Binocular vision parameters and visual performance in bilateral keratoconus corrected with spectacles versus rigid gas-permeable contact lenses / Parámetros de visión binocular y rendimiento visual en queratocono bilateral corregido con gafas versus lentes de contacto rígidos permeables al gas

Purpose: To analyze binocular vision of individuals aged 18 to 35 years diagnosed with keratoconus, utilizing spectacles and rigid gas-permeable (RGP) contact lenses. Research was led by the Universidad Autónoma de Aguascalientes, México and Fundación Universitaria del Área Andina Pereira, Colombia. Methods: A single center, prospective non-randomized, comparative, interventional, open-label study, in which the differences in binocular vision performance with both spectacles and RGP contact lenses was carried out from December 2018 to December 2019. Sampling was performed according to consecutive cases with keratoconus that met the inclusion criteria until the proposed sample size was reached. Results: Rigid gas-permeable (RGP) contact lenses notably enhanced distance and near visual acuity in keratoconus patients compared to spectacles. Visual alignment analysis shows exophoria at both distances and is slightly higher with RGP contact lenses. The difference was statistically significant (p<0.05), with 82.5 % presenting compensated phoria with spectacles and pnly 42.50% with RGP contact lenses. Stereoscopic vision improved while wearing RGP contact lenses (42.59 %), although accommodation and accommodative flexibility remained within normal ranges. Conclusions: Patients with keratoconus fitted with RGP contact lenses have improved binocular vision skills such as visual acuity, stereopsis, and accommodative flexibility. However, even when the vergence and motor system is decompensated with respect to normal ranges, the range between break and recovery points for both fusional reserves and the near point of convergence (NPC) improves with the use of RGP contact lenses, giving indications of an adaptive condition of the motor system from the medium to the long term.(AU)

Keratoconus and inflammatory bowel disease: mendelian randomization.

Background: Keratoconus is a diseased corneal dilation of unknown etiology. Studies have shown that inflammation may play a role in keratoconus. Inflammatory enteritis (IBD), including ulcerative colitis (UC), is a chronic, systemic inflammatory disease. We used Mendelian randomization to assess the causal relationship among IBD, UC and keratoconus. Methods: The instrumental variable of IBD and UC was selected, the information of the instrumental variable in keratoconus outcome was extracted, and the causal relationship was assessed by the inverse variance weighted method by primary analysis, and its relevant sensitivity analysis. Results: A causal relationship between IBD and keratoconus was observed significantly (P = 0.017, OR = 1.21, 95% CI = 1.03-1.41), and same as to UC and keratoconus (P = 0.038, OR = 1.25, 95% CI = 1.01-1.54). Conclusion: IBD may play a causal role in the development of keratoconus, but the mechanism needs to be further elucidated.

Could Automated Objective Measurements Acquired at the Preoperative Stage Estimate the Corrected Distance Visual Acuity after Corneal Cross-Linking in Keratoconus?

INTRODUCTION: Objective markers describing corneal optical density (COD), thinnest corneal thickness (TCT), and anterior (ARC) and posterior (PRC) surface radii over the 3 mm thinnest region of the cornea were investigated to provide a model for estimating corrected distance visual acuity (CDVA) after corneal cross-linking (CXL) in keratoconus. METHODS: CDVA, COD, TCT, ARC, and PRC were monitored (using Pentacam™) over 1 year in patients with (1) keratoconus treated with routine CXL (2) relatively stable untreated keratoconus, and (3) age/gender-matched controls. RESULTS: In group 1 (n = 77), the median logMAR CDVA (mode, interquartile range) improved significantly (p < 0.01) from 0.26 (0.22, 0.12-0.65) to 0.07 (0.00, 0.02-0.21). The mean (± standard deviation, 95% confidence interval) COD (in 0-100 grey scale units) in the 0-2 mm central anterior corneal region (0-2 ant), TCT (µm), ARC (mm), and PRC (mm) changed significantly (p < 0.01), from 21.2 (± 3.70, 20.4-22.0), 454 (± 40.0, 446-462), 6.49 (± 0.71, 6.33-6.65), and 4.81 (± 0.65, 4.66-4.96) to 31.5 (± 9.19, 29.5-33.6), 423 (± 49.3, 412-434), 6.78 (± 0.80, 6.60-6.98), and 4.74 (± 0.64, 4.59-4.88), respectively, but remained stable in groups 2 (n = 23) and 3 (n = 24). Significant relationships (p < 0.01) were uncovered between postop CDVA and preop values of COD, TCT, ARC, and PRC. Multilinear regression revealed significant correlations between CDVA at 1 year and preop COD, TCT, ARC, and PRC (r2 = 0.533, r20-2ant = 0.126, r2TCT = 0.321, r2ARC = 0.506, r2PRC = 0.467). Including preop CDVA further enhanced this correlation (r2 = 0.637, r2LogMAR CDVApreop = 0.566). CONCLUSION: CXL improved CDVA, increased COD and ARC, and reduced TCT and PRC. The chance of correctly estimating the CDVA at 1 year after CXL using preoperative markers of COD, TCT, ARC, and PRC is 53%, improving to 64% with the inclusion of preoperative CDVA. Objective measurements taken at the preoperative screening stage may be useful to estimate the likely postoperative CDVA when preoperative CDVA measures are unreliable or unobtainable. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT06522789.

