Progressive Keratoconus Research Articles

Ineffectiveness of KeraVio Treatment with Violet Light-Emitting Glasses Without Riboflavin Drops for Progressive Keratoconus

Background: KeraVio, a portable corneal cross-linking (CXL) treatment modality involving the use of violet light (VL)-emitting glasses, was originally used in conjunction with topical transepithelial riboflavin (BJO 2021). However, after our preliminary findings of endogenous riboflavin in the human cornea and the observation that the relatively low intensity of VL irradiation increased corneal stiffness in porcine corneas (TVST 2021), we evaluated the clinical results of KeraVio without riboflavin drops. Methods: Patients with progressive keratoconus were enrolled and randomly divided into a VL irradiation alone group (Group 1) and a no irradiation group (Group 2; control group) (jRCTs032190267). The eyes were exposed to VL (375 nm, irradiance 310 μW/cm2)-emitting glasses for 4.5 h daily for 6 months. Results: The mean changes in the maximum keratometry value (Kmax) from baseline to 6 months were 0.94 ± 2.65 diopters (D) and 1.76 ± 2.75 D in Group 1 and Group 2, respectively (p = 0.705). Conclusions: No differences were found between patients who did and did not receive VL irradiation in terms of the clinical outcomes of keratoconus. VL irradiation alone likely did not halt keratoconic progression, and the administration of riboflavin was necessary.

Spatial transcriptomics and single-cell RNA-sequencing revealed dendritic cell-mediated inflammation in keratoconus.

Keratoconus (KC) is a corneal disorder characterized by central corneal protrusion and thinning. In this study, spatial transcriptomics was employed to investigate molecular and cellular variations in KC, revealing a distinct pattern of inflammatory responses across the cornea. Upregulation of inflammatory processes was observed in the central cornea, while downregulation was noted in the periphery, indicating complex regional inflammatory changes in the KC cornea. Integration with single-cell RNA sequencing (scRNA-seq) further identified enhanced interactions between dendritic cells (DCs) and stromal cells, particularly mediated via the IL-1β pathway, alongside increased matrix metalloproteinase (MMP) production by corneal stromal cells, underscoring the role of inflammation in KC pathogenesis. In vitro and in vivo experiments confirmed that activated DCs promoted the matrix degradation activity of stromal cells, thereby exacerbating KC pathology. Notably, inhibition of the IL-1β pathway effectively mitigated the progression of KC. These findings provide a comprehensive spatial, cellular, and molecular characterization of KC, demonstrating its inflammatory nature. The results also highlight the importance of inflammation in the peripheral cornea for early diagnosis and suggest that anti-inflammatory treatments could serve as potential adjuvant therapy for KC.

Repeatability of Pentacam HR in Keratoconus According to Two Different Scan Protocols: 25-3D Scan and 50-Cornea Fine.

Background: This study aims to evaluate the repeatability of the Pentacam HR, comparing two different measurement modes (50-cornea fine and 25-3D scan) in patients affected by keratoconus. Methods: Multicenter retrospective study, conducted at Eye Clinic of the ASST-Spedali Civili-University of Brescia, Italy, and St. Paul's Eye Unit, Royal Liverpool University Hospital, United Kingdom. A total of 72 eyes from 72 patients with keratoconus underwent six consecutive measurements, three using the 25-3D scan mode and three with the 50-Cornea fine mode. Measurements were made by one single observer, using the Scheimpflug corneal tomographer camera (Pentacam HR, Oculus, Wetzlar, Germany). Repeatability was assessed using the within-subject SD (Sw) statistic from a two-way analysis of variance. Results: Both measurement modes had excellent repeatability. The interclass coefficient correlation (ICC) was excellent (>0.9) in all the parameters evaluated, apart from anterior and posterior astigmatic axes and posterior astigmatism (ICC > 0.8) and index of height asymmetry (IHA) (ICC < 0.6). However, in 18 of 29 parameters, the ICC was higher in case of 25-3D scan. Repeatability limit for Kmax was 1.00D in 25-3D scan mode and 1.02D in case of 50-cornea fine. Conclusions: 25-3D scan may be preferable to 50-Cornea fine, in view of having slightly higher ICC in case of patients with keratoconus. Repeatability limits reported may be helpful in clinical practice for assessing the progression of keratoconus.

