Corneal Cross-linking Protocols Research Articles

Comparative Evaluation of Anterior Segment Optical Coherence Tomography Findings Following Accelerated Corneal Crosslinking Protocols Using Different Riboflavin Formulations and Soaking Durations

Purpose To comparatively evaluate the influence of different riboflavin formulations and soaking durations on the anterior segment optical coherence tomography (AS-OCT) findings following accelerated corneal crosslinking (ACXL) at 9 mW/cm2 for in progressive keratoconus. Methods In this prospective study, consecutive patients with progressive keratoconus were randomized into 4 groups. Group 1: hydroxypropyl methylcellulose (HPMC)-based riboflavin for 10 min; Group 2: HPMC-based riboflavin for 20 min; Group 3: dextran-based riboflavin (0.1%) for 30 min. Riboflavin soaking was followed by ultraviolet-A irradiation at 9 mW/cm2 for 10 min in all three groups. Group 4 underwent conventional CXL (CCXL) using Dresden protocol. The AS-OCT features of the crosslinked cornea were evaluated at postoperative month 1 and correlated to the clinical outcomes at postoperative month 12. Results The study enrolled 26 eyes of 26 patients in each group. In groups 1 and 2, the AS-OCT findings were similar (p > .05) and the demarcation lines depth (DLD) were deep as obtained following CCXL. The DLD was significantly shallower in group 3 compared to the other groups (p < .01). There were no between-group differences in regards to the visual, refractive, keratometric, and tomographic outcomes at postoperative month 12. No significant endothelial cell loss or any other clinically significant adverse event was encountered in any patient’s eye at 12 months follow-up. Conclusion Although structural variations were noted in the crosslinked cornea, DLDs observed following ACXL (9 mW/cm2) using HPMC-based solution for 10 or 20 min were similar to those observed following CCXL. Whereas, ACXL (9 mW/cm2) using dextran-based solution for 30 min resulted in the shallowest DLD. Despite these remodeling differences, the visual, refractive and tomographic outcomes of all groups were comparable at postoperative 1-year follow-up. Studies with a greater number of patients and longer follow-ups are required to establish any relation between AS-OCT characteristics of crosslinked cornea and ACXL efficacy.

Development of graphitic carbon nitride quantum dots-based oxygen self-sufficient platforms for enhanced corneal crosslinking

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5’-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Outcomes of accelerated corneal cross-linking for pediatric and adult keratoconus: a comparative study.

To compare the visual, refractive, and topographic outcomes of a high irradiance accelerated corneal crosslinking (ACXL) protocol after a 12-month follow-up between pediatric and adult patients with progressive keratoconus (KC). Retrospective, comparative, cohort study. Patients with KC were divided into two groups: pediatric (≤ 18years) and adult (> 18years). All of them were managed with epi-OFF ACXL (30mW/cm2, 8min, pulsed 1:1 on and off = 7.2J/cm2). Visual, refractive, and topographic values were measured preoperatively and at 1, 3, 6, and 12months postoperative. KC progression, defined as a Kmax increase of ≥ 1D during follow-up, was recorded. Eighty-nine eyes (53 patients) were included for analysis; 45 (50.6%) eyes were from pediatric patients and 44 (49.4%) from adults. At one-year follow-up, pediatric patients experienced significantly higher rates of progression (22.2% vs. 4.5%, p = .014). Contrariwise, female gender (Beta = - 3.62, p = .018), a baseline uncorrected visual acuity of Snellen ≥ 20/60 (Beta = - 5.96, p = .007), and being ≥ 15years at ACXL treatment (Beta = - 0.31, p = .021) were associated with non-progressive disease. A significant improvement in best-corrected visual acuity, Kmin, Km, and Kmax was recorded in both groups. Overall, 86.5% of eyes from both groups showed Kmax stabilization or improvement. Despite the similarity in visual, refractive, and topographic outcomes in both groups, younger age was associated with KC progression after ACXL at one year of follow-up.

Use of Nanoindentation in Determination of Regional Biomechanical Properties of Rabbit Cornea After UVA Cross-Linking.

