Cross-linking For Keratoconus Research Articles

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

To evaluate the differences in corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus. 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. 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). 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.

This issue of ACTA

This issue of ACTA

Risk factors for progression following corneal collagen crosslinking in keratoconus.

To assess risk factors for progression following corneal collagen crosslinking (CXL) in eyes with keratoconus. Charts of patients who developed progression following conventional CXL treatment (Dresden protocol) were retrospectively evaluated in two centers (Center 1 and Center 2). 871 eyes of a total of 676 patients were analyzed. Progression was defined as > 1 diopter (D) increase in maximum keratometry (Kmax) readings compared to baseline. Progression was noted in 20 eyes of 20 patients (progression rate 3%). The mean age of the patients was 17.65 ± 5.76 (11-34)-years-old, and the mean follow-up following CXL was 36.70 ± 25.72 (12-84)-months-old. The gender distribution was 13 (65%) females and seven (35%) males. Four eyes (20%) had mild, 13 eyes (65%) had moderate, and three eyes (15%) had severe keratoconus at baseline. Fifteen eyes (75%) had allergic conjunctivitis, and 20 eyes (100%) reported eye-rubbing. Cone location was central in 17 (85%) eyes, and peripheral in 3 (15%) eyes. A mean of 2.21 ± 1.30 D (1.00-5.30 D) steepening was determined at Kmax 6 to 82months following CXL treatment. Progression rate was found to be higher in the patients under the age of 17years, female gender, allergic conjunctivitis, high preoperative Kmax (> 57 D), thin corneas (< 430µm). The majority of progressive patients were central cone and moderate keratoconus.

Кросслинкинг роговицы излучением эксимерного лазера на аргон-фторе

Purpose. To substantiate the expediency of using ablative and subablative energy densities of an argon-fluorine excimer laser for corneal crosslinking. Material and methods. In the period from 1 month to 6 years, the results of more than 500 photorefractive and phototherapeutic operations with saturation of the cornea with riboflavin and the effect of crosslinking were analyzed. To activate riboflavin, secondary radiation was used, induced by the use of ablative and subablative energy densities of an argon-fluorine excimer laser. For an objective assessment of the effect of excimer laser crosslinking, we used the techniques of computed keratotopography, aberrometry, optical coherence tomography, and densitometry. Results. Clinical observations have shown that in most cases of photorefractive surgery of the cornea for the prevention of keratoectasias, it is sufficient to carry out ablation after saturation of the corneal stroma with 0.25% isotonic riboflavin solution for 3-10 minutes, depending on the degree of ametropia and the volume of tissue removed. This provided photoprotective protection of deeper stromal structures from the negative effects of ablation-induced secondary radiation. At the same time, upon completion of ablation, secondary radiation initiated the effect of crosslinking in the adjacent layers, which did not violate the elastic properties of the cornea. In a number of cases, the cross-linking effect was enhanced by additional exposure to energy densities below the ablation threshold and the formation of a Bowman-like membrane structure on the ablation surface. For keratoconus and corneal pathology, without and in combination with keratoectasia, the technology of therapeutic cross-linking was used. This technology provided for the saturation of the stroma with 0.1% or 0.25% isotonic riboflavin solution and its activation by subablative radiation energy densities of an argon-fluorine excimer laser. During therapeutic crosslinking, according to OCT and densitometry, all the classic signs of traditional corneal crosslinking were revealed. Conclusion. The radiation of an argon-fluorine excimer laser with the use of ablative pulse energy densities can be recommended for prophylactic crosslinking in all cases of corneal thinning during photorefractive surgeries, while the use of energy densities below the ablation threshold allows for therapeutic crosslinking in keratoconus and corneal ectasias of various etiology. Key words: excimer laser crosslinking, cornea, keratoconus, photorefractive ablation, riboflavin.

