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Purpose of Review: To review corneal crosslinking for keratoconus and corneal ectasia, and recent developments in the field. This study will review the mechanism of crosslinking, clinical approaches, current results, and potential future innovations., Recent Findings: Corneal crosslinking for keratoconus was first approved by U.S. FDA in 2016. Recent studies have confirmed the general long-term efficacy of the procedure in decreasing progression of keratoconus and corneal ectasia. New types of crosslinking protocols, such as transepithelial treatments, are under investigation. In addition, adjunctive procedures have been developed to improve corneal contour and visual function in these patients., Summary: Crosslinking has been found to be well tolerated and effective with the goal of decreasing progression of ectatic corneal diseases, keratoconus and corneal ectasia after refractive surgery. Studies have shown its long-term efficacy. New techniques of crosslinking and adjunctive procedures may further improve treatments and results., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To quantitate corneal haze and analyze the postoperative time course of corneal haze after transepithelial corneal collagen cross-linking (TECXL) in patients with keratoconus., Methods: Patients underwent TECXL and were randomized into 2 groups. One group received intraoperative riboflavin 0.10% every minute, and the second group received riboflavin 0.10% every 2 minutes during ultraviolet exposure. Scheimpflug densitometry was measured preoperatively, and at 1, 3, 6, and 12 months to assess the postoperative time course. Densitometry measurements were also correlated with visual acuity, pachymetry, and topography outcomes., Results: Fifty-nine eyes of 43 patients with keratoconus were analyzed. Preoperative mean corneal densitometry was 20.45 ± 2.79. Mean densitometry increased at 1 month (22.58 ± 3.79; P < 0.001), did not significantly change between 1 and 3 months (22.64 ± 3.83; P = 0.8), and significantly improved between 3 and 12 months postoperatively (mean6 21.59 ± 3.39; P = 0.002, mean12 20.80 ± 3.27; P = 0.002). There was no difference between preoperative and 1-year densitometry measurements (P = 0.21). There was no significant difference between the 1-minute and 2-minute subgroups. In addition, corneal densitometry at either 3 months or 1 year did not correlate with uncorrected distance visual acuity (P = 0.4), corrected distance visual acuity (P = 0.1), or maximum keratometry (P = 0.5), 1 year after corneal collagen cross-linking (CXL)., Conclusions: After TECXL, corneal haze increased slightly at 1 month, plateaued between 1 and 3 months, and returned to baseline between 3 and 12 months. In general, corneal haze in this study was substantially less than the haze previously reported for the standard cross-linking procedure. CXL-associated corneal haze did not correlate with the postoperative visual or topographic outcomes 1 year after CXL.

Purpose: To determine preoperative patient characteristics that may predict topography and visual acuity outcomes of corneal collagen crosslinking (CXL)., Setting: Cornea and refractive surgery practice., Design: Cohort study., Methods: Crosslinking was performed in eyes with keratoconus or corneal ectasia. Multiple regression and odds ratio analyses were performed to determine independent predictors of changes in topography-derived maximum keratometry (K) and corrected distance visual acuity (CDVA) 1 year postoperatively. Preoperative characteristics included sex, age, uncorrected distance visual acuity (UDVA), CDVA, maximum keratometry (K), corneal thickness, corneal haze, disease group, and cone location. Postoperative improvement in maximum K was defined as flattening of 2.0 diopters (D) or more and worsening as steepening of 1.0 D or more. Improvement in CDVA was defined as a gain of 2 lines or more and worsening as a loss of 1 line or more., Results: The study comprised 104 eyes (66 keratoconus; 38 corneal ectasia). Eyes with a preoperative CDVA of 20/40 or worse were 5.9 times (95% confidence interval [CI], 2.2-6.4) more likely to improve 2 Snellen lines or more. Eyes with a maximum K of 55.0 D or more were 5.4 times (95% CI, 2.1-14.0) more likely to have topographic flattening of 2.0 D or more. No preoperative characteristics significantly predicted worsening of visual acuity or corneal topography., Conclusions: Patients with worse preoperative CDVA and higher K values, particularly with a CDVA of 20/40 or worse or a maximum K of 55.0 D or more, were most likely to have improvement after CXL. No preoperative characteristics were predictive of CXL failure., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the effect of preoperative topographic cone location on 1-year outcomes of