Long-Term Effectiveness of Scleral Lens Treatment in the Management of Keratoconus: A Systematic Review.

This systematic review evaluates the long-term effectiveness of scleral lenses in improving visual outcomes, patient satisfaction, and safety in patients with keratoconus. A systematic search of six databases (PubMed, Embase, Web of Science, Scopus, Cochrane Library, and MEDLINE) was performed followingPreferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The inclusion criteria included studies with more than or equal to three months of follow-up, included a minimum of 20keratoconus patients, published after year 2020 and outcomes reporting visual acuity, comfortor quality of life. Methodological quality was assessed using the Newcastle-Ottawa Scale and Murad et al.case series tool. Five studies (463 eyes) met the inclusion criteria. Scleral lenses consistently improved best-corrected visual acuity (BCVA) across studies, with visual gains from baseline logMAR 0.50-0.53 to post-treatment logMAR 0.08-0.09. Significant improvements in vision-related quality of life (National Eye Institute Visual Function Questionnaire (NEI-VFQ) scores) were observed in validated assessments. Complications were infrequently reported but included lens handling issues (10.4%-63%), fogging (58%), and physiological events (e.g., corneal epitheliopathy). Long-term follow-up indicated that 14.6% of the patients experienced worsening visual acuity due to keratoconus progression. Methodological quality was variable, with limitations including variable outcome reporting and limited follow-up duration. Scleral lenses provide substantial and sustained improvements in visual acuity and quality of life for keratoconus patients, particularly those with advanced disease. However, the evidence is limited by methodological shortcomings and a lack of long-term controlled studies. Future research should prioritise randomised trials with standardised reporting and longer follow-up to better assess complications and durability of outcomes.

Mechanical Strain of Corneal Epithelium Influences the Expression of Genes Implicated in Keratoconus.

Although mechanical injury to the cornea (e.g. chronic eye rubbing) is a known risk factor for keratoconus progression, how it contributes to loss of corneal integrity is not known. Here, we set out to determine how eye rubbing can influence keratoconus progression by exploring the expression of known disease markers in mechanically stressed corneal epithelial cells. To explore the effects of mechanical stress on the expression of genes implicated in keratoconus (e.g. WNT10A, COL12A1, and TGFB1), we measured their expression using an in vitro model that simulates eye rubbing by cyclic stretching of an immortalized human corneal epithelial cell line (hTCEpi) for 16hours. We further examined the influence of WNT10A expression in hTCEpi cells using loss-of-function approaches. Mechanical strain led to a marked reduction in WNT10A mRNA and protein expression, as well as decreased collagen XII mRNA and protein expression, in hTCEpi cells. Reduced expression of WNT10A protein in WNT10A knockdown cells resulted in reduced protein expression of collagens I and XII, and reduced mRNA expression of MMP9 and TGFB1. Conversely, primary keratocytes treated with recombinant WNT10A protein increased TGFB1 mRNA expression. We provide a molecular explanation for how mechanical strain results in reduced expression of WNT10A in the corneal epithelium, which, in turn, leads to depletion of collagen type I and XII, and TGFβ1 expression. These results provide a molecular link among mechanical strain, WNT10A expression, and the biomechanical failure of the keratoconus cornea.

Corneal crosslinking via the Dresden protocol versus the accelerated approach in pediatric patients - a retrospective comparative study.

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. 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. 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.

Vitamin D supplementation modifies clinical and biological markers of keratoconus progression

