Conventional Corneal Cross-linking Research Articles

Ten-year Results after Conventional Corneal Cross-linking in Korean Patients with Progressive Keratoconus

Purpose: To evaluate the long-term effects of conventional corneal cross-linking in patients with progressive keratoconus.Methods: A total of 18 eyes of 9 patients diagnosed with keratoconus were analyzed retrospectively. One eye was diagnosed with progressive keratoconus and conventional corneal crosslinking was performed. The other eye was classified as non-progressive and remained untreated. All patients were assessed with best corrected visual acuity (BCVA), maximum keratometry (Kmax), mean keratometry (Kmean), corneal astigmatism, and corneal thickness. Clinical data were collected before the procedure and at 1, 3, 6 months and 1 to 10 years after the procedure.Results: The BCVA significantly improved from 0.63 ± 0.18 logarithm of the minimum angle of resolution (logMAR) to 0.46 ± 0.25 logMAR at 10 years after conventional corneal crosslinking (p = 0.027). The Kmax and Kmean decreased from 65.90 ± 9.43 D and 52.82 ± 5.16 D to 62.83 ± 8.16 D and 51.52 ± 5.18 D, respectively (p = 0.021, p = 0.028, respectively). Corneal astigmatism decreased from 6.97 ± 2.21 D to 5.53 ± 1.64 D (p = 0.008). The thinnest corneal thickness decreased from 435.11 ± 53.37 μm to 369.22 ± 64.00 μm 1 month after the procedure (p = 0.008), and gradually improved over time. At 10 years, the thinnest corneal thickness increased to 410.11 ± 61.32 μm (p = 0.097). In the untreated eyes, the mean keratometry significantly increased after 4 years of follow-up, but other factors did not change significantly. Although corneal opacity persisted for up to 10 years in 3 eyes of the treatment group, there was no significant difference of BCVA compared to the treated eyes without corneal opacity (p = 0.714).Conclusions: In patients with progressive keratoconus, conventional corneal crosslinking is a safe and effective procedure that suppresses long-term progression.

Conventional versus accelerated corneal collagen cross-linking in cases of progressive keratoconus

Background Keratoconus is mainly a noninflammatory, bilateral corneal disease, which changes stability and refractive intensity. Aim Studying the visual acuity, refraction, and keratometric data of keratoconic patients who underwent either standard or accelerated cross-linking at 6-month duration. Patients and methods A randomized, comparative study with 60 eyes of 30 keratoconus patients. The study participants were categorized into two groups: A and B. Patients in group A underwent epi off conventional corneal crosslinking according to The Dresden’s protocol (3 mW/cm2 for 30 min), while patients in group B underwent epi off accelerated corneal crosslinking (30 mW/cm2 for only 3 min). Preoperative and postoperative outcomes were evaluated and then compared. Results The conventional corneal crosslinking group showed more improvement than the accelerated corneal crosslinking group in postoperative uncorrected distant visual acuity and corrected distant visual acuity at 6 months of follow-up. The two groups were similar in terms of spherical equivalent and manifest refraction. No significant change in K1 and K2 in the both groups from preoperative at 6 months. The same results were found for 6 months of f/up of corneal topography as well as central corneal thickness (CCT) and thinnest location of cornea thickness. Conclusions The study has increased the proof on the power of conventional corneal crosslinking in comparison with accelerated corneal crosslinking at 6 months of follow up.

Corneal Biomechanical Evaluation After Conventional Corneal Crosslinking With Oxygen Enrichment.

To assess corneal biomechanical changes after conventional corneal crosslinking (CXL), with and without oxygen enrichment. Sixty fresh porcine corneas were randomly divided into group 1 (control), group 2 (conventional CXL), and group 3 (conventional CXL in a high-oxygen environment during ultraviolet A [UVA] irradiation). After crosslinking, a 5-mm wide corneal strip was extracted using a double-bladed knife from 12 to 6'o clock. The Young's modulus of each strip was determined by stress-strain measurements. A comparison between the three groups was performed with a one-way analysis of variance. At 4% strain, the Young's modulus of the corneas in groups 1, 2, and 3 were: 0.68±0.20 megapascal (MPa), 1.01±0.23 MPa, and 1.12±0.24 MPa, respectively. The Young's modulus values for groups 2 and 3 showed no statistical significance (P>0.05), However, both groups 2 and 3 were significantly higher than group 1 (P<0.05). At 6% strain, the Young's modulus of the corneas in groups 1, 2, and 3 were: 0.97±0.21, 1.35±0.25, and 1.64±0.44 MPa, respectively, and at 8% strain, the Young's modulus was: 1.29±0.26, 1.72±0.45, 2.20±0.74 MPa, respectively. At 6% and 8% strain, the Young's modulus for the corneas in group 3 was significantly higher than those in both group 1 and group 2 (P<0.05). Increasing oxygen concentration during UVA irradiation may improve the efficacy of conventional CXL.

