Transepithelial Corneal Cross-linking Research Articles

Randomized clinical trial comparing customized corneal crosslinking: epi-on in high oxygen and epi-off in room air for keratoconus.

To compare clinical outcomes of customized transepithelial (epi-on) corneal crosslinking (CXL) in high oxygen and customized CXL with epithelial removal (epi-off) in room air for keratoconus (KC). Umeå University Hospital, Umeå, Sweden. Prospective, randomized, single-masked, intraindividually comparing study. 32 participants with bilateral progressive KC were treated with bilateral customized topography-guided CXL, 30 mW/cm 2 ; 7.2 to 15 J/cm 2 and were randomized to epi-on in one eye (32 eyes) and epi-off in the fellow eye (32 eyes). Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), maximal keratometry (Kmax), subjective ocular discomfort, low-contrast visual acuities (LCVAs) at 10% and 2.5% contrast, ocular and anterior corneal wavefront aberrations, manifest refractive spherical equivalent, endothelial cell count (ECC), and adverse events were assessed through 24 months. Both treatments showed improvements at 24 months in UDVA; -0.16 ± 0.24 ( P < .001) and -0.13 ± 0.20 logMAR ( P = .006), respectively, CDVA; -0.10 ± 0.11 ( P < .001) and -0.10 ± 0.12 ( P = .001), Kmax; -1.74 ± 1.31 ( P < .001) and -1.72 ± 1.36 D ( P < .001). LCVA 10% improved for both protocols ( P < .001), but LCVA 2.5% improved for epi-on CXL only ( P = .001). ECC was unaltered, and no adverse events occurred. The epi-on eyes had significantly less discomfort symptoms during the whole first week posttreatment ( P < .05). High-oxygen customized epi-on CXL is a viable alternative to room air customized epi-off CXL, with faster improvements in CDVA and LCVA and less early ocular discomfort.

Real-time monitoring of riboflavin concentration using different clinically available ophthalmic formulations for epi-off and epi-on corneal cross-linking.

To assess the feasibility of theranostics to determine the riboflavin concentration in the cornea using clinically available ophthalmic formulations during epithelium-off (epi-off) and transepithelial (epi-on) corneal cross-linking procedures. Thirty-two eye bank human donor corneas were equally randomized in eight groups; groups 1 to 3 and groups 4 to 8 underwent epi-off and epi-on delivery of riboflavin respectively. Riboflavin ophthalmic solutions were applied onto the cornea according to the manufacturers' instructions. The amount of riboflavin into the cornea was estimated, at preset time intervals during imbibition time, using theranostic UV-A device (C4V CHROMO4VIS, Regensight srl, Italy) and expressed as riboflavin score (d.u.). Measurements of corneal riboflavin concentration (expressed as µg/cm3) were also performed by spectroscopy absorbance technique (AvaLight-DH-S-BAL, Avantes) for external validation of theranostic measurements. At the end of imbibition time in epi-off delivery protocols, the average riboflavin score ranged from 0.77 ± 0.38 (the average corneal riboflavin concentration was 213 ± 190µg/cm3) to 1.79 ± 0.07 (554 ± 103µg/cm3). In epi-on delivery protocols, the average riboflavin score ranged from 0.17 ± 0.01 to 0.67 ± 0.19 (corneal riboflavin concentration ranged from 6 ± 5µg/cm3 to 122 ± 39µg/cm3) at the end of imbibition time. A statistically significant linear correlation (P ≤ 0.05) was found between the theranostic and spectrophotometry measurements in all groups. Real-time theranostic imaging provided an accurate strategy for assessing permeation of riboflavin into the human cornea during the imbibition phase of corneal cross-linking, regardless of delivery protocol. A large variability in corneal riboflavin concentration exists between clinically available ophthalmic formulations both in epi-off and epi-on delivery protocols.

