa during creep testing) was: △Dinitial=-0.0692mm±0.0266 and △Dfinal=-0.0671mm±0.0196] and modest corneal thermal denaturation shifts (avg △Tm=0.81±0.36) were noted in 3 of 3 samples. HRT stromal keratocyte changes included stellate and syncytial patterns of keratocyte activation as well as cell loss. These findings were noted only with 80mM, however, indicating that the treatment with 40mM was non-toxic while inducing cross-linking effects. There were no histologic abnormalities observed in the eyelid, lens or retina in the treated tissues

Conclusions : Topical application of a 40mM (0.5%) SMG eyedrop is well tolerated by the living rabbit eye and can increase corneal tissue stiffness without damaging keratocytes. This is an important example of favorable toxicity/fixation balance

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.