corneal collagen cross-linking (CXL)., Methods: In this prospective, randomized, controlled clinical trial, 99 eyes (66 keratoconus, 33 ectasia) from 76 patients underwent CXL. Cone location was defined by the coordinates of preoperative maximum keratometry (maximum K) using the anterior sagittal curvature topography map (Pentacam, Oculus Optikgeräte GmbH). Patients were divided into three groups: those with a maximum K located within the central 3-mm (central cone group), 3- to 5-mm (paracentral cone group), and outside the 5-mm (peripheral cone group) optical zones. Topography and visual acuity data were obtained preoperatively and at 1 year., Results: In the combined cohort, maximum K and uncorrected and corrected distance visual acuity significantly improved by -1.60±3.40 diopters (D) (P<.001), -0.08±0.25 logMAR (P=.001), and -0.10±0.18 log-MAR (P<.001), respectively. Comparing cone groups, maximum K decreased by 2.60±4.50 D (P<.001) in the central cone group, 1.10±2.50 D (P=.02) in the paracentral cone group, and 0.40±1.20 D (P=.08) in the peripheral cone group. Differences among groups were statistically significant (P<.001). Uncorrected distance visual acuity improved by -0.07±0.3 logMAR (P=.1) (central cone group), -0.1±0.17 logMAR (P=.004) (paracentral cone group), and -0.1±0.25 logMAR (P=.04) (peripheral cone group). Corrected distance visual acuity improved by -0.14±0.21 logMAR (P<.001) (central cone group), -0.08±0.17 logMAR (P=.01) (paracentral cone group), and -0.08±0.12 logMAR (P=.002) (peripheral cone group). For both UDVA and CDVA outcomes, these differences among groups were not statistically significant., Conclusions: After CXL, more topographic flattening occurs in eyes with centrally located cones and the least flattening effect occurs when the cone is located peripherally. This cone-location effect is found in eyes with both keratoconus and ectasia., (Copyright 2012, SLACK Incorporated.)

Purpose: To determine changes in higher-order aberrations (HOAs) after corneal collagen crosslinking (CXL)., Setting: Cornea and refractive surgery practice., Design: Prospective randomized controlled clinical trial., Methods: Corneal and ocular HOAs were measured and analyzed using the Pentacam device and Ladarwave aberrometer, respectively, at baseline and 12 months after CXL., Results: Ninety-six eyes (64 keratoconus, 32 ectasia) of 73 patients had CXL. A fellow-eye control group comprised 42 eyes. The mean preoperative total anterior corneal HOAs, total coma, 3rd-order coma, and vertical coma were 4.68 μm ± 2.33 (SD), 4.40 ± 2.32 μm, 4.36 ± 2.30 μm, and 4.04 ± 2.27 μm, respectively. At 1 year, the mean values decreased significantly to 4.27 ± 2.25 μm, 4.01 ± 2.29 μm, 3.96 ± 2.27 μm, and 3.66 ± 2.22 μm, respectively (all P<.001). There were no significant changes in posterior corneal HOAs. The mean preoperative total ocular HOAs, total coma, 3rd-order coma, trefoil, and spherical aberration were 2.80 ± 1.0 μm, 2.60 ± 1.03 μm, 2.57 ± 1.03 μm, 0.98 ± 0.46 μm, and 0.90 ± 0.42 μm, respectively. At 1 year, the mean values decreased significantly to 2.59 ± 1.06 μm, 2.42 ± 1.07 μm, 2.39 ± 1.07 μm, 0.88 ± 0.49 μm, and 0.83 ± 0.38 μm, respectively (all P=.01). After CXL, HOAs were significantly improved compared with the control group. Changes in HOAs were not statistically associated with an improvement in visual acuity or most subjective visual symptoms, however., Conclusion: Corneal and ocular HOAs decreased after CXL, suggesting an improvement in corneal shape., (Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the in vivo, corneal, biomechanical changes after corneal collagen cross-linking (CXL) using the Ocular Response Analyzer (ORA) in patients with keratoconus and post-laser in situ keratomileusis (LASIK) ectasia., Methods: Single-center, prospective, randomized, controlled, clinical trial. After CXL (69 eyes, 46 keratoconus and 23 post-LASIK), corneal hysteresis (CH) and corneal resistance factor (CRF) were measured using the ORA and analyzed in a treatment, sham control, and fellow eye control group at baseline and 1, 3, 6, and 12 months., Results: There were no significant changes in CH (change = 0.05 ± 1.5; P = 0.78) or CRF (change = 0.29 ± 1.4; P = 0.1) at 1 year compared with preoperative values. Changes in CH and CRF were not correlated with changes in clinical outcomes of uncorrected visual acuity, best spectacle-corrected visual acuity, and maximum keratometry. There were no significant changes in CH in the sham or fellow eye control groups (P(sham) = 0.7; P(FE) = 0.3) or CRF (P(sham) = 0.6; P(FE) = 0.72)., Conclusions: Despite an increase in CRF at one month, there were no statistically significant changes in CH and CRF measurements 1 year after CXL. Development of other in vivo biomechanical metrics would aid in evaluating the corneal response to CXL.

