Accelerated, Pulsed Collagen Cross-Linking versus the Dresden Protocol in Keratoconus: A Case Series.

PURPOSE: The aim of our study was to compare the depth of the demarcation line developing in the cornea after the standard Dresden protocol versus the accelerated, pulsed, epithelium-off corneal collagen cross-linking (CXL). METHODS: This was a nonrandomized, retrospective case series. Patients with progressive keratoconus were treated with either the standard Dresden protocol (Group 1) or accelerated, epithelium-off CXL using the Avedro (Waltham, MA, USA) device (Group 2). The accelerated CXL protocol involved 18 min of pulsed ultraviolet-A (20 mW/cm2, 7.2 J/cm2, pulsed pro-file: 1 s on, 2 s off). The depth of the demarcation line was measured about 3 months postoperatively. RESULTS: Fifty-nine eyes of 35 subjects were included in the analysis. Group 1 consisted of 19 eyes, and Group 2 of 40 eyes. The mean age of the participants was 22.21 years in Group 1 and 26.55 years in Group 2 (p = 0.184). The mean preoperative K value was 44.89 D in Group 1 and 45.20 D in Group 2 (p = 0.768). The depth of the demarcation line was 322.50 µm in Group 1 and 319.95 µm in Group 2 (p = 0.937). CONCLUSIONS: The demarcation line depth was not statistically significantly different between the two protocols. The significance of the demarcation line depth has not been fully clarified in the literature. Our results support the contention that these two techniques may have similar structural outcomes and ef-ficacies in the treatment of keratoconus.

An investigation into corneal enzymatic resistance following epithelium-off and epithelium-on corneal cross-linking protocols.

The aim of this study was to investigate corneal enzymatic resistance following epithelium off and on riboflavin/UVA cross-linking (CXL). One hundred and fourteen porcine eyes were divided into four non-irradiated control groups and seven CXL groups. The latter comprised; (i) epithelium-off, 0.1% iso-osmolar riboflavin, 9 mW UVA irradiation for 10 min, (ii) disrupted epithelium, 0.1% hypo-osmolar riboflavin, 9 mW UVA for 10 min, (iii) epithelium-on, 0.25% hypo-osmolar riboflavin with 0.01% benzylalkonium chloride (BACS), 9 mW UVA for 10 min, (iv) epithelium-on, 5 min iontophoresis at 0.1 mA for 5 min with 0.1% riboflavin solution, 9 mW UVA for 10 min or (v) 12.5 min, (vi) epithelium-on, prolonged iontophoresis protocol of 25 min with 1.0 mA for 5 min and 0.5 mA for 5 min with 0.25% riboflavin with 0.01% BACS, 9 mW UVA for 10 min or (vii) 12.5 min. Enzymatic resistance was assessed by daily measurement of a corneal button placed in pepsin solution and measurement of corneal button dry weight after 11 days of digestion. This study revealed that the enzymatic resistance was greater in CXL corneas than non-irradiated corneas (p < 0.0001). Epithelium-off CXL showed the greatest enzymatic resistance (p < 0.0001). The prolonged iontophoresis protocol was found to be superior to all other trans-epithelial protocols (p < 0.0001). A 25% increase in UVA radiance significantly increased corneal enzymatic resistance (p < 0.0001). In conclusion, although epithelium-on CXL appears to be inferior to epithelium-off CXL in terms of enzymatic resistance to pepsin digestion, the outcome of epithelium-on CXL may be significantly improved through the use of higher concentrations of riboflavin solution, a longer duration of iontophoresis and an increase in UVA radiance.

Rates of infectious keratitis and other ocular surface adverse events in corneal cross-linking for keratoconus and corneal ectasias performed in an office-based setting: a retrospective cohort study.

BACKGROUND: This study aimed to compare the complication rates of epithelium-off corneal cross-linking (epi-off CXL) performed in an office-based setting with those of epi-off CXL performed in an operating room. METHODS: A retrospective cohort study, comprising 501 consecutive epi-off CXL procedures, performed in a non-sterile procedure room without laminar flow ventilation at the ELZA Institute in Zurich, Switzerland, between November 2015 and October 2021, was conducted. RESULTS: No cases of postoperative infectious keratitis were observed, while sterile infiltrates occurred in 10 out of 501 (2.00%) patients, all of whom responded well to topical steroid therapy. Delayed epithelialization (> 7 days) occurred in 14 out of 501 (2.79%) patients. No other adverse events were noted. CONCLUSIONS: Office-based epi-off CXL does not appear to be associated with an increased risk of complications when compared to operating room settings.

