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First introduced over 20 years ago as a treatment for progressive keratoconus, the original "Dresden" corneal cross-linking (CXL) protocol involved riboflavin saturation of the stroma, followed by 30 min of 3 mW/cm 2 -intensity ultraviolet-A (UV-A) irradiation. This procedure generates reactive oxygen species (ROS) that cross-link stromal molecules, thereby stiffening the cornea and counteracting the ectasia-induced weakening. Due to their large size, riboflavin molecules cannot readily pass through the corneal epithelial cell tight junctions; thus, epithelial debridement was performed. Moreover, the Dresden protocol necessitates a minimal corneal thickness of 400 μm to protect the endothelium from UV-induced damage. While the Dresden protocol is highly effective at enhancing corneal biomechanical strength, there was a strong desire for CXL procedures that would deliver Dresden-like strengthening in a shorter time, in corneas thinner than 400 μm, and without requiring epithelial debridement. This review explores the advancements and scientific discoveries that have enabled such improvements. Accelerated CXL protocols, utilizing our increased knowledge about the role of oxygen and photochemical reactions in the cornea have shortened and simplified the procedure duration while maintaining efficacy and safety, improving clinical workflow and patient compliance. CXL is not confined to improving biomechanics in corneal ectasia, but rather represents a technique that modulates corneal physiology and biochemistry on multiple levels. Accordingly, CXL indications have expanded to include treating other corneal ectasias, corneal neovascularization, corneal sterile melting, inflammatory dry eye and importantly, infectious keratitis in a procedure termed photoactivated chromophore for keratitis-CXL (PACK-CXL). In PACK-CXL, ROS have a direct pathogen-killing effect, and cross-linking enhances the cornea's resistance to pathogen-produced protease digestion through steric hindrance. The distinct requirements of PACK-CXL compared to ectasia treatment have led to the development of different CXL protocols, including higher UV fluences and other chromophore/light combinations, specifically rose bengal and green light. Additionally, combining CXL with vision-enhancing procedures like individualized wavefront- or topographically-guided excimer ablation can regularize a biomechanically stable cornea, improve visual acuity, and potentially eliminate the need for corneal transplantation, leading to long-term improvements in quality of life., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: To evaluate the outcomes of patients treated with corneal allogeneic intrastromal ring segments cut with femtosecond laser (Femto-CAIRS) without concomitant corneal crosslinking., Methods: Patients with keratoconus treated with Femto-CAIRS at the American University of Beirut Medical Center were included (May 2022-January 2023). A proprietary software program was developed on the femtosecond laser to cut allogeneic segments. Visual, refractive, tomographic, aberrometric, and epithelial data by anterior segment optical coherence tomography were measured at baseline and 1, 3, 6, and 12 months postoperatively., Results: 20 eyes of 15 patients were included and followed up for 12 months. The manifest refraction spherical equivalent and cylinder improved from -6.79 ± 4.9 diopter (D) and -4.25 ± 1.8 D to -1.88 ± 2.9 D ( P < 0.001) and -2.64 ± 1.4 D ( P = 0.01) 12 months postoperatively, respectively. 75% of eyes gained 3 or more corrected distance visual acuity lines, most of which (65%) gained 4 lines or more 12 months postoperatively. The maximum keratometry and vertical coma decreased by 5.2 D ( P < 0.001) and 1 μm ( P = 0.001), respectively, 3 months postoperatively and remained stable until 12 months. The largest anterior stromal elevation over the central 5-mm diameter decreased from 36.0 ± 18.2 μm preoperatively to 19.9 ± 9.25 μm at 1 week postoperatively ( P < 0.001) and remained relatively stable. Epithelial thickness over the cone increased relative to baseline starting 1 month postoperatively and becoming stable after 6 months while the mean epithelial thickness central to the ring peaked at 1 month after which it decreased to reach a plateau at 6 months., Conclusions: The Femto-CAIRS procedure improves visual and tomographic parameters and allows repeatable and safe results with the possibility of customization for individualized management., Competing Interests: S. Jacob holds a patent for the special trephine and other devices and processes used to create corneal allogeneic intrastromal ring segments; Madhu Instruments, Ziemer Ophthalmic Systems. F. Müller is an employee of Ziemer Ophthalmic Systems AG, Port, Switzerland. S. T. Awwad is a consultant for Ziemer Ophthalmic Systems AG. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Keratoconus is a progressive eye disorder primarily affecting individuals in adolescence and early adulthood. The ectatic changes in the cornea cause thinning and cone-like steepening leading to irregular astigmatism and reduced vision. Keratoconus is a complex disorder with a multifaceted aetiology and pathogenesis, including genetic, environmental, biomechanical and cellular factors. Environmental factors, such as eye rubbing, UV light exposure and contact lens wearing, are associated with disease progression. On the cellular level, a complex interplay of hormonal changes, alterations in enzymatic activity that modify extracellular membrane stiffness, and changes in biochemical and biomechanical signalling pathways disrupt collagen cross-linking within the stroma, contributing to structural integrity loss and distortion of normal corneal anatomy. Clinically, keratoconus is diagnosed through clinical examination and corneal imaging. Advanced imaging platforms have improved the detection of keratoconus, facilitating early diagnosis and monitoring of disease progression. Treatment strategies for keratoconus are tailored to disease severity and progression. In early stages, vision correction with glasses or soft contact lenses may suffice. As the condition advances, rigid gas-permeable contact lenses or scleral lenses are prescribed. Corneal cross-linking has emerged as a pivotal treatment aimed at halting the progression of corneal ectasia. In patients with keratoconus with scarring or contact lens intolerance, surgical interventions are performed., (© 2024. Springer Nature Limited.)