Aims/Purpose: evaluation of vitamin D (Vit D) supplementation on clinical progression and systemic biomarkers in adolescent patients affected by keratoconus (KC) and Vit D insufficiency.Methods: forty adolescent patients (age range: 12–19) meeting the criteria of KC diagnosis and Vit D insufficiency ( &lt; 30 ng/mL) were enrolled and followed for 12 months. Vit D supplementation was prescribed for the first 6 months and patients were then followed up for additional 6 months. Clinical parameters, including best spectacle‐corrected visual acuity, maximal keratometry, and corneal thickness were measured at month 0, 2, 4, 6, 9, 12 after enrollment to monitor the KC progression. Moreover, at month 0 and 6 after enrollment we evaluated serum biomarkers, including Vit D levels and metabolism, collagen degradation, and inflammation by ELISA and RT‐PCR.Results: after 6 months of Vit D supplementation, serum Vit D levels were significantly increased and remained clinically stable up to month 12. Two‐thirds of patients responded to treatment and showed KC stabilization 12 months after enrollment. Interestingly, Vit D receptor was upregulated only in stable patients (p &lt; 0.01) at month 6. Serum markers indicated that type I collagen degradation product, procollagen type I carboxyl‐terminal propeptide, and the ratio between matrix metalloproteinase 9 and tissue inhibitor of matrix metalloproteinase 1 were statistically decreased (p &lt; 0.05) only in stable patients. Vit D supplementation was associated with increased expression of CD 14 (p &lt; 0.0001) and decreased levels of lactoferrin (p &lt; 0.0001).Conclusions: these data demonstrated that Vit D treatment stabilized KC progression in the majority of patients. These stable patients showed reduced systemic inflammation and collagen catabolism, thus suggesting that KC could be considered a systemic disease.

Corneal cross-linking.

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 30min of 3 mW/cm2-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 400μm 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 400μm, 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.

Evaluation of corneal epithelial changes after corneal collagen cross-linking by using anterior segment optical coherence tomography

Background The thickness of the corneal epithelium can be precisely measured using anterior segment optical coherence tomography (AS-OCT). Aim This study aimed to conduct an AS-OCT evaluation of changes in the corneal epithelial thickness following collagen cross-linking (CXL). Patient and methods This prospective interventional study utilized 23 eyes from 13 cases who underwent treatment for progressive keratoconus (KC) with epi-off corneal CXL according to the Dresden’s Protocol. Results After 6 months postoperative the central minimum epithelial thickness (0.0–2.0 mm) showed a statistically significant increase, while the mid-peripheral (5.0–7.0 mm) showed a statistically significant decrease compared with the preoperative level. The central average epithelial thickness (0.0–2.0 mm) showed statistically nonsignificant increase, while the mid-peripheral and peripheral (5.0–7.0, 7.0–9.0 mm) showed a statistically significant decrease in comparison to the level before the operation. At 6 months postoperative, a decrease in Mean k was associated with statistically significant elevation in average central and paracentral epithelial thickness (0.0–2.0, 2.0–5.0 mm) as compared with the preoperative level (negative correlation). At 6 months postoperative, reduction in thinnest pachymetry was associated with statistically significant increase in central and paracentral average epithelial thickness (0.0–2.0, 2.0–5.0 mm) (negative correlation) as compared with the preoperative and 3 months postoperative. Conclusions With AS-OCT, it is simple to track changes in the epithelium over time. Epithelial remodeling occurs after CXL in the areas of protrusion and thinning. The thickness of the epithelium is greatest at the cone’s base and diminishes as one moves away from it.

Effects of customized corneal cross-linking on higher-order aberrations in progressive keratoconus and low-grade myopia.

To evaluate the effects of customized corneal collagen cross-linking (CXL) on higher-order aberrations (HOAs) in keratoconus (KC): vertical coma (VC), horizontal coma (HC), spherical aberration (SA), trefoil (TF) and astigmatism, compared with the same effects in healthy eyes undergoing CXL for low-grade myopia. This mixed-designed study included 38 eyes of 38 patients with KC, treated and followed prospectively, who received customized epi-on CXL in high oxygen, and a retrospective control group of 23 eyes from 23 patients who underwent central 4-mm CXL treatment for low-grade myopia. VC, HC, SA, TF and keratometry values were obtained from Pentacam HR® measurements at baseline and at 1, 6, 12 and 24 months post-treatment. Statistical analyses included paired T-tests for changes over time and Pearson correlation tests to assess relationships between aberrations, best spectacle-corrected and low-contrast visual acuities (BSCVA and LCVA, respectively) and CXL parameters. Reduced HOAs and improved visual acuities were observed in KC. A 20% reduction in VC was observed at 24 months (from -1.82 ± 1.15 μm to -1.46 ± 1.01 μm; 95% CI: [0.155, 0.629], p = 0.002), while a 17% reduction in HC was observed at 12 months (from -0.35 ± 0.56 μm to -0.29 ± 0.62 μm; 95% CI: [0.003, 0.096], p = 0.037). A positive correlation was found between baseline VC and the level of improvement in VC at 24 months (R2 = 0.200, p = 0.015). SA increased by 126% at 24 months (from -0.21 ± 0.62 μm to 0.054 ± 0.52 μm; 95% CI: [0.143, 0.347], p ≤ 0.001). TF and astigmatism did not alter from the treatment. In myopia, the natural positive SA increased by 57% post-treatment (from 0.14 ± 0.061 μm to 0.22 ± 0.076 μm at 24 months; 95% CI: [0.067, 0.098], p ≤ 0.001), while changes in VC and HC were minor and BSCVA remained stable. Customized CXL effectively reduces HOAs in KC. For VC the improvement is larger in cases with higher preoperative VC, indicating that the concept of customization has its intended effect. Accordingly, SA and visual acuities improve in KC whereas CXL for low-grade myopia tends to increase corneal SA unfavourably.

