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1.
Corneal collagen cross-linking with and without simultaneous intrastromal corneal ring segment implantation: One-year pilot study.
Sharma, IP, Bakshi, R, Chaudhry, M
European journal of ophthalmology. 2021;(1):61-68
Abstract
AIM: The aim of this study was to assess and compare the visual, refractive, and topographic outcomes of keratoconic eyes treated with corneal collagen cross-linking combined with and without same day intrastromal corneal ring segment over the first 12 months. METHODS This prospective randomized study analyzed 38 eyes of 30 consecutive keratoconus patients aged 26.21 ± 6.97 (range = 15-41) years. A total of 20 eyes were treated with collagen cross-linking alone, and 18 eyes underwent collagen cross-linking combined with simultaneous femtosecond laser-assisted intrastromal corneal ring segment. Visual acuity, manifest refraction, and corneal topography (using a rotating Scheimpflug topographer) were assessed and compared between the two groups at baseline, 6, and 12 months. RESULTS On an average follow-up duration of 12.2 ± 0.50 (range = 11-13) months, both collagen cross-linking alone and collagen cross-linking with simultaneous intrastromal corneal ring segment implantation were effective. However, collagen cross-linking plus intrastromal corneal ring segment resulted in an additional improvement of uncorrected distance visual acuity of 0.16 (95% confidence interval = 0.01 to 0.32) logarithm of the minimum angle of resolution units (p = 0.035), cylindrical power by 1.16 D (95% confidence interval = 0.25 to 2.06, p = 0.014), and spherical equivalent by 1.40 D (95% confidence interval = -2.71 to -0.08, p = 0.038) at 1 year. During the study period, no serious intraoperative or postoperative complications were noted in either group. CONCLUSION One-year follow-up results suggest that collagen cross-linking with simultaneously combined intrastromal corneal ring segment implantation could yield an additive visual and refractive outcome. The combined procedure is safe and merits consideration for the treatment of progressive keratoconus to achieve better visual rehabilitation.
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2.
Accelerated Versus Standard Corneal Cross-Linking for Progressive Keratoconus: A Meta-Analysis of Randomized Controlled Trials.
Kobashi, H, Tsubota, K
Cornea. 2020;(2):172-180
Abstract
PURPOSE To compare the clinical results of accelerated corneal collagen cross-linking (ACXL) to standard corneal collagen cross-linking (SCXL) in progressive keratoconus by summarizing randomized controlled trials using a meta-analysis. METHODS Trials meeting the selection criteria were quality appraised, and data were extracted by 2 independent authors. A comprehensive search was performed using the Cochrane methodology to evaluate the clinical outcomes of ACXL and SCXL for treating progressive keratoconus. Estimates were evaluated by weighted mean difference (WMD) and 95% confidence interval (CI) for absolute changes of the outcomes during 12-month observation periods. Postoperative demarcation line depth was also compared. RESULTS We identified 6 randomized controlled trials that met the eligibility criteria for this meta-analysis. SCXL resulted in a significantly better outcome in postoperative changes in best spectacle-corrected visual acuity (WMD = -0.02; 95% CI, -0.03 to -0.01; P < 0.0001); however, the small differences may not be clinically significant. ACXL provided a significantly better improvement of cylindrical refraction after the 1-year follow-up (WMD = 0.15; 95% CI, 0.05-0.26; P = 0.005). Demarcation line depth at 1 month after SCXL was deeper than that after ACXL (WMD = -102.25; 95% CI, -157.16 to -47.35; P = 0.0003). No differences in the changes in maximum keratometry, central corneal thickness, uncorrected visual acuity, spherical equivalent refraction, corneal biomechanical properties, and corneal endothelial cell density were found among both groups. CONCLUSIONS An ACXL shows a comparable efficacy and safety profile at the 1-year follow-up, but it has less impact on improving best spectacle-corrected visual acuity when compared with the Dresden protocol. Overall, both methods similarly stop the disease progression.
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3.
Standard and accelerated corneal cross-linking long-term results: A randomized clinical trial.
