Ultrasound-enhanced penetration of topical riboflavin into the corneal stroma.
OBJECTIVE
To determine whether ultrasound treatment can promote the permeation of topical riboflavin into the corneal stroma.


METHODS
Fresh cadaveric rabbit eyes with intact epithelium were left for 45 minutes in riboflavin 0.1% solution and divided in the following groups: A--untreated, epithelium-on; B--ultrasound-treated (1 W/cm(2) at 880 kHz for 6 minutes) with epithelium-on; and C--epithelium-off (no ultrasound). Eyes were removed from the riboflavin solution, corneas were excised, and group B was divided into B1 (with epithelium maintained) and B2 (epithelium removed for the fluorescence analysis). Confocal microscopy was performed to quantify the fluorescence intensity in the cornea according to the distance from the surface (with epithelium in groups A and B1; without epithelium in groups B2 and C).


RESULTS
The average fluorescence intensity of riboflavin at a depth of 100, 150, 200, and 250 μm was 69.97, 58.83, 49.23, and 41.72 arbitrary units (A.U.) in group A, respectively; 255.26, 206.01, 159.81, 124.20 A.U. in group B1; 218.90, 177.90, 141.43, 110.45 A.U. in group B2; and 677.64, 420.10, 250.72 and 145.07 A.U. in group C. The difference in fluorescence was statistically significant between groups A and B1 (P = 0.001) and groups B2 and C (P < 0.0001).


CONCLUSIONS
Ultrasound treatment increased the entry of topical riboflavin into the corneal stroma despite the presence of a previously intact epithelial barrier. This approach may offer a means of achieving clinically useful concentrations of riboflavin within the cornea with minimum epithelial damage, thereby improving the risk profile of corneal cross-linking procedures.
Department of Ophthalmology, University of California, San Francisco, California 94143-0730, USA.
Ricardo
R
Lamy
Elliot
E
Chan
Hui
H
Zhang
Vasant A
VA
Salgaonkar
Sam D
SD
Good
Travis C
TC
Porco
Chris J
CJ
Diederich
Jay M
JM
Stewart
D000287:Administration, Topical; D000818:Animals; D003319:Corneal Stroma / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D015612:Phonophoresis / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D012256:Riboflavin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D017319:Photosensitizing Agents; D012256:Riboflavin
cornea; drug delivery systems; phonophoresis; riboflavin; ultrasonics