Clinical and Morphological in Vivo Confocal Microscopy Findings following a Modified Biphasic Higher Fluence Transepithelial Corneal Crosslinking

Purpose: To compare the refractive efficacy and morphological changes in the cornea following a novel biphasic higher fluence transepithelial corneal crosslinking (BI-TE-CXL) and transepithelial corneal crosslinking (TE-CXL) in adults keratoconus. Methods: Patients with progressive keratoconus who required corneal crosslinking were assigned to the BI-TE-CXL group (32 eyes, phase 1: 7.2 J/cm2 for 5 min and 20 s of pulsed-light exposure, KXL, Glaukos-Avedro; phase 2: 3.6 J/cm2 for 6 min and 40 s of continuous light exposure at the front curvature apex with a 6 mm diameter light spot, UVX-2000, IROC) or the TE-CXL group (32 eyes, uniform 7.2 J/cm2 for 5 min and 20 s of pulsed-light exposure, KXL, Glaukos-Avedro). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal fluorescein staining (CFS), corneal topography, anterior segment optical coherence tomography (AS-OCT), and in vivo corneal confocal microscopy (IVCM) were performed 3, 6, 12 and 24 months after surgery. Results: The CFS scores in the BI-TE-CXL group were significantly higher than those in the TE-CXL group on the first two days after surgery (p < 0.001). The Kmax (at 12 and 24 months) and CDVA (logMAR) were significantly lower in the BI-TE-CXL group than those in the TE-CXL group (p < 0.05). The corneal demarcation line under AS-OCT was visible in 81.3% of patients in the BI-TE-CXL group and 15.6% in the TE-CXL group. The depth of the demarcation line under IVCM was significantly deeper in the BI-TE-CXL group (248.3 ± 25.0 μm) than that of the TE-CXL group (136.5 ± 15.6 μm) in the central cornea (p < 0.001). The cross-linked collagen structures in the central cornea were still present after 12 months in the BI-TE-CXL group. No significant difference in sub-basal nerve density between the two groups (p > 0.05). Conclusions: Following BI-TE-CXL, CDVA was significantly improved, accompanied by deeper demarcation line depth and persistent crosslinked structures in the central corneal stroma.

Five-year results of iontophoresis-assisted transepithelial corneal cross-linking for keratoconus

PurposeTo assess long-term efficacy and safety of iontophoresis-assisted transepithelial corneal cross-linking (I-CXL) for keratoconus.Patients and methodsTwenty-seven eyes of 21 patients (15 M, 6F) affected by progressive keratoconus were evaluated. All subjects were treated with iontophoresis-assisted transepithelial CXL. The patients were examined at baseline and each 6 months after the CXL procedure. Only subjects who completed the follow-up of 5 years were considered in this study. The main outcome measures were uncorrected visual acuity (UCVA), corrected visual acuity (CDVA), corneal transparency and corneal parameters such as K-max, central corneal thickness (CCT) and at the thinnest point, and high-order ocular aberrations (HOAs). The ABCD system was used to determine the progression and re-progression of ectasia.SettingOphthalmology Clinic, University Hospital of Messina, Messina, Italy.ResultsAt 5 years, significant improvements of UCVA from 0.53 ± 0.33 logMAR to 0.4 ± 0.33 logMAR (p = 0.001) and HOAs (p = 0.01) were registered. No significant changes of CDVA (p = 0.4), K-max (p = 0.75), CCT (p = 0.5) were observed at the end of follow-up period.The ABCD system showed re-progression in 25.9% of eyes after 5 years. No adverse events such as corneal opacities and infections were reported.ConclusionsIontophoresis-assisted transepithelial CXL resulted to be safe and effective to stabilize progressive keratoconus in adults at a long-term follow-up.

Transepithelial corneal crosslinking with oxygen enhancement and pulsed light for progressive ectasia: one-year results.