Hashemi, H, Mohebbi, M, Asgari, S
European journal of ophthalmology. 2020;(4):650-657
Abstract
PURPOSE To compare long-term results between accelerated and standard corneal cross-linking protocols in the treatment of progressive keratoconus and compare their effectiveness between central (cone in the central 3 mm) and peripheral (cone beyond 3 mm) cases. METHODS In this randomized clinical trial, we compared 31 eyes treated with accelerated corneal cross-linking (18 mW/cm2, 5 min) and 31 eyes treated with standard corneal cross-linking (3 mW/cm2, 30 min), 16 central and 11 peripheral keratoconus in each group. In this report, 4-year changes in vision, refraction, topography, corneal biomechanics, and corneal cell count were evaluated. RESULTS Uncorrected distance visual acuity improvement was better with standard corneal cross-linking (0.19 ± 0.30 logMAR) than accelerated corneal cross-linking (0.08 ± 0.35 logMAR), but the intergroup difference was not statistically significant (p = 0.283). Cylinder and spherical equivalent significantly increased similarly in both groups. Among topographic indices, anterior Kmax-3 mm showed more reduction in standard corneal cross-linking than accelerated corneal cross-linking (1.35 ± 1.39 vs 0.36 ± 1.10 D, p = 0.011). Anterior Kmax-8 mm reduced by 1.50 ± 1.82 and 0.37 ± 1.58 D in the standard corneal cross-linking and accelerated corneal cross-linking groups, respectively (p = 0.029). Compared to 18-month results, none of the indices at 4 years showed any significant intergroup difference (all p > 0.05). In cases with peripheral keratoconus, changes in anterior Kmax-3 mm (+0.03 ± 0.66 vs -1.17 ± 1.15 D, p = 0.012) and anterior Kmax-8 mm (+0.43 ± 1.09 vs -1.57 ± 1.40 D, p = 0.003) were greater with standard corneal cross-linking. In central cases, no significant intergroup difference was observed. CONCLUSION At 4 years after the procedure, standard corneal cross-linking offered better anterior corneal flattening in the center and periphery. These differences concerned cases of peripheral keratoconus, and the two protocols were similarly effective in central cases. Beyond the 18th month, the two protocols appeared to be similarly effective.
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4.
Noninvasive real-time assessment of riboflavin consumption in standard and accelerated corneal crosslinking.
Lombardo, M, Lombardo, G
Journal of cataract and refractive surgery. 2019;(1):80-86
Abstract
PURPOSE To estimate the noninvasive riboflavin concentration in the corneal stroma using a new ultraviolet-A (UVA) theranostic device for corneal crosslinking (CXL). SETTING Vision Engineering Italy srl, Rome, Italy. DESIGN Experimental study. METHODS Fourteen human donor corneas were treated according to conventional (UVA irradiance of 3 mW/cm2 for 30 minutes) and rapid (10 mW/cm2 for 9 minutes) riboflavin-UVA CXL protocols using a theranostic UVA device. Five additional samples were treated by 0.5 mW/cm2 for 9 minutes and used as positive controls to determine riboflavin photodegradation under near ambient lighting conditions. A 20% dextran-enriched 0.1% riboflavin solution was used in all cases. The device consisted of a UVA light source; a red-green-blue camera, which acquires the fluorescence images of the cornea during treatment; and a single-board computer for managing the overall operations and the raw data processing. RESULTS Preirradiation stromal soaking for 30 minutes achieved highly consistent intrastromal riboflavin concentration in all tissues (mean 0.015% ± 0.003% [SD]). There were no differences in the kinetics curves of riboflavin consumption between the 2 UVA irradiation protocols; the intrastromal riboflavin concentration decreased exponentially, with a mean constant energy rate of 2.8 ± 0.2 J/cm2. In the control group, the intrastromal riboflavin concentration decreased quasilinearly. CONCLUSIONS The theranostic device provided estimates of the intrastromal concentration of riboflavin noninvasively during treatment. In the 3 to 10 mW/cm2 range of power densities, the consumption of riboflavin in the stroma by UVA irradiation was only energy dependent in accordance with the Bunsen-Roscoe law.
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5.