KeratoEL: Detection of keratoconus using corneal parameters with ensemble learning.

Background and Aims: Keratoconus is a progressive eye condition in which the normally round cornea thins and bulges outwards into a cone shape. This irregular shape causes light to scatter in multiple directions as it enters the eye, leading to distorted vision, increased sensitivity to light and frequent changes in the prescription of glasses or contact lenses. Detecting keratoconus at an early stage is not only difficult but also challenging. Methods: The study has proposed an ensemble-based machine learning (ML) technique named KeratoEL to detect keratoconus at an early stage. The proposed KeratoEL model combines the basic machine learning algorithms, namely support vector machine (SVM), decision tree (DT), random forest (RF) and artificial neural network (ANN). Before employing the ML model for keratoconus detection, the data set is first preprocessed manually by eliminating some features that don't contribute any significant value to predict the exact class. Moreover, the output features are labelled into three different classes and Extra Trees Classifier is used to find out the important features. Then, the features are sorted in descending order and top 45, 30, and 15 features are taken as input datasets against the output. Finally, different machine learning models are tested using the input datasets and performance metrics are measured. Results: The proposed model obtains 98.0%, 98.9% and 99.8% accuracy for top 45, 30, and 15 number of features respectively. Overall experimental results show that the proposed ensemble model outperforms the existing machine learning models. Conclusion: The proposed KeratoEL model effectively detects keratoconus at an early stage by combining SVM, DT, RF, and ANN algorithms, demonstrating superior performance over existing models. These results underscore the potential of the KeratoEL ensemble approach in enhancing early detection and treatment of keratoconus.

Hyperbaric Oxygenation Maintains Elevated Stromal Oxygen Availability During Corneal Collagen Crosslinking with and Without Epithelial Removal.

PURPOSE: Corneal collagen cross-linking (CXL) can halt corneal ectasia. Leaving corneal epithelium intact during treatment may reduce the incidence of complications. However, it is under debate whether this reduces efficacy and if oxygen supplementation may be necessary to optimize the cross-linking effect. This study aimed to investigate the impact of hyperbaric oxygenation (HBO) on intracorneal oxygen concentrations during epi-off and epi-on CXL. METHODS: CXL was performed using riboflavin and ultraviolet-A (UV-A) irradiance (3 mW/cm2 for 30 min) on porcine corneas under normobaric and hyperbaric conditions, with and without supplemented oxygen, with and without epithelium. Intracorneal oxygen concentrations were continuously monitored before and during irradiation. Biomechanical properties were assessed through tensile strength testing. RESULTS: HBO alone did not cause perceivable changes in stromal oxygen concentrations. Oxygen supplementation resulted in higher oxygen concentration in corneal stroma during CXL. HBO may cause a further increase in oxygen levels, although this was not statistically significant in this study. Notably, a tendency of oxygen levels to rise continuously during UV-irradiation was observed using HBO. Biomechanical properties showend no statistically significant differences between any groups. CONCLUSIONS: In this ex-vivo model, HBO increased stromal oxygen levels during CXL, regardless of the presence of corneal epithelium. The dynamics in oxygen concentrations in corneal stromal tissue during CXL suggest that time is an important factor to consider in modifications of established protocols. Also, we hypothesize that stromal levels of riboflavin and UV-A irradiance may be more critical to the CXL effect when oxygen is supplemented and epithelium is not removed.