Evaluating the safety and effectiveness of the sub-400 corneal cross-linking protocol: initial clinical and morphological findings.

To assess the safety and the efficacy of the "Sub-400 corneal cross-linking (CXL) protocol" for progressive keratoconus (KC) in ultrathin corneas. 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 398μm after epithelial removal. After the epithelium was removed, the following ultraviolet A irradiation was applied at a fluence of 3 mW/cm2 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 1year postoperatively. Stromal demarcation line depth (DL) was measured in the first postoperative month. 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 ± 44.05μm. 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). The "Sub-400 protocol" for CXL has a broad application possibility for ultrathin corneas with KC and has shown promising results.

Definition of Progressive Keratoconus: A Systematic Review.

To identify the definitions used for progressive keratoconus in the literature. A systematic literature review aimed to identify the definitions used for "progressive keratoconus" in the published articles. A comprehensive search from January 2018 to May 2023 was conducted across Cochrane Library, PubMed, Taylor & Francis, Web of Science, and other bibliographic databases at Oftalmosalud, Lima, Peru. The inclusion criteria were articles including patients with keratoconus without any previous surgical procedure and containing the definition of "progressive keratoconus" or "keratoconus progression" and a sample size greater than 10 eyes. A total of 221 articles were included for analysis. The 3 most frequent parameters to define progression included data from anterior curvature, pachymetry, and refraction used in 97.8% (216/221), 37.6% (83/221), and 32.1% (71/221) of the articles, respectively. Specifically, the most frequent criterion used was maximum keratometry (Kmax), used in 85.5% (189/221) of the articles. Progression was assessed between 6- and 12-month follow-up in 64.7% (143/221) of the articles. Data from posterior cornea were used in only 8.1% (18/221) of the studies. None of the studies included data from the corneal epithelium. The present study demonstrates the lack of unified criteria to define progression of keratoconus and an underutilization of the technology described. It also shows that the single point Kmax measurement is the most commonly used criterion, followed by a change in refractive astigmatism and thinning at the thinnest pachymetric point.

Eye-Rubbing Detection Tool Using Artificial Intelligence on a Smartwatch in the Management of Keratoconus.

Eye rubbing is considered to play a significant role in the progression of keratoconus and of corneal ectasia following refractive surgery. To our knowledge, no tool performs an objective quantitative evaluation of eye rubbing using a device that is familiar to typical patients. We introduce here an innovative solution for objectively quantifying and preventing eye rubbing. It consists of an application that uses a deep-learning artificial intelligence (AI) algorithm deployed on a smartwatch. A Samsung Galaxy Watch 4 smartwatch collected motion data from eye rubbing and everyday activities, including readings from the gyroscope, accelerometer, and linear acceleration sensors. The training of the model was carried out using two deep-learning algorithms, long short-term memory (LSTM) and gated recurrent unit (GRU), as well as four machine learning algorithms: random forest, K-nearest neighbors (KNN), support vector machine (SVM), and XGBoost. The model achieved an accuracy of 94%. The developed application could recognize, count, and display the number of eye rubbings carried out. The GRU model and XGBoost algorithm also showed promising performance. Automated detection of eye rubbing by deep-learning AI has been proven to be feasible. This approach could radically improve the management of patients with keratoconus and those undergoing refractive surgery. It could detect and quantify eye rubbing and help to reduce it by sending alerts directly to the patient. This proof of concept could confirm one of the most prominent paradigms in keratoconus management, the role of abnormal eye rubbing, while providing the means to challenge or even negate it by offering the first automated and objective tool for detecting eye rubbing.

