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Purpose: To compare haze and refractive outcomes in patients undergoing combined accelerated corneal cross-linking (A-CXL) and selective wavefront-guided transepithelial photorefractive keratectomy (WG-transPRK) without mitomycin C (MMC) versus those undergoing A-CXL., Methods: This prospective study analyzed 95 eyes (86 patients) with progressive keratoconus from October 2018 to October 2022. The first group underwent CXL combined with corneal or ocular WG-transPRK (CXL+PRK, n = 52), targeting higher order aberrations (HOAs). The second underwent CXL only (n = 43), both following the same accelerated CXL protocol without MMC on the SCHWIND Amaris laser platform (SCHWIND eye-tech-solutions). Baseline and postoperative evaluations (1, 3, 6, and 12 months) included uncorrected (UDVA) and corrected (CDVA) distance visual acuity, manifest refraction, tomography, corneal HOAs, and optical coherence tomography (OCT) scans. A patented machine learning algorithm objectively detected and quantified stromal haze on OCT scans in grayscale units., Results: In both groups, anterior corneal haze reflectivity and subepithelial haze peaked at 3 months postoperatively, then progressively decreased at 6 and 12 months. Haze did not differ between groups at any time point. By 12 months, CDVA increased by 2.5 lines in the CXL+PRK group ( P < .001) and by 0.7 lines in the CXL group ( P = .10), and maximum keratometry decreased from 51.70 ± 5.10 to 47.90 ± 7.90 diopters (D) (CXL+PRK group) ( P < .001) and from 51.20 ± 5.10 to 50.30 ± 4.60 D (CXL group) ( P = .004). Corneal HOAs decreased in both groups but more in the CXL+PRK group., Conclusions: Combining CXL with WG-transPRK without MMC does not result in increased haze when compared to A-CXL alone. This combined approach achieves greater improvements in visual, topographic, and aberrometric parameters. [ J Refract Surg . 2024;40(9):e583-e594.] .

Purpose: To compare the effects of corneal allogenic intrastromal ring segment (CAIRS) implantation on topographical measurements and visual outcomes of patients with keratoconus with and without corneal cross-linking (CXL) prior to the time of implantation., Methods: Sixty-seven eyes with corneal allograft intrastromal ring segment implantation (KeraNatural; Lions VisionGift) due to advanced keratoconus were included in the study. Thirty-seven eyes had no CXL and 30 eyes had had CXL before being referred to the authors. The changes in spherical equivalent (SE), uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), steep keratometry (K1), flat keratometry (K2), mean keratometry (Kmean), maximum keratometry (Kmax), and thinnest pachymetry were retrospectively analyzed 6 months after the implantation., Results: The median age was 29 years in the CXL group and 24.0 years in the non-CXL group ( P > .05), respectively. All topographical and visual parameters before implantation were similar in both groups ( P > .05 for all parameters). At 6 months, CDVA, K1, and Kmean showed higher improvement in the non-CXL group than the CXL group ( P = .030, .018, and .039, respectively)., Conclusions: CAIRS surgery has a flattening effect on both the corneas with and without CXL. The cornea with prior CXL treatment had less flattening effect due to the stiffening effect of prior CXL. [ J Refract Surg . 2024;40(6):e392-e397.] .

Purpose: To assess the safety and efficacy of treatment and secondarily determine the topographic changes, visual outcomes, and demarcation line depth after high-fluence pulsed light accelerated cross-linking (ACXL) in pediatric patients (younger than 18 years) with progressive keratoconus., Methods: This retrospective analysis included 32 eyes (25 children, aged 11 to 18 years), with progressive keratoconus treated with high-energy epithelium-off pulsed light ACXL (7.2 J/cm 2 , 15 mW/cm 2 , 12 minutes, 2 seconds on/1 second off). Corrected distance visual acuity (CDVA), Scheimpflug tomography, and anterior optical coherence tomography measurements were recorded preoperatively and 1, 2, and 3 years postoperatively., Results: A total of 32 eyes were included. Significant CDVA improvement, pachymetry, and maximum keratometry reduction were found at all follow-up visits. Mean keratometric values remained stable, and astigmatism showed a mild worsening (< 0.25 D) with statistical significance at 1 and 3 years. Total aberration showed discordant results and coma aberration had a slight improvement without statistical significance. The demarcation line depth was 265 ± 26 μm. Three patients developed mild haze without visual acuity loss. None of the patients underwent a second CXL procedure., Conclusions: In pediatric patients, high-fluence epithelium-off pulsed light ACXL appears to be a safe and effective procedure to halt the progression of keratoconus, slightly improving the CDVA and keratometric values. [ J Refract Surg . 2024;40(3):e148-e155.] .

Purpose: To assess 10-year visual and tomographic outcomes of topography-guided custom ablation (T-CAT) with corneal cross-linking (CXL) in eyes with keratoconus., Methods: T-CAT with CXL was performed in 600 eyes (522 patients). Based on the T-CAT ablation plan, the theoretical maximum ablation depth was 50 µm after epithelium removal. After ablation, accelerated corneal cross-linking (CXL) was performed in the central 8-mm zone (9 mW/cm 2 for 10 minutes in "epi-off" mode). The visual acuity and tomography were assessed., Results: There was significant improvement in uncorrected ( P = .001) and corrected ( P = .001) distance visual acuity after the procedure. Keratometry, root mean square lower order aberrations and higher order aberrations, defocus, coma 90°, and spherical aberration reduced significantly after surgery at 10 years of follow-up ( P < .005). All Pentacam (Oculus Optikgerate GmbH) tomographic variables showed significant changes indicating regularization after T-CAT ( P < .005). Flattening of greater than 5.00 diopters in maximum keratometry was noted in 6 eyes (1%). Two of 600 eyes progressed postoperatively and required repeat CXL., Conclusions: T-CAT plus CXL is a safe and effective technique even in the long term for regularizing the anterior corneal surface with significant visual improvement and reduction in higher order corneal aberrations. [ J Refract Surg . 2023;39(11):759-766.] .

Purpose: To present the 7-year experience of a tertiary eye hospital while exploring possible risk factors and incidence of infectious keratitis in patients undergoing standard corneal cross-linking (CXL)., Methods: This retrospective cohort study included patients with progressive keratoconus undergoing standard CXL in the Farabi Eye Hospital and all other patients who had undergone CXL in other facilities and were diagnosed as having infectious keratitis in the 7-year period of the study., Results: Among the total of 4,863 eyes that underwent CXL, 6 eyes developed infectious keratitis, yielding an incidence rate of 0.12%. Additionally, 13 eyes from 10 patients with a CXL history in other facilities who developed infectious keratitis were included. The mean age was 23.75 years, and 75% of patients were men and 25% were women. Gram-positive bacteria and Staphylococcus aureus were the most prevalent pathogens. Meibomian gland dysfunction, dry eye disease, or blepharitis were present in 12 patients. Medical treatment did not arrest the disease progress in 5 patients, which eventually required cases to undergo keratoplasty., Conclusions: This study supports the need for proper patient selection by using a comprehensive medical history. It also highlights the imperative role of rigorous patient education and follow-up, particularly in the first postoperative week. Finally, the study emphasizes aggressive early therapy for patients with suspicious findings. [ J Refract Surg . 2023;39(8):564-572.] .

Purpose: To evaluate the biomechanical changes and advanced oxidation protein products (AOPP) production after different corneal cross-linking (CXL) protocols with or without oxygen supplementation., Methods: Ovine eyes in the study were equally distributed to five groups as control, standard Dresden protocol, diluted alcohol- and iontophoresis-assisted CXL (DAI-CXL), and 0.1% and 0.2% riboflavin-mediated iontophoresis-assisted CXL with oxygen supplementation (I-CXL). Corneas that received CXL were divided into two equal parts, one part was used for uniaxial tensiometry and one part was used for AOPP measurement., Results: All treatment groups showed higher Young's modulus and stiffness compared to the control group ( P < .05). Both oxygen-assisted I-CXL groups with 0.1% and 0.2% riboflavin concentrations had higher corneal Young's modulus ( P = .009 and .006, respectively) and stiffness ( P = .009) values, whereas the DAI-CXL group had lesser Young's modulus and stiffness values ( P = .032) compared to the Dresden protocol group. All treatment groups showed higher AOPP concentrations compared to the control group ( P < .05). DAI-CXL and I-CXL groups showed similar AOPP formation compared to the Dresden protocol ( P = .673)., Conclusions: When the epithelium is intact, the desired increase in corneal stiffness might not be achieved. However, increasing the oxygen in the environment might provide a sufficient increase in stiffness in cases undergoing epitheliumon I-CXL, which might be promising in terms of shortening the CXL therapy and decreasing the complications. [ J Refract Surg . 2022;38(10):674-681.] .

Purpose: To examine central corneal thickness (CCT) changes during in vivo rose bengal-green light corneal cross-linking (RG-CXL) and compare the CXL efficacy of different rose bengal formulations., Methods: After epithelium removal, the right eyes of rabbits were immersed in rose bengal solution prepared by different solvents (water, phosphate buffered saline, dextran, and hydroxypropyl methylcellulos [HPMC]) for 2 or 20 minutes, then the rose bengal distribution in the corneal stroma was analyzed by confocal fluorescence detection. During the RG-CXL process, the CCT was measured at seven time points. The left eyes served as the untreated control group. Corneal enzymatic resistance and corneal biomechanics were tested to compare the RG-CXL efficacy., Results: The rose bengal infiltration depths were 120 and 200 µm for the 2- and 20-minute groups, respectively. CCT increased significantly after infiltration, then decreased significantly in the first 200 seconds of irradiation and decreased slowly for the next 400 seconds. The CCT of the 20-minute groups was significantly thicker than that of the 2-minute groups ( P < .0001). All RG-CXL treatments improved the corneal enzymatic resistance and corneal biomechanics, with the effects being greater in the 20-minute groups. The inclusion of 1.1% HPMC in the rose bengal formulation helped to maintain CCT during irradiation while not affecting either the infiltration of rose bengal or the efficacy of RG-CXL., Conclusions: Within the range studied, RG-CXL efficacy increased with infiltration time. The incorporation of a 20-minute infiltration of 0.1% rose bengal-1.1% HPMC into the RG-CXL procedure may further improve the safety of the treatment and its prospects for clinical use. [ J Refract Surg . 2022;38(7):450-458.] .

