Accelerated Corneal Cross-linking Research Articles

Prospective Objective Analysis of Corneal Haze Following Customized Transepithelial PRK Without Mitomycin C Combined With Accelerated Corneal Cross-Linking Versus Corneal Cross-Linking Alone.

To compare haze and refractive outcomes in patients undergoing combined accelerated corneal cross-linking (A-CXL) and selective wavefront-guided transepithelial photorefractive keratectomy (WG-transPRK) without mitomycin C (MMC) versus those undergoing A-CXL. This prospective study analyzed 95 eyes (86 patients) with progressive keratoconus from October 2018 to October 2022. The first group underwent CXL combined with corneal or ocular WG-transPRK (CXL+PRK, n = 52), targeting higher order aberrations (HOAs). The second underwent CXL only (n = 43), both following the same accelerated CXL protocol without MMC on the SCHWIND Amaris laser platform (SCHWIND eye-tech-solutions). Baseline and postoperative evaluations (1, 3, 6, and 12 months) included uncorrected (UDVA) and corrected (CDVA) distance visual acuity, manifest refraction, tomography, corneal HOAs, and optical coherence tomography (OCT) scans. A patented machine learning algorithm objectively detected and quantified stromal haze on OCT scans in grayscale units. In both groups, anterior corneal haze reflectivity and subepithelial haze peaked at 3 months postoperatively, then progressively decreased at 6 and 12 months. Haze did not differ between groups at any time point. By 12 months, CDVA increased by 2.5 lines in the CXL+PRK group (P < .001) and by 0.7 lines in the CXL group (P = .10), and maximum keratometry decreased from 51.70 ± 5.10 to 47.90 ± 7.90 diopters (D) (CXL+PRK group) (P < .001) and from 51.20 ± 5.10 to 50.30 ± 4.60 D (CXL group) (P = .004). Corneal HOAs decreased in both groups but more in the CXL+PRK group. Combining CXL with WG-transPRK without MMC does not result in increased haze when compared to A-CXL alone. This combined approach achieves greater improvements in visual, topographic, and aberrometric parameters. [J Refract Surg. 2024;40(9):e583-e594.].

Topography-guided photorefractive keratectomy combined with accelerated corneal collagen cross-linking versus cross-linking alone for progressive keratoconus: a long-term prospective cohort study

PurposeTo comprehensively compare the long-term outcome of the combined topography guided photorefractive keratectomy (TG-PRK) with accelerated corneal cross-linking (ACXL) and ACXL alone in eyes with progressive keratoconus. The analysis focused on the changes in the detailed corneal aberrometric values.MethodsThis single-center, prospective cohort study included 28 patients (30 eyes) of the TG-PRK plus ACXL group and 14 patients (15 eyes) of the ACXL alone group. The mean duration of the follow-up was 44 ± 10.18 months (ranged from 31 to 65 months). The preoperative data and the postoperative measurement data at the last follow-up visit, including demographic data, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, corneal topography, pachymetry, aberrometry and densitometry were analyzed.ResultsThe CDVA significantly improved in the TG-PRK plus ACXL group at the last follow-up visit (p = 0.006), while no significant improvement was found in the ACXL alone group (p = 0.432). The maximal keratometry of the anterior corneal surface (Kmax) of both groups significantly decreased at the last follow-up visit (p &amp;lt; 0.05). Compared with the ACXL alone group, the Kmax of the TG-PRK plus ACXL group showed a greater decline (p = 0.008). The total corneal aberrations, the corneal lower-order aberrations (LOAs), the corneal higher order aberrations (HOAs), the vertical coma and the spherical aberration (SA) at the 4.0 mm and 6.0 mm zone of the TG-PRK plus ACXL group significantly decreased at the last follow-up visit (all p &amp;lt; 0.05). The declines of the total corneal aberrations, the corneal LOAs, the corneal HOAs and the vertical coma at the 4.0 mm and 6.0 mm zone of the TG-PRK plus ACXL group were significantly higher than those in the ACXL alone group (p &amp;lt; 0.001).ConclusionCompared with ACXL alone, combined TG-PRK with ACXL procedure had a significantly higher reduction in the corneal HOAs and better CDVA, while providing a similar long-term stability and safety. For progressive keratoconus patients with adequate corneal thickness, the combined procedure might be a recommended treatment option.

