Permeation characteristics and cross-linking efficacy of iontophoresis-assisted riboflavin delivery for accelerated riboflavin-ultraviolet A scleral collagen cross-linking in porcine eyes.

The purpose of this study is to investigate whether the iontophoresis-assisted riboflavin delivery to posterior sclera with less delivery time, can achieve the same riboflavin permeation efficiency as the passive soaking way, and its effect on the mechanical properties of posterior sclera for accelerated scleral collagen cross-linking (A-SXL). In this study, 0.1% riboflavin solution was applied into the posterior sclera of porcine eyes either by the iontophoresis-assisted or passive soaking method, with delivery time of 5, 7.5, 10, 12.5, 15, 17.5, and 20 min, respectively. The fluorescence intensity and the distribution of riboflavin concentration in the 10 µm frozen sections of the sclera were evaluated by fluorescence inverted microscope. The posterior sclera with riboflavin treatment through either the iontophoresis-assisted or the passive soaking method for different durations ranging from 5 to 20 min was treated with ultraviolet A (UVA) irradiation at an intensity of 10 mW/cm2 for 9 min. The elastic modulus was determined at the physiological strain level using the uniaxial tensile test after ASXL. The results showed that the fluorescence intensity of riboflavin increased by prolonging the delivery time in both the iontophoresis and passive soaking groups, and the permeation depth of riboflavin remained constant over 15 min. The fluorescence intensity in the iontophoresis group was significantly higher than in the passive soaking group at 12.5 min and 15 min, respectively. The elastic modulus at 12.5 min in the iontophoresis group was significantly higher than in the passive soaking group at the same delivery time and showed no significant difference compared to the passive soaking group at 20 min. In conclusion, it indicated that iontophoresis-assisted delivery could not only shorten the surgery time but also achieve similar mechanical performance to the passive soaking method in ASXL.

A Comparison Between Cross-Linking Protocols in Patients With Progressive Keratoconus: A Review.

Keratoconus (KC) is a noninflammatory cornea disease leading to progressive thinning, causing it to change from its normal dome shape to a cone shape. One of the novel treatments of KC is corneal collagen cross-linking (CXL). Due to its importance, many studies have been conducted to compare corneal cross-linking protocols; this review article aims to discuss corneal cross-linking and compare its different treatment options, including Dresden, accelerated, and customized protocols in patients with progressive KC and their respective long-term outcomes. A search was performed in PubMed and Google Scholar with no language, dates, or study type restriction. Most of the results showed almost no difference between protocols over traditional cross-linking. However, published data are limited, long-term outcomes of novel age groups remain unclear, and further studies are needed.

Factors Affecting Visual Gain after Accelerated Crosslinking in Pediatric Keratoconic Cases.

OBJECTIVES: This study was designed to evaluate factors affecting visual gain following accelerated crosslinking (A-CXL) in pediatric cases with keratoconus. METHODS: Pediatric patients with a diagnosis of keratoconus who underwent A-CXL for 10 minutes ultraviolet A (UV-A) 9 mW/cm2 between February 2015 and May 2019 and had at least 1 year of follow-up data were analyzed retrospectively. Uncorrected visual acuity, best corrected visual acuity (BCVA), and refractive value changes (spherical, cylindrical values) at the preoperative and postoperative 12th month were compared. Correlation analysis was used to evaluate the relationships between visual gain and corneal topography values (K1, K2, Kmaximum [Kmax], anterior elevation, posterior elevation) obtained using a Sirius topography device (Costruzione Strumenti Oftalmici, Florence, Italy). RESULTS: A total of 33 eyes of 22 patients (mean age: 16.85±1.15 years) who underwent A-CXL (9 mW/cm2 UVA irradiation for 10 minutes) were included in the study. The mean BCVA had increased from 0.45±0.27 logMAR to a mean of 0.33±0.24 logMAR at the end of 1 year (p=0.014). Changes to spherical and cylindrical values were not statistically significant (p>0.05). The correlation analysis revealed a statistically significant relationship between visual gain and the preoperative BCVA and the preoperative Kmax. CONCLUSION: The study results indicated that the visual gain at 1 year after A-CXL (10 minutes at 9 mW/cm2) was associated with preoperative BCVA and Kmax values in pediatric cases of keratoconus.

Profile of infectious and sterile keratitis after accelerated corneal collagen cross-linking for keratoconus.

PURPOSE: The aim of this study was to assess the potential risk factors and causes of infectious and sterile keratitis after accelerated collagen cross-linking. METHODS: Case records of 968 eyes that underwent accelerated corneal collagen cross-linking (ACXL) over the period of 4 years were reviewed retrospectively. ACXL was done using (Avedro KXL® system, Waltham, MA, USA) 9 mW/cm2 for 10 min protocol providing total energy of 5.4 J/cm2. RESULTS: Of 968 eyes, a total of three eyes developed infectious keratitis and seven eyes developed sterile infiltrates. Three of this infectious keratitis had two cases which were resistant to fourth-generation fluoroquinolones. Seven cases of sterile infiltrates had excellent resolution after treatment with topical steroids. Sterile infiltrates were common in corneas with thinnest pachymetry of <400 µm, except in one case of intra stromal corneal ring segments (INTACS) + ACXL. CONCLUSION: Judicious use of steroids in the initial postoperative period is recommended so as to prevent any form of microbial keratitis. Very steep corneas and too thin corneas should be looked with high index of suspicion in view of chances of developing sterile infiltrates.

