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Purpose: To compare and assess the visual, refractive, and tomographic results of patients with corneal ectasia treated with either corneal allogenic intrastromal ring segments (CAIRS) or synthetic intrastromal corneal ring segments (ICRS) without concomitant corneal cross-linking., Methods: In this retrospective cohort study, 34 eyes with CAIRS were matched to 34 eyes with ICRS using the propensity score matching technique. Each group was matched on a oneto-one basis using multiple parameters such as central corneal thickness, vertical and horizontal coma, maximum anterior keratometry, steepest keratometry, and age. Visual, refractive, topographic, and aberrometric data were measured at baseline, 1 week, 1 month, 3 months, and 1 year postoperatively., Results: Initial preoperative parameters were similar between the two groups. Both groups showed significant improvement at last follow-up time in corrected distance visual acuity (CDVA) (0.52 ± 0.23 to 0.16 ± 0.18 logarithm of the minimum angle of resolution [logMAR], P < .001; 0.44 ± 0.27 to 0.17 ± 0.21 logMAR, P < .001), topographic astigmatism (4.45 ± 2.75 to 3.14 ± 1.93 diopters [D], P = .001; 3.66 ± 2.22 to 2.36 ± 1.46 D, P = .007), maximum anterior keratometry (55.85 ± 7.53 to 50.69 ± 6.38 D, P < .001; 54.59 ± 6.95 to 50.71 ± 4.51 D, P = .003), and vertical coma (1.49 ± 1.02 to 0.38 ± 0.65 D, P < .001; 1.22 ± 0.75 to 0.52 ± 0.57 D, P < .001) for CAIRS and ICRS, respectively. The improvements observed in both groups at the last follow-up visit were comparable; however, the CAIRS group demonstrated a higher percentage of eyes gaining two or more Snellen lines of CDVA (60% vs 31.58%, P = .04), and a greater magnitude of reduction in vertical coma compared to the ICRS group, although this difference did not reach statistical significance. No major complications were observed with both groups, and one eye lost one CDVA line in the ICRS group. The mean thickness of the CAIRS segments at the last follow-up visit was 401.06 ± 100.12 µm, compared to 435.29 ± 26.19 µm for ICRS. Both CAIRS and ICRS demonstrated significant compression of stromal thickness above the segment (36.19% and 32.00%, respectively)., Conclusions: When adequately matched for preoperative disease type and severity, eyes with CAIRS had a similar and notable clinical improvement compared to ICRS, with possibly better improvement in vertical coma and CDVA. [ J Refract Surg . 2024;40(11):e863-e876.] ., Competing Interests: Disclosure: SJ has a patent pending for special trephines, devices, and processes used to create these segments, as well as for the corneal allogenic intrastromal ring segments and various types of shaped corneal segments. The remaining authors have reported no potential conflicts of interest, financial or otherwise.

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 describe a novel technique for cutting asymmetric allogenic segments using the femtosecond laser for the management of cases of keratoconus with non-coinciding astigmatism and coma axes., Methods: Four eyes of 2 patients with irregular keratoconus and asymmetric allogenic segments were included. Visual, refractive, tomographic, and aberrometric outcomes, and optical coherence tomography (OCT) sections were measured preoperatively and 6 months postoperatively. Evaluations included slit-lamp examination, manifest refraction, uncorrected (UDVA) and corrected (CDVA) distance visual acuity, and simulated and maximum anterior keratometry (Kmax) using anterior segment OCT., Results: Spherical and cylindrical refractive errors decreased from -2.38 ± 2.96 and -2.94 ± 2.16 to -1.81 ± 2.77 ( P = .04) and -1.75 ± 2.07 ( P = .01) diopters (D), respectively, 6 months postoperatively. There was an average gain of three lines of CDVA. Kmax decreased from 50.02 ± 1.99 to 47.89 ± 3.05 D (P= .03) and coma from 1.05 ± 0.21 to 0.21 ± 0.19 D ( P = .01)., Conclusions: Asymmetric femtosecond laser-cut allogenic segments allow a higher level of customization based on size, shape, and arc length, in contrast to the limited range of available synthetic asymmetrical segments. [ J Refract Surg . 2023;39(12):856-862.] .

Purpose: To evaluate the visual, refractive, and tomographic results of patients with corneal ectasia treated with corneal allogenic intrastromal ring segments (CAIRS) insertion without concomitant corneal cross-linking., Methods: Fifty-two eyes from 39 patients with stable corneal ectasia and unsatisfactory visual acuity with contact lenses were included. All patients underwent CAIRS insertion with no concomitant corneal procedure at the American University of Beirut Medical Center between September 2019 and July 2022. Visual, refractive, topographic, aberrometric, epithelial, stromal, and segment thickness data were measured relative to baseline at 1 week, 1 month, and at least 3 months postoperatively. Evaluations included slit-lamp examination, manifest refraction, uncorrected (UDVA) and corrected (CDVA) distance visual acuity, and tomography using anterior segment optical coherence tomography., Results: Mean follow-up time was 6.9 ± 5.2 months. UDVA and CDVA improved from 0.97 ± 0.47 and 0.56 ± 0.19 preoperatively to 0.52 ± 0.21 ( P < .001) and 0.23 ± 0.19 ( P < .001) 3 months postoperatively. Manifest refraction spherical equivalent and cylinder improved from -6.71 ± 6.51 and -4.02 ± 2.24 diopters (D) preoperatively to -3.78 ± 4.07 D ( P < .001) and -2.35 ± 1.98 D ( P < .001) 3 months postoperatively, respectively. Maximum anterior keratometry and vertical coma decreased from 58.09 ± 7.92 D and 1.56 ± 1.09 µm to 52.48 ± 6.69 D ( P < .001) and 0.43 ± 0.77 µm, respectively ( P < .001). Corneal epithelium thickened proximal to the allogenic segment by 7.25 µm ( P < .001), whereas stromal elevation at the cone decreased from 38.61 ± 18.5 to 23.82 ± 13.4 µm, respectively ( P < .001). No major complications were observed and only 1 eye lost one line of CDVA., Conclusions: Treatment of corneal ectasia with CAIRS improved visual, refractive, topographic, and tomographic parameters. Epithelial thickening central to CAIRS, along with anterior stromal flattening is postulated to contribute to tomographic flattening and regularization. [ J Refract Surg . 2023;39(11):767-776.] .

