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Purpose: This is a case report of a 31-year-old male patient presenting progressive and markedly asymmetric keratoconus treated with sequential intracorneal ring segment (ICRS) implantation followed by accelerated corneal cross-linking (CXL)., Observations: The follow-up after the last procedure revealed a thin, opacified cornea with an unexpected massive flattening of up to 20.3 D. The central flattening attributed to the individual effect of CXL (post-ICRS-implant vs. post-CXL) was 19.1 D., Conclusions and Importance: This original case reports how CXL followed by ICRS implant may result in an early and extreme corneal remodeling. Moreover, such an unusual combination of extreme corneal flattening, thinning, and opacification may imitate a clinical manifestation of central toxic keratopathy and suggests that eyes with ICRS implantation must be followed closely if CXL is performed sequentially after., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors have no conflict of interest., (© 2024 The Authors.)

Purpose: To present a case series of patients with corneal scars who were successfully fitted with mini scleral contact lenses (mSCL)., Methods: Case series study., Results: Six eyes of six patients with corneal scars were fitted with mSCLs. All scars were situated in the visual axis within the scotopic pupillary zone. The sizes of the scars varied, with the smallest being confined to a central corneal area (case 5) and the largest covering the entire visual axis (case 2). In addition to compromising corneal transparency, these scars also induced significant corneal irregularities, especially in cases 1, 3, and 4. The average corrected distance visual acuity (CDVA) with spectacles was 20/80, with a range of 20/200 to 20/40. With the use of mSCLs, CDVA improved to an average of 20/25, ranging from 20/40 to 20/16. The mean visual acuity improvement observed was five optotype lines, with a range of 3 to 7 lines., Conclusion: Corneas with scars often exhibit increased higher-order aberrations (HOA), and affected patients not only experience reduced vision but also suffer from seriously reduced optical quality and optical phenomena such as photophobia. Utilizing mSCLs in such individuals can significantly enhance visual acuity and improve optical side effects resulting from corneal opacity and irregularity., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: This pilot ex vivo study and first clinical experience in Italy evaluate the impact of using pre-implantation crosslinking on all-femtosecond laser-cut corneal allogenic intracorneal ring segments (AFXL CAIRSs). Methods: Six human donor eye-bank corneas were used for this preclinical ex vivo human study. Three donor (D) corneas were used for AFXL CAIRSs. First, they were prepared with an IntraLase™ femtosecond laser (Johnson & Johnson, New Brunswick, NJ, USA). The allogenic tissue rings were crosslinked before implantation with Riboflavin-UV-A accelerated crosslinking protocol (ACXL) with a 0.1% HPMC Riboflavin isotonic solution (Vibex Rapid, Glaukos-Avedro, Burlington, MA, USA) and a new KXL UV-A emitter (Glaukos-Avedro, USA). Three corneas were used as recipients (Rs) of the AFXL CAIRSs. After completing the ex vivo phase, IRB approval and signing a specific informed consent, the first two Italian patients were treated. A single ACXL CAIRS was implanted in a 51-year-old male with 53.53 D K steep, 363 μm minimum corneal thickness (MCT) and a double ACXL CAIRS was implanted in a 46-year-old male patient with 58.30 D K steep, 443 μm MCT. The longest follow-up was at three months. Results: Crosslinking of the segments enhanced tissue stiffness and grip, facilitating manipulation and CAIRS insertion into the recipient tunnels, and the yellowish color of the crosslinked segments improved visibility. The segment's thickness and volume remained unaltered during the follow-up. Both patients improved UDVA and BSCVA. K steep and High-Order Aberrations (HOAs) were reduced and MCT increased. Conclusions: Pre-implantation ACXL facilitated CAIRS insertion preserving dimensions and volume during the follow-up, rendering this important step a promising candidate in method standardization. Functional data and MCT improved significantly without adverse events.

Background: As a key element of ocular accommodation, the inherent mechanical stiffness gradient and the gradient refractive index (GRIN) of the crystalline lens determine its deformability and optical functionality. Quantifying the GRIN profile and deformation characteristics in the lens has the potential to improve the diagnosis and follow-up of lenticular disorders and guide refractive interventions in the future., Methods: Here, we present a type of optical coherence elastography able to examine the mechanical characteristics of the human crystalline lens and the GRIN distribution in vivo. The concept is demonstrated in a case series of 12 persons through lens displacement and strain measurements in an age-mixed group of human subjects in response to an external (ambient pressure modulation) and an intrinsic (micro-fluctuations of accommodation) mechanical deformation stimulus., Results: Here we show an excellent agreement between the high-resolution strain map retrieved during steady-state micro-fluctuations and earlier reports on lens stiffness in the cortex and nucleus suggesting a 2.0 to 2.3 times stiffer cortex than the nucleus in young lenses and a 1.0 to 7.0 times stiffer nucleus than the cortex in the old lenses., Conclusions: Optical coherence tomography is suitable to quantify the internal stiffness and refractive index distribution of the crystalline lens in vivo and thus might contribute to reveal its inner working mechanism. Our methodology provides new routes for ophthalmic pre-surgical examinations and basic research., (© 2024. The Author(s).)