Purpose: To evaluate the long-term effects of ultraviolet-A corneal cross-linking (CXL) with different irrandiances on the biomechanical properties of rabbit corneas and the corresponding changes in stromal microstructure., Methods: The study involved the left eyes of 85 healthy white Japanese rabbits, randomly divided into five groups (n = 16 to 18 each). After removing the epithelium, the first four groups were exposed to riboflavin (0.22% concentration by volume) and ultraviolet-A (370 nm) at different CXL irradiations but with the same total dose (5.4 J/cm 2 ). The four groups were defined as standard CXL (SCXL; 3 mW/cm 2 for 30 minutes, n = 17), accelerated CXL1 (ACXL1; 9 mW/cm 2 for 10 minutes, n = 16), accelerated CXL2 (ACXL2; 18 mW/cm 2 for 5 minutes, n = 17), and accelerated CXL3 (ACXL3; 30 mW/cm 2 for 3 minutes, n = 17). The control group (n = 18) was treated with riboflavin without ultraviolet-A exposure. Nine months after CXL, 10 corneas from each group were tested ex vivo under inflation, and the tangent modulus (Et) was estimated using an inverse analysis process. The remaining six to eight specimens in each group were examined by electron microscopy to determine the mean fibril diameter and interfibrillar spacing., Results: The SCXL and ACXL1 groups showed statistically significant differences in Et at all stresses (0.005, 0.010, and 0.015 MPa) analyzed compared to the control group (all P < .01), but the differences were non-significant in the ACXL3 group ( P = 1.000, .785, and .679, respectively). For the ACXL2 group, there was no statistical difference in Et under the low stress of 0.005 MPa ( P = .155), but the differences became significant at 0.010 and 0.015 MPa when compared with the control group (all P < .05)., Conclusions: CXL had a significant effect on corneal biomechanics in both standard and accelerated procedures. However, standard CXL was the most effective, and this effectiveness decreased gradually with increasing ultraviolet-A power intensity. [ J Refract Surg . 2022;38(6):389-397.] .

Purpose: To compare the long-term results of accelerated corneal cross-linking (CXL) (9 mW/cm 2 , 10 min) with standard CXL (3 mW/cm 2 , 30 min) in patients with Down syndrome who had keratoconus., Methods: In this contralateral randomized clinical trial, 27 patients with Down syndrome aged 15.78 ± 2.46 years (range: 10 to 19 years) were enrolled. CXL was performed using the KXL System (Avedro, Inc) under general anesthesia, and patients were followed up for 3 years. The main outcome measure was a change in average keratometry in the 3-mm zone around the steepest point (zonal Kmax-3mm). Secondary outcomes were changes in Corvis ST (Oculus Optikgeräte GmbH) biomechanical parameters and vision, refraction, and corneal tomography measurements., Results: Mean 3-year changes in zonal Kmax-3mm were not significantly different between the accelerated and standard groups (-0.06 ± 0.75 and -0.35 ± 0.94 diopters [D], respectively, P = .727). Despite the contralateral design of the study, based on most baseline biomechanical indices, corneas in the standard group were weaker before treatment. The standard group also showed significantly fewer 3-year changes in the stress-strain index (-0.11 ± 0.21 vs -0.30 ± 0.32), integrated radius (+0.99 ± 3.48 vs +3.14 ± 2.84), and deformation amplitude ratio-2mm (-1.38 ± 1.33 vs +0.30 ± 1.75) (all P < .0167). Corneal stiffness in the accelerated group was stable for 2 years, and the decline mainly occurred during the third year., Conclusions: In young patients with Down syndrome who had keratoconus, accelerated and standard CXL showed a similar flattening effect. Standard CXL is better able to maintain corneal stiffness in weaker corneas. With accelerated CXL, despite stable results for 2 years, there was decreased corneal stiffness in the third year. Longer follow-up periods are warranted to study the decreased efficacy on keratoconus progression. [ J Refract Surg . 2022;38(6):381-388.] .

Purpose: To assess the flattening of central, paracentral, and peripheral cones following non-accelerated (non-A-CXL) and accelerated (A-CXL) epithelium-off corneal cross-linking with 10 times higher intensity., Methods: In this multicenter study of 200 eyes (100 in each group), following 10 minutes of soak time with riboflavin 0.1%, continuous CXL was performed for 30 minutes (intensity: 3 mW/cm 2 , fluence: 5.4 J/cm 2 ) in the non-A-CXL group and 3 minutes (intensity: 30 mW/cm 2 , fluence: 5.4 J/cm 2 ) in the A-CXL group. Anterior and posterior cone flattening were compared at 12 months. Multiple regression analysis was performed to establish correlation of age, sex, cone location, and preoperative maximum keratometry (Kmax) values with postoperative flattening at 12 months., Results: In the non-A-CXL and A-CXL groups, central cones were the steepest, followed by paracentral and peripheral cones. Both groups showed significant flattening in central (1.54 ± 1.94 and 1.09 ± 1.79 diopters [D]) and paracentral (0.62 ± 1.59 and 0.55 ± 0.98 D) cones only. In the non-A-CXL group, there was a positive correlation between postoperative flattening and preoperative Kmax values, whereas paracentral and peripheral cone locations were negatively related. In the A-CXL group, only paracentral location was negatively correlated to postoperative flattening and showed posterior cone steepening at 12 months., Conclusions: Although central cones were the steepest in both groups, there was no difference in postoperative flattening between the groups for all cone locations. In the non-A-CXL group, postoperative flattening was proportional to preoperative Kmax values in central cones and was less with paracentral and peripheral locations. With A-CXL, postoperative flattening was less only with paracentral location. In the A-CXL group, significant posterior cone steepening was noticed only in paracentral cones. [ J Refract Surg . 2022;38(5):310-316.] .

Purpose: To compare the 36-month visual, refractive, and topographic results and the optical quality of the cornea between mechanical and transepithelial phototherapeutic keratectomy (PTK) epithelium removal techniques prior to the accelerated corneal cross-linking (CXL) procedure in patients with progressive keratoconus., Methods: Keratoconic eyes that received either mechanical epithelium removal or transepithelial PTK epithelium removal prior to accelerated CXL with 36 months of follow-up were included. The uncorrected (UDVA) and corrected (CDVA) distance visual acuity, spherical equivalent (SE), manifest astigmatism, flat keratometry (K1), steep keratometry (K2), maximum keratometry (Kmax) readings, thinnest corneal thickness (TCT), topographic astigmatism, point spread function (PSF), and aberrometric parameters including root mean square higher order aberrations (RMS HOAs), vertical coma, and spherical aberration (SA) were assessed preoperatively and 12, 24, and 36 months postoperatively., Results: One hundred ten eyes of 110 patients with keratoconus were included (mechanical epithelium removal group: 69 eyes, transepithelial PTK epithelium removal group: 41 eyes). After the CXL procedure, the mean UDVA, CDVA, manifest astigmatism, RMS HOAs, SA, vertical coma, and PSF improved significantly throughout the follow-up visits in both groups ( P < .05 for all variables). The improvement in the mean UDVA, CDVA, manifest astigmatism, K1, K2, Kmax, RMS HOAs, SA, vertical coma, and PSF were significantly better in eyes that underwent transepithelial PTK epithelium removal when compared to eyes that underwent mechanical epithelium removal during the follow-up period ( P < .05 for all variables)., Conclusions: Transepithelial PTK-assisted accelerated CXL seems to be more efficient in improving the visual acuity and the optical quality while stabilizing the cornea compared to the accelerated CXL with mechanical epithelium removal in patients with progressive keratoconus. [ J Refract Surg . 2022;38(3):191-200.] .

Purpose: To compare standard epithelium-off corneal cross-linking (standard Epi-Off CXL) to corneal cross-linking with an epithelial flap (Epi-Flap CXL)., Methods: Patients who had undergone sequential bilateral CXL for progressive keratoconus were included in this comparative interventional case series. One eye was treated with the Epi-Off CXL technique and the fellow eye with the Epi-Flap CXL technique. Postoperative pain was measured using the Verbal Rating Scale and corneal densitometry using a Scheimpflug camera. Sex, age, corrected distance visual acuity, keratometry, and corneal thickness were also recorded., Results: Twenty-four eyes of 12 patients with keratoconus with a mean age of 27.15 ± 5.15 years were included. The Verbal Rating Scale scores were significantly lower in patients who had Epi-Flap CXL on the first (1.00 [interquartile range (IQR): 0.00 to 1.00] vs 3.00 [IQR: 3.00 to 3.75], P = .01) and third (0.00 [IQR: 0.00 to 1.00] vs 1.00 [IQR: 0.00 to 1.00], P = .01) postoperative day compared to the Epi-Off CXL group. No pain was observed in both groups after the third day. After 12 months, the Epi-Flap CXL group showed significantly less anterior corneal haze (measured as corneal densitometry) compared to the patients treated with Epi-Off CXL ( P = .01). Both groups demonstrated stability of keratometry and corneal thickness at 12 months after CXL ( P < .01)., Conclusions: Epi-Flap CXL is associated with less postoperative pain and anterior stromal haze in patients undergoing CXL for progressive keratoconus with no loss of efficacy. [ J Refract Surg . 2021;37(11):741-745.] .

Purpose: To assess corneal stability and corrected distance visual acuity (CDVA) 3, 6, and 12 months following corneal cross-linking (CXL) using the ABCD keratoconus staging system., Methods: This prospective longitudinal study included 31 eyes with keratoconus receiving CXL based on the standard Dresden protocol. CDVA, refraction, and Scheimpflug tomography with the Pentacam HR (Oculus Optikgeräte GmbH) were evaluated before and after surgery. Geometric and functional changes were assessed using the actual values and staging of each element of the ABCD keratoconus staging system. A, B, C, and D refer to the anterior and posterior radii of curvature in a 3-mm zone centered on the cor-neal thinnest point, minimum corneal thickness, and CDVA, respectively., Results: There were no significant changes in the actual values of anterior radius of curvature ( P = .497) and CDVA ( P = .082), whereas posterior radius of curvature ( P = .007) and corneal thinnest point ( P < .001) showed significant changes statistically. Pairwise comparison showed only a statistically significant steepening in posterior radius of curvature at 3 months after CXL compared to the preoperative radius ( P = .002) and a significant decrease in corneal thinnest point at 3 ( P < .001) and 6 ( P = .028) months after CXL compared to baseline assessment. Staging of each element of the ABCD keratoconus staging system indicated no change between baseline and 3, 6, and 12 months after CXL., Conclusions: The geometric and functional parameters included in the ABCD keratoconus staging system showed stability of corneal status and CDVA 1 year after CXL. [ J Refract Surg . 2021;37(10):700-706.] .

