Search

Keratoconus is a common pediatric corneal disease, leading to vision impairment and amblyopia. Compared to its adult counterpart, pediatric keratoconus has an advanced presentation, rapid progression, higher incidence of complications such as corneal hydrops, and greater potential impact on the quality of life. It typically manifests during puberty and can evolve rapidly to more severe stages if left untreated. This rapid progression underscores the importance of early diagnosis through regular screening in pediatric populations and vigilant monitoring of pediatric keratoconus suspects. Concomitant ocular allergies, ocular anomalies, systemic diseases (e.g. syndromes), and poor compliance with contact lenses might impede prompt intervention and frequently postpone rehabilitation. Corneal collagen crosslinking is a crucial intervention in the management of pediatric keratoconus because it strengthens the corneal microstructure and halts the disease progression. When conservative measures fail, keratoplasty remains a viable option with generally favorable outcomes, though with unique challenges in post-operative care, including concerns related to sutures, long-term graft survival and need for repeated examinations under anesthesia. A multidisciplinary approach involving ophthalmologists, optometrists, pediatricians, and other healthcare professionals, focusing on early diagnosis and timely intervention, is essential for the comprehensive management of pediatric keratoconus and to mitigate its impact on children's lives., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate demographic and tomographical parameters in predicting treatment response following transepithelial iontophoresis-assisted corneal cross-linking (I-CXL) for progressive keratoconus., Methods: Forty eyes (20 aged < 19 years and 20 aged ≥ 19 years) underwent I-CXL treatment between 2016 and 2022. Progression criteria based on the ABCD system, changes in asphericity (Q), demographic factors and keratoconus phenotypes were evaluated. Subjects were followed for 24 months after procedure., Results: Sixty percent of participants were male. The mean age at the time of treatment was 21.0 ± 6.0 years. All tomographical values showed progression after 2 years of follow-up (p < 0.05), particularly during the first 6 months, except for anterior curvature. Within the ABCD grading system, we observed: A) an increase in anterior curvature, more evident with lower initial values; B) an increase in posterior curvature, more pronounced with higher initial values. Two years after I-CXL, 20% of subjects met progression criteria in two or more parameters, with 62.5% being under 19 years of age. Patients with a family history of corneal ectasia exhibited a mean KMax progression of 1.94D ± 1.88, (p = 0.046). Only phenotypes 3 and 4 showed progression. Although patients under 19 years showed greater progression in all tomographical variables at the end of the study, this difference was not statistically significant., Conclusion: Treatment with I-CXL did not stop progression in the variables studied two years after the procedure in an effective manner, especially in patients younger than 19 years. A family history of corneal ectasia and subtype 4 keratoconus predicted a less favourable response to I-CXL., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. This work has not been previously published and is not under consideration for publication in another journal. All authors, as well as the entity where this study was carried out approve its publication. If the manuscript is accepted, it will not be published elsewhere without the written consent of the copyright holder., (© 2025. The Author(s).)

Purpose: To present baseline characteristics and to present the perioperative corneal thickness during corneal crosslinking (CXL) treatment for progressive keratoconus and to describe how the addition of sterile water (SW) efficaciously can maintain the corneal thickness. The treatment efficacy will be evaluated when the 1-year follow-up is complete., Methods: A randomised clinical study using epithelium-off CXL with continuous UVA irradiation (9 mW/cm 2 ) and two kinds of riboflavin solutions: (i) isoosmolar dextran-based riboflavin (n = 27) and (ii) hypoosmolar dextran-free riboflavin (n = 27)., Inclusion Criteria: progressive keratoconus with an increase in maximum keratometry value (Kmax) of 1.0 dioptre (12 months) or 0.5 dioptres (6 months). Corneae thinner than 400 μm were also included., Outcome Parameters: Perioperative corneal thickness and the effect of adding SW., Results: Seventy-four per cent of the patients in the isoosmolar group and 15% in the hypoosmolar group required the addition of SW, which effectively maintained a corneal thickness of 400 μm in all cases during CXL. The addition of SW was primarily needed during the irradiation procedure and not the preoperative soaking period., Conclusions: Especially during the CXL irradiation phase, isoosmolar riboflavin causes a significant dehydrating effect leading to corneal thinning during CXL. The customised addition of SW is efficacious in maintaining the corneal thickness during CXL and could increase the safety of the procedure., (© 2024 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Corneal cross-linking (CXL) is the standard of care in patients with keratoconus but presents unique challenges in children and developmentally delayed patients. We present our clinical decision-making algorithm, CXL surgical technique, and outcomes in these groups., Methods: A retrospective chart review was undertaken at a tertiary referral center of all patients who underwent CXL for keratoconus at University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh between October 1, 2017, and April 1, 2021. Demographic information along with preoperative, intraoperative, and postoperative ophthalmic examination findings were collected. The main outcome measures were indications of CXL, postoperative complications, and visual acuity (VA)., Results: Forty-eight eyes of 34 patients [21 patients (30 eyes) with developmental delay (DD) and 13 patients (18 eyes) with no DD (NDD)] underwent epithelium-off, standard CXL. General anesthesia was used for CXL in all patients except for 3 with NDD. A temporary central tarsorrhaphy was performed in all patients with DD and 7 patients with NDD. The remaining got a bandage contact lens. There were no immediate postoperative complications. A trend toward improvement in VA was noted postoperatively. The mean logMAR VA (with habitual correction) was 0.67 preoperatively and 0.57 postoperatively ( P = 0.3) in DD and 0.52 and 0.36, respectively ( P = 0.13), in NDD., Conclusions: This retrospective review presents a technique for assessment and treatment of keratoconus in children and those with DD. Our technique ensures timely diagnosis and provides a safe method for CXL in these groups. Temporary central tarsorrhaphy is a well-tolerated option to reduce postoperative pain., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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 changes in corneal backscattering after collagen cross-linking (CXL) for progressive keratoconus and compare its course with different techniques - standard epithelium-off CXL (SCXL), contact lens-assisted CXL (CACXL), and transepithelial CXL (TECXL)., Setting: Advanced Eye Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India., Design: Retrospective comparative study., Methods: Ninety-four eyes (SCXL: 47, CACXL: 30, and TECXL: 17) were compared. Corneal haze was quantified using Scheimpflug tomography, pre- and post-CXL at 1, 3, 6, and 12 months., Results: The baseline mean density score of the central anterior stromal layer was 16.14 ± 7.07, 15.85 ± 7.89 and 15.89 ± 7.21 in SCXL, CACXL, and TECXL groups, respectively ( P 0.93). After SCXL, the score increased to 28.83 and 31.34 at 1 and 3 months, respectively (both P < 0.001) and dropped at 6 months (28.66, P < 0.001) and 12 months (23.72, P 0.003). Post-CACXL, the mean densitometry peaked at 3 months (20.35, P 0.14) and returned toward baseline at 6 months (18.82, P 0.15). After TECXL, it increased slightly at 1 month (18.47, P 0.17), decreased at 3 months (14.88, P 0.7), and plateaued over 1 year. No correlation with visual acuity was seen., Conclusion: Corneal haze increased significantly after SCXL, peaking at 3 months, declining over 6-12 months, and returning to baseline at 12 months. In contrast, post-TECXL and -CACXL, there was an insignificant increase in anterior corneal haze, which returned to baseline within 3-6 months., (Copyright © 2024 Indian Journal of Ophthalmology.)

Purpose: To comparatively evaluate the influence of different riboflavin formulations and soaking durations on the anterior segment optical coherence tomography (AS-OCT) findings following accelerated corneal crosslinking (ACXL) at 9 mW/cm 2 for in progressive keratoconus., Methods: In this prospective study, consecutive patients with progressive keratoconus were randomized into 4 groups. Group 1: hydroxypropyl methylcellulose (HPMC)-based riboflavin for 10 min; Group 2: HPMC-based riboflavin for 20 min; Group 3: dextran-based riboflavin (0.1%) for 30 min. Riboflavin soaking was followed by ultraviolet-A irradiation at 9 mW/cm 2 for 10 min in all three groups. Group 4 underwent conventional CXL (CCXL) using Dresden protocol. The AS-OCT features of the crosslinked cornea were evaluated at postoperative month 1 and correlated to the clinical outcomes at postoperative month 12., Results: The study enrolled 26 eyes of 26 patients in each group. In groups 1 and 2, the AS-OCT findings were similar ( p  > .05) and the demarcation lines depth (DLD) were deep as obtained following CCXL. The DLD was significantly shallower in group 3 compared to the other groups ( p  < .01). There were no between-group differences in regards to the visual, refractive, keratometric, and tomographic outcomes at postoperative month 12. No significant endothelial cell loss or any other clinically significant adverse event was encountered in any patient's eye at 12 months follow-up., Conclusion: Although structural variations were noted in the crosslinked cornea, DLDs observed following ACXL (9 mW/cm 2 ) using HPMC-based solution for 10 or 20 min were similar to those observed following CCXL. Whereas, ACXL (9 mW/cm 2 ) using dextran-based solution for 30 min resulted in the shallowest DLD. Despite these remodeling differences, the visual, refractive and tomographic outcomes of all groups were comparable at postoperative 1-year follow-up. Studies with a greater number of patients and longer follow-ups are required to establish any relation between AS-OCT characteristics of crosslinked cornea and ACXL efficacy.