Purpose: To evaluate the effect of simulated repetitive eye rubbing on the corneal biomechanics of porcine eyes using an ex vivo model system., Methods: The average rubbing force that patients with keratoconus apply to their eyelids was previously determined. Fresh porcine eyes with eyelids were either exposed to 10,500 rub cycles from a custom-built eye rubbing machine that rubbed with a similar force to knuckle human eye rubbing (n = 33) or no rubbing at all (control; n = 37). A total of 10,500 rubs are equivalent to 1 year of rubbing six times daily, five movements per rub. The corneal biomechanical properties of these eyes were then tested by measuring the elastic modulus of 5-mm strips., Results: The elastic modulus at the range of 1% and 5% of strain was 1.219 ± 0.284 and 1.218 ± 0.304 N/mm 2 in the eye rubbing group and the no-rub control group, respectively. Corneal stiffness was similar in both groups ( P = .984)., Conclusions: The threshold to induce biomechanical changes (purely by eye rubbing) must be higher than 10,500 rubbing movements, suggesting that occasional eye rubbing may not affect corneal biomechanics in normal eyes, and likely only triggers keratoconus progression in predisposed corneas. Further in vivo studies assessing the impact eye rubbing has on inflammatory activity and the biomechanical properties of weakened corneas is warranted. [ J Refract Surg . 2022;38(9):610-616.] .

Purpose: To quantify the mechanical impact of intracorneal ring segment (ICRS) implantation of different dimensions in an ex vivo eye model., Methods: A total of 30 enucleated porcine eyes were assigned to ICRS implantation (thickness: 300 µm, angle: 120°, 210°, or 325°), tunnel creation only, or virgin control groups. For mechanical evaluation, each globe was mounted on a customized holder and intraocular pressure (IOP) was increased in steps of 0.5 mm Hg from 15 to 17 mm Hg, simulating physiologic diurnal IOP fluctuations. At each step, an optical coherence tomography volume scan was recorded. Deformations between subsequent scans and the locally induced axial strains were analyzed using a vector-based phase difference method. The effective E-modulus was derived from the overall induced strain as a measure of global mechanical impact., Results: ICRS implantation increased the effective E-modulus from 146 and 163 kPa in virgin and tunnel-only eyes to 149, 192, and 330 kPa in eyes that received a 5-mm optical zone ICRS with 120°, 210°, and 325° arc length, respectively; and to 209 kPa in a 6-mm optical zone ICRS with 325° arc length. The most consistent effect was a shift toward positive strains in the posterior stroma by 0.1% to 0.46% (factor 1.15 to 2.15) after ICRS surgery., Conclusions: ICRS implantation reduces the overall tissue strain under the load of the IOP and provokes posterior tissue relaxation. This effect is more prominent the longer the arc length and the smaller the optical zone of the ICRS is. ICRS have not only a geometrical, but also a mechanical impact on corneal tissue. This behavior might have clinical implications when ICRS implantation is performed in biomechanically weakened keratoconic corneas. [ J Refract Surg . 2022;38(7):459-464.] .

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 investigate the diagnostic capacity of spectral-domain optical coherence tomography (SD-OCT) combined with air-puff tonometry using artificial intelligence (AI) in differentiating between normal and keratoconic eyes., Methods: Patients who had either undergone uneventful laser vision correction with at least 3 years of stable follow-up or those who had forme fruste keratoconus (FFKC), early keratoconus (EKC), or advanced keratoconus (AKC) were included. SD-OCT and biomechanical information from air-puff tonometry was divided into training and validation sets. AI models based on random forest or neural networks were trained to distinguish eyes with FFKC from normal eyes. Model accuracy was independently tested in eyes with FFKC and normal eyes. Receiver operating characteristic (ROC) curves were generated to determine area under the curve (AUC), sensitivity, and specificity values., Results: A total of 223 normal eyes from 223 patients, 69 FFKC eyes from 69 patients, 72 EKC eyes from 72 patients, and 258 AKC eyes from 258 patients were included. The top AUC ROC values (normal eyes compared with AKC and EKC) were Pentacam Random Forest Index (AUC = 0.985 and 0.958), Tomographic and Biomechanical Index (AUC = 0.983 and 0.925), and Belin-Ambrósio Enhanced Ectasia Total Deviation Index (AUC = 0.981 and 0.922). When SD-OCT and air-puff tonometry data were combined, the random forest AI model provided the highest accuracy with 99% AUC for FFKC (75% sensitivity; 94.74% specificity)., Conclusions: Currently, AI parameters accurately diagnose AKC and EKC, but have a limited ability to diagnose FFKC. AI-assisted diagnostic technology that uses both SD-OCT and air-puff tonometry may overcome this limitation, leading to improved treatment of patients with keratoconus. [ J Refract Surg . 2022;38(6):374-380.] .

Purpose: To investigate the biomechanical properties of ex vivo human paired corneas after hyperopic correction via cap-based versus flap-based laser-assisted refractive surgery., Methods: In this prospective experimental study, 13 pairs of human corneas unsuitable for transplantation were equally divided into two groups. The pachymetry was performed in each eye just before the laser procedure. Corneas from the right eye were treated with small incision lenticule extraction (SMILE), whereas corneas from the left eye of the same donor were treated with femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). All corneas were subjected to a refractive correction of +6.00 diopters (D) sphere with a 6.5-mm zone under a 120-µm cap (SMILE) or a 7-mm zone under a 110-µm flap (FS-LASIK). For two-dimensional biomechanical measurements, the corneoscleral buttons underwent two testing cycles (preconditioning stress-strain curve from 0.03 to 9.0 N and stress-relaxation at 9.0 N during 120 seconds) to analyze the elastic and viscoelastic material properties. The effective elastic modulus was calculated. Statistical analysis was performed with a confidence interval of 95%., Results: In stress-strain measurements, the effective elastic modulus was not significantly different ( P > .311) between SMILE (13.5 ± 12.8 MPa) and FS-LASIK (7.56 ± 17.9 MPa). In stress-relaxation measurements, the remaining stress was not significantly different ( P = .841) between SMILE (124 ± 20 kPa) and FS-LASIK (126 ± 21 kPa)., Conclusions: Unlike myopic correction, after hyperopic correction the cap-based procedure (SMILE) and the flap-based technique (FS-LASIK) may be considered equivalent in terms of biomechanical stability when measured experimentally in ex vivo human fellow eye corneas. [ J Refract Surg . 2021;37(12):810-815.] .