Comparison of Efficacy and Safety Between Standard, Accelerated Epithelium-Off and Transepithelial Corneal Collagen Crosslinking in Pediatric Keratoconus: A Meta-Analysis.

Purpose: The purpose of the study is to compare the efficacy of standard epithelium-off CXL (SCXL), accelerated epithelium-off CXL (ACXL), and transepithelial crosslinking CXL (TECXL) for pediatric keratoconus. Methods: A literature search on the efficacy of SCXL, ACXL, and TECXL [including accelerated TECXL (A-TECXL)] for keratoconus patients younger than 18 years was conducted using PubMed, Cochrane Library, ClinicalTrials.gov, and EMBASE up to 2021. Primary outcomes were changes in uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) after CXL. Secondary outcomes were changes in best-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), and central corneal thickness (CCT). Estimations were analyzed by weighted mean difference (WMD) and 95% confidence interval (CI). Results: A number of eleven identified studies enrolled 888 eyes (SCXL: 407 eyes; ACXL: 297 eyes; TECXL: 28 eyes; A-TECXL: 156 eyes). For pediatric keratoconus, except for a significant greater improvement in BCVA at 24-month follow-up in SCXL (WMD = -0.08, 95%CI: -0.14 to -0.01, p = 0.03, I2 = 71%), no significant difference was observed in other outcomes between the SCXL and ACXL groups. SCXL seems to provide greater changes in UCVA (WMD = -0.24, 95% CI: -0.34 to -0.13, p < 0.00001, I2 = 89%), BCVA (WMD = -0.09, 95% CI: -0.15 to -0.04, p = 0.0008, I2 = 94%), and Kmax (WMD = -1.93, 95% CI: -3.02 to -0.85, p = 0.0005, I2 = 0%) than A-TECXL, with higher incidence of adverse events. Conclusion: For pediatric keratoconus, both SCXL and ACXL appear to be comparable in the efficacy of visual effects and keratometric outcomes; SCXL seems to provide greater changes in visual and pachymetric outcomes than A-TECXL.

The Safety Profile of FDA-Approved Epithelium-Off Corneal Cross-Linking in a US Community-Based Healthcare System.

Purpose: To determine the occurrence of early post-operative complications following FDA-approved epithelium-off corneal cross-linking in the United States. Materials and Methods: This multicenter, retrospective cohort study identified patients who underwent epithelium-off (epi-off) corneal cross-linking (CXL) for keratoconus and post-refractive keratectasia within the Kaiser Permanente Northern California healthcare system between 2016 and 2018. Post-operative complications including delayed epithelial healing, infection, and loss of visual acuity were recorded. Results: The study included 878 eyes of 654 patients. The mean age was 27±9.4 years (range 7-71). Five hundred ninety-nine patients (91.6%) had keratoconus while 55 had post-refractive corneal ectasia (8.4%). Forty-seven eyes had prolonged follow-up because of the occurrence of complications in the early post-operative period. The respective rates of delayed epithelial healing, and keratitis were 3.9% (95% CI 2.7-5.3%), and 1.5% (95% CI 0.8-2.5%). Four approaches for management of delayed epithelial healing were compared; epithelium healing duration was the longest in the repeat bandage contact lens (BCL) group (23.8 days) and the shortest in the antibiotic ointment group (14.3 days), with statistically significant differences (p < 0.05) in the healing time between these 2 groups. Conclusion: The concern for early clinical complications after epi-off CXL often leads to delayed CXL intervention and further keratoconus progression with increased economic burdens. A large retrospective review of 878 eyes found that FDA-approved epi-off CXL protocol appears to be safe with low occurrence rates of early post-operative complications. The recommended management for delayed epithelial healing is using antibiotic ophthalmic ointment.

