Conventional Versus Accelerated Collagen Cross-Linking for Keratoconus: A Comparison of Visual, Refractive, Topographic and Biomechanical Outcomes.
ABSTRACT: OBJECTIVE:The aim was to compare the visual, refractive, topographic and biomechanical outcomes in patients with progressive keratoconus treated with either conventional or accelerated crosslinking at one year follow up. METHODS:It is a prospective, non-randomised interventional study of 76 patients who underwent conventional (CXL; 3mW/cm2 for 30 minutes) or accelerated cross linking (KXL; 30mW/cm2 for 4 minutes) for progressive keratoconus. Baseline and postoperative visual acuity, manifest refraction, corneal topography, pachymetry, endothelial cell density and biomechanical parameters of corneal hysteresis and corneal resistance factor were evaluated and compared. RESULTS:The 2 groups were comparable in terms of uncorrected and best corrected visual acuity and spherical equivalent. Both groups showed no significant increase in K1, K2 and Kmean from baseline at 12 months. There was also no difference between the CXL and KXL group for postoperative corneal topography as well as central and minimal pachymetry up to 12 months. There was a significant increase in both corneal hysteresis (0.62mm Hg, P=0.04) and corneal resistance factor (0.91mm Hg, P=0.003) in the KXL group at 12 months but not in the CXL group. There was no significant endothelial cell loss throughout follow up in both the groups. CONCLUSION:We have established comparability of the 2 protocols in stabilizing the progression of keratoconus. Our findings also suggested an added biomechanical advantage of accelerated crosslinking at 1 year follow up.
Project description:The purpose of this study was to evaluate the safety and efficacy of transepithelial corneal collagen cross linking (TE-CXL) with modified riboflavin and accelerated UVA irradiance in thin corneas with pachymetry less than 400 microns at thinnest point, untreatable by epithelium off corneal collagen cross linking (CXL) in adult Pakistani population with progressive keratoconus.This quasi experimental study included twenty six eyes of 26 patients with progressive keratoconus who underwent accelerated transepithelial CXL in Armed forced institute of ophthalmology with 12 months follow up. Modified riboflavin, ParaCel ((riboflavin 0.25%, Benzalkonium chloride, EDTA, Trometamol, hydroxypropyl methylcellulose) and vibeX Xtra (riboflavin 0.25%) (Avedro, USA)) were applied to cornea in two stages. Uncorrected and Corrected Distant Visual Acuities (UDVA, CDVA), spherical equivalent (SE), astigmatism, pachymetry at thinnest point (Pachy thin), apex keratometry (Kmax), simulated and steep keratometry (Sim K, steep K) were measured at baseline and at 3, 6 and 12 months post operatively. The cornea was then exposed to accelerated UVA irradiance of 9mW/cm2 for 10 min (total dose 30 mW/cm2).The mean age of the patient was 24.54±5.16 years. UDVA, CDVA, SE, astigmatism significantly improved at all postoperative test points (p=0.000, 0.004, 0.000, 0.004 respectively). Kmax and pachy thin were significantly reduced over baseline at 1 year (p=0.000, 0.004 respectively). Topographic indices Sim K and steep K did not show significant changes. No intra or post-operative complications were reported.Transepithelial accelerated CXL with modified riboflavin is a safe and effective procedure which halt disease progression in thin corneas with progressive keratoconus.
Project description:PURPOSE: To assess the effects of preoperative patient characteristics on clinical outcomes of corneal crosslinking (CXL) treatment in patients with progressive keratoconus. METHODS: This retrospective study comprised 96 eyes of 96 patients who had unilateral CXL treatment for progressive keratoconus. All patients underwent a complete ophthalmological examination and corneal topography at baseline and 1 year. Subgroup analyses were performed according to the age (<30 and ≥ 30 years), gender, preoperative corrected distance visual acuity (CDVA, <0.3 and ≥ 0.3 logMAR (log of the minimum angle of resolution)), preoperative maximum keratometry (K, <54 and ≥ 54 D), baseline topographic cone location (central, paracentral, and peripheral), and preoperative thinnest pachymetry (<450 and ≥ 450 μm) to determine the associations between preoperative patient characteristics and outcomes (changes in visual acuity and maximum keratometry) of CXL treatment. RESULTS: In the entire study population, mean CDVA and maximum K significantly improved after CXL treatment (P<0.001). Patients with a preoperative CDVA of 20/40 Snellen equivalent or worse (≥ 0.3 logMAR) experienced more visual improvement after CXL treatment (P<0.001). However, an age ≥ 30 years and a baseline thinnest pachymetry less than 450 μm were found significantly associated with more flattening in maximum keratometry (P=0.024, P=0.005 respectively). Gender, preoperative maximum K, and baseline topographic cone location did not show significant effect on postoperative visual acuity and maximum keratometry (P>0.05). CONCLUSIONS: In patients with progressive keratoconus, age, baseline visual acuity, and baseline thinnest pachymetry seem to affect the success of the CXL treatment.