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 describe a new surgical technique where corneal cross-linking (CXL) (to treat corneal ectasias) and photo-activated chromophore for keratitis-CXL (PACK-CXL) are performed while the patient is seated in an upright position at the slit lamp., Methods: Topical anesthesia is applied in the waiting room, 10 minutes before the procedure. Once in the office or procedure room, eyelids and periorbital areas are disinfected with chloramphenicol and the patient is seated at the slit lamp. Epithelial debridement is performed with a cotton swab soaked in freshly prepared 40% ethanol, using 70 seconds of tapping, followed by gentle pressure to remove the epithelium. The patient is placed in the supine position for riboflavin application for 10 minutes. Stromal thickness is assessed using ultrasound pachymetry after 5 and 10 minutes. Finally, the patient is returned to the slit lamp to receive ultraviolet irradiation., Results: CXL at the slit lamp is an easy-to-perform technique that substantially reduces the infrastructure needed to perform CXL and PACK-CXL procedures., Conclusions: A significant advantage of allowing CXL treatment at the slit lamp is that CXL technology can now be used in clinics that do not have easy access to an operating room infrastructure. Slit-lamp CXL can also reduce procedure costs by eliminating the technical fees related to the use of an operating room, making this treatment not only more accessible for patients, but also affordable. [J Refract Surg. 2021;37(2):78-82.]., (Copyright 2021, 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 evaluate the biomechanical effect of corneal cross-linking (CXL) in paired human corneas following small incision lenticule extraction (SMILE) or photorefractive keratectomy (PRK) in an ex vivo model for postoperative ectasia., Methods: Twenty-six paired human corneas preserved in tissue culture medium were equally divided into two groups: right and left corneas were treated with PRK and SMILE, respectively. Corneal thickness was measured in all eyes before surgery. Corneas were stretched using an extensometer with two cycles of up to 9 N (570 kPA stress), followed by accelerated CXL with irradiance of 9 mW/cm 2 for 10 minutes (fluence 5.4 J/cm 2 ) in both groups. The elastic modulus was evaluated using two-dimensional stress-strain extensometry., Results: Following accelerated CXL, the ectatic cornea model showed a mean effective elastic modulus of 17.2 ± 5.3 MPa after PRK and 14.1 ± 5.0 MPa after SMILE. Although the elastic modulus in corneas previously subjected to PRK was higher, there was no significant biomechanical difference between the two groups (P = .093)., Conclusions: Under similar conditions, both experimental groups (PRK followed by CXL and SMILE followed by CXL) were characterized by similar biomechanical stability as measured experimentally on ex vivo human fellow corneas. The data suggest that, in the event of postoperative ectasia, the biomechanical improvement achieved by CXL may be similar after PRK and SMILE. [J Refract Surg. 2020;36(1):49-54]., (Copyright 2020, SLACK Incorporated.)

Purpose: To determine the relative impact of contact lens- assisted corneal cross-linking (CACXL) and standard protocol CXL (CXL) on regional corneal stiffness using Brillouin microscopy., Methods: CXL and CACXL were performed on 30 intact fresh porcine eyes (15 per group). Depth profile of stiffness variation and averaged elastic modulus of anterior, middle, and posterior stroma were determined by Brillouin maps. Corneas were cut into strips to conduct mechanical stress-strain tests after Brillouin microscopy to evaluate stiffness difference between CXL and CACXL. Each eye served as its own control., Results: CXL had a greater impact on corneal stiffness, with a maximum increase of 5.74% compared to 3.99% for CACXL (P < .001). CXL increased longitudinal modulus by 7.8% in the anterior, 1.7% in the middle, and -0.7% in the posterior regions compared to CACXL, which increased longitudinal modulus by 5.5% in the anterior (P < .001), 1.2% in the middle (P = .15), and -0.4% in the posterior regions (P = .60). Mechanical stress-strain tests showed that at 10% strain averaged Young's modulus was 5 MPa for CXL and 2.97 MPa for CACXL (P < .001)., Conclusions: Both CACXL and standard protocol CXL induced significant corneal stiffening primarily concentrated in the anterior cornea. CACXL leads to less stiffening compared with CXL. An attenuated but continuous stiffening effect can be observed through the whole cornea for both CACXL and CXL, although CACXL has a smaller stiffness gradient. [J Refract Surg. 2019;35(11):721-728.]., (Copyright 2019, SLACK Incorporated.)

Purpose: To investigate the biomechanical properties of the ex vivo human paired corneas after completion of photorefractive keratectomy (PRK) versus small incision lenticule extraction (SMILE) in the same donor., Methods: In this experimental study, 13 pairs of human corneas unsuitable for transplantation were equally divided into two groups. Corneal thickness was measured in each eye directly before laser refractive surgery. Corneas from the right eye were treated with PRK and corneas from the left eye with SMILE. All corneas were subjected to a refractive correction of -10.00 diopters (D) sphere and -0.75 D cylinder at 0° with a 7 mm zone, using either surface ablation (PRK) or 130 µm cap (SMILE). For two-dimensional biomechanical measurements, corneoscleral buttons underwent two testing cycles (preconditioning stress-strain curve from 0.03 to 9.0 N and stress-relaxation at 9.0 N during 120 seconds) to analyze the elastic and viscoelastic material properties. The effective elastic modulus was calculated. Statistical analysis was performed with a confidence interval of 95%., Results: In stress-strain measurements, the effective elastic modulus was not significantly different (P = .081) between SMILE (9.58 ± 4.26 MPa) and PRK (11.9 ± 4.90 MPa). The effect size was medium (Cohen's d = 0.58). In stress-relaxation measurements, the remaining stress was not significantly different (P = .878) between SMILE (122 ± 33 kPa) and PRK (123 ± 30 kPa)., Conclusions: The lenticule extraction procedure (SMILE) and the surface ablation technique (PRK) may be considered equivalent in terms of biomechanical stability when measured experimentally in ex vivo human fellow eye corneas. [J Refract Surg. 2019;35(8):501-505.]., (Copyright 2019, SLACK Incorporated.)