[Safety and efficiency of epithelium-off accelerated corneal cross-linking for progressive keratoconus in pediatric patients]. / Efficacité et tolérance du cross-linking cornéen épithélium-off accéléré dans le traitement du kératocône évolutif de l'enfant.

In adults, the management of keratoconus has evolved in recent years to achieve a well-codified treatment algorithm. The technique of cross-linking (CXL) has allowed us to stabilize the progression of keratoconus and has been largely developed. It is very effective, with few postoperative complications. Currently, there is no specific keratoconus management protocol for children. As we already know that keratoconus usually evolves more rapidly in children, we might consider whether a stabilizing treatment should be proposed as first-line therapy at the time of diagnosis. We carried out a retrospective study including patients less than 18 years of age with keratoconus who consulted the ophthalmology department at Edouard Herriot hospital in Lyon between 2013 and 2017. The main study parameter was whether or not CXL was performed. The other parameters were gender, age, ethnicity, eye rubbing, presence or absence of atopic disease, maximum keratometry (Kmax), minimal pachymetry, best corrected visual acuity (BCVA) and spherical equivalent. Forty-eight eyes of 34 patients were included. We found that two-thirds of the patients were Caucasian boys. Half of the patients had allergies, and over 60% of patients rubbed their eyes regularly. Only six percent of patients had a family history of keratoconus. The mean age of the patients was 14 (7-18) years at the time of diagnosis. Thirty-four eyes of 22 patients underwent CXL, for a total of 71% of our cohort. No postoperative complications occurred. After CXL, there was no significant difference in minimum pachymetry (455.6±37.25µm vs. 453.45±42.6µm after treatment (P=0.71)) or Kmax (50.23±7.17D vs. 50.99±7.01D after treatment (P=0.058)). There was a significant improvement in BCVA (from 0.30±0.3LogMar to 0.17±0.17LogMar after CXL (P=0.024)) and spherical equivalent (-1.91±2.1D to -2.54±1.89D after treatment (P=0.009)). The mean duration of follow-up was 32.2 months (12-59). CXL shows long-term disease stabilization in children with keratoconus. Nevertheless, this technique is indicated only for progressive keratoconus. Early diagnosis and management are essential in this population where the disease is rapidly changing. Treatment of atopy and performance of corneal topography when a child has irregular astigmatism should become automatic for early detection of this disease.

Chemically-Boosted Corneal Cross-Linking for the Treatment of Keratoconus through a Riboflavin 0.25% Optimized Solution with High Superoxide Anion Release.

The purpose of this study was to evaluate the effectiveness and safety of a novel buffered riboflavin solution approved for corneal cross-linking (CXL) in progressive keratoconus and secondary corneal ectasia. Following the in vivo preclinical study performed on New Zealand rabbits comparing the novel 0.25% riboflavin solution (Safecross®) containing 1% hydroxypropyl methylcellulose (HPMC) with a 0.1% riboflavin solution containing 0.10% EDTA, accelerated epithelium-off CXL was performed on 10 patients (10 eyes treated, with the contralateral eye used as control) through UV-A at a power setting of 9 mW/cm2 with a total dose of 5.4 J/cm2. Re-epithelialization was evaluated in the postoperative 7 days by fluorescein dye test at biomicroscopy; endothelial cell count and morphology (ECD) were analyzed by specular microscopy at the 1st and 6th month of follow-up and demarcation line depth (DLD) measured by anterior segment optical coherence tomography (AS-OCT) one month after the treatment. We observed complete re-epithelization in all eyes between 72 and 96 h after surgery (88 h on average). ECD and morphology remained unchanged in all eyes. DLD was detected at a mean depth of 362 ± 50 µm, 20% over solutions with equivalent dosage. SafeCross® riboflavin solution chemically-boosted corneal cross-linking seems to optimize CXL oxidative reaction by higher superoxide anion release, improving DLD by a factor of 20%, without adverse events for corneal endothelium.

Epithelium-Off vs. transepithelial corneal collagen crosslinking in progressive keratoconus: 3 years of follow-up.

