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Comparison between standard and transepithelial corneal crosslinking using a theranostic UV-A device

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  • Visionengineering Italy
  • Studio Italiano di Oftalmologia
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Abstract and Figures

Purpose: To assess corneal concentration of riboflavin in two different corneal crosslinking protocols performed by a novel image-guided therapeutic (or "theranostic") UV-A device. Methods: Ten human eye bank donor tissues were used in this work. The tissues underwent corneal cross-linking according to the conventional treatment protocol (n = 5; 30 min of stromal soaking followed by 30 min of 3 mW/cm2 UV-A irradiance) and the iontophoresis-assisted transepithelial protocol (n = 5; soaking for 5 min at 1 mA/min and 9 min of 10 mW/cm2 UV-A irradiance) using a theranostic UV-A device (Vision Engineering Italy srl, Italy). The device provided real time assessment of riboflavin concentration by hyperspectral image analysis of the cornea. A 0.1% riboflavin hypotonic solution (Ricrolin+, Sooft Italia Spa, Italy) was used in all cases. Results: Manual application of hypotonic riboflavin for 30 min into the stroma achieved greater corneal riboflavin concentration (425 ± 77 μg/cm3) than transepithelial delivery of riboflavin by corneal iontophoresis (195 ± 35 μg/cm3; P = 0.001). In both UV-A irradiation protocols, corneal riboflavin concentration decreased exponentially with a constant energy rate of 2.3 ± 0.5 J/cm2 and 1.8 ± 0.3 J/cm2 respectively. At the end of treatment, the average corneal concentration of riboflavin decreased by ≥ 85%, with values of 54 ± 29 μg/cm3 and 31 ± 9 μg/cm3 (P = 0.11), respectively. Conclusion: Manual application of riboflavin onto the stroma achieved almost 50% greater concentration of riboflavin than transepithelial delivery by corneal iontophoresis. The theranostic UV-A device provided a novel approach to estimate corneal concentration of riboflavin non-invasively during treatment.
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CORNEA
Comparison between standard and transepithelial corneal
crosslinking using a theranostic UV-A device
Giuseppe Lombardo
1,2
&Sebastiano Serrao
3
&Marco Lombardo
1,3
Received: 29 August 2019 /Revised: 20 December 2019 /Accepted: 27 December 2019
#Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract
Purpose To assess corneal concentration of riboflavin in two different corneal crosslinking protocols performed by a novel
image-guided therapeutic (or theranostic)UV-Adevice.
Methods Ten human eye bank donor tissues were usedin this work. The tissues underwent corneal cross-linking according to the
conventional treatment protocol (n= 5; 30 min of stromal soaking followed by 30 min of 3 mW/cm
2
UV-A irradiance) and the
iontophoresis-assisted transepithelial protocol (n=5; soaking for 5 min at 1 mA/min and 9 min of 10 mW/cm
2
UV-A irradiance)
using a theranostic UV-A device (Vision Engineering Italy srl, Italy). The device provided real time assessment of riboflavin
concentration by hyperspectral image analysis of the cornea. A 0.1% riboflavin hypotonic solution (Ricrolin+, Sooft Italia Spa,
Italy) was used in all cases.
Results Manual application of hypotonic riboflavin for 30 min into the stroma achieved greater corneal riboflavin concentration
(425 ± 77 μg/cm
3
) than transepithelial delivery of riboflavin by corneal iontophoresis (195 ± 35 μg/cm
3
;P= 0.001). In both UV-
A irradiation protocols, corneal riboflavin concentration decreased exponentially with a constant energy rate of 2.3 ± 0.5 J/cm
2
and 1.8 ± 0.3 J/cm
2
respectively. At the end of treatment, the average corneal concentration of riboflavin decreased by 85%,
with values of 54± 29 μg/cm
3
and 31 ± 9 μg/cm
3
(P=0.11),respectively.