Transepithelial corneal cross-linking assisted by two continuous cycles of iontophoresis for progressive keratoconus in adults: retrospective 5-year analysis

PurposeThe aim of this study is to compare the long-term effects of transepithelial corneal crosslinking with two continuous cycles of iontophoresis (EI-CXL) and conventional corneal crosslinking (C-CXL) in adults with progressive keratoconus.MethodsA retrospective analysis was conducted in adults who underwent C-CXL or EI-CXL between 2013 and 2015. Visual acuity, corneal tomography, anterior segment optical coherence tomography, in vivo corneal confocal microscopy (IVCM), and endothelial cell count (ECC) were performed preoperatively and 5 years postoperatively.ResultsSixty-eight patients with a mean age of (24.3 ± 3.8) years were included, 34 for each group. After CXL, UCVA or BCVA remained stable, while the spherical diopter, cylinder diopter, spherical equivalent, and Kmax significantly decreased at 1, 2, and 3 years in both groups than baseline (P < 0.05). No significant differences were found in any refractive or tomographic parameters as well as the minimal corneal thickness between groups during follow-up. At 5 years, Kmax was slightly higher in EI-CXL group (58.16 ± 6.28) than that of C-CXL group (57.46 ± 4.98). At 3 and 5 years, the minimal corneal thickness in C-CXL group was still significantly lower than baseline (P < 0.05). IVCM demonstrated the demarcation zone at a mean depth of (302.0 ± 41.7) μm after C-CXL, and at (251.2 ± 28.1) μm after EI-CXL (P < 0.001). Keratocyte repopulation was detectable at all follow-up timepoint in both groups. Postoperative complications including progression were recorded in 6 patients (11.7%) after C-CXL and 3 patients (8.8%) after EI-CXL. ECC remained stable in both groups.ConclusionEI-CXL showed approximate efficacy with C-CXL in stabilizing progressive keratoconus in adults. EI-CXL has the potential to be a preferable transepithelial protocol.

Long-term results of accelerated and conventional corneal cross-linking.

The aim of this study is to compare the long-term follow-up outcomes of traditional and accelerated corneal cross-linking (CXL) for keratoconus. This retrospective comparative cohort study included patients with keratoconus who underwent corneal cross-linking (CXL) between August 2008 and December 2016. Patients treated before August 2013 underwent the traditional Dresden protocol, and those treated subsequently received the accelerated protocol, i.e., 0.1% riboflavin soaking for 10 min, followed by pulsed UV-A irradiation at 30 mW/cm2 for 8 min, and a total irradiation power of 7.2 J/cm2. The primary outcome was the success rate in halting the disease progression. The postoperative changes in visual acuity, keratometry readings, endothelial cell count and complications following accelerated CXL and conventional CXL were compared. This study evaluated 113 eyes over a mean follow-up period of 37.61 ± 16.34 months. It was found that 89.6% and 95.7% of the eyes were successfully treated with the traditional and accelerated protocols, respectively (p = 0.239). The corrected-distance visual acuity improved in both groups, but it was significantly better following the accelerated protocol (p = 0.037). Traditional protocol group had more postoperative complications than the accelerated group (8.9% versus 2%), although not reaching statistically significant difference (p = 0.142). There were no significant differences in the topographic (p = 0.122) and refractive (p = 0.570) outcomes. Accelerated CXL and conventional CXL are both safe and effective, and the long-term follow-up showed that the accelerated protocol was similar to the standard one in terms of halting keratoconus and achieving visual outcomes. Because of its potential benefits, the accelerated protocol may be considered for the treatment of progressive keratoconus.

Time Course of Changes in Simulated Keratometry and Total Corneal Refractive Power after Corneal Collagen Cross-Linking for Progressive Keratoconus.