To evaluate the efficacy and safety of transepithelial accelerated crosslinking (TE-ACXL) using pulsed light and supplemental oxygen. Thirty eyes of 30 consecutive patients with progressive keratoconus or post-LASIK ectasia were enrolled in a prospective non-comparative study conducted at the Magrabi Eye Center (Jeddah, Saudi Arabia). All eyes underwent TE-ACXL with supplemental oxygen. Primary outcome measures were the mean change in corrected distance visual acuity (CDVA) (logMAR) and maximum keratometry (max K) from preoperatively to 12months postoperatively. Secondary outcome measures included change in manifest refractive spherical equivalent (MRSE), refractive cylinder, keratometry, symmetry index (SI), center-surrounding index (CSI) and ectasia index (EI) of the anterior and posterior corneal surfaces, corneal and epithelial thickness at corneal vertex and thinnest location, corneal densitometry, corneal high order aberrations (HOA) and endothelial cell density (ECD). Mean age was 29.6 ± 8.2years. At 1year, the follow up rate was 93.3%. CDVA improved statistically significantly at 12months (p = 0.027). Measures of corneal keratometry or pachymetry did not change significantly (p < 0.05). Postoperatively, a demarcation line was documented in 78.6% eyes at 1month, and in 12 (42.9%) eyes at 12months. The mean depth of the demarcation line was 341.9 ± 49.4µm. Corneal densitometry increased significantly at 1- and 3-months (p < 0.05) and returned to normal levels at 6- and 12-months postoperatively. TE-ACXL with oxygen supplement is effective at halting the progression of corneal ectasia for at least 1year and can be a refractive neutral procedure.

Long-term changes in crystalline lens transparency after accelerated transepithelial corneal cross-linking in patients with keratoconus.

To investigate the long-term clinical outcomes and changes in crystalline lens transparency after accelerated (45 mW/cm2) transepithelial corneal cross-linking (ATE-CXL) using the Pentacam imaging system in patients with progressive keratoconus. The study prospectively included 44 keratoconus eyes of 40 patients (mean age: 24.39 ± 5.61 years) who underwent ATE-CXL. The examinations, including assessment of uncorrected distance visual acuity, corrected distance visual acuity, corneal topography, and corneal endothelial cell density count, were conducted preoperatively and 1 month, 3 months, 6 months, 1 year, and 5 years postoperatively. Measurement of crystalline lens density using Pentacam images was also performed pre- and postoperatively. All surgeries were uneventful with no postoperative complications. All keratometry values and corneal thickness remained stable during the 5-year follow-up period (all p > 0.05). There were no significant differences in corneal endothelial cell density count, visual acuity, and anterior average lens density in the 0.5-, 1.0-, and 1.5-mm depth zones during the 5-year follow-up period compared with the preoperative values (all p > 0.05). The results of this study suggest that ATE-CXL at 45 mW/cm2 is safe and effective for the treatment of progressive keratoconus in terms of both crystalline lens density and endothelial cell density.

Norepinephrine as an Enhancer Promoting Corneal Penetration of Riboflavin for Transepithelial Corneal Crosslinking.

Previously, we found norepinephrine (NE) could affect the corneal epithelial integrity, herein we investigated the feasibility and safety of NE serving as a chemical enhancer to promote corneal penetration of riboflavin during transepithelial corneal crosslinking (CXL). The dosage of NE that could promote riboflavin diffusion through the healthy epithelial barrier without inducing epithelial damage in C57BL/6 mice was determined. The safety of NE treatment was confirmed by morphological and histological examinations of the whole cornea. The efficacy of NE in promoting riboflavin penetration was verified by slit lamp and scanning electron microscope (SEM), and corneal biomechanical measurement after CXL. To better fit the clinical scenario, increased NE dosage and shortened riboflavin infiltration time were further evaluated. The lowest dosage of NE (1 mg/mL) that facilitated transepithelial riboflavin permeation was 2 µL. No visible corneal structure alteration was observed after NE treatment. SEM indicated dissociation of intercellular junctions among corneal epithelial cells. Homogenous distribution of riboflavin throughout corneal stroma was observed. NE-treated corneas reached comparable biomechanical properties after CXL, including stress-relaxation curve and elastic modulus, with corneas treated with the commercially available transepithelial drug Peschke TE. To better fit the clinical scenario, increasing NE up to 5.5 µL helped riboflavin infiltrate the corneal stroma within 30 minutes. After CXL with 9 mW/cm2 ultraviolet-A (UVA) for 2.5 minutes, the cornea showed significantly enhanced corneal biomechanical properties with undisturbed corneal endothelium. NE serves as an effective enhancer in increasing riboflavin diffusion with limited impairment on corneal epithelium and has great potential for clinical application. NE serves as an effective enhancer for riboflavin penetration and clinical transepithelial CXL.