[Changes in the precorneal tear film at various stages of keratoconus]. / Izmenenie prekorneal'noi sleznoi plenki pri razlichnykh stadiyakh keratokonusa.

The combination of keratoconus (KC) with signs of dry eye disease (DES) has been described in numerous scientific publications. At the same time, there is a relationship between KC stage and an increase in the severity of DES symptoms, however, there is still no common understanding of the severity of xerotic process depending on the clinical course of keratectasia. PURPOSE: This study assesses the changes in the state of the precorneal tear film in KC relative to the stages of the disease. MATERIAL AND METHODS: The study included 50 patients (100 eyes) with bilateral non-operated KC from subclinical to stage IV. The following methods were used for a comprehensive assessment of the condition of the tear film: biomicroscopy of the anterior segment of the eye using vital dyes, functional tests (Norn, Schirmer, Jones tests), tearscopy of the lipid layer of the tear film with software processing of the results, OCT-meniscometry, as well as filling out the OSDI questionnaire by patients. RESULTS: The following significant changes were revealed as the KC stage progressed: an increase in the area of staining of the ocular surface with vital dyes, a decrease in the results of the Norn functional test and OCT-meniscometry, an increase in the areas of smaller thickness of lipids and areas of their complete absence according to tearscopy, as well as an increase in scores of the OSDI questionnaire. CONCLUSION: A comprehensive assessment of the condition of the tear film in KC indicates the relationship and the strengthening of the signs of DES as keratectasia progresses, and can be considered as justification for the need to prescribe tear replacement and reparative therapy that improves the condition of the ocular surface and stabilizes the precorneal tear film.

Early findings in a randomised controlled trial on crosslinking protocols using isoosmolar and hypoosmolar riboflavin for the treatment of progressive keratoconus.

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/cm2) 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.

A discrete-to-continuum model for the human cornea with application to keratoconus.

We introduce a discrete mathematical model for the mechanical behaviour of a planar slice of human corneal tissue, in equilibrium under the action of physiological intraocular pressure (IOP). The model considers a regular (two-dimensional) network of structural elements mimicking a discrete number of parallel collagen lamellae connected by proteoglycan-based chemical bonds (crosslinks). Since the thickness of each collagen lamella is small compared to the overall corneal thickness, we upscale the discrete force balance into a continuum system of partial differential equations and deduce the corresponding macroscopic stress tensor and strain energy function for the micro-structured corneal tissue. We demonstrate that, for physiological values of the IOP, the predictions of the discrete model converge to those of the continuum model. We use the continuum model to simulate the progression of the degenerative disease known as keratoconus, characterized by a localized bulging of the corneal shell. We assign a spatial distribution of damage (i.e. reduction of the stiffness) to the mechanical properties of the structural elements and predict the resulting macroscopic shape of the cornea, showing that a large reduction in the element stiffness results in substantial corneal thinning and a significant increase in the curvature of both the anterior and posterior surfaces.

Smart decision support system for keratoconus severity staging using corneal curvature and thinnest pachymetry indices.

BACKGROUND: This study proposes a decision support system created in collaboration with machine learning experts and ophthalmologists for detecting keratoconus (KC) severity. The system employs an ensemble machine model and minimal corneal measurements. METHODS: A clinical dataset is initially obtained from Pentacam corneal tomography imaging devices, which undergoes pre-processing and addresses imbalanced sampling through the application of an oversampling technique for minority classes. Subsequently, a combination of statistical methods, visual analysis, and expert input is employed to identify Pentacam indices most correlated with severity class labels. These selected features are then utilized to develop and validate three distinct machine learning models. The model exhibiting the most effective classification performance is integrated into a real-world web-based application and deployed on a web application server. This deployment facilitates evaluation of the proposed system, incorporating new data and considering relevant human factors related to the user experience. RESULTS: The performance of the developed system is experimentally evaluated, and the results revealed an overall accuracy of 98.62%, precision of 98.70%, recall of 98.62%, F1-score of 98.66%, and F2-score of 98.64%. The application's deployment also demonstrated precise and smooth end-to-end functionality. CONCLUSION: The developed decision support system establishes a robust basis for subsequent assessment by ophthalmologists before potential deployment as a screening tool for keratoconus severity detection in a clinical setting.