To evaluate the regional effects of different corneal cross-linking (CXL) protocols on corneal biomechanical properties. The study involved both eyes of 50 rabbits, and the left eyes were randomized to the five intervention groups, which included the standard CXL group (SCXL), which was exposed to 3-mW/cm2 irradiation, and three accelerated CXL groups (ACXL1-3), which were exposed to ultraviolet-A at irradiations of 9mW/cm2, 18mW/cm2, and 30mW/cm2, respectively, but with the same total dose (5.4 J/cm2). A control (CO) group was not exposed to ultraviolet-A. No surgery was done on the contralateral eyes. The corneas of each group were evaluated by the effective elastic modulus (Eeff) and the hydraulic conductivity (K) within a 7.5-mm radius using nanoindentation measurements. Compared with the CO group, Eeff (in regions with radii of 0-1.5mm, 1.5-3.0mm, and 3.0-4.5mm) significantly increased by 309%, 276%, and 226%, respectively, with SCXL; by 222%, 209%, and 173%, respectively, with ACXL1; by 111%, 109%, and 94%, respectively, with ACXL2; and by 59%, 41%, and 37%, respectively, with ACXL3 (all P < 0.05). K was also significantly reduced by 84%, 81%, and 78%, respectively, with SCXL; by 75%, 74%, and 70%, respectively, with ACXL1; by 64%, 62%, and 61%, respectively, with ACXL2; and by 33%, 36%, and 32%, respectively, with ACXL3 (all P < 0.05). For the other regions(with radii between 4.5 and 7.5mm), the SCXL and ACXL1 groups (but not the ACXL2 and ACXL3 groups) still showed significant changes in Eeff and K. CXL had a significant effect on corneal biomechanics in both standard and accelerated procedures that may go beyond the irradiated area. The effect of CXL in stiffening the tissue and reducing permeability consistently decreased with reducing the irradiance duration.

Short-Term Effect of Conventional Versus Accelerated Corneal Cross-Linking Protocol on Corneal Geography and Stability.

Purpose: To determine the 6-month effect of conventional (CXL30) and accelerated cross-linking with a UVA intensity of 9 mW/cm2 (CXL10) on corneal stability and to investigate whether there was a difference in ABCD grading system parameters regarding the two different procedures. Methods: Twenty-eight eyes of 28 patients with a documented keratoconus (KN) progression were included. Patients were selected to undergo either epi off CXL30 or CXL10. At the baseline and the follow-up visits after one (V1), three (V2), and six months (V3), the patients underwent complete ophthalmic examination and corneal tomography. Results: In the CXL30 group, all the parameters from the ABCD grading system significantly changed from baseline to V3; parameter A decreased (p = 0.048), B and C increased (p = 0.010, p < 0.001), and D decreased (p < 0.001). In the CXL10 group, there were no changes in parameters A (p = 0.247) and B (p = 0.933), though parameter C increased (p = 0.001) and D decreased (p < 0.001). After an initial decline after one month, visual acuity (VA) recovered on V2 and V3 (p < 0.001), and median maximal keratometry (Kmax) decreased in both groups (p = 0.001, p = 0.035). In the CXL30 group, there were significant changes in other parameters; average pachymetric progression index (p < 0.001), Ambrósio relational thickness maximum (ARTmax) (p = 0.008), front and back mean keratometry (p < 0.001), pachymetry apex (PA) (p < 0.001), and front elevation (p = 0.042). However, in the CXL10 group, there were significant changes only in ARTmax (p = 0.019) and PA (p < 0.001). Conclusion: Both epi-off CXL protocols showed similar short-term efficacy in improving VA and Kmax, halting the progression of KN, and both similarly changed tomographic parameters. However, the conventional protocol modified the cornea more significantly.

How Modifications of Corneal Cross-Linking Protocols Influence Corneal Resistance to Enzymatic Digestion and Treatment Depth.