Purpose: To compare the clinical and tomographic properties of adult patients with keratoconus treated with accelerated corneal cross-linking (A-CXL) versus accelerated contact lens-assisted corneal cross-linking (A-CACXL)., Methods: Patients who underwent A-CXL and A-CACXL due to progressive keratoconus were enrolled from January 2015 to January 2018 in this retrospective case-control study. The treatment group (minimum corneal thickness of less than 400 µm after epithelium removal; 30 patients, 30 eyes) was treated with A-CACXL; the control group (minimum corneal thickness of 400 µm or greater, 32 patients, 32 eyes) was treated with A-CXL. Assessments occurred before treatment and 12 months postoperatively. Demographic, clinical, and tomographic data were obtained from outpatient clinic reports., Results: Significant improvement in visual acuity was evident at 12-month follow-up for the control group in uncorrected distance visual acuity (0.62 ± 0.42 vs 0.43 ± 0.31 logMAR, P = .01) and the treatment group in corrected distance visual acuity (0.51 ± 0.30 vs 0.40 ± 0.49 logMAR, P = .03). Progression of keratoconus was halted at similar rates for both groups (76.7% treatment, 84.4% control, P = .21). Mean minimum corneal thickness showed minor but significant thinning at the 12-month follow-up visit compared to baseline (control group = 463 ± 31 vs 450 ± 35 µm, P > .01; treatment group = 398 ± 32 vs 388 ± 41 µm, P = .02)., Conclusions: A-CACXL halted keratoconus progression in 76.7% of eyes and achieved regression in 33.3% of eyes, with rates comparable to A-CXL. Visual outcomes improved for both groups, with similar keratometry changes. A-CACXL is an effective and safe option for patients with keratoconus and thin corneas, with results similar to A-CXL treatment in patients with a minimum corneal thickness of 400 µm or greater. [ J Refract Surg . 2021;37(9):623-630.] .

Purpose: To compare 1-year visual and tomographic outcomes of topography-guided photorefractive keratectomy (TGPRK) and topography-assisted phototherapeutic keratectomy (TPTK) with corneal cross-linking (CXL)., Methods: TGPRK and TPTK were performed in 72 eyes (68 patients) and 74 eyes (71 patients), respectively. Based on the TGPRK ablation plan, the eyes underwent TPTK where the theoretical minimum corneal thickness (MCT) after surgery was less than 400 µm. In the TGPRK group, the theoretical maximum ablation depth was 50 µm after epithelium removal. In TPTK, a decentered single-step PTK was performed only in the steepest anterior curvature zone and the stromal ablation depth was limited to 25 µm. After ablation, accelerated CXL was performed in the central 8-mm zone (9 mW/cm 2 for 10 minutes in "epithelium-off" mode) in both TGPRK and TPTK. The visual acuity and tomography were assessed., Results: Improvement in uncorrected ( P = .73) and corrected ( P = .66) distance visual acuity was similar between the two groups. However, TGPRK eyes had a greater decrease in keratometry, anterior defocus, and spherical aberration ( P < .001) at the cost of greater ablation of tissue ( P < .001). The median MCT decreased by 27 and 52.5 µm in the TPTK and TGPRK eyes, respectively. Both groups had similar decreases in anterior root mean square of lower ( P = .10) and higher ( P = .12) order aberrations., Conclusions: Both TGPRK and TPTK improved visual acuity in the keratoconic eyes at 1 year of follow-up. However, TPTK removed less volume of tissue. Further, it could be an alternative to TGPRK if the theoretical stromal ablation exceeds 50 µm in thin keratoconic corneas. [ J Refract Surg . 2021;37(8):562-569.] .

Purpose: To assess the long-term efficacy and safety of epithelium-off corneal cross-linking according to the standard (Dresden) protocol (S-CXL) in patients with progressive keratoconus older than 40 years., Methods: Seventy-six eyes of 64 patients with a mean age of 46.4 ± 5.2 years were included. At baseline and after 6, 12, 24, 36, 48, 60, 72, 84, and more than 96 months (when available) after S-CXL, all patients were assessed with distance-corrected visual acuity (DCVA) and corneal topography and tomography with Pentacam HR (OCULUS Optikgeräte GmbH). A generalized linear model was used to compare the groups. Outcome measures were maximum keratometry, thinnest point, coma, spherical, and higher order aberrations, and ABC values. Fixed and random factors were age, gender, atopy, laterality, and group., Results: The mean follow-up time was 62.1 ± 40.1 months (range: 12 to 144 months). The main outcome of the study was the evidence that S-CXL was able to safely stop the progression of keratoconus in all patients with none requiring repeat CXL. The generalized linear model analysis showed no significant change in DCVA over time ( P = 1.000), but atopy was negatively associated with DCVA ( P = .030, B = -0.69). The generalized linear model also showed that CXL was able to induce a significant flattening demonstrated as reduction of maximum keratometry ( P = .001, B = -0.35) and A value ( P =.001, B = -0.015) of the ABC display. Similarly, coma aberration was reduced over time ( P = .006, B = -0.005)., Conclusions: S-CXL was confirmed to be a safe and effective treatment for progressive keratoconus even after the age of 40 years, inducing a significant flattening of the cone. [ J Refract Surg . 2021;37(5):338-342.] .

Purpose: To determine the efficacy of interferometry for examining the spatial changes to the corneal biomechanical response to simulated intraocular pressure (IOP) fluctuations that occur after corneal cross-linking (CXL) applied in different topographic locations., Methods: Displacement speckle pattern interferometry (DSPI) was used to measure the total anterior surface displacement of human and porcine corneas in response to pressure variations up to 1 mm Hg from a baseline pressure of 16.5 mm Hg, both before and after CXL treatment, which was applied in isolated topographic locations (10-minute riboflavin soak [VibeX-Xtra; Avedro, Inc], 8-minute ultraviolet-A exposure at 15 mW/cm 2 ). Alterations to biomechanics were evaluated by directly comparing the responses before and after treatment for each cornea., Results: Before CXL, the corneal response to loading indicated spatial variability in mechanical properties. CXL treatments had a variable effect on the corneal response to loading dependent on the location of treatment, with reductions in regional displacement of up to 80% in response to a given pressure increase., Conclusions: Selectively cross-linking in different topographic locations introduces position-specific changes to mechanical properties that could potentially be used to alter the refractive power of the cornea. Changes to the biomechanics of the cornea after CXL are complex and appear to vary significantly depending on treatment location and initial biomechanics. Hence, further investigations are required on a larger number of corneas to allow the development of customized treatment protocols. In this study, laser interferometry was demonstrated to be an effective and valuable tool to achieve this. [ J Refract Surg . 2021;37(4):263-273.] .

Purpose: To assess the fellow eye as a predictor for keratoconus progression following bilateral same-day accelerated corneal cross-linking (A-CXL)., Methods: This was a post-hoc analysis of data from a prospective study of bilateral A-CXL for progressive keratoconus between 2013 and 2015. The primary outcome measures were absolute change in maximum keratometry (Kmax) (diopters [D]), relative change in Kmax (%), and A-CXL progression (increase in Kmax > 2.00 D). Responses in both eyes were measured by the change in Kmax, with the right eye serving as the "predictor" of progression for the left eye., Results: Three-hundred ninety-two eyes (196 patients) with a mean age of 26.8 ± 7.7 years were included. There was a significant correlation in absolute and relative Kmax change ( r = 0.26, P < .001 and r = 0.32, P < .001, respectively) between right and left eyes. In regression analysis, the only significant predictors of change in Kmax in the left eye were preoperative Kmax of the left eye ( P < .02) and change in Kmax of the right eye ( P < .001). Eyes that progressed in the right eye were more likely to progress in the left eye (29.4% versus 4.5%, odds ratio = 8.85, P < .001). In multiple regression, right eye progression of greater than 2.00 D was the significant predictor of left eye progression of greater than 2.00 D (odds ratio = 15.15, P < .007)., Conclusions: This large-scale study of keratoconus following A-CXL indicates that patients with progression in the right eye were 15.5 times more likely to have progression in the left eye. Patients with progression following A-CXL in one eye should be closely observed due to increased risk of progression in the fellow eye. [ J Refract Surg . 2021;37(3):186-191.] .

Purpose: To evaluate and compare corneal haze as determined by optical coherence tomography (OCT) after corneal cross-linking (CXL) for the treatment of mild to moderate keratoconus with or without mitomycin C (MMC) application., Methods: This was a retrospective analysis of 87 eyes of 72 patients with mild to moderate keratoconus. The first group (n = 44 eyes) underwent CXL between June 2013 and January 2015 and the second group (n = 43 eyes) underwent CXL with MMC (CXL+MMC) between February and December 2015, both following the Dresden protocol. Patients were evaluated preoperatively and at 1, 3, 6, and 12 months postoperatively. Main outcome measures were corneal reflectivity and haze reflectivity measured by a specially developed OCT image analysis software., Results: Anterior corneal reflectivity at 1 month and 1 year postoperatively was 14.79 ± 4.68 and 25.97 ± 15.01 (P < .001), and 13.88 ± 4.39 and 18.41 ± 9.25 (P = .025) for the CXL and CXL+MMC groups, respectively. The reflectivity of the anterior stromal haze region at 1 month and 1 year postoperatively was 23.15 ± 5.91 and 33.14 ± 16.58 (P = .005), and 20.58 ± 7.88 and 27.14 ± 12.80 (P = .049) for both groups, respectively. The changes in simulated keratometry from preoperatively to postoperatively were similar in both groups. The CXL+MMC group showed larger maximum keratometry flattening: 53.41 ± 6.88 diopters (D) preoperatively and 49.44 ± 5.66 D 1 year postoperatively versus 52.27 ± 5.78 and 50.91 ± 4.25 D for CXL alone (P = .008)., Conclusions: MMC application following CXL significantly increases corneal haze. Similar studies need to be performed on simultaneous CXL and photorefractive keratectomy to evaluate the role of MMC in haze formation in such procedures. [J Refract Surg. 2021;37(2):83-90.]., (Copyright 2021, SLACK Incorporated.)