Purpose: Corneal cross-linking (CXL) with riboflavin and UV-A induces several effects in the cornea, including biomechanical stiffening, generation of reactive oxygen species, and increased resistance to enzymatic digestion. Whereas the biomechanical stiffening effect is oxygen-dependent, little is known about the effect of oxygen on the resistance to enzymatic digestion. Here, we examined CXL-induced enzymatic resistance in the absence of oxygen., Methods: Ex vivo porcine corneas (n = 160) were assigned to 5 groups. Group 1 was the control group (abrasion and riboflavin application). Groups 2 and 3 received accelerated 10 and 15 J/cm 2 high-fluence CXL protocols in the presence of oxygen (9'15″ @ 18 mW/cm 2 and 8'20″ @ 30 mW/cm 2 , respectively), whereas groups 4 and 5 received accelerated 10 and 15 J/cm 2 high-fluence CXL protocols in the absence of oxygen (oxygen content less than 0.1%). After CXL, corneas were digested in 0.3% collagenase A solution. Mean time until complete dissolution was determined., Results: The mean times to digestion in groups 1 through 5 were 22.31 ± 1.97 hours, 30.78 ± 1.83 hours, 32.22 ± 2.22 hours, 31.38 ± 2.18 hours, and 31.69 ± 2.53 hours, respectively. Experimental CXL groups showed significantly higher ( P < 0.001) resistance to digestion than nonirradiated controls. There was no significant difference in time to digestion across all experimental CXL groups, irrespective of fluence delivered or the absence of oxygen., Conclusions: The resistance to digestion in accelerated high-fluence riboflavin/UV-A CXL is oxygen-independent, which is of particular importance when developing future optimized CXL protocols for corneal ectasia and infectious keratitis., Competing Interests: N. L. Hafezi is the CEO of EMAGine AG, a company producing a CXL device. The remaining authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate and compare functional and structural outcomes of accelerated corneal crosslinking (A-CXL) using riboflavin with hydroxypropyl methyl cellulose (HPMC) vs conventional corneal crosslinking (C-CXL) using riboflavin with dextran., Setting: American University of Beirut Medical Center, Beirut, Lebanon., Design: Retrospective analysis., Methods: Retrospective analysis of 83 eyes of 73 patients with mild to moderate keratoconus. First group (n = 44 eyes) underwent C-CXL using a 30-minute riboflavin/dextran soaking between June 2014 and March 2016. Second group (n = 39 eyes) underwent A-CXL using a 20-minute riboflavin/HPMC soaking between April 2016 and December 2017. Patients were evaluated preoperatively and at 1, 3, and 12 months postoperatively. Main outcome measures were simulated keratometry (simK), maximum axial keratometry (Kmax), demarcation line depth, and haze intensity measured using optical coherence tomography-based image analysis software., Results: Demarcation line (DL) was 298.30 ± 64.60 μm and 335.61 ± 99.76 μm for C-CXL and A-CXL groups, respectively ( P = .04). Haze profile was similar for both groups. The mean simK values were reduced from 46.93 ± 3.50 and 46.44 ± 2.93 preoperatively to 46.18 ± 3.65 and 45.54 ± 2.78 at 12 months postoperatively, for C-CXL and A-CXL, respectively ( P = .003 for both groups). The mean Kmax decreased from 52.46 ± 4.82 and 51.50 ± 3.87 preoperatively to 51.30 ± 4.42 and 50.30 ± 3.52 postoperatively, for the C-CXL and A-CXL, respectively ( P < .001 for both groups). There was no difference in the simK and Kmax changes between the C-CXL and A-CXL groups ( P = .814 and P = .913), visual acuity, and refraction between the 2 groups ( P > .05)., Conclusions: A-CXL with a 20-minute riboflavin/HPMC soaking produced deeper DL and similar corneal haze, topographic, refractive, and visual results to C-CXL with a 30-minute riboflavin/dextran soaking., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: This study evaluated the effect of high-fluence accelerated corneal cross-linking on the resistance to enzymatic digestion, assessing two chromophore/light combinations: riboflavin/UV-A light (RF/UV-A) and rose bengal/green light (RB/green)., Methods: Freshly prepared ex-vivo porcine corneas (n = 189) were divided into 8 groups groups. Group A corneas were unirradiated controls without chromophore soaking (A0), or soaked with riboflavin (A1) or rose bengal (A2). Group B corneas underwent accelerated epi-off RF/UV-A CXL at fluences of 5.4 J/cm² (B1), 10 J/cm² (B2), or 15 J/cm² (B3). Group C corneas underwent accelerated epi-off RB/green CXL at fluences of either 10 J/cm² (C1) or 15 J/cm² (C2). Following CXL, all corneas were digested in 0.3% collagenase-A solution, and the time until complete dissolution was measured., Results: Non-irradiated controls exposed to RF and RB enhanced corneal resistance to collagenase digestion, with RB having a stronger effect than RF. RF/UV-A-treated corneas showed significantly increased digestion resistance with increasing fluence levels. RB/green-treated corneas displayed enhanced digestion resistance with each increase in fluence up to 10 J/cm²; a 15 J/cm² fluence yielded similar digestion resistance times to a 10 J/cm² fluence, suggesting a plateau effect in accelerated RB/green CXL protocols., Conclusions: When compared to standard-fluence treatments, high-fluence accelerated epi-off CXL using both riboflavin and rose bengal significantly increases resistance to enzymatic digestion. The optimal settings for clinical protocols might be 15 J/cm² (30 mW/cm² for 8 min 20 s) for RF/UV-A and 10 J/cm² (15 mW/cm² for 11 min 7 s) for RB/Green Light., (© 2024. The Author(s).)

Purpose: The purpose of this study was to determine if concurrent riboflavin/UV-A light (RF/UV-A) and rose Bengal/green light (RB/green) epi-off PACK-CXL enhances corneal resistance to enzymatic digestion compared to separate chromophore/light treatments., Methods: Ex vivo porcine corneas were allocated as follows. Group A corneas were soaked with riboflavin (RF) and were either not irradiated (A1, controls) or were irradiated with 10 (A2) or 15 J/cm² (A3) UV-A light at 365 nm, respectively. Group B corneas were soaked with RB and either not irradiated (B1, controls) or were illuminated with 10 (B2) or 15 J/cm² (B3) green light at 525 nm, respectively. Corneas in group C were soaked with both RF and RB and were either not irradiated (C1, controls) or were subjected to the same session consecutive 10 J/cm2 (C2) or 15 J/cm2 (C3) UV-A and green light exposure. Following treatment, all corneas were exposed to 0.3% collagenase A to assess digestion time until corneal button dissolution., Results: A1 to A3 digestion times were 21.38, 30.5, and 32.25 hours, respectively, with A2 and A3 showing increased resistance to A1. B1-3 had digestion times of 31.2, 33.81, and 34.38 hours, with B3 resisting more than B1. C1 to C3 times were 33.47, 39.81, and 51.94 hours; C3 exhibited superior resistance to C1 and C2 (both P < 0.05)., Conclusions: Same-session combined RF/UV-A and RB/green PACK-cross-linking significantly increases corneal enzymatic digestion resistance over standalone treatments., Translational Relevance: Combining RF-based and RB-based PACK-CXL considerably increases corneal collagenase digestion resistance, potentially minimizing ulcer size in clinical contexts.