Project description:AIM:To compare corneal demarcation line (DL) depth in both accelerated epithelium-off and trans-epithelium cross linking (CXL) using anterior segment optical coherence tomography (AS-OCT) and its relation to maximum keratometry (Kmax) progression in both techniques. METHODS:A prospective comparative interventional study where patients with mild to moderate keratoconus (KC) were classified into two groups: accelerated epithelium-off and trans-epithelium CXL based on corneal pachymetry. Assessment of corneal DL depth was carried out after 3mo by AS-OCT. Kmax readings were evaluated after one year follow up using the Scheimpflug imaging system. RESULTS:Study included 74 eyes of 44 patients. Group A underwent epithelium-off CXL (41 eyes), while Group B underwent trans-epithelium CXL (33 eyes). At 3mo follow up, mean corneal DL depth in Group A was 219.9±58.4 µm while in Group B was 127.2±7.8 µm (P<0.05). The mean Kmax changed from 51.9±3.9 to 51.3±4.2 diopters in Group A and from 53.1±4.1 to 53.6±5 diopters in Group B with insignificant difference in Kmax changes in either group (P>0.05). In addition, no significant change in corneal pachymetry was found in both groups (mean change at 1y: 6.4±4.7 and -10.1±2.3 µm in Groups A and B respectively). CONCLUSION:Despite a significantly deeper corneal DL depth created by accelerated epithelium-off CXL technique compared to accelerated trans-epithelium CXL, there is no significant impact on keratoconus progression.
Project description:To investigate the effects of combined corneal wavefront-guided transepithelial photorefractive keratectomy (tPRK) and accelerated corneal collagen cross-linking (CXL) after intracorneal ring segment (ICRS) implantation in patients with moderate keratoconus.Medical records of 23 eyes of 23 patients undergoing combined tPRK and CXL after ICRS implantation were retrospectively analyzed. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent (MRSE), corneal indices based on Scheimpflug tomography, higher-order aberrations (HOAs), and corneal biomechanical properties were evaluated before and after ICRS implantation, and at 1, 3, and 6 months after combined tPRK and CXL.There were significant improvements in final logMAR UDVA and logMAR CDVA, and reductions in sphere, MRSE, and all corneal indices from baseline. Significant improvements in logMAR UDVA and reductions in sphere, MRSE, maximal keratometry, keratometry at the apex, mean keratometry, and keratoconus index were noted after ICRS implantation. After tPRK and CXL, significant improvements in logMAR UDVA and logMAR CDVA, and reductions in cylinder and all corneal indices were observed. There were significant improvements in final root mean square HOAs and coma aberrations from baseline, but no changes from baseline after ICRS implantation. Significant reductions in final radius and deformation amplitude from baseline were noted.Combined tPRK and accelerated CXL after ICRS implantation in moderate keratoconus appears to be a safe and effective treatment, providing an improvement in visual acuity, corneal indices, and HOAs.retrospectively registered (identification no. NCT03355430 ). Date registered: 28/11/2017.
