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Purpose: To evaluate and compare functional and structural outcomes of accelerated corneal crosslinking (A-CXL) using riboflavin with hydroxypropyl methyl cellulose (HPMC) vs conventional corneal crosslinking (C-CXL) using riboflavin with dextran. Setting: American University of Beirut Medical Center, Beirut, Lebanon. Design: Retrospective analysis. Methods: Retrospective analysis of 83 eyes of 73 patients with mild to moderate keratoconus. First group (n = 44 eyes) underwent C-CXL using a 30-minute riboflavin/dextran soaking between June 2014 and March 2016. Second group (n = 39 eyes) underwent A-CXL using a 20-minute riboflavin/HPMC soaking between April 2016 and December 2017. Patients were evaluated preoperatively and at 1, 3, and 12 months postoperatively. Main outcome measures were simulated keratometry (simK), maximum axial keratometry (Kmax), demarcation line depth, and haze intensity measured using optical coherence tomography--based image analysis software. Results: Demarcation line (DL) was 298.30 ± 64.60 mm and 335.61 ± 99.76 mm for C-CXL and A-CXL groups, respectively (P = .04). Haze profile was similar for both groups. The mean simK values were reduced from 46.93 ± 3.50 and 46.44 ± 2.93 preoperatively to 46.18 ± 3.65 and 45.54 ± 2.78 at 12 months postoperatively, for C-CXL and A-CXL, respectively (P = .003 for both groups). Themean Kmax decreased from 52.46 ± 4.82 and 51.50 ± 3.87 preoperatively to 51.30 ± 4.42 and 50.30 ± 3.52 postoperatively, for the C-CXL and A-CXL, respectively (P < .001 for both groups). There was no difference in the simK and Kmax changes between the C-CXL and A-CXL groups (P = .814 and P = .913), visual acuity, and refraction between the 2 groups (P > .05). Conclusions: A-CXL with a 20-minute riboflavin/HPMC soaking produced deeper DL and similar corneal haze, topographic, refractive, and visual results to C-CXL with a 30-minute riboflavin/dextran soaking. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether sunlight might be used to induce a biomechanical stiffening effect in riboflavin-soaked corneas similar to the effect observed in corneal crosslinking (CXL) using riboflavin and UV-A light. Setting: Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland. Design: Experimental study. Methods: 52 porcine eyes were assayed. The concentration of riboflavin in the corneal stroma was estimated using UV-A transmission in a preliminary experiment. Then, the duration of sunlight exposure to achieve a fluence of 7.2/cm² was calculated. Finally, deepithelialized corneas were divided equally into 3 groups and soaked with riboflavin 0.1% (control group and Group 1) or 0.5% (Group 2). Eyes from Groups 1 and 2 were then exposed to sunlight. The elastic modulus was calculated as an indicator of stiffness. Results: Riboflavin concentration in Group B was higher by a factor of 2.8 than Group A. According to live illuminance measurements and stromal riboflavin concentration, the sunlight exposure duration varied between 16 minutes and 45 minutes. Groups 1 and 2 had higher elastic modulus than controls (P < .0001) but did not differ between them (P = .194). The stiffening effect was 84% and 55%, respectively. Conclusions: Sunlight exposure of ex vivo corneas soaked in both riboflavin 0.1% and 0.5% resulted in increased corneal stiffness. Specifically, riboflavin 0.1% with longer UV-A exposure showed a trend for a greater stiffening effect, which might open new alleys for the use of oral riboflavin and fractioned sunlight exposure as less invasive CXL techniques. [ABSTRACT FROM AUTHOR]

Members of the ASCRS Cornea Clinical Committee performed a review of the current literature on the corneal crosslinking (CXL) procedure for treating corneal ectasia. The members explored the data on the techniques currently in use and under investigation, including their advantages, safety profiles, risks, and cost analyses, compared with data on corneal transplantation. They concluded that CXL limits the progression of keratoconus, thus reducing the need for transplantation. They also found that compared with permitting the disease to progress naturally, CXL techniques carry significant and long-term cost and safety benefits, primarily by reducing the need for corneal transplantation. Studies of various CXL techniques (eg, epithelium-on treatment, changes in ultraviolet light parameters, riboflavin composition) continue with the ultimate goal of improving the procedure's safety and efficacy. [ABSTRACT FROM AUTHOR]

Purpose To compare the outcomes of transepithelial photorefractive intrastromal corneal crosslinking (CXL) and photorefractive keratectomy (PRK) in eyes with low myopia. Setting Purpan Hospital, Toulouse, France. Design Prospective case series. Methods Myopic patients with a manifest refraction spherical equivalent (MRSE) of −1.00 to −2.50 diopters (D) and a cylindrical component of plano to −0.75 D were included. The dominant eye had PRK (PRK eyes). The nondominant eye had transepithelial photorefractive intrastromal CXL with riboflavin (ParaCel Part 1 and 2), 30 mW/cm2 pulsed ultraviolet-A irradiation centered on the pupil (Mosaic System) for 16 minutes and 40 seconds, and a supplemental oxygen delivery mask (CXL eyes). The primary outcome measure was the change in the MRSE. Other outcome measures were the uncorrected (UDVA) and corrected (CDVA) distance visual acuities, mean keratometry, and endothelial cell count (ECC) over a 6-month follow-up. Adverse events were assessed. Results Nineteen patients were included. By 6 months, the mean MRSE had decreased by 0.72 D ± 0.42 (SD) in CXL eyes and by 1.35 ± 0.46 D in PRK eyes (P <.001). The mean change in UDVA was −0.35 ± 0.21 logarithm of the minimum angle of resolution (logMAR) in CXL eyes and −0.66 ± 0.19 logMAR in PRK eyes (P <.001). No complications were reported. The change in the ECC and CDVA was not statistically significant. Conclusions Photorefractive keratectomy provided better visual and refractive outcomes than transepithelial photorefractive intrastromal CXL. Transepithelial photorefractive intrastromal CXL, however, showed the potential refractive effect of CXL but with a limited magnitude of myopic correction. [ABSTRACT FROM AUTHOR]

Purpose To estimate the noninvasive riboflavin concentration in the corneal stroma using a new ultraviolet-A (UVA) theranostic device for corneal crosslinking (CXL). Setting Vision Engineering Italy srl, Rome, Italy. Design Experimental study. Methods Fourteen human donor corneas were treated according to conventional (UVA irradiance of 3 mW/cm2 for 30 minutes) and rapid (10 mW/cm2 for 9 minutes) riboflavin–UVA CXL protocols using a theranostic UVA device. Five additional samples were treated by 0.5 mW/cm2 for 9 minutes and used as positive controls to determine riboflavin photodegradation under near ambient lighting conditions. A 20% dextran–enriched 0.1% riboflavin solution was used in all cases. The device consisted of a UVA light source; a red–green–blue camera, which acquires the fluorescence images of the cornea during treatment; and a single-board computer for managing the overall operations and the raw data processing. Results Preirradiation stromal soaking for 30 minutes achieved highly consistent intrastromal riboflavin concentration in all tissues (mean 0.015% ± 0.003% [SD]). There were no differences in the kinetics curves of riboflavin consumption between the 2 UVA irradiation protocols; the intrastromal riboflavin concentration decreased exponentially, with a mean constant energy rate of 2.8 ± 0.2 J/cm2. In the control group, the intrastromal riboflavin concentration decreased quasilinearly. Conclusions The theranostic device provided estimates of the intrastromal concentration of riboflavin noninvasively during treatment. In the 3 to 10 mW/cm2 range of power densities, the consumption of riboflavin in the stroma by UVA irradiation was only energy dependent in accordance with the Bunsen-Roscoe law. [ABSTRACT FROM AUTHOR]

Purpose To characterize the mechanical property improvement of riboflavin and ultraviolet light corneal crosslinking (CXL) procedure in artificially swollen human and porcine corneas. Setting Computational Biomechanics Research Laboratory, Mechanical and Industrial Engineering Department, University of Illinois at Chicago, Illinois, USA. Design Experimental study. Methods Porcine and human donor corneas were crosslinked at different hydration levels using riboflavin–dextran solutions of different osmolality. Four porcine groups (H w [hydration in mg H 2 O/mg dry tissue] = 3.3 ± 0.2 [SD]; 4.0 ± 0.1; 5.1 ± 0.1; 5.6 ± 0.1) and 3 human groups (H w = 3.2 ± 0.1; 3.9 ± 0.2; 5.3 ± 0.3) were considered. The mechanical properties were measured by uniaxial tensile experiments during which the hydration of samples was the same as the hydration at which they were crosslinked. Tensile properties of 2 porcine groups (H w = 5.1 ± 0.1; 5.6 ± 0.1) were also measured when their average hydration was lowered to 4.0 mg H 2 O/mg dry tissue. Results The CXL procedure significantly increased tensile properties of both human and porcine samples in each hydration group ( P < .05). The improvement in tensile properties was hydration-dependent, that is, samples crosslinked at higher hydration levels showed lower maximum tensile stress. The behavior of samples crosslinked at different initial hydration but tested mechanically at similar hydration showed insignificant difference ( P = .7). Conclusion Increasing the hydration of porcine and human corneal samples before the CXL treatment had insignificant influence on tensile property improvement, as measured by testing specimens at similar hydration. [ABSTRACT FROM AUTHOR]

