Topical Corneal Cross-Linking Solution Delivered Via Corneal Reservoir in Dutch-Belted Rabbits

通过角膜储液器向荷兰带兔输送局部角膜交联溶液

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作者:Mariya Zyablitskaya, Charles Jayyosi, Anna Takaoka, Kristin M Myers, Leejee H Suh, Takayuki Nagasaki, Stephen L Trokel, David C Paik

Conclusions

Topical cross-linking conditions that are safe and can increase corneal stiffness/strength in the living rabbit eye have been identified. Translational relevance: A topical corneal cross-linking solution delivered via corneal reservoir is shown to be both safe and effective at increasing tissue strength in living rabbit eyes and could now be tested in patients suffering from keratoconus and other conditions marked by corneal tissue weakness.

Methods

A series of experiments were carried out using Dutch-belted rabbits (3 months old, weighing 1.0-1.5 kg) and topical cross-linking solutions (sodium hydroxymethylglycinate) (10-250 mM) delivered via corneal reservoir. The application regimen included a one-time 30-minute application (10-40 mM sodium hydroxymethylglycinate) as well as a once per week 5-minute application (250 mM sodium hydroxymethylglycinate) for 7 weeks. Animals were evaluated serially for changes in IOP, pachymetry, epithelial integrity, and endothelial cell counts. Keratocyte changes were identified using intravital laser scanning confocal microscopy. Post mortem efficacy was evaluated by mechanical inflation testing.

Purpose

A topical corneal cross-linking solution that can be used as an adjunct or replacement to standard photochemical cross-linking (UV-riboflavin)

Results

Overall, there were very few differences observed in right eye treated versus left eye controls with respect to intraocular pressure, pachymetry, and endothelial cell counts, although 30-minute cross-linking techniques did cause transient increases in thickness resolving within 7 days. Epithelial damage was noted in all of the 30-minute applications and fully resolved within 72 hours. Keratocyte changes were significant, showing a wound healing pattern similar to that after riboflavin UVA photochemical cross-linking in rabbits and humans. Surprisingly, post mortem inflation testing showed that the lower concentration of 20 mM delivered over 30 minutes showed the most profound stiffening/strengthening effect. Conclusions: Topical cross-linking conditions that are safe and can increase corneal stiffness/strength in the living rabbit eye have been identified. Translational relevance: A topical corneal cross-linking solution delivered via corneal reservoir is shown to be both safe and effective at increasing tissue strength in living rabbit eyes and could now be tested in patients suffering from keratoconus and other conditions marked by corneal tissue weakness.

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