Purpose: To establish a numerical spectral-domain optical coherence tomography (SD-OCT)-based keratoconus (KC) staging system and compare it with existing KC staging systems., Setting: Eye Hospital of Wenzhou Medical University, Wenzhou, China., Designs: Retrospective case-control study., Methods: Scheimpflug tomography, air-puff tonometry, and SD-OCT were performed on 236 normal and 331 KC eyes. All SD-OCT-derived parameters of the corneal epithelium and stroma were evaluated based on their receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity to discriminate between normal and KC eyes. The best performing parameters were subsequently used to create an OCT-based staging system, which was compared with existing tomographic and biomechanical staging systems., Results: 236 eyes from 236 normal patients and 331 eyes from 331 KC patients of different stages were included. The highest ranked AUC ROC SD-OCT parameters, derived from stroma and epithelium, were stroma overall minimum thickness (ST: AUC 0.836, sensitivity 90%, specificity 67%) and epithelium overall SD (EP: AUC 0.835, sensitivity 75%, specificity 78%). A numerical SD-OCT staging system called STEP including 2 parameters-"ST" and "EP"-with 5 stages was proposed., Conclusions: The new SD-OCT-based KC staging system is the first to take the epithelium with its sublayer stroma information into account, showing a strong agreement to the existing staging systems. This system could be incorporated into daily practice, potentially leading to an overall improvement in KC treatment and follow-up management., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.)

Purpose: To assess whether sunlight might be used to induce a biomechanical stiffening effect in riboflavin-soaked corneas similar to the effect observed in corneal crosslinking (CXL) using riboflavin and UV-A light., Setting: Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland., Design: Experimental study., Methods: 52 porcine eyes were assayed. The concentration of riboflavin in the corneal stroma was estimated using UV-A transmission in a preliminary experiment. Then, the duration of sunlight exposure to achieve a fluence of 7.2/cm 2 was calculated. Finally, de-epithelialized corneas were divided equally into 3 groups and soaked with riboflavin 0.1% (control group and Group 1) or 0.5% (Group 2). Eyes from Groups 1 and 2 were then exposed to sunlight. The elastic modulus was calculated as an indicator of stiffness., Results: Riboflavin concentration in Group B was higher by a factor of 2.8 than Group A. According to live illuminance measurements and stromal riboflavin concentration, the sunlight exposure duration varied between 16 minutes and 45 minutes. Groups 1 and 2 had higher elastic modulus than controls ( P < .0001) but did not differ between them ( P = .194). The stiffening effect was 84% and 55%, respectively., Conclusions: Sunlight exposure of ex vivo corneas soaked in both riboflavin 0.1% and 0.5% resulted in increased corneal stiffness. Specifically, riboflavin 0.1% with longer UV-A exposure showed a trend for a greater stiffening effect, which might open new alleys for the use of oral riboflavin and fractioned sunlight exposure as less invasive CXL techniques., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Background: This study aimed to compare the complication rates of epithelium-off corneal cross-linking (epi-off CXL) performed in an office-based setting with those of epi-off CXL performed in an operating room., Methods: A retrospective cohort study, comprising 501 consecutive epi-off CXL procedures, performed in a non-sterile procedure room without laminar flow ventilation at the ELZA Institute in Zurich, Switzerland, between November 2015 and October 2021, was conducted., Results: No cases of postoperative infectious keratitis were observed, while sterile infiltrates occurred in 10 out of 501 (2.00%) patients, all of whom responded well to topical steroid therapy. Delayed epithelialization (> 7 days) occurred in 14 out of 501 (2.79%) patients. No other adverse events were noted., Conclusions: Office-based epi-off CXL does not appear to be associated with an increased risk of complications when compared to operating room settings., (© 2023. The Author(s).)

Purpose: To optimize artificial intelligence (AI) algorithms to integrate Scheimpflug-based corneal tomography and biomechanics to enhance ectasia detection., Design: Multicenter cross-sectional case-control retrospective study., Methods: A total of 3886 unoperated eyes from 3412 patients had Pentacam and Corvis ST (Oculus Optikgeräte GmbH) examinations. The database included 1 eye randomly selected from 1680 normal patients (N) and from 1181 "bilateral" keratoconus (KC) patients, along with 551 normal topography eyes from patients with very asymmetric ectasia (VAE-NT), and their 474 unoperated ectatic (VAE-E) eyes. The current TBIv1 (tomographic-biomechanical index) was tested, and an optimized AI algorithm was developed for augmenting accuracy., Results: The area under the receiver operating characteristic curve (AUC) of the TBIv1 for discriminating clinical ectasia (KC and VAE-E) was 0.999 (98.5% sensitivity; 98.6% specificity [cutoff: 0.5]), and for VAE-NT, 0.899 (76% sensitivity; 89.1% specificity [cutoff: 0.29]). A novel random forest algorithm (TBIv2), developed with 18 features in 156 trees using 10-fold cross-validation, had a significantly higher AUC (0.945; DeLong, P < .0001) for detecting VAE-NT (84.4% sensitivity and 90.1% specificity; cutoff: 0.43; DeLong, P < .0001) and a similar AUC for clinical ectasia (0.999; DeLong, P = .818; 98.7% sensitivity; 99.2% specificity [cutoff: 0.8]). Considering all cases, the TBIv2 had a higher AUC (0.985) than TBIv1 (0.974; DeLong, P < .0001)., Conclusions: AI optimization to integrate Scheimpflug-based corneal tomography and biomechanical assessments augments accuracy for ectasia detection, characterizing ectasia susceptibility in the diverse VAE-NT group. Some patients with VAE may have true unilateral ectasia. Machine learning considering additional data, including epithelial thickness or other parameters from multimodal refractive imaging, will continuously enhance accuracy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society., (Copyright © 2022. Published by Elsevier Inc.)

