Impact of corneal cross‐linking on topical drug penetration in humans

Abstract

ABSTRACT.Purpose: To analyse the influence of corneal cross-linking (CXL) with ultraviolet-A (UV-A) and riboflavin on drug permeability in human subjects. Methods: Keratoconus patients (n = 23; mean age 26.9 AE 5.8 years) undergoing a standard CXL procedure with UV-A (5.4 J/cm 2 , 30 min) and riboflavin in one eye were included in the study. The pupillary diameter, measured before and every 3 min for 30 min after the topical application of one drop of 2% pilocarpine, was used as an indirect measure of the corneal permeability. The pupillary diameter was measured with an infrared pupillometer device before (baseline) and 4 months after CXL. Results: Prior to pilocarpine application, no significant difference in the pupillary diameter was detected before CXL and 4 months later. The mean decrease in the pupillary diameter after the application of pilocarpine was similar at baseline and the 4-month follow-up visit: mean decreases of 3.9 and 3.7 mm were observed 30 min after pilocarpine application, respectively (p > 0.05). Conclusions: No significant influence of CXL on the corneal penetration of topically applied pilocarpine was observed in this clinical study.

Microbiologic, Pharmacokinetic, and Clinical Effects of Corneal Collagen Cross-Linking on Experimentally Induced Pseudomonas Keratitis in Rabbits

“…16 Furthermore, the timepoint of permeability measurements after CXL may play a crucial role. A significantly reduced permeability was detected when the measurements were taken directly after CXL in the porcine cornea, 14 whereas only a trend for reduced permeability, without reaching statistical significance, was found when measurements were collected 1 month after CXL in rabbits, 16 4 months after CXL in humans, 17 or 1 year after CXL in rabbits. 15 Presumably, inflammatory activity from CXL-related keratocyte apoptosis might interfere with the drug penetration through the cornea in the early phase after CXL.…”

“…In contrast to the present finding that CXL alone is not effective for This study used an accelerated CXL protocol that was recently proposed as an alternative for speeding up the procedure by delivering higher irradiance to the cornea, thus reducing the required light exposure time. 16,17 Using this procedure, only loose epithelium and the epithelium around the infectious site were removed. Recently, Rosetta et al 2 described a new protocol referred to as cross-linking window absorption (CXL-WA) for the treatment of microbial keratitis and infectious corneal ulcers.…”

“…Furthermore, no significant difference was reported in living rabbits after CXL in a later study by Litvin et al 16 that compared the concentrations of topically applied moxifloxacin in the aqueous humor before and 1 month after CXL. In addition, Tappeiner et al 17 have demonstrated that CXL with UV-A and riboflavin does not significantly alter corneal permeability of pilocarpine in an in vivo clinical trial in human subjects. Until now, no data about the impact of CXL on corneal permeability in a keratitis model have been available.…”

Corneal collagen cross‐linking for infectious keratitis: an update of clinical studies

“…A recent clinical study also demonstrated a reduced ocular penetration of topical medications after CXL (Tappeiner et al. ).…”

“…A recent clinical study also demonstrated a reduced ocular penetration of topical medications after CXL (Tappeiner et al 2014). The long-term safety issue of CXL on the corneal endothelium has not been addressed fully in most studies.…”