Collagen cross-linking (CXL) is considered as a successful therapeutic approach for corneal conditions like keratoconus and corneal ectasia. Despite its efficacy in stabilizing these conditions, the occurrence of post-CXL scars remains a concern. Keratoconus and other corneal ectasias are characterized by structural weaknesses in the cornea. This weakness contributes to the vulnerability of corneal scar formation. In addition, corneal biomechanics and tissue properties play a significant role in scar development. Procedural factors during CXL, including duration and intensity of ultraviolet light exposure, the concentration and type of riboflavin, and the precise application of treatment, have been identified as potential causes of scar formation. Individual patient factors such as variations in healing response and genetic predispositions, associated ocular allergy, and chronic contact lens wear can also impact scar development post-CXL. Understanding these variables is essential for risk stratification and personalized treatment approaches, ultimately optimizing patient outcomes. In addition, regular follow-up visits and patient education are essential to ensure optimal healing and minimize scar related complications. We have tried to explain the numerous reasons of scarring following epithelium-off CXL by conducting a thorough Medline search and reviewing our clinical images. This review serves as a concise overview of the causes and risk factors associated with scar formation after epithelium-off CXL., (Copyright © 2024 Indian Journal of Ophthalmology.)

Purpose: To report outcomes in patients with progressive keratoconus who underwent a standardized protocol of transepithelial phototherapeutic keratectomy (t-PTK) laser followed by accelerated corneal collagen crosslinking (CXL)., Methods: All patients with progressive keratoconus undergoing our protocol at a London clinic between 2019 and 2023 were included. The protocol involved t-PTK at 58-μm central ablation depth at a 9-mm treatment zone on the Schwind Amaris 1050RS platform. Preoperative K readings of 43.0D (both K1 and K2) were inputted for all cases. Patients then underwent CXL with a pulsed-light accelerated protocol (30 mW/cm 2 for 8 minutes of UVA exposure time with 1 second on/1 second off)., Results: Seventy-nine eyes from 55 patients were included with an average follow-up of 12 months (range 6-24 months). Both mean uncorrected distance visual acuity (UDVA) and best spectacle-corrected visual acuity improved significantly from 0.42 preoperatively to 0.29 postoperatively ( P < 0.01) and 0.11 to 0.06 postoperatively ( P < 0.01), respectively. The refractive cylinder reduced significantly from -3.07D to -2.63D ( P < 0.05). The mean Km improved from 46.15D to 45.44D ( P < 0.01) and mean Kmax from 54.03D to 52.52D ( P < 0.01). 77% of eyes (n = 61) exhibited Kmax improvement postoperatively, and 56% showed an improvement in UDVA (n = 44). 16% (n = 13) had worsening of vision, but of these, only 1 patient had visual loss of more than 2 lines. No eyes had corneal haze reported at the final follow-up, and none required additional treatment., Conclusions: This standardized simultaneous t-PTK and CXL protocol is safe and effective for the treatment of progressive keratoconus, providing visual, refractive, and topographic improvements., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To assess the safety and the efficacy of the "Sub-400 corneal cross-linking (CXL) protocol" for progressive keratoconus (KC) in ultrathin corneas., Methods: The study included thirty four patients with progressive KC, who underwent CXL using the "Sub-400" protocol due to intraoperative thinnest corneal pachymetry ranging from 295 to 398 μm after epithelial removal. After the epithelium was removed, the following ultraviolet A irradiation was applied at a fluence of 3 mW/cm 2 and the duration was adjusted based on the specific corneal stromal thickness. In addition to slit-lamp microscopy and visual acuity assessment, our evaluation included measurements of the maximal anterior keratometry value (Kmax), mean anterior and posterior K values (Kmean), thinnest corneal thickness (TCT), central corneal thickness, intraoperative pachymetry, and corneal endothelial cell density (ECD) preoperatively and 1 year postoperatively. Stromal demarcation line depth (DL) was measured in the first postoperative month., Results: At the first year postoperative follow-up visit, 88% (30 eyes) exhibited tomographic stability, with average values of change in Kmax (ΔKmax) 0.61 ± 6.45 D after CXL. None of the eyes showed signs of endothelial decompensation. The mean DL depth was 250.76 ± 44.05 μm. Moderate positive correlations were observed between DL and ultraviolet A irradiation time, DL, and intraoperative stromal thickness (r = 0.473, p = 0.005 and r = 0.517, p = 0.002, respectively). ΔKmax was negatively correlated with preoperative Kmax (r =  - 0.559, P = 0.001) and positively correlated with preoperative TCT (r = 0.373, P = 0.030)., Conclusion: The "Sub-400 protocol" for CXL has a broad application possibility for ultrathin corneas with KC and has shown promising results., Competing Interests: Declarations. Conflict of interests: The authors declare that there are no conflicts of interest or funding for this study., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

A woman in her early 20s with progressive keratoconus underwent corneal collagen cross-linking using the sub400 protocol. The central 5.5 mm of the epithelium was removed after the application of 20% alcohol. Topical riboflavin 0.1% was applied every 3 min for 30 min and then irradiated with UV-A light (irradiance of 3 mW/cm 2 for 16 min). At the end of the procedure, a therapeutic contact lens was placed and ofloxacin 0.3% (4 times daily), dexamethasone 0.1% (4 times daily) and lubricant (hourly) drops were prescribed.Two days after the procedure, the patient presented with a painless red eye. A 360° peripheral ring-like infiltrate was observed in the 5.5 mm zone, consistent with a sterile infiltrate. Dexamethasone 0.1% drops were prescribed and tapered for 1 month. Although the infiltrate gradually decreased under corticosteroid therapy, the patient's condition worsened after discontinuation of treatment. Treatment was resumed and complete recovery was observed 4 months later., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To validate the ability of theranostic imaging biomarkers in assessing corneal cross-linking (CXL) efficacy in flattening the maximum keratometry (K max ) index., Design: Prospective, randomized, multicenter, masked clinical trial (ClinicalTrails.gov identifier, NCT05457647)., Participants: Fifty patients with progressive keratoconus., Intervention: Participants were stratified to undergo epithelium-off (25 eyes) and epithelium-on (25 eyes) CXL protocols using an ultraviolet A (UV-A) medical device with theranostic software. The device controlled UV-A light both for performing CXL and assessing the corneal riboflavin concentration (riboflavin score) and treatment effect (theranostic score). A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epithelium-off and epithelium-on protocols, respectively. All eyes underwent 9 minutes of UV-A irradiance at 10 mW/cm 2 ., Main Outcome Measures: The primary outcome measure was validation of the combined use of theranostic imaging biomarkers through measurement of their accuracy (proportion of correctly classified eyes) and precision (positive predictive value) to classify eyes correctly and predict a K max flattening at 1 year after CXL. Other outcome measures included change in K max , endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction and central corneal thickness 1 year after CXL., Results: Accuracy and precision of the theranostic imaging biomarkers in predicting eyes that had >0.1 diopter (D) of K max flattening at 1 year were 91% and 95%, respectively. The K max value significantly flattened by a median of -1.3 D (IQR, -2.11 to -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 logarithm of the minimum angle of resolution (logMAR; IQR, -0.3 to 0.0 logMAR [P < 0.001] and -0.2 to 0.0 logMAR [P < 0.001], respectively). No significant changes in endothelial cell density (P = 0.33) or central corneal thickness (P = 0.07) were noted 1 year after surgery., Conclusions: The study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epithelium-off and epithelium-on CXL protocols. Concentration of riboflavin and its UV-A light mediated photoactivation in the cornea are the primary factors determining CXL efficacy., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess real-time intraoperative pachymetry changes occurring during corneal cross-linking (CXL) using microscope-integrated optical coherence tomography (Mi-OCT) and compare accuracy of various modalities of pachymetry assessment., Methods: This was a cross-sectional observational comparative study including 45 consecutive patients with progressive keratoconus planned for CXL. Mi-OCT (RESCAN 700) was used to measure central corneal thickness (CCT) during four stages of CXL: before epithelial debridement, after debridement, after riboflavin instillation, and after ultraviolet irradiation. Scheimpflug imaging, anterior segment OCT (AS-OCT), and ultrasound pachymetry were used to assess CCT preoperatively. All data were entered into Excel software (Microsoft Corporation) and analyzed., Results: The CCT significantly decreased after each step of CXL as measured on Mi-OCT ( P < .0001). Mi-OCT overestimated the CCT significantly by 1.12 times on average (range: 1.02 to 1.43) compared to ultrasound pachymetry ( P = .0004). CCT measured using Scheimpflug imaging and anterior segment OCT was statistically comparable to ultrasound pachymetry., Conclusions: Mi-OCT provides a real-time assessment of CCT during CXL. However, because it overestimates the pachymetry, ultrasound pachymetry remains the gold standard for decision-making during CXL. [ J Refract Surg . 2024;40(12):e934-e940.] ., Competing Interests: Disclosure: The authors have disclosed no potential conflicts of interest, financial or otherwise.