Prospective Randomized Trial of Corneal Cross-linking Riboflavin Dosing Frequencies for Treatment of Keratoconus and Corneal Ectasia.
Price, MO, Fairchild, K, Feng, MT, Price, FW
Ophthalmology. 2018;(4):505-511
Abstract
PURPOSE To investigate whether the riboflavin dosing frequency affects corneal cross-linking efficacy or safety, given that isotonic riboflavin solution is viscous and each installation coats the corneal surface with a film that absorbs some of the incident ultraviolet A light. DESIGN Prospective, randomized, single-center equivalence trial. PARTICIPANTS Patients with progressive keratoconus or ectasia after refractive surgery (n = 510). METHODS One eye per patient was prospectively randomized to 2-minute or 5-minute riboflavin dosing intervals with standard corneal cross-linking (epithelial removal and 30-minute irradiation with 3 mW/cm2 ultraviolet A light). Block randomization resulted in comparable representation of keratoconus and ectasia after refractive surgery in the 2 treatment arms. Treatment equivalence was assessed using the 2 one-sided test. Fellow eyes (n = 207) were treated with 5-minute dosing and considered in the safety analysis. MAIN OUTCOME MEASURES The primary hypothesis was equivalent change in the topography-derived maximum keratometry value from baseline to 6 months with 2-minute vs. 5-minute dosing. A ±0.75-diopter margin of equivalence for the treatment difference between dosing regimens was considered clinically relevant. Adverse events and changes from baseline to 6 months in corrected distance visual acuity (CDVA), uncorrected distance visual acuity, and minimum corneal thickness were assessed. RESULTS The mean reduction in maximum keratometry from baseline was equivalent with 2-minute and 5-minute riboflavin dosing intervals at 6 months (0.97 and 0.76 diopters, respectively; 90% confidence interval for treatment difference, -0.23 to 0.66; per-protocol population). With both dosing intervals, the mean improvement in CDVA was 0.07 logarithm of the minimum angle of resolution or 3.5 letters at 6 months. Of the 635 study and fellow eyes examined at 6 months, 134 (21%) gained and 32 (5%) lost 2 or more lines of CDVA. Three eyes (0.4%) developed sterile infiltrates, 1 (0.1%) had delayed epithelial healing with dendrites, and 3 (0.4%) had recurrent epithelial defects. Three eyes (0.4%) were re-treated. CONCLUSIONS The 2 riboflavin dosing regimens produced equivalent reduction in the maximum keratometry value, with a favorable safety profile.
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6.
Outcomes of Simultaneous and Sequential Cross-linking With Excimer Laser Surface Ablation in Keratoconus.
Bardan, AS, Lee, H, Nanavaty, MA
Journal of refractive surgery (Thorofare, N.J. : 1995). 2018;(10):690-696
Abstract
PURPOSE To evaluate the outcomes of simultaneous and sequential corneal crosslinking (CXL) and excimer laser surface ablation protocols in keratoconus. METHODS A literature review was conducted using MEDLINE. The studies were divided into three groups: the sequential group included studies with CXL followed by excimer laser surface ablation later, the simultaneous group included simultaneous excimer laser surface ablation and CXL, and the no CXL group included excimer laser surface ablation only with no CXL. The data on change in logMAR uncorrected distance visual acuity (UDVA), spectacle corrected distance visual acuity (CDVA), change in spherical equivalent (SE) and refractive astigmatism, change in maximum keratometry (Kmax), complications, and safety and efficacy indices were presented for the latest follow-up visits in all groups. RESULTS Twenty-one studies (3 = sequential; 11 = simultaneous, 7 = no CXL) were included. UDVA improved in all groups. CDVA improved more in the sequential group. SE change was greatest in the no CXL group and the refractive astigmatism reduced comparably in the sequential and no CXL groups but less in the simultaneous group. Kmax reduced in all groups. Only the sequential group showed no progression. Corneal haze was reported in 100%, 54.5%, and 57.1% studies, respectively. Safety and efficacy indices were 1.96 and 1.58, 1.41 ± 0.32 and 0.91 ± 0.41, and 1 and 0.82, respectively. CONCLUSIONS The sequential group showed greater improvement in CDVA, SE, and refractive astigmatism. Corneal haze was frequently reported in all protocols. Safety and efficacy indices were highest when CXL was performed before excimer laser and least when excimer laser was performed alone without CXL. [J Refract Surg. 2018;34(10):690-696.].