Purpose To determine whether the pulsed-light ultraviolet-A (UVA) accelerated corneal crosslinking (CXL) procedure is more efficacious and selective than its continuous-light counterpart in rabbits. Setting School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China. Design Experimental study. Methods Fifty-four rabbits were divided into 2 groups. Group 1 had continuous-light accelerated CXL using 9 mW/cm 2 UVA for 10 minutes (5.4 J/cm 2 ). Group 2 had pulsed-light accelerated CXL by exposing them to 9 mW/cm 2 UVA for 20 minutes (1 second on/1 second off). Corneal stromal demarcation line depth, in vivo confocal microscopic analysis, biomechanical stiffness, endothelial cell density, and keratocyte apoptosis were measured after performing these CXL procedures. Results The mean stromal demarcation line depth was 254.7 μm ± 47.4 (SD) in Group 1 and 341.1 ± 36.1 μm in Group 2 ( P < .01). One day after CXL, confocal analysis and histological staining identified keratocyte apoptotic fragments in the anterior stroma in the Group 2 corneas whereas all cells were obliterated in Group1. Seven days after treatment, the thicknesses in Group 1 were significantly greater than those in Group 2 ( P < .05). Endothelial cell losses were reversible; however, in Group 1, some losses were still evident on day 7. Increases in both the stress–strain relationship and tangent modulus in Group 2 were greater than those in Group 1. Conclusion The pulsed-light accelerated CXL protocol was less injurious and more efficacious at inducing CXL than the continuous-light accelerated CXL protocol in rabbit corneas. [ABSTRACT FROM AUTHOR]

Purpose To evaluate outcomes of corneal crosslinking (CXL) using a transepithelial technique for the treatment of keratoconus. Setting Cornea and refractive surgery subspecialty practice. Design Prospective case series. Methods Transepithelial CXL was performed in keratoconic eyes using riboflavin 0.1% and topical anesthetic containing benzalkonium chloride to facilitate riboflavin diffusion through the epithelium. Eyes were randomized to receive riboflavin administration either every 1 minute or every 2 minutes during ultraviolet-A exposure at 3mW/cm 2 . The principal outcome was change in maximum keratometry (K) and secondary outcomes included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, mean K, and comparison of randomized groups. Results Eighty-two eyes of 56 patients were treated. At 1 year, maximum K decreased significantly by 0.45 diopters (D) ± 1.94 (SD); it improved by 2.0 D or more in 11 eyes (13%) and worsened by 2.0 D or more in 4 eyes (5%). The mean UDVA significantly improved by 0.7 lines, whereas the CDVA improved by 0.2 lines. Two eyes showed both continued progression with loss of CDVA. Only the 1-minute subgroup showed significant improvements in maximum K (−0.73 D) and UDVA. Transient corneal erosion and epitheliopathy were reported in 21% of eyes. Conclusions Transepithelial CXL resulted in significant improvements in maximum K and UDVA over 1 year. There was a suggestion that increased riboflavin dosing might improve procedure outcomes. Further study is required to determine the relative advantages and disadvantages of different transepithelial approaches to the standard CXL protocol with epithelial removal. [ABSTRACT FROM AUTHOR]

Purpose To compare the corneal stromal riboflavin concentration and distribution using 2 transepithelial corneal crosslinking (CXL) systems. Setting Absorption Systems, San Diego, California, USA. Design Experimental study. Methods The stromal riboflavin concentration of 2 transepithelial CXL systems was compared in rabbit eyes in vivo. The systems were the Paracel/Vibex Xtra, comprising riboflavin 0.25% solution containing TRIS and ethylenediaminetetraacetic acid and an isotonic solution of riboflavin 0.25%, (Group 1) and the CXLO system (Group 2). Manufacturers’ Instructions For Use were followed. The intensity of riboflavin fluorescence by slitlamp observation 10, 15, and 20 minutes after instillation was graded on a scale of 0 to 5. The animals were humanely killed and the corneal stromal samples analyzed with liquid chromatography and mass spectrometry. Results The mean riboflavin fluorescence intensity grades in Group 1 (4 eyes) were 3.8, 4.8, and 4.8 at 10, 15, and 20 minutes, respectively. The mean grades in Group 2 (3 eyes) were 2.0, 2.3, and 2.0, respectively. The riboflavin distribution was uniform in Group 1 but not in Group 2. The mean riboflavin concentration by liquid chromatography and mass spectrometry was 27.0 μg/g stromal tissue in Group 1 and 6.7 μg/g in Group 2. A stromal riboflavin concentration theoretically adequate for CXL, 15 μg/g, was achieved in all eyes in Group 1 and no eyes in Group 2. Slitlamp grading correlated well with liquid chromatography and mass spectrometry concentration ( R 2 = 0.940). Conclusions The system used in Group 1 produced corneal riboflavin concentrations that were theoretically adequate for effective transepithelial CXL (≥15 μg/g), while the system in Group 2 did not. Slitlamp grading successfully estimated the corneal riboflavin concentration and can be used to ensure an adequate concentration of riboflavin in the cornea for transepithelial CXL. [ABSTRACT FROM AUTHOR]

Purpose To compare the demarcation line depth after contact lens–assisted corneal crosslinking (CXL) for progressive keratoconus using dextran-based and hydroxypropyl methylcellulose (HPMC)-based riboflavin solutions. Setting Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Design Retrospective case series. Methods Patients with preoperative epithelium-on (epi-on) minimum corneal thickness between 350 μm and 450 μm having contact lens–assisted CXL for progressive keratoconus were crosslinked with isoosmolar 0.1% riboflavin in 20% dextran 500 or HPMC 1.1%. The primary outcome measure was the mean demarcation line depth measured 1 month postoperatively on anterior-segment optical coherence tomography. The secondary outcome measure was change in endothelial cell density (ECD) 6 months from baseline. Results The study comprised 21 patients (21 eyes, 9 in the HPMC group and 12 in the dextran group). The mean demarcation line depth was deeper in the HPMC group (308.22 μm ± 84.19 [SD]) than in the dextran group (235.33 ± 64.87 μm) ( P < .04). This difference remained significant ( P = .02) even after controlling for the preoperative lesser epi-on minimum corneal thickness in the HPMC group (385.56 ±13.81 μm) versus the dextran group (413.08 ± 29.58 μm) ( P < .02). The ECD 6 months after contact lens–assisted CXL was comparable to the baseline levels in both groups ( P = .19 and P = .09, respectively). Conclusion During contact lens–assisted CXL, HPMC-based riboflavin seemed to be associated with a deeper demarcation line than dextran-based riboflavin, although both solutions were safe for the endothelium at 6 months. [ABSTRACT FROM AUTHOR]

Purpose To assess whether full biomechanical stiffening can be achieved with corneal crosslinking (CXL) when applying a reduced ultraviolet (UV) fluence during the standard irradiation time. Setting Laboratory of Ocular Cell Biology, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland. Design Experimental study. Methods Thirty-four freshly enucleated porcine corneas were deepithelialized and soaked with hypoosmolar riboflavin 0.1% solution for 30 minutes. Slow low-irradiance CXL (30 minutes at 1.5 mW/cm 2 , fluence 2.7 J/cm 2 ) was compared with standard CXL (30 minutes at 3 mW/cm 2 , fluence 5.4 J/cm 2 ). The controls were soaked with riboflavin but not exposed to UV light. Elastic (stress–strain) and viscoelastic (stress–relaxation) 2-dimensional testing was performed with a commercial stress–strain extensometer to quantify the biomechanical stiffening. Results Corneas crosslinked with low and standard UV irradiances had a significantly higher mean elastic modulus (65.9 MPa ± 15.7 [SD] and 67.1 ± 15.6 MPa, respectively) than controls (52.4 ± 12.3 MPa) ( P < .001). Also, the remaining stress after 120 seconds of stress–relaxation was significantly higher after CXL with low and standard UV irradiances (159 ± 21 kPa and 158 ± 25 kPa, respectively) compared with controls (135 ± 20 kPa) ( P ≤ .013). No difference was observed in low and standard irradiances between CXL conditions ( P = .64). Conclusions The UV fluence for CXL might be reduced while maintaining the biomechanical efficacy by using a lower UV irradiance and the same irradiation duration. This might open avenues in the treatment of extremely thin corneas. [ABSTRACT FROM AUTHOR]