Safety and efficacy of epithelial island crosslinking in keratoconus with thinnest pachymetry less than 400µ

PURPOSE:To evaluate the efficacy and safety of epithelial-island crosslinking (EI-CXL) in keratoconus with corneas thinner than 400 µm.METHODS:Twenty-six patients (30 eyes) underwent EI-CXL (preserving the epithelium over the thinnest area), using standard protocol (3 mW/cm2 for 30 min). Uncorrected and best spectacle-corrected distance visual acuity (UCDVA, BCDVA), manifest refractive spherical equivalent (SEQ), mean simulated keratometry (Kmean), maximum keratometry (Kmax), and thinnest corneal thickness (TCT) were determined preoperatively and at 1, 3, 6, and 12 months following CXL. Endothelial cell count (ECC) was determined preoperatively and at 6 months. Anterior segment optical coherence tomography (AS-OCT) was done at 1 month to determine the depth of the corneal stromal demarcation line (DL).RESULTS:After 1 year, mean UCDVA improved from 1.29 preoperatively to 1.17 (P = 0.001) and BCDVA from 0.62 to 0.57 (P = 0.011). Mean manifest SEQ decreased from -7.63 to-7.32D (P = 0.001). Mean Kmean decreased from 54.92 to 54.81D (P = 0.045), and Kmax from 67.60 to 67.42D (P = 0.072), and mean TCT changed minimally from 377.17 to 375.30 µ (P = 0.11). The mean ECC decreased from 2329 to 2268 cells/mm2 (2.6% decrease, P < 0.001). AS-OCT showed a DL in 29 out of 30 eyes at an average depth of 215.9 µ under the spared epithelium, and 299.9 µ in the de-epithelialized cornea.CONCLUSION:EI-CXL halted keratoconus progression over a 1-year period. This was associated with statistically significant endothelial loss, but less than seen with conventional epi-off CXL in thinner corneas.

Precorneal tear film after corneal collagen cross-linking in keratoconus (preliminary report)

To study the condition of precorneal tear film in keratoconus patients after corneal collagen cross-linking (CXL). The study enrolled 24 patients (30 eyes) with stages I-III progressive keratoconus. All study patients underwent standard (Dresden) protocol CXL. Patients were examined before the surgery and 1 week, 1 month, and 3 months postoperatively. The condition of precorneal tear film was evaluated based on the results of Norn test (the tear film break-up time), Schirmer test, Jones test, optical coherence tomography based lacrimal meniscometry, and improved tearscopy. One month after CXL, patients with keratoconus experienced transient changes in the precorneal tear film condition - the tear film break-up time was reduced, the tear secretion was elevated, the lacrimal meniscus biometry parameters were increased, and the thickness of the tear film lipid layer was decreased. Corneal changes resulting from CXL lead to transient disorders of the mucin and lipid layers of the precorneal tear film, which requires adequate tear substitute therapy in the postoperative period.

Nonhealing epithelial defect after collagen cross-linking for keratoconus with vernal keratoconjunctivitis

Here we report a case of nonhealing epithelial defect after corneal collagen cross-linking (C3R) in a 24-year-old young adult with progressive keratoconus and concomitant vernal keratoconjunctivitis (VKC). Epithelium off C3R with hypoosmolar riboflavin and ultraviolet -A irradiation was done in the right eye for progressive keratoconus. The preoperative minimum corneal thickness was 388 microns. Chronic VKC was stabilized with mast cell stabilizer and lubricants before C3R. The patient presented with nonhealing epithelial defect until 1-month post cross-linking due to possible limbal stem cell deficiency (LSCD) and underlying VKC with giant papillae. Amniotic membrane grafting was done twice for ocular surface stabilization which occurred at the end of 7 weeks. Final best-corrected visual acuity at 1 year was 6/12 with nebular corneal scarring. Preemptive management of giant papillae and proper stabilization of the ocular surface is essential before C3R. In cases of keratoconus with VKC, LSCD should be strongly suspected and reactivation of VKC with a prolonged course of epithelial healing can be a possible complication after C3R.