Purpose: To investigate the stiffening effect of localized corneal cross-linking (L-CXL) within and beyond the irradiated region in three dimensions., Methods: Ten porcine eyes were debrided of epithelium and incrementally soaked with 0.1% riboflavin solution. Using a customized, sharp-edged mask, half of the cornea was blocked while the other half was exposed to blue light (447 nm). The three-dimensional biomechanical properties of each cornea were then measured via Brillouin microscopy. An imaging system was used to quantify the optimal transition zone between cross-linked and non-cross-linked sections of the cornea when considering light propagation and scattering., Results: A broad transition zone of 610 µm in width was observed between the fully cross-linked and non-cross-linked sections, indicating the stiffening response extended beyond the irradiated region. Light propagation and the scattering induced by the riboflavin-soaked cornea accounted for a maximum of 25 and 159 ± 3.2 µm, respectively., Conclusions: The stiffening effect of L-CXL extends beyond that of the irradiated area. When considering L-CXL protocols clinically, it will be important to account for increased stiffening in surrounding regions. [J Refract Surg. 2019;35(4):253-260.]., (Copyright 2019, 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 investigate the biomechanical properties of the ex vivo human cornea after flap-based versus cap-based laser refractive surgery in the same donor., Methods: In this experimental study, 11 pairs of human corneas unsuitable for transplantation were equally divided into two groups. Corneas from the right eye were treated with femtosecond laser-assisted LASIK (FSLASIK) and corneas from the left eye with small incision lenticule extraction (SMILE). Pachymetry was measured in each eye directly before laser refractive surgery. All corneas were subjected to a refractive correction of -10.00 diopters (D) sphere and -0.75 D cylinder at 0° with a 7-mm zone, using either a 110-μm flap (FS-LASIK) or 130-μm cap (SMILE). For two-dimensional biomechanical measurements, corneoscleral buttons underwent two testing cycles (preconditioning stress-strain curve from 0.03 to 9.0 N and stress-relaxation at 9.0 N during 120 sec) to analyze the elastic and viscoelastic material properties. The effective elastic modulus was calculated. Statistical analysis was performed with a confidence interval of 95%., Results: In stress-strain measurements, the effective elastic modulus was 1.47 times higher (P = .003) after SMILE (median = 8.22 [interquartile range = 4.76] MPa) compared to FS-LASIK (median = 5.59 [inter-quartile range = 2.77] MPa). The effect size was large (r = 0.83). No significant differences (P = .658) were observed among stress-relaxation measurements, with a mean remaining stress of 181 ± 31 kPa after SMILE and 177 ± 26 kPa after FS-LASIK after relaxation., Conclusions: Compared to a flap-based procedure such as FS-LASIK, the SMILE technique can be considered superior in terms of biomechanical stability, when measured experimentally in ex vivo human fellow eye corneas. [J Refract Surg. 2018;34(6):419-423.]., (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 corneal weakening induced by different re-treatment options after small incision lenticule extraction (SMILE) and investigate the potential of corneal cross-linking (CXL) to reestablish the original corneal stress resistance., Methods: A total of 96 freshly enucleated porcine corneas were used. The initial refractive correction was defined to be -11.00 diopters (D) and the required enhancement to be -3.00 D. Three different re-treatment options were analyzed: -3D Re-SMILE, -3D photorefractive keratectomy (PRK) on top of the SMILE cap, and cap-to-flap conversion and -3D excimer ablation on the stromal bed (LASIK). The control condition did not receive any treatment. Subsequently, accelerated CXL (9 mW/cm 2 , 10 min) was performed in two groups with currently common enhancement techniques: following cap-to-flap conversion (-3D LASIK enhancement) and in controls. Biomechanical properties were measured with stress-strain extensometry ranging from 1.27 to 12.5 N., Results: The Re-SMILE and PRK enhancement did not significantly reduce the overall elastic modulus of the cornea compared to controls (24.7 ± 2.23 and 22.7 ± 2.61 versus 23.8 ± 3.35 MPa, P ≥ .176), whereas LASIK enhancement did (22.2 ± 3.37 MPa, P = .048). CXL treatment significantly increased the elastic modulus compared to all non-cross-linked conditions (P ≤.001). Refractive surgery decreased the overall elastic modulus by 7%, whereas CXL increased it by 20%., Conclusions: In enhancement, the corneal biomechanical integrity is less affected with both Re-SMILE and PRK enhancement. Corneal weakening through laser refractive surgery is small compared to the stiffening effect after CXL. [J Refract Surg. 2017;33(3):193-198.]., (Copyright 2017, SLACK Incorporated.)

Purpose: To develop an algorithm to predict the stiffening effect of CXL and to verify the accuracy with results obtained from experimental measurements., Methods: The algorithm considers different variables: the reaction kinetics of riboflavin diffusion and riboflavin photodegradation to determine the effective riboflavin concentration in different stromal layers; the oxygen diffusion and ultraviolet (UV) absorption to determine the amount of reactive oxygen species as a function of time and stromal depth. For the experimental comparison, corneas were deepithelialized, followed by riboflavin instillation for 30 minutes and UV irradiation. Different pulsed and continuous-light conditions were analyzed with irradiances ranging from 3 to 100 mW/cm 2 and irradiation times from 8 to 30 minutes. Stress-relaxation measurements were performed in fresh-enucleated porcine (n = 66) and rabbit (n = 2) eyes directly after treatment, using a load of 0.6 MPa., Results: A clear linear relationship was observed between the concentration of newly induced cross-links and the experimentally observed stiffening factor (R 2 = 0.9432). An additional 1 mol/m 3 of cross-links increased the mechanical stress resistance of the cornea by 50.4%. The efficacy of standard CXL in murine, lapine, and porcine corneas was inversely related to corneal thickness. The stiffening effect after CXL decreased by 4.1% per 100 µm (R 2 = 0.9961)., Conclusions: The proposed model, supported by data in porcine, murine, and lapine corneas, suggests a possibility of also predicting the biomechanical CXL efficacy in human corneas. The biomechanical efficacy of CXL may be increased by prolonged UV irradiation at reduced irradiances or by a higher oxygen pressure in the environment. Pulsed CXL does not accelerate CXL or increase its efficacy when compared to standard CXL of the same irradiation duration. This model might be used to calculate customized irradiation settings for high-risk cases, but also topography-guided CXL treatments. [J Refract Surg. 2017;33(2):128-136.]., (Copyright 2017, SLACK Incorporated.)

Purpose: To study whether repeated collagen cross-linking (CXL) performed in vivo in mice shows an additive effect on mechanical corneal stiffness., Methods: In this experimental study, epithelium-off CXL was performed in a total of 18 eyes from male C57BL/6 mice, with 0.27%-riboflavin solution applied for 20 minutes, followed by ultraviolet-A (UVA) irradiation (365 nm, 9mW/cm 2 ) for 2:50 minutes (fluence 1.53 J/cm 2 ). CXL was performed as either a single (1×CXL) or a repeated (2×CXL) treatment. Un-irradiated corneas served as controls. In the 2×CXL group, the procedure was performed on day 1 and day 4 to ensure complete reepithelialization between sessions. Biomechanical analysis was performed on day 7. Corneas were harvested with a small scleral ring and mounted on a customized two-dimensional flap holder. The biomechanical measurement consisted of three parts: (1) pre-conditioned during three cycles from 0.04 to 0.4 N, (2) stress relaxation during 120 seconds following 0.4 N force application, and (3) stress-strain curve until break., Results: After the relaxation period of 120 seconds, highly significant differences (P < .001) were found between the controls and both 1×CXL corneas and 2×CXL corneas. No significant difference (P = .70) was detected between the 1×CXL and 2×CXL groups. The stress remaining after relaxation was 355 ± 25.2 kPa in the control group, 457 ± 34.1 kPa in the 1×CXL group, and 463 ± 22.2 kPa in the 2×CXL group. No significant differences in the stress-strain curves were found between the conditions., Conclusions: Repeated CXL 3 days after the first procedure does not further increase corneal stiffness in mice in vivo. [J Refract Surg. 2017;33(1):56-60.]., (Copyright 2017, SLACK Incorporated.)