Conclusion Manual application of riboflavin onto the stroma achieved almost 50% greater concentration of riboflavin than
transepithelial delivery by corneal iontophoresis. The theranostic UV-A device provided a novel approach to estimate corneal
concentration of riboflavin non-invasively during treatment.
Keywords Corneal crosslinking .Riboflavin .Theranostics .Keratoconus .Iontophoresis
Introduction
Novel objective optical methodologies for measuring the ri-
boflavin concentration in the cornea are widening our under-
standing on the different stromal diffusion of ophthalmic ribo-
flavin solutions in various treatment protocols [15].
Theranostics is an emerging therapeutic paradigm that enables
image-guided therapy in clinic; theranostic devices make use
of real-time non-invasive molecular analysis to achieve
optimal treatment outcomes in the management of disease.
In previous studies [4,5], we have shown the reliability of a
theranostic UV-A device for image-guided corneal
crosslinking using the Dresden protocol in human donor tis-
sues and have compared the conventional UV-A irradiation
protocol (3 mW/cm
2
for 30 min) with accelerated UV-A irra-
diation of the stroma (10 mW/cm
2
for 9 min). The two UV-A
irradiation protocols have been shown to be almost equivalent
in terms of consumption of intrastromal riboflavin.
In this work, we used a theranostic UV-A device that, via
the acquisition and analysis of the fluorescence emitted from
the riboflavin when illuminated by UV-A light, measures in
real time the concentration of the therapeutic molecule in the
cornea. The scope of this work was to compare the corneal
riboflavin concentration in two corneal crosslinking protocols,
which were performed by the theranostic UV-A device, using
the same dextran-free riboflavin hypotonic ophthalmic solu-
tion [615]. The protocols included (1) the manual stromal
*Marco Lombardo
mlombardo@visioeng.it
1
Vision Engineering Italy srl, Via Livenza 3, 00198 Rome, Italy
2
CNR-IPCF, Istituto per i Processi Chimico-Fisici, Viale F. Stagno
DAlcontres 37, 98158 Messina, Italy
3
Studio Italiano di Oftalmologia, Via Livenza 3, 00198 Rome, Italy
https://doi.org/10.1007/s00417-019-04595-6
Graefe's Archive for Clinical and Experimental Ophthalmology (2020) 258:829834
/Published online: 3 January 2020
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Recently, a theranostic UV-A medical device has been made available for treating keratoconus by theranostic-guided corneal cross-linking. Pre-clinical studies have provided enough evidence on accuracy and precision of the theranostic UV-A medical device for inducing highly predictable tissue stiffening in human donor corneal tissues [33][34][35][36]. The novel UV-A device has emerged as a promising and powerful tool to precisely monitor the diffusion of riboflavin into the corneal stroma and its UV-A light mediated photo-degradation during treatment. ...
... The optics head of the UV-A device houses the electronic boards, the light sources, the iris aperture, the camera and the Placido disk, which is used to precisely focus the UV-A light beam onto the cornea to treat. The medical device has undergone safety testing according to the EMC EN 60601-1-2, EN 60601-1, ISO 15004-2:2007 and EN 64271:2010 standards; the performance of the UV-A medical device in question has been validated in laboratory studies, which have shown that the theranostic score had excellent accuracy and precision in predicting the tissue biomechanical strengthening induced by corneal cross-linking procedure in eye bank human donor tissues [33][34][35][36]. ...
... In the latter phase (UV-A light photo-therapy), the UV-A light is used both for quantitative imaging and therapy; during this phase, the UV-A device computes at run-time a theranostic score, which takes into account the corneal riboflavin concentration achieved prior to starting UV-A photo-therapy phase. The theranostic score has been validated in pre-clinical studies showing to highly correlate with increased tissue stiffening induced by CXL procedure, thus highlighting its potential of for real time prediction of CXL treatment efficacy in vivo [33][34][35][36]. ...