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.

Early changes in corneal densitometry after FS-LASIK combined with accelerated corneal cross-linking for correction of high myopia.

To observe the effects of femtosecond laser-assisted excimer laser in situ keratomileusis combined with accelerated corneal cross-linking (FS-LASIK Xtra) on corneal densitometry after correcting for high myopia. In this prospectively study, 130 patients underwent FS-LASIK or FS-LASIK Xtra for high myopia. Their right eyes were selected for inclusion in the study, of which 65 cases of 65 eyes in the FS-LASIK group, 65 patients with 65 eyes in the FS-LASIK Xtra group. Patients were evaluated for corneal densitometry at 1, 3, and 6mo postoperatively using Pentacam Scheimpflug imaging. Preoperative differences in corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups in different ranges were not statistically significant (P>0.05). Layer-by-layer analysis revealed statistically significant differences in the anterior (120 µm), central, and total layer corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups at 1 and 3mo postoperatively (all P<0.05), the FS-LASIK Xtra group is higher than that of the FS-LASIK group. Analysis of different diameter ranges showed statistically significant differences between the FS-LASIK group and the FS-LASIK Xtra group at 1mo postoperatively in the ranges of 0-2, 2-6, and 6-10 mm (both P<0.05); At 3mo postoperatively, the FS-LASIK Xtra group is higher than that of the FS-LASIK group in the ranges of 0-2 and 2-6 mm (P<0.05). At 6mo postoperatively, there were no statistically significant differences in corneal densitometry between the FS-LASIK group and the FS-LASIK Xtra group in different diameter ranges (all P>0.05). There is an increase in internal corneal densitometry during the early postoperative period after FS-LASIK Xtra for correction of high myopia. However, the densitometry values decreased to the level of conventional FS-LASIK at 6mo after surgery, with the most significant changes observed in the superficial central zone.

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.

Outcomes after corneal crosslinking treatment in paediatric patients with keratoconus.

This study aims to determine the efficacy and safety of accelerated corneal crosslinking in children with keratoconus. The study enrolled 64 patients aged 16years or younger, each contributing one eye for a total of 64 eyes for analysis. Participants underwent an accelerated form of corneal cross-linking with 15min of ultraviolet A irradiation at a rate of 7 mW/cm2, resulting in a cumulative energy dose of 5.4J/cm2. The primary outcome measures were best corrected visual acuity (BCVA) and corneal tomography at 6 and 12months post-intervention. Parameters assessed included BCVA, spherical and cylindrical refraction, keratometry (K1 and K2), maximum keratometry (Kmax) and thinnest corneal thickness (TCT). These metrics were documented preoperatively and then again at 6 and 12months postoperatively. In addition, any ocular or systemic conditions related to keratoconus were recorded for each participant. The results showed an improvement in BCVA at 12months after surgery. K1 showed a decrease at both post-operative follow-ups while K2 remained constant throughout the observation period. Kmax showed a notable decrease at the 12month postoperative follow-up. Although the TCT showed an initial decrease, it reached a stable state after 12months of crosslinking. Refractive values remained stable at all subsequent examinations. Notably, no complications such as corneal opacity, non-healing epithelial defects or corneal infections occurred during the follow-up period. The most common ocular comorbidity was allergic conjunctivitis (34.4%). The findings suggest that accelerated corneal crosslinking treatment is effective in slowing or halting the progression of keratoconus. Furthermore, there were no persistent overt complications observed at 12months after the procedure.