Purpose: To assess the efficacy of a modified high concentration riboflavin solution containing benzalkonium chloride 0.01% for transepithelial corneal cross-linking (CXL)., Methods: In this prospective, interventional multicenter cohort study, 26 eyes of 26 patients with documented progressive keratoconus who underwent transepithelial CXL were included. Follow-up at 6 and 12 months postoperatively included slit-lamp examination, uncorrected and corrected distance visual acuity (logMAR), maximum keratometry (Kmax), and corneal pachymetry (corneal thinnest point) as determined by Scheimpflug imaging. Statistical analysis was performed using repeated measures analysis of variance and the Friedman test for parametric and non-parametric data, respectively. P values less than .05 were considered significant., Results: Kmax did not change significantly at postoperative months 6 and 12. Changes in corneal thinnest point did not change postoperatively over 12 months. Uncorrected and corrected distance visual acuity did not change postoperatively. Progression (defined by an increase in Kmax greater than 1.00 diopter occurred in 46% of eyes at 12 months. Corneal epithelial defects were observed in 46% of the patients and marked punctate corneal epitheliopathy/loose epithelium in 23% of the patients in the immediate postoperative period. No corneal infection, sterile infiltrates, or haze were observed., Conclusions: Transepithelial CXL with an enhanced riboflavin solution did not effectively halt progression of keratoconus. Significant epithelium damage was evident in the immediate postoperative period. [J Refract Surg. 2016;32(6):372-377.]., (Copyright 2016, SLACK Incorporated.)

Purpose: To compare the stromal demarcation line depth in pulsed versus continuous corneal cross-linking (CXL) for keratoconus., Methods: Seventy eyes underwent epithelium-off cross-linking, with 0.1% riboflavin applied during 10 minutes prior to ultraviolet irradiation at 30 mW/cm2. Thirty-six eyes received pulsed irradiation (1 second on, 1 second off) for 8 minutes and 34 eyes underwent continuous irradiation for 4 minutes. Total fluence was 7.2 J/cm2 for both groups. Patients were evaluated at 3 months after the procedure., Results: A significantly deeper stromal demarcation line was observed in the pulsed group compared to the continuous group (201.11 ± 27.76 vs. 159.88 ± 20.86 µm; P < .001)., Conclusions: The pulsed corneal cross-linking protocol induced a significantly deeper stromal demarcation line when compared to the 4 minutes of highly accelerated continuous CXL protocol. Neither CXL protocol induced a shallower demarcation line comparable to less accelerated CXL protocols previously reported., (Copyright 2016, SLACK Incorporated.)

Purpose: To compare the currently available ultraviolet-A (UV-A) corneal cross-linking (CXL) treatment protocols for thin corneas with respect to oxygen, UV fluence, and osmotic pressure., Methods: Freshly enucleated murine (n = 16) and porcine (n = 16) eyes were used. The dependency on oxygen and the amount of UV absorption were evaluated using different CXL protocols, including standard CXL, contact lens-assisted CXL (caCXL), and CXL after corneal swelling. The CXL protocol was adapted from the treatment parameters of the human cornea to fit the thickness of murine and porcine corneas. Immediately after CXL, the corneas were subjected to biomechanical testing, including preconditioning, stress relaxation at 0.6 MPa, and stress-strain extensiometry. A two-element Prony series was fitted to the relaxation curves for viscoelastic characterization., Results: Standard CXL was most efficient; prior corneal swelling reduced the long-term modulus by 6% and caCXL by 15% to 20%. Oxygen reduction decreased the long-term modulus G∞ by 14% to 15% and the instantaneous modulus G0 by 2% to 5%, and increased the short-term modulus G2 by 22% to 31%. Reducing the amount of absorbed UV energy decreased the long-term modulus G∞ by 5% to 34%, the instantaneous modulus G0 by 7% to 29%, and the short-term modulus G2 by 17% to 20%. The amount of absorbed UV light was more important in porcine than in murine corneas., Conclusions: The higher oxygen availability in thin corneas potentially increases the overall efficacy of riboflavin UV-A CXL compared to corneas of standard thickness. Clinical protocols for thin corneas should be revised to implement these findings., (Copyright 2015, SLACK Incorporated.)

Purpose: To compare the 1-year results of total versus partial epithelium removal in corneal cross-linking in the treatment of progressive keratoconus., Methods: This retrospective study compared the results of total (the total group) versus partial (the partial group) approaches of epithelium removal in corneal cross-linking. Eighty eyes of 65 patients (40 eyes in each group) were enrolled. The mean age of the participants was 25.48 ± 4.80 years and 62.5% were male. One-year changes in vision parameters, refraction, and Pentacam (Oculus Optikgeräte GmbH, Wetzlar, Germany) indices were compared between the two groups using repeated measures analysis of variance., Results: One year after corneal cross-linking, uncorrected distance visual acuity in the total and partial group improved by 0.13 ± 0.42 and 0.12 ± 0.36 logMAR (P = .447), respectively, and corrected distance visual acuity improved by 0.00 ± 0.19 and 0.13 ± 0.20 logMAR (P = .001), respectively. Spherical equivalent decreased by 0.44 ± 1.25 diopters (D) in the total group and 0.56 ± 1.47 D in the partial group (P = .710). The decrease in maximum keratometry was 0.39 ± 0.93 and 0.01 ± 0.95 D in the total and partial group, respectively (P = .037), and the decrease in mean keratometry was 0.42 ± 0.93 and 0.00 ± 0.65 D (P = .015), respectively. Central corneal thickness decreased by 18.39 ± 20.66 μm in the total group and 0.11 ± 13.29 μm in the partial group (P < .001)., Conclusions: One year after corneal cross-linking, both approaches showed similar results in terms of uncorrected distance visual acuity. With the partial approach, there was slightly better corrected distance visual acuity improvement and central corneal thickness maintenance, but slightly better corneal flattening was achieved with the total removal. Long-term studies are needed to compare these two approaches in terms of stability of results and stopping the progression of keratoconus., (Copyright 2015, SLACK Incorporated.)