Article
Full-text available
The Assessment of theranostic guided riboflavin/UV-A corneal cross-linking for treatment of keratoconus (ARGO; registration number NCT05457647) clinical trial tests the hypothesis that theranostic-guided riboflavin/UV-A corneal cross-linking (CXL) can provide predictable clinical efficacy for halting keratoconus progression, regardless of treatment protocol, i.e., either with or without epithelial removal. Theranostics is an emerging therapeutic paradigm of personalized and precision medicine that enables real-time monitoring of image-guided therapy. In this trial, the theranostic software module of a novel UV-A medical device will be validated in order to confirm its accuracy in estimating corneal cross-linking efficacy in real time. During CXL procedure, the theranostic UV-A medical device will provide the operator with an imaging biomarker, i.e., the theranostic score, which is calculated by non-invasive measurement of corneal riboflavin concentration and its UV-A light mediated photo-degradation. ARGO is a randomized multicenter clinical trial in patients aged between 18 and 40 years with progressive keratoconus aiming to validate the theranostic score by assessing the change of the maximum keratometry point value at 1-year postoperatively. A total of 50 participants will be stratified with allocation ratio 1:1 using a computer-generated stratification plan with blocks in two treatment protocols, such as epithelium-off or epithelium-on CXL. Following treatment, participants will be monitored for 12 months. Assessment of safety and performance of theranostic-guided corneal cross-linking treatment modality will be determined objectively by corneal tomography, corneal endothelial microscopy, visual acuity testing and slit-lamp eye examination.
... These factors may be responsible both for treatment failure (recorded as K max progression at 1 year) and endothelial damage, which in turn could be caused by inadequate generation of crosslinking bonds between the corneal proteins and tissue photo-toxicity. In this view, it would be highly desirable to quantify these factors during treatment in order to personalize treatment safety and efficacy [77,78]. ...
Article
Full-text available
Background Riboflavin/UV-A corneal cross-linking (CXL) for treating keratoconus and iatrogenic corneal ectasia has been well-established as first treatment option to stabilize corneal tissue biomechanical instability. Although the plethora of clinical studies has been published into the field, there is no systematic review assessing the type and frequency of adverse events after CXL. Methods A systemic literature review on clinical safety and adverse events after CXL in patients with keratoconus and corneal ectasia was performed using PubMed. A literature search was performed for relevant peer-reviewed publications. The main outcome measures extracted from the articles were adverse events, endothelial cell density, corrected distance visual acuity and maximum simulated keratometry. Results The most frequent adverse events after CXL were corneal haze and corneal edema, which were mild and transient. The severe adverse events were infrequent (cumulative incidence: < 1.3%) after CXL. The clinical benefits of CXL highly outweighed the risks for the treatment of keratoconus and corneal ectasia. Conclusions The severe adverse events with permanent sequelae are infrequent after CXL ... and all are associated with... corneal de-epithelialization, such as infectious keratitis and corneal scarring.
... to other techniques. 27,36,38,39 Mastropasqua et al. 27 reported using iontophoresis and additives to achieve stromal riboflavin concentrations that were 21% and 44%, respectively, compared to the standard Dresden protocol using HPLC. Additionally, Cui et al. 36 reported a peak stromal concentration of 50% standard measured via two-photon fluorescence after transepithelial BAK treatment. ...
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Purpose: This study describes a femtosecond laser (FS) approach to machine corneal epithelial microchannels for enhancing riboflavin (Rf) penetration into the cornea prior to corneal crosslinking (CXL). Methods: Using a 1030-nm FS laser with 5- to 10-µJ pulse energy, the corneal epithelium of slaughterhouse rabbit eyes was machined to create 2-µm-diameter by 25-µm-long microchannels at a density of 100 or 400 channels/mm2. Rf penetration through the microchannels was then determined by applying 1% Rf in phosphate-buffered saline for 30 minutes followed by removal of the cornea and extraction from the central stromal button. Stromal Rf concentrations were then compared to those obtained using standard epithelial debridement or 0.01% benzalkonium chloride (BAK) to disrupt the epithelial barrier. Results: Microchannels formed using a 5-µJ/pulse at a density of 400 channels/mm2 achieved a stromal Rf concentration that was 50% of that achieved by removal of the corneal epithelium and imbibing with 1% Rf. Stromal Rf levels were also equal to that of debrided corneas soaked with 0.5% Rf, threefold higher than those soaked with 0.1% Rf, and twofold higher than corneas soaked in BAK without epithelial debridement. Organ culture of treated corneas showed a normal corneal epithelium following FS machining while BAK-treated corneas showed extensive epithelial and stromal damage at 24 hours posttreatment. Conclusions: FS corneal epithelial machining can be used to enhance penetration of Rf into the stroma for corneal CXL. Translational relevance: The creation of epithelial microchannels allows for stromal Rf concentrations high enough to perform true transepithelial crosslinking.