Success Rates and Prognostic Factors in the Management of Keratoconus: A 10-Year Retrospective Cohort Study at Siriraj Hospital

Objective: To evaluate the success rates of different treatment modalities, identify prognostic factors associated with treatment outcomes and factors influencing disease progression in keratoconus patients. Materials and Methods: A retrospective cohort study of keratoconus patients at Siriraj Hospital during January 2013 to December 2023 was done. Patient characteristics, symptoms and signs related to keratoconus, outcomes of corneal topography, treatment modalities, and best-corrected visual acuity (BCVA) before and after treatment were recorded. Treatment outcome was defined as a “success” when the BCVA post-treatment was equal to or better than 6/12. Progression of keratoconus was based on the Belin ABCD progression criteria. Results: Total 119 patients (231 eyes) were analyzed. The mean age at diagnosis was 28.0 ± 9.5 years. Two hundred and sixteen eyes (93.5%) were clinical keratoconus. The overall success rate of all treatment modalities was 87.4%. Contact lenses were the most frequent treatment modality (147 eyes, 72.4%) with the highest success rate (90.5%). A worse initial BCVA, high keratometric reading and thinner cornea were risk factors for treatment failure in this group. Of 133 eyes disease progression could be evaluated (median follow-up time; 33 months) and 58 eyes(43.6%) met criteria for disease progression (median survival time; 8.8 years). No significant factors were found to be associated with disease progression. Conclusion: Success rate in keratoconus treatment at Siriraj Hospital was 87.4%. Contact lenses were most frequently applied 72.4%. Factors associated with treatment failure were found in this group but for disease progressionremained unclear due to limitations of the study.

Microscope-Integrated OCT-Assisted Real-time Monitoring of Central Corneal Thickness During Corneal Cross-linking.

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. 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. 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. 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.].

Advances in Corneal Diagnostics Using Machine Learning

This paper provides comprehensive insights into the cornea and its diseases, with a particular focus on keratoconus. This paper explores the cornea’s function in maintaining ocular health, detailing its anatomy, pathological conditions, and the latest developments in diagnostic techniques. Keratoconus is discussed extensively, covering its subtypes, etiology, clinical manifestations, and the application of the Q-value for quantification. Several diagnostic techniques, such as corneal topography, are crucial points of discussion. This paper also examines the use of machine learning models, specifically Decision Tree and Nearest Neighbor Analysis, which enhance the accuracy of diagnosing based on topographical corneal parameters from corneal topography. These models provide valuable insights into disease progression and aid in clinical decision making. Integrating these technologies in medical research opens promising avenues for enhanced disease detection. Our findings demonstrate the effectiveness of Decision Tree and Nearest Neighbor Analysis in classifying and predicting conditions based on corneal parameters. The Decision Tree achieved classification accuracy of 62% for training and 65.7% for testing, while Nearest Neighbor Analysis yielded 65.4% for training and 62.6% for holdout samples. These models offer valuable insights into the progression and severity of keratoconus, aiding clinicians in treatment and management decisions.

Cost-Effectiveness of Corneal Collagen Crosslinking for Progressive Keratoconus: A Brazilian Unified Health System Perspective.

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.

Progressive Keratoconus Treatment with Transepithelial Two-Step Phototherapeutic Keratectomy Combined with Corneal Crosslinking (CXL): Clinical Outcomes and Postoperative Management Including Potential Complications of the Modified Athens Protocol Designed for US-Approved Excimer Laser Specifications.