Objective: This study assessed the effect of combining corneal collagen cross-linking (CXL) with refractive laser ablation techniques for the treatment of keratoconus, a progressive corneal disorder., Methods: We performed a systematic review and meta-analysis to assess the effect of combined CXL and refractive techniques. We included all published clinical trials or observational studies published by September 1, 2023. We calculated and compared the standardized mean difference (SMD) between CXL alone and CXL plus laser ablation for uncorrected distance visual acuity, best-corrected distance visual acuity, spherical equivalent manifest refraction, sphere and cylinder, flat keratometry (K 1 ), steep keratometry (K 2 ), and central corneal thickness., Results: We identified 13 studies that fulfilled our inclusion and exclusion criteria. The average follow-up was 21.3 ± 11.8 months. The CXL plus laser ablation group showed improvement in uncorrected distance visual acuity logMAR (SMD, -0.35; 95% CI, -0.67 to -0.04; p = 0.029), best-corrected distance visual acuity logMAR (SMD, -0.17; 95% CI, -0.30 to -0.03; p = 0.014), spherical equivalent manifest refraction (SMD, -0.28; 95% CI, 0.06-0.50; p = 0.013), and change in maximal corneal curvature (K max ; SMD, -0.41; 95% CI, -0.69 to -0.13; p = 0.004) compared with CXL alone. However, central corneal thickness decreased further among patients who underwent CXL plus laser ablation (SMD, -0.37; 95% CI, -0.66 to -0.07; p = 0.016). No effect was observed in terms of sphere (p = 0.878), cylinder (p = 0.859), K 1 (p = 0.907), or K 2 (p = 0.169). Ectasia was not observed as an adverse effect resulting from the additional corneal ablation performed during the CXL treatments., Conclusions: This study showed that combining refractive laser ablation techniques with standard or accelerated CXL treatment improved visual and refractive outcomes and anterior corneal curvature values., Competing Interests: Footnotes and Disclosure Asaf Achiron and Tal Yahalomi contributed equally to this paper. The authors have no proprietary or commercial interest in any materials discussed in this article. Supported by: This study was supported by a Marguerite Stolz research grant., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Keratoconus is a burden to health systems and patients worldwide. Corneal collagen crosslinking (CXL) treatment has been shown abroad to be cost-effective for treating progressive keratoconus. However, no cost-effectiveness studies have been performed in Brazil. The aim of this study was to assess the cost-effectiveness of corneal collagen crosslinking (CXL) compared with the conventional treatment for progressive keratoconus from the Brazilian Unified Health System (SUS) payer's perspective. A lifetime microsimulation model was utilized to compare the lifetime costs and quality-adjusted life years for patients undergoing corneal collagen CXL or conventional treatment. Two groups of 5000 18-year-old patients were simulated, with one group receiving corneal CXL at the outset and the control group remaining untreated. The TreeAge Pro Healthcare 2024 software was used for modeling and analysis. Corneal collagen CXL demonstrated superior cost-effectiveness compared to the conventional treatment, with an incremental cost-effectiveness ratio of 58.26 USD/quality-adjusted life years (QALY) gained (95% CI: 58.17-58.36) and a positive incremental net monetary benefit of USD 11,613.82 (95% CI: 11,605.66-11,621.99). CXL significantly reduced the number of required corneal transplants, with a mean of 968.8 (95% CI: 959-978.58) fewer transplants per 10,000 eyes treated. The variable with the most significant impact on the incremental net monetary benefit was the duration of the CXL effect. This study concluded that corneal CXL is a highly cost-effective intervention for progressive keratoconus within the Brazilian SUS. These findings advocate for broader accessibility to this vision-saving treatment within the SUS.

Purpose: Keratoconus presents certain peculiarities in pediatric patients when compared with adults. The greatest challenge in children is that the disease is more severe and faster in progression. In this retrospective study, we aimed to compare the accelerated and Dresden protocols for corneal crosslinking in patients aged <18 years who were followed-up for at least 12 months. Methods: A total of 36 eyes from 27 patients were included in the study. The best corrected and uncorrected visual acuity, maximal keratometry, corneal thickness, foveal thickness, and endothelial microscopy findings were evaluated at baseline and during the postoperative period at one, three, and six months. Thereafter, the patients were evaluated at one, three, six and twelve months postoperative. Corneal crosslinking was performed in all patients via the Dresden protocol (n=21 eyes) or the accelerated protocol (n=15 eyes). Data between the two groups were compared and XY statistical analysis was used., Results: Both protocols were effective in halting keratoconus progression. No patient had progression at the 12-month follow-up. A significant reduction in Kmax and improvement in the corrected distance visual acuity were observed only in the Dresden protocol group. Although the Dresden protocol was superior to the accelerated protocol in reducing Kmax (p=0.002), there was no significant difference in corrected distance visual acuity between the two groups., Conclusion: The accelerated protocol is as efficient as the Dresden protocol in stabilizing keratoconus progression. Although the Dresden protocol was superior to the accelerated protocol in reducing the Kmax, it did not produce better clinical results. Thus, the accelerated protocol is an efficient option. Furthermore, considering the advantages of reduced surgical time, the accelerated protocol is effective in halting keratoconus progression in the pediatric age group.

Purpose: To assess the short and mid-term outcomes of epithelium-off (epi-off) corneal collagen cross-linking using Riboflavin with Vitamin E TPGS (Epi-off Ribocross® CXL) for progressive keratoconus (KC)., Design: Retrospective, single-center non-comparative interventional study., Methods: Patients with progressive keratoconus who underwent CXL using (Epi-off Ribocross® CXL) from May 2021 to May 2022 who completed at least 12 months of follow-up in Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Corrected distance visual acuity with spectable (CDVA), tomographic parameters (Belin ABCD) and topographic parameters were evaluated at baseline and at last follow up., Results: Twenty eyes of twenty patients fulfilled inclusion criteria. CDVA remained stable at last follow up (0.88 ± 0.19 from 0.83 ± 0.21, p = 0.45) with a significant reduction in cylinder (1.97 ± 1.69 from 2.78 ± 2.19, p = 0.03). Kmax significantly improved from 53.18D ± 6.32 to 50.96 ± 5.3D (p = 0.005). At the last follow up, no case of progression was noted., Conclusions: Epi-off Ribocross® CXL proved to be a safe treatment for progressive KC, with a stabilization of all cases at the one year follow up. Further studies are needed to confirm long-term stability., Competing Interests: Declarations Conflicts of interest The authors declare no competing interests. Ethical approval This study was performed in line with the principles of the Declaration of Helsinki. Informed consent Informed consent, including consent for publication of the images, was obtained from the patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To evaluate the biomechanical and tomographic outcomes of keratoconus patients up to four years after corneal crosslinking (CXL)., Methods: In this longitudinal retrospective-prospective single-center case series, the preoperative tomographic and biomechanical results from 200 keratoconus eyes of 161 patients undergoing CXL were compared to follow-up examinations at three-months, six-months, one-year, two-years, three-years, and four-years after CXL. Primary outcomes included the Corvis Biomechanical Factor (CBiF) and five biomechanical response parameters obtained from the Corvis ST. Tomographically, the Belin-Ambrósio deviation index (BAD-D) and the maximal keratometry (K max ) measured by the Pentacam were analyzed. Additionally, Corvis E-staging, the thinnest corneal thickness (TCT), and the best-corrected visual acuity (BCVA) were obtained. Primary outcomes were compared using a paired t-test., Results: The CBiF decreased significantly at the six-month (p < 0.001) and one-year (p < 0.001) follow-ups when compared to preoperative values. E-staging behaved accordingly to the CBiF. Within the two- to four-year follow-ups, the biomechanical outcomes showed no significant differences when compared to preoperative. Tomographically, the BAD-D increased significantly during the first year after CXL with a maximum at six-months (p < 0.001), while K max decreased significantly (p < 0.001) and continuously up to four years after CXL. The TCT was lower at all postoperative follow-up visits compared to preoperative, and the BCVA improved., Conclusion: In the first year after CXL, there was a temporary progression in both the biomechanical CBiF and E-staging, as well as in the tomographic analysis. CXL contributes to the stabilization of both the tomographic and biomechanical properties of the cornea up to four years postoperatively., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Ethics Committee from Ruprecht-Karls University of Heidelberg (trial registration number: S-621/2021) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individual participants included in the study. Conflict of interest: R. Khoramnia reports grants, personal fees, and nonfinancial support from Johnson & Johnson Vision, Alcon Laboratories, Hoya Corp., Kowa Co., Ltd., Oculentis GmbH/Teleon, Physiol S.A., Sifi Medtech Srl, and Rayner Intraocular Lenses Ltd.; grants and personal fees from Oculus Optikgeräte GmbH, Carl Zeiss Meditec AG, and Ophtec BV; and grants from Acufocus Inc. outside the submitted work. G.U. Auffarth reports lecture fees and research grants from Johnson & Johnson Vision, Alcon Laboratories, Carl Zeiss Meditec AG, Hoya Corp., Kowa Co., Ltd., Oculentis GmbH/Teleon, Physiol S.A., Rayner Intraocular Lenses Ltd., Oculus Optikgeräte GmbH, Ophthec BV, Santen, Sifi Medtech Srl, Acufocus Inc., Novartis, Ursapharm and Biotech; nonfinancial support from Rheacell, Contamac, Cristalens, Croma, EyeYon, Hanita, and VSY outside the submitted work. V. A. Augustin reports research grants from Eye Yon and Kowa Co. outside the submitted work. The remaining authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