Purpose of Review: The aim of this study was to summarize the recent developments in corneal cross-linking (CXL) and its indications, including corneal ectasias, refractive surgery and infectious keratitis., Recent Findings: Advances in CXL technology, such as the use of higher-intensity LED ultraviolet (UV) light sources and a better understanding of the UV-riboflavin photochemical reaction, have enabled safer and more effective methods of cross-linking thin and ultra-thin corneas, and more effective accelerated transepithelial/'epi-on' CXL procedures that are beginning to supplant the Dresden protocol as the 'gold standard' CXL method. CXL is also being used in combination with laser surgery, not only to expand the patient base who can receive refractive surgery, but also to help rehabilitate vision in patients with ectasia. CXL, and CXL combined with photorefractive keratectomy (PRK), can result in corneal flattening of 1-2 D, and corneal regularization of 4-5 D, respectively. Finally, photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) has been shown to be an effective therapy for infectious keratitis, both alone, and in combination with antimicrobial drugs., Summary: CXL has evolved from a single technique to treat a single corneal ectasia, keratoconus, to several techniques with several indications, spanning a spectrum of corneal ectasias, as well as visual rehabilitation, refractive procedures and infectious keratitis treatment., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this study is to assess the effect of various fluence levels on prophylactic corneal cross-linking (CXL) combined with femtosecond laser in situ keratomileusis (FS-LASIK-Xtra) or transepithelial photorefractive keratectomy (TransPRK-Xtra) on biomechanics, demarcation line (DL), and stromal haze., Methods: Prospective analysis where two prophylactic CXL protocols (lower/higher fluence [LF/HF]: 30 mw/cm 2 , 60/80 s, 1.8/2.4 J/cm 2 ) were performed as part of either an FS-LASIK-Xtra or TransPRK-Xtra procedure. Data were collected preoperatively and at 1 week and 1, 3, and 6 months postoperatively. Main outcome measures were (1) dynamic corneal response parameters and the stress-strain index (SSI) from Corvis, (2) actual DL depth (ADL), and (3) stromal haze on OCT images analysed by a machine learning algorithm., Results: Eighty-six eyes from 86 patients underwent FS-LASIK-Xtra-HF (21 eyes), FS-LASIK-Xtra-LF (21 eyes), TransPRK-Xtra-HF (23 eyes), and TransPRK-Xtra-LF (21 eyes). SSI increased similarly by around 15% in all groups 6 months postoperatively (p = 0.155). All other corneal biomechanical parameters were statistically significant worsening postoperatively, but the change was similar in all groups. At 1 month postoperatively, there was no statistical difference in mean ADL among four groups (p = 0.613), mean stromal haze was similar between the two FS-LASIK-Xtra groups, but higher in the TransPRK-Xtra-HF group compared with the TransPRK-Xtra-LF group., Conclusions: FS-LASIK-Xtra and TransPRK-Xtra lead to a similar ADL and improve SSI equally. Lower fluence prophylactic CXL might be recommended as it achieves similar mean ADL with potentially less induced stromal haze, especially in TransPRK. The clinical relevance and applicability of such protocols remains to be assessed., (© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate whether repeated application of riboflavin during corneal cross-linking (CXL) has an impact on the corneal biomechanical strength in ex-vivo porcine corneas., Design: Laboratory investigation., Methods: Sixty-six porcine corneas with intact epithelium were divided into three groups and analyzed. All corneas were pre-soaked with an iso-osmolar solution of 0.1% riboflavin in a phosphate-buffered saline (PBS) solution ("riboflavin solution"). Then, the corneas in Groups 1 and 2 were irradiated with a standard epi-off CXL (S-CXL) UV-A irradiation protocol (3 mW/cm 2 for 30 min); while the corneas in Group 3 were not irradiated and served as control. During irradiation, Group 1 (CXL-PBS-Ribo) received repeated riboflavin solution application while corneas in Group 2 (CXL-PBS) received only repeated iso-osmolar PBS solution. Immediately after the procedure, 5-mm wide corneal strips were prepared, and elastic modulus was calculated to characterize biomechanical properties., Results: Significant differences in stress-strain extensiometry were found between two cross-linked groups with control group (P = 0.005 and 0.002, respectively). No significant difference was observed in the normalized stiffening effect between Groups 1 and 2 (P = 0.715)., Conclusions: The repeated application of riboflavin solution during UV-A irradiation does not affect the corneal biomechanical properties achieved with standard epi-off CXL. Riboflavin application during CXL may be omitted without altering the biomechanical stiffening induced by the procedure., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 record the axial strain field in the cornea directly after creating a stromal tunnel and implanting an intracorneal ring segment (ICRS)., Methods: Freshly enucleated porcine eyes were obtained and assigned to either ICRS implantation, tunnel creation only, or virgin control groups. Immediately after manual tunnel creation and ICRS positioning, the entire eye globe was mounted on a customized holder and intraocular pressure (IOP) was adjusted to 15 mm Hg. Then, IOP was inreased to 20 mm Hg, in steps of 1 mm Hg. At each step, an optical coherence tomography volume scan was recorded. Displacements between subsequent scans were retrieved using a vector-based phase difference method. The induced corneal strain direction was determined by taking the axial gradient. In addition, corneal surface was detected and sagittal curvature maps computed., Results: Corneal tissue presented a localized compressive strain in the direct vicinity of the stromal tunnel, which was independent of IOP change. The central and peripheral (exterior to the ICRS) cornea demonstrated compressive strains on IOP increase, and tensile strains on IOP decrease. ICRS implantation induced an annular-shaped tensile strain at its inner border, particularly during IOP increase. The compressive strains close to the tunnel remained after ICRS implantation. Corneal curvature changes were concentrated on regions where strain was induced., Conclusions: ICRS implantation induces localized strains in the regions subjected to refractive changes, suggesting that corneal strain and curvature are directly related. Studying corneal strain in response to surgical intervention may provide new insights on underlying working principles. [ J Refract Surg . 2022;38(3):210-216.] .

