Identification of Keratoconus-Related Phenotypes in Three Ppip5k2 Mouse Models.

Purpose: It is necessary to establish a mouse model of keratoconus (KC) for research and therapy. We aimed to determine corneal phenotypes in 3 Ppip5k2 mouse models. Methods: Central corneal thickness (CCT) was determined using spectral domain optical coherence tomography (SD-OCT) in Ppip5k2+/K^ (n = 41 eyes), Ppip5k2K^/K^ (n = 17 eyes) and 2 knock-in mice, Ppip5k2S419A/+ (n = 54 eyes) and Ppip5k2S419A/S419A (n = 18 eyes), and Ppip5k2D843S/+ (n = 42 eyes) and Ppip5k2D843S/D843S (n = 44 eyes) at 3 and 6 months. Pachymetry maps were generated using the Mouse Corneal Analysis Program (MCAP) to process OCT images. Slit lamp biomicroscopy was used to determine any corneal abnormalities, and, last, hematoxylin and eosin (H&E) staining using corneal sections from these animals was used to examine morphological changes. Results: CCT significantly decreased from 3 to 6 months in the Ppip5k2+/K^ and Ppip5k2K^/K^ mice compared to their littermate controls. OCT-based pachymetry maps revealed abnormally localized thinning in all three models compared to their wild-type (WT) controls. Slit lamp examinations revealed corneal abnormalities in the form of bullous keratopathy, stromal edema, stromal scarring, deep corneal neovascularization, and opacities in the heterozygous/homozygous mice of the three models in comparison with their controls. Corneal histological abnormalities, such as epithelial thickening and stromal layer damage, were observed in the heterozygous/homozygous mice of the three models in comparison with the WT controls. Conclusions: We have identified phenotypic and histological changes in the corneas of three mouse lines that could be relevant in the development of animal models of KC.

Assessment of large-diameter and small-diameter SoftK specialty contact lenses for early-stage keratoconus.

INTRODUCTION: Soft contact lenses may be a good alternative for early-stage keratoconus (KC) patients who do not tolerate rigid gas permeable (RGP) lenses due to ocular discomfort or complications. This prospective study compared outcomes obtained after 2 weeks of wearing two types of soft silicone hydrogel contact lenses for keratoconus that varied in their diameter and central thickness (cc). METHODS: Patients with Amsler-Krumeich grades I or II KC were fitted with small-diameter (14.2 or 14.8 mm) SoftK (SD-SoftK, cc = 0.48 mm) and large-diameter (17 mm) SoftK (LD-SoftK, cc = 0.60 mm) lenses, each worn for 2 weeks in a crossover design. Low (10%;10VA) and high (100%;100VA) contrast visual acuity, contrast sensitivity (CS, Pelli-Robson), higher order aberrations (HOAs, Visionix Vx130), the number of trial lens modifications during fitting and the subjectively preferred lens were compared using Friedman tests with post-hoc analysis. RESULTS: Forty eyes (N = 20, 10 males, mean age: 39.0 ± 9.9 years, range: 23-55 years) were examined. Their habitual median (interquartile1, interquartile3) 10VA (LogMAR), 100VA (LogMAR) and CS (LogCS) were 0.52 (0.30, 0.50), 0.14 (0.10, 0.15) and 1.35 (1.35, 1.50), respectively. For the SD-SoftK condition, the values were 0.23 (0.17, 0.30), 0.02 (0.00, 0.05) and 1.50 (1.50, 1.65), respectively. For the LD-SoftK condition, the respective values were 0.36 (0.27, 0.44), 0.09 (0.05, 0.13) and 1.50 (1.50, 1.60). SD-SoftK lenses significantly improved 10VA compared with habitual and LD-SoftK. SD-SoftK also significantly improved CS compared with habitual, but not LD-SoftK. LD-SoftK significantly improved spherical aberration compared with uncorrected (0.03 ± 0.10 µ vs. 0.07 ± 0.13 µ) but not SD-SoftK (0.04 ± 0.07 µ). Both lenses required a mean of 1.5 modifications prior to final lens fitting. Fewer adverse events were seen with SD-SoftK (N = 3) compared with LD-SoftK (N = 8), and 75% of participants preferred SD-SoftK lenses. CONCLUSION: SD-SoftK lenses were preferred by 75% of subjects, were associated with fewer adverse events and significantly improved 10VA compared with LD-SoftK lenses. SD-SoftK lenses also significantly improved CS compared with the habitual correction, but this did not differ significantly from the LD-SoftK lenses.