Purpose To determine the intrastromal concentration of riboflavin in nanotechnology-based transepithelial corneal crosslinking. Setting Consiglio Nazionale delle Ricerche, Messina, Italy. Design Experimental study. Methods Six human donor sclerocorneal tissues were used to evaluate penetration of nanotechnology-based riboflavin 0.1% solution in the stroma through the intact epithelium. Three additional tissues were deepithelialized and soaked with dextran 20.0%–enriched riboflavin 0.1% solution for 30 minutes. After corneal soaking with riboflavin, all tissues were irradiated using a 10 mW/cm 2 device for 9 minutes. Two-photon emission fluorescence (TPEF) axial scanning measurements were collected in all specimens before treatment and immediately after corneal soaking with riboflavin and ultraviolet-A (UVA) irradiation of the cornea. The absorbance spectra of each tissue were collected at the same time intervals. The TPEF signals and absorbance spectra were used to calculate the concentration-depth profile of riboflavin in the corneal stroma during treatments. Results The mean stromal riboflavin concentration was 0.008% ± 0.003% (SD) and 0.017% ± 0.001% after transepithelial soaking with the nanotechnology-based solution and standard soaking, respectively ( P = .001). After UVA irradiation of the cornea, the mean consumption of riboflavin was 52% ± 13% and 67% ± 2% in the study group and control group, respectively ( P < .01). Conclusions The nanotechnology-based platform was effective in enriching the anterior stroma with riboflavin through the intact epithelium, although the riboflavin concentration–depth profile rapidly decreased across the mid and posterior stroma. The treatment-induced stiffening effect on the corneal stroma was not assessed in this study. [ABSTRACT FROM AUTHOR]

Purpose To evaluate corneal collagen crosslinking (CXL) with conventional and accelerated ultraviolet-A (UVA) irradiation using riboflavin with methylcellulose. Setting Department of Ophthalmology, Oslo University Hospital, Oslo, Norway. Design Prospective randomized case series. Methods Patients with keratoconus were randomized to have CXL using conventional 3 mW/cm 2 UVA irradiation for 30 minutes (CXL30) or accelerated 9 mW/cm 2 UVA irradiation for 10 minutes (CXL10). In both groups, a solution of riboflavin 0.1% with hydroxypropyl methylcellulose 1.1% (methylcellulose–riboflavin) was used. The endothelial cell density (ECD), visual acuity, and tomography were measured at baseline and after 12 months. Anterior segment optical coherence tomography and in vivo confocal microscopy (IVCM) were performed after 1 month. Results The study comprised 40 patients (40 eyes). A complete absence of keratocytes in all eyes at 100 μm depths was found on IVCM. At 300 μm, 400 μm, and preendothelial levels, the differences were 83.3% versus 31.3% ( P = .02), 64.7% versus 20.0% ( P = .01), and 42.1% versus 5.9% ( P = .02) in the CXL30 and CXL10 groups. No statistically significant differences were found in the change in visual acuity or maximum keratometry between the groups after 12 months. There was no relationship between the depth of keratocyte absence and the ECD change after 12 months. Conclusions Marked deep structural changes with an absence of keratocytes occurred when CXL was used with conventional or accelerated UVA irradiation; however, the changes were more pronounced with the use of conventional UVA irradiation. The use of methylcellulose–riboflavin might explain the deep alterations and raises a long-term safety concern. [ABSTRACT FROM AUTHOR]

Purpose To determine whether riboflavin-induced collagen crosslinking (CXL) could be precisely achieved in the corneal stroma of ex vivo rabbit eyes using nonlinear optical excitation with a low numerical aperture lens and enlarged focal volume. Setting Gavin Herbert Eye Institute, University of California Irvine, Irvine, California, USA. Design Experimental study. Methods The corneal epithelium was removed and the corneas were soaked in 0.5% riboflavin solution. Using a 0.1 numerical aperture objective, a theoretical excitation volume of 150 μm × 3 μm was generated using 1 W of 760 nm femtosecond laser light and raster scanned with 4.4 μm line separation at varying effective speeds over a 4.50 mm × 2.25 mm area. Corneal sections were examined for collagen autofluorescence. Results Collagen autofluorescence was enhanced 2.9 times compared with ultraviolet-A (UVA) CXL. Also, increasing speed was linearly associated with decreasing autofluorescence intensity. The slowest speed of 2.69 mm/s showed a mean of 182.97 μm ± 52.35 (SD) long autofluorescent scan lines axially in the central cornea compared with 147.84 ± 4.35 μm for UVA CXL. Conclusions Decreasing dwell time was linearly associated with decreasing autofluorescence intensity, approaching that of UVA CXL at a speed of 8.9 mm/s. Using an effective speed of 8.9 mm/s, nonlinear optical CXL could be achieved over a 3.0 mm diameter area in fewer than 4 minutes. Further development of nonlinear optical CXL might result in safer, faster, and more effective CXL treatments. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose To determine intraoperative changes in corneal thickness and outcomes of corneal collagen crosslinking (CXL) using 2 intraoperative regimens: riboflavin–dextran or hypotonic riboflavin. Setting Cornea and refractive surgery practice, Teaneck, New Jersey, USA. Design Prospective randomized case series. Methods Eyes with keratoconus or corneal ectasia were treated. All eyes received preloading with riboflavin 0.1% in 20% dextran. During ultraviolet-A (UVA) exposure, patients were randomly assigned to 1 of 2 study arms; that is, riboflavin–dextran or hypotonic riboflavin. Intraoperative pachymetry was measured before and after the corneal epithelium was removed, after initial riboflavin loading, and after UVA light exposure. Patients were evaluated for maximum keratometry (K), uncorrected distance visual acuity (UDVA), corrected distance visual acuity, corneal thickness, and endothelial cell count (ECC). Results Forty-eight eyes were treated. After removal of the epithelium and riboflavin loading, the mean pachymetry was 430 μm and 432 μm in the standard group and hypotonic group, respectively. Immediately after 30-minute UVA administration, the mean pachymetry was 302 μm and 342 μm, respectively. There was no statistically significant difference in the postoperative maximum K change, UDVA, corneal thickness, or ECC between the 2 groups. Conclusions The cornea thinned substantially during the CXL procedure. The use of hypotonic riboflavin rather than riboflavin–dextran during UVA administration decreased the amount of corneal thinning during the procedure by 30%, from 128 μm to 90 μm. However, there were no significant differences in clinical efficacy or changes in ECC or function between groups postoperatively. In general, corneal thinning during CXL did not seem to compromise the safety of the endothelium. Financial Disclosures Dr. Hersh is a consultant to Avedro, Inc. Dr. Rosenblat has no financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose To determine the diffusion of riboflavin from intrastromal channels through the effective diffusion coefficients compared with traditional axial diffusion with epithelium on or off. Setting Advanced Optical Imaging Laboratory, University College Dublin, and Wellington Eye Clinic, Sandyford, Dublin, Ireland. Design Experimental study. Methods The rate of diffusion in whole-mounted porcine eyes was monitored for a 30 minutes using an optical setup with a charge-coupled device camera and a bandpass filter (central wavelength 550 nm and 40 nm bandpass) to image the fluorescence under ultraviolet illumination (365 nm wavelength). For comparison, an isotropic corneal stroma with an annular channel was modeled numerically for different diffusion constants and boundary conditions. Results Numerical and experimental results were compared, allowing determination of the effective diffusion coefficient for each case. Experimental results for 6 different riboflavin solutions were in all cases found to be higher than for the common crosslinking (CXL) riboflavin protocol, where the diffusion constant is D 0 = 6.5 × 10 −5 mm 2 /sec. For the intrastromal channel, 2 isotonic solutions containing riboflavin 0.1% correlated with a diffusion constant of 5 D 0 = 32.5 × 10 −5 mm 2 /sec. Hypotonic solutions and transepithelium had a higher diffusion coefficient approaching 10 D 0 = 65.0 × 10 −5 mm 2 /sec, which is an order-of-magnitude increase compared with the typical diffusion coefficient found in standard CXL. Conclusions In this study, riboflavin had a faster stromal diffusion when injected into a corneal channel than when applied as drops to the anterior corneal surface. Further numerical modeling might allow optimization of the channel structure for any specific choice of riboflavin. Financial Disclosures Dr. Mrochen has a financial and commercial interest in the products and companies mentioned herein. Dr. Mrochen states interests in other from IROC Innocross/Avedro Inc., outside the submitted work. In addition, Dr. Mrochen has a patent issued and UV devices that were sponsored by IROC Innocross. A PhD grant is also partially financed by IROC Innocross. None of the other authors has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the stromal concentration of 2 commercially available transepithelial riboflavin 0.1% solutions in human donor corneas with the use of spectrophotometry. Setting University of Calabria, Rende, Italy. Design Experimental study. Methods The absorbance spectra of 12 corneal tissues were measured in the 330 to 700 nm wavelength range using a purpose-designed spectrophotometry setup before and after transepithelial corneal soaking with a 15% dextran-enriched riboflavin 0.1% solution (n = 6) or a hypotonic dextran-free riboflavin 0.1% solution (n = 6). Both ophthalmic solutions contained ethylenediaminetetraacetic acid and trometamol as enhancers. In addition, 4 deepithelialized corneal tissues underwent stromal soaking with a 20% dextran-enriched riboflavin 0.1% solution and were used as controls. All the riboflavin solutions were applied topically for 30 minutes. The stromal concentration of riboflavin was quantified by analysis of absorbance spectra of the cornea collected before and after application of each solution. Results The mean stromal riboflavin concentration was 0.012% ± 0.003% (SD), 0.0005% ± 0.0003% ( P < .001), and 0.004% ± 0.001% ( P < .01) in tissues soaked with 20% dextran-enriched, 15% dextran-enriched, and hypotonic dextran-free solutions, respectively. The difference of stromal riboflavin concentration between the 2 transepithelial solutions was statistically significant ( P < .01). Conclusions Dextran-enriched solutions required complete corneal deepithelialization to permit effective stromal soaking with riboflavin. Nevertheless, riboflavin in hypotonic dextran-free solution with enhancers permeates across stroma through an intact epithelium. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose To examine the effect of standard and accelerated corneal collagen crosslinking (CXL) on corneal enzymatic resistance. Setting School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom. Design Experimental study. Methods Sixty-six enucleated porcine eyes (with corneal epithelium removed) were assigned to 6 groups. Group 1 remained untreated, group 2 received dextran eyedrops, and groups 3 to 6 received riboflavin/dextran eyedrops. Group 4 had standard CXL (3 mW/cm 2 ultraviolet-A for 30 minutes), whereas groups 5 and 6 received accelerated CXL (9 mW/cm 2 for 10 minutes and 18 mW/cm 2 for 5 minutes, respectively). Trephined central 8.0 mm buttons from each cornea underwent pepsin digestion. Corneal diameter was measured daily, and the dry weight of 5 samples from each group was recorded after 12 days of digestion. Results All CXL groups (4 to 6) took longer to digest and had a greater dry weight at 12 days ( P < .0001) than the nonirradiated groups (1 to 3) ( P < .0001). The time taken for complete digestion to occur did not differ between the standard and accelerated CXL groups, but the dry weights at 12 days showed significant differences between treatments: standard CXL 3 mW > accelerated CXL 9 mW > accelerated CXL 18 mW ( P < .0001). Conclusions Standard and accelerated CXL both increased corneal enzymatic resistance; however, the amount of CXL might be less when accelerated CXL is used. The precise amount of CXL needed to prevent disease progression is not yet known. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose To analyze the spatial distribution and time course of corneal light backscattering before and after transepithelial corneal crosslinking using iontophoresis. Setting Fondazione G.B. Bietti-IRCCS, Rome, Italy. Design Experimental study. Methods Three donor human eyes with an intact corneal epithelium had transepithelial iontophoresis corneal crosslinking (using rapid ultraviolet-A [UVA] irradiation), and 3 donor eyes without corneal epithelium had standard corneal crosslinking (using standard UVA irradiation). In addition, 3 donor eyes had iontophoresis and rapid corneal crosslinking after corneal deepithelialization (epi-off iontophoresis corneal crosslinking). Scheimpflug images (Pentacam HR) of each eye globe were acquired before and immediately after administration of riboflavin 0.1% solutions and 5, 10, 30, and 120 minutes after the corneal crosslinking procedures. Corneal light backscattering was quantified across the anterior 280 μm thickness at several points from the optical center to 3.0 mm from the center. Results Light backscattering significantly increased after iontophoresis ( P < .001) in specimens with and without intact epithelium. It decreased significantly after transepithelial iontophoresis corneal crosslinking and epi-off iontophoresis corneal crosslinking ( P < .001), approaching the baseline values. After standard stromal soaking with riboflavin, a large increase in corneal light backscattering was found compared with baseline measurements ( P < .001) that remained unchanged up to 30 minutes after standard corneal crosslinking ( P = .92). The light backscattering increase after iontophoresis in corneas with epithelium was lower than after standard soaking ( P = .01). No differences were found between specimens without epithelium after iontophoresis and standard stromal soaking ( P = .06). Conclusions Scheimpflug photography provided an indirect biomarker of stromal permeation of riboflavin. Iontophoresis efficiently delivered riboflavin through the epithelium. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

