Evaluation of perioperative pachymetry of thin corneas during corneal crosslinking using hypo-osmolar riboflavin and hydroxypropyl methylcellulose

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

Inflammatory and genomic interactions within keratoconus susceptible patients: a nationwide registered case-control study.

PURPOSE: This study aimed to investigate the association between variants in the interleukin (IL)-1 gene cluster and susceptibility to keratoconus (KC) in an Iranian population. METHODS: In the case group, there were 188 KC patients diagnosed by clinical findings and corneal tomography. The control group included all 205 healthy controls with no personal or family history of eye-related, metabolic, or immune system-related disease. Using the standard salting out extraction procedure, genomic DNA was isolated from peripheral blood leukocytes. The genotypes were determined by applying agarose gel electrophoresis for the IL-1RN 86 bp VNTR and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for rs16944 and rs1143634. RESULTS: The results showed a significant association between the IL-1ß rs1143634 (rs1143634 T allele, P = 0.008) and IL-1RN 86 bp VNTR polymorphisms (LL and LS genotype, P = 0.048 and 0.012 respectively) and susceptibility to KC in the Iranian population. The genotype distributions of rs1143634 (P = 0.004) and rs2234663 (P = 0.042) significantly differed between case and control groups, with certain genotypes demonstrating a protective effect against KC. Logistic regression analysis revealed a protective effect of the IL-1RN L allele [odds ratio (OR) = 0.367, 95% confidence interval (CI): 0.240-0.562; P = 0.000] and certain haplotypes (OR = 0.628, 95% CI: 0.447-0.884; P = 0.007) against KC. However, no significant association was found for the IL-1ß rs16944 polymorphism. CONCLUSION: This study provides evidence for an association between variants in the IL-1 gene cluster and susceptibility to KC in an Iranian population. Further research on larger and more diverse populations is warranted to validate these findings and explore the underlying mechanisms involved.

The development of a machine learning model to train junior ophthalmologists in diagnosing the pre-clinical keratoconus.

Purpose: This study aims to evaluate the diagnostic performance of a machine learning model (ML model) to train junior ophthalmologists in detecting preclinical keratoconus (PKC). Methods: A total of 1,334 corneal topography images (The Pentacam HR system) from 413 keratoconus eyes, 32 PKC eyes and 222 normal eyes were collected. Five junior ophthalmologists were trained and annotated the images with or without the suggestions proposed by the ML model. The diagnostic performance of PKC was evaluated among three groups: junior ophthalmologist group (control group), ML model group and ML model-training junior ophthalmologist group (test group). Results: The accuracy of the ML model between the eyes of patients with KC and NEs in all three clinics (99% accuracy, area under the receiver operating characteristic (ROC) curve AUC of 1.00, 99% sensitivity, 99% specificity) was higher than that for Belin-Ambrósio enhanced ectasia display total deviation (BAD-D) (86% accuracy, AUC of 0.97, 97% sensitivity, 69% specificity). The accuracy of the ML model between eyes with PKC and NEs in all three clinics (98% accuracy, AUC of 0.96, 98% sensitivity, 98% specificity) was higher than that of BAD-D (69% accuracy, AUC of 0.73, 67% sensitivity, 69% specificity). The diagnostic accuracy of PKC was 47.5% (95%CI, 0.5-71.6%), 100% (95%CI, 100-100%) and 94.4% (95%CI, 14.7-94.7%) in the control group, ML model group and test group. With the assistance of the proposed ML model, the diagnostic accuracy of junior ophthalmologists improved with statistical significance (p < 0.05). According to the questionnaire of all the junior ophthalmologists, the average score was 4 (total 5) regarding to the comprehensiveness that the AI model has been in their keratoconus diagnosis learning; the average score was 4.4 (total 5) regarding to the convenience that the AI model has been in their keratoconus diagnosis learning. Conclusion: The proposed ML model provided a novel approach for the detection of PKC with high diagnostic accuracy and assisted to improve the performance of junior ophthalmologists, resulting especially in reducing the risk of missed diagnoses.