Purpose: To report the use of accelerated photoactivated chromophore for keratitis-corneal collagen cross-linking (PACK-CXL) as a first-line treatment in a patient with an atypical fungal keratitis., Methods: Case report and literature review., Results: A patient who presented with a painful peripheral corneal infiltrate underwent PACK-CXL with a local limited abrasion and accelerated ultraviolet-A irradiation at 365 μm and 9 mW/cm² for 10 minutes. Cultures grew Aureobasidium pullulans. The corneal epithelium closed completely within 3 days and the infiltrate was completely eradicated without administration of antibiotics., Conclusions: Accelerated PACK-CXL was successfully used as a first-line and sole treatment in a case of early fungal keratitis caused by Aureobasidium pullulans. Further characterization of the antifungal effect of PACK-CXL is needed in prospective studies., (Copyright 2014, SLACK Incorporated.)

Purpose: To investigate whether optimized photoactivated chromophore for keratitis-corneal collagen cross-linking (PACK-CXL) treatment settings allow accelerating treatment while maintaining antibacterial efficacy., Methods: Staphylococcus aureus and Pseudomonas aeruginosa strains were irradiated with ultraviolet-A light of equal fluence but different intensity settings (18 mW/cm² for 5 minutes and 36 mW/cm² for 2.5 minutes). The killing rate was determined by comparing the number of colony-forming units between cross-linked specimens and non-irradiated controls. The potential additional effect of 0.001% benzalkonium chloride was also investigated., Results: The killing rates for Staphylococcus aureus were 92.5% ± 5.5% (5 minutes at 18 mW/cm²) and 94.4% ± 2.9% (2.5 minutes at 36 mW/cm²). For Pseudomonas aeruginosa, the killing rates were 93.2% ± 8.3% (5 minutes at 18 mW/cm²) and 92.9% ± 5.0% (2.5 minutes at 36 mW/cm²). The presence of benzalkonium chloride in the riboflavin solution did not increase the killing rate significantly., Conclusions: The antibacterial efficacy of PACK-CXL follows the Bunsen-Roscoe law of reciprocity and can be maintained even when the irradiation intensity is considerably increased. These optimized settings may allow a shortened treatment time in the future for PACK-CXL and thus help facilitate the transition from the operating room to the slit lamp for treatment., (Copyright 2014, SLACK Incorporated.)

Purpose: To report the long-term clinical outcome in a patient diagnosed as having bilateral progressive keratoconus who received a single corneal collagen cross-linking (CXL) treatment in the right eye and repeated CXL in the left eye., Methods: Observational case report. Topographical changes were assessed by high-resolution Scheimpflug imaging. The right eye underwent a standard epithelium-off CXL procedure in February 2008, followed by the left eye 4 weeks later. In 2012, the left eye was treated with CXL for a second time. Irradiation was performed in all cases at a fluence of 5.4 J/cm². Energy settings were 30 minutes @ 3 mW/cm² for the CXL procedures performed in 2008, and 10 minutes @ 9 mW/cm² for the second CXL procedure of the left eye that was performed in 2012., Results: The right eye that underwent a single CXL procedure showed a flattening of keratometry values between 2008 and 2012, followed by stabilization. The left eye showed a similar flattening effect between 2008 and 2012, followed by another flattening effect after the second CXL procedure and accompanied by a distinct increase in corrected distance visual acuity., Conclusions: Following repeated CXL, the corneal stroma and endothelium remained inconspicuous, and postoperative haze and visibility of the stromal demarcation line was similar to what is usually observed after a single CXL procedure. Whether the additive flattening effect of the anterior surface observed in this single case goes along with an additive increase in biomechanical stiffness remains to be seen., (Copyright 2014, SLACK Incorporated.)

Purpose: To evaluate the need for and quantify the extent of nomogram adjustments to compensate for potential changes in the amount of effective corneal stroma ablated in previously cross-linked corneas., Methods: Ex vivo porcine corneas were divided into two groups (the corneal cross-linking [CXL] group, n = 30; and the control group, n = 3): these experimental corneas underwent CXL including deepithelialization, instillation of riboflavin solution for 25 minutes, and ultraviolet-A irradiation at 9 mW/cm2 for 10 minutes. The control group was deepithelialized only. Four consecutive excimer laser ablations of 50 pm each were performed (AMARIS 750S; SCHWIND eye-tech-solutions, Kleinostheim Germany), and stromal bed thickness was measured with a built-in optical coherence pachymeter. To determine the potential influence of riboflavin, a third group (the riboflavin group, n = 12) underwent deepithelialization and instillation of riboflavin, but no ultraviolet-A irradiation., Results: The mean individual ablation depth across the four ablations was significantly smaller in cross-linked corneas (-17%) when compared to untreated control corneas (P < .001). A consistent reduction of 12% was observed via a cumulative analysis when assessing the relative isolated effect of CXL on the ablation rate. There was no significant effect from riboflavin in the deeper ablations, except for the first ablation (68.6 + 1.1 mm [range: 1 to 50 pm]). This may be due to a measurement error in pachymetric readings due to the thin film of riboflavin on the surface that resists even extensive rinsing., Conclusions: CXL reduces the corneal ablation depth of excimer lasers in the anterior 200 pm of the porcine cornea by approximately 12%. Further clinical studies are needed to validate these findings in human corneas.

Purpose: To report the long-term clinical outcome of a patient diagnosed as having Terrien marginal degeneration (TMD) who was subjected to corneal collagen cross-linking (CXL) with ultraviolet-A and riboflavin in both eyes., Methods: Topographical changes were assessed by high-resolution Scheimpflug imaging and anterior segment optical coherence tomography. Eccentric epithelium-off CXL was performed in both eyes while protecting the corneal limbus. Irradiation was performed with a fluence of 5.4 J/cm(2), using 3 mW/cm(2) for 30 minutes., Results: Five years of postoperative follow-up showed regression of the keratometric values, a local thickening of the corneal stroma, and bilateral improvement of corrected distance visual acuity., Conclusions: CXL may arrest progression in TMD and even reverse the catabolic process in the corneal stroma. CXL might represent an alternative therapeutic approach for the management of TMD., (Copyright 2014, SLACK Incorporated.)