Techniques and outcomes of transepithelial corneal crosslinking for the treatment of keratoconus: A current update

Techniques and outcomes of transepithelial corneal crosslinking for the treatment of keratoconus: A current update

Sequential intracorneal ring segment implantation followed by transepithelial phototherapeutic keratectomy and corneal cross-linking

To evaluate the safety and visual outcomes of intrastromal corneal ring segment (ICRS) implantation followed by transepithelial phototherapeutic keratectomy (te-PTK) and corneal cross-linking (CXL) in patients with mild keratoconus. Patients with mildkeratoconusand contact lens intolerance who underwent sequential ICRS implantation followed by phototherapeutic keratectomy and corneal CXL between April 2015 and July 2018 were retrospectively included in the study. Refractive and visual outcomes, satisfaction questionnaire and complications were recorded at the last follow-up (mean 9.5 months postoperatively). Twenty eyes of 17 patients were enrolled, including 5 women and 15 men. The mean time between the two procedures was 16 months. Based on values before the first procedure and 9.5 months after the second procedure, significant improvements were noted in uncorrected distance visual acuity (UDVA) (0.80±0.35 logMAR vs. 0.46±0.38 logMAR), corrected distance visual acuity (CDVA) (0.38±0.23 logMAR vs. 0.13±0.16 logMAR), maximal K (56.11±4 diopters [D] vs. 50.6±3.56 D), mean K (51.87±3.43 D vs. 48.45±2.91 D), cylinder (7.99±3.94 D vs. 4.23±3.49 D), and spherical equivalent (-3.84±3.36 D vs. -0.99±2.15 D) (P<0.01). Among the outcomes, we noted 5 (25%) superficial corneal scarring (haze); 75% of eyes gained>=1 logMAR line of CDVA. In all, 94.5% of patients reported that they were satisfied with their outcomes. Combining ICRS implantation followed by te-PTK and corneal CXL appears to be a safe and effective approach for improving visual outcomes and quality of life in keratoconus patients.

Transepithelial Corneal Cross-linking with Supplemental Oxygen in Keratoconus Treatment - Corneal Stromal Demarcation Line and Safety

Purpose: To evaluate the corneal stromal demarcation line and safety of transepithelial corneal cross-linking (CXL) with supplemental oxygen in progressive keratoconus treatment. Methods: This is a retrospective review of 25 patients with progressive keratoconus who underwent epithelial-on CXL with supplemental oxygen from December 2019 to February 2022. Outcomes measured include corneal stromal demarcation line depth, volume of cornea treated, endothelial cell count, best-corrected visual acuity, keratometric parameters and post-treatment adverse events. Results: 25 eyes of 25 patients were included and mean age was 28.3 years. Mean follow-up period was 11.5 ± 1.39 months. Pre-operatively, mean ± standard deviation (SD) of K1, K2, Kmax and minimal corneal thickness were 45.9D ± 3.79D, 50.2D ± 4.83D, 57.5D ± 6.98D and 482.3um ± 36.8um respectively. There is no significant difference between pre and post-treatment corneal topographic parameters. There was improvement in BCVA post-treatment. The mean post-treatment corneal stromal demarcation line depth was 367.3 ± 89.8um. The volume of treated cornea including the central corneal epithelial thickness was 73.3 ± 4.39%. There was no reduction in endothelial cell count (ECC) post-procedure (pre-treatment mean ECC±SD: 2695.4 ± 224.5 cells/mm2, post-treatment ECC 2730.1 ± 252.0 cells/mm2, p-value = 0.33). Post-treatment corneal haze was mild and seen in 8 patients postoperatively. One patient developed a non-visual axis involving stromal infiltrate that resolved with topical broad-spectrum anti-microbials. Conclusion: Trans-epithelial CXL with supplemental oxygen for keratoconus treatment achieved comparable corneal stromal demarcation line depth comparable to that of conventional epithelial-off corneal cross-linking and had a similar safety profile.