Deep anterior lamellar keratoplasty in eyes previously treated with collagen crosslinking for keratoconus: 3-year results

To evaluate the 3-year results of deep anterior lamellar keratoplasty (DALK) using the big-bubble technique in keratoconus patients with previous corneal collagen crosslinking (CXL) treatment. Twenty eyes of 20 keratoconus patients who underwent DALK surgery using the big-bubble technique after CXL treatment between January 2011 and September 2015 were retrospectively reviewed. All patients completed 3years follow-up. Intraoperative and postoperative complications were recorded. Uncorrected visual acuity (UCVA), best spectacle corrected visual acuity (BSCVA), maximum keratometry, keratometric astigmatism and endothelial cell density (ECD) were analysed. The mean interval between CXL and DALK surgery was 47.5 ± 24.0months (mean ± SD). DALK was completed in all eyes. Big-bubble was successfully achieved in 16 eyes (80%), and manual dissection was performed in four eyes (20%). Microperforation occurred in three eyes (15%). Postoperatively, persistent epithelial defect occurred in three eyes (15%). The mean UCVA and mean BSCVA values were significantly improved preoperatively to all postoperative visits (p < 0.001). UCVA was 20/100 or lower in all eyes preoperatively and 20/100 or better in 18 eyes (80%) at 3years; BSCVA was 20/40 or better in all eyes (100%) and 20/20 or better in three eyes (15%), and keratometric astigmatism was lower than 4 dioptres in 14 eyes (70%) at 3years. The mean ECD loss was 6.3 ± 4.4% at 1year, 9.0 ± 6.3% at 2years and 11.2 ± 7.4% at 3years. Previous CXL treatment in keratoconus patients did not cause a negative impact on the visual, refractive and surgical outcomes of DALK surgery using the big-bubble technique. DALK surgery seems to be a safe and effective surgical approach in these patients.

Outcome of Corneal Collagen Cross-Linking in Keratoconus: Introducing the Predictive Factors.

Purpose:To evaluate the multiple pretreatment characteristics and topographic factors of keratoconus (KC) patients and their relationship to clinical outcomes of corneal collagen cross-linking (CXL).Methods:In this prospective study, 61 patients (106 eyes) with KC as candidates for CXL were included. Demographic data including age, sex, place of birth and residence, atopic constitution, family history, rubbing history, sleep apnea, and blood group were collected via a structured checklist. Complete ophthalmologic examination and tear collection to assess tear interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) level were performed. Topometric parameters were evaluated using a rotating Scheimpflug topography device. Changes in best corrected visual acuity (BCVA) and maximum keratometry (K-max) were considered the main predicted variables. Predictive variables were analyzed by univariate and multivariate regression.Results:The use of multivariate analysis changes in K-max was significantly associated with rubbing frequency (coefficient = 0.94, P = 0.02), blood group (coefficient = 4.52, P = 0.005), pretreatment corneal asphericity (coefficient = −3.99, P ≤ 0.001), and pretreatment central keratoconus index (CKI) (coefficient = −55.38, P = 0.001). Regarding the changes in BCVA, the multivariate analysis showed a significant association with place of birth (coefficient = −0.08, P = 0.03), pretreatment BCVA (coefficient = −0.67, P < 0.001), pretreatment central corneal thickness (CCT) (coefficient = −0.005, P = 0.04), and pretreatment keratoconus index (KI) (coefficient = 0.53, P = 0.04). Other parameters assessed in the multivariable analysis did not appear to have an individual effect on treatment outcomes.Conclusion:Our results demonstrated that blood group, rubbing of eye, place of birth, corneal asphericity, pretreatment BCVA, CKI, KI, and CCT were statistically associated with the outcome of KC following CXL.