Effect of accelerated high-fluence riboflavin and rose bengal-mediated corneal cross-linking on resistance to enzymatic digestion

PurposeThis study evaluated the effect of high-fluence accelerated corneal cross-linking on the resistance to enzymatic digestion, assessing two chromophore/light combinations: riboflavin/UV-A light (RF/UV-A) and rose bengal/green light (RB/green).MethodsFreshly prepared ex-vivo porcine corneas (n = 189) were divided into 8 groups groups. Group A corneas were unirradiated controls without chromophore soaking (A0), or soaked with riboflavin (A1) or rose bengal (A2). Group B corneas underwent accelerated epi-off RF/UV-A CXL at fluences of 5.4 J/cm² (B1), 10 J/cm² (B2), or 15 J/cm² (B3). Group C corneas underwent accelerated epi-off RB/green CXL at fluences of either 10 J/cm² (C1) or 15 J/cm² (C2). Following CXL, all corneas were digested in 0.3% collagenase-A solution, and the time until complete dissolution was measured.ResultsNon-irradiated controls exposed to RF and RB enhanced corneal resistance to collagenase digestion, with RB having a stronger effect than RF. RF/UV-A-treated corneas showed significantly increased digestion resistance with increasing fluence levels. RB/green-treated corneas displayed enhanced digestion resistance with each increase in fluence up to 10 J/cm²; a 15 J/cm² fluence yielded similar digestion resistance times to a 10 J/cm² fluence, suggesting a plateau effect in accelerated RB/green CXL protocols.ConclusionsWhen compared to standard-fluence treatments, high-fluence accelerated epi-off CXL using both riboflavin and rose bengal significantly increases resistance to enzymatic digestion. The optimal settings for clinical protocols might be 15 J/cm² (30 mW/cm² for 8 min 20 s) for RF/UV-A and 10 J/cm² (15 mW/cm² for 11 min 7 s) for RB/Green Light.

Simultaneous Topography-guided Custom Ablation With Corneal Cross-linking for Keratoconus: 10-Year Prospective Outcomes

Purpose: To assess 10-year visual and tomographic outcomes of topography-guided custom ablation (T-CAT) with corneal cross-linking (CXL) in eyes with keratoconus. Methods: T-CAT with CXL was performed in 600 eyes (522 patients). Based on the T-CAT ablation plan, the theoretical maximum ablation depth was 50 µm after epithelium removal. After ablation, accelerated corneal cross-linking (CXL) was performed in the central 8-mm zone (9 mW/cm 2 for 10 minutes in “epi-off” mode). The visual acuity and tomography were assessed. Results: There was significant improvement in uncorrected ( P = .001) and corrected ( P = .001) distance visual acuity after the procedure. Keratometry, root mean square lower order aberrations and higher order aberrations, defocus, coma 90°, and spherical aberration reduced significantly after surgery at 10 years of follow-up ( P &lt; .005). All Pentacam (Oculus Optikgerate GmbH) tomographic variables showed significant changes indicating regularization after T-CAT ( P &lt; .005). Flattening of greater than 5.00 diopters in maximum keratometry was noted in 6 eyes (1%). Two of 600 eyes progressed postoperatively and required repeat CXL. Conclusions: T-CAT plus CXL is a safe and effective technique even in the long term for regularizing the anterior corneal surface with significant visual improvement and reduction in higher order corneal aberrations. [ J Refract Surg . 2023;39(11):759–766.]

Accelerated corneal cross-linking (18mW/cm2 for 5 min) with HPMC-riboflavin in progressive keratoconus – 5 years follow-up