The purpose of this study was to determine the effects of the Photoactivated Chromophore for Keratitis Corneal Cross-Linking (PACK-CXL) protocol modifications on corneal resistance to enzymatic digestion and treatment depth. Eight hundred one ex vivo porcine eyes were randomly divided into groups of 12 to 86 corneas, treated with various epi-off PACK-CXL modifications, including acceleration (30 > 2 minutes, 5.4J/cm2), increased fluence (5.4 > 32.4J/cm2), deuterium oxide (D2O) supplementation, different carrier types (dextran versus hydroxypropyl methylcellulose [HPMC]), increased riboflavin concentration (0.1 > 0.4%), and riboflavin replenishment during irradiation (yes/no). Control group eyes did not receive PACK-CXL. A pepsin digestion assay was used to determine corneal resistance to enzymatic digestion. A phalloidin fluorescent imaging assay was used to determine the PACK-CXL treatment effect depth. Differences between groups were evaluated using a linear model and a derivative method, respectively. PACK-CXL significantly increased corneal resistance to enzymatic digestion compared to no treatment (P < 0.03). When compared to a 10 minute, 5.4J/cm2 PACK-CXL protocol, fluences of 16.2J/cm2 and higher increased corneal resistance to enzymatic digestion by 1.5- to 2-fold (P < 0.001). Other protocol modifications did not significantly change corneal resistance. A 16.2J/cm2 fluence also increased collagen compaction in the anterior stroma, whereas omitting riboflavin replenishment during irradiation increased PACK-CXL treatment depth. Increasing fluence will likely optimize PACK-CXL treatment effectiveness. Treatment acceleration reduces treatment duration without compromising effectiveness. The generated data help to optimize clinical PACK-CXL settings and direct future research efforts.

Comparison Between Pulsed and Continuous Accelerated Corneal Cross-Linking Protocols.

To compare between two accelerated corneal cross-linking (A-CXL) protocols in the management of keratoconus (KC) as regard to the extent of corneal treatment. This retrospective, comparative study included patients having mild to moderate, progressive KC. The study population was divided into two groups; group 1 enrolled 103 eyes of 62 patients who received pulsed light A-CXL (pl-CXL) at a power of 30 mW/cm2 with an irradiation time of 4 minutes, while group 2 comprised 87 eyes of 51 patients who received continuous light A-CXL (cl-CXL) at a power of 12 mW/cm2 with an irradiation time of 10 minutes. Recordings of the central and peripheral demarcation line depths (DD), and the maximum (DDmax) and minimum (DDmin) DD, using anterior segment optical coherence tomography, were compared between the two studied groups one month after the treatment protocol. Treatment stability was also evaluated pre and postoperatively (one year following surgery) by comparing the refractive and keratometric outcomes in both groups. The differences between the preoperative corneal thickness (minimum and central) and the epithelial thickness measurements between both groups were not statistically significant. Although group 1 had slightly larger central DD (223.4 ± 62.3 um), DDmax (240.4 ± 61.8 um), and DDmin (201 ± 54 um) than those of group 2 (221.8 ± 37 um, 229.1 ± 38.4 um, and 212 ± 37.2 um, respectively), the differences between both groups' measurements were not statistically significant. Also, the two groups showed statistically insignificant differences regarding the subjective refraction and the average and maximum keratometry pre and postoperatively, denoting visual, refractive, and keratometric stability in both groups. Longer duration cl-CXL seems to be as effective as pl-CXL regarding both postoperative stability and the extent of corneal tissue penetration by the ultraviolet treatment.

A Comparison Between Cross-Linking Protocols in Patients With Progressive Keratoconus: A Review.

Keratoconus (KC) is a noninflammatory cornea disease leading to progressive thinning, causing it to change from its normal dome shape to a cone shape. One of the novel treatments of KC is corneal collagen cross-linking (CXL). Due to its importance, many studies have been conducted to compare corneal cross-linking protocols; this review article aims to discuss corneal cross-linking and compare its different treatment options, including Dresden, accelerated, and customized protocols in patients with progressive KC and their respective long-term outcomes. A search was performed in PubMed and Google Scholar with no language, dates, or study type restriction. Most of the results showed almost no difference between protocols over traditional cross-linking. However, published data are limited, long-term outcomes of novel age groups remain unclear, and further studies are needed.

