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      Changes in higher order aberrations after central corneal regularization - a comparative two-year analysis of a semi-automated topography-guided photorefractive keratectomy combined with corneal cross-linking

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          Abstract

          Background

          The optical quality in progressive keratoconus deteriorates due to ectasia and distortion of the corneal shape and optics. While corneal cross-linking (CXL) aims at stopping disease progression, “CXL-Plus” combines CXL with excimer laser ablation to improve visual function. Central Corneal Regularization (CCR) represents a therapeutic excimer laser modality specifically designed to smoothen the ectatic corneal shape and to reduce higher order aberrations (HOA). We set out to compare CXL-Plus, consisting of CXL combined with CCR, with CXL by itself for patients with progressive keratoconus.

          Methods

          Retrospective 2-year matched group analysis of patients who either underwent CXL-Plus ( n = 28) or CXL as a sole procedure ( n = 28) for progressive keratoconus. Main outcome parameters were HOA, visual function and tomographic results 12 and 24 months postoperatively.

          Results

          After 12 months, the total HOA root mean square wavefront error was reduced from 0.79 ± 0.30 to 0.40 ± 0.19 μm (CXL-Plus; p <  0.0001) and changed from 0.71 ± 0.28 to 0.73 ± 0.36 μm (CXL; p = 0.814). Uncorrected distance visual acuity improved from 0.70 ± 0.35 to 0.36 ± 0.29 logMAR (CXL-Plus; p = 0.0002) and from 0.65 ± 0.39 to 0.46 ± 0.37 logMAR (CXL; p = 0.067), translating to gains of three or more lines in 50% (CXL-Plus) and 36% (CXL) of patients. The steepest keratometry value (Kmax) regressed by 5.84 D (CXL-Plus; p <  0.0001) and 0.66 D (CXL; p = 0.752). For none of the investigated parameters a statistically significant change could be shown between 12 and 24 months.

          Conclusions

          CXL-Plus in the form of a CCR reduces HOA and Kmax more effectively than CXL as a sole procedure.

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          Most cited references25

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          A randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus: three-year results.

          To report the refractive, topographic, and clinical outcomes 3 years after corneal collagen cross-linking (CXL) in eyes with progressive keratoconus. Prospective, randomized controlled trial. One hundred eyes with progressive keratoconus were randomized into the CXL treatment or control groups. Cross-linking was performed by instilling riboflavin 0.1% solution containing 20% dextran for 15 minutes before and during the 30 minutes of ultraviolet A irradiation (3 mW/cm(2)). Follow-up examinations were arranged at 3, 6, 12, 24, and 36 months. The primary outcome measure was the maximum simulated keratometry value (Kmax). Other outcome measures were uncorrected visual acuity (UCVA; measured in logarithm of the minimum angle of resolution [logMAR] units), best spectacle-corrected visual acuity (BSCVA; measured in logMAR units), sphere and cylinder on subjective refraction, spherical equivalent, minimum simulated keratometry value, corneal thickness at the thinnest point, endothelial cell density, and intraocular pressure. The results from 48 control and 46 treated eyes are reported. In control eyes, Kmax increased by a mean of 1.20±0.28 diopters (D), 1.70±0.36 D, and 1.75±0.38 D at 12, 24, and 36 months, respectively (all P <0.001). In treated eyes, Kmax flattened by -0.72±0.15 D, -0.96±0.16 D, and -1.03±0.19 D at 12, 24, and 36 months, respectively (all P <0.001). The mean change in UCVA in the control group was +0.10±0.04 logMAR (P = 0.034) at 36 months. In the treatment group, both UCVA (-0.15±0.06 logMAR; P = 0.009) and BSCVA (-0.09±0.03 logMAR; P = 0.006) improved at 36 months. There was a significant reduction in corneal thickness measured using computerized videokeratography in both groups at 36 months (control group: -17.01±3.63 μm, P <0.001; treatment group: -19.52±5.06 μm, P <0.001) that was not observed in the treatment group using the manual pachymeter (treatment group: +5.86±4.30 μm, P = 0.181). The manifest cylinder increased by 1.17±0.49 D (P = 0.020) in the control group at 36 months. There were 2 eyes with minor complications that did not affect the final visual acuity. At 36 months, there was a sustained improvement in Kmax, UCVA, and BSCVA after CXL, whereas eyes in the control group demonstrated further progression. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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            Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light.