Corneal densitometry changes after femtosecond laser-assisted intracorneal ring segments implantation in keratoconus.

Background: Intrastromal corneal ring segments are commonly implanted in the corneas of eyes with mild-to-moderate keratoconus; however, changes in corneal densitometry (CD) after implantation are a matter of debate in the current literature. We evaluated the changes in CD 1 and 3 months after femtosecond laser-assisted Keraring implantation. Methods: This retrospective, non-comparative, multicenter, case series study included patients with keratoconus who underwent femtosecond laser-assisted implantation of double segments with 90° and 160° arc lengths or two 160° arc length Keraring segments. Demographic and baseline clinical ophthalmic data were recorded. Corneal topography and tomography data acquired using a Pentacam HR Scheimpflug tomography system (Pentacam High Resolution; Oculus, Wetzlar, Germany) with a best-fit sphere were used as a reference surface. Using the Pentacam HR, CD measurements were acquired over a corneal area of 12 mm in total and at four concentric zones (0-2, 2-6, 6-10, and 10-12 mm) of three corneal stromal depths: 120 µm of the anterior corneal stromal layer, 60 µm of the posterior corneal stromal layer, and the central layer of stroma lying between these two layers. Results: We included 40 eyes of 40 patients, including 8 (20%) male and 32 (80%) female individuals, with a mean (standard deviation) age of 21.0 (6.4) years. We observed a significant improvement in the topographic values of steep keratometry (K), flat K, maximum K, and corneal astigmatism (all P < 0.05), but not in the mean K, thinnest corneal pachymetry, corneal thickness at the apex, back elevation, or front elevation (all P > 0.05). The mean total anterior, central, and posterior CD differed significantly among the time points, with a significant increase from the preoperative to the 1-month and 3-month postoperative visits (all P < 0.05) and no difference between those of the 1-month and 3-month postoperative visits (all P > 0.05). The mean CD for the anterior layer in the central, paracentral, and mid-peripheral zones, and the central layer in all four zones, differed significantly among time points, with a significant increase from the preoperative to the 1-month and 3-month postoperative visits (all P < 0.05), which remained unchanged from the 1-month to the 3-month postoperative visit (all P < 0.05), except for the central 2-6-mm zone, which decreased significantly from the 1-month to the 3-month postoperative visit (P < 0.001). The CD of the central 10-12-mm zone did not differ significantly in each pairwise comparison (all P > 0.05). In contrast, CD for the posterior layer in the paracentral zone decreased significantly from the preoperative to the 1-month and 3-month postoperative visits but increased, to a lesser extent, from the 1-month to the 3-month postoperative visit (all P < 0.05). Conclusions: Femtosecond laser-assisted Keraring implantation significantly changes CD, with improvement in most topography parameters. Further longitudinal studies with larger sample sizes are required to verify these preliminary findings.

Keratoconus: imaging modalities and management.

Background: Keratoconus (KCN) is characterized by gradual thinning and steepening of the cornea, which can lead to significant vision problems owing to high astigmatism, corneal scarring, or even corneal perforation. The detection of KCN in its early stages is crucial for effective treatment. In this review, we describe current advances in the diagnosis and treatment of KCN. Methods: This narrative review focuses on recent advancements in the diagnosis and treatment of KCN, especially evolving approaches and strategies. To ensure the inclusion of the most recent literature, relevant publications discussing advanced imaging techniques and treatment options for KCN were extensively gathered from the PubMed/MEDLINE and Google Scholar databases. The following index terms and keywords were used for the online search: keratoconus, diagnosis of keratoconus, advances in the diagnosis of keratoconus, topography or tomography, anterior segment optical coherence tomography, treatment of keratoconus, advances in the treatment of keratoconus, collagen crosslinking, intrastromal ring, keratoplasty, and new techniques in keratoconus. Results: Various screening methods such as corneal topography, tomography, anterior segment optical coherence tomography, and assessment of corneal biomechanics have been developed to identify KCN in its early stages. After diagnosis, KCN management focuses on preventing disease progression. Corneal collagen crosslinking is a minimally invasive treatment that can slow or stop the progression of the condition. Recent research has also explored the use of copper sulfate eye drops (IVMED-80) as a noninvasive treatment to prevent the progression of KCN. Current treatment options for visual improvement include scleral lenses, intracorneal ring segments, corneal allogeneic intrastromal ring segments, and deep anterior lamellar keratoplasty. Recently, novel alternative procedures, such as isolated Bowman layer transplantation, either as a corneal stromal inlay or onlay, have demonstrated encouraging outcomes. Artificial intelligence has gained acceptance for providing best practices for the diagnosis and management of KCN, and the science of its application is contentiously debated; however, it may not have been sufficiently developed. Conclusions: Early detection and advancements in screening methods using current imaging modalities have improved diagnosis of KCN. Improvement in the accuracy of current screening or diagnostic tests and comparison of their validities are achievable by well-designed, large-scale, prospective studies. The safety and effectiveness of emerging treatments for KCN are currently being investigated. There is an ongoing need for studies to track progress and evaluate clinicians' knowledge and practices in treating patients with KCN. Artificial intelligence capabilities in management approach considering the currently available imaging modalities and treatment options would best benefit the patient.