Background: Infectious keratitis is a major cause of global blindness. We tested whether standalone photoactivated chromophore corneal cross-linking (PACK-CXL) may be an effective first-line treatment in early to moderate infectious keratitis, compared with standard antimicrobial treatment., Methods: This is a randomized, controlled, multinational phase 3 clinical trial. Participants in five centers in Egypt, India, Iran, Israel, and China, aged ≥ 18 years, with infectious keratitis of presumed bacterial, fungal, or mixed origin, were randomly assigned (1:1) to PACK-CXL, or antimicrobial therapy. Outcomes measures included healing, defined as time to re-epithelialization of the corneal epithelial defect in the absence of inflammatory activity in the anterior chamber and clearance of stromal infiltrates. Treatment success was defined as the complete resolution of signs of infection., Results: Between July 21, 2016, and March 4, 2020, participants were randomly assigned to receive PACK-CXL (n = 18) or antimicrobial therapy per American Academy of Ophthalmology (AAO) guidelines (n = 21). No participants were lost to follow-up. Four eyes were excluded from the epithelialization time analysis due to treatment failure: two in the antimicrobial therapy group, and two in the PACK-CXL group. Success rates were 88.9% (16/18 patients) in the PACK-CXL group and 90.5% (19/21 patients) in the medication group. There was no significant difference in time to complete corneal re-epithelialization (P = 0.828) between both treatment groups., Conclusions: PACK-CXL may be an alternative to antimicrobial drugs for first-line and standalone treatment of early to moderate infectious keratitis of bacterial or fungal origin. Trial registration This trial is registered at ClinicalTrials.gov, trial registration number: NCT02717871., (© 2022. The Author(s).)

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 validate and evaluate the use of a new biomechanical index known as the Corvis biomechanical index-laser vision correction (CBI-LVC) as a method for separating stable post-LVC eyes from post-LVC eyes with ectasia., Setting: 10 clinics from 9 countries., Design: Retrospective, multicenter, clinical study., Methods: The study was designed with 2 purposes: to develop the CBI-LVC, which combines dynamic corneal response (DCR) parameters provided by a high-speed dynamic Scheimpflug camera (CorVis ST; OCULUS Optikgeräte GmbH) and then to evaluate its ability to detect post-LVC ectasia. The CBI-LVC includes integrated inverse radius, applanation 1 (A1) velocity, A1 deflection amplitude, highest concavity and arclength, deformation amplitude ratio of 2 mm, and A1 arclength in millimeters. Logistic regression with Wald forward stepwise approach was used to identify the optimal combination of DCRs to create the CBI-LVC and then separate stable from LVC-induced ectasia. Eighty percentage of the database was used for training the software and 20% for validation., Results: 736 eyes of 736 patients were included (685 stable LVC and 51 post-LVC ectasia). The receiver operating characteristic curve analysis showed an area under the curve of 0.991 when applying CBI-LVC in the validation dataset and 0.998 in the training dataset. A cutoff of 0.2 was able to separate stable LVC from ectasia with a sensitivity of 93.3% and a specificity of 97.8%., Conclusions: The CBI-LVC was highly sensitive and specific in distinguishing stable from ectatic post-LVC eyes. Using CBI-LVC in routine practice, along with topography and tomography, can aid the early diagnosis of post-LVC ectasia and allow intervention prior to visually compromising progression., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.)

Background/aims: The International Council of Ophthalmology (ICO) offers fellowship programmes to help young ophthalmologists, mainly from low-resource countries, improve their practical or research skills in ophthalmology subspecialty areas. Using questionnaires, the objective of the present study was to evaluate how the ICO Fellowship Programme has impacted on improving knowledge, skills and the careers of young ophthalmologists from low-resource countries., Methods: From 2001 to 2019 overall 1140 ICO fellowships were awarded. A questionnaire was sent to ICO fellows after the conclusion of their fellowship and another 3 years later. Part 1 contained 26 questions, while Part 2 had 21 questions. The answers were collected through an online platform and analysed descriptively thereafter., Results: 1101 Part 1 questionnaires had been sent to former fellows, with a return rate of 47% (516 responses) and 829 Part 2 questionnaires with a return rate of 47% (390 responses). Overall, 98.3% strongly or somewhat agreed that knowledge in their subspecialty has improved considerably. Whereas only 19% of them held a lecturer, senior lecturer or head of subspecialty department position prior to the fellowship, 46% of them held such a position 3 years after the fellowship was completed., Conclusions: The ICO Fellowship Programmes aim to promote the enhancement of eye care delivery and eye health in low-resource countries, the professional development of young leaders and the improvement of eye care. The results of the current study confirm the expectation of such a positive impact. Moreover, almost half of the responding participants have been appointed to a local leadership position in their home country., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Ehlers-Danlos syndrome (EDS) is a genetic disease leading to abnormalities in mechanical properties of different tissues. Here we quantify corneal biomechanical properties in an adult classic EDS mouse model using two different measurement approaches suited for murine corneal mechanical characterization and relate differences to stromal structure using Second Harmonic Generation (SHG) microscopy. Quasi-static Optical Coherence Elastography (OCE) was conducted non-invasively during ambient pressure modulation by - 3 mmHg. 2D-extensometry measurements was conducted invasively consisting of a pre-conditioning cycle, a stress-relaxation test and a rupture test. In a total of 28 eyes from a Col5a1 +/- mouse model and wild-type C57BL/6 littermates (wt), Col5a1 +/- corneas were thinner when compared to wt, (125 ± 11 vs 148 ± 10 μm, respectively, p < 0.001). Short-term elastic modulus was significantly increased in OCE (506 ± 88 vs 430 ± 103 kPa, p = 0.023), and the same trend was observed in 2D-extensometry (30.7 ± 12.1 kPa vs 21.5 ± 5.7, p = 0.057). In contrast, in stress relaxation tests, Col5a1 +/- corneas experienced a stronger relaxation (55% vs 50%, p = 0.01). SHG microscopy showed differences in forward and backward scattered signal indicating abnormal collagen fibrils in Col5a1 +/- corneas. We propose that disturbed collagen fibril structure in Col5a1 +/- corneas affects the viscoelastic properties. Results presented here support clinical findings, in which thin corneas with global ultrastructural alterations maintain a normal corneal shape., (© 2021. The Author(s).)