PurposeTo evaluate long-term results of accelerated corneal cross-linking (ACXL) in patients with progressive keratoconus, seventy-four eyes of 53 patients with progressive keratoconus (documented Kmax progression > 1D/a) who underwent ACXL (18mW/cm2 for 5 min) were included in a retrospective observational clinical study. The investigation focused on tomographic and keratometric parameters, refractive data, and visual outcomes at 5 years follow-ups.MethodsCorrected distance visual acuity (CDVA), slit lamp, and Pentacam® examinations were conducted, including assessments of thinnest corneal point (TP), minimum radius (Rmin), corneal astigmatism, and maximum anterior keratometry (Kmax). These examinations were performed two weeks before the surgery and, on average, 56 months after the surgery. In a subgroup of 24 eyes, Pentacam® examination data from an intermediate visit at 12 months until the final visit was evaluated to confirm continuous stability.The ACXL protocol included corneal abrasion, hydroxypropylmethylcellulose (HPMC)-riboflavin eye drops administered every 5 min for a total duration of 30 min, and irradiation with 18mW/cm2 for 5 min using riboflavin eye drops applied every minute during the irradiation process. Intraoperatively, minimal corneal pachymetry of > 400 µm was ensured in every patient.ResultsAfter 56 months, all values exhibited statistically significant changes (paired t-test; CDVA p = 0.002; Kmax p < 0.001; Rmin p < 0.001; astigmatism p = 0.03; TP p < 0.001).In the subgroup analysis of 24 eyes, which included tomographical and keratometric parameters, no statistically significant changes were observed during the last 12 months of observation (paired t-test; Kmax p = 0.72; Rmin p = 0.67; astigmatism p = 0.72).Treatment failure was strictly defined as an increase in Kmax (> 1D) during the 5-year follow-up and was observed in only 3 eyes (4%).ConclusionsACXL is an effective and safe treatment for patients with progressive keratoconus. Our results demonstrate improvements in functional and tomographical outcomes even after high-energy ACXL (18mW/cm2 for 5 min) over a long-term period of 56 months. Our analysis indicates stable conditions in previously progressive keratoconus, particularly during the final year of the observation period. The treatment failure rate was 4%.

Progressive high-fluence epithelium-on accelerated corneal crosslinking: a novel corneal photodynamic therapy for early progressive keratoconus.

To assess the preliminary clinical results of a new, progressively higher fluence-pulsed light Epi-On accelerated crosslinking nomogram (PFPL M Epi-On ACXL) in the treatment of progressive keratoconus (KC). Siena Crosslinking Center, Siena, Italy. A prospective pilot open, non-randomized interventional study, including 32 eyes of 32 young-adult patients over 26 years old with Stages I-III progressive KC undergoing PFPL M Epi-On ACXL, was conducted. Riboflavin loading was performed by using Paracel I 0.25% for 4 min and Paracel II 0.22% for 6 min. The Avedro KXL System (Glaukos-Avedro, Burlington, USA) was used for pulsed-light accelerated crosslinking (ACXL) at air room 21% oxygenation and 13 min of UV-A irradiation. The treatment fluence was set at 7.2 J/cm2, 8.6 J/cm2, and 10.0 J/cm2 in corneas with baseline pachymetry <420 μm (group 1: 8 eyes), ≥ 420 μm <460 μm (group 2, 11 eyes), and ≥ 460 μm (group 3, 13 eyes), respectively. Uncorrected distance visual acuity (UDVA), best-spectacle corrected visual acuity (BSCVA), Scheimpflug corneal tomography, and anterior segment OCT (AS-OCT) data were collected at baseline and postoperatively at 1, 3, and 6 months. UDVA and BSCVA improved in all groups (P ≤ 0.05). Maximum keratometry values (K max) showed a significant decrease in the 10.0 J/cm2 group (Δ -1.68 D). The coma (HOAs) value improved significantly by the sixth month in all groups. OCT average demarcation lines were 211 ± 19 μm in group 1, 245 ± 23 μm in group 2, and 267 ± 21 μm in group 3. The preliminary results show that pachymetry-based PFPL M Epi-On ACXL nomogram stabilizes ectasia progression. Higher fluence Epi-On ACXL increases CXL penetration, with better functional outcomes in the absence of complications.

Development of interface haze after femtosecond laser-assisted in situ keratomileusis with accelerated corneal crosslinking: a case series.

Femtosecond laser-assisted in situ keratomileusis (FS-LASIK) with accelerated corneal crosslinking (FS-LASIK Xtra) is a recent procedure to achieve safer corneal ablation in myopic patients with borderline corneal thickness. Despite its well-accepted effectiveness, the development of remarkable interface haze is a potential concern but has rarely been reported and discussed. We report for the first time a case series of 11 eyes of 7 patients who developed typical interface haze 1-3months after FS-LASIK Xtra for the correction of myopia with astigmatism, with intensity grades ranging from 0.5 + to 3 + at the time of onset. The preclinical spherical diopters of the 7 patients ranged from - 2.25 D to - 9.25 D and cylindrical diopters ranged from - 0.25 D to - 2.50 D. The haze tended to be self-limiting, and topical anti-inflammatory therapy was given to moderate and severe cases, who responded well to treatment. The development of clinically significant interface haze is a relatively rare complication after FS-LASIK Xtra but tends to have a higher incidence and intensity compared to conventional stromal surgery such as FS-LASIK. Timely treatment and close follow-up are essential to patients undertaking FS-LASIK Xtra.