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 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: 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 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 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 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: To determine whether combinations of devices with different measuring principles, supported by artificial intelligence (AI), can improve the diagnosis of keratoconus (KC)., Methods: Scheimpflug tomography, spectral-domain optical coherence tomography (SD-OCT), and air-puff tonometry were performed in all eyes. The most relevant machine-derived parameters to diagnose KC were determined using feature selection. The normal and forme fruste KC (FFKC) eyes were divided into training and validation datasets. The selected features from a single device or different combinations of devices were used to develop models based on random forest (RF) or neural networks (NN) trained to distinguish FFKC from normal eyes. The accuracy was determined using receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity., Results: 271 normal eyes, 84 FFKC eyes, 85 early KC eyes, and 159 advanced KC eyes were included. A total of 14 models were built. Air-puff tonometry had the highest AUC for detecting FFKC using a single device (AUC = 0.801). Among all two-device combinations, the highest AUC was accomplished using RF applied to selected features from SD-OCT and air-puff tonometry (AUC = 0.902), followed by the three-device combination with RF (AUC = 0.871) with the best accuracy., Conclusion: Existing parameters can precisely diagnose early and advanced KC, but their diagnostic ability for FFKC could be optimized. Applying an AI algorithm to a combination of air-puff tonometry with Scheimpflug tomography or SD-OCT could improve FFKC diagnostic ability. The improvement in diagnostic ability by combining three devices is modest., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: To report cases of progressive keratoconus (KC) in patients aged ≥48 years and the successful arrest of progression using corneal cross-linking (CXL) with riboflavin and ultraviolet-A light., Observations: Five eyes from four patients with progressive KC aged 48, 48, 51 and 54 years are reported in this case series. All eyes were followed regularly after initial diagnosis. K max was used as an indicator of progression and KC progressed at a rate of 1.4 diopters in 6 months and 14.6 diopters in 14 months. All patients eventually received CXL, and all were aged ≥50 years at the time of the procedure. One eye required two CXL procedures to successfully stabilize the patient's cornea., Conclusion: Despite the probability of KC progression strongly declining after the age of 40 years, it never becomes zero. It is therefore advisable to continue regular follow-up corneal tomography examinations in patients with KC, even in their fifth and sixth decades of life., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: F. Hafezi is a coinventor of the ultraviolet-A irradiation light source, PCT/CH application 2012/000090. The remaining authors have no conflicts of interest to disclose. No other authors have financial disclosures, proprietary or commercial interest in any materials discussed in this article.., (Copyright © 2022 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Abstract: When treating corneal ectasias, successful corneal cross-linking (CXL) requires three factors: riboflavin saturation of the corneal stroma, ultraviolet (UV) light, and oxygen. Riboflavin is too large to pass through epithelial tight junctions, so traditionally epithelial debridement is performed before riboflavin is applied making this approach an epithelium-off (epi-off) technique. However, this can result in pain as the epithelium regrows, corneal haze, and an increased infection risk postoperatively, which needs careful management with pharmacotherapy. Epithelium-on (epi-on) CXL should reduce the extent of these issues. Riboflavin can be passed through the epithelium into the stroma either by iontophoresis or with penetration enhancers, however this alone results in suboptimal cross-linking effects, as the epithelium not only absorbs around 20% of incoming UV energy, it also acts as a barrier to oxygen diffusion into the stroma. While it is simple to adjust the UV fluence delivered to the stroma to compensate for the energy lost in the epithelium, compensating for the lack of stromal oxygen is less simple. Several approaches (including oxygen goggles) have been taken to achieve this. However, adding iontophoresis and supplemental oxygen through goggles in the operating theater adds complexities that could be engineered out. Accordingly, the technique has advanced in the laboratory to a point where penetration enhancers, optimized UV irradiation profiles, and atmospheric oxygen can now provide epi-on CXL with the same corneal strengthening efficacy as epi-off CXL, suggesting simple, effective epi-on CXL could soon be in clinical use., Competing Interests: The author has no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. 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 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 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.] .