Purpose To assess the simulated keratometry (Sim K) and the total corneal refractive power (TCRP) in eyes undergoing conventional corneal cross-linking (CXL). Methods This study comprised 20 eyes of 20 keratoconic patients (14 men and 6 women; median age (25th and 75th percentile), 26.5 (21.8, 38.0) years) who underwent CXL. The Sim K and TCRP were measured with a rotating Scheimpflug system (Pentacam HR, Oculus), preoperatively and 1, 3, 6, and 12 months postoperatively. Results The values of Sim K were 52.65 (46.00, 55.70), 52.45 (45.85, 56.88), 51.70 (45.78, 55.83), 51.40 (45.68, 56.80), and 51.25 (46.08, 56.15) D preoperatively and 1, 3, 6, and 12 months postoperatively, respectively. The corresponding figures of TCRP were 52.10 (45.48, 55.08), 51.30 (45.18, 55.20), 50.95 (45.15, 54.50), 50.00 (45.18, 55.08), and 49.80 (45.48, 54.15) D, respectively. The variances of the Sim K and TCRP data were not statistically significant (p=0.994 and p=0.970, respectively, Kruskal–Wallis test). The Sim K was significantly larger than the TCRP before CXL and at 1, 3, 6, and 12 months after CXL (p<0.001, Wilcoxon signed-rank test). Conclusions Not only the Sim K but also TCRP was decreased by approximately 1 D after CXL. The Sim K readings may overestimate the TCRP, even after CXL for progressive keratoconus.

The effects of collagen cross-linking on corneal density: a comparison between accelerated and conventional methods.

To compare the corneal density before and after accelerated versus conventional corneal cross-linking (CXL). Pentacam densitometry and corneal mapping were performed before and 6months following the randomly assigned intervention. Corneal density was measured over different zones and layers of the cornea by two independent ophthalmologists. Total corneal density was calculated. The patients were followed up for the occurrence of procedure-related and unrelated complication 1week, 1month and a final visit around 6months (180 ± 10days) after the procedure, during which the corneal density was remeasured and recorded. Twenty-three patients were enrolled. There was a significant increase in corneal density over the anterior layer (P < 0.001) and middle corneal layer (P = 0.035). Additionally, the corneal density significantly increased in 0-2 and 2-6mm zones (P < 0.001), as well as total density (P = 0.002) following corneal CXL. Although there was no significant difference in the corneal density between the two CXL groups, the increase in corneal density was only significant in group A for the 6-10mm zone and the posterior corneal layer. Both the conventional and accelerated CXL methods increase the overall corneal density with exception of posterior central corneal layer and the 6-10mm zone, which is only increased in the accelerated method.

Prospective, randomized contralateral eye study of accelerated and conventional corneal cross-linking in pediatric keratoconus.

To compare the outcomes of two different cross-linking (CXL) protocols, in pediatric keratoconus eyes. In this prospective randomized contralateral eye interventional study, 68 eyes of 34 patients, 9-16years old, underwent CXL and enrolled between October 2011 and October 2013. Group A represents conventional riboflavin-ultraviolet A (UVA)-induced CXL with 30min of exposure to UVA irradiation of 3mW/cm2. Group B represents accelerated cross-linking with 5min of continuous UVA irradiation of 18mW/cm2. In either group, total energy delivered was adjusted to 5.4J/cm2. Follow-up of all patients was accomplished throughout the postoperative 3years, and the data from the preoperative, 12, 24, and 36months visits were analyzed and compared in both groups. Uncorrected visual acuity, corrected distance visual acuity, steepest keratometry (Kmax), corneal astigmatism (simulated K), total wavefront aberrations, central corneal thickness (CCT), corneal densitometry, manifest refraction spherical equivalent, and endothelial cell density (ECD) were evaluated at baseline, 12, 24, and 36months post-CXL. At 1-year assessment, the mean value of UCVA, CDVA, and Kmax showed a statistically significant difference between both groups, without any documented change in the variables throughout the remaining follow-up (1-3-year) period. Twelve months postoperatively, mean LogMAR UCVA and CDVA were (0.11 ± 1.60) and (0.03 ± 1.60), respectively, in accelerated CXL group, compared to conventional CXL group values of (0.20 ± 1.00) and (0.06 ± 1.22), showing a statistically significant difference (P < 0.05). Mean Kmax in accelerated CXL group (45.47 ± 0.44) showed a statistically significant difference (P < 0.05) compared to conventional CXL group (46.41 ± 1.59) at 12months post-CXL. On the other hand, wavefront aberrations, simulated K, corneal densitometry, ECD, and CCT changes showed nonstatistically significant difference in conventional CXL group, compared to accelerated CXL group (P > 0.05) throughout the follow-up course. Both conventional and accelerated CXL improved UCVA and CDVA, attenuated disease progression, and reduced corneal steepness and wavefront aberrations at 1, 2, and 3years postoperatively. In no case did keratoconus progress over the 36-month follow-up.