Ovalbumin-Induced Allergic Inflammation Diminishes Cross-Linked Collagen Structures in an Experimental Rabbit Model of Corneal Cross-Linking.

BackgroundAllergic conjunctivitis (AC) is one of the reported potential risk factors of progression in keratoconus patients after corneal cross-linking surgery; however, the causal relationship is still inconclusive. Recent studies have indicated that various inflammatory cytokines play a vital role in the development of primary keratoconus. It is still unclear whether these inflammatory mediators also trigger CXL failures. This study aimed to investigate the impact of AC on the rabbit corneas after trans-epithelial corneal cross-linking (TCXL).MethodsA total of six rabbits were kept untreated as the normal control (NC) group. A total of 18 rabbits were treated by TCXL and divided into three groups (six in each group), namely, no treatment (TCXL group); induction of AC (TCXL + AC group); and induction of AC plus topical prednisolone acetate (TCXL + AC + PA group), according to additional treatment. AC was induced by topical application of ovalbumin after intraperitoneal pre-sensitization with ovalbumin. Rabbits were evaluated by slit lamp, in vivo laser scanning confocal microscopy, anterior segment optical coherence tomography, and measurement of corneal biomechanics. The cornea specimens were collected for the transmission electron microscope, the collagenase I digestion test, and PCR assay for TNF-α, IL-6, IL-1β, matrix metalloproteinase 9 (MMP-9), lysyl oxidase (LOX), and tissue inhibitor of metalloproteinases 1 (TIMP-1) on the day (D) 28.ResultsOn D28, the TNF-α, IL-6, IL-1β, MMP-9, and LOX levels were significantly increased while the TIMP-1 was decreased in the TCXL + AC group when compared with the TCXL and TCXL + AC + PA groups. In vivo confocal microscopy revealed that at a depth of 150–210 μm, a trabecular patterned hyperdense structure surrounded by elongated needle-like processes could be observed in the TCXL and TCXL + AC + PA groups, but hardly seen in the TCXL + AC group. The demarcation lines were indistinct and blurred in the TCXL + AC group. An electron microscope demonstrated less interlacing fibril lamellae and higher interfibrillar spacing in the TCXL + AC group. The stability of corneal biomechanics and resistance to collagenase were decreased in the TCXL + AC group.ConclusionThe corneal microstructures induced by TCXL and biomechanical stability were diminished in rabbits with AC but could be maintained by topical anti-inflammatory treatment. Our results supported the causal relationship between altered cytokine profiles and corneal microstructure after primary corneal cross-linking.

Engineering Hibiscus‐Like Riboflavin/ZIF‐8 Microsphere Composites to Enhance Transepithelial Corneal Cross‐Linking (Adv. Mater. 21/2022)

Corneal Cross-Linking ln article number 2109865, Rongrong Gao, Jinhai Huang, Xingtao Zhou, and co-workers report novel engineering of hydrangea-like RF@ZIF-8 microsphere composites with outstanding trans-epithelial corneal cross-linking (TE-CXL) efficacy, suggesting a promising nanomedicine strategy. The described use of the metal–organic framework as carrier to transfer hydrophilic negatively charged Riboflavin-5-phosphate (RF) molecules to the hydrophobic corneal epithelium, with excellent TE-CXL efficacy, may open up a new field of CXL.