Ophthalmology is a highly technical specialty, especially in the area of diagnostic equipment. While the field is innovative, the access to cutting-edge technology is limited with reference to the global population. A significant way to improve overall healthcare is to understand the needs and possibilities of all possible consumers when developing sophisticated and accurate medical devices. The Smartphone-based Keratograph (SBK), is an example of a new project that uses real world feedback, addresses an unmet medical need, and implements commercially available components to create a device that is affordable, portable and simplistic to operate. The long-term goal of the SBK is to collect data from users for supervised machine-learning. This machine-learning aspect will ultimately aid in the development of an artificial intelligence device to enable even earlier detection of keratoconus, especially in children and adolescents. Again, the ultimate goal of any medical device should be to improve patient care, and to make a significant improvement on vision healthcare for the global population, providing access to this technology is essential.

Keratoconus (KCN) has been typically known as a disorder with effects limited to the cornea. Because of this viewpoint, less attention has been devoted to its effects on the posterior segment structures. We aimed to provide a comprehensive review of the literature to understand the potential link between KCN and posterior segment structures and their functions. It is clear from the extensive evidence in the literature that KCN can be associated with morphological and functional changes in different parts of the posterior segment. It is worth noting that anatomical changes have been not only noted in several layers of the retina but also in the optic nerve head and the choroid. Several mechanisms have been proposed to explain this observation, including incidents induced by oxidative stress in keratoconic corneas and retinal adaptions to the distorted image that lands on the retina. Consequently, when KCN has been diagnosed, it seems practical to consider assessing the retinal and choroidal profile using optical coherence tomography and potentially functional abnormalities through electrophysiology procedures., (Copyright © 2021. Published by Elsevier Inc.)

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.)

Purpose: To evaluate the safety and efficacy of reduced fluence CXL (lower dose of UV-A irradiation) in mild to moderate keratoconus., Setting: Farabi Eye Hospital, Tehran, Iran., Design: Non-randomized prospective comparative interventional case series. Every eligible patient included in the study (mild to moderate progressive keratoconus) was randomly allocated to case (reduced fluence) and control (standard) groups, except for bilateral patients. In these patients the eye with more advanced disease was allocated to control group and the other eye was randomly assigned in either case or control group. Operators performing refraction and images and the data analyst were masked, but patients and physicians were not., Methods: Forty-six eyes of 38 patients were recruited. Group 1 received 7 min (fluence of 3.8 J/cm 2 ), while group 2 received 10 min of 9 mW/cm 2 UV-A (fluence of 5.4 J/cm 2 ). Visual, keratometric and biomechanical outcomes were compared between groups., Results: At last follow-up (mean12 months, range 6-24 months), there were no statistically significant differences in changes in uncorrected visual acuity, best corrected distance visual acuity, Kmax, Kmean, corneal hysteresis, corneal resistance factor, endothelial cell counts, demarcation line depth, and intraoperative pain scores between groups (all p -values < 0.05)., Conclusion: The results of this study show comparable one-year outcomes between 3.8 and 5.4 J/cm 2 accelerated CXL in mild to moderate keratoconus. Should the results of this study be confirmed in longer follow-ups, using a reduced fluence setting could be considered as an alternative to standard treatment in these patients.

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.)

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.)

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.

