July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Evaluation of a topical corneal cross-linking solution using sodium hydroxymethylglycinate by intravital confocal microscopy in the Dutch-belted rabbit: a follow up report on keratocyte morphologic changes.
Author Affiliations & Notes
  • David C Paik
    Ophthalmology, Columbia University, New York, New York, United States
  • Mariya Zyablitskaya
    Ophthalmology, Columbia University, New York, New York, United States
  • Anna Takaoka
    Ophthalmology, Columbia University, New York, New York, United States
  • Jaya R. Mehta
    Ophthalmology, Columbia University, New York, New York, United States
  • Estee Hong
    Ophthalmology, Columbia University, New York, New York, United States
  • Sara Fallahi
    Ophthalmology, Columbia University, New York, New York, United States
  • Leejee Suh
    Ophthalmology, Columbia University, New York, New York, United States
  • Takayuki Nagasaki
    Ophthalmology, Columbia University, New York, New York, United States
  • Stephen L. Trokel
    Ophthalmology, Columbia University, New York, New York, United States
  • Footnotes
    Commercial Relationships   David Paik, none (P); Mariya Zyablitskaya, None; Anna Takaoka, None; Jaya Mehta, None; Estee Hong, None; Sara Fallahi, None; Leejee Suh, None; Takayuki Nagasaki, None; Stephen Trokel, none (P)
  • Footnotes
    Support  NEI R01EY020495 (dcp), NEI P30 EY019007, NCRR UL1RR024156, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 354. doi:
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      David C Paik, Mariya Zyablitskaya, Anna Takaoka, Jaya R. Mehta, Estee Hong, Sara Fallahi, Leejee Suh, Takayuki Nagasaki, Stephen L. Trokel; Evaluation of a topical corneal cross-linking solution using sodium hydroxymethylglycinate by intravital confocal microscopy in the Dutch-belted rabbit: a follow up report on keratocyte morphologic changes.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):354.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To develop a topical corneal cross-linking solution that can be used in an office procedure for intensive therapy or in an eyedrop that could be self-administered over an extended period of time. Either of these methods could provide a more patient-friendly way to stabilized the keratoconic cornea since they would not require epithelial debridement or UV light exposure.

Methods : Corneal cross-linking solutions containing using sodium hydroxymethylglycinate (SMG) [20-240mM] were applied to the corneal surface of 1.0-1.5kg Dutch-belted rabbits (n=28) using either of two methods, a corneal reservoir (CR) [n=14] or viscous eyedrops (VE) [n=14]. CR treatments were carried out as a single procedure or at weekly intervals for up to 7 weeks. In the case of VE, 50ul was generally applied three times per day for up to 3 months. The animals were serially evaluated in real-time by intravital confocal microscopy (HRT3-RCM) prior to treatment and at 1-4 week intervals.

Results : Loss of hyper-reflective keratocyte nuclei occurred within the first two days of CR treatment. Morphologic features of keratocyte activation that include stellate and spindle nuclear forms with hyper-reflective cytoplasm in either a syncytial or striated pattern were seen and occurred in clustered regions. These areas of increased cell migration and proliferation are reminiscent of HRT findings reported in rabbits and patients following CXL. In addition, areas of broad-banded hyper-reflectivity, representing newly synthesized disorganized collagen, were seen primarily following one-time CR therapy (30min). Anterior, mid, and posterior changes were seen at one week and normalized by week 10 using this method. At lower concentrations of SMG, this effect was limited to the anterior and mid layers and caused to delay in onset by one week, consistent with a concentration-dependent effect.

Conclusions : These real time findings suggest a form of wound healing response in the topically cross-linked cornea similar to that seen following CXL. Keratocyte migration, proliferation, and activation are significant and can be modulated based on delivery method and concentration of SMG.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Time and depth dependent changes in keratocyte morphology as seen by intravital confocal microscopy following one-time (30min) topical corneal cross-linking.

Time and depth dependent changes in keratocyte morphology as seen by intravital confocal microscopy following one-time (30min) topical corneal cross-linking.

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