Iontophoresis Corneal Cross-linking With Oxygen Supplementation in Ovine Eyes.

To evaluate the biomechanical changes and advanced oxidation protein products (AOPP) production after different corneal cross-linking (CXL) protocols with or without oxygen supplementation. Ovine eyes in the study were equally distributed to five groups as control, standard Dresden protocol, diluted alcohol- and iontophoresis-assisted CXL (DAI-CXL), and 0.1% and 0.2% riboflavin-mediated iontophoresis-assisted CXL with oxygen supplementation (I-CXL). Corneas that received CXL were divided into two equal parts, one part was used for uniaxial tensiometry and one part was used for AOPP measurement. All treatment groups showed higher Young's modulus and stiffness compared to the control group (P < .05). Both oxygen-assisted I-CXL groups with 0.1% and 0.2% riboflavin concentrations had higher corneal Young's modulus (P = .009 and .006, respectively) and stiffness (P = .009) values, whereas the DAI-CXL group had lesser Young's modulus and stiffness values (P = .032) compared to the Dresden protocol group. All treatment groups showed higher AOPP concentrations compared to the control group (P < .05). DAI-CXL and I-CXL groups showed similar AOPP formation compared to the Dresden protocol (P = .673). When the epithelium is intact, the desired increase in corneal stiffness might not be achieved. However, increasing the oxygen in the environment might provide a sufficient increase in stiffness in cases undergoing epitheliumon I-CXL, which might be promising in terms of shortening the CXL therapy and decreasing the complications. [J Refract Surg. 2022;38(10):674-681.].

Identification of Treatment Protocols for Effective Cross-Linking of the Peripheral Cornea: An Experimental Study.

This study aimed to test and evaluate modified corneal cross-linking (CXL) protocols regarding improved treatment effects on the peripheral cornea in terms of tissue stability and cellular response. Peripheral CXL (pCXL) was performed within a ring of 9-11mm of 36 human donor corneas with variations in applied energy (5.4, 7.2, and 10J/cm2) at 9mW/cm2 irradiance. Each energy level was additionally modulated regarding the oxygen level surrounding the cornea during treatment (21%; 100%). Stress-strain tests with endpoints at 12% strain and collagenaseA-assisted digestions to complete digestion were performed to evaluate the rigidity and resistance of treated and control tissue. Further, corneas were processed histologically via TUNEL assay and H&E staining to demonstrate the effects on stromal cells during treatment under varying CXL conditions. Increases in energy dosage achieved significant increases in resistance to stress in all variations except when comparing protocolsA and B under normoxic conditions. Supplemental oxygen significantly increased rigidity in protocolsB (p < 0.01) and C (p = 0.018). Hyperoxic conditions significantly increased resistance to digestion in all protocols. The number of DNA strand breaks in TUNEL assay staining showed significant increases in all increases in energy as well as with oxygen supplementation. Increases in energy and supplemental oxygen improved the effect of CXL, though endothelial safety could not be verified with confidence in high-fluence CXL with supplemental oxygen. Results suggest that CXL protocols using 7.2J/cm2 with 100% O2 or 10J/cm2 without supplemental oxygen prove most effective without anticipated risk of endothelial damage.

Bactericidal Efficacy of High Irradiance Ultraviolet A Photoactivation of Riboflavin Versus Standard Corneal Cross-Linking Protocol In Vitro.