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: To compare the effect of eye rubbing on Scheimpflug imaging parameters and corneal biomechanics in eyes with keratoconus and healthy eyes., Setting: Oftalmosalud Instituto de Ojos, Lima, Peru., Design: Prospective cohort study., Methods: The study included healthy and keratoconus patients who attended the institution between January 2017 and July 2017. Eye rubbing was performed for 1 minute followed by a 5-second break, followed by further rubbing for 1 minute. Baseline tests were performed before rubbing; post-rubbing tests were performed immediately after (0 minutes), and then again at 7 minutes and 14 minutes. Parameters related to anterior and posterior curvature and elevation, pachymetry, and corneal biomechanics obtained from tomography with a rotating Scheimpflug camera (Pentacam HR) and a dynamic bidirectional applanation device (Ocular Response Analyzer) were measured and compared between healthy and keratoconic eyes., Results: The study included 30 healthy eyes and 31 keratoconic eyes. In the healthy group, the immediate mean changes in steeper anterior keratometry, posterior astigmatism, anterior chamber volume (ACV), flattest posterior keratometry, and Goldmann-correlated intraocular pressure (IOPg) after eye rubbing were 0.07 diopters (D) ± 0.15 (SD), -0.01 ± 0.08 D, 0.03 ± 7.06 mm 3 , -0.001 ± 0.04 mm, and -1.21 ± 1.99 mm Hg, respectively, whereas the mean changes in the keratoconus group were -0.03 ± 0.32 D, 0.14 ± 0.50 D, -5.09 ± 8.45 mm 3 , 0.03 ± 0.06 mm, and -1.61 ± 1.41 mm Hg, respectively. There were statistically significant differences between the preoperative and postoperative eye-rubbing values of posterior astigmatism, ACV, and IOPg in the keratoconus group (P = .03, P = .0003, and P = .001, respectively) but not in the healthy group (P = .65, P = .85, and P = .23, respectively)., Conclusions: Unlike the healthy eyes group, the keratoconus group experienced significant changes in ACV, IOP, and corneal posterior astigmatism after eye rubbing., (Copyright © 2019. Published by Elsevier Inc.)

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.)

Purpose: To compare the relative 12-month corneal crosslinking (CXL) functional outcomes using standard protocol and accelerated protocols in patients with progressive keratoconus., Methods: CXL was performed using 3 epithelium-off protocols: standard [3 mW/cm for 30 minutes, 5.4 J/cm (S3/30-CXL)], accelerated with equivalent total irradiance [9 mW/cm for 10 minutes, 5.4 J/cm (A9/10-CXL)], and accelerated with increased total irradiance [30 mW/cm for 4 minutes, 7.2 J/cm (A30/4-CXL)]. Efficacy measurements were evaluated 12 months after treatment with Scheimpflug imaging (Pentacam HR) and included change in maximum keratometry (K Max), corrected distance visual acuity (CDVA), other keratometric variables, pachymetry, keratoconus indices, astigmatism, asphericity, manifest refraction, and higher order aberrations., Results: Ninety-three eyes (67 patients) were evaluated: 35 eyes (26 patients) with S3/30-CXL, 29 eyes (19 patients) with A9/10-CXL, and 29 eyes (22 patients) with A30/4-CXL. Mean [INCREMENT]K Max was -1.53 ± 2.1 diopter (D) for S3/30-CXL, -0.71 ± 1.3 D for A9/10-CXL, and -0.70 ± 2.3 D for A30/4-CXL (P = 0.37). Mean [INCREMENT]CDVA(logMAR) was -0.18 ± 0.2 for S3/30-CXL, -0.13 ± 0.2 for A9/10-CXL, and -0.18 ± 0.2 for A30/4-CXL (P = 0.79). [INCREMENT]K Mean (r = -0.29 to -0.46), anterior asphericity (r = -0.34 to -0.40), and central keratoconus index (r = -0.18 to -0.38) best correlated with [INCREMENT]CDVA. S3/30-CXL had greater changes in index of surface variance, index of vertical asymmetry, keratoconus index, and regularization index compared to A9/10-CXL and A30/4-CXL. There were no other differences between protocols., Conclusions: All 3 protocols showed improvements in K Max, CDVA, and other variables, with similar functional outcomes for each despite greater change in keratoconus indices after S3/30-CXL. Correlations between change in measured variables and CDVA were poor overall; however, K Mean, central keratoconus index, and anterior asphericity were better correlated with CDVA than K Max.