Purpose: We evaluated the timing at and extent to which midterm to long-term keratometric changes can occur in year 1 to 7 after corneal collagen cross-linking (CXL) in patients with keratoconus., Methods: We conducted a subgroup analysis of a retrospective cohort study of all consecutive patients who underwent CXL at our cornea center between 2007 and 2011. The inclusion criteria comprised CXL according to the Dresden protocol and a full set of keratometry parameters collected by Scheimpflug tomography preoperatively and at year 1, 3, 5, and 7 after CXL. In addition, best-corrected visual acuity was evaluated., Results: Sixty-three eyes of 47 patients were enrolled. Mean age was 25.46 years ±7.39 years (80.9% male patients). All relevant keratometric parameters showed significant improvement at year 1 after CXL (except for posterior astigmatism). According to mixed-effects model analysis, they all showed further significant change at different points in time between year 1, 3, 5, and 7 (except for K1). In addition, best-corrected visual acuity improved statistically significant between year 1, 3, 5, and 7. Suspected disease progression was noted in 22.2% of patients, mostly between year 1 and 3 after CXL., Conclusions: After initial improvement 1 year after CXL, keratometric and functional parameters were stable until year 5 after CXL in most cases; further improvement can take place even after up to 7 years post-CXL. By contrast, in case of disease progression, changes seem to occur already between year 1 and 3 after CXL., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate progression of keratoconus in patients where CXL treatment was interrupted due to insufficient swelling of the cornea., Methods: A retrospective review was conducted of all patients with keratoconus diagnosis who underwent CXL at the Department of Ophthalmology, Örebro University Hospital (USÖ) during the years 2010-2017. In total 377 eyes of 280 patients were screened for inclusion. In 17 eyes (15 patients), the treatment was interrupted due to insufficient swelling of the cornea. Patient journals were reviewed and keratometry examinations were analysed for long-term progression., Results: Eleven eyes (nine patients) were included in the study. Five eyes showed no signs of progression after the interrupted CXL treatment. In one eye progression continued, however, first after a period of a number of years, indicating a delayed course of clinical progression., Conclusion: This study indicates that debridement of the corneal epithelium and riboflavin administration without intense UVA radiation may slow or arrest the progression of keratoconus, likely due to photosensitisation from ambient light., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the (place name of institution and/or national research committee) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the regional ethical board, Uppsala, Sweden (ref. 218/372). Informed consent was obtained from all individual participants included in the study. Conflict of interest: Both authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (© 2024. The Author(s).)

Purpose: Research on crosslinking has focused mainly on trying to slow the progression of keratoconus. The objective of this bibliometric analysis is to determine the relationships between the different publications and authors. As well as to identify the different areas of research on crosslinking. Methods: Web of Science (WOS) was the database for the search of publications for the period 1972 to December 2023, using the terms: crosslinking, cross-linking, ocular, vision, visual, cornea, ectasia AND Keratoconus. The analysis of the publication was performed using the CitNetExplorer, VOSviewer and CiteSpace software. Results: 7161 publications and 59415 citation networks were found. The year with the most publications is 2021, a total of 571 (7.97%) publications and 135 citation networks. The most cited publication was "Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus" published by Wollensak et al. in 2003, with a citation index of 1780. Using the Clustering function, five groups were found that cover the main research areas in this field: keratoconus, corneal transplantation, cataracts, corneal inflammation and axial growth. Conclusion: The treatment of keratoconus continues to be the topic of interest in this area of research. However, in recent years there has been an increase in research on how crosslinking helps to slow down axial growth., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To evaluate the safety and efficacy of different time-point combinations of intrastromal corneal ring segment (ICRS) implantation using femtosecond technology) and corneal collagen crosslinking (CXL) for the treatment of moderate-to-severe keratoconus (KCC)., Methods: This study included 69 eyes of 69 patients with keratoconus who underwent ICRS and CXL treatment at an Eye Hospital between March 2020 and March 2023. The patients were divided into two groups: Group 1 (n = 33 eyes of 33 patients), which received ICRS and CXL treatment in one session, and Group 2 (n = 36 eyes of 36 patients), which included treatment with ICRS for at least 6 months following CXL application. Preoperative and postoperative evaluations included visual acuity, autorefractometer refraction, corneal tomographic measurements using the Sirius (CSO) Scheimpflug camera and the TONOREF™ III device, and documentation of observed complications. Uncorrected visual acuity (UCVA) and best-corrected spectacle visual acuity (BCVA) were measured in each eye individually, and visual acuity was assessed using the logarithm of the minimum angle of resolution (logMAR)., Results: In Group 1, mean UCVA improved from 0.81 ± 0.34 to 0.45 ± 0.25 (p < 0.01), and mean BCVA improved from 0.76 ± 0.35 to 0.38 ± 0.20 (p < 0.01). In Group 2, mean UCVA improved from 0.71 ± 0.32 to 0.43 ± 0.30 (p < 0.01), and mean BCVA improved from 0.65 ± 0.25 to 0.31 ± 0.23 (p < 0.01). Both groups showed significant reductions in manifest spherical and cylindrical refraction (p < 0.01). Group 1 exhibited greater reductions in maximum keratometry (Kmax), flat keratometry (K1), steep keratometry (K2) (p < 0.05), and astigmatic aberration compared with group 2 (p < 0.01). The use of simultaneous or separate CXL and ICRS does not significantly increase the incidence of complications., Conclusions: Both combined and separate CXL and ICRS treatments resulted in significant improvement in UCVA and BCVA and reduced manifest refraction. Although improvements were observed in groups 1 and 2 in terms of K1, K2, and Kmax at 6 months, the improvements were more pronounced in Group 1. These results highlight the potential benefits of simultaneous ICRS + CXL treatment and underscore the importance of optimising the timing of CXL treatment to achieve the best visual outcomes., (© 2024. The Author(s).)

Trabeculectomy is a primary surgical procedure used to reduce intraocular pressure (IOP) in patients with glaucoma. Despite its effectiveness, it can lead to significant complications, including hypotony, choroidal effusion, blebitis, and bleb leaks. Bleb leaks require prompt medical or surgical intervention to prevent severe complications such as blebitis and bleb-associated endophthalmitis. In recent years, the indications for collagen cross-linking (CCL) have expanded beyond corneal ectatic diseases to include various ocular conditions such as keratitis and leaking blebs. Here, we present the case of a 70-year-old male patient with a leaking avascular cystic bleb. Following treatment with a combination of conjunctival CCL, topical gentamicin, a dorzolamide/timolol combination, and a therapeutic contact lens, the patient experienced cessation of bleb leakage and an increase in IOP., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2024 by the Turkish Ophthalmological Association / Turkish Journal of Ophthalmology published by Galenos Publishing House.)

Purpose: Accelerated Collagen Crosslinking (A-CXL) is widely used worldwide as an effective treatment for keratoconus due to its efficiency and rapidity. This paper aims to identify relevant changes in visual acuity parameters and topographic measurements before and six months after treatment., Methods: A total of 30 eyes from 20 patients who underwent A-CXL between May 2021 and June 2023 and had at least six months of follow-up were analyzed retrospectively. Comparisons between uncorrected visual acuity, best corrected visual acuity, spherical and cylinder diopters, and topographic measurements like Kmax, SIf, SIb, KVf, KVb, BCVf, BCVb, TCT, and CCT were made before and six months after surgery., Results: After the accelerated Collagen crosslinking (A-CXL), BCVA improved, cylinder diopters and Kmax values were reduced, and central corneal thickness (CCT) and thinnest corneal thickness (TCT) were elevated., Discussion: The study has shown results comparable with other studies regarding the heterogeneity of the group study, good outcomes in measuring the corneal central thickness and thinnest corneal thickness, and good evolution of the refraction and visual acuity. Regarding the specific topography markers, like SIf/SIb, KVf/KVb, BCVf/BCVb, and K max , minor differences were observed at 6 months follow-up and were not considered statistically relevant. Other studies show a better correlation at 1-year check-ups and similar results at 6-month follow-ups., Conclusion: This method's main benefits are its brief duration and minimum intrusion, improvement of visual acuity, and the possibility of reintervention for better outcomes., Competing Interests: The authors state no conflict of interest., (© 2024 The Authors.)