Keratoconus Progression Determined at the First Visit: A Deep Learning Approach With Fusion of Imaging and Numerical Clinical Data.

Purpose: Multiple clinical visits are necessary to determine progression of keratoconus before offering corneal cross-linking. The purpose of this study was to develop a neural network that can potentially predict progression during the initial visit using tomography images and other clinical risk factors. Methods: The neural network's development depended on data from 570 keratoconus eyes. During the initial visit, numerical risk factors and posterior elevation maps from Scheimpflug imaging were collected. Increase of steepest keratometry of 1 diopter during follow-up was used as the progression criterion. The data were partitioned into training, validation, and test sets. The first two were used for training, and the latter for performance statistics. The impact of individual risk factors and images was assessed using ablation studies and class activation maps. Results: The most accurate prediction of progression during the initial visit was obtained by using a combination of MobileNet and a multilayer perceptron with an accuracy of 0.83. Using numerical risk factors alone resulted in an accuracy of 0.82. The use of only images had an accuracy of 0.77. The most influential risk factors in the ablation study were age and posterior elevation. The greatest activation in the class activation maps was seen at the highest posterior elevation where there was significant deviation from the best fit sphere. Conclusions: The neural network has exhibited good performance in predicting potential future progression during the initial visit. Translational Relevance: The developed neural network could be of clinical significance for keratoconus patients by identifying individuals at risk of progression.

Diagnostic utility of in vivo confocal microscopy in Acanthamoeba keratitis following corneal crosslinking.

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.

[Comparative analysis of clinical and functional parameters in patients with stable stage II-III keratoconus after implantation of corneal segments and fitting of scleral rigid contact lenses]. / Sravnitel'nyi analiz kliniko-funktsional'nykh pokazatelei u patsientov so stabil'nym keratokonusom II­III stadii posle implantatsii rogovichnykh segmentov i podbora skleral'nykh zhestkikh kontaktnykh linz.

The modern treatment strategy for keratoconus (KC) involves sequential application of medical technologies aimed at stabilizing pathological changes in the cornea and restoring visual acuity. PURPOSE: This study compares the effect of implantation of intrastromal corneal ring segment (ICRS) and fitting of individual scleral rigid contact lenses (RCLs) on visual functions in patients with stage II-III KC after previously performed corneal collagen cross-linking. MATERIAL AND METHODS: The Helmholtz National Medical Research Center of Eye Diseases examined and treated 34 patients (69 eyes) aged 18 to 33 years with stage II-III KC. The study included patients who had previously undergone standard corneal collagen cross-linking. Depending on the type of optical correction, the patients were divided into two groups: patients in group 1 underwent ICRS implantation using a femtosecond laser; patients in group 2 were fitted with individual scleral RCLs. RESULTS: Improvement in clinical and functional parameters was observed in both groups. A higher clinical and functional result was achieved in group 2. CONCLUSION: For patients with stable stage II-III KC, it is advisable to recommend fitting of individual scleral RCLs for visual rehabilitation.

[Alternative methods of surgical treatment of keratoconus]. / Al'ternativnye metody khirurgicheskogo lecheniya keratokonusa.

The introduction of early diagnostic methods for keratoconus into clinical practice has become the basis for the development of surgical treatment techniques for this pathology, such as corneal collagen crosslinking and interlamellar keratoplasty with implantation of intrastromal segments. The article analyzes the results of research by Russian and foreign specialists in these areas and presents the data on the combination of SMILE surgery and corneal crosslinking, the Rome protocol of corneal crosslinking, modifications of interlamellar keratoplasty, the use of femtosecond laser technologies, and some pilot studies. Modern requirements for ophthalmological care require a personalized approach to each patient, and therefore the surgeon should have a wide range of surgical methods of treatment applicable to different patient cohorts. The described methods of treatment, according to the authors, are the most promising.