The purpose of this study was to compare the efficacy of high ultraviolet A (UVA) irradiance photoactivation of riboflavin (vitamin B2) versus the standard corneal cross-linking protocol on bacterial viability. Methicillin-sensitive Staphylococcus aureus (MSSA) Newman strain and methicillin-resistant multidrug-resistant S. aureus (MDR-MRSA) USA300, CA409, CA127, GA656, and NY315 strains were exposed to a UVA energy dose of 5.4 to 6 J/cm 2 by 2 high irradiance regimens: A) 30 mW/cm 2 for 3 minutes and B) 10 mW/cm 2 for 10 minutes with B2 0.1%. Control groups included B2/UVA alone, CA409 exposed to standard B2 0.1% + UVA (3 mW/cm 2 for 30 minutes), and an untreated sample. Cell viability was assessed. Triplicate values were obtained. The Mann-Whitney test and Student t test were used for statistical analysis. There was no difference comparing the median bacterial load (log CFU/mL) of the untreated samples versus regimen A: Newman P = 0.7, CA409 P = 0.3, USA300 P = 0.5, CA127 P = 0.6, GA656 P = 0.1, and NY315 P = 0.2 ( P ≥ 0.1); and B: Newman P = 0.1, CA409 P = 0.3, USA300 P = 0.4, CA127 P = 0.6, GA656 P = 0.1, and NY315 P = 0.3 ( P ≥ 0.1). Standard regimen killed 100% of CA409. Photoactivation of B2 by high UVA irradiance does not seem to be effective for bacterial eradication in this study.

Corneal Haze and Densitometry in Keratoconus after Collagen Cross-Linking by Three Different Protocols

Purpose:To evaluate postoperative corneal haze and corneal densitometry following three different corneal cross-linking (CXL) protocols; standard, accelerated, and trans-epithelial (TE).Methods:The study recruited 104 eyes (53 patients) with progressive keratoconus divided into three groups: Group I were subjected to standard CXL, Group II to TE-CXL, and Group III to accelerated CXL (A-CXL) (10 mW/cm2 for 9 min). Subjective and objective corneal haze measures were evaluated before and 3, 6, and 12 months post-CXL using slit-lamp biomicroscopy and Pentacam Sheimpflug camera.Results:There was a significant difference in corneal densitometry between the three groups at 3 and 6 months post-CXL (P < 0.0001). By the 12th month, a significant statistical difference was observed only in zones (0–2 mm) and (2–6 mm) in both the anterior and the central layers. In Group I, the densitometry value of the preoperative anterior stromal layer (anterior 120 μm) was 19.42 ± 1.81. Then, it peaked at 23.12 ± 1.21 at 3 months (P < 0.0001), reached 19.82 ± 1.19 at 6 months (P = 0.007), and decreased to 19.33 ± 3.23 (P > 0.05) at 12 months. In Group II, the preoperative densitometry value of the anterior layer was 19.41 ± 1.21, peaked at 19.72 ± 1.12 at 3 months (P = 0.02), reached 19.04 ± 1.18 at 6 months (P = 0.052), and increased to 19.13 ± 1.37 at 12 months (P = 0.84). In Group III, the preoperative densitometry value of the anterior stromal layer was 19.53 ± 2.23. Then, it peaked at 24.80 ± 1.08 at 3 months (P < 0.0001), decreased to 21.75 ± 1.11 at 6 months (P < 0.0001), and reached 19.77 ± 2.26 at 12 months (P = 0.047). There was no significant correlation between the visual acuity changes and the total corneal densitometry.Conclusion:The TE-CXL group showed a better and earlier recovery from the haze, while the A-CXL group showed a delay in recovering and persistent increased corneal densitometry, mainly in the anterior 120 μ.

Comparison between three protocols of corneal collagen crosslinking in adults with progressive keratoconus: Standard versus accelerated CXL for keratoconus.

The study aimed to compare eye outcomes between the standard and accelerated corneal cross-linking (CXL) protocols over a 1-year follow-up, and assess whether the accelerated protocols are non-inferior to the standard. A retrospective cohort study including patients older than 18 years diagnosed with progressive keratoconus who underwent a CXL procedure. The primary outcome was defined as an increase of more than 1.5 diopter (D) in Kmax. The analysis included intra- and inter-group comparisons assessing differences in eye characteristics before and 12 months after the procedure. Furthermore, we assessed whether the accelerated procedures were non-inferior to the standard regarding Kmax change after 12 months. Eighty-four patients included in the study of which 23, 37 and 23 underwent the standard CXL (group I), 10-min. (group II) and the 3-min. (group III) accelerated procedures, respectively. Intra-group comparison before and after 12 months of mean Ksteep and anterior corneal astigmatism showed significant improvement only for group I (-0.3D decrease for both). Inter-group comparison showed better results after 12 months for group I (-0.9 ± 1.2) compared to group III (0.1 ± 0.8) in Ksteep, Kmean (-0.5+1. vs 0.1+0.7, respectively) and anterior astigmatism (-0.5 + 0.9 vs 0.3+1.1, respectively). We could not declare that the accelerated CXLs are non-inferior to the standard (p-value = 0.11 and 0.15). The standard CXL showed better results for keratometry and astigmatism in comparison with the accelerated. Therefore, the wide use of the accelerated CXL should be considered and reviewed for longer follow-up time and larger sample size in focus on the visual acuity parameters.

