Collagen Crosslinking For Progressive Keratoconus Research Articles

Effect of Corneal Collagen Crosslinking with Riboflavin in Patients of Progressive Keratoconus: A Prospective Cohort Study

Introduction: Keratoconus is a non inflammatory disease characterised by progressive corneal thinning that results in a cone-like ectasia, irregular astigmatism, and decreased vision. Advanced disease can result in corneal scarring and blindness, necessitating penetrating keratoplasty. The only treatment believed to have the ability to stop or decrease the progression of keratoconus is Collagen Cross-Linking (CXL). Aim: To evaluate the efficacy of corneal collagen cross-linking with riboflavin (C3R) in patients with keratoconus by studying the outcomes in terms of Uncorrected Visual Acuity (UCVA), Best Corrected Visual Acuity (BCVA), manifest refraction, and corneal topography. Materials and Methods: A hospital-based prospective cohort study was conducted at the Regional Institute of Ophthalmology, Government Medical College, Thiruvananthapuram, Kerala, India from June 2017 to June 2018. Fifteen eyes of 12 patients who underwent corneal collagen cross-linking for progressive keratoconus were included. Routine ophthalmological examinations was done for all patients. Patients under the age of 35 years with progressive keratoconus, an average K value not exceeding 60 D, and who had not undergone any other surgical modalities of treatment were included in the study. Patients with scarred cornea or hydrops, active ocular infection, or pachymetry <400 µm were excluded. Detailed informed consent was obtained from all patients before surgery. Preoperative UCVA, BCVA cylinder, Spherical Equivalent (SE), and topography values were obtained. All patients were followed-up at three and six months postoperative period to look for changes in UCVA, BCVA, manifest refraction, and corneal topography. Data were expressed as the mean±Standard Deviation (SD) pre- and postoperatively and analysed statistically using the paired t-test, with p<0.05 considered statistically significant. Analysis was conducted using Statistical Package for Social Sciences (SPSS) version 16.0. Results: On follow-up at six months post-treatment, UCVA (log MAR) improved from 0.87±0.40 to 0.65±0.35 (p-value=0.001), and BCVA (log MAR) changed from 0.37±0.21 to 0.17±0.22 (p-value=0.001). K max decreased from 54.90±6.05 to 52.67±5.02 (p-value=0.001), and K min decreased from 48.14±4.24 to 45.93±4.07 (p-value=0.001). Astigmatism and SE also showed statistically significant improvement post-procedure (p-value 0.001 and 0.002, respectively). Astigmatism reduced from -3.50±1.58 to -2.90±1.37. SE reduced from -4.93±3.92 to -4.28±3.48. No significant complications were noted in any of the patients. Conclusion: The CXL is an effective procedure for stabilising the progression of keratoconus, thus reducing the burden of preventable blindness and the need for keratoplasty.

Mechanical Epithelial Debridement versus Transepithelial Phototherapeutic Keratectomy Followed by Accelerated Corneal Collagen Crosslinking for Progressive Keratoconus.

To compare the visual and topographic outcomes between mechanical epithelial debridement followed by accelerated corneal collagen cross linking (CXL) vs. transepithelial phototherapeutic keratectomy followed by accelerated CXL for treatment of progressive keratoconus. Quasi experimental study. Place and Duration of the Study: Armed Forces Institute of Ophthalmology (AFIO), National University of Medical Sciences, Rawalpindi, Pakistan, from December 2020 to December 2021. On the basis of surgical technique used, patients were divided into two groups, Group A comprising of twenty eyes that underwent mechanical epithelial removal followed by accelerated CXL, and Group B comprising of twenty-two eyes that underwent transepithelial phototherapeutic keratectomy (t-PTK) followed by accelerated CXL. All variables were recorded preoperatively and 6 and 12 months postoperatively and included uncorrected visual acuity (UCVA), corrected distance visual acuity (CDVA), MRSE (manifest refraction spherical equivalent), and keratometric indices (flat K, steep K, Kmax , mean K, thinnest pachymetry, KPI, K prob, CLMIaa, and I-S). Forty-two eyes of twenty-nine patients were included in the study and were divided into two groups; Group A (mechanical epithelial removal followed by accelerated CXL) and Group B (t-PTK followed by accelerated CXL). The visual acuity improved in both the groups at 6 and 12 months, with more significant improvement in Group B in both UCVA (p=0.005) and CDVA (p=0.004) parameters. Keratometric outcomes showed significant differences in median values for flat K (p=0.048) and thinnest pachymetry (p=<0.001) in Group A, while significant difference in Kmax (p=0.024) and thinnest pachymetry (p=<0.001) in Group B. At 6 and 12 months, the CLMIaa, PPK, and I-S values were significantly lower in Group B (p=0.002 for all three indices). Transepithelial PTK followed by accelerated CXL yielded better outcomes regarding visual acuity and keratomertic indices as compared to mechanical epithelial removal followed by accelerated CXL and did not show any significant decrease in corneal pachymetry. Mechanical, Corneal Collagen Crosslinking (CXL), Transepithelial, Phototherapeutic keratectomy, Keratoconus.