Project description:Our main purpose was to compare safety and efficacy in the treatment of progressive keratoconus with "epithelium-on" and "epithelium-off" corneal collagen cross-linking (CXL). Our secondary purpose was to evaluate efficacy of CXL when hypotonic 0.5% riboflavin is used as photosensitizer.One eye of 20 patients with bilateral progressive keratoconus was randomly treated for "epithelium-on" CXL (group 1) while the fellow eye underwent "epithelium-off" CXL (group 2). Hypotonic 0.5% riboflavin was used in both groups. Visual acuity, refraction, corneal topography, and wavefront aberrometry were evaluated at baseline and after 1, 6, and 12 months. Specular microscopy was performed on 10 patients preoperatively and after 12 months. Postoperative pain was evaluated using a patient questionnaire.Uncorrected and corrected distance visual acuity improved significantly in both groups. Refraction, topography, and aberrometry showed nonsignificant changes from the preoperative status throughout the 12-month follow-up in both groups. Moreover, the outcomes between the groups were comparable at all follow-up points. Endothelial cell-count was stable. Postoperative pain length was shorter in group 1 (P < 0.001)."Epithelium-on" and "epithelium-off" CXL using hypotonic 0.5% riboflavin were equally safe and effective in stabilization of keratoconus. Topography and aberrometry outcomes in both groups failed to show any significant improvements. This study is registered at ClinicalTrials.gov: NCT01181219.
Project description:To compare the visual, refractive, keratometric, topographic, and pachymetric outcomes of corneal collagen cross-linking (CXL) for progressive keratoconus following epithelial removal by transepithelial phototherapeutic keratectomy (PTK) or manual debridement.In this analysis, 339 eyes (78% male, 22% female) that had undergone CXL following manual epithelial debridement (n = 180) or ablation via PTK (n = 159) were evaluated preoperatively and at 6, 12, and 24 months postoperatively for uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), maximum corneal keratometry, pachymetry, and spherical equivalent. The data were analyzed in a t test to evaluate the relative efficacy of each epithelial removal procedure.Manual epithelial debridement and ablation via PTK produce equivalent changes for all variables at each time interval with the exception of maximum corneal keratometry at 6 months postoperatively, for which PTK exhibited a significantly improved (flatter) result. This difference was present but not statistically significant at 12 and 24 months postoperatively.Prior to CXL, both manual epithelial debridement and ablation via PTK result in equivalent visual, refractive, and keratometric outcomes up to 24 months postoperatively. [J Refract Surg. 2016;32(10):699-704.].
Project description:To evaluate the effectiveness and safety of combined epithelium-off cross-linking (CXL) with photorefractive keratectomy (CXL Plus) for correction of the myopic and astigmatic components of keratoconus.Seventy-nine eyes of 46 patients who underwent CXL Plus were enrolled in this retrospective, multicenter, noncomparative clinical study. Uncorrected distance visual acuity, corrected distance visual acuity, refraction, keratometry, and pachymetry measurements were recorded preoperatively and at 3, 6, 12, and 18 months during follow-up.The mean (±SD) preoperative uncorrected distance visual acuity and corrected distance visual acuity were 1.00 ± 0.22 logarithm of the minimum angle of resolution (logMAR) and 0.62 ± 0.38 logMAR, respectively, and improved to 0.71 ± 0.36 logMAR and 0.32 ± 0.18 logMAR postoperatively. The mean k value, mean corneal thickness at the thinnest location, and mean myopic and astigmatic components decreased from 46.58 ± 0.97 D, 473 ± 29 ?m, 3.65 ± 1.72 D, and 1.83 ± 0.69 D preoperatively to 43.79 ± 1.17 D, 431 ± 38 ?m, 1.02 ± 0.78 D, and 1.15 ± 0.26 D, respectively, during follow-up. Eleven eyes had delayed epithelial healing, 2 had stromal opacities, 1 had primary herpes simplex keratitis, and 5 showed progression of keratoconus.CXL Plus improved the refractive status of keratoconus during 18 months of follow-up, despite its potential early postoperative complications of delayed epithelial healing and corneal haze. CXL Plus reduced the myopic component more than the astigmatic component of keratoconus. However, the safety and stability of the procedure were offset by longer-term postoperative complications and a high rate of postoperative progression of keratoconus.