Objectives: To report a novel application within the USA of excimer ablation for the normalization of central corneal refractive irregularity, combined with higher fluence CXL in the effective management and visual rehabilitation of progressive keratoconus. Methods: 17 consecutive cases with progressive keratoconus were treated with corneal surface excimer laser ablation normalization using topography-guided (Contura) myopic ablation for customized corneal re-shaping with a 6 mm optical zone. The epithelial removal was accounted for by adding a -2.75 diopter correction to this topography-guided normalizing surface ablation followed by a second wavefront-optimized hyperopic excimer treatment of +2.75 diopters also with a 6 mm optical zone. The two sequential excimer ablations applied on the intact epithelium were followed by corneal crosslinking (CXL). Visual acuity, refraction, and keratoconus documentation via keratometry, topography, and pachymetry, as well as endothelial cell density were evaluated over 36 months. Results: Keratoconus stabilized in all cases. The severity and stage of keratoconus determined by the Amsler-Krumeich criteria improved for the OD from an average of 2.2 to 1. The median UDVA showed marked improvement at one-year follow-up (all values in LogMAR), from 0.8 preoperative to 0.3 at 12 months, and was stable through the 3 years at 0.3. The median CDVA increased from 0.5 to 0.1 at 1 year and was stable at 0.1 at 3 years. The average minimal corneal thickness decreased from 466 μm to 396 μm, as recorded the first year postoperatively, and then slightly increased to 405 μm at the 3-year follow-up. Conclusions: We introduce herein the initial clinical data for the use of a novel, off-label therapeutic excimer laser surface ablation application. It was designed to perform both epithelial removal and anterior corneal stroma reshaping and combined with CXL to apply the Athens Protocol CXL with US excimer laser-approved specifications.

Enhancing keratoconus detection with transformer technology and multi-source integration

Keratoconus is a progressive eye disease characterized by the thinning and conical distortion of the cornea, leading to visual impairment. Early and accurate detection is essential for effective management and treatment. Traditional diagnostic methods, relying primarily on corneal topography, often fail to detect early-stage keratoconus due to their subjective nature and limited scope. In this research, we present a novel multi-source detection approach utilizing transformer technology to predict keratoconus progression more accurately. By integrating and analyzing diverse data sources, including corneal topography, aberrometry, pachymetry, and biomechanical properties, our method captures subtle changes indicative of disease progression. Transformer networks, known for their capability to model complex dependencies in data, are employed to handle the multimodal datasets effectively. Experimental results demonstrate that our approach significantly outperforms existing methods, such as SVM-based, Random Forests-based, and CNN-based models, in terms of accuracy, precision, recall, and F-score. Moreover, the proposed system exhibits lower execution times, highlighting its efficiency in clinical settings. This innovative methodology holds the potential to revolutionize keratoconus management by enabling earlier and more precise interventions, ultimately enhancing patient outcomes and contributing significantly to both the medical and machine learning communities.

Corneal endothelial iayer changes in various stages of keratoconus and their correlation with topographic findings: a cross-sectional study

Background. Keratoconus (KCN) is a multifactorial progressive corneal disease that leads to significant disturbances in visual function. Various layers of the cornea, such as the endothelium, are affected by this condition. This study aimed to evaluate the corneal endothelial layer in different stages of the KCN and its correlation to topographic findings. Methods. It is a cross-sectional study of 110 eyes of 70 patients (28 females and 42 males) with KCN. The KCN severity staging in this study was based on the Amsler-Krumeich criteria and topographic findings. Specular microscopy was used to evaluate and compare the condition of the endothelial layer in different stages of KCN. Results. The prevalence of the various stages of KCN was 10%, 33.6%, 13.6%, and 42.8%, respectively, for stages I to IV. There was no significant difference between various stages of OCN regarding endothelial cell density and polymegethism (P=0.759 and P=0.052, respectively). However, the mean frequency of the hexagonal endothelial cells (6A) in stage IV was 7.8% lower than in stage II eyes (P=0.025). In addition, the Kmax had a positive correlation with polymegethism (P&lt;0.001, r2=0.110) and a negative correlation with 6A (P=0.007, r2 =0.066). Conclusion. According to our findings, the progression of KCN could be associated with increased endothelial cell pleomorphism, and higher Kmax could be associated with polymegethism. However, there was no significant difference in endothelial cell density or polymegethism between the various stages of KCN. Practical Implications. Regarding the possible changes in the corneal endothelial layer with KCN progression, the pre-operative endothelial evaluations could improve the surgical plans in these patients.