Corneal Collagen Cross-Linking for Progressive Keratoconus in Pediatric Patients: Up to 14 Years of Follow-up

To assess the long-term outcomes of corneal collagen cross-linking according to the Dresden protocol (S-CXL) in progressive pediatric keratoconus (KC). Retrospective, single-center noncomparative interventional study. Patients aged <18 years who underwent S-CXL from June 2007 to January 2011 in Humanitas Clinical and Research Center, Rozzano, Milan, Italy, and completed at least 10 years of follow-up were included. Corrected distance visual acuity (CDVA), refraction, and tomography were evaluated at baseline and ≥10 years after S-CXL. Meeting 2 of the following 3 criteria indicated reprogression: progression above 95% CI for post-CXL population of A or B values or a decrease in minimal thickness C evaluated with the ABCD display. Thirty-eight eyes of 24 patients fulfilled inclusion criteria. At a mean of 11.6 years postoperation (maximum 14 years), the CDVA improved significantly (from 0.703 ± 0.33 decimal fraction to 0.887 ± 0.2, P < .001). Similarly, the A value significantly improved from 2.550 ± 1.7 to 1.627 ± 1.68 (P=.019). Thirteen eyes (34%) showed significant postoperative progression in 2 of the 3 parameters A, B, and C. Of these, only 3 eyes (7.9%) of 3 patients showed a statistically significant change in the A value. S-CXL proved to be a safe treatment for progressive KC in pediatric patients with an anterior curvature progression rate of up to 7.9% at ≥10 years of follow-up.

Study Of Macular Function and Morphology After Transepithelial Accelerated Corneal Collagen Cross-linking in Progressive Keratoconus

Objective The aim of this work is to evaluate the effect of transepithelial accelerated cross-linking (Epi-on CXL) on the macular function and morphology in progressive keratoconus. Patients and Methods The study included 25 patients with progressive keratoconus with age ranged between 18 and 32 years. Epi-On Accelerated CXL was done for all cases. Evaluation was performed 2 and 6 weeks postoperatively after transepithelial (Epi-on) accelerated CXL by Optical coherence tomography (OCT) and multifocal electroretinography (mf-ERG). Results The central foveal thickness (CFT) decreased from 165.1 ± 21.5 µm to 163.4 ± 24.2 µm 2 weeks postoperatively to 164.8 ± 23.9 µm 6 weeks postoperatively, with no statistically significant difference. The preoperative retinal response density (RRD) decreased in macular ring 1 (foveal area of 2.8 degrees) from 179.5 ± 52.1 nV/deg2 preoperatively to 134.7 ± 43.2 nV/deg2 and 146.7 ± 41.6 nV/deg2 in 2 and 6 weeks, respectively postoperatively with statistically significant difference (p = 0.012), while the other 4 rings showed statistically insignificant difference (p &gt;0.05) .On the other hand, implicit time latency (Pl) showed statistically insignificant difference between preoperative and postoperative values (p &gt;0.05) in all macular rings. Conclusion There is a minimal change in macular morphology after Epi-on accelerated CXL in progressive keratoconus, however, no significant change in macular function without any structural changes in progressive keratoconus 6 weeks postoperatively. A longer follow-up period studies are recommended to provide more information.

Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and meta-analysis of randomized controlled trials.