We report 4 eyes with infectious keratitis treated with riboflavin/ultraviolet-A irradiation (corneal collagen crosslinking [CXL]) in addition to medical treatment. In 2 eyes with bilateral keratitis, the fellow eye was treated with medical treatment alone. The other 2 eyes had refractory keratitis. The results suggest that CXL may be more worthwhile in cases refractory to conventional medical treatment. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To determine the ability of moxifloxacin to penetrate the rabbit eye after corneal collagen crosslinking (CXL) with riboflavin and ultraviolet-A light irradiation. Setting: Harlan Biotech Israel, Rehovot, Israel. Design: Experimental study. Methods: One eye of 10 New Zealand white rabbits had CXL treatment. One month after treatment and 1 hour before an aqueous humor sample was obtained, 1 drop of 5 mg/mL moxifloxacin (Vigamox) was applied to both eyes of each rabbit every 15 minutes for a total of 4 drops. The aqueous humor samples were sent for high-performance liquid chromatography for antibiotic-concentration analysis. The eyes were enucleated and sent for histology analysis. Results: Moxifloxacin levels were obtained and analyzed for all 20 eyes. The mean level of moxifloxacin was 2.26 μg/mL ± 0.89 (SD) (range 1.09 to 4.20 μg/mL) in the treated eyes and 2.43 ± 1.17 μg/mL (range 0.89 to 4.72 μg/mL) in the untreated eyes. The difference between the groups was not statistically significant. Of the 10 eye pairs, lower moxifloxacin aqueous humor concentrations were found in 6 treated eyes and 4 untreated eyes. Conclusion: Penetration of moxifloxacin into the anterior chamber of rabbits was not influenced by previous CXL treatment. Financial Disclosures: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of accelerated corneal collagen crosslinking (CXL) with riboflavin for keratoconus by the change in dioptric power and corneal topography. Setting: Private practice, Tokyo, Japan. Design: Case series. Methods: The accelerated CXL treatments (KXL system) were performed using a 10-minute riboflavin 0.1% (Vibex Rapid) soak and a 3-minute ultraviolet-A (UVA) irradiance at a level of 30 mW/cm2. This corresponds to a total radiant exposure of 5.4 J/cm2. Preoperative and 1, 3, and 6 months postoperative examinations were performed. Results: The study enrolled 39 eyes of 22 patients. The mean uncorrected distance visual acuity showed a statistically significant improvement, from 1.11 ± 0.42 logMAR preoperatively to 0.89 ± 0.53 logMAR 6 months postoperatively (P<.01). The mean maximum keratometry readings also changed significantly, from 49.95 ± 6.11 diopters (D) preoperatively to 49.19 ± 5.82 D at 6 months (P<.01). There were no statistically significant changes in the endothelial cell density between preoperatively and postoperatively. Conclusions: The changes after accelerated CXL were similar to those after conventional CXL. Thus, accelerated CXL has the potential to efficiently treat and halt the progression of keratoconus and may be an effective, efficient therapeutic option for treating corneal ectatic disease. Financial Disclosures: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To determine the heterogeneous through-thickness strains in the cornea at physiologic intraocular pressures before and after corneal collagen crosslinking (CXL) using noninvasive ultrasound. Setting: Department of Biomedical Engineering, Ohio State University, Columbus, Ohio, USA. Design: Experimental study. Methods: Sixteen paired canine corneoscleral shells were divided into 2 groups. The CXL group completed a standard CXL protocol using riboflavin–ultraviolet-A (UVA) irradiation. The control group was given an identical treatment except UVA irradiation. Ultrasound scans (at 55 MHz) of the cornea were obtained before and after treatment as the corneoscleral shell was inflated from 5 mm Hg to 45 mm Hg to calculate the distributive through-thickness strains in the cornea. The mean radial and tangential strains of the whole cornea layer, as well as those of the anterior, middle, and posterior thirds of the cornea, were compared before and after treatment in the control group and CXL group using linear mixed models with repeated measures. Results: Significant reductions in tangential and radial strains occurred in the CXL group (P=.003 and P=.0025, respectively) but not the control group (P=.08 and P=.63, respectively). The anterior third had the smallest strains in all pretreated corneas (P<.001) and posttreated corneas (CXL group, P=.023; control group, P=.01). Conclusions: Ultrasound speckle tracking showed heterogeneous strain distributions through the cornea and confirmed that CXL results in a stiffer corneal response (ie, smaller strains during physiologic loadings). This technique may provide a clinical tool to quantify the biomechanical effects of CXL. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To evaluate the safety of corneal collagen crosslinking (CXL) combined with laser in situ keratomileusis (LASIK). Setting: Shinagawa LASIK Center, Tokyo, Japan. Design: Case series. Methods: Bilateral myopic LASIK patients had unilateral accelerated CXL (KXL System) in the nondominant eye. After LASIK, riboflavin 0.1% was instilled in the residual stromal bed for 60 seconds. After the riboflavin was washed out and the flap placed in its original position, ultraviolet-A light (30 mW/cm2) was administered for 60 seconds. The LASIK–CXL eyes and the LASIK-only eyes were compared. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, manifest refraction spherical equivalent (MRSE), keratometry values, endothelial cell density (ECD), pachymetry, optical coherence tomography (OCT), corneal hysteresis (CH), corneal resistance factor (CRF), keratoconus match index (KMI), and 37 parameters from a dynamic bidirectional applanation device (Ocular Response Analyzer) were analyzed. Morphologic changes were evaluated using confocal microscopy. Results: No significant differences in UDVA, CDVA, MRSE, ECD, dynamic bidirectional applanation readings (eg, CH, CRF, KMI), or 37 additional parameters were found between the 2 groups (P>.05). Increased hyperreflectivity and a demarcation line similar to that seen after CXL were observed in the LASIK–CXL eyes. The demarcation line (mean depth 200.04 μm ± 27.01 [SD]; range 178 to 278 μm) was present in 23 eyes (95.8%); the line was well defined in 2 eyes (8.3%) and faint in 21 eyes (87.5%). Conclusion: Combined LASIK–CXL was safe, causing insignificant corneal biomechanical and morphologic changes similar to those with CXL treatment only. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To compare central corneal thickness (CCT) with and without using an eyelid speculum during corneal collagen crosslinking (CXL). Setting: University Medical Center Utrecht, Utrecht, the Netherlands. Design: Prospective nonrandomized comparative study. Methods: Eyes with progressive keratoconus were treated by CXL and consecutively divided into 2 groups. In Group A, an eyelid speculum remained in place throughout the entire CXL procedure. In Group B, the eyelids remained closed during the 30-minute riboflavin instillation. Intraoperative ultrasound pachymetry measurements were performed at different timepoints. The visual acuity, refraction, keratometry, pachymetry, and endothelium were evaluated 6 months after CXL. The main outcome measures were intraoperative CCT measurements and the clinical CXL effect after 6 months. Results: Fifty-two eyes (50 patients) were treated. After riboflavin instillation, a statistically significant difference in CCT reduction was found between the 2 groups (P < .001), with a mean CCT decrease of 62 μm ± 53 (SD) (13% ± 11%) in Group A and 11 ± 35 μm (2% ± 8%) in Group B. No statistically significant between-group differences were found after epithelial removal or ultraviolet-A (UVA) irradiation. Six months after CXL, no statistically significant between-group difference was found in the visual acuity, refraction, keratometry, pachymetry, or endothelium. Conclusions: Avoidance of an eyelid speculum during riboflavin instillation resulted in less CCT reduction during CXL. This finding could increase the chance of attaining the required pachymetry safety margin for applying UVA and thus decrease the chance of premature CXL treatment termination. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate pachymetry changes during standard corneal crosslinking (CXL) and the effect of closed eyelids and hypotonic riboflavin in thin corneas. Setting: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. Design: Comparative case series. Methods: Eyes with progressive keratoconus had standard epithelium-off CXL. In Group 1, a lid speculum was used during the procedure. In Group 2, the lids were closed during saturation with riboflavin. In Group 3, hypotonic riboflavin was used. In Groups 1 and 2, swelling was performed with hypotonic riboflavin if pachymetry was less than 400 μm. The thinnest corneal pachymetry (TCP) was measured preoperatively, after epithelium removal, and every 10 minutes thereafter. Results: Thirty-five eyes were evaluated. After epithelium removal, the mean TCP was 401 μm ± 15 (SD), 411 ± 35 μm, and 400 ± 24 in Groups 1, 2, and 3, respectively. In Group 1, the TCP decreased to 355 ± 23 μm after the first 30 minutes. In Group 2, the TCP remained stable throughout the saturation phase. In Group 3, the TCP increased. During the irradiation phase, a reduction in pachymetry occurred in all groups. Thinnest corneal pachymetry readings less than 400 μm were found in all eyes irrespective of the protocol. Conclusions: Corneal desiccation with riboflavin with 20% dextran can be avoided when removing the lid speculum during saturation with riboflavin. The use of hypotonic riboflavin solution increased corneal pachymetry, although the final TCP remained unchanged. To increase endothelial safety, new isooncotic solutions are needed. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of epithelial-disruption collagen crosslinking (CXL) for progressive keratoconus using a corneal disruptor device and a riboflavin solution designed for a transepithelial technique. Setting: Magna Graecia University Eye Clinic, Catanzaro, Italy. Design: Prospective comparative case series. Methods: The most severely affected eye of patients with bilateral progressive keratoconus was treated. The fellow eye served as a control. Follow-up was 12 months. A corneal disruptor device was used to create pockmarks in the epithelium. Riboflavin solution was applied for 30 minutes and irradiation for 30 minutes. Three days postoperatively, patients were asked to assess the level of pain. Results: The study comprised 28 patients (mean age 28 years). The mean postoperative pain score was 4.3, 2.6, and 2.1 at 1 day, 2 days, and 3 days. The mean preoperative uncorrected (UDVA) and corrected (CDVA) distance visual acuities improved from 0.73 logMAR ± 0.21 (SD) and 0.30 ± 0.11 logMAR to 0.48 ± 0.15 logMAR and 0.25 ± 0.1 logMAR, respectively, at 12 months (P=.02). The mean spherical equivalent refraction decreased 0.96 diopter (D). The mean baseline apical keratometry, apical gradient curvature, average pupillary power, inferior–superior index, and cone area were 59.21 D, 8.91 D, 47.9 D, 11.49 mm2, and 10.32 mm2, respectively. At 12 months, these values were 56.18 D, 7.32 D, 41.34 D, 9.65 mm2, and 7.75 mm2, respectively. No adverse effects were observed. Conclusions: Corneal epithelial-disruption CXL was safe and effective in medium-term stabilization of keratoconus with an improvement in topographic and refractive parameters and less patient discomfort. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of phototherapeutic keratectomy (PTK) combined with implantation of a single inferior intrastromal corneal ring segment (ICRS) and riboflavin with ultraviolet-A collagen crosslinking (CXL) performed sequentially on the same day in the management of keratoconus. Setting: Cornea Unit, Toronto Western Hospital, Toronto, Ontario, Canada. Design: Case series. Methods: This retrospective review comprised consecutive patients with progressive keratoconus having transepithelial PTK followed by femtosecond laser–enabled placement of a single inferior ICRS and CXL on the same day by the same surgeon between December 2010 and August 2011. The main outcome measures included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), mean refraction spherical equivalent, keratometry (K), and total higher-order aberrations. Results: Sixteen eyes of 13 patients were included in the study. Six months after same-day PTK combined with implantation of a single inferior ICRS and CXL, there was a significant improvement in UDVA, CDVA, and the mean and steep K values. No patient lost CDVA lines. Conclusion: Phototherapeutic keratectomy combined with implantation of a single inferior ICRS and CXL on the same day was a safe, effective treatment for improving visual acuity in select patients with progressive keratoconus. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To determine the effect of the duration of irradiation on the biomechanical parameters of combined riboflavin–ultraviolet-A (UVA) collagen crosslinking (CXL) in rabbit sclera. Setting: Department of Ophthalmology, Provincial Hospital affiliated with Shandong University, Shandong, China. Design: Experimental study. Methods: Thirty-six New Zealand rabbits were divided into 6 groups based on the duration of irradiation (10, 20, 30, 40, 50, or 60 minutes). After the application of riboflavin 0.1% drops (without dextran) as a photosensitizer, the animals were irradiated with 3 mW/cm2 UVA at 365 nm. Only the left eye of each rabbit was treated. All the animals were humanely killed 24 hours postoperatively. One eye in each treated group was used for light microscopy. The other treated eye and all control eyes were prepared for biomechanical testing. The biomechanical parameters were ultimate stress, Young modulus, and the physiological modulus. Results: The eyes irradiated for 10 or 20 minutes did not differ significantly from the control eyes. Stress–strain measurement of scleral strips irradiated for 40 minutes or longer showed a significant increase in the ultimate stress, Young modulus, and the physiological modulus. There was a significant increase in the physiological modulus of scleral strips irradiated for 30 minutes or longer. Eyes that were irradiated for 50 minutes and 60 minutes had retinal damage. Conclusions: Riboflavin–UVA CXL can lead to a noticeable increase in the biomechanical stiffness of the sclera. The physiological modulus is the most sensitive tool to measure stiffness. In this study, the optimum duration of irradiation was 40 minutes. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To evaluate the efficacy of single or paired intrastromal corneal ring segments (ICRS) combined with ultraviolet-A and riboflavin collagen crosslinking (CXL) in patients with keratoconus. Setting: Cornea Unit, Toronto Western Hospital, Toronto, Ontario, Canada. Design: Retrospective comparative case series. Methods: Consecutive patients with keratoconus had femtosecond laser–assisted ICRS implantation combined with same-day CXL between 2008 and 2011. The main outcome measures included improvement in visual acuity, subjective refractive error, keratometry values, and total higher-order aberration (HOA). Results: Eighty-five eyes of 74 patients with keratoconus (paired ICRS: 47 eyes of 40 patients; single ICRS: 38 eyes of 34 patients) were included in the study. The uncorrected distance visual acuity was significantly improved after single ICRS (3.4 lines; P=.04) and paired ICRS (2.7 lines; P=.01) implantation combined with CXL, while corrected distance visual acuity (CDVA) remained stable. The single and paired ICRS groups had a significant reduction in mean cylinder at 1 year (single ICRS: −3.84 diopters [D] ± 1.72 [SD] versus −2.19 ± 1.54 D, P=.02; paired ICRS: −3.91 ± 1.45 D versus −2.96 ± 1.92 D) (P=.02). There was no significant difference in total HOAs. Single ICRS implantation and paired ICRS implantation with CXL were equivalent in all refractive parameters. No patient lost lines of CDVA. Conclusion: As determined by corneal topography, implantation of single or paired ICRS combined with same-day CXL was safe and effective in patients with keratoconus. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of using forward second harmonic generation (SHG) and 2-dimensional fast Fourier-transform (2D-FFT) analysis for the label-free characterization and quantification of morphologic changes in the corneal stroma after collagen crosslinking (CXL). Setting: Department of Physics, National Taiwan University, Taipei, Taiwan. Design: Experimental study. Methods: En face forward SHG imaging and 2D-FFT analysis were performed on ex vivo porcine corneas at the depths of 100, 200, 400, and 800 μm. Morphologic changes in stromal collagen fiber in control, ultraviolet-A (UVA), riboflavin, and riboflavin–UVA treated porcine corneas were assessed. Hematoxylin–eosin staining and Sirius red staining were performed for comparison. Results: Corneas after CXL treatment tended to have collagen fibers that were wavy compared with the linear pattern in normal corneas. Quantitative 2D-FFT analysis of forward SHG images also showed an increase in the standard deviations of the distribution of stromal collagen fiber orientations, which is indicative of the changed pattern of crosslinked stromal collagen fibers. Conclusions: Second harmonic generation imaging showed the morphologic changes in stromal collagen after CXL treatment. The linear collagen fibers in normal corneal stroma became wavy after treatment. With the introduction of 2D-FFT analysis, the morphologic changes can be quantified. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Photodynamic collagen crosslinking (CXL) using ultraviolet-A (UVA) irradiation combined with the photosensitizer riboflavin has been introduced as a new treatment for progressive keratoconus. The results of clinical studies are promising, but the efficacy of the treatment in halting the progression depends on the stability of the induced biomechanical effects. The effects of corneal CXL on corneal rigidity; collagen fiber diameter; and resistance to heat degradation, enzymatic digestion, and swelling due to hydration are reviewed in this paper. The collective results indicate that CXL using UVA and riboflavin enhances the biomechanical properties of the corneal tissue, which remain stable over time. Therefore, this treatment could become the future standard therapy for keratoconus or used to halt the progression of keratoconus and postpone the need for corneal transplantation. The increase in availability and popularity of the CXL technique accentuates the requirement for reliable and accurate techniques for measuring corneal biomechanical properties before and after treatment. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To assess the hypothesis that during corneal crosslinking (CXL) treatment, riboflavin and ultraviolet-A (UVA) may have a toxic effect on human limbal epithelial cells. Setting: Center for Eye Research, Department of Ophthalmology, Oslo University Hospital Ullevål, Oslo, Norway. Design: Experimental study. Methods: In this vitro study, limbal biopsies from corneoscleral rims collected after corneal transplantation were treated with the following combinations: riboflavin–UVA, riboflavin only, or UVA only; a control group received no treatment. After 3 weeks of cell culture, outgrowth of epithelium from the biopsies was evaluated by measuring the area of cell expansion and the number of cell layers. The explanted biopsies were analyzed for proliferation using immunohistochemistry marker Ki-67 and for apoptosis using the terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) assay. Results: The mean outgrowth from the biopsies was 2.25 mm2 ± 6.90 (SD) in the riboflavin–UVA group, 181.4 ± 94.8 mm2 in the riboflavin-only group, 128.5 ± 129.5 mm2 in the UVA-only group, and 176.2 ± 114.0 mm2 in the control group. There were no statistically significant between-group differences in the number of cell layers except in the riboflavin–UVA group, in which no cells were found. Detection of apoptosis with the TUNEL-assay was found in the riboflavin–UVA group only (4/5 sections). The proliferation marker Ki-67 was positive in some sections in all groups. Conclusion: Cytotoxicity and reduced cell expansion of human limbal epithelial cells occurred after riboflavin–UVA treatment in vitro, emphasizing the importance of avoiding riboflavin–UVA on the limbus during CXL. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To assess transepithelial stromal riboflavin absorption with an enhanced riboflavin solution (riboflavin 0.1%, 15% dextran T500 with trometamol (Tris-[hydroxymethyl]aminomethane) and sodium ethylenediaminetetraacetic acid by analyzing light-transmission properties of ex vivo rabbit corneas. Setting: School of Optometry and Vision Sciences, Cardiff, Wales. Design: Experimental study. Methods: The enhanced riboflavin drops (Ricrolin TE) were applied every 3 minutes for 1 hour to 12 corneas (4 with intact epithelium, 4 with superficial scratches, 4 with 8.0 mm epithelial debridement). As a comparison, riboflavin drops without the enhancers (riboflavin 0.1%, 20% dextran T500) (normal riboflavin group) were applied to 12 corneas (4 with intact epithelium, 4 with superficial scratches, 4 with central epithelial debridement). A control group of 4 corneas with intact epithelium received balanced saline 0.9%. To assess enhanced riboflavin absorption, light-transmission spectra of the corneas were analyzed with a spectrophotometer. Results: The spectra in corneas with intact epithelium in both riboflavin groups and in eyes with superficial scratches treated with normal riboflavin were similar to controls. Those with enhanced riboflavin and superficial scratches showed a homogeneous yellow discoloration of the cornea with a dip in light transmission between 400 and 490 nm, similar to that of the enhanced riboflavin solution. This was also seen, albeit of a greater magnitude, with complete epithelial removal, with eyes receiving enhanced riboflavin having a greater dip in transmission than eyes receiving normal riboflavin. Conclusions: Administration of enhanced riboflavin and superficial epithelial scratches allowed sufficient riboflavin stromal absorption to homogeneously alter the transmission spectra of rabbit corneas. This did not occur to the same extent with an intact epithelium or normal riboflavin with superficial scratches. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To evaluate the effectiveness of intracorneal riboflavin injection for combined collagen crosslinking (CXL) and intrastromal corneal ring segment (ICRS) implantation. Setting: Kudret Eye Hospital, Ankara, Turkey. Design: Noncomparative case series. Methods: Keratoconic eyes had combined ICRS (Intacs) implantation and transepithelial CXL with 20% alcohol application and riboflavin injection into the corneal channel. Outcome measures were uncorrected (UDVA) and corrected (CDVA) distance visual acuities, sphere, cylinder, and keratotomy (K) readings. Results: The study enrolled 131 eyes (105 patients) with a mean follow-up of 7.07 months ± 4.66 (SD). The mean improvement was 0.26 ± 0.16 logMAR in UDVA and 0.24 ± 0.16 logMAR in CDVA (both P<.05). The mean manifest spherical refraction decreased from −3.87 ± 4.55 diopters (D) to −1.25 ± 2.31 D, the mean manifest cylinder improved from −3.89 ± 1.97 D to −2.27 ± 2.18 D, and the mean K reading improved from 50.50 ± 5.26 D to 46.03 ± 4.51 D (all P<.05). There were no intraoperative or postoperative complications. Conclusions: Combined ICRS and CXL treatment with intracorneal riboflavin injection was effective in keratoconic eyes. Intracorneal riboflavin injection into the tunnel was safe and may provide more penetration without epithelial removal. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To evaluate the modulatory effect of various riboflavin 0.1% and 0.2% compositions on the central corneal thickness (CCT) in fresh porcine corneas. Setting: Department of Ophthalmology, Johannes Gutenberg University of Mainz, Mainz, Germany. Design: Experimental study. Methods: The CCT in freshly enucleated porcine globes was measured by ultrasound pachymetry before and after (if applicable) deepithelialization and every 10 minutes thereafter during 120 minutes of eyedrop application. In Groups 1 and 2 (controls), no eyedrops were applied. In Groups 3 and 4, isotonic riboflavin eyedrops were used. In Groups 5 to 9, hypotonic riboflavin eyedrops were given. In Groups 10 and 11, preparations for transepithelial crosslinking were applied. In Groups 2 to 9, deepithelialization was performed. The final CCT in the groups was compared by analysis of variance. Results: One hundred ten freshly enucleated porcine globes were used. The mean final CCT compared with preoperative values was 97% ± 4% (SD) in Group 1, 91% ± 4% in Group 2, 66% ± 5% in Group 3, 151% ± 13% in Group 4, 65% ± 2% in Group 5, 105% ± 3% in Group 6, 120% ± 4% in Group 7, 130% ± 4% in Group 8, 132% ± 4% in Group 9, 114% ± 2% in Group 10, and 114% ± 4% in Group 11. The differences between Group 1 and each of Groups 3, 4, 5, 7, 8, and 9 were statistically significant (P<.05). Conclusion: There was considerable variation in the final CCT as a result of varying riboflavin eyedrop compositions. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To evaluate the efficacy of transepithelial collagen crosslinking (CXL) in patients with bilateral progressive keratoconus. Setting: Outpatient ophthalmic clinic. Design: Cohort study. Methods: Patients with a history of bilateral progressive keratoconus were recruited. The worst eye was treated with transepithelial CXL, while the fellow eye was left untreated as a control. Transepithelial CXL was performed by applying an enhanced riboflavin solution (riboflavin 0.1%, dextrane T500 with trometamol [Tris-hydroxymethyl aminomethane] and EDTA [ethylenediaminetetraacetic] sodium salt) on the intact corneal epithelium for 30 minutes before irradiation with ultraviolet A (370 nm at 3 mW/cm2) for 30 minutes. Follow-up was 18 months in all eyes. Results: The study enrolled 20 patients. Transient hyperemia and mild foreign-body sensation occurred in 8 eyes (40%) after treatment; both resolved after 24 hours. In treated eyes, there were statistically significant improvements in uncorrected and corrected visual acuity and topography-derived keratometry, cone apex power, and higher-order aberrations (P<.05). In untreated control eyes, there was a general trend toward worsening of these parameters. No complications were reported. Conclusions: Transepithelial CXL treatment appeared to halt keratoconus progression, with a statistically significant improvement in visual and topographic parameters. The treatment was safe and well tolerated. Its noninvasive nature makes it potentially useful in cases in which epithelial debridement is ideally avoided, such as pediatric cases, uncooperative patients, and thin corneas with thicknesses nearing 380 μm. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To assess the spatial distribution and time course of increased corneal light scattering after corneal collagen crosslinking (CXL) with riboflavin and ultraviolet-A irradiation. Setting: Umeå University Hospital Eye Clinic, Umeå, Sweden. Design: Case series. Methods: Eyes with keratoconus were examined with Scheimpflug photography before and 1 and 6 months after CXL. Corneal light scattering was quantified throughout the corneal thickness at 8 measurement points 0.0 to 3.0 mm from the central cornea. Results: The study comprised 11 eyes of 11 patients. Central corneal light scattering increased significantly 1 month after CXL (P<.001). At 6 months, it decreased (P=.002); however, it was still higher than pretreatment values (P<.001). Light scattering at 1 month was more pronounced in the superficial stroma, gradually diminishing to zero at 240 μm depth. It was greater at the corneal center than 1.0 to 3.0 mm from the center. At 6 months, a second peak of light scattering occurred between 240 μm and 340 μm depth. No increased light scattering deeper than 340 μm was seen at either time point. Conclusions: Corneal light scattering after CXL showed distinctive spatial and temporal profiles. Analysis of corneal light scattering may give an impression of tissue changes, the depth of the CXL treatment effect, and the corneal response to the treatment. Scheimpflug photography appears to be useful for this purpose. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To evaluate 1-year outcomes of corneal collagen crosslinking (CXL) for treatment of keratoconus and corneal ectasia. Setting: Cornea and refractive surgery subspecialty practice. Design: Prospective randomized controlled clinical trial. Methods: Collagen crosslinking was performed in eyes with keratoconus or ectasia. The treatment group received standard CXL and the sham control group received riboflavin alone. Principal outcomes included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, astigmatism, and topography-derived outcomes of maximum and average keratometry (K) value. Results: The UDVA improved significantly from 0.84 logMAR ± 0.34 (SD) (20/137) to 0.77 ± 0.37 logMAR (20/117) (P = .04) and the CDVA, from 0.35 ± 0.24 logMAR (20/45) to 0.23 ± 0.21 logMAR (20/34) (P<.001). Fifteen patients (21.1%) gained and 1 patient lost (1.4%) 2 or more Snellen lines of CDVA. The maximum K value decreased from baseline by 1.7 ± 3.9 diopters (D) (P<.001), 2.0 ± 4.4 D (P = .002), and 1.0 ± 2.5 D (P = .08) in the entire cohort, keratoconus subgroup, and ectasia subgroup, respectively. The maximum K value decreased by 2.0 D or more in 22 patients (31.0%) and increased by 2.0 D or more in 3 patients (4.2%). Conclusions: Collagen crosslinking was effective in improving UDVA, CDVA, the maximum K value, and the average K value. Keratoconus patients had more improvement in topographic measurements than patients with ectasia. Both CDVA and maximum K value worsened between baseline and 1 month, followed by improvement between 1, 3, and 6 months and stabilization thereafter. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes. [Copyright &y& Elsevier]

