Official ESCRS | European Society of Cataract & Refractive Surgeons


Impact of oxygen, UV parameters, and drug formulation on accelerated epi-on corneal cross-linking

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Session Details

Session Title: Corneal Cross-Linking

Session Date/Time: Monday 16/09/2019 | 16:00-18:00

Paper Time: 16:18

Venue: South 5

First Author: : D.Gore UK

Co Author(s): :    J. HIll   C. Liu   P. Deardorff   V. Thompson   M. Raizman   D. Adler              

Abstract Details


Performing corneal collagen crosslinking (CXL) through an intact epithelium (epi-on) at a high irradiance can potentially improve patient comfort, visual recovery, and clinical workflow compared to conventional low-irradiance epi-off CXL. However, the intact epithelium limits stromal delivery of the oxygen, photosensitizing drug, and ultraviolet-A (UVA) radiation needed to drive CXL. This ex vivo study evaluated the biomechanical and topographic effects of three different epi-on CXL protocols with varying paradigms for oxygen delivery, drug formulation, and UVA parameters. Endpoints included mid-stromal oxygen levels, stiffness of crosslinked tissue, and acute flattening of whole eyes.


This study was performed in a laboratory setting using fresh, whole porcine eyes.


Eyes were held in a chamber to control environmental parameters and oxygen concentration (21% or >90%). Intrastromal oxygen was monitored before, during, and after UVA using a fiberoptic probe. Two epi-on protocols using irradiance of 30mW/cm2, dose of 10J/cm2, 1sec : 1sec pulsing, and riboflavin with benzalkonium chloride were studied, with and without supplemental oxygen. A third epi-on protocol using 4mW/cm2, 4.1J/cm2, 15sec : 15sec pulsing, room air, and riboflavin with sodium iodide was studied. Negative (no CXL) and positive (epi-off, 3mW/cm2, 5.4J/cm2, room air) controls were performed. Stiffness and flattening were measured using an extensiometer and Pentacam tomographer.


Intrastromal measurements showed that delivery of supplemental oxygen around the eye resulted in a ~5x increase in mid-stromal oxygen levels prior to CXL. During high-irradiance epi-on UVA delivery under hyperoxic conditions, mid-stromal oxygen levels stabilized at ~15%. Conversely, under normoxic conditions, mid-stromal oxygen rapidly depleted to 0 – 5% for all other protocols regardless of drug formulation and UVA parameters. Accordingly, the high-irradiance hyperoxic protocol generated significantly more change in corneal stiffness (11.93MPa) and flattening (-1.58D) than the other epi-on protocols (8.25 to 10.64MPa, -0.69 to -0.96D), closely approaching the results of the positive epi-off control group (13.32MPa, -2.68D).


This study demonstrated the potential for accelerated epi-on CXL to deliver effects comparable to epi-off Dresden CXL. Supplemental oxygen enables equilibrium between stromal supply and demand, the surfactant BAC ensures sufficient photosensitizer delivery, and the elevated irradiance of 30mW/cm2 and dose of 10J/cm2 ensures sufficient UVA levels in the mid-stroma. Through this combination of factors, the accelerated hyperoxic epi-on protocol delivers significant corneal stiffening and flattening. Conversely, epi-on CXL using riboflavin with sodium iodide, lower irradiance and dose, longer pulsing, and normoxic conditions did not produce measurable effects compared to negative controls, highlighting the criticality of careful protocol optimization.

Financial Disclosure:

is employed by a for profit company with an interest in the subject of the presentation, receives consulting fees, retainer, or contract payments from a company producing, developing or supplying the product or procedure presented

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