Late-onset corneal edema after customized crosslinking for progressive keratoconus.

Purpose: We describe a patient after customized crosslinking (CXL) for progressive keratoconus who developed corneal edema with spontaneous resolution. Observations: A 24-year-old male with progressive keratoconus of the left eye underwent a customized CXL procedure with a total energy of 10 J/cm2 for 16.4 minutes. Preoperative corrected distance visual acuity (CDVA) was 20/30 with a maximum keratometry (K)-value of 58.6 diopter (D) and the thinnest point measured 414 µm. The preoperative endothelial cell density (ECD) was 2414 cells/mm2. During treatment, corneal thickness was 325 µm after epithelial debridement and 375 µm after the application of 0.1 % riboflavin containing HPMC. After the treatment, antibiotic and steroid drops were prescribed for 5 days and 3 weeks, respectively. At the 1-month post-CXL visit the patient had no complaints, visual acuity and clinical examination showed no irregularities. At the 4-months post-CXL visit the patient complained of blurry vision. The CDVA was 20/100 and slit-lamp examination showed microcystic corneal edema. The corneal thickness at the thinnest point measured 440 µm. One month later the edema had resolved spontaneously and CDVA had restored to 20/25. Corneal thickness at the thinnest point measured 415 µm, the ECD was 1514 cells/mm2 and confocal microscopy showed normal structural changes in the anterior stroma after CXL, with the demarcation line located at a depth of 414 µm, just above the corneal endothelium. Conclusions and importance: We report a case of corneal edema following customized CXL with endothelial cell loss that resolved spontaneously. We recommend either adhering to a minimal stromal thickness of 400 µm before administering UV-A irradiation, using a contact lens or adjusting the irradiation to prevent this complication.

Utility of artificial intelligence in the diagnosis and management of keratoconus: a systematic review.

Introduction: The application of artificial intelligence (AI) systems in ophthalmology is rapidly expanding. Early detection and management of keratoconus is important for preventing disease progression and the need for corneal transplant. We review studies regarding the utility of AI in the diagnosis and management of keratoconus and other corneal ectasias. Methods: We conducted a systematic search for relevant original, English-language research studies in the PubMed, Web of Science, Embase, and Cochrane databases from inception to October 31, 2023, using a combination of the following keywords: artificial intelligence, deep learning, machine learning, keratoconus, and corneal ectasia. Case reports, literature reviews, conference proceedings, and editorials were excluded. We extracted the following data from each eligible study: type of AI, input used for training, output, ground truth or reference, dataset size, availability of algorithm/model, availability of dataset, and major study findings. Results: Ninety-three original research studies were included in this review, with the date of publication ranging from 1994 to 2023. The majority of studies were regarding the use of AI in detecting keratoconus or subclinical keratoconus (n=61). Among studies regarding keratoconus diagnosis, the most common inputs were corneal topography, Scheimpflug-based corneal tomography, and anterior segment-optical coherence tomography. This review also summarized 16 original research studies regarding AI-based assessment of severity and clinical features, 7 studies regarding the prediction of disease progression, and 6 studies regarding the characterization of treatment response. There were only three studies regarding the use of AI in identifying susceptibility genes involved in the etiology and pathogenesis of keratoconus. Discussion: Algorithms trained on Scheimpflug-based tomography seem promising tools for the early diagnosis of keratoconus that can be particularly applied in low-resource communities. Future studies could investigate the application of AI models trained on multimodal patient information for staging keratoconus severity and tracking disease progression.

