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Mariya Zyablitskaya, Anna Takaoka, Alexandra H. Scanameo, Daeryl E. Amponin, Leejee H Suh, Stephen Trokel, Takayuki Nagasaki, David C Paik; Evaluation of topical corneal therapeutic tissue cross-linking (TXL) using sodium hydroxymethylglycinate (SMG) by intravital confocal microscopy in rabbits. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4344.
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The success of riboflavin photochemical (CXL) corneal stabilization in keratoconus has proven that in vivo tissue cross-linking can be used as an effective therapy. Several drawbacks remain, however, and include the need for epithelial debridement and the use of ultraviolet-A irradiation. The current study was undertaken to evaluate the safe use of a candidate topical therapeutic tissue cross-linking (TXL) agent that is in current commercial use as a cosmetic preservative
Therapeutic tissue cross-linking using a 0.5-3% (40-250mM) solutions of sodium hydroxymethylglycinate (SMG) was carried out on Dutch-belted rabbits (n=10) using 3 different methods, a corneal reservoir (CR), viscous eyedrop (VE), and drug-soaked hydrogel contact lens (CL). The longest treatment was carried out on a weekly basis (7 times over 7 weeks) using 250mM solutions applied for 5 minutes via CR. The effects were followed in real time using intravital confocal microscopy (HRT3-RCM)
The parameters for non-toxic cross-linking treatments were defined for CR, VE, and CL (250mM X 5 minutes for CR, 40mM twice daily for VE, and 40mM soaked etafilcon A (58% water content) CL applied for 15 minutes]. Confocal microscopy identified 3 major patterns of keratocyte change, particularly prominent during prolonged treatment via CR (7 treatments over 7 weeks). Anterior stromal keratocyte death occurred within the first few days of the initial treatment, mid stromal keratocyte activation (spindle-like) occurred from weeks 1-3, and anterior stromal keratocyte activation (syncytial-like) occurred beginning at week 3. Corneal thickness, endothelial cell density, and epithelial defect changes were not significantly affected by any method of application
Topical application of a 3% SMG solution (for 5 minutes) via a corneal reservoir method appears to be safe to the rabbit cornea and induces a wound healing response in the corneal stroma. Similar changes by confocal microscopy have been reported for CXL albeit at later time points. In addition, three different methods for safe topical application of SMG TXL solution are possible and include a CR, VE, and CL. These methods holds promise for clinical use since neither epithelial debridement nor UVA irradiation are necessary
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
HRT-RCM images for 2 corneal depths - control and treated eye over 2,5 months period
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