Purpose: To investigate the effect of high-fluence corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A in the management of progressive keratoconus., Methods: Preliminary results from a prospective cohort study. Seven eyes from 7 patients with progressive keratoconus subjected to CXL were included. CXL was performed as a standard epithelium-off procedure, irradiating with high-fluence settings (18 mW/cm(2) for 5 minutes). Endothelial cell density (ECD), speed of postoperative epithelial healing, maximal and average keratometric readings (Kmax and Kmean, respectively) of the anterior corneal surface, and corrected distance visual acuity (CDVA) were evaluated preoperatively and at 1 and 6 months after CXL. One-way analysis of variance was applied for statistical analysis. P values less than .05 were considered significant., Results: ECD did not change significantly postoperatively and complete epithelial healing occurred in all eyes within 96 hours postoperatively. No morphological alterations in the corneal limbus were observed. Kmax, Kmean, and CDVA showed no significant changes at 1 and 6 months postoperatively. No complications were observed postoperatively., Conclusions: Although the preliminary results are not sufficient for a valid evaluation of the biomechanical effect and the overall safety profile of high-fluence CXL in vivo, they demonstrate that CXL at 18 mW/cm(2) for 5 minutes affects neither endothelial cell density nor the speed of epithelial healing, an indirect indicator of limbal stem cell function., (Copyright 2013, SLACK Incorporated.)

Purpose: To investigate the effect of fluorescein on the antimicrobial efficacy of photoactivated riboflavin in corneal collagen cross-linking (CXL) in vitro., Methods: The ultraviolet light-A (UVA) absorption by fluorescein and riboflavin in different concentrations was analyzed with a spectrophotometer. The killing rate of Staphylococcus aureus strains after CXL with UV-A irradiation using different solutions containing riboflavin and/or fluorescein, was evaluated in vitro., Results: Fluorescein absorbed UV-A to a significant extent, which augmented with increasing concentration. Moreover, addition of fluorescein to the riboflavin solution contributed to a significant reduction of the killing rate of S. aureus strains after 30 minutes of UV-A irradiation in vitro with a killing rate of 85%, whereas it was 47% in the presence of 2% fluorescein (P = .0247)., Conclusions: The results indicate that fluorescein competes with riboflavin for the absorption of UV-A during CXL and reduces the antimicrobial effect of the procedure. The authors recommend that physicians treating infectious ulcerative keratitis by CXL should not stain the cornea with fluorescein for visualization of the corneal ulceration prior to CXL

Purpose: To highlight two cases of keratoconus with significant variations of corneal curvature during pregnancy that reversed several months after delivery., Methods: Case reports and literature review., Results: Two women experienced a significant decrease of corrected distance visual acuity during pregnancy. Evaluation of corneal topography by Scheimpflug imaging revealed transitory variations of the keratometric values in both patients during the gestational period. These topographical alterations were evident not only during pregnancy, but also in the postpartum period, with stabilization of corneal topography several months after delivery., Conclusions: These clinical cases indicate that hormonal changes occurring regularly during gestation may have a severe impact on the progression of keratoconus. However, these changes are transient and fully reversible. Therefore, physicians should be reluctant to perform cross-linking during or directly after pregnancy and should wait until the corneal curvature has been stabilized., (Copyright 2013, SLACK Incorporated.)

Purpose: To study the progression rate of keratoconus and assess the clinical outcome of corneal collagen cross-linking (CXL) with riboflavin and ultraviolet A light in children and adolescent patients up to 3 years after treatment., Methods: Fifty-nine eyes from 42 children and adolescents (aged 9 to 19 years) with confirmed keratoconus were included in this retrospective interventional cohort study. Refraction, slit-lamp examination, Placido-based corneal topography, and Scheimpflug imaging were performed bilaterally in all patients preoperatively and at 6 and 12 months postoperatively. Maximal keratometry readings (Kmax), corrected distance visual acuity (CDVA), corneal thickness, and the keratoconus index (KI) were analyzed. Follow-up was up to 36 months (mean follow-up: 26.3 months [range: 12 to 36 months])., Results: Fifty-two of the 59 eyes enrolled in this study showed progression, corresponding to a progression rate of 88%. Forty-six eyes were treated by CXL. Maximal keratometry, CDVA, and KI showed significant changes over the follow-up period. However, significant Kmax reduction observed up to 24 months after CXL lost significance at 36 months., Conclusions: Cross-linking seems to be safe in children and adolescents. Progression of keratoconus occurred in 88%. We propose that awaiting documentation of progression is not mandatory and CXL in children and adolescents should be performed as soon as the diagnosis has been made. However, the effect of arrest of disease progression might not be as long-lasting as in adults and longer follow-up is needed to verify this trend., (Copyright 2012, SLACK Incorporated.)

Purpose: To report a patient who developed a left paracentral stromal scar due to infectious keratitis that occurred after corneal collagen cross-linking (CXL) for progressive keratoconus. The flattening effect of the scar led to an increase in visual acuity., Methods: The corneal scar and flattening effect on the anterior corneal curvature were assessed by slit-lamp photography, high-resolution Scheimpflug imaging, and corneal confocal microscopy., Results: Three days after CXL, a corneal bacterial infection occurred in the left cornea and was treated with local antibiotics that led to a paracentral scar. Twenty-one days after CXL, a flattening of the anterior curvature of >11.00 diopters was observed. As a consequence, corrected distance visual acuity improved by five lines., Conclusions: Corneal remodeling may lead to a homogenization of the anterior corneal surface and an increase in visual acuity. Remodeling may not only occur spontaneously following CXL, but also following an event that results in focal corneal scarring, such as corneal infection. In a highly irregular keratoconic cornea, the benefit of the flattening effect of a scar may outweigh the increase in aberrations and light scatter., (Copyright 2012, SLACK Incorporated.)

Addressing these business and financial components of research, we believe that including a section on translational vision research especially for refractive surgery will be a welcome addition to the readership of the Journal. Although the section "Translational Science" is new, the Journal has published a number of articles in past years that would have been ideal candidates for such a section. The inaugural Translational Science article in this month's issue is fron Santhiago and colleagues on short-term cell death and inflammation after intracorneal inlay implantation in rabbits. Although not all scientists are in agreement with the promotion of this term, the Journal aims to provide different outlooks and modern usage of translational research in this way to advance the field of refractive surgery.