Corneal cross-linking (CXL), introduced by Wollensak et al. in 2003, is a minimally invasive procedure to halt the progression of keratoconus. Conventional CXL is recommended in eyes with corneal thickness of at least 400 microns after de-epithelialization to prevent endothelial toxicity. However, most of the keratoconic corneas requiring CXL may not fulfill this preoperative inclusion criterion. Moderate-to-advanced cases are often found to have a pachymetry less than this threshold. There are various modifications to the conventional method to circumvent this issue of CXL thin corneas while avoiding the possible complications. This review is an update on the modifications of conventional CXL for thin corneas., Competing Interests: None

We describe the association of rapid progression of keratoconus in a 49-year-old woman on selective tissue estrogenic activity regulator (STEAR) therapy for endometriosis. Approximately 4 months after initiation of therapy with STEAR therapy and 3 months after ovariectomy, Scheimpflug images showed a massive increase in the previously stable ectasia. During this period, the maximum increase in the keratometry values was 2.7 diopters (D) in the right eye and 3.8 D in the left eye. Corneal crosslinking (CXL) was performed in both eyes. This resulted in excessive flattening of 5.5 D in the right eye and 6.1 D in the left eye at 9 months postoperatively. Patients having STEAR therapy must be monitored closely for corneal changes., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Background/aim: Keratoconus (KC) is a ectatic corneal disorder with marked progression during childhood and puberty that may lead to severe visual loss. In addition to KC prevalence, estimate shows major geographical variations; recent studies using Scheimpflug technology are in contrast to the 1980s and 1990s literature. The present study aims to determine the prevalence of KC in paediatric patients in Riyadh, Saudi Arabia (KSA)., Methods: This prospective, cross-sectional, observational, multicentre study collected data from paediatric patients from 6 years and 21 years of age who were seen at multiple non-ophthalmic emergency departments within KSA. Bilateral corneal measurements were performed using a rotational Scheimpflug corneal tomography system. Two masked examiners established the diagnosis of KC using both objective and subjective screening criteria. Cohen's kappa coefficient (κ) was used to qualitatively analyse the interexaminer agreement., Results: There were 522 patients (1044 eyes) evaluated, with an average age of 16.8±4.2 years (range 6-21 years). KC prevalence was 5.56% for examiner 1 and 3.83% for examiner 2. The κ was 0.81 (almost perfect agreement), with discrepancy in nine cases, which were jointly evaluated and consensus obtained. Final KC prevalence was 4.79% (95% CI 2.96 to 6.62) or 1:21 patients., Conclusions: The prevalence of KC among paediatric patients in the KSA is considerably higher than numbers reported from earlier studies and from similar studies in other countries. This increase might be due to geographical variations in disease prevalence or due to the ability of screening technology to detect undiagnosed KC with greater accuracy., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To evaluate the correlation between anterior axial curvature difference maps following corneal cross-linking (CXL) for progressive keratoconus obtained from Scheimpflug-based tomography and Placido-based topography., Design: Between-devices reliability analysis of randomized clinical trial data., Methods: Corneal imaging was collected at a single-center institution preoperatively and at 3, 6, and 12 months postoperatively using Scheimpflug-based tomography (Pentacam; Oculus Inc, Lynnwood, Washington, USA) and scanning-slit, Placido-based topography (Orbscan II; Bausch & Lomb, Rochester, New York, USA) in patients with progressive keratoconus receiving standard protocol CXL (3 mW/cm 2 for 30 minutes). Regularization index (RI), absolute maximum keratometry (K Max), and change in K Max (ΔK Max) were compared between the 2 devices at each time point., Results: Fifty-one eyes from 36 patients were evaluated at all time points. Values were significantly different at all time points (56.01 ± 5.3 diopters [D] Scheimpflug vs 55.04 ± 5.1 D scanning-slit preoperatively [P = .003]; 54.58 ± 5.3 D Scheimpflug vs 53.12 ± 4.9 D scanning-slit at 12 months [P < .0001]) but strongly correlated between devices (r = 0.90-0.93) at all time points. The devices were not significantly different at any time point for either ΔK Max or RI but were poorly correlated at all time points (r = 0.41-0.53 for ΔK Max, r = 0.29-0.48 for RI). At 12 months, 95% limits of agreement were 7.51 D for absolute K Max, 8.61 D for ΔK Max, and 19.86 D for RI., Conclusions: Measurements using Scheimpflug and scanning-slit Placido-based technology are correlated but not interchangeable. Both devices appear reasonable for separately monitoring the cornea's response to CXL; however, caution should be used when comparing results obtained with one measuring technology to the other., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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 evaluate changes in regional corneal epithelial thickness after corneal crosslinking (CXL) using higher fluence (7.2 J/cm 2 ) and accelerated treatment time (4 minutes) in eyes with progressive keratoconus using spectral-domain optical coherence tomography (SD-OCT) and to correlate focal epithelial and focal anterior curvature changes., Setting: Academic medical center in the United States., Design: Prospective case series., Methods: Patients had anterior segment SD-OCT (RTVue-100) with focal stromal and epithelial measurements and Scheimpflug imaging before and 1, 3, 6, and 12 months after accelerated CXL., Results: Twenty-seven eyes from 20 patients were evaluated. Before the accelerated CXL, the epithelium was thinnest in the inferior inner and outer temporal regions, whereas at 12 months postoperatively, the epithelium was significantly thinned in multiple inferior and nasal regions by 1.1 to 3.2 μm (P < .05, all measurements), with no significant changes from 6 to 12 months. Epithelial thickness standard deviation across the central 6.0 mm was significantly reduced by 3 months (1.4 μm, P = .09) and remained stable at 12 months (P = .009). Change in epithelial thickness was poorly correlated to change in anterior curvature (r = -0.035)., Conclusions: Significant epithelial remodeling occurred after accelerated CXL in eyes with progressive keratoconus, with improved regularity across the central 6.0 mm, by 6 months after treatment. There was poor correlation between focal epithelial thickness and anterior curvature changes, with wide variability between patients. Establishing the pattern of epithelial remodeling after CXL might help optimize future custom treatment protocols., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