Purpose: To review the evidence on the safety and effectiveness of epithelium-off corneal collagen cross-linking (CXL) for the treatment of progressive corneal ectasia., Methods: A literature search of the PubMed database was most recently conducted in March 2024 with no date restrictions and limited to studies published in English. The search identified 359 citations that were reviewed in abstract form, and 43 of these were reviewed in full text. High-quality randomized clinical trials comparing epithelium-off CXL with conservative treatment in patients who have keratoconus (KCN) and post-refractive surgery ectasia were included. The panel deemed 6 articles to be of sufficient relevance for inclusion, and these were assessed for quality by the panel methodologist; 5 were rated level I, and 1 was rated level II. There were no level III studies., Results: This analysis includes 6 prospective, randomized controlled trials that evaluated the use of epithelium-off CXL to treat progressive KCN (5 studies) and post-laser refractive surgery ectasia (1 study), with a mean postoperative follow-up of 2.4 years (range, 1-5 years). All studies showed a decreased progression rate in treated patients compared with controls. Improvement in the maximum keratometry (Kmax) value, corrected distance visual acuity (CDVA), and uncorrected distance visual acuity (UDVA) was observed in the treatment groups compared with control groups. A decrease in corneal thickness was observed in both groups but was greater in the CXL group. Complications were rare., Conclusions: Epithelium-off CXL is effective in reducing the progression of KCN and post-laser refractive surgery ectasia in most treated patients with an acceptable safety profile., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate corneal stiffening after epithelium-off accelerated corneal cross-linking (CXL; 9 mW/cm²) in progressive keratoconus (KC) with different methods of epithelial debridement., Methods: This was a retrospective, interventional, and non-randomized study. In group 1, the epithelium was removed using a hockey knife (N = 45). In group 2 (N = 39) and group 3 (N = 22), the epithelial thickness was measured by optical coherence tomography (OCT) and the epithelium was ablated by excimer laser, but, in group 3, stromal ablation was performed additionally to correct high order aberrations (HOAs). Corneal biomechanics (integrated invers radius [IIR], stress-strain index [SSI]) and corneal tomography (thinnest corneal thickness [TCT]) were assessed with Corvis ST and Pentacam prior to and 1 month after CXL., Results: Corneal tomography did not differ among the groups preoperatively (P > 0.05). TCT decreased significantly in all groups after surgery (all P < 0.05). Nonetheless, corneal biomechanical stiffening was found in all three groups indicated by a decreased IIR and an increased SSI (all P < 0.05). For group 3, the HOA improved significantly (P < 0.001). Among the groups, there were no significant differences in changes of biomechanical parameters, but TCT was significantly reduced after laser ablation., Conclusions: Corneal stiffening after CXL is independent from epithelial removal. In particular, despite the removal of stromal tissue to correct HOA, a stiffening effect was achieved in keratoconic corneas, even it was less pronounced compared to mechanical epithelial removal. The reduction in HOA indicates a possible improvement in visual acuity., Translation Relevance: Cross-linking stiffens the keratoconus independent of epithelial debridement technique and may compensate minor stromal laser ablation.

Purpose: This study aimed to identify preoperative factors that predict visual acuity and Kmax 3 years after corneal cross-linking (CXL) in patients with keratoconus (KC), and to develop a prediction model., Methods: We enrolled 68 patients with KC and followed up on 100 eyes that received CXL for at least 3 years. Preoperative data, including age, UDVA, CDVA, cylinder, SE, and the parameters of tomography including Kmax were collected as predictors. The primary outcomes were changes in CDVA (Delta CDVA) and Kmax (Delta Kmax) postoperatively. Univariate and multivariate linear regression were used to identify the correlation between the primary outcomes and predictors and establish prediction models., Results: Both CDVA and Kmax remained stable from baseline to 3 years after CXL: from 0.25 ± 0.18 to 0.22 ± 0.20 (P = 0.308) and from 58.70 ± 9.52 D to 57.02 ± 8.83 D (P = 0.187), respectively. Multivariate analysis showed that worse preoperative CDVA (ß coefficient - 0.668, P < 0.001) and lower preoperative Kmean (ß coefficient 0.018,P < 0.001) were associated with greater improvement in CDVA after CXL. A smaller preoperative eccentricity (ß coefficient 8.896, P = 0.01) and a higher preoperative Kmean (ß coefficient - 1.264, P < 0.001) predicted a more flattening of postoperative Kmax. The prediction model for CDVA (R 2  = 0.43) and Kmax (R 2  = 0.37) could accurately estimate treatment outcomes., Conclusions: CXL is highly effective in halting or preventing further progression of KC. The preoperative factors CDVA and Kmean were able to predict visual acuity changes 3 years after CXL. And preoperative eccentricity and Kmean could predict Kmax changes 3 years after CXL., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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.] .

Objectives: To evaluate the 10-year visual, refractive, and tomographic outcomes of epithelium-off accelerated corneal collagen cross-linking (ACCL) in paediatric patients with progressive keratoconus (KC) and to compare the stages in terms of re-progression., Methods: Patients under 18 years of age with progressive KC who underwent ACCL between 2010 and 2012 and completed at least 10 years of follow-up were included in this retrospective study. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refractive errors, and corneal tomography parameters were evaluated preoperatively and at 1, 5, and 10 years postoperatively. The effect of stage and age on re-progression was analysed., Results: The study included 175 eyes of 97 patients (mean age: 14.46 ± 2.17 years). Improvement in UDVA and CDVA was observed in all postoperative periods compared to the preoperative period (each p-value < 0.05). The increase in spherical equivalent (SE), flattening of keratometry values, and decrease in thinnest corneal thickness (TCT) were statistically significant in the tenth year compared to preoperatively (each p-value < 0.05). Re-progression was observed in 16 eyes (9.14%). Haze was observed in 13 eyes (7.43%), 4 of which were permanent. Deep anterior lamellar keratoplasty was performed in 3 eyes (1.7%) and a second ACCL in 3 eyes (1.7%)., Conclusions: ACCL is an effective and safe long-term strategy to prevent progression of KC in paediatric patients. In the light of this study with a 10-year follow-up re-progression rate of 9.14%, long-term follow-up of patients after ACCL for possible re-progression and the need for re-CCL or keratoplasty may be recommended., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Changes in the biomechanical and biochemical properties of the human cornea play an important role in the pathogenesis of ectatic diseases. A number of conditions in primarily acquired (keratoconus or pellucid marginal degeneration) or secondarily induced (iatrogenic keratectasia after refractive laser surgeries) ectatic disorders lead to decreased biomechanical stability. Corneal collagen cross-linking (CXL) represents a technique to slow or even halt the progression of ectatic pathologies. In this procedure, riboflavin is applied in combination with ultraviolet A radiation. This interaction induces the production of reactive oxygen species, which leads to the formation of additional covalent bonds between collagen molecules and subsequent biomechanical corneal strengthening. This procedure is so far the only method that partially interferes etiopathogenetically in the treatment of ectatic diseases that slows or stops the process of corneal destabilization, otherwise leading to the need for corneal transplantation. Besides, CXL process increases markedly resistance of collagenous matrix against digesting enzymes supporting its use in the treatment of corneal ulcers. Since the discovery of this therapeutic procedure and the first laboratory experiments, which confirmed the validity of this method, and the first clinical studies that proved the effectiveness and safety of the technique, it has been spread and adopted worldwide, even with further modifications. Making use of the Bunsen-Roscoe photochemical law it was possible to shorten the duration of this procedure in accelerated CXL and thus improve the clinical workflow and patient compliance while maintaining the efficacy and safety of the procedure. The indication spectrum of CXL can be further expanded by combining it with other vision-enhancing procedures such as individualized topographically-guided excimer ablation. Complementing both techniques will allow a patient with a biomechanically stable cornea to regularize it and improve visual acuity without the need for tissue transplantation, leading to a long-term improvement in quality of life., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The purpose of this review was to summarize the different surgical approaches combining photorefractive keratectomy (PRK) and corneal crosslinking (CXL), present each protocol template in a simple format, and provide an overview of the primary outcomes and adverse events., Methods: A literature review was conducted as outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Eight different databases were searched. Papers were included if PRK was immediately followed by CXL., Results: Thirty-seven papers met the inclusion criteria of a total yield of 823. The latest research into simultaneous PRK and CXL has been shown to not only stabilize the cornea and prevent keratoconus progression but also improve the visual acuity of the patient. Improvements in uncorrected distance visual acuity and (spectacle) corrected distance visual acuity were found to be significant when considering all protocols. There were also significant reductions in K1, K2, mean K, Kmax, sphere, cylinder, and spherical equivalent. Random-effects analysis confirmed these trends. Corrected distance visual acuity was found to improve by an average of 0.18 ± 1.49 logMAR (Cohen's D [CD] 0.12; P <0.02). There was also a significant reduction of 2.57 ± 0.45 D (CD 5.74; P <0.001) in Kmax. Cylinder and spherical equivalent were also reduced by 1.36 ± 0.26 D (CD 5.25; P <0.001) and 2.61 ± 0.38 D (CD 6.73; P <0.001), respectively., Conclusions: Combining the 2 procedures appears to be of net benefit, showing stabilization and improvement of ectatic disease, while also providing modest gains in visual acuity. Since customized PRK and CXL approaches appear superior, a combination of these would likely be best for patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aimed to analyze variations in intraoperative corneal thickness during corneal cross-linking in patients with keratoconus and to investigate its possible correlation with presurgical maximal keratometry (Kmax) and pachymetry., Methods: This was a prospective case series. We used a method similar to the Dresden protocol, with the application of hydroxypropyl methylcellulose 0.1% hypo-osmolar riboflavin in corneas between 330 and 400 µm after epithelium removal. Corneal thickness was measured using portable calipers before and immediately after epithelium removal, and 30 and 60 min after the procedure., Results: The 30 patients in this study were followed up for one year. A statistically significant difference was observed in pachymetry values during the intraoperative period (p<0.0001) and an increase of 3.05 µm (95%C1: 0.56-5.54) for each diopter was seen after epithelium removal (p0.019). We found an average Kmax difference of -2.12 D between men and women (p0.013). One year after treatment, there was a statistically significant reduction in pachymetry (p<0.0001) and Kmax (p0.0170) values., Conclusions: A significant increase in pachymetry measurements was seen during the procedure, and most patients showed a regression in Kmax and pachymetry values one year after surgery.