Purpose: To compare the elastic modulus of thin corneal lamellas using 2D stress-strain extensometry in healthy ex vivo human corneal lamellas with or without the presence of Bowman layer., Setting: Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Switzerland; ELZA Institute, Dietikon, Switzerland; Department of Ophthalmology, Philipps University of Marburg, Germany., Design: Prospective experimental laboratory study., Methods: Healthy human corneas were stripped of Descemet membrane and the endothelium for Descemet membrane endothelial keratoplasty. After epithelium removal, corneas were divided into 2 groups. In Group 1, Bowman layer was ablated with an excimer laser (20 μm thick, 10 mm). In Group 2, Bowman layer was left intact. Then, a lamella was cut from the anterior cornea with an automated microkeratome. Elastic and viscoelastic material properties were analyzed by 2D stress-strain extensometry between 0.03 and 0.70 N., Results: Twenty-six human corneas were analyzed. The mean lamella thickness was 160 ± 37 μm in corneas with Bowman layer and 155 ± 22 μm in corneas without. No statistically significant differences between flaps with and without Bowman layer were observed in the tangential elastic modulus between 5% and 20% strain (11.5 ± 2.9 kPa vs 10.8 ± 3.7 kPa, P > .278)., Conclusions: The presence or absence of Bowman layer did not reveal a measurable difference in corneal stiffness. This may indicate that the removal of Bowman layer during photorefractive keratectomy does not represent a disadvantage to corneal biomechanics., (Copyright © 2021 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: To evaluate an automated method for detecting the cone shape characteristics and to assess the cornea specialists' subjective variability of these measures using different maps., Methods: Topographic images of the anterior and posterior surface of each eye were presented to 12 clinicians in two different types of map: tangential curvature and relative elevation to the best-fit sphere. They were asked to mark the cone center and its boundaries in the two maps without knowing that they belonged to the same patient. The results between the maps were compared to assess the subjective variability dependent on the map type and the automated method was compared against both estimations to assess its accuracy., Results: Considering the results of anterior and posterior surfaces, there was low agreement between the cone center estimations using different types of maps for 10 of the 12 cases ( P < .05), whereas the comparison between the automated method and the two map estimations did not show differences in 11 of the 12 cases ( P > .05). There was high variability, up to 55%, among clinicians' estimations of the cone area. The results of the automated method were within the range of the expert's estimations., Conclusions: An objective, mathematically derived method of determining morphological dimensions of the cone was consistent with clinicians' evaluations. Although there was high variability among the experts' subjective estimates, which were highly influenced by the type of map, the objective method provided a reliable evaluation of the keratoconus shape independent of maps or color scale. [ J Refract Surg . 2021;37(6):414-421.] .

Purpose: To assess clinical results of the 9 mW/5.4 J/cm 2 accelerated crosslinking (ACXL) in the treatment of progressive keratoconus (KC) over a span of 5 years., Methods: The prospective open non-randomized interventional study (Siena Eye-Cross Study 2) included 156 eyes of 112 patients with early progressive KC undergoing the Epi-Off 9 mW/5.4 J/cm 2 ACXL at the Siena Crosslinking Centre, Italy. The mean age was 18.05 ± 5.6 years. The 20-min treatments were performed using the New KXL I (Avedro, Waltham, USA), 10 min of 0.1% HPMC Riboflavin soaking (VibeX Rapid, Avedro, Waltham, USA) and 10 min of continuous-light UV-A irradiation. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), Kmax, coma, minimum corneal thickness (MCT), surface asymmetry index (SAI), endothelial cell count (ECC) were measured, and corneal OCT performed., Results: UDVA and CDVA improved significantly at the 3rd (P = 0.028), Δ + 0.17 Snellen lines and 6th postoperative month, respectively (P < 0.001), Δ + 0.23 Snellen lines. Kmax improved at the 6th postoperative month (P = 0.03), Δ - 1.49 diopters from the baseline value. Also, coma aberration value improved significantly (P = 0.004). A mild temporary haze was recorded in 14.77% of patients without affecting visual acuity and without persistent complications. Corneal OCT revealed a mean demarcation line depth at 332.6 ± 33.6 μm., Conclusion: The 5-year results of Epi-Off 9 mW/5.4 J/cm 2 ACXL demonstrated statistically significant improvements in UCVA and CDVA, corneal curvature and corneal higher-order aberrations which confers a long-term stability for progressive ectasia. Based on the results of the Siena Eye-Cross Study 2, the 9 mW/5.4 J/cm 2 ACXL is a candidate to be  the natural evolution of Epi-Off CXL treatment for the management of early progressive corneal ectasia, and thus optimize clinic workflow.

Purpose: To assess whether optimized technical settings for accelerated epithelium-off corneal cross-linking may lead to increases in biomechanical stiffness similar to the benchmark 30-minute epithelium-off Dresden protocol., Methods: Three-hundred porcine eyes were divided equally into six groups for analysis. All samples underwent epithelial debridement and soaking with 0.1% iso-osmolar riboflavin solution for 20 minutes. Corneal cross-linking (CXL) was performed using epithelium-off protocols varying in acceleration and total fluence (intensity in mW/cm² * time in minutes, total fluence in J/cm²): standard (S)-CXL (3*30, 5.4), accelerated (A)-CXL (9*10, 5.4), A-CXL (9*13'20″, 7.2), A-CXL (18*6'40″, 7.2), and A-CXL (18*9'15″, 10). Control corneas were not irradiated. The elastic modulus of 5-mm wide corneal strips was measured as an indicator of corneal stiffness., Results: All irradiated groups had significantly higher elastic modulus than controls (P < 0.05), with a stiffening effect of 133% S-CXL (3*30, 5.4), 122% A-CXL (9*10, 5.4), 120% A-CXL (9*13'20″, 7.2), 114% A-CXL (18*6'40″, 7.2) and 149% A-CXL (18*9'15″, 10). The high-fluence accelerated epithelium-off protocol (18*9'15″, 10) showed the highest stiffening effect. Elastic modulus at 5% strain (1%-5% strain) showed significant differences between A-CXL (18*9'15″, 7.2) and three other accelerated protocols: A-CXL (9*10, 5.4; P = 0.01), A-CXL (9*13'20″, 7.2; P = 0.003), and A-CXL (18*6'40″, 10; P = 0.0001)., Conclusions: An accelerated high-fluence epithelium-off CXL protocol (18 mW/cm² for 9'15″) was identified to provide a significantly greater stiffening effect than any other accelerated protocols and is indistinguishable from the Dresden protocol, with accelerating irradiation times ranging from 30 to 9 minutes; by combining gentle acceleration with higher fluence, such a protocol does not require supplemental oxygen., Translational Relevance: This A-CXL (18*9'15″, 10) protocol has the potential to become a new standard in epithelium-off CXL, delivering Dresden protocol-like strengthening over a shorter period.