Comparing the clinical applicability of wavefront phase imaging in keratoconus versus normal eyes.

The aim of this work is to quantitatively assess the wavefront phase of keratoconic eyes measured by the ocular aberrometer t·eyede (based on WaveFront Phase Imaging Sensor), characterized by a lateral resolution of 8.6 µm without requiring any optical element to sample the wavefront information. We evaluated the parameters: root mean square error, Peak-to-Valley, and amplitude of the predominant frequency (Fourier Transform analysis) of a section of the High-Pass filter map in keratoconic and healthy cohorts. Furthermore, we have analyzed keratoconic eyes that presented dark-light bands in this map to assess their period and orientation with the Fourier Transform. There are significant statistical differences (p value < 0.001) between healthy and keratoconic eyes in the three parameters, demonstrating a tendency to increase with the severity of the disease. Otherwise, the quantification of the bands reveals that the width is independent of eye laterality and keratoconic stage as orientation, which tends to be oblique. In conclusion, the quantitative results obtained with t·eyede could help to diagnose and monitor the progression of keratoconus.

Does collagen cross linking have any effect on retinal circulation in patients with keratoconus? An optical coherence tomography angiography (OCTA) study.

BACKGROUND: We aimed to employ Optical Coherence Tomography Angiography (OCTA) to comprehensively assess changes in the optic nerve head (ONH) and macular perfusion before and after the Corneal Collagen Cross-Linking (CCL) procedure in patients with keratoconus. METHODS: A total of 22 keratoconus patient's candidate for CCL procedures were included based on specific criteria, with meticulous exclusion criteria in place to minimize potential confounders. Participants underwent OCTA assessments of the ONH and macula using the Spectralis OCT (Heidelberg) before CCL, as well as at 1- and 3-months post-CCL. MATLAB software was utilized for image analysis. RESULTS: The mean age of the participants was 20.09 ± 6.11, including 59% male, and the mean intraocular pressure (IOP) before the surgery was 13.59 ± 2.85 mmHg. Peripapillary Retinal nerve fiber layer (ppRNFL) thickness and overall retinal thickness remained stable post-CCL. However, significant alterations were observed in macular vessel density, emphasizing regional variations in vascular response. For macular large vessel density (LVD), both superficial and deep vascular complex (SVC and DVC) demonstrated significant differences between before surgery and the 3 months post-surgery follow-up (p < 0.001 and p = 0.002, respectively). Optic nerve head markers demonstrated relative stability, except for changes in avascular complex density, which was 49.2 ± 2.2% before the surgery and decrease to 47.6 ± 1.7% three months after the operation (P-value = 0.005). CONCLUSION: While CCL appears to maintain the integrity of certain ocular structures, alterations in macular perfusion post-CCL suggest potential effects on retinal blood supply. Long-term monitoring is crucial to understand the implications of these changes, particularly in the context of conditions such as diabetes.

[Effect of keratoplasty on the quality of life of keratoconus patients]. / Effet de la kératoplastie sur la qualité de vie des patients atteints de kératocône.

Corneal deformations caused by keratoconus produce high levels of optical aberration (OA). Despite appropriate optical correction, these alter the quality of vision and diminish the patient's quality of life, especially since the affected population is predominantly young and of working age. When thinning is too severe or corneal transparency too impaired, a corneal transplant may be considered. In this study, we compare the quality of life of patients with keratoconus in the early (stages 1 and 2) or advanced (stages 3 and 4) stages of the Krumeich classification, as well as patients who have had keratoconus treated by keratoplasty. Quality of life was assessed using the NEI-VFQ 25 questionnaire, the most widely used for keratoconus. An aberrometric examination (OQAS®; HD Analyser, Visiometrics, Terrassa, Spain) was also performed to assess patients' quality of vision. Our results show that keratoplasty provides an improvement in quality of life compared with advanced-stage keratoconus in the areas of distance (p=0.0083) and near vision (p=0.029) activities. This improvement also applies to Best-Corrected Visual Acuity (BCVA) (p=0.032) and transparency (OSI) (p=0.049). Our study shows that keratoplasty improves corneal transparency, and it is interesting to note that it improves patients' quality of life over the long term.