The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus (PK) population at short and long-term. A systematic review and meta-analysis was conducted. A total of eight literature databases were searched (up to February 15, 2022). Randomized controlled trials (RCTs) comparing CXL versus placebo/control or comparing different CXL protocols in the PK population were included. The primary objective was assessment of outcomes of CXL versus placebo and comparison of different CXL protocols in terms of maximum keratometry (Kmax) or Kmax change from baseline (Δ), spherical equivalent, best corrected visual acuity (BCVA), and central corneal thickness (CCT) in both at short term (6 months) and long term (1st, 2nd, and 3rd year or more). The secondary objective was comparative evaluation of safety. For the meta-analysis, the RevMan5.3 software was used. A total of 48 RCTs were included. Compared to control, CXL was associated with improvement in Δ Kmax at 1 year (4 RCTs, mean difference [MD], -1.78 [-2.71, -0.86], P = 0.0002) and 2 and 3 years (1 RCT); ΔBCVA at 1 year (7 RCTs, -0.10 [-0.14, -0.06], P < 0.00001); and Δ CCT at 1 year (2 RCTs) and 3 years (1 RCT). Compared to conventional CXL (C-CXL), deterioration in Δ Kmax, ΔBCVA and endothelial cell density was seen at long term in the transepithelial CXL (TE-CXL, chemical enhancer). Up to 2 years, there was no difference between TE-CXL using iontophoresis (T-ionto) and C-CXL. At 2 and 4 years, C-CXL performed better compared to accelerated CXL (A-CXL) in terms of improving Kmax. Although CCT was higher in the A-CXL arm at 2 years, there was no difference at 4 years. While exploring heterogeneity among studies, selection of control eye (fellow eye of the same patient vs. eye of different patient) and baseline difference in Kmax were important sources of heterogeneity. CXL outperforms placebo/control in terms of enhancing Kmax and CCT, as well as slowing disease progression over time (till 3 years). T-ionto protocol, on the other hand, performed similarly to C-CXL protocol up to 2 years.

The outcome of corneal collagen cross-linking in progressive keratoconus: A 24-month follow-up

Purpose: The purpose of this study is to evaluate the effect of corneal collagen cross-linking on visual acuity and corneal parameters like keratometry and pachymetry. Methods: It was a retrospective, noncomparative, open-label study conducted at a tertiary eye care center. The eyes that underwent epithelium-off CXL (corneal collagen cross-linking) for progressive keratoconus between 2018 January and 2019 December, and who completed 24 months' post-CXL follow-up, were included in the study. Data regarding uncorrected and best spectacle-corrected visual acuity (UCVA and BSCVA) and corneal topography parameters, that is, K max, K min, and pachymetry at thinnest point, were collected prior to the procedure and 2 years after the procedure. Results: A total of 92 eyes of 65 patients were included in the study. There was a significant improvement of logMAR BCVA from preoperative 0.40 ± 0.24 to 0.28 ± 0.19 at 24 months after CXL (P &lt; 0.001). UCVA also increased from preoperative value of logMAR 0.70 ± 0.28 to 0.61 ± 0.26 2 years postoperatively (P &lt; 0.001). The number of eyes achieving BCVA of 0.3 logMAR or better significantly increased from 54 (58.7%) preoperatively to 72 (78.26%) at 2 years and it was found to be statistically significant (P &lt; 0.001). There was a significant improvement in K max 49.38 ± 3.70 to 49.07 ± 3.45 (P = 0.0005) and K min 45.65 ± 2.69 to 45.19 ± 2.46 (P &lt; 0.001) following CXL. Conclusion: Corneal collagen cross-linking is a treatment modality to stabilize and even improve UCVA in patients with mild-to-moderate keratoconus.

Safety and Efficacy of Repeated Corneal Collagen Crosslinking in Progressive Keratoconus.