Article
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Theranostics is an emerging therapeutic paradigm of personalized medicine; the term refers to the simultaneous integration of therapy and diagnostics. In this work, theranostic‐guided corneal cross‐linking was performed on ten human sclero‐corneal tissues. The samples were soaked with 0.22% riboflavin formulation and underwent 9 minutes UV‐A irradiance at 10 mW/cm2 using theranostic device, which provided both a measure of corneal riboflavin concentration and a theranostic score estimating treatment efficacy in real time. A three‐element viscoelastic model was developed to fit the deformation response of the cornea to air‐puff excitation of dynamic tonometry and to calculate the mean corneal stiffness parameter before and after treatment. Significant correlation was found between the theranostic score and the increase in mean corneal stiffness (R=0.80; P<0.001). Accuracy and precision of the theranostic score in predicting the induced corneal tissue stiffening were both 90%. The riboflavin concentration prior to starting the UV‐A photo‐therapy phase was the most important variable to allow corneal cross‐linking to be effective. Theranostic UV‐A light mediated imaging and therapy enables the operator to adopt a precise approach for achieving highly predictable biomechanical strengthening on individual corneas. This article is protected by copyright. All rights reserved.
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Riboflavin‐5‐phosphate (RF) is the most commonly used photosensitizer in corneal cross‐linking (CXL), but its hydrophilicity and negative charge limit its penetration through the corneal epithelium into the stroma. To enhance the corneal permeability of RF and promote its efficacy in the treatment of keratoconus, novel hibiscus‐like RF@ZIF‐8 microsphere composites [6RF@ZIF‐8 NF (nanoflake)] were prepared using ZIF‐8 nanomaterials as carriers, which are characterized by their hydrophobicity, positive potential, biocompatibility, high loading capacities, and large surface areas. Both hematoxylin and eosin endothelial staining and TUNEL assays demonstrated excellent biocompatibility of 6RF@ZIF‐8 NF. In in vivo studies, the 6RF@ZIF‐8 NF displayed excellent corneal permeation, and outstanding transepithelial CXL (TE‐CXL) efficacy, slightly better than the conventional CXL protocol. Furthermore, the special hibiscus‐like structures of 6RF@ZIF‐8 NF meant that it had better TE‐CXL efficacy than that of 6RF@ZIF‐8 NP (nanoparticles) due to the larger contact area with the epithelium and the shorter RF release passage. These results suggest that the 6RF@ZIF‐8 NF are promising for transepithelial corneal cross‐linking, avoiding the need for epithelial debridement. This article is protected by copyright. All rights reserved
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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.
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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/cm² 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.