Accelerated versus conventional corneal crosslinking for refractive instability: an update.

Corneal crosslinking (CXL) is a relatively new treatment modality offering refractive stability in patients with ectatic disorders. The procedure as initially described (Dresden protocol) is time consuming; accelerated protocols have been lately developed. The purpose of this review is to present the recent findings regarding the comparison of accelerated CXL with the conventional Dresden protocol. A variety of accelerated protocols are described in the literature. Safety and efficacy of the procedures with regard to stability seem to be equivalent in initial studies but indirect measures of efficacy, such as demarcation line depth and laboratory measurements, do not always confirm equivalence of accelerated protocols in comparison to conventional one. Modified accelerated protocols must be developed in order to overcome this. Accelerated CXL protocols seem to be a valid alternative to the conventional protocol; however, more comparative long term studies are needed to confirm the validity and to elucidate which accelerated protocol is ideal in each case.

Initial results from mechanical compression of the cornea during crosslinking for keratoconus

To compare refractive changes after corneal crosslinking with and without mechanical compression of the cornea. In a prospective, open, randomized case-control study conducted at the Department of Ophthalmology, Umeå University Hospital, Sweden, sixty eyes of 43 patients with progressive keratoconus aged 18-28 years planned for corneal crosslinking and corresponding age- and sex-matched control subjects were included. The patients were randomized to conventional corneal crosslinking (CXL; n = 30) or corneal crosslinking with mechanical compression using a flat rigid contact lens sutured to the cornea during treatment (CRXL; n = 30). Subjective refraction and ETDRS best spectacle-corrected visual acuity (BSCVA), axial length measurement, keratometry and pachymetry were performed before and 1 and 6 months after treatment. The keratoconus patients had poorer BSCVA, higher refractive astigmatism and higher keratometry readings than the control subjects at baseline (p < 0.01). In the CXL group, BSCVA increased from 0.19 ± 0.26 to 0.14 ± 0.18 logMar (p = 0.03), and the spherical equivalent improved from -1.9 ± 2.8 D to -1.4 ± 2.4 D (p = 0.03). Maximum keratometry readings decreased after CXL from 53.1 ± 4.9 D to 52.6 ± 5.2 D (p = 0.02), and the axial length decreased in the CXL group, likely due to post-treatment corneal thinning (p = 0.03). In the CRXL group, all the above variables were unaltered (p > 0.05). At 6 months, the refractive results from CRXL did not surpass those of conventional CXL treatment. Rather, some variables indicated a slightly inferior effect. Possibly, stronger crosslinking would be necessary to stabilize the cornea in the flattened configuration achieved by the rigid contact lens.

Comparison of accelerated and conventional corneal collagen cross-linking for progressive keratoconus

Purpose: To compare outcomes of accelerated and conventional corneal cross-linking (CXL) for progressive keratoconus (KC).Materials and methods: Patients were divided into two groups as the accelerated CXL group and the conventional CXL group. The uncorrected distant visual acuity (UDVA), corrected distant visual acuity (CDVA), refraction and keratometric values were measured preoperatively and postoperatively. The data of the two groups were compared statistically.Results: The mean UDVA and CDVA were better at the six month postoperative when compared with preoperative values in two groups. While change in UDVA and CDVA was statistically significant in the accelerated CXL group (p = 0.035 and p = 0.047, respectively), it did not reach statistical significance in the conventional CXL group (p = 0.184 and p = 0.113, respectively). The decrease in the mean corneal power (Km) and maximum keratometric value (Kmax) were statistically significant in both groups (p = 0.012 and 0.046, respectively in the accelerated CXL group, p = 0.012 and 0.041, respectively, in the conventional CXL group). There was no statistically significant difference in visual and refractive results between the two groups (p > 0.05).Conclusions: Refractive and visual results of the accelerated CXL method and the conventional CXL method for the treatment of KC in short time period were similar. The accelerated CXL method faster and provide high throughput of the patients.