Purpose: To evaluate changes in corneal topography indices after corneal collagen crosslinking (CXL) in patients with keratoconus and corneal ectasia and analyze associations of these changes with visual acuity., Setting: Cornea and refractive surgery subspecialty practice., Design: Prospective randomized controlled clinical trial., Methods: Corneal collagen crosslinking was performed in eyes with keratoconus or ectasia. Quantitative descriptors of corneal topography were measured with the Pentacam topographer and included 7 indices: index of surface variance, index of vertical asymmetry, keratoconus index, central keratoconus index, minimum radius of curvature, index of height asymmetry, and index of height decentration. Follow-up was 1 year., Results: The study comprised 71 eyes, 49 with keratoconus and 22 with post-LASIK ectasia. In the entire patient cohort, there were significant improvements in the index of surface variance, index of vertical asymmetry, keratoconus index, and minimum radius of curvature at 1 year compared with baseline (all P < .001). There were no significant differences between the keratoconus and ectasia subgroups. Improvements in postoperative indices were not correlated with changes in corrected or uncorrected distance visual acuity., Conclusions: There were improvements in 4 of 7 topography indices 1 year after CXL, suggesting an overall improvement in corneal shape. However, no significant correlation was found between the changes in individual topography indices and changes in visual acuity after CXL., (Copyright © 2011. Published by Elsevier Inc.)

Purpose: To determine the changes in corneal thickness over time after corneal collagen crosslinking (CXL) for keratoconus and corneal ectasia., Setting: Cornea and refractive surgery subspecialty practice., Design: Prospective randomized controlled clinical trial., Methods: Corneal thickness at the apex, thinnest point, and pupil center were measured using Scheimpflug imaging (Pentacam) at baseline and 1, 3, 6, and 12 months after CXL. The treatment group was compared with both a sham-procedure control group and a fellow-eye control group. Associations with clinical outcomes (uncorrected and corrected distance visual acuities and maximum keratometry) were analyzed., Results: The study comprised 82 eyes, 54 with keratoconus and 28 with ectasia after laser in situ keratomileusis. The mean preoperative thinnest pachymetry was 440.7 μm ± 52.9 (SD). After CXL, the cornea thinned at 1 month (mean change -23.8 ± 28.7 μm; P<.001) and from 1 to 3 months (mean change -7.2 ± 20.1 μm, P=.002), followed by a recovery of the corneal thickness between 3 months and 6 months (mean +20.5 ± 20.4 μm; P<.001). At 1 year, apex and pupil-center thicknesses returned to baseline (P=.11 and P=.06, respectively); however, the thinnest pachymetry remained slightly decreased from baseline to 12 months (mean change -6.6 ± 22.4 μm; P=.01). The recovery of corneal thickness was more rapid in ectasia than in keratoconus. There was no association between the degree of corneal thinning at 3 months and clinical outcomes after CXL., Conclusions: After CXL, the cornea thins and then recovers toward baseline thickness. The cause and implications of corneal thickness changes after CXL remain to be elucidated., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate 1-year outcomes of corneal collagen crosslinking (CXL) for treatment of keratoconus and corneal ectasia., Setting: Cornea and refractive surgery subspecialty practice., Design: Prospective randomized controlled clinical trial., Methods: Collagen crosslinking was performed in eyes with keratoconus or ectasia. The treatment group received standard CXL and the sham control group received riboflavin alone. Principal outcomes included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, astigmatism, and topography-derived outcomes of maximum and average keratometry (K) value., Results: The UDVA improved significantly from 0.84 logMAR ± 0.34 (SD) (20/137) to 0.77 ± 0.37 logMAR (20/117) (P = .04) and the CDVA, from 0.35 ± 0.24 logMAR (20/45) to 0.23 ± 0.21 logMAR (20/34) (P<.001). Fifteen patients (21.1%) gained and 1 patient lost (1.4%) 2 or more Snellen lines of CDVA. The maximum K value decreased from baseline by 1.7 ± 3.9 diopters (D) (P<.001), 2.0 ± 4.4 D (P = .002), and 1.0 ± 2.5 D (P = .08) in the entire cohort, keratoconus subgroup, and ectasia subgroup, respectively. The maximum K value decreased by 2.0 D or more in 22 patients (31.0%) and increased by 2.0 D or more in 3 patients (4.2%)., Conclusions: Collagen crosslinking was effective in improving UDVA, CDVA, the maximum K value, and the average K value. Keratoconus patients had more improvement in topographic measurements than patients with ectasia. Both CDVA and maximum K value worsened between baseline and 1 month, followed by improvement between 1, 3, and 6 months and stabilization thereafter., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the natural history of collagen crosslinking (CXL)-associated corneal haze measured by Scheimpflug imagery and slitlamp biomicroscopy in patients with keratoconus or ectasia after laser in situ keratomileusis., Setting: Cornea and refractive surgery subpecialty practice, United States., Design: Prospective randomized controlled clinical trial., Methods: The treatment group received ultraviolet-A/riboflavin CXL therapy. The control group received riboflavin alone without epithelial debridement. To objectively measure CXL-associated corneal haze, corneal densitometry using Scheimpflug imagery was measured and the changes in haze were analyzed over time. A similar analysis was performed using clinician-determined slitlamp haze. Correlation of CXL-associated corneal haze with postoperative outcomes was analyzed., Results: The mean preoperative corneal densitometry was 14.9 ± 1.93 (SD) (Pentacam Scheimpflug densitometry units). Densitometry peaked at 1 month (mean 23.4 ± 4.40; P<.001), with little change at 3 months (mean 22.4 ± 4.79; P = .06) and decreased between 3 months and 6 months (19.4 ± 4.48; P<.001) and between 6 months and 12 months. By 12 months, densitometry had not completely returned to baseline in the entire cohort (mean 17.0 ± 3.82; P<.001) and the keratoconus subgroup; however, it returned to baseline in the ectasia group (16.1 ± 2.41; P = .15). The postoperative course of slitlamp haze was similar to objective densitometry measurements. Increased haze, measured by densitometry, did not correlate with postoperative clinical outcomes., Conclusions: The time course of corneal haze after CXL was objectively quantified; it was greatest at 1 month, plateaued at 3 months, and was significantly decreased between 3 months and 12 months. Changes in haze did not correlate with postoperative clinical outcomes., (Copyright © 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess subjective visual function after corneal collagen crosslinking (CXL). Setting: Cornea and refractive surgery subspecialty practice. Design: Prospective randomized controlled clinical trial. Methods: Patients completed a subjective questionnaire regarding visual symptoms administered preoperatively and 1 year after CXL. Patients ranked self-reported symptoms of photophobia, difficulty night driving, difficulty reading, diplopia, fluctuations in vision, glare, halo, starburst, dryness, pain, and foreign-body sensation on a scale from 1 to 5. Possible associations of symptoms with changes in corrected distance visual acuity (CDVA) and maximum keratometry were also analyzed. Results: One hundred seven eyes of 76 patients had CXL for keratoconus (n = 71) or ectasia (n = 36). The mean preoperative to 1-year postoperative changes in night driving (3.2 ± 1.5 [SD] to 2.8 ± 1.5), difficulty reading (3.1 ± 1.5 to 2.9 ± 1.3), diplopia (2.5 ± 1.3 to 2.1 ± 1.2), glare (3.1 ± 1.4 to 2.7 ± 1.2), halo (2.9 ± 1.4 to 2.5 ± 1.3), starbursts (2.6 ± 1.5 to 2.4 ± 1.4), and foreign-body sensation (1.8 ± 1.1 to 1.6 ± 0.9) were statistically significant. There were no associations between the change in any symptom and changes in CDVA. There was a weak association between the change in night driving, pain, and foreign-body sensations and the change in maximum keratometry. Conclusions: After CXL, patients noted subjective improvement in visual symptoms, specifically night driving, difficulty reading, diplopia, glare, halo, starbursts, and foreign-body sensation. These subjective outcomes corroborate quantitative clinical improvements seen after CXL. Financial Disclosure: Dr. Hersh is medical monitor for Avedro, Inc. No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]