Purpose: To determine the possible effect of corneal collagen crosslinking (CXL) with riboflavin and ultraviolet A (UVA) on intraocular pressure (IOP) measurements by Goldmann applanation tonometry (GAT). Setting: Institute of Vision and Optics, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. Design: Prospective case series. Methods: This noncomparative study measured IOP by GAT before CXL and 6 months and 12 months after CXL. Results: The study evaluated 55 eyes (55 patients). There was a statistically significant increase in the measured IOP 6 months and 12 months after CXL (both P<.001). The mean measured IOP was 9.95 mm Hg ± 3.01 (SD) before CXL, 11.40 ± 2.89 mm Hg at 6 months, and 11.35 ± 3.38 mm Hg at 12 months. The change in IOP measurements at both postoperative examinations was not correlated with patient age, preoperative pachymetry, or preoperative keratometry readings. Conclusion: After riboflavin–UVA CXL in eyes with keratoconus, there was a significant increase in IOP measured by GAT that was probably caused by an increase in corneal rigidity. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To determine the changes in corneal properties induced by riboflavin–ultraviolet A (UVA) irradiation using a noninvasive ultrasound (US) method in a porcine eye model. Setting: Department of Biomedical Engineering, Ohio State University, Columbus, Ohio, USA. Methods: Fresh porcine globes acquired within 24 hours postmortem were divided into equal groups. In the collagen crosslinking (CXL) group, the globes were irradiated with UVA in combination with riboflavin application following the standard protocol. The control group had the same procedures as the CXL group but with no UVA irradiation. Corneal properties were measured before and after treatments in both groups using a quantitative US method. Changes in corneal thickness, density, and stiffness were examined and the difference between the changes in the CXL group and the control group was analyzed. Results: Each group comprised 14 porcine globes. After riboflavin–UVA treatment, there was a significant increase in corneal stiffness (mean 2.59 ± 0.08 GPa before and 2.70 ± 0.08 GPa after CXL) (P<.001) and in the speed of sound in corneal tissue (1557 ± 23 m/s versus 1588 ± 22 m/s) (P<.001). There was no significant change in corneal stiffness or in the speed of sound in the control group. Corneal thickness increased significantly after the treatment in both groups. No significant change in corneal density was observed in either group. Conclusion: Corneal stiffness increased after riboflavin–UVA CXL, a finding detected using a noninvasive US technique. Financial Disclosure: Dr. Liu has filed a patent application for the general ultrasound technique used in the study. No other author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