Purpose: Investigate trends in keratoconus (KCN) treatment patterns and diagnosis age from 2015 to 2020 and evaluate sociodemographic associations with the treatment approach., Design: Retrospective cohort study., Participants: Patients with a new KCN diagnosis from 2015 to 2020 were identified in the Academy IRIS® Registry (Intelligent Research in Sight)., Methods: Associations between sociodemographic factors and treatment were evaluated using multivariable logistic regression., Main Outcome Measures: Outcomes included percentages and rates of each treatment (collagen crosslinking [CXL], keratoplasty, or no procedure) from 2015 to 2020, age at diagnosis during this period, and sociodemographic factors associated with treatment type., Results: A total of 66 199 patients with a new diagnosis of KCN were identified. The percentage of patients undergoing CXL increased from 0.05% in 2015 to 29.5% in 2020 (P = 0.008). The average age (standard deviation) of KCN patients decreased from 44.1 (±16.9) years in 2015 to 39.2 (±16.9) years in 2020 (P < 0.001). In multivariable analyses comparing CXL versus no procedure and keratoplasty versus no procedure, patients undergoing CXL tended to be younger with the odds of having CXL decreasing with increasing age, for example, comparing CXL and no procedure patients, using ages 0-20 years as reference, the odds ratio (OR) (95% confidence interval [CI]) decreased from 0.62 (0.57-0.67; P < 0.0001) for patients aged 21-40 years to 0.03 (0.02-0.04; P < 0.0001) for patients aged > 60 years. Men were more likely than women to have CXL (OR, 1.31; 95% CI, 1.23-1.40; P < 0.0001) and keratoplasty (OR, 1.30; 95% CI, 1.19-1.42; P < 0.0001). Black patients were less likely than White patients to have CXL (OR, 0.70; 95% CI, 0.63-0.77; P < 0.0001) and more likely to have keratoplasty (OR, 2.24; 95% CI, 2.01-2.50; P < 0.0001). Likewise, Hispanic patients had higher odds of CXL (OR, 1.12; 95% CI, 1.00-1.24; P < 0.05) and keratoplasty (OR, 1.29; 95% CI, 1.12-1.50; P < 0.001) compared with non-Hispanic patients. Collagen crosslinking and keratoplasty also varied by region and insurance status., Conclusions: A significant increase in use of CXL was noted from 2015 to 2020. Sociodemographic differences in treatment among KCN patients may reflect differences in access, use, or care patterns, and future studies should aim to identify strategies to improve access for all patients., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyse the temperature of the corneal surface in keratoconus during corneal customized crosslinking (CXL) with a preserved epithelium (epi-on) under oxygen flow, and epi-off CXL in room air, and to assess the effect of pre-heating the oxygen., Methods: This masked, intra-individual comparing randomized study included 14 participants with bilateral progressive keratoconus treated with bilateral CXL: one eye with epi-on CXL under a flow of 2.5 L/min oxygen; the fellow eye with epi-off CXL in room air. In a second setting involving 12 healthy participants, room-tempered oxygen was flushed over one eye and oxygen pre-heated to 37°C over the fellow eye. The corneal surface temperature was assessed with infrared photography., Results: A reduction in corneal surface temperature was seen from the pre-treatment application of topical riboflavin in the epi-off group (-1.1 ± 1.0°C, p < 0.001). The temperature increased during the first half of the CXL treatment in both groups (+0.7 ± 1.2°C, p = 0.041 for epi-on; +0.7 ± 0.9°C, p = 0.023 for epi-off CXL, respectively). In epi-on CXL an overall temperature increase was seen during the treatment (+0.8 ± 1.2°C, p = 0.016). In the second setting, pre-heating the oxygen rendered a surface temperature increase of +1.8 ± 0.2°C (p < 0.001)., Conclusion: In epi-off CXL, the application of topical room-tempered riboflavin decreases the corneal surface temperature, likely due to increased evaporation. A slight temperature increase is seen during CXL with both epi-on and epi-off CXL, albeit far below the corneal safety limit. The corneal temperature can, however, be increased by applying pre-heated oxygen, a possible approach to modify or augment the treatment effect in CXL., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To compare clinical outcomes of customized transepithelial (epi-on) corneal crosslinking (CXL) in high oxygen and customized CXL with epithelial removal (epi-off) in room air for keratoconus (KC)., Setting: Umeå University Hospital, Umeå, Sweden., Design: Prospective, randomized, single-masked, intraindividually comparing study., Methods: 32 participants with bilateral progressive KC were treated with bilateral customized topography-guided CXL, 30 mW/cm 2 ; 7.2 to 15 J/cm 2 and were randomized to epi-on in one eye (32 eyes) and epi-off in the fellow eye (32 eyes). Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), maximal keratometry (Kmax), subjective ocular discomfort, low-contrast visual acuities (LCVAs) at 10% and 2.5% contrast, ocular and anterior corneal wavefront aberrations, manifest refractive spherical equivalent, endothelial cell count (ECC), and adverse events were assessed through 24 months., Results: Both treatments showed improvements at 24 months in UDVA; -0.16 ± 0.24 ( P < .001) and -0.13 ± 0.20 logMAR ( P = .006), respectively, CDVA; -0.10 ± 0.11 ( P < .001) and -0.10 ± 0.12 ( P = .001), Kmax; -1.74 ± 1.31 ( P < .001) and -1.72 ± 1.36 D ( P < .001). LCVA 10% improved for both protocols ( P < .001), but LCVA 2.5% improved for epi-on CXL only ( P = .001). ECC was unaltered, and no adverse events occurred. The epi-on eyes had significantly less discomfort symptoms during the whole first week posttreatment ( P < .05)., Conclusions: High-oxygen customized epi-on CXL is a viable alternative to room air customized epi-off CXL, with faster improvements in CDVA and LCVA and less early ocular discomfort., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose of Review: To review corneal crosslinking for keratoconus and corneal ectasia, and recent developments in the field. This study will review the mechanism of crosslinking, clinical approaches, current results, and potential future innovations., Recent Findings: Corneal crosslinking for keratoconus was first approved by U.S. FDA in 2016. Recent studies have confirmed the general long-term efficacy of the procedure in decreasing progression of keratoconus and corneal ectasia. New types of crosslinking protocols, such as transepithelial treatments, are under investigation. In addition, adjunctive procedures have been developed to improve corneal contour and visual function in these patients., Summary: Crosslinking has been found to be well tolerated and effective with the goal of decreasing progression of ectatic corneal diseases, keratoconus and corneal ectasia after refractive surgery. Studies have shown its long-term efficacy. New techniques of crosslinking and adjunctive procedures may further improve treatments and results., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To establish new criteria for the progression of keratoconus, taking into account a Pentacam HR (high resolution) tomographeŕs repeatability limit., Methods: This is a retrospective observational study, including 224 eyes in 154 patients diagnosed with keratoconus and patients treated with crosslinking, with a follow-up of at least one year, in which the new progression score of the Cruces University Hospital for keratoconus progression was analyzed. This score takes into account: maximum keratometry, thinnest corneal thickness, maximum posterior elevation, vertical coma and RMS of high order aberrations, all based on the tomographer repeatability limit. The effectiveness or not of crosslinking was determined., Results: The Receiver Operating Characteristics (ROC) curves obtained in our validation met the criteria by being far from the reference diagonal. Moreover, young patients are more likely to have keratoconus that progresses, and the percentage of patients that showed progression was 14.3% of the eyes studied, with the most advanced keratoconus showing the least progression. Taking into account the new progression score of the Cruces Hospital, we would have indicated crosslinking in 2 eyes only and we observed that none progressed one year after treatment., Conclusions: The the new progression score of the Cruces University Hospital is a method based on the real repeatability limit for keratoconic eyes. Moreover, it is easy to interpret and can be implemented with Pentacam software. It provides a numerical value that evaluates both the anterior and posterior surfaces of the cornea and corneal aberrations in the evolution of keratoconus., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose of Review: This manuscript summarizes contemporary research from 2018 to 2023 evaluating long-term (≥2 years) outcomes of corneal crosslinking (CXL) for progressive keratoconus (KCN)., Recent Findings: The standard Dresden protocol (SDP) has been utilized clinically since the early 2000 s to treat ectatic disorders, primarily progressive KCN and postrefractive ectasia. Various modifications have since been introduced including accelerated and transepithelial protocols, which are aimed at improving outcomes or reducing complications. This review summarizes data demonstrating that the SDP halts disease progression and improves various visual and topographic indices (UDVA, CDVA, Kmax, K1, K2) up to 13 years postoperatively. Accelerated and transepithelial protocols have been found to be well tolerated alternatives to SDP with similar efficacy profiles. Studies focusing on pediatric populations identified overall higher progression rates after CXL. All protocols reviewed had excellent safety outcomes in adults and children., Summary: Recent studies revealed that SDP successfully stabilizes KCN long term, and a variety of newer protocols are also effective. Pediatric patients may exhibit higher progression rates after CXL. Further research is required to enhance the efficacy and ease of these protocols., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To study the aetiology, diverse clinical manifestations, therapeutic interventions, and prognoses in patients with corneal thinning after collagen cross-linking (CXL) treatment., Methods: a retrospective observational study of all patients presenting with corneal thinning after collagen cross-linking, in a tertiary eye care hospital in south India from 2011 to 2017. Preoperative details were noted. Patients who presented with corneal thinning were subjected to investigative measures to assess thinning, received appropriate management, and underwent follow-up evaluations., Results: Among the 12 patients, 8 were female and 4 were male, all of whom had undergone standard classical CXL. The duration between CXL and corneal melting/thinning onset varied from 5 to 12 years. Notably, among female patients, 2 were pregnant, 2 were lactating mothers, 1 was undergoing in vitro fertilization (IVF) treatment, and 1 had comorbid diabetes mellitus and hyperthyroidism. Clinical examination revealed corneal thinning accompanied by hypopyon in 1 patient, corneal perforation with shallow anterior chamber in 1 patient, and epithelial defect with crystalline deposit in another patient, the remaining patients exhibited corneal thinning. Corneal thinnest corneal thickness measurements ranged from 212 to 351 µm. Treatment approaches included penetrating keratoplasty (PKP) in 2 patients, deep anterior lamellar keratoplasty (DALK) in 1 patient, cyanoacrylate glue application in 1 patient, and awaiting DALK/PKP in three patients, 4 patients showing no signs of increased thinning., Conclusion: The incidence of corneal thinning after collagen cross-linking is less but fulminant, requiring timely and appropriate management to prevent visual complications., Competing Interests: The authors state no conflict of interest., (© 2024 The Authors.)