Purpose: To determine whether corneal cross-linking (CXL) with individualized fluence ("sub400 protocol") is able to stop keratoconus (KC) progression in ultrathin corneas with 12-month follow-up., Design: Retrospective, interventional case series., Methods: Thirty-nine eyes with progressive KC and corneal stromal thicknesses from 214 to 398 μm at the time of ultraviolet irradiation were enrolled. After epithelium removal, ultraviolet irradiation was performed at 3 mW/cm 2 with irradiation times individually adapted to stromal thickness. Pre- and postoperative examinations included corrected distance visual acuity (CDVA), refraction, Scheimpflug, and anterior segment optical coherence tomography imaging up to 12 months after CXL. Outcome measures were arrest of KC progression at 12 months postoperatively and stromal demarcation line (DL) depth., Results: Thirty-five eyes (90%) showed tomographical stability at 12 months after surgery. No eyes showed signs of endothelial decompensation. A significant correlation was found between DL depth and irradiation time (r = +0.448, P = .004) but not between DL depth and change in K max (r = -0.215, P = .189). On average, there was a significant change (P < .05) in thinnest stromal thickness (-14.5 ± 21.7 μm), K max (-2.06 ± 3.66 D) and densitometry (+2.00 ± 2.07 GSU). No significant changes were found in CDVA (P = .611), sphere (P = .077), or cylinder (P = .915)., Conclusions: The "sub400" individualized fluence CXL protocol standardizes the treatment in ultrathin corneas and halted KC progression with a success rate of 90% at 12 months. The sub400 protocol allows for the treatment of corneas as thin as 214 μm of corneal stroma, markedly extending the treatment range. The DL depth did not predict treatment outcome. Hence, the depth is unlikely related to the extent of CXL-induced corneal stiffening but rather to the extent of CXL-induced microstructural changes and wound healing., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The corneal cross-linking (CXL) photochemical reaction is essentially dependent on oxygen and hypothermia, which usually leads to higher dissolved oxygen levels in tissues, with potentially greater oxygen availability for treatment. Here, we evaluate whether a reduction of corneal temperature during CXL may increase oxygen availability and therefore enhance the CXL biomechanical stiffening effect in ex vivo porcine corneas., Methods: One hundred and twelve porcine corneas had their epithelium manually debrided before being soaked with 0.1% hypo-osmolaric riboflavin. These corneas were equally assigned to one of four groups. Groups 2 and 4 underwent accelerated epithelium-off CXL using 9 mW/cm 2 irradiance for 10 min, performed either in a cold room temperature (group 2, 4 °C) or at standard room temperature (group 4, 24 °C). Groups 1 and 3 served as non-cross-linked, temperature-matched controls. Using a stress-strain extensometer, the elastic moduli of 5-mm wide corneal strips were analyzed as an indicator of corneal stiffness., Results: Accelerated epithelium-off CXL led to significant increases in the elastic modulus between 1 and 5% of strain when compared to non-cross-linked controls (P < 0.05), both at 4 °C (1.40 ± 0.22 vs 1.23 ± 0.18 N/mm) and 24 °C (1.42 ± 0.15 vs 1.19 ± 0.11 N/mm). However, no significant difference was found between control groups (P = 0.846) or between groups in which CXL was performed at low or standard room temperature (P = 0.969)., Conclusions: Although initial oxygen availability should be increased under hypothermic conditions, it does not appear to play a significant role in the biomechanical strengthening effect of epithelium-off CXL accelerated protocols in ex vivo porcine corneas.

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.)

Before the advent of modern tomographic imaging and corneal cross-linking (CXL), diagnosis and treatment of ectatic disease were limited to disease severity where changes on the anterior corneal surface lead to visual complaints. Rigid contact lenses and/or penetrating keratoplasty addressed late stage disease, as identifying early or subclinical disease was not possible, or its need appreciated. The emergence of CXL as a viable treatment to alter the natural progression of keratoconus heightened the need for improved diagnostics.Several methods have been described in the literature to evaluate and document progression in keratoconus, but there has been no consistent definition of ectasia progression. Newer imaging techniques (ie, tomography) allowed the detection of earlier ectatic disease, before visual loss and subjective complaints. The Belin ABCD classification/staging system was introduced on a Scheimpflug imaging system [Pentacam, (Oculus GmbH, Wetzlar, Germany)] to address previous shortcomings. The ABCD system utilizes 4 parameters: Anterior ("A") and posterior ("B" for Back) radius of curvature taken from a 3.0 mm optical zone centered on the thinnest point, "C" is minimal Corneal thickness, and "D" best spectacle Distance visual acuity. The first 3 parameters (A, B, C) are machine-generated objective measurements that can be used to determine progressive change.The staging system is not limited to a specific commercial entity and can be incorporated in any tomographic imaging system. The ABCD Progression Display graphically displays each parameter and shows when statistical change above measurement noise is reached. This should allow the clinician the ability to diagnose progressive disease at a much earlier stage than was previously possible, with the confidence that earlier intervention could prevent visual loss.