Five years outcomes after corneal cross-linking for keratoconus

Five years outcomes after corneal cross-linking for keratoconus

MyoRing Implantation in Comparison with MyoRing Implantation Combined with Corneal Collagen Crosslinking for Keratoconus

Purpose: tо estimate the effectiveness of complete corneal ring (MyoRing) implantation compared with MyoRing implantation combined with corneal collagen crosslinking (CXL) for keratoconus treatment for 36 months follow-up. Patients and Methods. There were 101 patients (124 eyes) with progressing keratoconus aged 18–59 years in the study. Intracorneal rings were implanted in all patients. The patients were divided into 2 groups. MyoRing implantation was performed in a series of 59 patients (76 eyes) with keratoconus II–III Amsler classification, 42 patients (48 eyes) had MyoRing implantation combined with CXL. Implantation of a MyoRing in the corneal pocket was performed using a PocketMaker microkeratome and corneal intrastromal implantation system. Results. Keratometry was reduced in both groups; after MyoRing implantation for 8,45 D and MyoRing combined with CXL for 7,44 D, the spherical equivalent decreased for 7,72 and 6,29 D respectively, after 36 months. The cylinder decreased to 3,33 D with MyoRing alone and to 3,11 D with MyoRing combined with CXL. The smallest corneal thickness remained stable during 36 months after the procedure. There was an improvement in uncorrected and corrected visual acuity, and the difference in the CRF within the period of up to 12 months after the operation. It can be explained by the pseudochase formation in the group with a combined procedure. Conclusion. The implantation of the MyoRing IRC and the combination of MyoRing with CXL showed efficacy and safety in stabilizing keratoconus stabilization, as well as correction of comorbided ametropia 3 years after surgery. Both MyoRing implantation and MyoRing combined with CXL were effective in the stabilization of progressive keratoconus, as well as the correction of ametropia 3 years after surgery. There was no significant difference in MyoRing implantation and its combination with corneal crosslinking in visual and refractive results. The refractive power of the cornea was only one exeption. Long follow-up and randomized prospective studies with a large number of patients are needed.

Progression Analysis with ABCD Grading System following Corneal Collagen Cross-Linking in Keratoconus.

Objectives:To evaluate the ABCD grading system used in follow-up of keratoconus progression after the corneal collagen cross-linking (CXL) treatment in different Kmax groups.Methods:This study included 57 eyes of 43 patients applied with CXL treatment for progressive keratoconus. All the patients were applied with the standard CXL protocol (Dresden). According to the changes in the Kmax value at the end of 12 months postoperatively (0–1D, 1–2D, >2D), the groups were separated as steepening and flattening. Scheimpflug progression parameters, such as ABCD keratoconus grading systems, were evaluated in six different groups. The Paired Samples t-test was used in the evaluation of parameters with normal distribution and the Wilcoxon test for parameters not showing normal distribution. A value of p<0.05 was accepted as statistically significant.Results:Mean age of patients was 18.37±3.86 years (11–28 years). According to the ABCD grading system, 0.19 significant regression was determined in grade A (p=0.014) and 0.24 in grade D (p<0.0001). 0.10 progression was seen in grade B (p=0.089), and 0.11 in grade C (p=0.011). In the mean Kmax value 0.25±0.42, D flattening was seen (p=0.137).Conclusion:The anterior corneal surface grade in ABCD system is correlated with Kmax in different groups. However, the posterior corneal surface parameter is not correlated with Kmax in 1-2 D steepening and >2D flattening groups. Although there is an increase in posterior elevation after CXL, despite excessive Kmax flattening, it would be inaccurate to consider this increase as an indicator of topographic progress.

