Ricardo Lamy

Effects of corneal cross-linking on contrast sensitivity, visual acuity, and corneal topography in patients with keratoconus.

Purpose: To assess the effects of corneal collagen cross-linking (CXL) on contrast sensitivity (CS), visual acuity, and corneal topography investigating possible predictors of efficacy. Methods: Sixty-eight eyes of 34 patients with progressive keratoconus were enrolled in this prospective study. CXL was performed in one eye and the other eye was left untreated as a control. CS, best spectacle–corrected visual acuity (BSCVA), simulated keratometry in the steepest meridian (SimK-s), mean power in the central 3-mm zone (C-MP), mean power in the paracentral 3- to 5-mm zone (P-MP), maximum keratometric power in the central zone (C-Kmax), and maximum keratometric power in the paracentral zone (P-Kmax) were evaluated at baseline, 40 days, 3 months, 6 months, 1 year, and after 2 years of follow-up. Results: Treated eyes showed an improvement (P < 0.001) of +0.16 logCS and −0.16 logarithm of the minimum angle of resolution (logMAR) and a reduction in SimK-s of −0.61 diopter (D), C-Kmax −1.11 D, P-Kmax −0.99 D, C-MP −0.39 D, and P-MP −0.30 D. Of the treated eyes, 43.3% had a decrease in C-Kmax greater than 1 D, 50% by 0 to 0.99 D, and 6.7% had an increase of up to +0.89 D. Treated eyes with keratometric apex in the central 3-mm zone (CKA) improved BSCVA −0.19 logMAR and CS +0.19 logCS; whereas in treated eyes with paracentral keratometric apex (PKA), the improvement was −0.13 logMAR and +0.16 logCS. Conclusions: CXL with riboflavin and UV-A improved CS and inhibited the progression of keratoconus. As a predictor of treatment efficacy, eyes with CKA showed greater improvement in BSCVA after CXL when compared with eyes with PKA.

Ultrasound-enhanced penetration of topical riboflavin into the corneal stroma.

PURPOSE 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.

Cross-Linking with Ultraviolet-A and Riboflavin Reduces Corneal Permeability

PURPOSE To investigate the effect of cross-linking treatment on corneal permeability in a live animal model. METHODS Rabbit eyes were selected at random to be left unoperated or to undergo epithelial debridement with or without treatment consisting of cross-linking (CXL) with riboflavin and ultraviolet-A. Nine eyes received a total dose of 3.6 J/cm² and after epithelial healing the corneas were placed in a two-chamber system for quantification of the diffusion of fluorescein compared with controls. Thirty eyes received a total dose of 5.4 J/cm² and, after epithelial healing, in vivo corneal permeability was quantified as the pupillary response over a 30-minute period to a dose of topical pilocarpine compared with controls. RESULTS In the ex vivo assay, the mean permeability coefficient in the CXL group (2.42 × 10⁻⁷) was reduced when compared with the unoperated controls (3.73 × 10⁻⁷; P = 0.007) and to the eyes that received epithelial debridement alone (3.74 × 10⁻⁷; P = 0.01). In the in vivo permeability assay, the change in pupillary diameter at 30 minutes after pilocarpine administration was smaller in the CXL group (-1.9 mm), compared with the epithelial debridement group (-2.6 mm; P < 0.001) and with the unoperated controls (-2.7 mm; P = 0.003). CONCLUSIONS Corneal cross-linking with ultraviolet-A and riboflavin results in a statistically significant reduction in corneal permeability. These findings suggest that dosing of topical medications may need to be increased in eyes with a history of CXL to achieve expected therapeutic effects, and they may have implications for the long-term health of the cornea.

Riboflavin and ultraviolet A as adjuvant treatment against Acanthamoeba cysts

Experimental studies have shown that the standard dose of riboflavin (R) or R + ultraviolet‐A (UVA) as solo treatment are not able to exterminate Acanthamoeba cysts or even trophozoites. The purpose of this study is to determine whether the application of R + UVA can enhance the cysticidal effects of cationic antiseptic agents in vitro.

Advanced Glycation End-Product Accumulation Reduces Vitreous Permeability

PURPOSE To evaluate the effect of nonenzymatic cross-linking (glycation) upon the permeability of the vitreous to small- and large-solute diffusion. METHODS Vitreous from freshly excised porcine eyes was treated for 30 minutes with control or 0.01%, 0.1%, or 1% methylglyoxal (MG) solution. The efficacy of the glycation regimen was verified by measuring nonenzymatic cross-link density by fluorescence in the vitreous samples. Resistance to collagenase digestion as well as N(ε)-(carboxyethyl) lysine (CEL) content were also measured. The permeability coefficient for fluorescein and fluorescein isothiocyanate (FITC)-IgG diffusion through 3 mL of the vitreous samples was determined by using a custom permeability tester. RESULTS Vitreous cross-linking with MG treatment was confirmed by increased fluorescence, increased CEL concentration, and increased resistance to collagenase digestion. Vitreous glycation resulted in a statistically significant decrease in the permeability coefficient for fluorescein diffusion when either 0.1% or 1% MG solution was used (5.36 ± 5.24 × 10(-5) cm s(-1), P = 0.04; and 4.03 ± 2.1 × 10(-5) cm s(-1), P = 0.001; respectively, compared with control, 9.77 ± 5.45 × 10(-5) cm s(-1)). The permeability coefficient for diffusion of FITC-IgG between control (9.9 ± 6.37 × 10(-5) cm s(-1)) and treatment groups was statistically significant at all MG concentrations (0.01% MG: 3.95 ± 3.44 × 10(-5) cm s(-1), P = 0.003; 0.1% MG: 4.27 ± 1.32 × 10(-5) cm s(-1), P = 0.004; and 0.1% MG: 3.72 ± 2.49 × 10(-5) cm s(-1), P = 0.001). CONCLUSIONS Advanced glycation end-product (AGE) accumulation reduces vitreous permeability when glycation is performed in ex vivo porcine vitreous. The permeability change was more pronounced for the larger solute, suggesting a lower threshold for AGE-induced permeability changes to impact the movement of proteins through the vitreous when compared with smaller molecules.