Comparison of two different 360-degree intrastromal corneal rings combined with simultaneous accelerated-corneal cross-linking.

to compare five-year outcomes of two complete intracorneal implants (MyoRing versus annular-shaped intracorneal implant [AICI]) combined with accelerated corneal cross-linking (A-CXL) in progressive KCN. In this historical cohort study, preoperative and postoperative visual, refractive, tomographic, biomechanical, and aberrometric parameters of 27 eyes of 27 patients who underwent implantation of two complete rings (13 AICI and 14 MyoRing) combined with A-CXL were recorded. The mean age of patients in "AICI plus A-CXL" and "MyoRing plus A-CXL" groups were 28.1 ± 4.6 and 26.3 ± 3.8 years, respectively. All pre- and postoperative visual and refractive parameters between the two groups were not significantly different (p > 0.05). Comparing pre- and postoperative tomographic measurements showed that anterior corneal surface (ACS) flat-K and corneal thickness at pachymetric apex significantly improved for MyoRing plus A-CXL group after five years (p < 0.05). On the other hand, ACS K-max and mean-K values were significantly improved for AICI plus A-CXL group after five years (p < 0.05). Both groups revealed significant improvements in ACS steep-K and corneal astigmatism (p < 0.05). Five years after surgery, the high order aberration in the AICI group (2.60 ± 0.83) was significantly better than the MyoRing group (1.70 ± 0.43) (p = 0.007). Both complete intrastromal rings (MyoRing or AICI) combined with A-CXL significantly Improved visual, refractive, and corneal aberrometric, biomechanical, and tomographic parameters and halt the progression of KCN with comparable long-term outcomes.

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.

Subjective and objective evaluation of corneal haze after accelerated corneal crosslinking for corneal ectasias.

To evaluate the relationship between subjective (slit lamp examination [SLE]) and objective (densitometry) measurements of corneal haze after accelerated corneal crosslinking (aCXL), assess the relationship between densitometry and corrected distance visual acuity (CDVA), and determine the effect of baseline characteristics on densitometry after aCXL in eyes with progressive keratoconus and other ectasias. Kensington Eye Institute and Bochner Eye Institute, Toronto, Canada. Retrospective analysis of a prospective interventional cohort study. Scheimpflug-derived corneal densitometry, CDVA, maximum keratometry (Kmax ), and central corneal thickness were measured preoperatively and up to 1year after aCXL, and post-operative haze was estimated with SLE (n=483 eyes). A random effect model was used to examine the relationship between post-operative subjective haze with SLE and densitometry. Linear mixed models were used to examine the relationship between densitometry, pre-operative baseline characteristics, and CDVA. There was a significant association between subjective haze with SLE and densitometry (p < 0.001). There was a significant relationship between CDVA and densitometry: for every 10 GSUs of increased densitometry in the 0-2 mm zone, CDVA worsened by approximately half a Snellen line (p < 0.001). Age and pre-operative Kmax were significant predictors of densitometry. For every 10 years of age, densitometry increased by 0.68 GSUs (95% CI [0.27 to 1.07], p < 0.001). For every 10 D of increased preoperative Kmax , densitometry increased by 0.69 GSUs (95% CI [0.41 to 0.98], p < 0.001). Subjective haze after aCXL estimated with SLE, is significantly associated with densitometry. Increased densitometry after aCXL is associated with a reduction in CDVA.

Evaluation of Biomechanical Changes After Accelerated Cross-Linking in Progressive Keratoconus: A Prospective Follow-Up Study.