Purpose: To evaluate the efficacy and safety of transepithelial corneal cross-linking (CXL) with supplemental oxygen., Methods: This was a prospective, non-comparative, pilot cohort study conducted at the National Reference Center for Keratoconus (Toulouse, France) on patients with progressive keratoconus. Transepithelial, pulsed, accelerated CXL was performed in an oxygen-rich atmosphere. Oxygen goggles were applied to the eyes to maintain a high level of oxygen during treatment. The main efficacy outcome was the mean change from baseline in maximum keratometry (Kmax) and the secondary outcomes were the mean changes in flat keratometry (K1), steep keratometry (K2), mean keratometry (Km), corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), and demarcation line depth. The safety outcomes were the incidence of adverse events, the mean change in pachymetry, and endothelial cell count., Results: Thirty-four eyes of 34 patients were included. At 12 months postoperatively, the Kmax decreased by 1.56 ± 1.71 diopters (D) (P < .0001) and CDVA improved by 0.093 ± 0.193 logMAR (P < .02). The K2 and Km decreased by 0.51 ± 1.03 D (P < .02) and 0.40 ± 0.78 D (P < .01), respectively. There was no change in K1 and UDVA. The most frequent adverse event was corneal haze (64.78%). There were neither cases of infectious keratitis or loss of more than two lines in CDVA nor changes in pachymetry or endothelial cell count., Conclusions: Transepithelial CXL performed in an oxygen-rich atmosphere results in improved Kmax and CDVA with good safety. These promising findings suggest that this procedure could be safe and capable of halting the progression of keratoconus. [J Refract Surg. 2021;37(1):42-48.]., (Copyright 2021, SLACK Incorporated.)

Purpose: To assess the long-term efficacy and safety of epithelium-off corneal cross-linking according to the Dresden protocol (S-CXL) in progressive keratoconus., Methods: Patients treated with S-CXL from April 2006 to January 2010 at Humanitas Clinical and Research Center, Rozzano, Italy, who completed at least 10 years of follow-up were included. Corrected distance visual acuity (CDVA), refraction, and corneal topography and tomography with Pentacam (OCULUS Optikgeräte GmbH) were evaluated at baseline and 10+ years after the procedure. The definition of progression after S-CXL was two of the following three criteria: increase of "A" value, increase of "B" value, or decrease of minimum thickness evaluated with the ABCD progression display above 95% CI for the post-CXL population., Results: Twenty-seven eyes of 22 patients were included. At a mean of 11 years of follow-up (maximum 13 years), S-CXL was able to maintain CDVA and induce significant regularization of the corneal surface as demonstrated by a significant decrease of the central keratoconus index (P = .035) and a decrease of anterior curvature ("A" value) starting from 2.54 ± 2.46, which reduced to 1.14 ± 1.60 (P = .005) at 10+ years of follow-up. Two of 27 eyes included showed significant progression after S-CXL (7.4%)., Conclusions: S-CXL was confirmed to be a safe and effective treatment for progressive keratoconus with a failure rate of 7.4% at up to 13 years of follow-up. The authors suggest the use of a combined progression system that evaluates anterior and posterior curvature and with thickness map together with the knowledge of the noise level of the testing system. [J Refract Surg. 2020;36(12):838-843.]., (Copyright 2020, SLACK Incorporated.)

Purpose: To investigate the long-term efficacy and safety of continuous light-accelerated corneal cross-linking (CXL) in patients with progressive keratoconus., Methods: This retrospective study analyzed 29 eyes of 29 consecutive patients with progressive keratoconus treated with epithelium-off riboflavin-ultraviolet induced accelerated CXL (30 mW/cm 2 -7.2 joules/cm 2 ). Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, keratometry measurements at 3 and 6 mm (Kmax, Kmin, and Kmean), topographic astigmatism, central corneal thickness, anterior corneal aberrometric analysis (at 3 and 6 mm), endothelial cell density, and central foveal thickness were evaluated before and 24 and 60 months after surgery., Results: UDVA significantly improved at 60 months postoperatively (P = .028). Kmax and Kmean at 3 mm significantly decreased at 24 (P = .009 and .006, respectively) and 60 (P = .017 and .034, respectively) months postoperatively, whereas Kmin significantly decreased only at 24 months postoperatively (P = .032). Kmax at 6 mm significantly decreased at 24 and 60 months postoperatively (P = .035 and .027, respectively). Cylinder error significantly decreased at 24 and 60 months postoperatively (P = .001 and .023, respectively). Wavefront aberration variables remained unchanged after surgery, except for spherical aberration at 6 mm that decreased at 24 and 60 months postoperatively (P = .038 and .031, respectively) and trefoil at 0° that significantly decreased at 24 months postoperatively (P < .005). Endothelial cell density and central foveal thickness showed no changes from baseline., Conclusions: Accelerated CXL was found to be effective in halting keratoconus progression and improving some of the visual, topographic, and wavefront aberration variables evaluated. High energy irradiance did not induce significant changes in corneal transparency, endothelial cell density, and central foveal thickness. [J Refract Surg. 2020;36(11):724-730.]., (Copyright 2020, SLACK Incorporated.)

Purpose: To evaluate the results of epithelium-off continuous light accelerated corneal cross-linking (CXL) with a total dose of 7.2 J/cm 2 for treating progressive keratoconus in a Chinese population during 24 months of follow-up., Methods: In this retrospective, interventional case series, 45 eyes of 31 consecutive patients with progressive keratoconus were evaluated. All patients underwent accelerated CXL with settings of 30 mW/cm 2 for 4 minutes, corresponding to a total dose of 7.2 J/cm 2 . Visual acuity, manifest refraction, epithelial thickness, topography, tomography, aberrometry, endothelial cell count, and intraocular pressure were evaluated at baseline and at 1, 3, 6, 12, 18, and 24 months postoperatively., Results: Progressive keratoconus was stabilized in 91.11% and 93.33% of the patients at 12 and 24 months, respectively. The improvement in corrected distance visual acuity was significant throughout the postoperative follow-up period (P < .05), excluding month 1. A significant decrease in the maximum keratometric values (0.67 ± 1.68, 0.92 ± 1.78, and 0.97 ± 1.73 D) was observed at months 12, 18, and 24, respectively (P < .05 for all). Corneal irregularity improved, particularly total root mean square and higher order aberrations at 12 to 24 months after CXL. In bilateral CXL, the progression of the first eye was highly predictive of the outcome of the second eye., Conclusions: CXL with a total dose of 7.2 J/cm 2 maintains long-term results in halting the progression of keratoconus, with significant improvement in the corrected distance visual acuity and stability of keratometric values. Further clinical studies with longer follow-up periods and larger samples are necessary to confirm these results. [J Refract Surg. 2020;36(11):731-739.]., (Copyright 2020, SLACK Incorporated.)

Purpose: To compare immediate sequential bilateral corneal cross-linking (CXL), wherein both eyes are treated on the same day, to delayed sequential bilateral CXL, where each eye is treated on different days for bilateral progressive keratoconus., Methods: This was a retrospective case note review of all patients who underwent sequential CXL or delayed CXL for keratoconus at Royal Liverpool University Hospital, United Kingdom. Parameters assessed were the change in maximum keratometry and minimum central corneal thickness on corneal tomography scan, corrected distance visual acuity, and cost estimates of treatment., Results: A total of 38 patients (31 men and 7 women) with keratoconus with a mean age of 25.3 ± 7.0 years were included. Twenty patients received sequential CXL and 18 received delayed CXL treatment. In both the sequential CXL and delayed CXL groups, the treated eye(s) showed no evidence of progression after the corneal CXL treatment at last follow-up visit after 358 ± 158 days for sequential CXL and 451 ± 205 days for delayed CXL. There were no complications from the treatment in either group. In the delayed CXL group, the mean time interval between the two CXL procedures was 146 ± 129 days. Five of 18 patients (27%) showed progression of keratoconus in their second eye during the waiting time. Economical evaluation showed that four visits were saved for each sequential CXL treatment compared to delayed CXL., Conclusions: Delayed CXL carries a risk of progression in the second eye and is associated with a higher economic burden. [J Refract Surg. 2020;36(8):552-556.]., (Copyright 2020, SLACK Incorporated.)

Purpose: To assess 3-year safety and efficacy of enhanced-fluence pulsed-light iontophoresis cross-linking (EF I-CXL) in patients with progressive keratoconus., Methods: This prospective interventional pilot study included 24 eyes of 20 patients, with a mean age of 23.9 years (range: 15 to 36 years). Iontophoresis with riboflavin solution was used for stromal imbibition. The treatment energy was optimized at 30% (7 J/cm 2 ) and ultraviolet-A power set at 18 mW/cm 2 × 6.28 minutes of pulsed-light on-off exposure, with a total irradiation time of 12.56 minutes. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal tomography, and corneal optical coherence tomography (OCT) at baseline and 1, 3, 6, 12, 24, and 3 years postoperatively were evaluated., Results: At 3 years, average UDVA decreased from 0.50 ± 0.10 to 0.36 ± 0.08 logMAR (P < .05), average maximum keratometry decreased from 52.94 ± 1.34 to 51.4 ± 1.49 diopters (D) (Delta: -1.40 ± 0.80 D; P < .05), average coma improved from 0.24 ± 0.05 to 0.12 ± 0.02 µm (P = .001), and symmetry index decreased from 4.22 ± 1.01 to 3.53 ± 0.90 D. Corneal OCT showed demarcation line detection at 285.8 ± 20.2 µm average depth in more than 80% at 1 month postoperatively., Conclusions: The 3-year results of EF I-CXL showed satisfactory I-CXL functional outcomes, increasing the visibility and the depth of demarcation line closer to epithelium-off standard CXL. [J Refract Surg. 2020;36(5):286-292.]., (Copyright 2020, SLACK Incorporated.)