Keratoconus is a progressive visually impairing disorder. Despite the beneficial effects of epithelial off-crosslinking (CXL) on the stabilization of keratoconus, progression may still occur. We report the efficacy and safety of a repeated CXL for significant progression of keratoconus after a single CXL procedure. This retrospective study includes patients diagnosed with progressive keratoconus who were previously treated with CXL and underwent repeated CXL. Demographic, clinical, and surgical data were retrieved and analyzed. Ten consecutive eyes of nine patients who developed progressive keratoconus after CXL were identified. The mean age at diagnosis of keratoconus was 20.2 ± 6.0 years. The post-repeated CXL follow-up period was 2.1 ± 1.3 years. The mean best corrected visual acuity (BCVA) remained stable throughout the follow-up period. The mean Kmax at baseline was 60.4 ± 3.6 D. Before the repeated CXL, Kmax progressed significantly ( P = 0.018) and was 62.2 ± 6.3 D, and at the last follow-up, the value decreased significantly ( P = 0.037) and was 60.3 ± 6.4 D. The mean minimal pachymetry was 464.0 ± 27.0 µ at base line. Before the repeated CXL, minimal pachymetry was significantly lower ( P = 0.018), and after the repeated CXL, the minimal pachymetry was stable ( P = 0.2). No intra- or postoperative complications were noted. Repeated CXL is a safe and effective treatment option when failure of the initial CXL is diagnosed, even in young patients. This procedure may prevent visual deterioration and a potential need for keratoplasty.

Accelerated corneal collagen cross-linking in progressive keratoconus: Five-year results and predictors of visual and topographic outcomes.

To analyze the 5-year results of accelerated corneal collagen crosslinking (CXL) for progressive keratoconus and identify preoperative characteristics predictive of visual and topographic outcomes. A prospective interventional case series. Nineteen eyes of 19 patients receiving accelerated CXL with settings of 18 mW/cm2 for 5 min were included. Clinical and topographic parameters were assessed. Linear regression and logistic regression were used to compare the R2 and odds ratio (OR), respectively, between baseline characteristics and postoperative outcomes. Corrected distance visual acuity (CDVA) remained stable from 0.28 ± 0.21 to 0.25 ± 0.18 logMAR (P = 0.486). The mean cylindrical refraction was stable (P = 0.119). The maximal keratometry (Kmax) decreased from 61.99 ± 10.37 to 59.25 ± 7.75 D (P < 0.001), flattening in the flattest and steepest meridians and mean keratometry were also observed (P ≤ 0.040). The mean anterior elevation at the apex reduced from 21.42 ± 16.69 to 18.53 ± 12.74 μm (P = 0.013) and changes in posterior elevation were non-significant (P = 0.629). Preoperative Kmax best predicted the postoperative change in Kmax (R2 = 0.55, P < 0.001) compared to the other baseline characteristics (P ≤ 0.028), whereas preoperative CDVA was the only significant predictor of postoperative change in CDVA (R2 = 0.41, P = 0.003). Accelerated CXL is less likely to fail in eyes with a steeper preoperative Kmax (OR = 0.74, P = 0.040) or greater posterior elevation at the apex (OR = 0.91, P = 0.042). Kmax significantly decreased following accelerated CXL. Eyes with worse preoperative CDVA and higher Kmax were more likely to have an improvement in visual acuity and corneal flattening.

Evaluation of macular function and morphology following accelerated collagen cross-linking in progressive keratoconus.

To assess any changes in macular function and morphology in patients with progressive keratoconus undergoing accelerated corneal cross-linking (CXL). This prospective case series included 9 eyes of 8 patients with progressive keratoconus undergoing CXL using a high intensity accelerated protocol (9 mW/cm2 for 14 min) with a total surface dose of 7.5 J/cm2. Visual acuity assessment, slit lamp biomicroscopy, dilated fundoscopy, corneal tomography, multifocal electroretinography (mfERG) and spectral domain optical coherence tomography scan were performed at baseline, 2 weeks and 6 weeks postoperatively. Uncorrected and corrected distance visual acuity did not change significantly at 2 weeks and 6 weeks following accelerated CXL compared to baseline. Retinal response density (RRD) of mfERG significantly decreased at 2 weeks postoperatively compared to baseline (p = 0.008) but did not differ from the baseline value at 6 weeks postoperatively in the fovea (ring 1) (p = 0.95). Similarly, P1 latency significantly decreased at 2 weeks (p = 0.04) but did not change at 6 weeks (p = 1.00) postoperatively compared to baseline in the fovea. No changes in RRD or P1 latency were observed in the retinal rings surrounding the fovea (rings 2 to 5). Central foveal thickness did not change at 2 weeks and 6 weeks postoperatively compared to baseline (p = 0.53 and p = 0.93, respectively). A short-term reversible decrease in macular electrical activity without any structural changes seems to occur after accelerated CXL in patients with progressive keratoconus. The return of macular response to the preoperative values shows the safety of the CXL protocol.