Engineering Hibiscus-Like Riboflavin/ZIF-8 Microsphere Composites to Enhance Transepithelial Corneal Cross-Linking.

Riboflavin-5-phosphate (RF) is the most commonly used photosensitizer in corneal cross-linking (CXL), but its hydrophilicity and negative charge limit its penetration through the corneal epithelium into the stroma. To enhance the corneal permeability of RF and promote its efficacy in the treatment of keratoconus, novel hibiscus-like RF@ZIF-8 microsphere composites [6RF@ZIF-8 NF (nanoflake)] are prepared using ZIF-8 nanomaterials as carriers, which are characterized by their hydrophobicity, positive potential, biocompatibility, high loading capacities, and large surface areas. Both hematoxylin and eosin endothelial staining and TUNEL assays demonstrate excellent biocompatibility of 6RF@ZIF-8 NF. In in vivo studies, the 6RF@ZIF-8 NF displayed excellent corneal permeation, and outstanding transepithelial CXL (TE-CXL) efficacy, slightly better than the conventional CXL protocol. Furthermore, the special hibiscus-like structures of 6RF@ZIF-8 NF meant that it has better TE-CXL efficacy than that of 6RF@ZIF-8 NP (nanoparticles) due to the larger contact area with the epithelium and the shorter RF release passage. These results suggest that the 6RF@ZIF-8 NF are promising for transepithelial corneal cross-linking, avoiding the need for epithelial debridement.

Comparison of contact lens-assisted and transepithelial corneal crosslinking with standard epithelium-off crosslinking for progressive keratoconus: 24-month clinical results.

To compare the outcomes of contact lens-assisted corneal crosslinking (CACXL) and transepithelial CXL (TECXL) with standard epithelium-off (epi-off) CXL for progressive keratoconus. Advanced Eye Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Retrospective, comparative study. Patients with progressive keratoconus undergoing CXL with a minimum follow-up of 24 months were included. CACXL and TECXL were performed in patients with epithelium-on minimal pachymetry between 350 μm and 450 μm. The main outcome measures included change in maximum keratometry (Kmax), corrected distance visual acuity (CDVA), and efficacy in halting progression (increase in Kmax ≥1 diopter [D]). Standard epi-off CXL, CACXL, and TECXL were performed in 34, 14, and 10 eyes, respectively. Baseline Kmax and CDVA were comparable for all groups. Kmax reduced significantly by -2.83 ± 3.35 D, -3.18 ± 2.74 D, and -2.02 ± 1.66 D in the standard epi-off CXL (P < .01), CACXL (P = .001), and TECXL (P = .004) groups, respectively; the reduction was comparable for all groups (P = .63). CDVA improved by -0.14 ± 0.24, -0.04 ± 0.19, and -0.12 ± 0.17 logMAR in the standard epi-off CXL (P = .006), CACXL (P = .42), and TECXL (P = .05) groups, respectively; the reduction was comparable for all groups (P = .46). Progression was documented in 2 eyes (6%) in the standard epi-off CXL group and in 0 eyes of the CACXL and TECXL groups (P = .61). CACXL and TECXL were comparable with the standard epi-off CXL for progressive keratoconus.

Three-year results of accelerated transepithelial cross-linking (30 mW/cm2 × 3 min) for keratoconus: a prospective study

ObjectiveTo assess the long-term efficacy and safety of accelerated transepithelial corneal cross-linking (ATE-CXL) with 30 mW/cm2 × 3 min.Methods and AnalysisThirty-four eyes of 23 patients with progressive keratoconus (KCN) recruited...