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7.
Low light visual function after accelerated corneal Cross-Linking Protocols: 18 mW/cm2 vs. 9 mW/cm2.
Asgari, S, Hashemi, H, Jafarzadehpur, E, Mohamadi, A, Mehravaran, S, Fotouhi, A
Romanian journal of ophthalmology. 2018;(4):270-276
Abstract
Objective. To compare one-year results of vision, corneal aberrometry and contrast sensitivity (CS) in low light conditions between 5- and 10-minute accelerated cross-linking (CXL) protocols. Methods. Thirty eyes were evaluated in each studied group. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity by the SC-2000 Snellen chart, corneal higher order aberrations using the OPD Scan III and CS using MonCv3System was tested under mesopic (20 lux) and scotopic (0.5 lux) light conditions at pre-CXL and 6 and 12 months post-CXL. Results. At 12 months, a mean improvement of 0.06±0.22 (22.2%) and 0.02±0.25 logMAR (7.9%) in mesopic UDVA and 0.01±0.13 (14.3%) and 0.07±0.13 logMAR (87.9%) in mesopic CDVA was observed in the 5- and 10-minute groups, respectively. Mean decline in scotopic UDVA was 0.01±0.16 (1.0%) and 0.03±0.17 logMAR (11.9%) and mean improvement in scotopic CDVA was 0.03±0.10 (35.5%) and 0.02±0.07 logMAR (22.2%), respectively. Inter-group differences in the decrease of corneal aberrations were not statistically significant. Among CS variables, only inter-group changes in corrected CS 0.5 to 2.2 was significantly different (all P<0.050). The linear regression analysis showed that these differences were related to baseline values not CXL protocols; corrected CS 0.5 (Pgroup=0.261 and Pbaseline value<0.001), CS 1.1 (Pgroup=0.250 and Pbaseline value<0.001), and CS 2.2 (Pgroup=0.101 and Pbaseline value=0.054). Conclusions. Changing the intensity of UV in cross-linking from 18mW/ cm2 to 9mW/ cm2 does not affect the visual function under low-light conditions.
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8.
Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intrapatient comparative study.
Sadoughi, MM, Einollahi, B, Baradaran-Rafii, A, Roshandel, D, Hasani, H, Nazeri, M
International ophthalmology. 2018;(1):67-74
Abstract
PURPOSE To compare the outcomes of the conventional and accelerated corneal collagen cross-linking (CXL) in patients with bilateral progressive keratoconus (KC). METHODS Fifteen consecutive patients with bilateral progressive KC were enrolled. In each patient, the fellow eyes were randomly assigned to the conventional CXL (3 mW/cm2 for 30 min) or accelerated CXL (ACXL) (9 mW/cm2 for 10 min) groups. Manifest refraction; uncorrected and corrected distant visual acuity; maximum and mean keratometry; corneal hysteresis and corneal resistance factor; endothelial cell density and morphology; central corneal thickness; and wavefront aberrations were measured before and 12 months after the CXL. RESULTS Manifest refraction spherical equivalent and refractive cylinder improved significantly only in conventional group. Uncorrected and corrected distant visual acuity did not change significantly in either group. Also there was no significant change in the maximum and mean keratometry after 12 months. There was significant decrease in central corneal thickness in both groups which was more prominent in conventional group. Endothelial cell density reduced only in the conventional group which was not statistically significant (P = 0.147). CH, CRF, and wavefront aberrations did not change significantly in either group. We did not observe any significant difference in the changes of the variables between the two groups. CONCLUSIONS Accelerated CXL with 9 mW/cm2 irradiation for 10 min had similar refractive, visual, keratometric, and aberrometric results and less adverse effects on the corneal thickness and endothelial cells as compared with the conventional method after 12 months follow-up. However, randomized clinical trials with longer follow-ups and larger sample sizes are needed.
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9.