The mid-term effect of corneal collagen cross-linking for progressive keratoconus and the changes in rigid gas permeable contact lens fitting parameters

Objective: To investigate the effect of corneal collagen cross-linking (CXL) for progressive keratoconus and to evaluate changes in the parameters of rigid gas permeable contact lens (RGPCL) fitting after surgery. Methods: It was a prospective cohort study. Fifty-three eyes of 41 keratoconus patients received accelerated CXL in Qingdao Eye Hospital of Shandong First Medical University from May to December 2018. There were 31 males and 10 females, aged (20.46±4.15) years. According to the corneal thickness, de-epithelial CXL (33 eyes) or trans-epithelial CXL (20 eyes) was performed. The best spectacle-corrected visual acuity, refractive power and the thinnest corneal thickness at baseline and at 6 weeks were compared. Corneal topography was performed at baseline and at 6 weeks, 3, 6 and 12 months postoperatively. Rose K RGPCLs were used before and 6 weeks after surgery, and the fitting status was monitored until 12 months after surgery. The t test was performed to analyze the difference before and after the operation. Results: The best spectacle-corrected visual acuity, refractive power, and the thinnest corneal thickness were not significantly changed over 6 weeks of follow-up, but the Kf, Ks and Kmax values were significantly increased in all patients (all P<0.05). In the de-epithelial group, the Kmax values before the operation, at 3, 6 and 12 months after the operation were (55.00±5.51) diopters (D), (54.73±5.34) D, (54.58±6.15) D and (54.20±5.49) D, respectively, and the decrease at 12 months was significant [(0.80±2.05) D; t=2.25, P=0.001]. In the trans-epithelial group, the Kmax values were (59.43±8.98) D, (57.97±8.79) D, (58.19±8.37) D and (56.94±7.19) D at the four time points, respectively, and the decreases at 3, 6 and 12 months were all significant [(1.46±2.09) D, (1.25±1.82) D, (2.49±3.64) D; t=3.12, 3.06, 3.50; P=0.006, 0.006, 0.007]. The best RGPCL-corrected visual acuity, the diameter and the average diopters of RGPCLs showed no significant change in both groups. The RGPCL base curve decreased by 0.07 mm in the de-epithelial group and by 0.13 mm in the trans-epithelial group (both P<0.05). The design of edge lifting was used in 10 eyes postoperatively in the de-epithelial group compared with 8 eyes preoperatively, and in 4 eyes postopratively in the trans-epithelial group compared with 7 eyes preoperatively. The number of eyes using the toric peripheral design of the lens was increased to 3 compared with 2 preoperatively in the de-epithelial group and from 1 to 4 in the trans-epithelial group. The acceptance rate of RGPCL fitting in both groups increased at 6 and 12 months after surgery compared to 6 weeks after surgery. Conclusions: The corneal curvature became steep slightly at 6 weeks after CXL and gradually recovered and flattened. The Kmax in the trans-epithelial group decreased earlier and more than that in the de-epithelial group. The base curve of the RGPCLs was slightly reduced after 6 weeks, and the toric peripheral design was increasingly needed, but the requirement for the design of the lifted edge was different between the two groups. A good RGPCL fitting can be achieved within 1 year after CXL.

Trans-epithelial accelerated corneal collagen cross-linking for progressive keratoconus

Trans-epithelial accelerated corneal collagen cross-linking for progressive keratoconus

Tomographic changes after corneal collagen cross-linking for progressive keratoconus - one-year follow-up study