Exome sequencing confirms the clinical diagnosis of both joubert syndrome and klinefelter syndrome with keratoconus in a han Chinese family.

Introduction: Joubert syndrome a rare genetic disorder, is characterized by abnormalities in the development of the central nervous system with "molar signs" on magnetic resonance imaging of the brain and accompanied by cerebellar vermis hypoplasia, ataxia, hypotonia, and developmental delay. Keratoconus (KC) is a kind of genetically predisposed eye disease that causes blindness characterized by a dilated thinning of the central or paracentral cornea conically projected forward, highly irregular astigmatism, and severe visual impairment. Klinefelter syndrome is caused by an extra X chromosome in the cells of male patients, and the main phenotype is tall stature and dysplasia with secondary sex characteristics. This study was intended to identify the genetic etiology and determine the clinical diagnosis of one Han Chinese family with specific clinical manifestations of keratoconus and multiorgan involvement. Methods: A comprehensive ocular and related general examination was performed on one patient and his asymptomatic parents and brother. Pathogenic genes were tested by exome sequencing. CNV-seq was used to verify the copy number variation, and peripheral blood was cultured for karyotype analysis. The pathogenicity of the identified variant was determined subject to ACMG guidelines. The Gene Expression Omnibus (GEO) dataset of keratoconus-related genes in the NCBI database was obtained to analyze the differentially expressed genes in corneal tissues of the keratoconus group and the normal control group, and analysis of protein-protein interaction networks (PPI) was performed. Results: Proband, a 25-year-old male, had sudden loss of vision in the left eye for 1 week. Best corrected visual acuity (BCVA): 0.5 (-1.00DS/-5.00DC*29°) in the right eye, counting fingers/40 cm in the left eye. Slit-lamp microscopy of the right eye showed mild anterior protrusion of the cornea and thinning of the cone-topped cornea. The left eye showed marked thinning of the central region of the cornea, rounded edema in the form of a cone-like bulge, epithelial bullae, edema and turbidity of the stroma, and bulging of the Descemet's membrane. Cranial magnetic resonance imaging (MRI) revealed changes in the midbrain and cerebellum, with a "molar sign" and a "bat-winged" ventriculus quartus cerebri. General check-up: 168 cm in height, decreased muscle tone in all four limbs, knee jerk elicited, negative Babinski sign, abdominal reflexes elicited, finger-to-nose test positive, intentional tremor evident in both hands, positive Romberg's sign, instability of gait, level I intellectual disability, poor adaptive behavior, communication disorders, teeth all dentures, a peculiar face with blepharophimosis, wide inner canthus distance, mild ptosis, severe positive epicanthus, high palatal arches, exotropia, hypotrichosis of beard and face, inconspicuous prominentia laryngea, and short upper and lower limbs. Exome sequencing detected compound heterozygous frameshift variants M1:c.9279dup:p.His3094Thrfs*18 and M2:c.6515_6522del:p.Lys2172Thrfs*37 in the patient's CPLANE1 gene and the presence of duplication-type CNV on the X chromosome. Sanger sequencing showed that the mother and father carried the M1 and M2 variants, respectively, and the younger brother carried the M2 variant, which was a novel variant. CNV-seq analysis showed the presence of a duplication-type CNV Xp22.33-Xq28 (2757837-156030895) of approximately 155 Mb on the X chromosome of the proband, which was a de novo variant and carried by neither of the parents. The two heterozygous frameshift variants and duplication-type CNV were pathogenic according to the ACMG guidelines. Differential expression analysis of keratoconus-related genes showed that CPLANE1 was upregulated in the corneal tissues of keratoconus patients compared with normal controls, and such a difference was statistically significant (p = 0.000515, <0.05). PPI analysis showed that the CPLANE1-NPHP3 complex protein acted as a bridge between cilia and extracellular matrix tissue. According to the genetic test results and clinical phenotype analysis, the family was finally diagnosed with Joubert syndrome combined with Keratoconus and Klinefelter syndrome. Discussion: In this study, we report a proband in a Han Chinese family with both Joubert syndrome and X-linked Klinefelter syndrome as well as keratoconus, and the phenotype spectrum of CPLANE1-Joubert syndrome may be expanded accordingly. Meanwhile, the significance of exome sequencing was emphasized in aiding the clinical diagnosis of complex cases, which is difficult to make.

