July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Biomechanical Impact of Drug Formulation, Supplemental Oxygen, and UV Delivery on Epi-On CXL
Author Affiliations & Notes
  • Desmond Christopher Adler
    Research and Development, Avedro, Inc., Waltham, Massachusetts, United States
  • Jason Hill
    Research and Development, Avedro, Inc., Waltham, Massachusetts, United States
  • Cailing Liu
    Research and Development, Avedro, Inc., Waltham, Massachusetts, United States
  • Phillip Deardorff
    Research and Development, Avedro, Inc., Waltham, Massachusetts, United States
  • Michael Raizman
    Ophthalmic Consultants of Boston, Waltham, Massachusetts, United States
  • Rajesh Rajpal
    Avedro, Inc., Waltham, Massachusetts, United States
    See Clearly Vision Group, Virginia, United States
  • Footnotes
    Commercial Relationships   Desmond Adler, Avedro, Inc. (I), Avedro, Inc. (E); Jason Hill, Avedro, Inc. (I), Avedro, Inc. (E); Cailing Liu, Avedro, Inc. (I), Avedro, Inc. (E); Phillip Deardorff, Avedro, Inc. (I), Avedro, Inc. (E); Michael Raizman, Avedro, Inc. (I), Avedro, Inc. (C); Rajesh Rajpal, Avedro, Inc. (I), Avedro, Inc. (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 317. doi:
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    • Get Citation

      Desmond Christopher Adler, Jason Hill, Cailing Liu, Phillip Deardorff, Michael Raizman, Rajesh Rajpal; Biomechanical Impact of Drug Formulation, Supplemental Oxygen, and UV Delivery on Epi-On CXL. Invest. Ophthalmol. Vis. Sci. 2019;60(9):317.

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

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Abstract

Purpose : Effective corneal crosslinking (CXL) requires sufficient photosensitizer, oxygen, and UV in the stroma to induce free radical formation. Delivery of all three constituents is challenging with an intact epithelium. This study provides ex vivo measurements comparing stromal riboflavin loading, oxygen availability, and biomechanical impact of two epi-on protocols using different paradigms for drug formulation, supplemental oxygen, and UV delivery.

Methods : Porcine eyes were partially de-epithelialized to approximate the thickness of human epithelium and held in an environmental chamber. Two protocols were evaluated. The first used 0.25% riboflavin with BAC followed by 0.22% riboflavin without BAC. Supplemental oxygen was delivered to the chamber and UV delivery was 30mW/cm2, 1sec : 1sec pulsing, and 10J/cm2. The second protocol used 0.50% riboflavin with 0.015% sodium iodide, room air, and UV delivery at 4mW/cm2, 15sec : 15sec pulsing, and 4.1J/cm2.

Depth-resolved riboflavin loading was measured with a confocal fluorescence microscope. Stromal oxygen was measured with a fiberoptic probe inserted into a laser-cut flap at 230 um. Stiffness was measured using an extensiometer.

Results : Stromal riboflavin and oxygen levels were higher in the first protocol. Riboflavin was likely higher due to the effects of BAC, which opens epithelial tight junctions, compared to the effects of sodium iodide, which is not known to alter the epithelial barrier function. Stromal oxygen was higher due to increased diffusion from the hyperoxic environment around the eye, even though irradiance was 7.5x higher in the first protocol. The combination of increased riboflavin and stromal oxygen, and more effective UV delivery, resulted in significantly more corneal stiffening (p=0.013) in eyes crosslinked with the first protocol.

Conclusions : In ex vivo porcine eyes, a combination of BAC additive, supplemental oxygen, and 30 mW/cm2, 10 J/cm2 UV resulted in more stiffening compared to an alternate epi-on protocol.

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

 

Stromal riboflavin measured with confocal microscopy. Paracel with BAC improves anterior loading compared to formulation with sodium iodide.

Stromal riboflavin measured with confocal microscopy. Paracel with BAC improves anterior loading compared to formulation with sodium iodide.

 

Left: Stromal oxygen before, during, and after UV. First protocol (Avedro) provides increased stromal oxygen compared to second (alternate) protocol. Right: Biomechanical assessment with extensiometer. First protocol provides increased corneal stiffness compared to second protocol.

Left: Stromal oxygen before, during, and after UV. First protocol (Avedro) provides increased stromal oxygen compared to second (alternate) protocol. Right: Biomechanical assessment with extensiometer. First protocol provides increased corneal stiffness compared to second protocol.

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