Accelerated and Standard Corneal Cross-Linking Protocols in Patients with Down Syndrome: A Non-inferiority Contralateral Randomized Trial.

IntroductionTo compare the results of an accelerated corneal cross-linking (CXL) protocol (9 mW/cm2, 10 min) with the standard CXL protocol (3 mW/cm2, 30 min) in patients with Down syndrome (DS) who have keratoconus (KC).MethodsTwenty-seven 10- to 20-year-old patients with DS who had bilateral progressive KC were enrolled in a contralateral randomized trial and completed 2 years of follow-up examinations. Fellow eyes were randomly allocated to the accelerated CXL group or the standard CXL group. The main outcome measure was change in maximum keratometry (Kmax) centered on the steepest point (zonal Kmax − 3 mm) with a non-inferiority margin of 1.0 diopter (D). Vision and refraction tests, ophthalmic examinations, and corneal tomography were performed at baseline and at 6, 12, and 24 months after CXL. Failure was defined as an increase of ≥ 1.0 D in zonal Kmax − 3 mm within a 12-month period.ResultsThe mean age (± standard deviation) of the patients was 15.71 ± 2.40 years. The within-group change in zonal Kmax − 3 mm was not significant after 2 years in either group, and within-group zonal Kmax − 3 mm remained stable. At 2 years after CXL, the mean change in the zonal Kmax − 3 mm was – 0.02 ± 0.81 D and – 0.31 ± 0.86 D in the accelerated CXL and standard CXL groups, respectively (P = 0.088). At 1 year of follow-up, three patients in the accelerated CXL group showed treatment failure (mean change in zonal Kmax − 3 mm + 2.12 ± 0.11 D); no patients in the standard CXL group showed treatment failure. At 2 years of follow-up, these three patients showed a decrease of – 0.43 ± 0.18 D in zonal Kmax − 3 mm from a baseline value of 55.11 ± 0.32 D. The 2-year trends of the inferior–superior asymmetry and vertical coma were statistically significantly different between the two groups, with the accelerated CXL protocol showing superiority in patients with higher baseline values.ConclusionIn young patients with Down syndrome, the accelerated CXL protocol was able to halt disease progression and may be an alternative for the standard CXL protocol. In advanced KC, the efficacy of the accelerated approach was delayed and appeared later in the follow-up. In asymmetric cornea, the accelerated CXL resulted in centralization of the corneal cone.Trial RegistrationIranian Registry of Clinical Trials, IRCT20100706004333N3Electronic supplementary materialThe online version of this article (10.1007/s40123-020-00303-4) contains supplementary material, which is available to authorized users.

Comparison of Two Different Accelerated Corneal Cross-linking Procedure Outcomes in Patients with Keratoconus