Purpose: To compare the outcomes of accelerated photoactivated chromophore for keratitis corneal cross-linking (PACK-CXL) as an adjunct treatment for bacterial keratitis (PACK-CXL plus standard antibiotic therapy) for patients receiving only standard antibiotic therapy., Methods: Retrospective cohort study of outcomes of patients with moderate infectious presumed bacterial keratitis (ulcer diameter 2 to 7 mm and stromal depth < 300 µm) were compared before and after initiation of a new treatment protocol of PACK-CXL in addition to standard antibiotic treatment., Results: A total of 70 eyes of 70 patients were included: 39 eyes in the PACK-CXL plus antibiotic (PACK-ABX) group and 31 eyes in the antibiotic only (ABX) control group. The PACK-ABX group showed shorter times to complete reepithelialization (9.3 ± 6.0 vs 16.0 ± 12.7 days, P = .01) and did not require tectonic emergency keratoplasty (0% versus 19.4%, P = .006). The PACK-ABX group also showed a higher percentage of eyes with complete reepithelialization in 6 days or less (46.2% vs 6.5%, P < .001) and a trend for shorter hospitalizations (6.3 ± 5.0 vs 8.5 ± 4.5 days, P = .06). A multivariate analysis controlling for age showed that PACK-ABX treatment remained significantly associated with early ulcer reepithelialization (odds ratio = 0.09, 95% confidence interval = 0.02 to 0.48, P = .005)., Conclusions: This study validates previous findings regarding the use of accelerated PACK-CXL in the treatment of bacterial keratitis. Adding PACK-CXL improved clinical outcomes (reducing healing time) when compared to antibiotics alone. [J Refract Surg. 2020;36(4):258-264.]., (Copyright 2020, SLACK Incorporated.)

Purpose: To determine 2-year efficacy of accelerated corneal cross-linking (CXL) in keratoconus treatment using standard riboflavin-dextran or hypotonic riboflavin solutions., Methods: Patients undergoing accelerated CXL (epitheliumoff 10 minutes, 9 mW/cm 2 protocol) with standard riboflavin solution (48 eyes of 48 patients) or hypotonic riboflavin solution (43 eyes of 43 patients) were included and followed up for 2 years. Thinnest corneal thickness (TCT), maximum keratometry, and visual acuity were measured and changes from baseline to postoperative 6, 12, and 24 months were compared between the two groups., Results: The preoperative mean TCT with intact epithelium was 472.0 ± 23.9 and 427.5 ± 22.3 µm in the standard riboflavin and hypotonic riboflavin groups, respectively (P < .001). The decreases in the mean TCT values from baseline to postoperative 6 months were similar between the standard riboflavin (from 472 to 436 µm) and hypotonic riboflavin (from 427 to 394 µm) groups. This suggested that the hypotonic riboflavin solution was comparable with the standard riboflavin solution in preserving corneal thickness in keratoconus. There were no significant differences between the study groups regarding the postoperative changes in maximum keratometry or visual acuity., Conclusions: The efficacy of accelerated CXL with hypotonic riboflavin solution was comparable to that with the standard riboflavin solution in reducing keratoconus progression in a 2-year follow-up period. [J Refract Surg. 2020;36(2):110-117.]., (Copyright 2020, SLACK Incorporated.)

Purpose: To evaluate vision and corneal surface regularity after each step of a three-step surgical treatment of keratoconus and post-laser in situ keratomileusis (LASIK) ectasia (implantation of intracorneal ring segments [ICRS], corneal cross-linking [CXL], and implantation of toric intraocular contact lenses [ICLs])., Methods: Thirty-one eyes of 24 patients with moderate to severe keratoconus and post-LASIK ectasia (stages II and III of Amsler-Krumeich classification) were included. All eyes underwent all three steps. The time interval between ICRS implantation and CXL was 4 to 6 weeks, and ICL implantation was performed 6 to 8 months after CXL. Visual acuity, refraction, and corneal topometric indices were evaluated with the Pentacam system (index of surface variance [ISV], index of vertical asymmetry [IVA], keratoconus index [KI], central keratoconus index [CKI], index of height asymmetry [IHA], index of height decentration [IHD], and corneal wavefront parameters [eg, higher order aberrations, spherical aberration, and coma])., Results: Decimal uncorrected distance visual acuity (UDVA) improved from 0.13 ± 0.17 preoperatively to 0.69 ± 0.18 at 1 year, whereas corrected distance visual acuity (CDVA) improved from 0.56 ± 0.24 to 0.80 ± 0.18, respectively. The topometric indices ISV, IVA, KI, and IHD also improved significantly, whereas CKI and IHA showed no significant improvement. Higher order aberrations, spherical aberration, and coma improved significantly compared to baseline., Conclusions: The combined use of ICRS, CXL, and ICL implantation significantly improves visual acuity, higher order aberrations, and corneal shape in moderate and severe keratoconus and post-LASIK ectasia. [J Refract Surg. 2020;36(2):104-109.]., (Copyright 2020, SLACK Incorporated.)

Purpose: To compare the long-term outcomes of corneal cross-linking (CXL) for the treatment of keratoconus using two different techniques for epithelial removal: transepithelial phototherapeutic keratectomy (t-PTK) and mechanical epithelial debridement., Methods: In this prospective, comparative, interventional case series, 26 patients (30 eyes) with progressive keratoconus underwent CXL treatment. Fifteen eyes (13 patients) underwent epithelial removal with t-PTK (Cretan protocol) and 15 eyes (13 patients) underwent mechanical epithelial debridement (Dresden protocol) during CXL. Visual, refractive, and keratometric outcomes were evaluated preoperatively and at 1, 2, 3, and 4 years postoperatively., Results: No intraoperative or postoperative complications were observed in any of the patients. In the Cretan protocol group, mean uncorrected (UDVA) and corrected (CDVA) visual acuity improved from 0.99 ± 0.42 and 0.33 ± 0.28 logMAR preoperatively to 0.75 ± 0.32 (P = .018) and 0.21 ± 0.16 (P = .024) logMAR at 4 years postoperatively, respectively. In the Dresden protocol group, mean UDVA improved from 0.83 ± 0.47 logMAR preoperatively to 0.63 ± 0.40 logMAR (P = .033) at 4 years postoperatively, whereas mean CDVA did not demonstrate a statistically significant improvement postoperatively (P > .05). In the Cretan protocol group, mean corneal astigmatism improved from -6.19 ± 4.54 diopters (D) preoperatively to -4.68 ± 3.10 D (P = .041) at last follow-up, whereas in the Dresden protocol group there was no statistically significant difference postoperatively (P > .05)., Conclusions: Epithelial removal with t-PTK during CXL (Cretan protocol) resulted in better visual, refractive, and keratometric outcomes compared with mechanical epithelial debridement over a long-term follow-up. [J Refract Surg. 2019;35(10):650-655.]., (Copyright 2019, SLACK Incorporated.)

Purpose: To evaluate the safety and efficacy of accelerated contact lens-assisted cross-linking (A-CACXL) for patients with keratoconus and thin corneas., Methods: This retrospective study included consecutive patients undergoing A-CACXL for progressive keratoconus from 2015 to 2017. Patients with a minimum corneal thickness of 400 µm or less after epithelium removal who underwent A-CACXL (9 mW/cm 2 for 10 minutes, using iso-osmolar 0.1% riboflavin solution and a 90-µm thick, daily disposable bandage soft contact lens) with a follow-up time of 12 months or more were included. The main outcome measures were uncorrected (UDVA) and corrected (CDVA) distance visual acuity and minimum corneal thickness at the last visit. Progression (increase) and flattening (decrease) were defined as a change of 1.00 diopters (D) or greater in maximum keratometry or 1.50 D or greater in mean keratometry., Results: Overall, 24 eyes of 24 patients were included with a follow-up time of 18.2 ± 6.3 months and a mean minimum corneal thickness, after epithelial debridement, of 353.13 µm. There was a significant improvement in UDVA (P = .009), maximum keratometry (P = .03), anterior steep keratometry (P = .04), anterior astigmatism (P = .02), and posterior astigmatism (P = .04) with no significant change in minimum corneal thickness (P = .11). There was a significant improvement in UDVA (0.90 ± 0.63 to 0.64 ± 0.47 logMAR, P = .009), maximum keratometry (61.20 ± 6.30 to 59.90 ± 5.70 D, P = .03), anterior steep keratometry (55.10 ± 3.90 to 54.50 ± 4.10 D, P = .04), anterior astigmatism (5.50 ± 2.40 to 4.60 ± 2.10 D, P = .02), and posterior astigmatism (0.90 ± 0.40 to 0.80 ± 0.40 D, P = .04) with no significant change in minimum corneal thickness (from 399.8 ± 30.7 to 391.0 ± 43.8 μm, P = .11). Flattening occurred in 45.8% (n = 11) and progression in 20.8% (n = 5). There were no serious adverse events. Persistent clinically significant stromal haze occurred in one case and completely resolved by 6 months. There was no significant change in endothelial cell density (P = .10)., Conclusions: In patients with keratoconus and thin corneas, A-CACXL halted keratoconus progression in 80%, led to flattening in 45%, and significantly improved UDVA and keratometry values without any evidence of damage to the corneal endothelium or permanent adverse events. [J Refract Surg. 2019;35(10):642-648.]., (Copyright 2019, SLACK Incorporated.)