Introduction/Objective. The aim of this study was to evaluate the outcome of corneal collagen crosslinking (CXL) in patients with progressive keratoconus. Methods. This retrospective single-centered interventional study included 52 eyes of 41 patients who underwent epithelium-off CXL procedure at the age &gt; 18 years. Corneal tomography data, uncorrected, and best spectacle-corrected distant visual acuity (UDVA and CDVA, respectively) were analyzed at baseline and postoperatively over the initial 12-month period. In addition, the natural course of corneal tomographic changes was demonstrated at one, three, six, nine, and 12 months after the CXL procedure. Results. At one year, mean UDVA improved significantly from 0.15 ? 0.22 (0.3 min ? logMAR ? 0 max logMAR) at baseline to 0.06 ? 0.09 logarithm of minimum angle resolution (logMAR) (0.1 min logMAR ? 0 max logMAR) (p = 0.024). Mean CDVA was 0.45 ? 0.39 0.45 ? 0.39 logMAR (0.8 min logMAR ? 0 max logMAR) at baseline and 0.06 ? 0.13 logMAR (1 min logMAR ? 0 max logMAR) at one year (p = 0.039). Maximum keratometry showed a significant flattening of 1.36 D ? 1.53 D (p = 0.0032) at one year after CXL. Minimum keratometry significantly decreased with a mean change of 1.15 ? 1.20 (p = 0.011). Mean anterior and posterior best fit sphere (ABFS and PBFS, respectively) remained stable during the entire follow-up period. Mean reduction of corneal thickness after CXL was 47 ? 61 ?m (p = 0.003). At one year, 29 (56%) eyes showed K max regression, 22 (53%) showed stabilization, and one (2%) showed progression. Spearman correlation coefficients were calculated to assess the correlation between difference in preoperative corneal thickness (CT), in posterior elevation corneal thickness (PECT), and minimum corneal thickness, ?CT (PECT ? minCT) and radius difference ?r (r1-r2). Spearman rs &gt; 0.3 proved statistical significance and correlation. Conclusion. In our study, CXL effectively prevented progression of keratoconus in 98% of eyes at one year, while improving visual acuity. The effect of CXL can be evaluated at the earliest after six months; at that time, the stability of the corneal shape was provided by following the CXL procedure. The main limitation of this study is the small number of patients included.

Long-term study of topographic changes following pulsed accelerated corneal collagen cross-linking in progressive keratoconus

Purpose To evaluate long-term stability following pulsed accelerated cross-linking (CXL) in patients with progressive keratoconus by studying the changes in corneal topography. Patients and methods A retrospective study was conducted on patients with progressive grades 1–3 keratoconus who underwent epithelium-off pulsed-light accelerated corneal CXL (30 mW/cm2 for 8 min) using the KXL system (Avedro Inc.). Follow-up period was 12–36 months. Topographic changes including maximum keratometry (Kmax), minimum keratometry (Kmin), topographic cylinder, central corneal thickness, and thinnest point (TP) were recorded and analyzed. Results A total of 72 eyes of 38 patients were included. The 12-month results showed significant reduction in Kmin (P=0.038), central corneal thickness (P&lt;0.001), and TP (P&lt;0.001). At 24 and 36 months, there were no significant changes in corneal topography, except for reduction in TP (P=0.024 and 0.002, respectively). Conclusion Pulsed accelerated CXL is an effective long-term method of arresting keratoconus progression.

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

PurposeTo 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. MethodsIn 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. ResultsAfter 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). ConclusionAlthough 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.

Comparative 2-year outcomes of conventional and accelerated corneal collagen crosslinking in progressive keratoconus.

To compare the safety and efficacy of conventional versus accelerated (9 mW/cm2) corneal collagen crosslinking (CXL) in progressive keratoconus at the 2-year follow-up. In this prospective study, consecutive progressive keratoconus patients were randomized to receive either conventional CXL (CCXL) or accelerated CXL (ACXL; using hydroxypropyl methylcellulose-assisted riboflavin imbibition for 10min at 9 mW/cm2). Visual, refractive, keratometric, topographic, and aberrometric outcomes and stromal demarcation line depth (DLD) measurements were compared at the end of a 2-year follow-up. Thirty-two eyes from 32 patients in the CCXL and 27 eyes from 27 patients in the ACXL groups completed 2-year follow-up. At 2y post-CXL, both uncorrected and corrected visual acuities improved significantly in both groups. The improvements in keratometric readings, flattening rate (flattening of the maximum keratometry more than 1 D), 3 topographic indices, and vertical coma were significantly better in the CCXL group compared to the ACXL group (P<0.05). The DLD as measured by anterior segment optical coherence tomography or in vivo confocal microscopy was better detectable and significantly deeper in the CCXL group compared to the ACXL group. The deeper DLD was found to be significantly correlated with improvements in the mean keratometry measurements. Progression was noted in 11.1% of eyes in the ACXL group, whereas progression was not observed in any patient eye in the CCXL group. In this prospective randomized study, ACXL is less effective in halting the progression of keratoconus at a 2-year follow-up compared to CCXL.