PURPOSE: To compare the efficacy of epithelium-off corneal collagen crosslinking (CXL) with transepithelial CXL in patients with progressive keratoconus with a follow-up of 3 years, taking into account the patients' age and the location of the corneal ectasia. METHODS: In this prospective study participated 64 eyes with progressive keratoconus were included in this long-term study, of which 31 eyes were treated by epithelium-off CXL and 33 by transepithelial CXL. All of the patients with a follow-up of 36 months were evaluated for visual variables (corrected distance visual acuity (CDVA), corneal aberrations, and corneal densitometry), structure variables (astigmatism, keratometry, corneal asphericity, maximum posterior elevation, corneal thickness, and corneal volume), and keratoconus index variables. RESULTS: After corneal CXL, CDVA improved significantly in both central and paracentral keratoconus, with greater improvement in the centrals (p = 0.001), asphericity at 6 mm improved in central keratoconus (p = 0.047). In the epi-off group, there was a significant improvement in coma-like (p = 0.038), higher-order aberrations (p = 0.036), asphericity at 8 mm (p = 0.049), asphericity at 10 mm (p = 0.049), and index of surface variance (p = 0.049). CONCLUSION: Although both techniques halted and stabilized the progression of keratoconus, epithelium-off CXL was more effective. In addition, after the corneal CXL, there was a greater degree of regularization of the corneal surface and, therefore, a greater improvement in the CDVA with central keratoconus than with paracentral keratoconus.

Comparison of corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus.

AIM: To evaluate the differences in corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus. METHODS: In our prospective clinical trial, 40 patients (60 eyes) with progressive keratoconus were randomized to undergo corneal cross-linking with transepithelial (TE group, n=30) or epithelium-off (EO group, n=30) keratoconus. Examinations comprised topography, corneal biomechanical analysis and specular microscopy at 6mo postoperatively. RESULTS: The keratometer values were not significantly different between the TE and EO corneal cross-linked groups in different periods (each P>0.05). The corneal thickness of the EO group was greater than that of the TE group at 1wk after the operation (each P<0.05). Regarding corneal biomechanical responses, the EO group showed a longer second applanation length than TE group (P=0.003). Regarding the corneal endothelial function, standard deviation of the endothelial cell size, and coefficient of variation in the cell area, the values of EO group were larger than those of TE group at 1wk (P=0.011, 0.026), and the percentage of hexagonal cells in EO group was lower than that in TE group at 1 and 6mo (P=0.018, 0.019). CONCLUSION: Epithelium-off corneal cross-linking may strengthen corneal biomechanics better than TE procedure can. However, the TE procedure with a lower ultraviolet-A irradiation intensity would be safer for corneal endothelial function.

Corneal collagen cross-linking epithelium-on vs. epithelium-off: a systematic review and meta-analysis.

BACKGROUND: The purpose of the study was to determine the advantages and disadvantages of epi-on corneal cross-linking (CXL) techniques compared with standard epi-off CXL. METHODS: We searched MEDLINE and EMBASE for randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) and we evaluated the selected papers according to the Cochrane risk of bias tool. We considered, as primary outcomes, average Kmax flattening, changes in uncorrected and corrected distance visual acuity (UDVA and CDVA); as secondary outcomes, we considered changes in pachymetry values and endothelial cell density (ECD). We also investigated adverse events related to the treatments and treatment failure. Meta-analysis was conducted with a fixed or random-effects model using weighted mean difference (MD) with 95% confidence interval (CI) as the effect size. RESULTS: A total of 15 studies were included and among these 15 trials, 9 were RCTs and 6 were NRSIs, but only 4 studies showed no high risk of bias and were included in this meta-analysis. Our analysis revealed significant postoperative differences in CDVA (MD = 0.07; 95% CI 0.04 to 0.10; P < 0.001), and no significative differences in UDVA, Kmax, central corneal thickness (CCT) and ECD (P > 0.05). Epi-on CXL protocol was found to be significantly less prompt to have risks of delay in epithelial healing (P = 0.035) and persistent stromal haze (P = 0.026). CONCLUSION: Epi-on CXL is as effective as epi-off CXL. Except for a higher significant improvement in CDVA with current epi-on protocols, our meta-analysis demonstrates that epi-on and epi-off CXL have comparable effects on visual, topographic, pachymetric, and endothelial parameters. Epi-on CXL has clinical advantages in terms of comfort and avoidance of complications as it reduces the risk of developing delay in epithelial healing and persistent stromal haze.