Comparative evaluation of biomechanical changes and aberration profile following accelerated collagen cross-linking using hypo-osmolar and iso-osmolar riboflavin: A prospective study.

PURPOSE: To compare the changes encountered in corneal biomechanics and aberration profile following accelerated corneal collagen cross-linking (CXL) using hypo-osmolar and iso-osmolar riboflavin in corneal thicknesses of <400 and >400 microns, respectively. METHODS: This is a prospective, interventional, comparative study involving 100 eyes of 75 patients with progressive keratoconus. Eyes were divided into two groups based on corneal thickness: group 1 included eyes with a corneal thickness of <400 microns who underwent hypo-osmolar CXL, and group 2 included eyes with a corneal thickness of >400 microns who underwent iso-osmolar CXL. Corneal biomechanical and aberration profiles were evaluated and compared between groups. RESULTS: In group 1, all higher-order aberrations (HOA) except secondary astigmatism significantly decreased from baseline; however, in group 2, only coma and trefoil decreased. The corneal resistance factor and corneal hysteresis significantly improved in both groups, which was significantly greater in group 2 than in group 1. The change in inverse radius, deformation amplitude, and tomographic biomechanical index was significantly improved in group 2 as compared to group 1. CONCLUSION: Improvement in corrected distance visual acuity and decrease in HOA were significantly better in the hypo-osmolar CXL group; however, the improvement in biomechanical strength of the cornea was significantly better in the iso-osmolar group.

Differences Between Simulated Keratometry and Total Corneal Power in Eyes With Keratoconus and a Formula to Improve IOL Power Calculation Results.

PURPOSE: To compare simulated keratometry (SimK) and total corneal power (TCP) in keratoconic eyes, to determine whether the differences are systematic and predictable and to evaluate an adjusted TCP-based formula for intraocular lens (IOL) power calculation. METHODS: In a consecutive series of keratoconic eyes, measurements of SimK, TCP, posterior keratometry, and anterior and posterior corneal asphericities (Q-values) were retrospectively collected. The difference between SimK and TCP was linearly correlated to the biometric parameters. In a separate sample of keratoconic eyes that had undergone cataract surgery, IOL power was calculated with the Barrett Universal II, Hoffer QST, Holladay 1, Kane, and SRK/T formulas using the SimK and an adjusted TCP power. The respective prediction errors were calculated. RESULTS: A total of 382 keratoconic eyes (271 patients) were enrolled. An increasing overestimation of SimK by TCP was detected from stage I to III, with a significant correlation between the SimK and TCP difference and SimK in the whole sample (P < .0001, r2 = 0.1322). Approximately 7% of cases presented an underestimation of SimK by TCP. IOL power calculation with the adjusted TCP improved outcomes, achieving a maximum of 80% of eyes with a prediction error within ±0.50 diopters with the Hoffer QST, Holladay 1, and Kane formulas. CONCLUSIONS: Overall, SimK overestimated TCP. Such a difference could not be predicted by any variable. The proposed TCP-adjustment formula (TCPadj = TCP + 0.56 diopters) in keratoconic eyes for IOL power calculation might be valuable for improving refractive outcomes. [J Refract Surg. 2024;40(4):e253-e259.].

Comparative Evaluation of Topographic Parameters Using Three Different Topographers in Keratoconic and Cross-linked Keratoconic Corneas.