Extreme corneal flattening following collagen crosslinking for progressive keratoconus.

To study the clinical, tomographic and densitometric features of eyes that showed >5 D of corneal flattening following collagen crosslinking (CXL) for progressive keratoconus and to identify preoperative predictive factors for such a response. This was a retrospective case control study of 548 eyes with progressive keratoconus which had undergone epithelium-off CXL (Dresden protocol) with a follow-up of 1 to 10 years. Eyes that showed ⩾5 D corneal flattening in maximum keratometry (Kmax) following CXL (group A) were compared with one eye of the remaining patients in the same cohort (group B). Changes in refraction and visual acuity, Kmax and thinnest pachymetry were compared between both groups. Univariate and multivariate regression analysis identified preoperative risk factors for unusual corneal flattening. Forty three eyes in group A were compared with 502 eyes in group B. At the time of maximum flattening, group A showed more flattening (-7.6 ± 3.2 D) and thinning (-53.7 ± 45.2 µ) than group B (-1.69 ± 2.9 D and -26.6 ± 36.7 µ, respectively). Multivariate analysis based on parameters suggested by a univariate regression analysis identified pre-op Kmax to be the most significant predictor of intense corneal flattening. A subgroup analysis of K-matched eyes revealed that the duration of time following CXL was a significant risk factor for extreme corneal flattening following CXL. An intense corneal flattening >5 D in Kmax was documented in 7.85% of a cohort of keratoconus patients who underwent CXL. High preoperative Kmax and the duration of time following CXL were significant predictors of this response which was accompanied by significant corneal thinning.

Comparative Results Between "Epi-Off" Conventional and Accelerated Corneal Collagen Crosslinking for Progressive Keratoconus in Pediatric Patients.

PurposeThe aim of our study was to evaluate the efficacy and safety of epi-off conventional and accelerated corneal collagen cross-linking in the treatment of progressive keratoconus in pediatric patients up to 4 years after treatment.Patients and methodsConventional (standard) CXL epi-off technique was performed in 37 eyes (S-CXL group) and accelerated CXL in 27 eyes (A-CXL group). Refraction, keratometry, cylindrical equivalent, spherical equivalent, slit lamp examination, pachymetry, corneal tomography, anterior segment ocular coherence tomography and visual acuity were performed up to 4 years.ResultsIn the S-CXL group: the flat K values decreased from 47.41±3.39 D to 45.36±3.62 D at 4 years (p=0.004); steep K decreased from 51.98±4.11 to 50.21±4.81 D at 4 years (p=0.0078); mean K decreased with 1.99 D at 4 years (p=0.009). In the A-CXL group: the flat K values decreased from 46.97±4.17 D to 44.97±4.24 D at 4 years (p=0.048); steep K decreased from 50.55±4.10 D to 48.75±4.17 D at 4 years (p=0.0287); mean K decreased from 48.79±3.86 D to 46.86±4.11 D at 4 years (p=0.0356). The preoperative mean UCVA in the S-CXL group was 0.8 ±0.23 logMar and improved during the follow-up reaching 0.65 ±0.24 logMar at 4 years (p=0.072). The baseline mean UCVA in A-CXL group was 0.77±0.25 logMar and increased during the follow-up to 0.63 ±0.25 logMar at 4 years (p=0.0039). A similar improvement of BCVA was observed during the follow-up.ConclusionEpi-off conventional and accelerated CXL are efficient procedures for progressive keratoconus in pediatric patients. Accelerated and conventional CXL were comparable at all time points and both represent viable options for the therapy of KC in these patients.

Clinical Results of Repeated Corneal Collagen Cross-linking in Progressive Keratoconus.