Purpose: Photoactivated chromophore for keratitis cross-linking (PACK-CXL) is used as an adjunct therapy to antibiotic medication in infectious keratitis. This experimental study aimed at quantifying the PACK-CXL efficacy as a function of UV fluence using several bacterial strains and irradiated volumes., Methods: Six distinct bacterial strains, including standardized strains and clinically isolated strains from patients with keratitis, were analyzed. Bacterial concentrations between 10 and 10 cells/mL were used (simulating small corneal ulcers). Volumes of either 11 μL (≈285 μm stromal thickness) or 40 μL (≈1000 μm stromal thickness) were irradiated within a microtiter plate at different fluences (5.4-27 J/cm) and irradiances (3, 9 and 18 mW/cm). The ratio of bacterial killing (B†) was determined to evaluate the antimicrobial efficacy of PACK-CXL., Results: B† was similar (51 ± 11%) in bacterial concentrations between 10 and 10 per ml. In 11 μL volume, Staphylococcus aureus (SA) 8325-4 ATCC 29213, Bacillus subtilis (BS) 212901, and Pseudomonas aeruginosa (PA) 2016-866624 were most sensitive to PACK-CXL at 5.4 J/cm (on average B† = 49 ± 8%), whereas Klebsiella oxytoca (KO) 2016-86624 (B† = 25%) was least sensitive. When irradiating a larger volume, B† was on average lower in 40 μL (19 ± 18%), compared with 11 μL (45 ± 17%, P < 0.001). By contrast, applying a higher UV fluence increased B† of SA ATCC 29213, from 50% at 5.4 J/cm to 92% at 10.8 J/cm, to 100% at 16.2 J/cm and above., Conclusions: Applying higher UV fluences substantially increases the bacterial killing rates. Safety limits for clinical application require further investigation.

Background: To determine the average amount of mechanical forces applied to the lids of keratoconus patients during eye rubbing., Methods: Fifty-seven patients (41 male, 16 female, average age 34.8 years) with a clinically and topographically diagnosed keratoconus and a history of eye rubbing were prospectively asked to perform their individual eye rubbing movement on a high-precision balance. The type of eye-rubbing movement and the force applied, represented in newtons (N), were recorded and analyzed., Results: We detected three different types of eye rubbing. Rubbing with the fingertip was most frequent (51%), followed by rubbing with the knuckle (44%) and rubbing with the fingernail (6%). Each type of eye rubbing showed different average forces, with knuckle type eye rubbing applying significantly more force (9.6 ± 6.3 N) on the lids than fingertip (4.3 ± 3.1 N) and fingernail (2.6 ± 3.3 N) types (p < 0,001 and p = 0,016, respectively)., Conclusions: There were major variations in the force exerted on the lids, depending on the type of eye rubbing employed. This data will help determine the forces that need to be applied in future experimental eye rubbing models.

Purpose: Quasi-static optical coherence elastography (OCE) is an emerging technology to investigate corneal biomechanical behavior in situations similar to physiological stress conditions. Herein OCE was applied to evaluate previously inaccessible biomechanical characteristics of human corneal tissue and to study the role of Bowman's layer in corneal biomechanics., Methods: Human corneal donor buttons (n = 23) were obtained and Descemet's membrane and endothelium were removed. In 11 corneas, Bowman's layer was ablated by a 20 µm stromal excimer laser ablation. Buttons were mounted on an artificial anterior chamber and subjected to a pressure modulation from 10 to 30 mm Hg, and back to 10 mm Hg, in steps of 1 mm Hg. At each step, a spectral-domain optical coherence tomography scan was obtained. Displacements were analyzed by optical flow tracking, and strain over the entire stromal depth was retrieved from the phase gradient of the complex interference signal., Results: During pressure increase, corneal tissue moved upward (486-585 nm/mm Hg) but did not fully recover (Δ= 2.63 to 8.64 µm) after pressure decrease. Vertical corneal strain distribution was negative in the anterior and positive in the posterior cornea, indicating simultaneous corneal compression and expansion, respectively. Bowman's layer caused minor localized differences in corneal strain distribution., Conclusions: Corneal strain distribution is more complex than previously assumed, with a fundamental difference in mechanical response between the anterior and posterior stroma. Clinically, OCE technology might be used to monitor the progression of corneal ectatic diseases and to determine the success of corneal cross-linking.

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 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 compare the difference and agreement of corneal higher-order aberrations (HOAs) in keratoconic eyes using Scheimpflug and dual Scheimpflug-Placido imaging systems., Setting: Emory University, Atlanta, Georgia, and the University of Southern California, Los Angeles, California, USA., Design: Retrospective between-devices reliability and agreement study., Methods: Patients diagnosed with keratoconus were evaluated sequentially by Scheimpflug and dual Scheimpflug-Placido devices. Differences, correlations, and agreement between values for total root mean square (RMS), trefoil, coma, and spherical aberration were analyzed, and Bland-Altman plots were generated., Results: Fifty eyes from 50 patients (31 men, 19 women) were evaluated. Trefoil at 30 degrees, spherical aberration, and total RMS were significantly different between groups (P < .05), whereas trefoil at 0 degrees and total coma values were not statistically different. There was a weak positive correlation between devices for trefoil at 0 degrees (r = 0.228), and a moderate positive correlation for trefoil at 30 degrees (r = 0.473), horizontal coma (r = 0.430), and for total corneal RMS (r = 0.637). Vertical coma (r = 0.816) and spherical aberration (r = 0.874) showed a strong positive correlation. The 95% limits of agreement (LoA) for absolute values were 1.963 μm for trefoil at 30 degrees, 2.449 μm for trefoil at 0 degrees, 3.530 μm for horizontal coma, 2.145 μm for vertical coma, 1.242 μm for spherical aberration, and 10.527 μm for RMS., Conclusion: Significant differences were found between measurements of corneal HOAs generated by Scheimpflug and dual Scheimpflug-Placido devices in patients with keratoconus, with generally limited correlations and wide LoA. HOAs measurements from these devices should not be considered equivalent., (Copyright © 2019 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)