Delayed Re-epithelialization After Epithelium-Off Crosslinking: Predictors and Impact on Keratoconus Progression.

Purpose: To investigate the demographic and corneal factors associated with the occurrence of delayed reepithelialization (DRE) after epithelium-off crosslinking (epi-off CXL). Design:Retrospective case series. Methods:A chart review was performed to identify patients treated with epi-off CXL. DRE was defined as a corneal epithelial defect detected by fluorescein staining that persisted for more than 10 days. Slit-lamp examination, anterior segment optical coherence tomography, corneal topography, and corneal in vivo confocal microscopy (IVCM) were always performed preoperatively and at each follow-up visit (1, 3, 6, 12 months). A generalized estimating equation was used to assess the baseline factors associated with DRE. Results:Data from 153 eyes were analyzed. The mean age of patients was 24.9 ± 8.5 years, and 47 (30.7%) were women. The average reepithelization time was 4.7 ± 1.8 days. Six eyes (3.9%) experienced DRE. In the multivariate model, both the age of the patient (OR = 1.30; p = 0.02) and the corneal steepest meridian (OR = 0.44, p = 0.047) were associated with DRE. Baseline nerve count was also associated with DRE (0.87, p = 0.03). Male gender was associated with a slower early nerve regrowth (1-6 months) (p = 0.048), but not with the occurrence of DRE (p = 0.27). Preoperative central corneal thickness was not related to DRE (p = 0.16). DRE was not associated with keratoconus progression after epi-off CXL (p = 0.520). Conclusions:The association between DRE and age may reflect the age-related decrease in the corneal healing response. Also, low baseline corneal nerve count is associated with DRE. Gender seems to affect reinnervation measured by IVCM but not the reepithelization time. DRE does not seem to affect the efficacy of epi-off CXL.

Accelerated epithelium-on or accelerated epithelium-off corneal collagen cross-linking: Contralateral comparison study.

PURPOSE: The aim of the study is to compare the accelerated epithelial-on corneal collagen cross-linking (epi-on CXL) and accelerated epithelial-off corneal collagen cross-linking (epi-off CXL) in terms of clinical and confocal microscopy results. MATERIALS AND METHODS: Forty-two eyes of 21 patients with progressive keratoconus and simultaneously undergoing accelerated epi-on CXL in one eye and accelerated epi-off CXL in other eye were evaluated. Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) with spectacle in logMAR and topographic findings (mean keratometry [K mean] and maximum keratometry [Kmax]) were recorded at 1, 3, 6, 12, 18, 24, and 30 months. Eyes were compared in terms of subjective pain scores after the procedures. Furthermore, anterior segment optical coherence tomography and confocal microscopy were performed at 1 month. RESULTS: Kmean and Kmax were less than baseline in both the groups; however, the reduction was significantly higher in epi-off CXL than epi-on CXL eyes at 18 and 30 months. The UCVA and BCVA increased approximately 1 Snellen line at the end of mean follow-up in epi-off CXL and in epi-on CXL. Stromal demarcation line for epi-off CXL is 276.4 ± 58.9 while 148.3 ± 24.8 for epi-on CXL (P = 0.001). Furthermore, subepithelial nerves were observed in any eye in epi-off CXL; however, subepithelial nerves were observed in 12 eyes (80%), in epi-on CXL (P = 0.01). CONCLUSION: Both techniques were able to stop progression; however, in contrast to expectations, the pain was felt more in epi-on CXL than epi-off CXL.

Diffuse lamellar keratitis after epi-off corneal crosslinking: An under-recognized complication?