Purpose: To report the safety and long-term efficacy of topography-guided partial-refraction PRK combined with corneal cross-linking (CXL) (the Athens Protocol), refractive, topographic, and pachymetric changes of keratoconic eyes treated were studied., Methods: Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction, keratometry, qualitative and quantitative assessment of corneal keratometric, and pachymetric properties recorded by topography and tomography were evaluated for 10 years postoperatively., Results: A total of 144 eyes were followed up for a mean 128 ± 4 months (range: 120 to 146 months). Mean UDVA markedly improved at 1 year (0.19 ± 0.17 to 0.53 ± 0.21 decimal) with further improvement to 0.55 ± 0.19 decimal at 10 years. CDVA increased from 0.59 ± 0.21 to 0.80 ± 0.17 decimal at 1 year and further to 0.81 ± 0.19 decimal at 10 years. Corneal thickness decreased from 468.74 ± 35.05 to 391.14 ± 40.07 μm at 1 year (P < .01) and up to 395.42 ± 32.21 μm at 10 years. Steep keratometry decreased from 50.57 ± 2.80 to 45.87 ± 2.70 diopters (D) (P < .01) at 1 year and to 44.00 ± 3.22 D at 10 years. Maximum keratometry decreased from 53.43 ± 2.97 to 46.17 ± 1.18 D at 1 year and 44.75 ± 2.14 D at 10 years (P < .01). A total of 94.4% demonstrated ectasia stabilization and 3.5% showed progressive "overcorrection" or "hyperopic" shift., Conclusions: The Athens Protocol confirms long-term safety and efficacy for corneal ectasia and visual function. Most parameters had little change after 1 year, through year 10. [J Refract Surg. 2019;35(8):478-483.]., (Copyright 2019, SLACK Incorporated.)

Purpose: To present the Tel-Aviv Protocol for patients with progressive keratoconus, which consists of epithelial photorefractive keratectomy (ePRK), and corneal cross-linking (CXL)., Methods: This was a retrospective case series of 20 consecutive patients diagnosed as having progressive keratoconus at Care-Vision Laser Centers, Tel Aviv, Israel. The Tel-Aviv Protocol included laser epithelial ablation using the EX500 excimer laser (Alcon Laboratories, Inc., Fort Worth, TX) with 50% of the manifest refractive astigmatism (on the same axis) while the spherical ablation is added so as not to exceed a total of 50-µm ablation of the epithelium and anterior stroma. Afterward, all patients underwent CXL. Data collected included thinnest corneal thickness (TCT), subjective astigmatism, mean keratometric power, maximum keratometric power (K max ), uncorrected distance visual acuity (UDVA), and corrected distance visual acuity (CDVA)., Results: A total of 20 eyes of 20 patients with a mean age of 28.0 ± 6.5 years (range: 13 to 40 years) and a mean follow-up of 823 ± 337 days (range: 266 to 1,749 days) were included. There was a significant improvement in both UDVA (from 0.95 ± 0.73 to 0.22 ± 0.15 logMAR, P < .001) and CDVA (from 0.24 ± 0.13 to 0.13 ± 0.12 logMAR, P < .001) at the end of the follow-up period. There was a significant improvement in mean keratometry (from 46.86 ± 2.48 to 45.00 ± 2.27 diopters [D], P < .001), K max (from 48.18 ± 2.74 to 45.97 ± 2.55 D, P < .001), and K min (from 45.54 ± 2.35 to 44.03 ± 2.12 D, P < .001). TCT was significantly lower following the procedure (from 450.90 ± 35.99 to 404.90 ± 43.96 µm, P < .001). No complications and no progression in keratoconus severity were noticed during the follow-up period., Conclusions: The Tel-Aviv Protocol for patients with progressive keratoconus provides good improvement in visual acuity and astigmatism while halting the progression of keratoconus. [J Refract Surg. 2019;35(6):377-382.]., (Copyright 2019, SLACK Incorporated.)

Purpose: To investigate the effect of accelerated corneal cross-linking (CXL) on epithelial thickness change and refractive outcome after myopic transepithelial photorefractive keratectomy (TPRK)., Methods: This study compared epithelial thickness changes in 49 patients undergoing TPRK-CXL with 49 patients undergoing TPRK who were matched for age and refractive error. Corneal epithelial thickness, obtained using spectral-domain optical coherence tomography preoperatively and 12 months postoperatively, was compared between the groups. Regression analysis was performed to investigate the association between changes in epithelial thickness and keratometric power. Factors affecting myopic regression (> 0.50 diopters] were evaluated using logistic regression analysis., Results: For TPRK, the mean epithelial thickness of the center (2-mm diameter), paracenter (2- to 5-mm diameter), and pericenter (5- to 6-mm diameter) increased by 6.5 ± 3.1, 7.0 ± 2.9, and 4.9 ± 2.9 µm, respectively; increases of 4.8 ± 3.0, 5.9 ± 2.8, and 4.8 ± 2.7 µm were observed following TPRK-CXL, indicating a significant difference in the center (P = .013). Epithelial thickness increased linearly to the magnitude of myopic correction and was negatively correlated with the optical zone diameter of ablation. Change in epithelial thickness showed a linear correlation with the change in keratometric power between 1 and 12 months postoperatively, indicating regression in eyes following TPRK. Corneal epithelial thickening was significantly associated with myopic regression and simultaneous CXL tended to reduce the risk of regression., Conclusions: TPRK-CXL induces less epithelial hyperplasia than does TPRK, presumably owing to the effect of CXL, and the magnitude of epithelial thickening seemed to be associated with myopic regression. [J Refract Surg. 2019;35(6):354-361.]., (Copyright 2019, SLACK Incorporated.)

Purpose: To test for an association between stiffening following corneal cross-linking (CXL) and demarcation line depth., Methods: Sixty-six eyes of 66 patients treated with CXL for progressive keratoconus were included. Dynamic corneal response parameters (DCRs) were measured with the Corvis ST (Oculus Optikgeräte GmbH; Wetzlar, Germany) on the day of CXL and after 1 month. Demarcation line was measured 4 weeks after CXL. A multivariate general linear model was used to test for an association between the change in DCRs and the ratio between demarcation line depth and the postoperative pachymetry., Results: The authors found no significant associations between the change in inverse concave integrated radius (1/R) and the demarcation line ratio (P = .46), age (P = .33), sex (P = .11), preoperative maximum keratometry (P = .10), and laterality (P = .82). Similarly, there was no significant correlation between the change in 1/R and the demarcation line ratio (R 2 = .002 and P = .75). However, there was a significant association between the preoperative values of 1/R and the respective change in 1/R (P < .0001). The change in 1/R was inversely proportional to the patient's preoperative 1/R; stiffer corneas (lower values of 1/R) were less affected than less stiff corneas (R 2 = .23, P < .0001)., Conclusions: CXL is associated with changes in DCRs, suggesting a change in corneal biomechanics following CXL. These changes do not appear to be associated with the demarcation line depth. [J Refract Surg. 2019;35(3):202-206.]., (Copyright 2019, SLACK Incorporated.)

Purpose: To compare the 2-year follow-up outcomes of three groups of patients with keratoconus treated with transepithelial iontophoresis (I-CXL), iontophoresis with epithelial removal (I-SCXL), and standard epithelium-off (S-CXL) CXL for progressive keratoconus., Methods: Sixty eyes of 60 patients treated with CXL for progressive keratoconus were included in this comparative, prospective clinical study. Twenty patients were included in each group (I-CXL, I-SCXL, and S-CXL). Corrected distance visual acuity (CDVA), refraction, corneal topography, Scheimpflug tomography, and aberrometry were assessed at baseline and at 1, 3, 6, 12, and 24 months of follow-up. To assess the long-term safety and efficacy of these treatments, the preoperative values were compared with the values at 24 months of follow-up., Results: The main outcome of the study was the non-statistically significant difference between the three protocols in induced change in most of the parameters, including visual acuity (P = .665), topographic indexes (all P > .05), and maximum keratometry (P = .611) after 2 years of follow-up. There were no significant differences in the change in refractive error following CXL in all groups or between groups (all P > .05). Conversely, I-CXL induced significantly less corneal thinning (P = .0299 and .0121) and a significantly greater reduction of higher order aberrations and coma (all P < .0001) compared to S-CXL and I-SCXL. All protocols induced a significant increase in visual acuity (S-CXL P = .0004, I-SCXL P = .0045, and I-CXL P = .004)., Conclusions: The 2-year results of this comparative, prospective clinical study demonstrate the efficacy and safety of I-CXL to treat progressive keratoconus and overcome the limitations of CXL with epithelial debridement. [J Refract Surg. 2019;35(3):184-190.]., (Copyright 2019, SLACK Incorporated.)

Purpose: To investigate the results after photorefractive keratectomy (PRK) followed immediately by standard 30-minute corneal cross-linking (CXL) for keratoconus., Methods: This retrospective study included 26 eyes of 16 patients with keratoconus. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent (SE) and cylinder, apical keratometry, corneal higher order aberrations (HOAs), and corneal haze were evaluated., Results: Mean follow-up was 32 ± 8 months (range: 19 to 50 months) and mean patient age was 31 ± 5 years (range: 24 to 40 years). Mean UDVA improved significantly from 0.80 ± 0.39 to 0.32 ± 0.36 logMAR after surgery (P < .001), but the mean CDVA worsened significantly from 0.07 ± 0.09 to 0.15 ± 0.14 logMAR after surgery (P = .006). Thirteen eyes (50%) lost at least one line of CDVA, 3 eyes (12%) lost two lines, and 4 eyes (15%) lost three lines. SE, cylinder, and apical keratometry decreased significantly. Corneal haze grade 1 was found in 15 eyes (57.7%), grade 2 in 6 eyes (23.1%), and grade 3 in 1 eye (3.8%). A significant correlation was seen between postoperative CDVA loss and corneal haze (P = .001) and history of atopy (P < .01), but not with corneal HOA change., Conclusions: Despite an improvement in UDVA and topographic values, the loss of CDVA, explained by postoperative haze, demonstrates that this procedure should be approached with caution, may not be as safe as initially thought, especially in patients with atopy and can cause severe visual acuity loss. [J Refract Surg. 2019;35(2):109-114.]., (Copyright 2019, SLACK Incorporated.)