Evaluation of corneal and lens density changes after cross-linking in keratoconus

Background Corneal cross-linking (CXL) is an important modality for keratoconus therapy. Lens and corneal density are reported to change in keratoconus and with CXL. However, these changes are not well studied. Aim The aim of this study was to evaluate the changes in corneal and lens density in patients with keratoconus after corneal CXL. Patients and methods This is a prospective case series study that was conducted in a private Eye Laser Center, Menoufia Governorate, Egypt. The study consisted of patients with bilateral clinical keratoconus whose age ranging between 15 and 40 years with clear lenses. Bilateral minimum corneal thickness of 400 µm, measured with Pentacam, was essential. All study patients were examined preoperatively and 1, 3, and 6 months postoperatively. Ophthalmic examination included uncorrected distance visual acuity, corrected distance visual acuity, and manifest refraction as well as corneal thickness, thinnest location, maximal keratometric reading (Kmax), and corneal and lens densitometry measured by Pentacam. Results The preoperative mean corneal density on the axis 0–180 was 17.3±1.8, which changed to 20.7±2.01 after 6 months postoperatively (P=0.001). Although the preoperative mean corneal density on the axis of 90–270 was 17.4±2.06, it changed to 19.9±2.4 after 6 months postoperatively (P=0.04). No significant changes were encountered in lens density after CXL. Conclusion Corneal CXL significantly increased the corneal but not the lens density. This increase was maximal after 1 month and gradually returned toward the baseline. CXL is considered as a safe procedure for the lens.

Two-year topographic and densitometric outcomes of accelerated (45\u2009mW/cm2) transepithelial corneal cross-linking for keratoconus: a case-control study

BackgroundConventional corneal cross-linking is effective for retarding the progression of keratoconus. However the long-term efficacy and safety of accelerated (45 mW/cm2) transepithelial corneal cross-linking (ATE-CXL) on progressive keratoconus (KC) treatment is not fully understood. The purpose of this study is to evaluate the 2-year changes in corneal topographic parameters and densitometry values after ATE-CXL for KC.MethodsTwenty-five progressive eyes of 25 KC patients (KC group) and 25 eyes of 25 myopes without KC (control group) were enrolled. Corneal topography and densitometry values were evaluated pre-operatively and at 6, 12 and 24 months post-operatively in the KC group.ResultsThe mean values of flat keratometry (K1), steep keratometry (K2), mean keratometry (Km), corneal astigmatism (CA), maximum keratometry (Kmax), central corneal thickness (CCT), thinnest corneal thickness (TCT), anterior corneal elevation (ACE) and posterior corneal elevation (PCE) all remained unchanged over time (all P values > 0.05). The densitometry values of the anterior, central, posterior and total layers over the annular diameters 0 mm to 2 mm (Φ0-2 mm) and Φ2–6 mm all decreased significantly (all P values < 0.05). At post-operative month 24, except for the densitometry value of the posterior layer (Φ0-2 mm), which was significantly lower than that of the control group (post hoc P = 0.010), all densitometry values obtained from the remaining locations of the KC eyes were equal to those of the control group (All post hoc P values > 0.05). Subgroups with Km ≥ 50.30D or ACE ≥35.3 μm progressed significantly when compared with those with Km < 50.30D (F = 8.167, P = 0.004) or ACE< 35.3 μm (F = 5.207, P = 0.022).ConclusionsK1, K2, Km, CA, Kmax, CCT, TCT, ACE, and PCE values may remain stable but severer KC patients tend to have poorer long-term outcomes. The densitometry values of the full corneal thickness (total layer over Φ0-2 mm and Φ2–6 mm) may decrease to normal levels at 2 years after ATE-CXL for KC.

Simultaneous Transepithelial Topography-Guided Photorefractive Keratectomy and Accelerated Cross-Linking in Keratoconus: 2-Year Follow-Up