Quality of life and vision assessment with scleral lenses in keratoconus.

PURPOSE: The purpose of the study is to evaluate the visual outcomes and improvement in quality of life (QOL) of patients with keratoconus with scleral lenses. METHODS: In this prospective study, 14 patients (28 eyes) with bilateral keratoconus were fitted with scleral lenses (McAsfeer 16.00 mm) in Pune city, Maharashtra, India. Uncorrected visual acuity (VA), best spectacle-corrected VA, and VA with scleral lenses were evaluated. The patients were given the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) for judging the QOL, before and after using scleral lenses for 3 months. RESULTS: The mean uncorrected VA of the 14 patients with a mean age of 28.64 ± 6.57 years was 1.18 ± 0.19 logMAR. Best spectacle-corrected high-contrast VA improved from 0.47 ± 0.25 logMAR to 0.03 ± 0.07 logMAR with scleral lenses (P < 0.001). Best spectacle-corrected low-contrast VA improved from 0.68 ± 0.22 logMAR to 00.47 ± 0.10 logMAR with scleral lenses (P < 0.001). Along with the increase in overall median scores on the NEI VFQ-25 from 1735 to 2930 points (P < 0.001), the distance and near activities (P < 0.001), vision-specific mental health (P < 0.002), social functioning (P < 0.004), and driving (P < 0.005) improved after using scleral lenses for 3 months. CONCLUSION: Scleral lenses can be an effective and safe management option for patients with keratoconus leading to an improved vision and QOL.

Diagnosis of forme fruste keratoconus with scheimpflug photography in Ghanaian patients.

AIM: This study aimed to differentiate moderate to high myopic astigmatism from forme fruste keratoconus using Pentacam parameters and develop a predictive model for early keratoconus detection. METHODS: We retrospectively analysed 196 eyes from 105 patients and compared Pentacam variables between myopic astigmatism (156 eyes) and forme fruste keratoconus (40 eyes) groups. Receiver operating characteristic curve analysis was used to determine the optimal cut-off values, and a logistic regression model was used to refine the diagnostic accuracy. RESULTS: Statistically significant differences were observed in most Pentacam variables between the groups (p < 0.05). Parameters such as the Index of Surface Variance (ISV), Keratoconus Index (KI), Belin/Ambrosio Deviation Display (BAD_D) and Back Elevation of the Thinnest Corneal Locale (B.Ele.Th) demonstrated promising discriminatory abilities, with BAD_D exhibiting the highest Area under the Curve. The logistic regression model achieved high sensitivity (92.5%), specificity (96.8%), accuracy (95.9%), and positive predictive value (88.1%). CONCLUSION: The simultaneous evaluation of BAD_D, ISV, B.Ele.Th, and KI aids in identifying forme fruste keratoconus cases. Optimal cut-off points demonstrate acceptable sensitivity and specificity, emphasizing their clinical utility pending further refinement and validation across diverse demographics.

Detecting early changes in choroidal vascularity and thickness using optical coherence tomography in patients with corneal crosslinking for keratoconus.

AIM: To investigate changes in choroidal thickness and vascularity in keratoconus patients treated with corneal crosslinking. METHODS: This study evaluated 28 eyes of 22 patients with keratoconus who underwent corneal crosslinking. The choroidal thicknesses were evaluated on enhanced depth imaging optical coherence tomography at the preoperative and postoperative 3d, 1, and 3mo. Choroidal thickness in the four cardinal quadrants and the fovea were evaluated. The choroidal vascularity index was also calculated. RESULTS: There was no significant difference in central choroidal thickness between the preoperative and postoperative 3d, 1mo (P>0.05). There was a significant increase in the 3mo (P=0.034) and a significant decrease in the horizontal choroidal vascularity index on the postoperative 3d (P=0.014), there was no statistically significant change in vertical axes and other visits in horizontal sections (P>0.05). CONCLUSION: This study sheds light on choroidal changes in postoperative corneal crosslinking for keratoconus. While it suggests the procedure's relative safety for submacular choroid, more extensive research is necessary to confirm these findings and their clinical significance.