The aim of this study was to analyze the biomechanical effect of accelerated corneal cross-linking (9*10) in progressive keratoconus (KC) in comparison to untreated fellow eyes using Scheimpflug-based tonometry (Corvis ST, CVS). Forty-three eyes of 43 patients with KC showed progressive KC and were treated using accelerated corneal cross-linking. Twenty-five untreated fellow eyes were used as the control group. All eyes were examined biomechanically (CVS) and tomographically (Pentacam) at baseline, after 1-month, 6-month, and 12-month follow-up. Statistical analysis was performed using a linear mixed model. A logistic regression was performed to attribute the effects of changes in each parameter to treatment status (treated or untreated). Maximum keratometry values decreased statistically significantly at 12 months by -1.1 D (95 confidence interval: -2.0 to -0.1, P = 0.025) compared with baseline. Thinnest corneal thickness decreased significantly after 1 month ( P < 0.001) and recovered to baseline after 12 months ( P = 0.752). In the corneal cross-linking (CXL) group, biomechanical changes were observed by an increased bIOP, a shorter A2 time, and a lower integrated radius after 1 month (all P < 0.05). No biomechanical and tomographical changes were observed in the control group (all P > 0.05). Logistic regression pointed out that treated eyes can be separated from untreated eyes by differences in bIOP, corneal thickness, A1 velocity, integrated radius, and Kc mean at 1, 6, and 12 months. The alterations in biomechanical parameters indicated a corneal stiffening effect after CXL treatment, which was mostly detectable 1 month after treatment, although corneal thickness was reduced. The logistic regression model showed an adequate separation between CXL-treated and untreated eyes.

Corneal changes in adult patients with progressive keratoconus after accelerated corneal cross-linking: prospective 6-month interim study results

Corneal changes in adult patients with progressive keratoconus after accelerated corneal cross-linking: prospective 6-month interim study results

Corneal biomechanical stiffness and histopathological changes after in vivo repeated accelerated corneal cross-linking in cat eyes

Corneal cross-linking (CXL) has been proved efficiency for treating progressive keratoconus and other corneal ectasia diseases by stabilizing corneal geometry and biomechanics. However, the necessity of repeated CXL treatment in patients is unknown. This study aimed to investigate corneal biomechanical stiffness and change in corneal histopathological characteristics after repeated accelerated CXL (A-CXL) in cat eyes. A-CXL was performed with 0.1% riboflavin applied for 10 min, followed by ultraviolet A irradiation at 30 mW/cm2 for 3 min at 365 nm in 15 domestic cats. Corneas (n = 30) were divided into three groups: one-time accelerated corneal cross-linking (A-CXL*1 group), repeated accelerated corneal cross-linking (A-CXL*2 group), and an untreated control group. In A-CXL*2 group, A-CXL was repeated at 1-month intervals. In vivo ocular examinations were performed pre- and postoperatively. Biomechanical analysis was performed using a biotester biaxial testing system. We used the Mooney–Rivlin strain-energy function to describe corneal material properties. No infection in any case after A-CXL was observed. Biomechanical tests showed that the stress-strain curves of the two A-CXL groups were significantly different from those of the control group (P < 0.01), whereas stress-strain curve of the A-CXL*2 group was similar to that of the A-CXL*1 group (P > 0.05). Delayed epithelial healing and haze were observed 1 month after surgery. Stromal demarcation line depth measured with anterior spectral-domain optical coherence tomography was 187.6 ± 20.4 and 197.1 ± 11.5 μm for the A-CXL*1 and A-CXL*2 groups, respectively (P > 0.05). These results show that A-CXL can increase corneal biomechanics in cat eyes. The biomechanical enhancement of cat corneas treated with repeated A-CXL at 1-month intervals was similar to that of performing a one-time A-CXL. Repeated cross-linking procedures at short intervals may increase the risk of adverse reactions, and more caution should be taken in clinical applications.

Evaluation of Dynamic Corneal Response Parameters and the Biomechanical E-Staging After Accelerated Corneal Cross-Linking in Keratoconus.