PURPOSE: To report diffuse lamellar keratitis (DLK) occurring in an eye that underwent epithelium-off (epi-off) corneal cross-linking (CXL) as a treatment for post-surgical ectasia and the successful treatment of progressive ectasia with a novel epi-on CXL and conductive keratoplasty (CK) treatment. OBSERVATIONS: A 42-year-old man presented with corneal ectasia in his right eye 3 years after laser in situ keratomileusis (LASIK) surgery. He underwent epi-off corneal CXL using the Dresden protocol. Grade II DLK was diagnosed within days of CXL. Despite successful treatment of DLK, best-corrected visual acuity in the right eye deteriorated over the next 4 months due to progression of ectasia and remained worse than the patient's pre-operative baseline 1 year after epi-off CXL. Because of apparent disease progression, despite his CXL treatment, the patient underwent a novel, transepithelial CXL (TE-CXL) treatment combined with conductive keratoplasty (CK). This treatment improved his vision and stabilized his ectasia without subsequent DLK. Approximately 3 years after CK and TE-CXL, his eye remains stable with 4 Snellen lines of improved vision and no progression of ectasia. CONCLUSION AND IMPORTANCE: Epithelium-off CXL is used increasingly to treat post-LASIK ectasia. First, in this case, DLK occurred after epi-off CXL. We suggest careful scrutiny of such cases as DLK is difficult to identify after epi-off CXL. Second, the epi-off CXL was unsuccessful in stopping the post-LASIK ectasia. Transepithelial CXL successfully treated the ongoing ectasia after resolution of the DLK with no subsequent re-occurrence of DLK. We suggest that TE-CXL may provide a successful initial treatment for post-LASIK ectasia that also minimizes the epithelial disruption that can lead to DLK.

Standard cross-linking versus photorefractive keratectomy combined with accelerated cross-linking for keratoconus management: a comparative study.

PURPOSE: To compare the safety and efficacy of standard 30 min epithelium-off cross-linking (CXL) versus photorefractive keratectomy (PRK) combined with accelerated epithelium-off cross-linking (AXL) for the treatment of progressive keratoconus (CXL-Plus). METHODS: This study was a prospective multicentre comparative clinical study. A total of 125 eyes of 75 patients with grade 1 keratoconus and documented progression were divided into two groups. Group A included 58 eyes treated with standard CXL. Group B included 67 eyes treated with combined PRK and AXL. The recorded data included UDVA, CDVA, subjective and objective refraction, keratometry and pachymetry using corneal topographies preoperatively and postoperatively at 3, 6, 12 and 24 months of follow-up. RESULTS: In group A, at 24 months of UDVA and CDVA were improved from 1.12 ± 0.38 and 0.58 ± 0.42 to 0.66 ± 0.20 and 0.20 ± 0.12 (LogMAR±SD). The spherical equivalent was reduced from 4.03 ± 1.18 to 1.78 ± 1.04 D. The cylinder reduction was 0.32 ± 0.19 D. In group B, at 24 months of UDVA and CDVA were improved from 1.26 ± 0.52 and 0.68 ± 0.36 to 0.58 ± 0.28 and 0.20 ± 0.16 (LogMAR ± SD). The spherical equivalent was reduced from 4.23 ± 0.95 to 1.92 ± 0.74 D. The cylinder reduction was ±1.76 D. CONCLUSION: Surprisingly, standard CXL showed close results to CXL-Plus at the 24th follow-up month. Standard CXL acted as a stabilizing procedure associated with a late myopic component reduction. CXL-Plus acted as a refractive and stabilizing procedure with an early effect on both the myopic and the astigmatic component but no later improvements. Standard CXL seems to be more powerful than AXL in its long-term effect. Therefore, in the future, we want to test the combination of PRK with standard CXL.

Safety Of High Intensity Accelerated Corneal Collagen Cross-Linking In Keratoconus Patients On Basis Of Endothelial Cell Density.