Associations between endothelial cell characteristics and corneal topography findings in different stages of keratoconus.

PURPOSE: This study aimed to compare and correlate specular microscope indices and corneal topography indices in different stages of keratoconus. METHODS: Two hundred forty-six eyes of 123 participants were enrolled in the study. Corneal topography was performed using Sirius (CSO, Italy), with a rotating Scheimpflug camera and a Placido disc topographer. Corneal endothelial cell indices were assessed using a specular microscope (Nidek CEM-530, Japan). Eyes were graded as keratoconus stages 0-4 according to the Amsler-Krumeich classification. Corneal topography and endothelial cell indices were compared among the groups, and the correlations between them were analyzed. RESULTS: The mean age of the patients was 23.26 ± 6.75 years (range, 14-47 years). Forty-eight cases were male (39%) and 75 were female (61%). There were no statistically significant age (p = 0.578) or sex ratio (p = 0.529) differences between the groups. Twenty-nine eyes were included in the control group (11.78%), while 41 (16.67%) had stage 1 keratoconus, 88 (35.77%) had stage 2, and 88 (35.77%) had stage 3. Measurement was not possible in stage 4 keratoconus. No statistically significant difference was determined in specular microscopy values according to the stage of keratoconus, except for the number of analyzed cells (NUM) (p > 0.05). The lowest NUM values were observed in stages 1, 2, and 3, with values of 184.34 ± 67.62 cells/mm2, 155.07 ± 59.48 cells/mm2, and 127.06 ± 64.39 cells/mm2, respectively (p = 0.001). In the keratoconus group, weak statistically significant negative correlations were observed between NUM and SimK1, SimK2, KVf, BCVf, KVb, and BCVb, while a weak positive correlation was noted between NUM and central corneal thickness (p < 0.05). CONCLUSIONS: NUM seems to decrease, while endothelial cell density exhibits no significant changes, with the progression of keratoconus. It appears that as keratoconus index values increase, NUM may decrease in different stages of keratoconus.

Influence of different parameters on the corneal asphericity (Q value) assessed with progress in biomedical optics and imaging - A review.

The corneal eye diseases such as Keratoconus cause weakening of the cornea, with this disease the cornea can change in shape. This condition affects between 1 in 3,000 to 1 in 10,000 people. The main reason for the development of such conditions is unknown and can have significant impacts. Over the last decade, with advancements in computerized corneal topography assessments, researchers have increasingly expressed interest in corneal topography for research as well as clinical activities. Up till now, several aspheric numerical models have been developed as well as proposed to define the complex shape of the cornea. A commonly used term for characterizing the asphericity in an eye is the Q value, a common indicator of the aspherical degree of the cornea. It is one of the critical parameters in the mathematical description model of the cornea as it represents the cornea's shape and the eye's characteristics. Due to the utmost importance of this Q value of the cornea, a couple of studies have attempted to explore this parameter and its distribution, merely in terms of its influence on the human eye's optical properties. The corneal Q value is an important factor that needs to be determined to treat for any refractive errors as corneal degeneration are disease that can lead to potential problems with the structure of the cornea. This study aims to highlight the need to understand Q value of the cornea as this can essentially assist with personalising corneal refractive surgeries and implantation of intraocular lenses. Therefore, the relevance of corneal Q value must be studied in association with different patients, especially ones who have been diagnosed with cataracts, brain tumours, or even COVID-19. To address this issue, this paper first carries out a literature review on the optics of the cornea, the relevance of corneal Q value in ophthalmic practice and studies corneal degenerations and its causes. Thereafter, a detailed review of several noteworthy relevant research studies examining the Q value of the cornea is performed. To do so, an elaborate database is created, which presents a list of different research works examined in this study and provides key evidence derived from these studies. This includes listing details on the age, gender, ethnicity of the eyes assessed, the control variables, the technology used in the study, and even more. The database also delivers important findings and conclusions noted in each study assessed. Next, this paper analyses and discusses the magnitude of corneal Q value in various scenarios and the influence of different parameters on corneal Q value. To design visual optical products as well as to enhance the understanding of the optical properties of an eye, future studies could consider the database and work presented in this study as useful references. In addition, the work can be used to make informed decisions in clinical practice for designing visual optical products as well as to enhance the understanding of the optical properties of an Eye.