Purpose: This study aimed to report the long-term results of combined topography-guided photorefractive keratectomy (PRK) and accelerated corneal collagen cross-linking (CXL) for keratoconus using the Zeiss refractive coordinated system., Methods: A prospective interventional study was conducted in a tertiary eye care hospital in South India. Patients with mild-to-moderate progressive keratoconus and corneal pachymetry greater than 450 µm were included. They underwent customized topography-guided PRK followed by CXL. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and keratometry readings and complications were evaluated at 1, 3, 6, 12, and 24 months postoperatively., Results: Thirty patients (30 eyes) were included in the study. All study parameters showed a statistically significant improvement postoperatively over baseline values. At 24 months, the mean UDVA improved from 0.8 ± 0.180 logarithm of the minimum angle of resolution (logMAR) to 0.38 ± 0.118 logMAR ( P -value <0.001) and CDVA improved from 0.467 ± 0.142 logMAR to 0.227 ± 0.078 logMAR ( P -value <0.001). The mean flat, steep, and maximum keratometry values were significantly reduced by 2.133, 3, and 4.54 diopters, respectively, at the last follow-up examination ( P -value <0.001)., Conclusion: The combined topography-guided PRK and accelerated CXL procedure seem to be a promising treatment alternative for early keratoconus. This is the first such study on the Zeiss refractive coordinated system. However, further studies with a larger study population and longer follow-up periods are required to draw final conclusions about the benefits of this procedure in keratoconus., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Purpose: Photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) stabilizes the corneal stroma and eliminates microorganisms. Numerous PACK-CXL protocols, using different energy sources and chromophores, have been applied in preclinical studies, including live animal studies, with various experimental designs and endpoints. So far, a systematic mapping of the applied protocols and consistency across studies seems lacking but is essential to guide future research., Methods: The scoping review protocol was in line with the JBI Manual for Evidence Synthesis. Electronic databases were searched (Embase, MEDLINE, Scopus, Web of Science) to identify eligible records, followed by a two-step selection process (title and abstract screening, full text screening) for record inclusion. We extracted information on (1) different PACK-CXL protocol characteristics; (2) infectious pathogens tested; (3) study designs and experimental settings; and (4) endpoints used to determine antimicrobial and tissue stabilizing effects. The information was charted in frequency maps., Results: The searches yielded 3654 unique records, 233 of which met the inclusion criteria. With 103 heterogeneous endpoints, the researchers investigated a wide range of PACK-CXL protocols. The tested microorganisms reflected pathogens commonly associated with infectious keratitis. Bacterial solutions and infectious keratitis rabbit models were the most widely used models to study the antimicrobial effects of PACK-CXL., Conclusions: If preclinical PACK-CXL studies are to guide future translational research, further cross-disciplinary efforts are needed to establish, promote, and facilitate acceptance of common endpoints relevant to PACK-CXL., Translational Relevance: Systematic mapping of PACK-CXL protocols in preclinical studies guides future translational research.

Purpose: To report the first case of Rhizopus sp keratitis in a 15-year-old male patient who had undergone a conventional Epi-off CXL procedure for progressive keratoconus., Methods: A 15-year-old male studying at school presented with defective vision in both eyes recently. He was diagnosed with progressive keratoconus in the right eye more than left eye. After the conventional CXL procedure, the patient developed corneal ulcer on third postoperative day., Results: The microbiological diagnosis of both BCL and ulcer revealed Rhizopus sp. The patient responded to topical antifungals, and the ulcer entirely healed with a large central scar., Conclusion: Rhizopus keratitis is rare in a healthy individual. Ours is the first case report of Rhizopus keratitis in patient undergone CXL., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Corneal crosslinking (CXL) is the standard treatment of progressive keratoconus (KC). We evaluated the safety and 10-year outcomes of conventional "epithelial-off" CXL for progressive KC for the first time in a cohort in France., Methods: We conducted a retrospective review of patients undergoing conventional CXL (Dresden protocol) in our tertiary ophthalmology department from 2006 to 2011 with 10-year follow-up. The primary outcome was change in preoperative versus postoperative keratometry measured by maximum keratometry (Kmax), steep keratometry (K2), flat keratometry (K1), mean keratometry (Km), and topographic cylinder. Secondary outcomes were changes in visual and refractive outcomes. We report postoperative complications and adverse events., Results: Eighty-nine eyes from 76 patients (67% male patients, mean age 22.7 ± 7.6 years) were included. Mean Kmax (-2.31 ± 2.98 diopters (D); P < 0.00001), K2 (-2.07 ± 3.15 D; P < 0.00001), K1 (-1.00 ± 2.29 D; P = 0.00008), Km (-1.53 ± 2.47 D; P < 0.00001), and topographic cylinder (-1.15 ± 2.53 D; P = 0.00004) significantly decreased 10 years after CXL compared with preoperative baseline. Significant decreases were still observed between 5 and 10 years after for mean Kmax, mean K2, mean K1, and mean Km. Mean distance best spectacle-corrected visual acuity and mean manifest refraction spherical equivalent were significantly improved after 10 years versus before CXL. The 10-year rate of repeat CXL was n = 3/76 patients (4%) (all younger than 18 years at first CXL) and of loss of >3 lines in best spectacle-corrected visual acuity was n = 1/76 patients (1%)., Conclusions: Progressive KC was effectively stabilized with a prolonged flattening and maintenance of functional vision improvements after 10 years. Repeat CXL was rare and only required among younger patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To investigate the clinical efficacy and safety of the modified Cretan protocol in patients with post-laser in situ keratomileusis ectasia (PLE)., Materials and Methods: In this retrospective study, 26 eyes of 16 patients with PLE were treated with the modified Cretan protocol (combined transepithelial phototherapeutic keratectomy and accelerated corneal collagen cross-linking). Visual, refractive, tomographic, and aberrometric outcomes and point spread function (PSF) were recorded preoperatively and at 6, 12, and 24 months after treatment., Results: Both uncorrected and best corrected visual acuity were stable at 24 months postoperatively compared to baseline (from 0.89±0.36 to 0.79±0.33 logarithm of the minimum angle of resolution [LogMAR] and 0.31±0.25 to 0.24±0.19 LogMAR, respectively, p>0.05 for all values). The mean K1, K2, Kmean, thinnest corneal thickness, and spherical aberration at baseline were 45.76±5.75 diopters (D), 48.62±6.17 D, 47.13±5.89 D, 433.16±56.86 μm, and -0.21±0.63 μm respectively. These values were reduced to 42.86±6.34 D, 45.92±6.74 D, 44.21±6.4 D, 391.07±54.76 μm, and -0.51±0.58 μm at 24 months postoperatively (p<0.001, p=0.002, p<0.001, p=0.001, and p=0.02, respectively). The mean spherical equivalent, manifest cylinder, Kmax, central corneal thickness, other corneal aberrations (root mean square, trefoil, coma, quatrefoil, astigmatism), and PSF remained stable (p>0.05 for all variables), while anterior and posterior elevation were significantly improved at 24 months postoperatively (p<0.001 and p=0.02, respectively). No surgical complications occurred during the 24-month follow-up., Conclusion: The modified Cretan protocol is a safe and effective treatment option for PLE patients that provides visual stabilization and significant improvement in topographic parameters during the 24-month follow-up. Further studies are needed to support our results., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2024 by the Turkish Ophthalmological Association / Turkish Journal of Ophthalmology published by Galenos Publishing House.)

