Optimization of Oxygen Dynamics, UV-A Delivery, and Drug Formulation for Accelerated Epi-On Corneal Crosslinking

Visual and Topographic Improvement with Epithelium-On, Oxygen-Supplemented, Customized Corneal Cross-Linking for Progressive Keratoconus

“…The epithelium is a barrier to the absorption of riboflavin and metabolically consumes oxygen. Laboratory studies have indicated that the additional of supplemental oxygen to the corneal surface increases the rate of oxygen diffusion to the corneal stroma [ 15 ]. The addition of supplemental oxygen aimed to increase stromal oxygen levels for the cross-linking reaction.…”

“…While cross-link formation is possible under both conditions, the aerobic pathway leads to more efficient generation of oxygen radicals compared to the anaerobic pathway. The addition of supplemental oxygen may improve the efficiency of epi-on cross-linking by increasing the rate of diffusion to the corneal stroma, such that oxygen is replenished faster than it is consumed [ 15 ]. This may be particularly relevant in epi-on protocols, where in addition to reduced oxygen bioavailability, the lipophilic epithelium also presents a physical barrier limiting the diffusion of riboflavin [ 13 ].…”

“…Epithelium-on (epi-on) CXL has been proposed to reduce the risk profile of the procedure and to improve patient comfort by eliminating the epithelial debridement step [ 12 ]. The epithelium acts as a natural barrier to riboflavin, ultraviolet light, and oxygen, three key components of cross-linking photochemistry, which may limit the effectiveness of epi-on CXL [ 13 , 14 , 15 ]. Modifications to the epi-on treatment approach include the development of transepithelial riboflavin formulations [ 16 , 17 ] or iontophoresis to enhance delivery to the corneal stroma [ 18 ], pulsed, accelerated UVA irradiation protocols to reduce the rate of oxygen consumption [ 19 , 20 ], and most recently, the addition of supplemental oxygen at the corneal surface to increase the rate of oxygen diffusion [ 15 , 21 , 22 ].…”

Oxygen Kinetics During Corneal Cross-linking With and Without Supplementary Oxygen

“…With an anticipated flap-thickness of >200 microns their results are in agreement to ours. Recently, also Hill et al 11 found no oxygen at 200 microns depth using 3mW/cm 2 in an atmospheric environment, however, with similar consumption times of around 30 seconds. On the other hand, our finding of stromal oxygen down to 300 microns at 3mw/cm 2 and down to 200 microns at 9mW/cm 2 at atmospheric oxygen conditions matches to clinically determined demarcation line depth.…”

“…Richoz and coworkers 9 performed crosslinking in an oxygen-free environment and found no significant stiffening effect emphasizing the importance of oxygen in CXL. To date, only few reports have been published on the basics of corneal oxygen kinetics during crosslinking 10,11 or on the biomechanical effect of supplementary oxygen during CXL. 10,12 The aim of this study was to provide experimental data on the oxygen consumption during CXL by determination of the oxygen profile at different depths using different irradiances and oxygen environments.…”