Predictive factors of the accelerated transepithelial corneal cross-linking outcomes in keratoconus

BackgroundThis study aimed to evaluate the clinical outcomes and assess preoperative characteristics that may predict outcomes in keratoconus 1 year after accelerated transepithelial corneal cross-linking (ATE-CXL).MethodsThis prospective study included 93 eyes of 84 consecutive keratoconus patients with 1-year follow-up after ATE-CXL. Preoperative characteristics included corneal astigmatism, anterior chamber depth, anterior chamber volume, radius of curvature, posterior elevation, central corneal thickness (CCT), thinnest corneal thickness, steepest meridian keratometry, flattest meridian keratometry, and the maximum keratometry (Kmax). Data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. The patient eyes were grouped into 3 subgroups according to CCT and Kmax values to observe the changes of keratoconus progression.ResultsAll patients were successfully operated without complications at any follow-up time point. Mean changes of Kmax from baseline at 6 and 12 months were − 0.60 ± 2.21 D (P = 0.011) and − 0.36 ± 1.58 D (P = 0.030), respectively. Eyes with a thinner CCT and higher Kmax values exhibited a tendency for topographic flattening of ≥1.0 D (P = 0.003; P = 0.003). In the subgroup comparison, the Kmax values decreased significantly at 6 and 12 months after ATE-CXL in the group with CCT ≤ 450 μm (P = 0.018 and P = 0.045); the Kmax values of the group with Kmax > 65.0 D decreased significantly at 6 months postoperatively (P = 0.025).ConclusionATE-CXL is a safe and effective treatment for keratoconus patients. Patients with thinner CCT and higher Kmax values are more likely to benefit from ATE-CXL.

Repeatability and comparison of Corvis ST parameters before and after accelerated transepithelial corneal cross-linking in keratoconus eyes

AIM: To evaluate the repeatability and comparison of corneal visualization scheimpflug technology (Corvis ST) parameters in keratoconus eyes before and after accelerated transepithelial corneal cross-linking (ATE-CXL). METHODS: Thirty eyes of 30 progressive keratoconus patients were included in the prospective study. Three repeated corneal biomechanical measurements were performed preoperatively and one month postoperatively by Corvis ST. The interclass correlation coefficient (ICC) and 95% confidence interval (CI), Cronbach’ α, repeatability coefficient (RC), and coefficient of variation (CV) were used to evaluate the repeatability of Corvis ST parameters. Paired t test or Wilcoxon rank test was used to evaluate the differences between preoperative and postoperative data. RESULTS: At preoperative, 26 of 39 (66.67%) parameters showed good to excellent repeatability, 6 (15.38%) showed moderate, and 7 (17.95%) showed poor repeatability. Similarly, 34 (87.18%) parameters showed good to excellent repeatability, 3 (7.69%) showed moderate, and 2 (5.13%) showed poor repeatability after ATE-CXL. After ATE-CXL 1mo, the intraocular pressure (IOP), biomechanical corrected IOP (bIOP), first applanation time (A1T), Radius, deformation amplitude at the first applanation (A1DA), deflection length at the maximum deformation (HCDLL) and stiffness parameter at first applanation (SP A1) parameters increased, while the steep keratometry (Ks), flat keratometry (Kf), mean keratometry (Kmean), second applanation time (A2T), DA Ratio Max (2 mm) and integrated radius parameters decreased (all P&lt;0.05). CONCLUSION: The repeatability of the Corvis ST parameters before and 1mo ATE-CXL follow up were both acceptable, and the corneal stiffness was improved after 1-month ATE-CXL.

Long-Term Follow-Up of Accelerated Transepithelial Corneal Crosslinking for Post-LASIK Ectasia: A Pilot Prospective Observational Study.