PurposeTo investigate intraoperative anterior segment optical coherence tomography (AS-OCT) to compare pachymetry changes between two methods (group 1: speculum-on, group 2: speculum-off during riboflavin instillation stage) during corneal cross-linking /CXL) (9 mW/cm 2 for 10 min) in keratoconic patients.MethodsIn this interventional case series, 11 eyes (11 patients) in group 1 and 14 eyes (14 patients) in group 2 were enrolled. Pachymetry measurements by spectral domain OCT was performed at baseline, after epithelial removal, after 30 min of imbibition with riboflavin, and after UV irradiation. Repeated measures analysis of variance was used to compare the trend of changes in different stages of the procedure within and between two groups.ResultsThe corneal thinnest pachymerty (CTP) at baseline, after epithelial removal, 30 min of riboflavin instillation, and irradiation was 469.8±26.5, 438.0±27.1, 354.3±28.4, 367.1±31.8 microns in group 1 and 463.2±25.1, 438.0±27.1, 421.6±54.0, 386.9±34.0 microns in group 2, respectively. Group 1 showed a significantly greater decrease in the corneal pachymetry (P<0.001) during riboflavin instillation, while in group 2 a greater decrease in CTP was observed during the UV irradiation phase (P=0.002).ConclusionsUsing the intraoperative OCT, the speculum-off group had a more stable corneal pachymetry during riboflavin instillation time. Despite this, the effect was not lasting throughout the procedure; significant changes were noted in the corneal pachymetry at the end of operation in both groups; further highlighting the limitations imposed by corneal stromal shrinkage using isotonic dextran containing riboflavin solution for CXL.