Corneal higher-order aberrations in different types of irregular cornea.

OBJETIVE: To assess differences in corneal higher-order aberrations (i.e., HOAs) between six different types of irregular corneas (i.e, keratoconus (KC), keratoglobus (KG), pellucid marginal degeneration (PMD), laser-assisted in situ keratomileusis (LASIK), penetrating keratoplasty (PK), and intrastromal corneal ring segments (ICRS)). METHODS: Corneal aberration data from the 3rd and 4th order together with secondary vertical and horizontal coma, and secondary spherical aberration were retrospectively retrieved from a corneal tomographer and compared between irregular cornea types and for 3-, 5-, and 7-mm pupil diameters. RESULTS: Significant differences were observed in vertical coma, oblique trefoil, secondary oblique astigmatism, primary spherical, and secondary spherical between irregular cornea types across all three pupil sizes (all p≤0.025). Vertical coma consistently exhibited the greatest magnitude of HOA across all irregular cornea types and pupil diameters. For the larger pupil diameters (5 and 7 mm), the 3rd order aberrations (mainly coma-like), the 4th order aberrations (mainly spherical-like), and total HOA RMS were significantly lower in the LASIK group compared to all other irregular cornea types (all p≤0.003). Additionally, at pupil sizes of 5 and 7 mm, the 3rd, 4th, coma-like, spherical-like, and total HOA RMS were significantly lower in KC compared to the ICRS and PK groups (all p≤0.01). Furthermore, the 4th, spherical-like, and total HOA RMS were significantly lower in KC compared to KG at pupil diameters of 3 and 7 mm, 5 and 7 mm, and 7 mm, respectively (all p≤0.03). CONCLUSIONS: Vertical coma was the most elevated HOA across all irregular cornea types and pupil diameters. Corneal aberrations were lower in LASIK and KC, and higher in KG and PK.

Static magnetic field effects on the secondary structure and elasticity of collagen molecules; a possible biophysical approach to treat keratoconus.

Type I collagen is among the major extracellular proteins that play a significant role in the maintenance of the cornea's structural integrity and is essential in cell adhesion, differentiation, growth, and integrity. Here, we investigated the effect of 300 mT Static Magnetic Field (300 mT SMF) on the structure and molecular properties of acid-solubilized collagens (ASC) isolated from the rat tail tendon. The SMF effects at molecular and atomic levels were investigated by various biophysical approaches like Circular Dichroism Spectropolarimetery (CD), Fourier Transform Infrared Spectroscopy (FTIR), Zetasizer light Scattering, and Rheological assay. Exposure of isolated type I collagen to 300 mT SMF retained its triple helix. The elasticity of collagen molecules and the keratoconus (KCN) cornea treated with SMF decreased significantly after 5 min and slightly after 10, 15, and 20 min of treatments. The exposure to 300 mT SMF shifted the Amid I bond random coil to antiparallel wave number from 1647 to 1631 cm-1. The pH of the 300 mT SMF treated collagen solution increased by about 25 %. The treatment of the KCN corneas with 300 mT SMF decreased their elasticity significantly. The promising results of the effects of 300 mT SMF on the collagen molecules and KCN cornea propose a novel biophysical approach capable of manipulating the collagen's elasticity, surface charges, electrostatic interactions, cross binding, network formation and fine structure. Therefore, SMF treatment may be considered as a novel non-invasive, direct, non-chemical and fast therapeutic and manipulative means to treat KCN cornea where the deviated physico-chemical status of collagen molecules cause deformation.