            To examine to which depth of the cornea the stiffening effect is biomechanically detectable. Department of Ophthalmology, University of Dresden, Dresden, Germany. Of 40 enucleated porcine eyes, 20 eyes were treated with the photosensitizer riboflavin (0.1%) and ultraviolet A (UVA) light (370 nm, 3 mW/cm2, 30 minutes); the other 20 eyes served as control. From each eye, 2 flaps of 200 microm thickness were cut with a microkeratome, and strips of 5 mm width and 7 mm length were prepared. Stress-strain behavior was measured with a material tester to characterize the stiffening effect. Five pairs of human donor eyes were tested in the same way. In porcine corneas, the stiffening effect was stronger in the anterior-treated flaps than in the posterior-treated flaps and the control flaps (P = .001). A 5% strain was achieved at a stress of 261.7 +/- 133.2 x 10(3) N/m2 in the anterior-treated flaps and 104.1 +/- 52.7 x 10(3) N/m2 in the anterior control flaps. The posterior-treated flaps (105.0 +/- 55.8 x 10(3) N/m2) and the posterior control flaps (103.7 +/- 61.8 x 10(3) N/m2) showed no difference (P = .95). A similar stiffening effect was observed in human eyes, but contrary to findings in porcine corneas, in human corneas the anterior control flaps were stiffer than the posterior control flaps (P = .027). Treatment of the cornea with riboflavin and UVA significantly stiffened the cornea only in the anterior 200 microm. This depth-dependent stiffening effect may be explained by the absorption behavior for UVA in the riboflavin-treated cornea. Sixty-five percent to 70% of UVA irradiation was absorbed within the anterior 200 microm and only 20% in the next 200 microm. Therefore, deeper structures and even the endothelium are not affected.
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              Normative values for corneal densitometry analysis by Scheimpflug optical assessment.

              To describe the normative data for corneal Scheimpflug densitometry based on a cohort of normal participants. A total of 445 healthy participants were recruited for assessment (794 eyes). Left and right eyes were considered separately. All participants were assessed using the corneal densitometry analysis add-on to the standard software of the Oculus Pentacam. Densitometry measurements were obtained and expressed in standardized grayscale units (GSU). All participants were Caucasian; 42% were male and 58% were female. The mean age was 48.0 ± 15.3 years (range, 20.2-84.2 years). Mean corneal densitometry over the 12-mm-diameter area was 19.74 ± 3.89 GSU. When divided by radial zone, densitometry values were lowest in the central zone (16.76 ± 1.87 GSU) and highest in the periphery (27.36 ± 7.47 GSU). There was no difference between central zone and the surrounding 2- to 6-mm annulus (P > 0.05), though the 6- to 10-mm and the 10- to 12-mm zones displayed higher densitometry values (P < 0.001). When divided by depth, the anterior layer displayed the highest densitometry reading of 25.81 ± 5.14 GSU, which was significantly higher than that of both the central (P < 0.001) and the posterior layers (P < 0.001). Changes in corneal densitometry were correlated with age, though not within the central 6-mm-diameter ring. No sex difference was seen within the cohort. This add-on to the standard imaging software allows rapid and objective assessment of the corneal densitometry. We provide normative data that may be used as a reference facilitating research and complementing clinical examination.
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                Author and article information

                Contributors
                katja.iselin@luks.ch
                Journal
                Eye Vis (Lond)
                Eye Vis (Lond)
                Eye and Vision
                BioMed Central (London )
                2326-0254
                3 March 2020
                3 March 2020
                2020
                : 7
                : 10
                Affiliations
                [1 ]GRID grid.413354.4, ISNI 0000 0000 8587 8621, Department of Ophthalmology, , Lucerne Cantonal Hospital, ; Lucerne, Switzerland
                [2 ]Medignition Healthcare Innovations, Zurich, Switzerland
                Author information
                http://orcid.org/0000-0001-8896-037X
                Article
                179
                10.1186/s40662-020-00179-2
                7053096
                32161770
                a3dd3aab-e702-44fe-8d77-fde26cee3caf
                © The Author(s) 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 September 2019
                : 11 February 2020
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                keratoconus,corneal cross-linking,cxl-plus,photorefractive keratectomy,central corneal regularization,higher order aberrations,coma-like aberrations

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