Purpose: To compare the long-term changes in corneal biomechanics, topography, and tomography before and 4 years after corneal cross-linking (CXL) with the Dresden protocol and correlate these changes with visual acuity., Methods: In this longitudinal study, 18 eyes of 18 patients with progressive keratoconus who were treated with CXL were included. All patients received a standard ophthalmological examination and were examined by Placido disc-based topography, Scheimpflug tomography, and biomechanical assessments with the Corvis ST (OCULUS Optikgeräte GmbH, Wetzlar, Germany) and Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Buffalo, NY) before and 4 years after CXL. The main outcome measures were dynamic corneal response (DCR) parameters obtained from the Corvis ST, corneal hysteresis (CH), corneal resistance factor (CRF), visual acuity, refraction, corneal curvature, and corneal thickness., Results: There were no significant differences in mean visual acuity, refraction, intraocular pressure, corneal topography, corneal astigmatism in both corneal surfaces, maximum keratometry, corneal thickness at apical and thinnest points, thickness profile indices, corneal volume, and specular microscopy before and 4 years after CXL (P > .05). Significant changes were observed in many DCR parameters, including radius at highest concavity and integrated inverse radius, both of which were consistent with stiffening. The CH and CRF values after CXL were not statistically significant. The new parameters using the Corvis ST include integrated inverse concave radius, which showed a significant decrease 1.07 ± 0.93 mm -1 , consistent with stiffening. The corneal stiffness parameter at the first applanation, Ambrósio's Relational Thickness to the horizontal profile, deformation amplitude ratio, and Corvis Biomechanical Index as a combined biomechanical screening parameter did not show significant changes., Conclusions: CXL is a minimally invasive treatment option to prevent keratoconus progression over 4 years. Pressure-derived biomechanical parameters obtained from the ORA did not show any change following CXL at 4 years of follow-up, whereas the Corvis ST DCR parameters detected changes in corneal biomechanical properties. [J Refract Surg. 2018;34(12):849-856.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To evaluate the impact of varying treatment time on the efficacy of iontophoresis-assisted transepithelial corneal cross-linking (I-CXL) in ex vivo porcine corneas., Methods: One hundred twelve porcine corneas with intact epithelium were divided into 7 groups and analyzed. Groups 1, 2, and 3 received standard epitheliumoff CXL (S-CXL) with hypo-osmolaric 0.1% riboflavin and 30 minutes of ultraviolet-A (UV-A) irradiation at 3 mW/cm 2 , 10 minutes at 9 mW/cm 2 , or were not irradiated (controls). Groups 4, 5, 6, and 7 received I-CXL for either 60 minutes at 1.5 mW/cm 2 , 30 minutes at 3 mW/cm 2 , 10 minutes at 9 mW/cm 2 , or were not irradiated (controls). Elastic modulus and stress after relaxation of 5-mm wide corneal strips were analyzed., Results: In the S-CXL groups, significant differences (P ≤ .05) in stress-strain extensometry were found between controls and 3 mW/cm 2 for 30 minutes (group 1) and between controls and 9 mW/cm 2 for 10 minutes (group 2). In the I-CXL groups, only the 1.5 mW/cm 2 for 60 minutes setting (group 4) showed a significant stiffening effect. All epithelium-off groups provided a stiffening effect significantly stronger than I-CXL: with a stiffening effect of 149% and 112%, groups 1 and 4 were the groups with greater elastic modulus between the S-CXL and I-CXL groups, respectively., Conclusions: The biomechanical effect of I-CXL increased significantly when using a low irradiance/long irradiation setting. Oxygen diffusion thus represents a limiting factor even when riboflavin penetration is improved via iontophoresis. Still less effective than S-CXL, this modification may help establish transepithelial CXL as a treatment option in selected cases. [J Refract Surg. 2018;34(11):768-774.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To evaluate the outcomes of simultaneous and sequential corneal crosslinking (CXL) and excimer laser surface ablation protocols in keratoconus., Methods: A literature review was conducted using MEDLINE. The studies were divided into three groups: the sequential group included studies with CXL followed by excimer laser surface ablation later, the simultaneous group included simultaneous excimer laser surface ablation and CXL, and the no CXL group included excimer laser surface ablation only with no CXL. The data on change in logMAR uncorrected distance visual acuity (UDVA), spectacle corrected distance visual acuity (CDVA), change in spherical equivalent (SE) and refractive astigmatism, change in maximum keratometry (Kmax), complications, and safety and efficacy indices were presented for the latest follow-up visits in all groups., Results: Twenty-one studies (3 = sequential; 11 = simultaneous, 7 = no CXL) were included. UDVA improved in all groups. CDVA improved more in the sequential group. SE change was greatest in the no CXL group and the refractive astigmatism reduced comparably in the sequential and no CXL groups but less in the simultaneous group. Kmax reduced in all groups. Only the sequential group showed no progression. Corneal haze was reported in 100%, 54.5%, and 57.1% studies, respectively. Safety and efficacy indices were 1.96 and 1.58, 1.41 ± 0.32 and 0.91 ± 0.41, and 1 and 0.82, respectively., Conclusions: The sequential group showed greater improvement in CDVA, SE, and refractive astigmatism. Corneal haze was frequently reported in all protocols. Safety and efficacy indices were highest when CXL was performed before excimer laser and least when excimer laser was performed alone without CXL. [J Refract Surg. 2018;34(10):690-696.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To report 3 cases with continued long-term flattening after corneal cross-linking (CXL) for keratoconus and to determine its prevalence., Methods: Case series., Results: Three eyes of three patients presented with an ongoing corneal flattening over 10 years after CXL in the absence of corneal opacities. Of the initial 433 eyes treated with CXL between 2005 to 2007, only 45 eyes completed the 10-year follow-up period, indicating a prevalence of 6.7%., Conclusions: Besides continuous flattening due to scars and intense early flattening, a third entity of continuous flattening can be observed after CXL. Continuous long-term flattening after CXL seems to affect more patients than initially anticipated and should be considered as a late-onset complication of CXL. [J Refract Surg. 2018;34(8):567-570.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To examine the clinical characteristics, treatments, and prognosis of all cases of infectious keratitis resistant to conventional therapy and treated by photo-activated chromophore for keratitis corneal cross-linking (PACK-CXL) in one institution between 2012 and 2016., Methods: A database search of patients who underwent PACK-CXL (ultraviolet-A for 10 minutes for irradiance of 9 mW/cm 2 ) for infectious keratitis unresponsive to medical treatment at a tertiary care hospital was conducted. The following parameters were documented: patient demographic information, corrected distance visual acuity (CDVA) before the procedure and at the end of follow-up, characteristics of the ulcer, antibiotic treatment prior to CXL, culture results, and long-term complications. Cases with less than 1 year of follow-up were excluded., Results: PACK-CXL was performed in 18 consecutive eyes. CDVA at the time of presentation was 1.47 logMAR (mean 1.47 ± 0.72 logMAR, range: 0.00 to 2.79 logMAR). Culture results were positive in 72% of eyes (13 of 18 patients) and no pathogens were identified in 28% of eyes (5 of 18 patients). All patients were treated with more than one antibiotic. The mean CDVA at the end of follow-up was 1.22 logMAR (mean: 1.22 ± 0.89 logMAR, range: 0 to 2.07 logMAR). There was no significant change between CDVA at presentation to CDVA at the end of follow-up (matched pair, P = .126). One eye underwent an emergency therapeutic penetrating keratoplasty., Conclusions: Patients with large, central corneal ulcer and poor CDVA who were resistant to conventional treatment underwent PACK-CXL. At the end of follow-up, only one eye required emergency penetrating keratoplasty. This low rate might be attributed to a good response to CXL. [J Refract Surg. 2018;34(8):559-563.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To evaluate and compare epithelial remodeling after standard corneal cross-linking (S-CXL) and iontophoresis-assisted CXL (I-CXL) in eyes with keratoconus by anterior segment optical coherence tomography (AS-OCT)., Methods: In this prospective, observational study, AS-OCT and corneal topography were performed before and 1, 3, and 6 months after surgery. Corneal pachymetry was performed and epithelial and stromal thicknesses (central and 16 points on the 6-mm central zone) and the maximum simulated keratometry value (Kmax) were measured., Results: Two groups of 30 patients (60 eyes total) with progressive keratoconus underwent S-CXL or I-CXL. Before surgery, both groups of patients presented with an irregular epithelial thickness profile. At 6 months postoperatively, localized corneal epithelial thinning was observed in the superior (P = .026), inferior (P = .034), inferonasal (P = .024), and nasal (P = .035) areas at 3 mm and in the superior (P = .039), nasal (P = .043), and inferior (P = .01) areas at 6 mm in the SCXL group. Localized corneal epithelial thinning was observed at 3 (P = .04) and 6 (P = .01) mm in the inferior area in the I-CXL group. No significant stromal changes were observed for either group. Kmax was stable in both groups at 6 months., Conclusions: Significant epithelial remodeling occurs after S-CXL, resulting in a thinner, more regular thickness profile than after I-CXL. Epithelial thickness profile measurements after I-CXL could be used as an adjunctive follow-up tool for monitoring the efficacy of CXL in progressive keratoconus. [J Refract Surg. 2018;34(8):551-558.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To assess the safety and efficacy of a novel pulsed-light enhanced-fluence iontophoresis corneal cross-linking (EF I-CXL) procedure in patients with progressive keratoconus., Methods: This prospective interventional pilot study included 12 eyes of 10 patients. Iontophoresis with Ricrolin+ solution (Sooft, Montegiorgio, Italy) was used for stromal imbibition. The treatment energy dose (fluence) was optimized at 30% (from 5.4 J to 7 J/cm 2 ) and ultraviolet-A (UV-A) power set at 18 mW/cm 2 × 6.28 minutes of exposure time, pulsing the light 1 second on/1 second off with a total irradiation time of 12.56 minutes. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), Scheimpflug corneal tomography data, and corneal optical coherence tomography (OCT) at baseline and 1, 3, 6, and 12 months postoperatively were evaluated., Results: Twelve-month statistically significant average data (P < .05) showed UDVA decreased from 0.50 ± 0.10 to 0.36 ± 0.08 logMAR, maximum keratometry decreased from 52.86 ± 1.50 to 51.49 ± 0.90 diopters (D), surface asymmetry index decreased from 2.34 ± 0.36 to 2.13 ± 1.12 D, symmetry index decreased from 4.22 ± 1.01 to 3.56 ± 0.90 D, and coma decreased from 0.25 ± 0.05 to 0.14 ± 0.06 μm. Corneal OCT showed greater than 80% demarcation line detection at 295.8 ± 20.2 μm depth on average in the first postoperative month., Conclusions: The preliminary results of the EF I-CXL protocol demonstrate its capability to increase I-CXL efficacy closer to standard CXL. [J Refract Surg. 2018;34(7):438-444.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To report the long-term clinical outcomes of a patient with Terrien's marginal degeneration who underwent successful peripheral corneal cross-linking (CXL) to arrest progression., Methods: Clinical assessment included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal topography, anterior segment optical coherence tomography, ultrasonic pachymetry, corneal hysteresis, and corneal resistance factor. Eccentric epithelium-off CXL was performed in both eyes after limbal conjunctival resection. Following the Dresden protocol, fluence irradiation was set at 5.4 J/cm 2 , using 3 mW/cm 2 for a total exposure time of 30 minutes., Results: Nine years of postoperative follow-up showed significant bilateral improvement in visual acuity, refraction, and corneal topography with no signs of progression of Terrien's marginal degeneration. In the right eye, UDVA improved from 0.05 to 0.3 decimal and CDVA from 0.8 to 1.2 decimal, cylinder was reduced from -14.00 to -3.00 diopters (D), simulated keratometry improved from 10.50 to 3.70 D, and the thinnest point on pachymetry remained almost unchanged (from 483 to 469 μm). In the left eye, UDVA improved from 0.1 to 0.2 decimal and CDVA remained unchanged at 1.2 decimal, cylinder was reduced from -6.00 to -2.75 D, simulated keratometry improved from 5.60 to 3.30 D, and the thinnest point on pachymetry remained stable at 486 μm., Conclusions: Eccentric peripheral CXL can be a safe, noninvasive alternative therapeutic approach for the management of Terrien's marginal degeneration with peripheral thinning. [J Refract Surg. 2018;34(6):424-429.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To evaluate remodeling of the corneal epithelium after epithelium-off corneal cross-linking (CXL)., Methods: In this prospective single-center study, 93 eyes of 93 patients with progressive keratoconus underwent standard CXL. The maximum keratometry was assessed before and after CXL with Scheimpflug imaging, and the epithelial thickness profile across the central 5 mm of the cornea was assessed with spectral-domain optical coherence tomography anterior segment imaging., Results: The mean patient age was 27 ± 11 years; 76 patients (81%) were male and 17 (19%) were female. Between baseline and 6 months after CXL, the mean corneal maximum keratometry flattened from 58.90 to 57.80 diopters (P < .0001). The mean minimum epithelial thickness increased slightly (from 41 ± 6 to 42 ± 7 μm, P = .12), whereas the mean maximum epithelial thickness decreased slightly (from 65 ± 6 to 64 ± 7 μm, P = .067), reducing the net difference between the minimum and maximum epithelial thickness (from 24 ± 9 to 22 ± 9 μm, P = .0023). The difference between the minimum and maximum epithelial thickness was strongly positively correlated with the maximum keratometry reading at baseline (R 2 = 0.38) and at 6 months after CXL (R 2 = 0.59)., Conclusions: Epithelium-off CXL resulted in modest regularization of the epithelial thickness profile across the central 5 mm of the cornea at 6 months. This could slightly mask flattening of the underlying stroma. [J Refract Surg. 2018;34(6):408-412.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To present a case of bilateral, asymmetric keratoconus presenting unilaterally after partial thyroidectomy with delayed presentation in the second eye after thyrotoxicosis, with disease stabilization following corneal cross-linking (CXL)., Methods: Case report and literature review., Results: A 17-year-old girl with a history of Graves' disease underwent partial thyroidectomy without thyroid hormone replacement therapy with normal baseline ophthalmic examination of corrected distance visual acuity (CDVA) of 20/20 and no manifest astigmatism in either eye. At age 29 years, keratoconus manifested in the right eye and standard protocol CXL was performed. At age 40 years, the right eye remained stable after CXL, but keratoconus manifested in the left eye and epithelium-off accelerated CXL was performed with subsequent disease stabilization., Conclusions: This case demonstrates the association between thyrotoxicosis and keratoconus and the bilateral nature of keratoconus, and highlights the potentially asymmetric presentation of thyroid-induced keratoconus. CXL had a long-term stabilizing effect over 10 years despite the ongoing effects of thyroid gland dysfunction. [J Refract Surg. 2018;34(5):354-356.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To describe a new technique for the treatment of keratoconus using corneal allogenic intrastromal ring segments (CAIRS)., Methods: CAIRS trephined from donor cornea using a double-bladed trephine were implanted into mid-depth femtosecond laser-dissected channels in the cornea of patients with keratoconus in the 6.5-mm optic zone, followed by accelerated corneal cross-linking (A-CXL)-either conventional or contact lens-assisted CXL (A-CACXL), depending on minimum corneal thickness., Results: Twenty patients (24 eyes) with stage 1 to 4 keratoconus (Amsler-Krumeich grading) were included. Mean follow-up was 11.58 ± 3.6 months (range: 6 to 18 months). There was significant improvement in uncorrected (2.79 ± 2.65 lines; range: 0 to 8 lines) and corrected (1.29 ± 1.33 lines; range: 0 to 5 lines) distance visual acuity, spherical equivalent, simulated maximum keratometry, steepest keratometry, topographic astigmatism, anterior and posterior best fit spheres, and mean power in the 3- and 5-mm zones. No eye showed progression during the entire follow-up. All segments remained well positioned and no segment-induced complications were seen. No other major intraoperative or postoperative complications were observed., Conclusions: This pilot study indicates that CAIRS with CXL may be a simple, safe, and effective option for treating keratoconus. Further studies are recommended to determine long-term outcomes. [J Refract Surg. 2018;34(5):296-303.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To present a case of new-onset, bilateral, rapidly progressive keratoconus induced by secondary hypothyroidism after radioactive iodine therapy during the sixth decade of life that was successfully treated with corneal cross-linking., Methods: Case report and literature review., Results: A 53-year-old woman with no ocular complaints but with a history of Graves' disease and thyrotoxicosis was treated with radioactive iodine therapy and oral levothyroxine for secondary acquired hypothyroidism 3 years prior. Initially, uncorrected distance visual acuity (UDVA) was 20/40 and corrected distance visual acuity (CDVA) was 20/25 in both eyes. Over the following 3 years, the patient developed worsening UDVA and CDVA, with increasing manifest astigmatism of greater than 7.00 diopters (D) in the right eye and 4.75 D in the left eye, with corneal thinning and focal steepening and was diagnosed as having bilateral progressive keratoconus. The patient underwent sequential corneal cross-linking with resultant postoperative CDVA of 20/20 and reduced maximum keratometry and manifest astigmatism in both eyes. The patient's thyroid levels were within normal limits throughout the clinical course., Conclusions: This case provides evidence of the relationship between keratoconus development and thyroid gland dysfunction. The pathophysiology of this relationship has yet to be completely elucidated, but elevated levels of thyroxine in the aqueous humor and tear film and thyroxine receptors in the cornea likely play a role. Screening topographies for patients with thyroid gland dysfunction may be of value for these higher risk patients. [J Refract Surg. 2018;34(5):351-353.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To determine the relationship between mechanical behavior in cross-linked corneas and changes in the corneal ultrastructure after corneal cross-linking (CXL)., Methods: Porcine corneas were treated following the "Dresden" protocol, the current gold standard for clinical treatment, consisting of dropwise application of 0.1% riboflavin in 20% dextran followed by 30 minutes of ultraviolet-A (UVA) irradiation. The effect of CXL was assessed using uniaxial tensile testing, transmission electron microscopy, and Fourier transform infrared spectroscopy, with results compared against corneas treated with each of the treatment solution components individually., Results: UVA/riboflavin cross-linked corneas displayed 28% ± 17% increase in the material tangent modulus compared with dextran treatment alone, and altered collagen architecture within the first 300 µm of stromal depth consisting of 5% increase in the thickness of collagen fibrils, no significant changes to interfibrillar spacing, and an 8% to 12% decrease in number of fibrils per unit area. Fourier transform infrared spectroscopy confirmed formation of interfibrillar bonds (P = .012) induced by UVA-mediated CXL., Conclusions: The data support a model wherein collagen fibril diameter and structural density are fundamental parameters in defining tissue stiffening following UVA/riboflavin CXL and provide benchmarks against which modifications to the Dresden CXL protocol can be evaluated. [J Refract Surg. 2018;34(4):264-272.]., (© 2018 Chang, Mohammadvali, Chen, et al.)