Purpose: To study the mid-term effects of implanting a single intracorneal ring segment (ICRS) for treatment of mild to moderate progressive keratoconus., Methods: This retrospective study was conducted on patients with progressive keratoconus treated with ICRS. The mean follow-up time was 15.2 ± 8.8 (range, 7-26) months before and 27.8 ± 7.5 (range, 18-35) months after surgery. Patients received no other treatment during this time. Of the cases studied, 59.1% had inferior keratoconus., Results: Thirty eyes of 30 patients with a mean age of 27.5 ± 4.6 years were included in the study. Corrected distance visual acuity decreased by 1 line during the preoperative follow-up and improved by 2 lines after surgery (P < 0.05). Maximum keratometry (Kmax) of the anterior (2.39 ± 0.75 D) and posterior (0.33 ± 0.32 D) corneas at 3 mm and anterior Kmax at 8 mm (2.39 ± 0.95 D) decreased after treatment (all P < 0.05). The posterior Q value shifted toward a more oblate curvature (0.50 ± 0.52, P = 0.023). Decreases in anterior elevation at the thinnest point (5.22 ± 7.21 μm) and posterior corneal central elevation (8.89 ± 11.26 μm) were significant (both P < 0.05). Corneal thickness at the center (11.11 ± 12.38 μm) and thinnest point (15.89 ± 12.75 μm) increased after treatment (all P < 0.001). Other significant changes included postoperative decreases in the keratoconus index (0.12 ± 0.06), index of height decentration (0.06 ± 0.05), index of surface variance (27.32 ± 13.08), index of vertical asymmetry (0.42 ± 0.21), index of height asymmetry (8.42 ± 20.57), and an increase in the center keratoconus index (0.01 ± 0.02) (P < 0.001)., Conclusions: This study demonstrates that ICRS implantation provides favorable mid-term outcomes in treatment of mild and moderate progressive keratoconus and can improve corneal indices compared with their preoperative states.

Purpose: To investigate the composition and concentration of individual riboflavin compounds in the corneal stroma in vivo after soaking with various commercially available riboflavin formulations., Methods: Experiments were performed in 26 rabbit corneas in vivo: 24 corneas were soaked with riboflavin formulations for 30 minutes or with 0.9% NaCl for control (n = 2). After treatment, corneas were excised and prepared for ultra-high-pressure liquid chromatography (UHPLC) analysis. Additionally, computational chemical analysis of riboflavin compounds and keratan sulfate were performed., Results: The amount of riboflavin and riboflavin phosphate isomers in cornea decreased by a factor of 10 to 100, when compared to the amount in riboflavin formulations. In particular, we found an inverse relationship in the ratio of riboflavin to riboflavin phosphate isomer concentration between formulations and cornea. The electronegativity and ionization potential of riboflavin and phosphate isomers are different., Conclusions: The inverse relationship observed might be explained by a stronger electronegativity of the phosphate isomers, leading to a stronger repulsion by corneal proteoglycans. Indicating the individual concentration of riboflavin compounds in formulations is more representative than the total riboflavin concentration. Riboflavin formulations and CXL protocols might be improved considering the differences in diffusion and ionization potentials of the different riboflavin compounds.

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 long-term outcomes of accelerated and standard corneal cross-linking protocols in the treatment of progressive keratoconus., Design: Prospective randomized clinical trial., Methods: Thirty-one eyes with keratoconus were treated with an accelerated protocol (18 mW/cm(2), 5 min) and all contralateral eyes were treated with the standard method (3 mW/cm(2), 30 min) using the same overall fluence of 5.4 J/cm(2)., Results: At 18 months after the procedure, the standard group showed significant improvement in spherical equivalent (P < .05), K-readings (P < .05), Q value (P < .05), index of surface variance (P < .05), and keratoconus index (P = .008) and decline in central corneal thickness (P < .05), but no significant change in visual acuity, corneal hysteresis, corneal resistance factor, P2 area, or endothelial cell density. In the accelerated group, central corneal thickness was the only parameter with statistically significant change. However, neither of these parameters showed significant differences between the standard and the 18 mW/cm(2) accelerated protocol, except K-reading (P = .059) and index surface variance (P = .034)., Conclusion: An accelerated cross-linking protocol, using 18 mW/cm(2) for 5 minutes, shows a comparable outcome and safety profile when compared to the standard protocol, but better corneal flattening is achieved with the standard method than the accelerated method. Overall, both methods stop the disease progression similarly. This study will continue to examine more long-term results., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Since its inception in the late 1990s, corneal cross-linking has grown from an interesting concept to a primary treatment for corneal ectatic disease worldwide. Using a combination of ultraviolet-A light and a chromophore (vitamin B2, riboflavin), the cornea can be stiffened, usually with a single application, and progressive thinning diseases such as keratoconus arrested. Despite being in clinical use for many years, some of the underlying processes, such as the role of oxygen and the optimal treatment times, are still being worked out. More than a treatment technique, corneal cross-links represent a physiological principle of connective tissue, which may explain the enormous versatility of the method. We highlight the history of corneal cross-linking, the scientific underpinnings of current techniques, evolving clinical treatment parameters, and the use of cross-linking in combination with refractive surgery and for the treatment of infectious keratitis., (Copyright © 2015 Elsevier Inc. All rights reserved.)