A 19-year-old woman presented with a 3-day history of pain, redness, and diminution of vision occurring one day after collagen crosslinking (CXL) with riboflavin and ultraviolet-A had been performed for keratoconus in the right eye. On presentation, severe keratitis with a 7.0mm×6.0mm central infiltrate was present. Culture results from the patient''s contact lens and corneal scrapings were positive for Pseudomonas aeruginosa. Keratitis can occur following CXL because of the presence of an epithelial defect, use of a soft bandage contact lens, and topical corticosteroids in the immediate postoperative period, and patients should be counseled about it. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To evaluate the safety and efficacy of corneal collagen crosslinking (CXL) in patients with painful pseudophakic bullous keratopathy (PBK). Setting: University of São Paulo, São Paulo and Sadalla Amin Ghanem Eye Hospital, Joinville, Santa Catarina, Brazil. Methods: This prospective study included consecutive eyes with PBK that had CXL. After a 9.0 mm epithelial removal, riboflavin 0.1% with dextran 20% was applied for 30 minutes followed by ultraviolet-A irradiation (370 nm, 3 mW/cm2). Therapeutic contact lenses were placed for 1 week. Corneal transparency, central corneal thickness (CCT), and ocular pain were assessed preoperatively and 1 and 6 months postoperatively. Statistical analysis was by paired t tests. Results: Fourteen patients (14 eyes) with a mean age 71.14 years ± 11.70 (SD) (range 53 to 89 years) were enrolled. Corneal transparency was better in all eyes 1 month after surgery. At 6 months, corneal transparency was similar to preoperative levels (P = .218). The mean CCT was 747 μm preoperatively and 623 μm at 1 month; the decrease was statistically significant (P<.001). At 6 months, the mean CCT increased to 710 μm, still significantly thinner than preoperatively (P = .006). Pain scores at 6 months were not significantly different than preoperatively (P = .066). Conclusions: Corneal CXL significantly improved corneal transparency, corneal thickness, and ocular pain 1 month postoperatively. However, it did not seem to have a long-lasting effect in decreasing pain and maintaining corneal transparency in patients with PBK. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To evaluate the role of the preocular riboflavin film in ultraviolet-A (UVA) absorption in corneal collagen crosslinking (CXL). Setting: Eye Laser Institute, Department of Ophthalmology, Martin-Luther-University, Halle, Germany. Methods: The absorption of UVA light was measured in human donor and porcine postmortem corneas with and without riboflavin film using 3 solutions: standard dextran–riboflavin, methylcellulose–riboflavin, and hypoosmolar riboflavin–sodium chloride without dextran. The breakup time of the solutions and their absorbance were also determined. Results: After 30-minute instillation of riboflavin solution, the corneal absorption coefficient of the combined stroma–riboflavin film system was 56.36 cm−1 in human corneas and 51.46 cm−1 in porcine corneas using dextran–riboflavin; 69.87 cm−1 and 53.86 cm−1, respectively, using methylcellulose–riboflavin; and 48.19 cm−1 and 42.68 cm−1, respectively, using hypoosmolar riboflavin. For the stroma alone without riboflavin film, the absorption coefficient was reduced to 36.95 cm−1 in human corneas and 28.91 cm−1 in porcine corneas using dextran–riboflavin; 38.26 cm−1 and 32.49 cm−1, respectively, using methylcellulose–riboflavin; and 38.88 cm−1 and 28.42 cm−1, respectively, using hypoosmolar riboflavin solution. The breakup time was 22 minutes for the dextran–riboflavin film, 32 minutes for methylcellulose, and 90 seconds for the hypoosmolar solution. Conclusion: Results indicate that the cornea including the riboflavin film can be considered a composite 2-compartment system and that the riboflavin film is an integral part of the CXL procedure and important in achieving the correct stromal and endothelial UVA irradiance. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To compare 2 sequences of combined intrastromal corneal ring segment (ICRS) implantation and ultraviolet/riboflavin–mediated corneal collagen crosslinking (CXL) in progressive keratoconus. Setting: Dunya Eye Hospital, Istanbul, Turkey. Methods: In this prospective comparative randomized consecutive study, CXL was followed by ICRS implantation (Group 1) or ICRS implantation was followed by CXL (Group 2). Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, spherical equivalent (SE), manifest cylinder (cylinder), and mean keratometry (K) were compared preoperatively and postoperatively. Results: The mean interval between treatments was 7 months ± 2 (SD) (mean follow-up, 13 ± 1 months). The mean UDVA and CDVA improved in both groups (UDVA: 0.07 ± 0.09 to 0.25 ± 0.12, Group 1, and 0.11 ± 0.09 to 0.32 ± 0.21, Group 2; CDVA: 0.24 ± 0.11 to 0.41 ± 0.20 and 0.22 ± 0.16 to 0.55 ± 0.2, respectively). The mean SE, cylinder, and mean K values decreased in both groups (SE: −7.13 ± 3.34 D to −2.98 ± 2.33 D, Group 1, and −7.05 ± 5.54 D to −2.81 ± 4.08 D, Group 2; cylinder: −4.38 ± 2.03 D to −2.62 ± 1.93 D and −4.68 ± 2.60 D to −2.20 ± 1.67 D, respectively; mean K: 52.47 ± 4.01 D to 48.31 ± 3.65 D and 52.06 ± 4.93 D to 48.08 ± 4.13 D, respectively). Overall, there was more improvement in CDVA, SE, and mean K in Group 2 than in Group 1. Conclusion: Implantation of ICRS followed by CXL resulted in greater improvement of keratoconus. [Copyright &y& Elsevier]