This study evaluated the biomechanical E-staging in progressive keratoconus (KC) corneas before and after epithelium-off accelerated corneal cross-linking (CXL, 9mW/cm2, 10min, 5.4J/cm2). German university-based retrospective longitudinal cohort study. The biomechanical E-staging for ectatic corneal diseases was applied retrospectively on 49 progressive KC corneas of 41 patients who underwent CXL. Main outcome parameters included the Corvis Biomechanical Factor (CBiF, the linearized Corvis Biomechanical Index), the biomechanical E-staging (E1 to E4 result of dividing the CBiF value range into 5 groups), maximal anterior keratometry (Kmax), anterior radius of curvature (ARC), and thinnest corneal thickness (TCT). They were evaluated at 2.1±2.0 months preoperatively (n=49 corneas, 41 patients) and postoperatively after 5.4±1.4, 11.3±1.8, and 23.4±1.6 months. The CBiF decreased (5.1±0.5 | 5.0±0.5, P=0.0338) and the E-staging increased significantly (2.4±0.9 | 2.6±0.8, P=0.0035) from preoperatively to the first postoperative follow-up. The difference was not significant after 11 months and there were same values after 23 months. Kmax, ARC, and TCT slightly decreased (Kmax: 56.9±6.3, 54.3±5.1, 56.2±6.6, 54.0±5.2; ARC: 49.8±3.5, 48.9±3.2, 50.8±5.6, 49.0±3.7; TCT: 470±34, 454±36, 459±35, 466±39; preoperatively and 5, 11, and 23 months postoperatively). A postoperatively decreased TCT was associated with an increased E-stage, whereas an equal or increased TCT measurement after CXL was associated with equal or lower E-staging results. The biomechanical E-staging in KC corneas is influenced by TCT measurements and increases within the first postoperative months after CXL. On the long term, it indicates a postoperative KC stabilization, with comparable E-values to preoperatively at 11 and 23 months after CXL.

Reliability analysis of successive Corvis ST® measurements in keratoconus 2 years after accelerated corneal crosslinking compared to untreated keratoconus corneas

PurposeTo assess the reliability of successive Corvis ST® measurements (CST, Oculus, Wetzlar, Germany) in keratoconus (KC) ≥ 2 years after accelerated corneal crosslinking (9 mW/cm2, 10 min, 5.4 J/cm2) compared to untreated KC corneas.MethodsThree successive CST measurements per eye were performed in ≥ 2 years after CXL (CXLG, n = 20 corneas of 16 patients) and a control group consisting of non-operated, ABC-stage-matched KC corneas according to Belin’s ABCD KC grading (controls, n = 20 corneas, 20 patients). Main outcome measures included maximal keratometry (Kmax), the Belin/Ambrósio-Enhanced-Ectasia-Deviation-Index BAD-D; the biomechanical parameters A1 velocity, deformation amplitude (DA) ratio 2 mm, Ambrósio relational thickness to the horizontal profile (ARTh), integrated radius, stiffness parameter A1 (SP-A1), and the Corvis Biomechanical Factor (CBiF, the linearized term of the Corvis Biomechanical Index). Mean values, standard deviations, and Cronbach’s alpha (CA) were calculated.ResultsBoth groups were tomographically comparable (BAD: 11.5 ± 4.7|11.2 ± 3.6, p = 0.682, Kmax: 60.5 ± 7.2|60.7 ± 7.7, p = 0.868 for controls|CXLG, paired t-test). A1 velocity (mean ± SD: 0.176 ± 0.02|0.183 ± 0.02, p = 0.090, CA: 0.960|0.960), DA ratio 2 mm (6.04 ± 1.13|6.14 ± 1.03, p = 0.490, CA: 0.967|0.967), integrated radius (12.08 ± 2.5|12.42 ± 1.9, p = 0.450, CA: 0.976|0.976), and CBiF (4.62 ± 0.6|4.62 ± 0.4, p = 0.830, CA: 0.965|0.965) were also comparable (controls|CXLG). ARTh was significantly higher in controls (177.1 ± 59, CA: 0.993) than after CXL (155.21 ± 65, p = 0.0062, CA: 0.993) and SP-A1 was significantly higher after CXL (59.2 ± 13, CA: 0.912) than in controls (52.2 ± 16, p = 0.0018, CA: 0.912).ConclusionARTh and SP-A1 differed significantly between controls and CXLG. Biomechanical measurements were generally of excellent reliability in both groups. CXL seems to affect biomechanical measurements of human corneas over more than 2 years.