BACKGROUND: This study was conducted to evaluate the safety of accelerated corneal collagen crosslinking (CXL) in keratoconus patients on basis of endothelial cell density measurements. METHODS: We studied 24 patients (42 eyes) with diagnosed keratoconus who underwent accelerated CXL with 9 Mw/cm2 UVA irradiance for 10minutes. All patients underwent detailed examination and video keratography (VKG) for classification and confirmation of keratoconus. Patients with central corneal thickness (CCT) of ≥400µ were included in the study. Specular microscopy was done to note endothelial cell density (ECD) preoperatively and then at the end of 1st, 4th and 12th weeks' post-operative period. RESULTS: The study included 24 patients (42 eyes) from October 2016 to June 2017. Among these 13 were females and 11 males with mean age of 20.15±6.73 years. Eighteen patients underwent the procedure in both eyes while 6 had the procedure in one eye. The pre-operative ECD mean±SD of right eye was 2743.97±542.77/mm2 and left eye was 2763.35±532.57/mm2. The post-operative ECD mean±SD of right and left eyes at the end of 12th post-op weak were 2806.34±520.11/mm2 and 2823.30±628.57/mm2 respectively. The pre and post-op ECD comparison showed p-values at first week post-op are 0.474 and 0.683 for right and left eyes respectively. Similarly, the p-values at 4th and 12 weeks post-op for right eye are 0.266 and 0.280 respectively. The p-values at 4th and 12th weeks for left eye are 0.913 and 0.404 respectively. CONCLUSIONS: Accelerated CXL protocols is safe and effective procedure and did not lead to significant change in ECD in our study population in three months post-procedural follow up. However further research is required to determine the effect of high intensity UVA radiation on other ocular structures with larger group of patients and long-term follow up.

Iontophoretic collagen cross-linking versus epithelium-off collagen cross-linking for early stage of progressive keratoconus - 3 years follow-up study.

PURPOSE: To compare 3-year iontophoretic corneal collagen cross-linking (I-CXL) outcomes with epithelium-off corneal collagen cross-linking (epi-off CXL) for early stage of progressive keratoconus. METHODS: Eighty eyes of 80 patients with early progressive keratoconus treated by I-CXL (n = 40) or epi-off CXL (n = 40) were included in this study. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, corneal topography and pachymetry were assessed at baseline and at 1, 3, 6, 12, 24 and 36 months of follow-up. RESULTS: Visual acuity (VA) showed a significant improvement (p < 0.05) at the end of follow-up in both groups. In the I-CXL group, the UDVA showed a rapid recovery after 3 months (p = 0.04). There was a statistically significant different trend in CDVA between groups with a more favourable outcome for the standard CXL group (p < 0.01). The cylinder improved beginning with 3 months after CXL in both groups. Maximum keratometry showed a significant reduction by 0.9 dioptres (D) in the I-CXL group and by 1.2 D in the epi-off CXL group after 36 months (p = 0.283). Pachymetry values decreased at 3 months while a statistically significant increase occurred in both groups at 24 months. Progression occurred to one patient (2.5%) in I-CXL group. Adverse effects occurred to eight eyes (20%) in the epi-off CXL group. CONCLUSION: Iontophoretic corneal collagen cross-linking (I-CXL) is non-inferior to epi-off CXL for stopping the progression of keratoconus in its early stages with a higher degree of safety for the patients and a faster recovery of VA.

Comparison of transepithelial corneal crosslinking with epithelium-off crosslinking (epithelium-off CXL) in adult Pakistani population with progressive keratoconus.

PURPOSE: The purpose of this study is to compare the safety and efficacy of transepithelial corneal crosslinking (CXL) with epithelium-off crosslinking (epithelium-off CXL) in the treatment of progressive keratoconus in adult Pakistani population. MATERIALS AND METHODS: Sixty-four eyes of 64 consecutive patients of progressive keratoconus were included in this quasi-experimental study. Thirty-two eyes received transepithelial CXL with Peschke TE (0.25% riboflavin (Vitamin B2), 1.2% hydroxypropyl methylcellulose (HPMC), 0.01% benzalkonium chloride) and 32 eyes received epithelium-off CXL with Peschke M (0.1% riboflavin (Vitamin B2) 0.1%, HPMC 1.1%.) The cornea was then exposed to ultraviolet A light at an irradiance of 3 mW/cm2 for 30 min. The primary outcome measure, clinical stabilization of keratoconus was defined as an increase of no more than 1D in Kmax at 1 year. Other parameters evaluated at baseline and 3, 6, 12, and 18 months postoperatively were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent (SE), astigmatism (Ast), simulated keratometry, steep keratmetry (steep K), and corneal thickness at thinnest point (pachy thin). RESULTS: Both epithelium-off CXL and transepithelial CXL groups showed a significant reduction in Kmax, steep K, simulated K, corneal pachymetry at all test points (P < 0.05) with significantly greater reductions achieved in epithelium-off CXL group at 18 months follow-up. The mean UDVA, CDVA, SE, Ast significantly improved in both groups (P < 0.05). The mean postoperative UDVA and CDVA between the groups were not significant at 12 months (P = 0.650, 0.018, respectively). Clinical stabilization was achieved in 94% of eyes in epithelium-off CXL and 75% of eyes in transepithelial CXL. In epithelium-off CXL, three eyes exhibited stromal haze resolved by corticosteroid treatment. No complication was documented in transepithelial CXL group. CONCLUSION: Transepithelial CXL is not recommended to be replaced completely by standard epithelium-off CXL due to continued ectatic progression in 25% of cases. However, thin corneas, unfit for standard epithelium-off CXL, can benefit from transepithelial CXL.