Purpose: To compare the severity of postoperative pain and the rate of penetration of riboflavin between eyes treated by corneal crosslinking (CXL) using excimer laser superficial epithelial removal and mechanical full-thickness epithelial removal. Setting: Departments of Ophthalmology, Ullevål University Hospital, Oslo, and University Hospital of Northern Norway, Tromsø, Norway. Methods: Patients with corneal ectasia were treated with superficial corneal epithelial removal using the excimer laser programmed to 35 μm of phototherapeutic keratectomy (Group 1) or mechanical full-thickness epithelial removal with a brush (Group 2). Pain was evaluated postoperatively by the patients'' subjective evaluation and need for analgesia. The duration of topical application of riboflavin to achieve stromal saturation was measured. Results: Thirty eyes of 30 patients, 15 in each group, were treated. Postoperative pain was severe in 40.0% of patients in Group 1 and in no patient in Group 2 (P = .009) and moderate in 53.3% and 33.3%, respectively (no significant difference). The mean time to riboflavin saturation was 43.7 minutes ± 10.8 (SD) in Group 1 and 31.3 ± 3.0 minutes in Group 2 (P = .001). Conclusion: Superficial epithelial removal using the excimer laser resulted in more postoperative pain and the need for prolonged application of riboflavin to achieve corneal saturation. [Copyright &y& Elsevier]