Insights into atypical segmental layer thicknesses and phase retardation in thick corneas using ultrahigh-resolution polarization-sensitive optical coherence tomography.

BACKGROUND: Accurately assessing corneal structural status is challenging when thickness deviates from the average. Polarization-sensitive optical coherence tomography (PS-OCT) measures tissue-specific polarization changes, providing additional contrast for accurate segmentations and aids in phase retardation (PR) measurements. Previous studies have shown PR's effectiveness in identifying sub-clinical keratoconus (KC) in asymmetric cases. Thus, this study aims to assess PR distribution in thick corneas with and without KC. METHODS: In this retrospective and cross-sectional study, 45 thick corneas from 30 Asian-Indian subjects, categorized into healthy (n = 26) and KC (n = 19) groups were analyzed. All eyes underwent standard clinical evaluations, tomographic assessments, and corneal biomechanics measurements. PR and individual layer thicknesses were measured using custom-designed ultrahigh-resolution PS-OCT. PR en-face maps were generated. Individual layer thicknesses and PR analysis was conducted across multiple zones, extending up to 8-10 mm in diameter. All eyes in the study had not undergone interventions, received topical medications, or had previous corneal disease history. RESULTS: Significant differences were found in spherical and cylindrical powers, keratometry, pachymetry, and biomechanical indices (all P < 0.01). Thickness profiles from PS-OCT showed significant differences in the 4-8 mm zones only. Bowman's layer thickness significantly differed only in the central 2 mm zone (P = 0.02). The median PR values showed marginal differences in the central 2 mm zone (P = 0.0565). Additionally, there were significant differences observed in the 2-4 mm and 4-6 mm zones (P = 0.0274 and P = 0.0456, respectively). KC eyes exhibited an atypical PR distribution and corneal thinning, while normal eyes maintained a uniform Bowman's layer thickness and PR maps with larger areas of higher PR. CONCLUSION: The study revealed distinctive PR distribution in thick corneas among healthy and KC groups. Using an ultrahigh-resolution PS-OCT the significance of Bowman's layer thickness in these groups was also emphasized. The study offered potential improvements in clinical diagnostics by enhancing our understanding of corneal structure and its altered function.

Simultaneous Muraine Sutures and Excimer Laser-Assisted Penetrating Keratoplasty for Acute Keratoconus.

Background: Acute keratoconus (acute KC), which affects approximately 1.6-2.8% of keratoconus (KC) patients, is a pathological condition of the cornea characterized by stromal edema due to entry of aqueous humor through a tear in Descemet's membrane. Methods: We present a novel combination of surgical procedures that allows swifter visual recovery in a consecutive, retrospective case series. The new surgical procedure for acute KC consists of a combination of Muraine corneal sutures to smooth the corneal curvature and Excimer laser-assisted penetrating keratoplasty and was performed in six acute KC patients from 2019 to 2022 at the Department of Ophthalmology, University Hospital of Martin-Luther-University Halle-Wittenberg (UMH), Germany. We monitored data on preoperative status, operative details, intraoperative and postoperative complications and visual outcomes were analyzed. Results: The mean age was 41.5 ± 13.5 years (3 OD, 3 OS). Neurodermatitis was present in 3 patients (50%). All patients received significant visual benefits from the procedure. Preoperative BCVA was hand motion (logMAR 3.0) in all patients; postoperatively, BCVA improved significantly logMAR 0.03 ± 0.09 [range: 0.2-0.4; p < 0.001, FUP 20+/-10 months). Visual acuity remained stable throughout the roughly biannual follow-ups. One patient developed endothelial graft rejection after 2 years. During the last examination, all eyes had clear grafts and stable curvatures, K1 and K2 being 42.43 ± 4.17 D and 44.95 ± 4.07 D, respectively, and mean corneal astigmatism was 2.61 ± 1.74 D. The thinnest corneal thickness was 519 ± 31 µm. A graft size of 8.0 × 8.1 mm was the most beneficial. Conclusions: in patients with acute KC and hydrops, a penetrating keratoplasty with Muraine corneal sutures is successful in terms of graft clarity and visual outcome. Combining the procedures allows quicker visual recovery. Patients with a history of neurodermatitis should have preoperative and postoperative dermatologic treatment and close follow-up for possible complications.