Background:Corneal cross-linking treatment is the unique treatment method that can cease the progression of keratoconus disease. Because of the long duration of conventional treatment, accelerated cross-linking treatment methods are being developed.Aims:To compare two different accelerated corneal cross-linking protocols in terms of postoperative visual acuity and topographic findings (higher-order aberrations and keratometry values).Study Design:Retrospective comparative study.Methods:Sixty-five eyes of 43 patients (30 men and 13 women) who underwent two different accelerated corneal cross-linking protocols (10 min, 9 mW/cm2 and 5 min, 18 mW/cm2) for progressive keratoconus were retrospectively analyzed. Patients were divided into two groups according to the accelerated corneal cross-linking treatment protocol: group 1 (10 min, 9 mW/cm2, 32 eyes of 21 patients) and group 2 (5 min, 18 mW/cm2, 33 eyes of 22 patients). Uncorrected visual acuity and best-corrected visual acuity values and topographic findings (central corneal thickness and flat and steep keratometry values) were recorded preoperatively and 6 months after corneal cross-linking treatment. High-order aberration values measured with Pentacam preoperatively and 6 months after corneal cross-linking were also recorded.Results:In both groups, a significant improvement was detected in the uncorrected visual acuity and best-corrected visual acuity levels preoperatively and 6 months postoperatively (group 1: p=0.001, p=0.001 and group 2: p=0.001, p=0.001, respectively). In addition, central corneal thickness values decreased significantly in both groups (p=0.006 and 0.001). Trefoil values showed no significant difference preoperatively and 6 months postoperatively in group 1 (p=0.160 and 0.620, respectively). In groups 1 and 2, coma values were found to decrease significantly in the 6th postoperative month compared with preoperative values (p=0.001 and 0.020, respectively). There was no significant difference between preoperative and 6th month postoperative horizontal and vertical trefoil values in both groups (p=0.850 and 0.140, respectively). There was no significant difference between the two groups in terms of preoperative and 6th month postoperative higher-order aberrations, refractive errors, keratometry values, and uncorrected visual acuity and best-corrected visual acuity levels.Conclusion:Both accelerated corneal cross-linking procedures provide similar improvement in topographic findings, coma values and visual acuity.

Accelerated corneal crosslinking in children with keratoconus: 5-year results and comparison of 2 protocols

To evaluate long-term clinical results of 2 different accelerated corneal crosslinking (CXL) protocols in pediatric patients with keratoconus. Beyoğlu Eye Training and Research Hospital, Istanbul, Turkey. Retrospective case-control study. Patients who were younger than 18 years were included in the study. Group 1 received 4 minutes of illumination at 30 mW/cm, and Group 2 received 5 minutes of illumination at 18 mW/cm. Uncorrected and corrected distance visual acuities, manifest refraction, corneal topographic parameters, and corneal higher-order aberrations (HOAs) were evaluated at baseline and during 1-, 3-, and 5-year follow-up visits. A total of 143 eyes from 86 patients were included in the study. There were 30 eyes in Group 1 and 113 eyes in Group 2. The mean follow-up time was 4.15 ± 0.99 years. Mean keratometry (K) and/or maximum K progressed ≥1.00 diopter (D) in 7 eyes (23.3%) in Group 1 and 19 eyes (16.8%) in Group 2 (P = .411). Mean K and/or maximum K decreased ≥2.00 D in 2 eyes (6.7%) in Group 1 and 24 eyes (21.2%) in Group 2 (P = .06). In Group 1, there were no statistically significant differences in topographic parameters during follow-up. In Group 2, there was a statistically significant reduction in total HOA and coma during the 5-year visit when compared with the preoperative visit (P = .005 and P = .045, respectively). Accelerated CXL is beneficial in terms of halting the progression of keratoconus in pediatric patients throughout 5 years of follow-up examinations. An increased irradiance with a reduced application time reduces the topographic effects of CXL.

Comparison of High Intensity Accelerated Corneal Cross Linking Protocols in Treatment of Progressive Keratoconus;