Background: Keratectasia after corneal refractive surgery is a rare but serious postoperative complication, and reports on accelerated transepithelial corneal crosslinking (ATE-CXL)-based treatment of patients with post-laser-assisted in situ keratomileusis (LASIK) ectasia are limited. Therefore, this study evaluated the long-term efficacy and safety of ATE-CXL for progressive post-LASIK ectasia. Methods: This prospective observational study was conducted at the Eye and ENT Hospital, Fudan University, Shanghai, China, and 25 eyes from 25 patients with post-LASIK ectasia undergoing ATE-CXL were examined. Clinical examinations were conducted preoperatively and postoperatively to assess parameters such as manifest refraction, corrected distance visual acuity (CDVA), endothelial cell density; keratometry, corneal thickness, posterior elevation and topometric indices were measured using Pentacam; sectoral pachymetry and epithelial thickness were evaluated using optical coherence tomography. A paired t-test, Wilcoxon rank-sum test, Kruskal-Wallis test, and repeated measures analysis of variance were used for statistical analysis. Results: Participants were examined for an average of 46 months. No severe complications occurred during or after ATE-CXL. CDVA improved from 0.25 ± 0.31 preoperatively to 0.15 ± 0.17 postoperatively (p = 0.011). Maximum keratometry decreased from 55.20 ± 8.33 D to 54.40 ± 7.98 D, with no statistical significance (p = 0.074), and the central corneal thickness increased from 414.92 ± 40.96 μm to 420.28 ± 44.78 μm (p = 0.047) at the final follow-up. Posterior elevation, pachymetry, and epithelial thickness remained stable (p > 0.05) throughout the follow-up. No significant differences were noted in topometric indices, except the central keratoconus index, which decreased significantly (p < 0.001) at the final follow-up. Conclusion: Improvements in CDVA and stabilization in corneal keratometry and posterior elevation after ATE-CXL were noted at the 46-months follow-up, demonstrating that ATE-CXL is a safe and effective treatment for progressive post-LASIK ectasia.

Irregular Astigmatism Induced by Irregular Epithelial Remodeling After Conductive Keratoplasty and Transepithelial CXL

PURPOSE: To describe the evaluation and management of irregular astigmatism induced by persistent irregular epithelial remodeling in the absence of persistent underlying stromal curvature irregularity following photorefractive keratectomy (PRK) re-treatment after remote myopic laser in situ keratomileusis (LASIK) with subsequent conductive keratoplasty (CK) and transepithelial corneal cross-linking (CXL). METHODS: Case report. RESULTS: A 41-year-old woman presented for evaluation 1 year after developing blurred vision. She had irregular astigmatism in her right eye following PRK re-treatment for regression after remote myopic LASIK, with a subsequent combined CK and modified transepithelial CXL procedure 1 month after PRK. Scheimpflug tomography demonstrated a post-myopic ablation pattern with an apparent decentered optical zone. Anterior segment optical coherence tomography (AS-OCT) revealed an irregular epithelial thickness pattern, with an asymmetric focal region of epithelial thickness para-centrally temporally. Superficial keratectomy was performed. Following the procedure, the patient's uncorrected distance visual acuity improved by two lines to 20/20, and her subjective blur symptoms resolved and remained stable during 12 months of follow-up. Repeat AS-OCT demonstrated a more uniform epithelial thickness pattern. Scheimpflug tomography showed resolution of the optical zone decentration, confirming that the irregular epithelial remodeling caused the curvature irregularity, and the underlying stromal curvature was not significantly irregular at the time of treatment. CONCLUSIONS: Although uncommon, irregular epithelial remodeling can occur without permanent underlying stromal irregularity. The authors surmise that a temporary induced stromal curvature change from combined CK and transepithelial CXL regressed, but epithelial remodeling did not return to the anticipated regular postoperative pattern. This phenomenon would be unrecognizable in the absence of epithelial mapping and highlights the need for thorough evaluation and targeted management strategies to improve epithelial regularization. [ Journal of Refractive Surgery Case Reports . 2021;1(2):e23–e30.]

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.