Purpose: To evaluate the clinical results of epitheliumoff corneal cross-linking (CXL) during a 7-year follow-up., Methods: This retrospective, non-randomized, single-center interventional study enrolled 34 consecutive eyes of 24 patients with progressive keratoconus undergoing CXL surgery with epithelium removal. Visual, refractive, corneal topographic, pachymetric, and anterior segment changes were evaluated at 1, 3, and 7 years after surgery., Results: Significant reduction of refraction was observed at 1 year postoperatively (P ≤ .006), with an additional significant reduction between the 1- and 3-year postoperative visits (P ≤ .002) and no significant changes afterward (P ≥ .156). Regarding corrected distance visual acuity (CDVA), a significant improvement was detected at 1 year after surgery (P < .001), with an additional improvement between 1 and 3 years postoperatively (P = .001), and no significant changes at the end of the follow-up (P = .518). Significant corneal flattening was observed at 1, 3, and 7 years after surgery (P ≤ .041). Likewise, a significant central thinning was observed at 1 year postoperatively (P < .001), with no significant changes afterward (P ≥ .112). Anterior maximum elevation only changed significantly between 1 and 3 years after surgery (P = .002), whereas the posterior maximum elevation changed significantly at all time points of the follow-up (P ≤ .034). No significant changes with surgery in anterior segment volume (P ≥ .377) and anterior chamber depth (P ≥ .142) were detected., Conclusions: The effect of epithelium-off CXL in progressive keratoconus is maintained 7 years after surgery. Long-term corneal changes after this procedure may be influenced by an age-related corneal stiffening process. [J Refract Surg. 2018;34(3):181-186.]., (Copyright 2018, SLACK Incorporated.)