Project description:We studied changes in gene transcription after corneal crosslinking (CXL) in the rabbit cornea in vivo and identified potential molecular signaling pathways.A total of 15 corneas of eight male New-Zealand-White rabbits were de-epithelialized and equally divided into five groups. Group 1 served as an untreated control. Groups 2 to 5 were soaked with 0.1% riboflavin for 20 minutes, which in Groups 3 to 5 was followed by UV-A irradiation at a fluence of 5.4 J/cm2. Ultraviolet A (UVA) irradiation was delivered at 3 mW/cm2 for 30 minutes (Group 3, standard CXL protocol), 9 mW/cm2 for 10 minutes (Group 4, accelerated), and 18 mW/cm2 for 5 minutes (Group 5, accelerated). At 1 week after treatment, corneal buttons were obtained; mRNA was extracted and subjected to cDNA sequencing (RNA-seq).A total of 297 differentially transcribed genes were identified after CXL treatment. CXL downregulated extracellular matrix components (collagen types 1A1, 1A2, 6A2, 11A1, keratocan, fibromodulin) and upregulated glycan biosynthesis and proteoglycan glycosylation (GALNT 3, 7, and 8, B3GALT2). Also, CXL activated pathways related to protein crosslinking (transglutaminase 2 and 6). In 9.1% of the significantly different genes, CXL at 3 mW/cm2 (Group 1) induced a more distinct change in gene transcription than the accelerated CXL protocols, which induced a lower biomechanical stiffening effect.Several target genes have been identified that might be related to the biomechanical stability and shape of the cornea. Stiffening-dependent differential gene transcription suggests the activation of mechano-sensitive pathways.A better understanding of the molecular mechanisms behind CXL will permit an optimization and individualization of the clinical treatment protocol.
Project description:The purpose of this study was to evaluate the efficacy and safety of iontophoretic collagen cross-linking (I-CXL) compared to epithelium-off standard collagen cross-linking (CXL) in treating the early stages of progressive keratoconus.This retrospective cohort study at Oftaprof Clinic, Iasi, Romania included 40 eyes of 40 patients with progressive keratoconus stage I according to the Amsler classification who underwent I-CXL and the results were compared with a matched group of 40 eyes from 40 patients who received standard CXL. The follow-up period was 24 months. Uncorrected (UCVA) and corrected (CDVA) distance visual acuities, corneal topography, and pachymetry were evaluated in all patients.The mean patient age was 26.52 ± 3.77 years for the standard CXL group and 28.32 ± 4.91 for the I-CXL group. The mean UCVA and CDVA improved significantly in both groups. At 12 months, the improvement of UCVA was greater in the I-CXL group (P < 0.05). There was a statistically significant different trend in CDVA between groups with a more favorable outcome for the standard CXL group (P < 0.01). The manifest cylinder decreased by a mean of 0.962 ± 0.114 D in the epithelium-off CXL group and by 0.831 ± 0.082 D in the I-CXL group (P < 0.001). At 24 months, the K max values improved by 1.2 ± 0.199 D in the standard group and by 0.908 ± 0.177 D in the I-CXL group (P < 0.001).All parameters either improved or remained unchanged after the iontophoretic collagen cross-linking intervention. I-CXL was found to be as effective as the standard technique.
Project description:Purpose:To evaluate whether Accelerated CXL for 10 minutes is as effective as standard CXL for 30 minutes for the treatment of progressive keratoconus. Patients and Methods:Eighty-two eyes of 62 patients with keratometry examinations performed before and 6 months after surgery were studied. A total of 39 eyes underwent standard CXL with UVA irradiation of 3 mW/cm2 for 30 minutes and 32 eyes underwent Accelerated CXL UVA irradiation of 9 mW/cm2 for 10 minutes. The eyes of all patients had corneal thicknesses of at least 450 microns (400 microns after epithelium removal). Results:The means of the keratometry measurements in the preoperative period for the eyes subjected to standard CXL were 46.27 dioptres (D) on the flat axis (K1) and 48.93 D on the steep axis (K2). Postoperatively, K1 was 46.21 D and K2 was 48.97 D, a difference without statistical significance (p = 0.47 and p = 0.48, respectively). In the Accelerated CXL protocol, the preoperative measurements were 44.55 D and 46.19 D for K1 and K2, respectively. In the postoperative period, K1 was 43.37 D, and K2 was 46.64 D (p = 0.38 and p = 0.27, respectively). In the standard group, the mean maximum keratometry (Kmax) preoperatively was 55.87 D, with no statistical significance (p = 0.29). In the preoperative period, the Kmax of the Accelerated group was 51.15 D, with no statistical significance (p = 0.32). Conclusion:Based on the keratometry results, the accelerated protocol was as effective as the standard protocol for keratoconus stabilization.