Purpose: To report the effect of corneal collagen cross-linking (CXL) with riboflavin and ultraviolet A (UVA) on the optical and material characteristics of a posterior chamber phakic intraocular lens (Visian ICL, STAAR Surgical)., Methods: Optical and material characteristics were assessed in vitro, analyzing potential changes in riboflavin staining, dioptric power, transmission characteristics, and surface structure. A total of 9 lenses were analyzed: 3 lenses were irradiated with 0.23 mW/cm², the maximal intensity that may be encountered during actual surgery; 3 lenses were irradiated with 2.3 mW/cm², 10 times the maximal intensity encountered during surgery; and 3 lenses served as controls., Results: Following CXL with UVA and riboflavin, no changes were observed in the parameters tested; in particular, dioptric power and transmission characteristics were similar before and after CXL., Conclusions: Cross-linking with UVA and riboflavin does not affect the optical and material characteristics of the Visian ICL after irradiation with the maximal UVA energy levels that may be encountered during surgery. Even when the UVA irradiation dose was increased by a factor of 10, no changes were observed., (Copyright 2010, SLACK Incorporated.)

Purpose: To analyze intra- and postoperative variation in Ocular Response Analyzer (ORA, Reichert Ophthalmic Instruments) parameters in 24 keratoconic eyes undergoing corneal cross-linking (CXL)., Methods: In a prospective clinical study, corneal hysteresis (CH), corneal resistance factor (CRF), peak 1 and peak 2 amplitude, corneal-compensated and Goldmann-correlated intraocular pressure (IOP) were evaluated using the ORA. The thinnest cornea point was measured with the Pentacam (Oculus Inc). Corneal topography and endothelial cell count were performed. Measurements were recorded at baseline; intraoperatively after epithelium removal, riboflavin impregnation, and ultraviolet A irradiation; and postoperatively after corneal re-epithelialization and at 1, 6, and 12 months., Results: A statistically significant reduction of the thinnest cornea point from 462±23.24 μm was observed at the end of the CXL procedure intraoperatively and at 1- and 6-month follow-up (P<.05). A significant increase in the thinnest cornea point to 624±31.72 μm was found after re-epithelialization (P<.05), and no significant changes were observed at 1 year postoperatively. Mean CH and CRF did not change significantly after de-epithelialization, but were noted to significantly increase after CXL intraoperatively and postoperatively at 1-month follow-up. At 6 and 12 months postoperatively, CH and CRF were not statistically significantly different from pre-operatively. Peak 1 and peak 2 decreased intraoperatively from 276±52 and 228±47 to 172±42 and 131±42, respectively, at the conclusion of CXL (P<.05), and were noted to increase to 493±41 and 444±51, respectively, at 6-month follow-up. Corneal-compensated IOP and Goldmann-correlated IOP increased at 1 month after CXL (P>.05)., Conclusions: The results showed a significant change in ORA parameters and the thinnest cornea point during and after the CXL procedure and a high correlation between peak amplitudes and corneal asymmetry, providing insight to the bioelastic and biomechanical behavior of the cornea during and after CXL., (Copyright 2010, SLACK Incorporated.)

Purpose: To report persistent subepithelial haze in two patients following femtosecond LASIK associated with creation of a thin flap., Methods: Subepithelial haze was assessed by slit-lamp photography, high-resolution Scheimpflug imaging, and corneal confocal microscopy., Results: Two patients showed distinct subepithelial haze and reduced corrected distance visual acuity at 3 months after LASIK with a think-flap generated by a femtosecond laser. The extent of haze was documented, and the haze was treated topically with steroids up to 12 weeks. The haze was localized approximately 20 to 40 microm below Bowman's layer and dissolved slowly during the 2 months of treatment. At 6 months after surgery, uncorrected visual acuity was 20/20., Conclusions: Subepithelial haze formation represents a new potential complication in the thin-flap LASIK.

Purpose: To assess the progression of keratoconus in patients treated with collagen cross-linking with riboflavin and ultraviolet A (UVA) irradiation., Methods: Thirty-eight eyes of 19 patients with progressive keratoconus were enrolled in a prospective comparative study. Average follow-up was 9 +/- 2 months (range: 5 to 12 months). The worse eye was treated with collagen cross-linking, and the fellow eye served as the control. Corneal epithelium was mechanically removed. Riboflavin 0.1% solution in dextran T-500 20% solution was applied every 2 to 3 minutes for 30 minutes throughout the irradiation. Ultraviolet A irradiation (370 nm) was performed using a commercially available UVA lamp for 30 minutes., Results: The group treated with collagen crosslinking demonstrated a mean decrease (less myopic) in spherical equivalent refraction and cylinder of 1.03 +/- 2.22 diopters (D) (range: -5.25 to +3.75 D) and 1.04 +/- 1.44 D (range: -2.00 to +4.00 D), respectively (P < .01), and an increase in uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA) of 0.06 +/- 0.05 (range: 0.00 to 0.20) and 0.10 +/- 0.14 (range: -0.10 to 0.34), respectively (P < .01). The maximal curvature decreased by 1.57 +/- 1.14 D (range: 0.00 to 3.90 D), and intraocular pressure increased by 2 +/- 2 mmHg (range: -1 to 6 mmHg), which was statistically significant. No statistical difference was noted regarding central corneal thickness (P = .06) and endothelial cell count (P = .07). The untreated group showed no statistical difference for any of the clinical parameters, apart from UCVA and BSCVA, which decreased by 0.08 +/- 0.12 (range: -0.40 to 0.10) and 0.06 +/- 0.09 (range: -0.20 to 0.10), respectively (P < .01)., Conclusions: Riboflavin/UVA collagen cross-linking appears to be efficacious in inhibiting the progression of keratoconus by reducing the corneal curvature, spherical equivalent refraction, and refractive cylinder in eyes with progressive keratoconus at average 9-month follow-up.

Purpose: The aim of this study was to use a 500-Hz scanning spot laser (Concept500, WaveLight Laser Technologie AG, Erlangen, Germany) to investigate potential side effects that might be associated with the use of a high repetition rate laser platform., Methods: Seven eyes were treated using a 500-Hz scanning spot laser for laser in situ keratomileusis (LASIK). The local frequency of the ablation was kept below 40 Hz to avoid local heating of corneal tissue. With the exception of the high repetition rate (500 Hz), all other laser parameters such as fluence, algorithm, ablation profile, and spot diameter were identical to a standard WaveLight Allegretto laser system. Patients were examined at 1 month and 1 year after initial treatment. Preoperative and postoperative examination included manifest sphere and cylinder, uncorrected and best spectacle-corrected visual acuity (BSCVA)., Results: All eyes were treated for myopia or myopic astigmatism. Five eyes received spherocylindrical and two eyes spherical ablation only. No adverse events correlated with the use of a high repetition rate laser system were observed during surgery or at any point during follow-up. All eyes maintained or had improved BSCVA at 12 months after treatment when compared to preoperative values., Conclusion: The use of an excimer laser with a maximal repetition rate of 500 Hz and a local repetition rate of less than 40 Hz was free of any specific side effect that might be associated with the use of such a high repetition rate.