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Objective Analysis of the crosslink time, depth and efficacy profiles of UV-light-activated corneal collagen crosslinking (CXL). Methods A modeling system described by a coupled dynamic equations are numerically solved and analytic formulas are derived for the crosslinking time (T*) and crosslinking depth (z*). The z-dependence of the CXL efficacy is numerically produced to show the factors characterizing the profiles. Results Optimal crosslink depth (z*) and maximal CXL efficacy (Ceff) have opposite trend with respective to the UV light intensity and RF concentration, where z* is a decreasing function of the riboflavin concentration (C0). In comparison, Ceff is an increasing function of C0 and the UV exposure time (for a fixed UV dose), but it is a decreasing function of the UV light intensity. CXL efficacy is a nonlinear increasing function of [C0/I0]-0.5 and more accurate than that of the linear theory of Bunsen Roscoe law. Depending on the UV exposure time and depth, the optimal intensity ranges from 3 to 30 mW/cm² for maximal CXL efficacy. For steady state (with long exposure time), low intensity always achieves high efficacy than that of high intensity, when same dose is applied on the cornea. Conclusions The crosslinking depth (z*) and the crosslinking time (T*) have nonlinear dependence on the UV light dose and the efficacy of corneal collagen crosslinking should be characterized by both z* and the efficacy profiles. A nonlinear scaling law is needed for more accurate protocol.
Article
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Purpose: To compare 1-year transepithelial corneal collagen cross-linking with iontophoresis (I-CXL) outcomes with standard CXL (S-CXL) epithelium-off for progressive keratoconus. Methods: Forty eyes of 40 patients with progressive keratoconus were included in this comparative, prospective clinical study. Corrected distance visual acuity (CDVA), spherical equivalent, cylinder refraction, corneal topography, Scheimpflug tomography, aberrometry, and endothelial cell count were assessed at baseline and at 1, 3, 6, and 12 months of follow-up. Results: Patients received either I-CXL (20 eyes) or S-CXL (20 eyes). Functional parameters (visual acuity and aberrometry) showed a significant improvement (P < .05) after 6 and 12 months of follow-up in both groups. In the I-CXL group, the CDVA showed a rapid recovery of vision after 3 months (P = .01) compared to baseline. Morphological parameters showed a significant reduction of maximum keratometry in the S-CXL group by -1.05 ± 1.51 diopters (D) after 12 months, whereas the I-CXL group curvature was stable (-0.31 ± 1.87 D). Minimum pachymetry values were stable even after 12 months of follow-up in the I-CXL group, whereas a significant corneal thinning 12 months following treatment was recorded in the S-CXL group (P < .001). None of the patients had continuous progression of keratoconus or had to repeat CXL procedures. Endothelial cell counts did not change significantly (P > .05). Conclusions: The 1-year outcomes suggest that I-CXL might be comparable to S-CXL in stabilizing the progression of the degenerative ectatic disease. Additionally, quicker improvement of functional parameters was reported in the I-CXL group. [J Refract Surg. 2016;32(10):672-678.].
Article
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Purpose: To compare the results of standard corneal crosslinking (CXL) and transepithelial iontophoresis-assisted CXL after 24 months follow-up. Material and methods: Corneal crosslinking (CXL) was performed in a series of 149 eyes of 119 patients with keratoconus I–II of Amsler classification. Depending on the CXLmethod, patients were divided into two groups: (1) 73 eyes with standard CXL and (2) 76 eyes with transepithelial iontophoresis-assistedCXL. Depending on the group, epithelium removal or administration of riboflavin solution by iontophoresis for 10 min was performed, after which standard surface UVA irradiation (370 nm, 3 mW/cm2) was performed at a 5-cm distance for 30 min. Results: A statistically significant difference in corrected distance visual acuity (CDVA) was observed between the two groups, with a better outcome in the second group after 6 months (p = 0.037); however, no significant difference was found 24 months after treatment (p = 0.829). Stabilization and regression of keratometry values were achieved in both groups, but standard CXL was more effective. The average demarcation line depth in the standard CXL group was 292 ± 14 microns after 14 days and 172 ± 16 microns in the transepithelial iontophoresis-assisted CXL group. No demarcation line was detected after 1 month and 3 months in 45% and 100% of the eyes in the second group respectively. Conclusion: Transepithelial iontophoresis-assisted collagen crosslinking showed to be less effective than standard CXL after 24 months of follow-up, possibly due to a more superficial formation of corneal collagen crosslinks, however the stopping of disease progression was achieved 24 months after procedure.