PURPOSE: To compare the parameters of three different topographic devices (Pentacam HR, Oculus Optikgeräte GmbH; Sirius, Costruzione Strumenti Oftalmici; and Cassini, i-Optics) in grading the severity of keratoconus in cross-linked and non-cross-linked eyes. METHODS: This was a prospective comparative interventional study done in a tertiary eye care center, wherein 114 eyes of 68 patients with keratoconus were divided into two groups: 62 eyes that were observed and 52 eyes that were cross-linked. All eyes were evaluated on all three topographers at baseline, 3-month follow-up, and 6-month follow-up. RESULTS: The Sirius showed significantly lower values of mean flat keratometry in comparison to the Pentacam HR (limits of agreement [LoA]: 1.75 to 3.51%) and Cassini (LoA: 1.75 to 3.51%). The mean steep keratometry values were higher for the Cassini in comparison to the Pentacam HR (LoA: 4.39 to 7.02%) and Sirius (LoA: 3.51 to 6.14%). The mean steep keratometry values of the Sirius were significantly lower than those of the Pentacam HR and in both the cross-linked and observation groups (LoA: 3.51 to 6.14%). The mean keratometry values were significantly higher in the Cassini compared to the Pentacam HR (LoA: 3.51 to 8.77%) and significantly lower in the Sirius in comparison to the Pentacam HR (LoA: 3.51 to 6.14%). The mean difference in astigmatism was also statistically significant between the three tomographers in both groups, with the Cassini showing higher values (LoA: 3.51 to 5.26%) and the Sirius lower values than the Pentacam HR (LoA: 5.26 to 6.14%). CONCLUSIONS: The authors conclude the three devices cannot be used interchangeably. The Cassini showed better agreement and correlation with the Pentacam HR in the staging of keratoconus, whereas the Sirius tended to underdiagnose and under-stage the disease. [J Refract Surg. 2024;40(4):e260-e269.].

Higher order aberrations in keratoconus .

INTRODUCTION: Keratoconus is a progressive disorder of the cornea that causes thinning (Sedaghat et al. in Sci Rep 11(1):11971, 2021), ectasia, and irregular astigmatism, resulting in poor visual acuity that cannot be corrected with standard sphero-cylindrical spectacle lenses. One feature distinguishing keratoconic corneas is ocular aberrations, manifesting up to five or six times the amount of higher-order aberrations than a normal, healthy eye. These aberrations can cause visual disturbances even at the very early stages of the disease. METHODS: In the past, a diagnosis was derived from clinical symptoms, but technological advances have revealed multiple pre-clinical features, allowing for the differentiation between keratoconic and normal eyes at a much earlier stage. These include anterior and posterior corneal surface elevations, the corneal pachymetry profile, corneal epithelial patterns, wavefront aberration metrics, and corneal biomechanics (Sedaghat et al. in Sci Rep 11(1):11971, 2021).This review discusses the aberrations associated with keratoconus, how to measure them, and treatment methods to minimize their negative influence. CONCLUSIONS: Early diagnosis can lead to early treatment and may allow for arresting progression, thereby improving the long-term prognosis. With the acceleration of refractive surgery, it is important to identify patients with keratoconus, as they are usually contraindicated for refractive surgery.

Evaluation of dynamic corneal response parameters and the biomechanical E-staging after Intacs® SK implantation in keratoconus.

PURPOSE: This retrospective longitudinal study evaluated the biomechanical E-staging in KC corneas before and after intracorneal ring segment (ICRS) implantation (Intacs® SK, Addition Technology, Illinois, United States). METHODS: Biomechanical E-staging for ectatic corneal diseases was applied retrospectively on 49 KC corneas of 41 patients who underwent ICRS implantation. The main outcome parameters included the Corvis Biomechanical Factor (CBiF, the linearized Corvis Biomechanical Index and the biomechanical parameters included), the resulting biomechanical E-staging, the stress-strain index, thinnest corneal thickness (TCT), maximal anterior keratometry (Kmax), and the anterior radius of curvature (ARC). They were evaluated at 1.9 ± 1.1 months preoperatively and postoperatively after 2.8 ± 0.7, 5.8 ± 1.0, and 10.6 ± 2.3 months. RESULTS: The CBiF decreased (4.9 ± 0.5 | 4.7 ± 0.5, P = 0.0013), and the E-staging increased significantly (2.8 ± 0.8 | 3.1 ± 0.9, P = 0.0012, paired t-test) from preoperatively to the first postoperative follow-up. The difference remained significant after 6 months; however, there was no more difference after 11 months. TCT was stable, whereas Kmax and ARC significantly decreased after ICRS implantation (TCT: 464 ± 49, 470 ± 51, 467 ± 38, 461 ± 48; Kmax: 56.3 ± 4.5, 54.7 ± 4.5, 54.2 ± 4.8, 54.1 ± 4.3; ARC: 51.5 ± 3.4, 48.3 ± 3.8, 48.6 ± 3.0, 48.6 ± 3.2 preoperatively and 3, 6, and 11 months postoperatively, respectively). Besides Kmax and ARC, Ambrósio's relational thickness to the horizontal profile (ARTh) was the only parameter that was significantly lower than preoperatively at any follow-up (P ≤ 0.0024, Wilcoxon matched-pairs test). CONCLUSION: Intacs® SK implantation results in an increasing biomechanical E-staging in the first postoperative months with stabilization near preoperative values after 1 year. Significantly lower ARTh values at any follow-up document the ICRS effect and contribute to a slightly higher postoperative biomechanical E-staging value.