To evaluate the effectiveness of repeated corneal collagen cross-linking (CXL) in eyes with progressive keratoconus after primary CXL. Twelve eyes of 10 patients who underwent repeated CXL were included in this study. All cases were treated with a second CXL when disease progression was noted. Uncorrected visual acuity, best-corrected distance visual acuity, and corneal tomography were performed before and after repeated CXL. Common risk factors for progression were recorded. The mean age of the patients was 23.4 ± 6.2 (14-34) years. Eye rubbing was detected in 6 patients. The preoperative maximum keratometry (Kmax) value was >58.0 diopters (D) in 11 eyes (62.2 ± 4.9 D). Repeated CXL was performed with a mean interval of 19.3 months after the first CXL procedure when a disease progression of 2.3 D on average in Kmax was determined. With a mean follow-up of 36 months, Kmax regressed in 8 eyes, remained stable in 2 eyes, and progressed in 2 eyes after repeated CXL. Uncorrected and corrected visual acuity remained unchanged. No complications were observed. Repeated CXL seems to be effective in stabilizing keratoconus progression after failure of primary CXL. Patients should be followed up at least for 2 years after primary CXL.

Effectiveness and safety of accelerated (9 mW/cm2) corneal collagen cross-linking for progressive keratoconus: a 24-month follow-up.

To examine the effectiveness and safety of accelerated corneal collagen cross-linking (CXL) for keratoconus over a 24-month period and to explore potential prognostic factors for post-treatment visual outcome and progression. A retrospective, non-comparative, interventional case series. All patients who underwent accelerated epithelium-off CXL, using 9 mW/cm2 ultraviolet-A irradiation for 10 min, for progressive keratoconus in Sunderland Eye Infirmary, UK, between May 2014 and July 2016 were included. All patients completed 24 months' post-CXL follow-up. Significant post-CXL progression of keratoconus was defined as >1 D increase in Kmax from preoperative to 24-month visit. Fifty-two eyes of 48 patients were included. At 24-month post-CXL, there was a significant improvement in corrected-distance visual acuity (CDVA; -0.05 LogMAR; p = 0.026), Kmax (-1.68 D; p < 0.001), K1 (-0.64 D; p = 0.002) and Kmean (-0.50 D; p = 0.009). The proportion of eyes with CDVA ≥ 0.3 LogMAR significantly improved from 43 (82.7%) eyes preoperatively to 50 (96.2%) eyes at 24 months (p = 0.026). Corneal haze (12, 23.1%) was the only postoperative complication and no adverse event was noted. Final CDVA was associated with lower CDVA (p = 0.002) and greater Kmax (p = 0.018) at baseline. Post-CXL progression of keratoconus was associated with greater preoperative Kmax (p = 0.12) and Kmean (p = 0.11), though statistical significances were not achieved. Accelerated CXL (9 mW/cm2) serves as an effective and safe treatment for halting the progression of keratoconus and stabilising the vision over a 24-month period. Our observation suggests that accelerated CXL might be more effective in stabilising keratoconus of milder severity; however further larger studies are required to elucidate this finding.

Safety and Efficacy of Corneal Cross-linking in Pediatric Patients with Keratoconus and Vernal Keratoconjunctivitis.

PURPOSE:The purpose of the study is to determine the safety and efficacy of corneal collagen cross-linking for keratoconus in pediatric patients with and without vernal keratoconjunctivitis (VKC).METHODS:This is a retrospective analysis of 89 eyes of 58 patients <18 years of age that underwent corneal collagen cross-linking for progressive keratoconus; inclusion criteria included a minimum of 2-year follow-up after cross-linking. The main outcomes measures included keratometry, pachymetry, vision, and complications following epithelial-off cross-linking with the Dresden protocol.RESULTS:VKC patients were more likely to be male; 81.6% of the non-VKC patients and 96.3% of VKC patients were male (P = 0.038). Comparing pretreatment to the 2-year follow-up, there was no statistically significant change in the mean steep or flat keratometry, corneal thickness, and uncorrected visual acuity or best spectacle-corrected visual acuity in either group. There were no statistically significant differences in the mean visual, keratometric, or adverse event outcomes between the two groups. The proportion exhibiting progression of ectasia at 2 years was 18.5% in the VKC group and 16.7% in the non-VKC group (P = 0.83).CONCLUSIONS:Cross-linking appears to be as safe and effective in pediatric patients with vernal keratoconjunctivits as in those without, with similar outcomes, adverse events, and progression of keratoconus after treatment. The proportion of patients exhibiting progression appears to be higher in pediatric patients than adults, and there is an association between male sex and diagnosis of VKC.