Article
Purpose: To evaluate the 2-year clinical outcomes of corneal crosslinking (CXL) using transepithelial iontophoresis CXL (T-ionto CXL) in comparison with standard CXL for the treatment of progressive keratoconus. Setting: Single-site study. Design: Randomized controlled clinical trial with identifier code NCT02117999. Methods: The eyes of the participants were randomized to have either T-ionto CXL and/or standard CXL. Assessments of uncorrected (UDVA) and corrected (CDVA) distance visual acuities (logarithm of the minimum angle of resolution [logMAR]), manifest refraction spherical equivalent, maximum simulated keratometry (K) (diopters [D]), corneal higher-order aberrations (HOAs), central corneal thickness (CCT), and endothelial cell density (ECD) were performed at 3 days, 7 days, and 1, 3, 6, 12, and 24 months postoperatively. Results: The study comprised 34 eyes (25 patients). There were 22 eyes in the T-ionto CXL group and 12 eyes in the standard CXL group. Two years after T-ionto CXL and standard CXL, the mean maximum K flattened by -1.05 ± 1.20 D (P = .07) (20 eyes) and -1.51 ± .89 D (P < .001) (11 eyes), respectively. Two study cases (10%) and no control showed maximum K steepening of more than 1.0 D at 24 months postoperatively. The mean change in CDVA was -0.08 ± 0.15 logMAR (P = .04) and -0.02 ± 0.06 logMAR (P = .34) after T-ionto CXL and standard CXL, respectively. A significant average decrease in the myopic defocus (+0.81 D; P < .05) was found in both groups. No significant differences in the outcome measures between treatments were found at 24 months. The corneal HOAs, CCT, and ECD values did not change significantly in any group at 2 years postoperatively. Conclusions: Clinically significant topographic, visual, and refractive improvements were found 2 years after T-ionto CXL; standard CXL showed more significant corneal apex flattening than the transepithelial iontophoresis protocol.
Article
Purpose: To compare clinical outcomes of transepithelial corneal cross-linking using iontophoresis (T-ionto CL) and standard corneal cross-linking (standard CL) for the treatment of progressive keratoconus 12 months after the operation. Design: Prospective randomized controlled clinical trial. Participants: Thirty-four eyes of 25 participants with progressive keratoconus were randomized into T-ionto CL (22 eyes) or standard CL (12 eyes). Methods: T-ionto CL was performed using an iontophoresis device with dextran-free 0.1% riboflavin-5-phosphate solution with enhancers and by irradiating the cornea with a 10 mW/cm(2) ultraviolet A device for 9 minutes. Standard CL was performed according to the Dresden protocol. Main outcome measures: The primary outcome measure was stabilization of keratoconus after 12 months through analysis of maximum simulated keratometry readings (Kmax, diopters). Other outcome measures were corrected distance visual acuity (CDVA, logarithm of the minimum angle of resolution [logMAR]), manifest spherical equivalent refraction (D), central corneal thickness (CCT, micrometers) and endothelial cell density (ECD). Follow-up examinations were arranged at 3 and 7 days and 1, 3, 6, and 12 months. Results: Twelve months after T-ionto CL and standard CL, Kmax on average flattened by -0.52±1.30 D (P = 0.06) and -0.82±1.20 D (P = 0.04), respectively. The mean change in CDVA was -0.10±0.12 logMAR (P = 0.003) and -0.03±0.06 logMAR (P = 0.10) after T-ionto CL and standard CL, respectively. The manifest spherical equivalent refraction changed on average by +0.71±1.44 D (P = 0.03) and +0.21±0.76 D (P = 0.38), respectively. The CCT and ECD measures did not change significantly in any group at 12 months. Significant differences in the outcome measures between treatments were found in the first week postoperatively. No complications occurred in the T-ionto CL group; 1 eye (8%) had sterile corneal infiltrates, which did not affect the final visual acuity, in the standard CL group. Conclusions: Significant visual and refractive improvements were found 12 months after T-ionto CL, though the average improvement in corneal topography readings was slightly lower than the Dresden protocol in the same period.
Article
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.