Keratoconus disease classification with multimodel fusion and vision transformer: a pretrained model approach.

OBJECTIVE: Our objective is to develop a novel keratoconus image classification system that leverages multiple pretrained models and a transformer architecture to achieve state-of-the-art performance in detecting keratoconus. METHODS AND ANALYSIS: Three pretrained models were used to extract features from the input images. These models have been trained on large datasets and have demonstrated strong performance in various computer vision tasks.The extracted features from the three pretrained models were fused using a feature fusion technique. This fusion aimed to combine the strengths of each model and capture a more comprehensive representation of the input images. The fused features were then used as input to a vision transformer, a powerful architecture that has shown excellent performance in image classification tasks. The vision transformer learnt to classify the input images as either indicative of keratoconus or not.The proposed method was applied to the Shahroud Cohort Eye collection and keratoconus detection dataset. The performance of the model was evaluated using standard evaluation metrics such as accuracy, precision, recall and F1 score. RESULTS: The research results demonstrated that the proposed model achieved higher accuracy compared with using each model individually. CONCLUSION: The findings of this study suggest that the proposed approach can significantly improve the accuracy of image classification models for keratoconus detection. This approach can serve as an effective decision support system alongside physicians, aiding in the diagnosis of keratoconus and potentially reducing the need for invasive procedures such as corneal transplantation in severe cases.

Evaluation of the results of contact lens assisted corneal cross-linking treatment in keratoconus patients with thin corneas.

PURPOSE: We aimed to compare the efficacy and safety of accelerated contact lens-assisted cross-linking (CA-CXL) with Lotrafilcon B and Comfilcon A lenses in keratoconus (KC) patients with thin corneas. STUDY DESIGN: Retrospective, single-center study. MATERIALS AND METHODS: We retrospectively included 51 eyes of 39 KC patients with corneal thickness <400µm after epithelial scraping (Epi-off), who underwent accelerated CA-CXL treatment with Lotrafilcon B (n=20) and Comfilcon A (n=31). Uncorrected and corrected distance visual acuity (UDVA and CDVA), manifest refraction values, corneal topographic data and endothelial cell density were recorded at preoperative and postoperative 1st, 3rd and 6th month controls. RESULTS: CDVA in the Comfilcon A group was higher than CDVA before surgery at 6 months postoperatively (p<0.001). When the two lenses were compared, CDVA was found to be significantly higher in the Lotrafilcon B group in the preoperative, postoperative 1st month and 3rd month values, but there was no significant difference between the postoperative 6th month values (p=0.028, p=0.018, p=0.044, p=0.181, respectively). The maximum keratometry (Kmax) value at the 6th month after surgery in the Comfilcon A group was significantly lower than in the Lotrafilcon B group (p=0,009). There was no significant difference between the endothelial cell density values between the groups (p=0.623, p=0.609, p=0.794, p=0.458, respectively). There was no significant difference between the progression, regression, and stability rates of the two groups (p=0.714). CONCLUSIONS: Accelerated CA-CXL with Lotrafilcon B and Comfilcon A silicone hydrogel lenses is a safe and effective method to stop progression in patients with thin corneas.