Epithelium-off versus transepithelial corneal collagen crosslinking for progressive corneal ectasia: a randomised and controlled trial.
Rush, SW, Rush, RB
The British journal of ophthalmology. 2017;(4):503-508
Abstract
AIM: To compare the outcomes of corneal collagen crosslinking (CXL) for the treatment of progressive corneal ectasia using a standard epithelium-off technique versus a transepithelial technique with enhanced riboflavin solution. METHODS One hundred and forty-four eyes with progressive corneal ectasia were prospectively randomised into a transepithelial CXL study arm or an epithelium-off CXL control arm. Follow-up examinations were set at 3, 6, 12 and 24 months. The primary outcome measure was change in the maximum simulated keratometry value (Ksteep) after 24 months of follow-up. The secondary outcome measure was change in the best spectacle-corrected visual acuity (BSCVA) after 24 months follow-up. RESULTS One hundred and thirty-one eyes completed the 24-month follow-up interval. Change in Ksteep was -1.52±0.66 dioptres (D) for the control group versus -0.54±0.58 D for the study group at 24 months of follow-up (p=0.0320). Change in BSCVA was -0.18±0.09 logMAR for the control group versus -0.14±0.08 logMAR for the study group at 24 months of follow-up (p=0.4978). Two eyes in the control group had minor postoperative complications that did not affect the final visual acuity, and one eye in the control group underwent keratoplasty during the study interval. CONCLUSIONS At 24 months of follow-up, subjects in the epithelium-off CXL group demonstrated a greater improvement in Ksteep compared with subjects in the transepithelial CXL group, but no statistically significant difference in BSCVA was found between groups. TRIAL REGISTRATION NUMBER NCT01708538; pre-results.
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10.
Randomized Controlled Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis with the Dresden Protocol in Progressive Keratoconus.
Lombardo, M, Giannini, D, Lombardo, G, Serrao, S
Ophthalmology. 2017;(6):804-812
Abstract
PURPOSE To compare clinical outcomes of transepithelial corneal cross-linking using iontophoresis (T-ionto CL) and standard corneal cross-linking (standard CL) for the treatment of progressive keratoconus 12 months after the operation. DESIGN Prospective randomized controlled clinical trial. PARTICIPANTS Thirty-four eyes of 25 participants with progressive keratoconus were randomized into T-ionto CL (22 eyes) or standard CL (12 eyes). METHODS T-ionto CL was performed using an iontophoresis device with dextran-free 0.1% riboflavin-5-phosphate solution with enhancers and by irradiating the cornea with a 10 mW/cm2 ultraviolet A device for 9 minutes. Standard CL was performed according to the Dresden protocol. MAIN OUTCOME MEASURES The primary outcome measure was stabilization of keratoconus after 12 months through analysis of maximum simulated keratometry readings (Kmax, diopters). Other outcome measures were corrected distance visual acuity (CDVA, logarithm of the minimum angle of resolution [logMAR]), manifest spherical equivalent refraction (D), central corneal thickness (CCT, micrometers) and endothelial cell density (ECD). Follow-up examinations were arranged at 3 and 7 days and 1, 3, 6, and 12 months. RESULTS Twelve months after T-ionto CL and standard CL, Kmax on average flattened by -0.52±1.30 D (P = 0.06) and -0.82±1.20 D (P = 0.04), respectively. The mean change in CDVA was -0.10±0.12 logMAR (P = 0.003) and -0.03±0.06 logMAR (P = 0.10) after T-ionto CL and standard CL, respectively. The manifest spherical equivalent refraction changed on average by +0.71±1.44 D (P = 0.03) and +0.21±0.76 D (P = 0.38), respectively. The CCT and ECD measures did not change significantly in any group at 12 months. Significant differences in the outcome measures between treatments were found in the first week postoperatively. No complications occurred in the T-ionto CL group; 1 eye (8%) had sterile corneal infiltrates, which did not affect the final visual acuity, in the standard CL group. CONCLUSIONS Significant visual and refractive improvements were found 12 months after T-ionto CL, though the average improvement in corneal topography readings was slightly lower than the Dresden protocol in the same period.