Purpose: Corneal collagen crosslinking (CXL) is the primary treatment for progressive keratoconus which has a significant impact on vision and quality of life. Our study aimed to compare the efficacy and safety of epithelium-on versus epithelium-off CXL to treat keratoconus., Methods: We searched PubMed, Medline, Embase, Web of Science, and Scopus databases. We included studies that compared standard epithelium-off with epithelium-on CXL. The primary outcome measures were changes in corrected distance visual acuity (CDVA) and maximum keratometry (Kmax), and the secondary outcomes were uncorrected distance visual acuity (UDVA), central corneal thickness (CCT), and adverse events. A meta-analysis was performed on the primary and secondary outcomes based on the weighted mean differences between baseline to 12-month follow-up., Results: The search retrieved 887 publications with 27 included in the systematic review. A total of 1622 eyes (1399 patients; age 25.51 ± 4.02 years) were included in comparisons of epithelium-off to epithelium-on CXL in keratoconus. Epithelium-off CXL treated 800 eyes and epithelium-on CXL for 822 eyes. At 12-month follow-up, CDVA and Kmax showed no significant difference between the epithelium-off and epithelium-on CXL. The secondary outcomes showed that UDVA was better in epithelium-off CXL (- 0.11D, 95% CI - 0.12, - 0.1; p < 0.001) and there was more thinning in CCT in epithelium-off CXL (- 3.23 μm, 95% CI - 4.64, - 1.81; p <0.001)., Conclusion: Epithelium-off and epithelium-on CXL were both effective to treat progressive keratoconus. Further research is needed to compare the long-term outcomes and safety of both CXL protocols for adaptation into clinical practice., (© 2023. The Author(s).)

Objective: To define how estimates of keratoconus progression following collagen cross-linking (CXL) vary according to the parameter selected to measure corneal shape., Materials and Methods: We estimated progression following CXL in 1677 eyes. We compared standard definitions of keratoconus progression based on published thresholds for Kmax, front K2, or back K2, or progression of any two of these three parameters, with the option of an increased threshold for Kmax values ≥ 55D. As corneal thickness reduces unpredictably after CXL, it was excluded from the principal analysis. We then repeated the analysis using novel adaptive estimates of progression for Kmax, front K2, or back K2, developed separately using 6463 paired readings from keratoconus eyes, with a variation of the Bland-Altman method to determine the 95% regression-based limits of agreement (LoA). We created Kaplan-Meier survival plots for both standard and adaptive thresholds. The primary outcome was progression five years after a baseline visit 9-15 months following CXL., Results: Progression rates were 8% with a standard (≥ 1.5D) threshold for K2 or 6% with the static multi-parameter definition. With a ≥ 1D threshold for Kmax, the progression was significantly higher at 29%. With adaptive Kmax or K2, the progression rates were similar (20%) but less than with the adaptive multi-parameter method (22%)., Conclusions: Estimates of keratoconus progression following CXL vary widely according to the reference criteria. Using adaptive thresholds (LoA) to define the repeatability of keratometry gives estimates for progression that are markedly higher than with the standard multi-parameter method., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Primary corneal collagen cross-linking (CXL) stabilises 96% of progressive keratoconus. There is limited evidence for the treatment of choice when this fails. We present 10 years of repeat CXL and compare with our published experience of primary CXL to (1) identify perioperative risk factors of primary CXL failure and (2) demonstrate the safety and efficacy of repeat CXL., Methods: Patients undergoing repeat accelerated epithelium-off CXL at St James's University Hospital, Leeds, UK January 2012-August 2022 were identified through electronic patient record, and compared with a previously published cohort of primary CXL patients at the same site., Results: Twenty-one eyes underwent repeat CXL. The mean interval between primary and repeat CXL treatments was 47.1 months (SD 22.5). Twenty (95%) eyes stabilised after repeat CXL at a mean follow-up of 29.9 months. These cases were compared with 151 cases of primary CXL from our previous study. Patients failing primary CXL were significantly younger (21.3 years (SD 7.0) vs 26.7 years (SD 6.5), p=0.0008). Repeat CXL and primary CXL induced a similar amount of flattening of Kmax (-1.2 D (SD 3.9) vs -0.7 D (SD 4.4), p=0.22). A small, but clinically insignificant, improvement in best-corrected visual acuity was found in the repeat CXL group (-0.04 (SD 0.17) vs -0.05 (SD 0.13), p=0.04). No complications of repeat CXL were noted., Conclusion: Younger age may be associated with failure of primary CXL. Repeat CXL is an effective and safe treatment for progressive keratoconus despite primary CXL., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Acanthamoeba keratitis (AK) is a rare but potentially sight-threatening complication of corneal collagen crosslinking (CXL) for keratoconus. In this report, we describe an early adolescent male who underwent routine CXL for progressive keratoconus in his left eye. Preprocedural left visual acuity (VA) was 6/9. At day 5 postprocedure, multifocal corneal infiltrates were identified. Corneal scrape, bandage contact lens cultures and herpetic and Acanthamoeba PCR were negative. In vivo, confocal microscopy (IVCM) identified Acanthamoeba cysts within the corneal stroma. Intensive amoebicidal therapy was initiated, but recovery was complicated by significant inflammation, resulting in widespread aggressive corneal vascularisation necessitating topical steroids and steroid-sparing agents. At 10 months, his left VA was 6/24. This report emphasises the importance of maintaining a high index of suspicion for AK in cases of post-CXL microbial keratitis and highlights the diagnostic value of IVCM, particularly in culture-negative and PCR-negative cases., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The primary factor underlying the virulence of Candida albicans is its capacity to form biofilms, which in turn leads to recurrent complications. Over-the-counter antifungal treatments have proven ineffective in eliminating fungal biofilms and the inflammatory cytokines produced during fungal infections. Chitosan nanoparticles offer broad and versatile therapeutic potential as both antifungal agents and carriers for antifungal drugs to combat biofilm-associated Candida infections. In our study, we endeavoured to develop chitosan nanoparticles utilising chitosan and the antifungal crosslinker phytic acid targeting C. albicans. Phytic acid, known for its potent antifungal and anti-inflammatory properties, efficiently crosslinks with chitosan. The nanoparticles were synthesised using the ionic gelation technique and subjected to analyses including Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential analysis. The synthesised nanoparticles exhibited dimensions with a diameter (Dh) of 103 ± 3.9 nm, polydispersity index (PDI) of 0.33, and zeta potential (ZP) of 37 ± 2.5 mV. These nanoparticles demonstrated an antifungal effect with a minimum inhibitory concentration (MIC) of 140 ± 2.2 µg/mL, maintaining cell viability at approximately 90% of the MIC value and reducing cytokine levels. Additionally, the nanoparticles reduced ergosterol content and exhibited a 62% ± 1.2 reduction in biofilm susceptibility, as supported by colony-forming unit (CFU) and XTT assays-furthermore, treatment with nanoparticles reduced exopolysaccharide production and decreased secretion of aspartyl protease by C. albicans. Our findings suggest that the synthesised nanoparticles effectively combat Candida albicans infections. In vivo studies conducted on a mouse model of vaginal candidiasis confirmed the efficacy of the nanoparticles in combating fungal infections in vivo., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)