Purpose: To compare the safety and efficacy of Accelerated Corneal Cross Linking (AXL) protocols ,9mW/cm2 for 10 min with 18mW/cm2 for 5 min in terms of refractive and topographic keratometric indices in patients with progressive keratoconus over 3, 6, 12 and 18 months follow-up.&#x0D; Study Design: Quasi experimental study.&#x0D; Place and Duration of Study: Armed Forces Institute of Ophthalmology Rawalpindi Pakistan, from Nov 2016 to Jun 2018.&#x0D; Material and Methods: Sixty eyes, 30 in each group, of 55 consecutive patients diagnosed with progressive keratoconus were enrolled through convenience sampling and were subjected to AXL with irradiance protocols of 18 watt/cm2 for 5 minutes in group 1 and 9mwatt/cm2 for 10 minutes in group 2. All patients underwent a comprehensive ophthalmic examination at baseline and postoperative follow up visits at 3, 6, 12 and 18 months. Primary outcome parameter was disease stability defined as increase in maximum keratometry over baseline K max of no more than 1 diopter at 1 year after AXL. Statistical analysis of data was performed with IBM SPSS software (version 20.0 SPSS). P value of &lt; 0.05 was considered as statistically significant.&#x0D; Results: Disease stability was 96 % in each group. At the final time point of 18 months, group 2 (AXL 9mmwatt/cm2 for 10 min) was superior as compared to group 1 (AXL 18mmwatt/cm2 for 5 min) in terms of flattening of steep and sim K (p = 0.007, 0.023 respectively).&#x0D; Conclusion: The two AXL protocols are safe and appear to show comparable efficacy in disease stability. They can be used alternatively in the treatment of progressive keratoconus.

The effects of corneal collagen cross-linking on the corneal structure in keratoconus

The article reviews the key information regarding morphological changes in keratoconic corneas and dramatic alterations of the corneal tissue induced by corneal cross-linking according to data obtained with in vivo corneal confocal microscopy, presents basic information on keratoconus visualization techniques widely used for diagnosis, monitoring of ectasia, as well as efficacy assessment of its treatment, and lists basic principles of corneal cross-linking procedure and confocal microscopy with consideration of morphology specifics of keratoconic corneas. The article also discusses prospective benefits of further research and longitudinal studies aimed to define the origin of keratoconus and to develop advanced corneal cross-linking protocols.

Depth-Dependent Reduction of Biomechanical Efficacy of Contact Lens-Assisted Corneal Cross-linking Analyzed by Brillouin Microscopy.

To determine the relative impact of contact lens- assisted corneal cross-linking (CACXL) and standard protocol CXL (CXL) on regional corneal stiffness using Brillouin microscopy. CXL and CACXL were performed on 30 intact fresh porcine eyes (15 per group). Depth profile of stiffness variation and averaged elastic modulus of anterior, middle, and posterior stroma were determined by Brillouin maps. Corneas were cut into strips to conduct mechanical stress-strain tests after Brillouin microscopy to evaluate stiffness difference between CXL and CACXL. Each eye served as its own control. CXL had a greater impact on corneal stiffness, with a maximum increase of 5.74% compared to 3.99% for CACXL (P < .001). CXL increased longitudinal modulus by 7.8% in the anterior, 1.7% in the middle, and -0.7% in the posterior regions compared to CACXL, which increased longitudinal modulus by 5.5% in the anterior (P < .001), 1.2% in the middle (P = .15), and -0.4% in the posterior regions (P = .60). Mechanical stress-strain tests showed that at 10% strain averaged Young's modulus was 5 MPa for CXL and 2.97 MPa for CACXL (P < .001). Both CACXL and standard protocol CXL induced significant corneal stiffening primarily concentrated in the anterior cornea. CACXL leads to less stiffening compared with CXL. An attenuated but continuous stiffening effect can be observed through the whole cornea for both CACXL and CXL, although CACXL has a smaller stiffness gradient. [J Refract Surg. 2019;35(11):721-728.].

Invasive Pharmacology Outcomes with Different Corneal Cross-Linking Protocols: A Review.

Collagen corneal cross-linking (CXL) is an invasive pharmacological treatment strategy used for corneal ectatic disorders and is currently the only treatment capable of halting the progression of the disease. In the past 20 years, the conservative management of progressive corneal ectasia has changed, thanks to this procedure that produces strengthening of the corneal tissue through the photochemical reaction generated by the combined action of riboflavin and ultraviolet A radiation. Many modified protocols have been implemented to halt the progression of the disease and to delay or prevent visual loss and surgical procedures such as corneal transplantation. Because of the variety of different protocols that are currently used, the results that are being reported are very variable, and could generate some confusion in relation to the true efficacy of the procedure. The aim of this review was to provide an overview of the aforementioned protocols that are designed to maintain the efficacy of CXL in halting the progression of the disease but avoiding the major limitations of the procedure.