Purpose: To evaluate intrastromal concentrations of riboflavin with and without epithelium to ensure the efficacy and safety of corneal crosslinking (CXL) by the standard and transepithelial procedures. Setting: Department of Ophthalmology and Department of Pharmacology G. Segre, Siena University, Siena, Italy. Methods: This study comprised keratoconic patients enrolled for penetrating keratoplasty (PKP) and warm-stored sclerocorneal rings unsuitable for transplantation. Half the PKP specimens were debrided, and half were left with the epithelium in situ. One of the latter and 1 debrided sample were not exposed to riboflavin (controls). Samples in both groups were soaked with 0.1% riboflavin–dextran 20% solution instilled every 2 minutes for 5, 15, and 30 minutes. Riboflavin concentrations were determined by high-performance liquid chromatography (HPLC). Results: The study evaluated 14 PKP specimens and 16 sclerocorneal rings. Control samples did not show a riboflavin emission peak. In exposed samples with epithelium, the mean riboflavin concentration was 91.88 ng/g after 5 minutes of exposure, 95.60 ng/g after 15 minutes, and 94.92 ng/g after 30 minutes. In the debrided samples, the mean riboflavin concentration was 14.42 μg/g, 20.92 μg/g, and 24.06 μg/g, respectively. No differences were seen between the in vivo samples and the ex vivo samples. Conclusions: The HPLC quantitative study showed that stromal concentrations of riboflavin increased with exposure time only if the epithelium was removed. A theoretically safe and effective riboflavin concentration of 15 μg/g was obtained for ultraviolet A-induced CXL only after the epithelium was removed and after at least 10 minutes of riboflavin application every 2 minutes. [Copyright &y& Elsevier]

A 32-year-old man with keratoconus developed corneal melting 5 days after riboflavin/ultraviolet-A corneal collagen crosslinking (CXL). Corneal scraping was positive for Acanthamoeba. The patient was unaware that he was wearing a bandage contact lens and repeatedly rinsed his face and eyelids with tap water. Because of corneal perforation, a large therapeutic keratoplasty à chaud was performed. Although CXL is considered a safe procedure, this case emphasizes the potential risks. We discuss the potential effects of deepithelialization, contact lens placement, instillation of topical nonsteroidal antiinflammatory drugs and anesthetic agents, and the possible role of apoptosis when performing CXL treatment for keratoconus. [Copyright &y& Elsevier]

Corneal collagen crosslinking (CXL) with riboflavin and ultraviolet-A light is a method for treating progressive keratectasia. The currently accepted treatment parameters induce collagen crosslinking in the anterior 250 to 350 μm of corneal stroma. To protect the endothelium, CXL inclusion criteria require a minimum corneal thickness of 400 μm after removal of the epithelium. In advanced keratoconus, however, progressive corneal thinning often leads to a remaining stromal thickness of less than 400 μm. We have therefore modified the current treatment protocol by preoperatively swelling thin corneas to a stromal thickness of at least 400 μm using hypoosmolar riboflavin solution. This treatment protocol was performed in a case series of 20 patients, and no complications were observed. Preoperative swelling of the cornea safely broadens the spectrum of CXL indications to thin corneas that would otherwise not be eligible for treatment. [Copyright &y& Elsevier]

Purpose: To test the biomechanical efficiency of corneal crosslinking with riboflavin without epithelial debridement (C3-R). Setting: Moscow Helmholtz Research Institute of Eye Diseases, Moscow, Russia. Methods: The left eyes of rabbits were crosslinked using standard crosslinking including epithelial removal (Group 1), using benzalkonium chloride–containing proxymetacaine eyedrops without epithelial removal (Group 2), or using preservative-free oxybuprocaine eyedrops without epithelial removal (Group 3). All left eyes received riboflavin solution and were irradiated with an ultraviolet-A double diode for 30 minutes (irradiance 3 mW/cm2). The animals were killed 1 day after crosslinking. Biomechanical and histological analyses were performed. Results: Fourteen eyes were evaluated. There was a statistically significant increase in Young''s modulus in Group 1 (102.45%) and in Group 2 (21.30%). In Group 3, no biomechanical changes were measured. Histology showed complete cell loss of keratocytes and endothelium in Group 1 and inhomogeneous keratocyte loss down to 200.0 μm in Group 2. No changes were observed in Group 3. Conclusions: Corneal crosslinking without epithelial debridement reduced the biomechanical effect by approximately one fifth compared with standard crosslinking, probably because of restricted and inhomogeneous stromal distribution of riboflavin. The cytotoxic damage was restricted to 200.0 μm stromal depth, which is an advantage over the standard method. Therefore, C3-R is not recommended for the routine treatment of keratoconus but primarily for cases with a corneal thickness less than 400.0 μm in which standard crosslinking cannot be used without serious risk to the endothelium. [Copyright &y& Elsevier]