Higher order optical aberrations and visual acuity in a randomized controlled trial comparing transepithelial versus epithelium-off corneal crosslinking for progressive keratoconus.

PURPOSE: The purpose of this study was to compare the effects of transepithelial crosslinking (trans-CXL) versus epithelium-off crosslinking (epi-off CXL) for progressive keratoconus with respect to the development of higher order aberrations (HOAs) and their effects on visual acuity. MATERIALS AND METHODS: A total of 61 patients were randomized and examined preoperatively and 1, 3, 6, and 12 months postoperatively in an academic referral center. Total corneal HOAs were compared between the two treatment groups using mixed linear modeling. Types of HOAs (coma, trefoil, and spherical aberration) that differed between groups were entered in a multivariable analysis to test their effect on uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA). RESULTS: The epi-off CXL group had more flattening in maximal keratometry compared to the trans-CXL group (P=0.02). UDVA did not differ significantly between the groups (P=0.59); however, CDVA was significantly more improved in the trans-CXL group (P=0.02). Horizontal trefoil improved more in the epi-off group compared to the trans-CXL group (P=0.04), whereas the other HOAs were virtually unchanged in both groups. Differences in changes in HOAs between the two groups had no effect on either UCVA (P=0.76) or CDVA (P=0.96). CONCLUSION: Although HOAs are clinically relevant determinants of vision quality in keratoconus patients, the change in total HOAs post treatment did not differ between the trans-CXL and epi-off CXL groups. Only horizontal trefoil differed significantly post treatment between the trans-CXL and epi-off CXL groups. However, this difference did not independently affect either UDVA or CDVA. Trans-CXL provides no benefit over epi-off CXL regarding visual relevant HOAs.

Collagen cross-linking: when and how? A review of the state of the art of the technique and new perspectives.

Since the late 1990s corneal crosslinking (CXL) has been proposed as a new possibility to stop progression of keratoconus or secondary corneal ectasia, with the promising aim to prevent progressive visual loss due to the evolution of the pathology and to delay or avoid invasive surgical procedures such as corneal transplantation. The possibility of strengthening corneal tissue by means of a photochemical reaction of corneal collagen by the combined action of Riboflavin and ultraviolet A irradiation (UVA), radically modified the conservative management of progressive corneal ectasia. This is a review of the state of the art of CXL, reporting basic and clinical evidence. The paper describes basic principles, advantages and limits of different CXL techniques and possible future evolution of the procedure.

Epithelium-off photochemical corneal collagen cross-linkage using riboflavin and ultraviolet a for keratoconus and keratectasia: a systematic review and meta-analysis.

This report presents the results of a systematic review and meta-analyses of studies on epithelium-off photochemical corneal collagen cross-linkage for the management of keratoconus and secondary ectasia. The literature search identified 3,400 records of which 49 were considered for inclusion in the meta-analyses. Eight papers reported 4 unique randomized controlled trials, 29 studies were prospective, and 12 were retrospective studies. The majority of the studies (39/49) were graded as very low quality evidence. Twenty-six studies described adverse events and were included in the safety analysis. Meta-analyses are presented for changes in four outcomes: visual acuity, topography, refraction and astigmatism, and central corneal thickness. Statistically significant improvements were found in all efficacy outcomes at 12 months after the operation. Common side effects were pain, corneal edema, and corneal haze, which resolved usually within a few days after the procedure. The remaining uncertainty is duration of benefit to establish the procedure's potential benefit in avoiding or delaying disease progression and possibly reducing the need for corneal transplantation.