Accelerated versus standard corneal collagen cross-linking in pediatric keratoconus patients: 24 months follow-up results.

PURPOSE: To compare the 24 month visual, refractive, topographic and aberrometric results of the accelerated and standard corneal collagen cross-linking (CXL) in pediatric keratoconus patients. METHODS: 87 eyes of 64 consecutive keratoconus patients under 18 years old with 24 month follow-up period following standard or accelerated CXL were included. 38 eyes received standard CXL (3 Mw/cm2, 30 min), while 49 eyes had accelerated CXL (9 mW/cm2, 10 min). Changes in the uncorrected (UCVA) and best corrected visual acuity (BCVA), spherical equivalent (SE), manifest astigmatism (MA), corneal topographic parameters, and corneal aberrations such as spherical aberration (SA), high order aberrations (HOAs), horizontal and vertical coma were evaluated. Corneal haze was graded and progression rate was assessed. RESULTS: The difference between baseline and 24 months postoperative UCVA, BCVA, SimK (keratometry)-1, SimK-2, Kmax, and the corneal aberrations were not significantly different between the two groups (p > 0.05 for all). The mean reduction in thinnest corneal pachymetry from baseline to 24 months after CXL was higher in accelerated CXL group (p = 0.007). The progression rate was 13.1% in standard and 16.3% in accelerated group (p = 0.754). There were no differences in the grade of corneal haze between the two groups (p = 0.249). No complications were observed in the both groups. CONCLUSION: The 24 month results of accelerated and standard CXL revealed that, the efficacy and safety of accelerated CXL were the same with standard CXL in pediatric keratoconus patients. As being a rapid procedure, accelerated CXL appears to be more benefical for pediatric patients.

Accelerated versus Conventional Corneal Collagen Cross-Linking for Progressive Keratoconus.

We aimed to compare the effect of accelerated and conventional corneal collagen cross-linking (CXL) on visual, refractive, and topographic parameters in patients with progressive keratoconus. Between December 2014 and February 2016, at Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Iran, we compared 37 eyes of 21 patients treated by conventional CXL (CCXL; 3 mW/cm2 in 30 minutes) with 34 eyes of 18 patients treated by accelerated CXL (ACXL; 18 mW/cm2 in 5 minutes) based on generalizing estimation equation analysis in terms of corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), corneal endothelial cell indices, and topographic parameters before and at 3, 6 and 12 months after the operation. The mean UDVA and spherical equivalent changes were similar in the two groups, but an improvement in CDVA was only observed in the CCXL group (P = 0.003). Keratometry (minimum and maximum) was significantly decreased in the CCXL group (P = 0.043 and P = 0.008, respectively). Indices of keratoconus progression-surface asymmetry index (SAI), keratoconus prediction index (KPI), and keratoconus index (KCI)-were significantly lower in the CCXL group than in the ACXL group (P = 0.002, P < 0.001, and P < 0.001, respectively). The thinnest corneal thickness (TCT) was not significantly different between the two groups (P = 0.15). The reduction of corneal endothelial cell density was also similar between the two groups; however, polymorphism and polymegethism were significantly lower in the ACXL group than in the CCXL group. In conclusion, we showed that although ACXL at 18 mW/cm2 slowed keratoconus progression safely during a 1-year follow-up, CCXL at 3 mW/cm2 may be superior in the prevention of keratoconus progression.

Accelerated versus conventional corneal collagen cross-linking in the treatment of mild keratoconus: a comparative study.

AIM: To evaluate the use of accelerated corneal collagen cross-linking in the management of mild and moderate progressive keratoconus in comparison with conventional cross-linking. PATIENTS AND METHODS: Prospective randomized interventional case-control clinical trial. A total 25 eyes of 18 patients were randomly divided into two groups: group A included 14 eyes that received accelerated collagen cross-linking; and group B included eleven eyes that received conventional cross-linking (Dresden protocol). Cases with grade 1 and 2 keratoconus (Krumeich classification) with topographic evidence of progression were included. The uncorrected visual acuity and best spectacle-corrected visual acuity were recorded. Pentacam(®) corneal analysis imaging was used: The maximum and minimum keratometry and the central corneal thickness were recorded. Ocular Response Analyzer(®) (ORA) measurements were carried out to document the biomechanical parameters. Corneal hysteresis and corneal resistance factor were recorded. Postoperative evaluation included uncorrected visual acuity, best corrected visual acuity, and Pentacam and ORA measurements at 6 and 12 months. The follow-up period was 12 months. RESULTS: A progressive decrease in the flat keratometry, steep keratometry, and mean keratometry was noted throughout the follow-up period in both the accelerated and conventional groups. The improvement in keratometry was not statistically significant. The best spectacle-corrected visual acuity showed a statistically significant improvement in both groups by 1 year. The corneal hysteresis and corneal resistance factor showed nonsignificant improvement in both groups. The central corneal thickness showed a significant thinning at 6 months in both groups but approached baseline values by 12 months. CONCLUSION: Accelerated corneal collagen cross-linking appears to show comparable results to conventional cross-linking in arresting the progression of mild keratoconus.