Purpose To evaluate the visual, refractive, and topographic outcomes after simultaneous topography-guided transepithelial photorefractive keratectomy (transepithelial TG-PRK) using the Amaris Excimer laser platform and accelerated corneal cross-linking (CXL) in eyes with keratoconus. Materials and Methods Patients with 2 years of follow-up were included in this retrospective case series. Manifest refraction (MR), uncorrected (UDVA) and corrected (CDVA) distance visual acuity, corneal topography, and pachymetry were evaluated at 1, 3, 6, 12, and 24 months after surgery. The root-mean-square of total higher-order aberrations (total HOA-RMS), coma (Coma-RMS), and spherical aberration (SA-RMS) were calculated for 4- and 6-mm diameters. Results Forty-six eyes of 46 patients were included in the study. Stromal ablation was ≤50 μ in all patients. MR was −3.78±3.26 preoperatively and −1.39±1.82 postoperatively. Significant improvements were seen in the UDVA and Coma-RMS values at 1 month, CDVA and total HOA-RMS values at 3 months, and SA-RMS values at 1 year compared to preoperative levels. UDVA values further improved after 2 years, compared to the 1-year values. No patient lost two or more lines and keratoconus progression was not observed in any patient. Conclusion Simultaneous transepithelial TG-PRK and accelerated CXL resulted in significant gains in CDVA without compromising CXL efficacy.

Outcome of UVA-Riboflavin collagen cross-linking of cornea in patients with keratoconus

Purpose: In this study, we aimed to show changes of central corneal thickness and effects of treatment on visual acuity after corneal collagen cross-linking in keratoconus patients.Materials and Methods: 26 eyes of 51 patients with keratoconus who undergone corneal collagen cross-linking were included in to the study. Central corneal thickness measurements and best corrected visual acuity were recorded before and after 1st and 6th month of corneal collagen cross-linking operation.Results: Mean central corneal thickness measurements were recorded as; 435,43±44,35 μm, 376,68±66,55 μm and 392,62±64,21 μm before and after 1st and 6th month of corneal collagen cross-linking, respectively. There was a statistically significant difference between pre-op and postop 1st month, pre-op and postop 6th month and post-op 1st month and post-op 6th month central corneal thickness measurements. Also, there was a statistically significant increase in best corrected visual acuity after the operation.Conclusion: There was a statistically significant difference between pre-op, post-op 1st month and postop 6th month central corneal thickness and best corrected visual acuity measurements.

Appropriate Sequence of Combined Intracorneal Ring Implantation and Corneal Collagen Cross-Linking in Keratoconus: A Systematic Review and Meta-Analysis.

To compare surgical sequences of combined intracorneal ring segment (ICRS) implantation and corneal collagen cross-linking (CXL) in keratoconus and corneal ectasia in terms of visual, refractive, and keratometric outcomes. A comprehensive electronic search (in PubMed, Web of Science, Scopus, Embase, and Cochrane Library) was conducted in accordance with the PRISMA statement to find articles on combined ICRS implantation and CXL in keratoconus and corneal ectasia. The search period was from the inception of the database up to April 2017. Eligible articles were categorized into 3 surgical sequences (same day, ICRS first, and CXL first) and assessed qualitatively. Articles with 12 months of follow-up data after combined surgery were included in the meta-analysis. The initial search identified 120 related articles, of which 17 were included in the review after screening. The quality assessment showed that visual, refractive, and keratometric improvement was observed in all studies in all 3 groups of combined surgery. Meta-analysis on 6 studies that reported 12-month follow-up outcomes showed no significant differences between the 3 groups regarding uncorrected and best-corrected visual acuity and cylindrical refractive error. However, results with simultaneous surgery were superior to the CXL-first technique in terms of spherical refractive errors and flat-K (P = 0.011 and P = 0.0001, respectively) and to both CXL first and ICRS first in terms of steep-K (P = 0.002 and P = 0.007, respectively). Simultaneous ICRS implantation and CXL may provide better outcomes than staged techniques for improving the corneal shape.

Outcomes following crosslinking for keratoconus in pediatric population

Outcomes following crosslinking for keratoconus in pediatric population

Contact lens fitting after corneal cross-linking for keratoconus: A comparative study

Contact lens fitting after corneal cross-linking for keratoconus: A comparative study

In Vitro Effects of Ascorbic Acid on Corneal Collagen Cross-Linking in Keratoconus

In Vitro Effects of Ascorbic Acid on Corneal Collagen Cross-Linking in Keratoconus