Prediction model for treatment outcomes 3 years after corneal cross-linking for keratoconus.

PURPOSE: This study aimed to identify preoperative factors that predict visual acuity and Kmax 3 years after corneal cross-linking (CXL) in patients with keratoconus (KC), and to develop a prediction model. METHODS: We enrolled 68 patients with KC and followed up on 100 eyes that received CXL for at least 3 years. Preoperative data, including age, UDVA, CDVA, cylinder, SE, and the parameters of tomography including Kmax were collected as predictors. The primary outcomes were changes in CDVA (Delta CDVA) and Kmax (Delta Kmax) postoperatively. Univariate and multivariate linear regression were used to identify the correlation between the primary outcomes and predictors and establish prediction models. RESULTS: Both CDVA and Kmax remained stable from baseline to 3 years after CXL: from 0.25 ± 0.18 to 0.22 ± 0.20 (P = 0.308) and from 58.70 ± 9.52 D to 57.02 ± 8.83 D (P = 0.187), respectively. Multivariate analysis showed that worse preoperative CDVA (ß coefficient - 0.668, P < 0.001) and lower preoperative Kmean (ß coefficient 0.018,P < 0.001) were associated with greater improvement in CDVA after CXL. A smaller preoperative eccentricity (ß coefficient 8.896, P = 0.01) and a higher preoperative Kmean (ß coefficient - 1.264, P < 0.001) predicted a more flattening of postoperative Kmax. The prediction model for CDVA (R2 = 0.43) and Kmax (R2 = 0.37) could accurately estimate treatment outcomes. CONCLUSIONS: CXL is highly effective in halting or preventing further progression of KC. The preoperative factors CDVA and Kmean were able to predict visual acuity changes 3 years after CXL. And preoperative eccentricity and Kmean could predict Kmax changes 3 years after CXL.

Multi-dataset identification of innovative feature genes and molecular mechanisms in keratoconus.

This study aimed to identify feature genes and explore the molecular mechanisms of keratoconus (KC). We downloaded data files from NCBI GEO public database. The Limma package was used for differential expression analysis of gene profiles. Lasso regression was used to identify the feature genes. The CIBERSORT algorithm was used to infer the proportion of immune-infiltrating cells and analyse the correlation between gene expression levels and immune cells. Related transcription factors and miRNAs of key genes were predicted using the Cistrome DB and Mircode databases. Analysis of expression differences in disease genes was based on the GeneCards database. The CMap was used to analyse targeted therapeutic drugs. IHC was performed to verify the expression levels of ATOH7 and MYRF in corneas. Exactly 593 upregulated and 473 downregulated genes were identified. Lasso regression analysis identified ATOH7, DBNDD1, RNF217-AS1, ARL11, MYRF and SNORA74B as feature genes for KC. All key genes were correlated with immune infiltration and the levels of activated memory CD4+ T cells and plasma cells were significantly increased. miRNA, IRF and STAT families were correlated to feature genes. The expression levels of key genes were significantly correlated to KC-related genes. Entinostat, ochratoxin-a, diphencyprone and GSK-3-inhibitor-II were predicted as potential KC medications. The expression of MYRF was significantly higher in the KC samples, contrary to the expression of ATOH7. KC is related to both immune infiltration and genetic factors. MYRF and ATOH7 were newly identified and verified feature genes of KC.

Trio-based whole-exome sequencing of 200 Chinese patients with keratoconus.

Keratoconus (KC) is a complex corneal disorder with a well-recognized genetic component. In this study, we aimed to expand the genetic spectrum of 200 Chinese patients with keratoconus and their unaffected parents. Trio-based whole-exome sequencing was performed in 200 patients with sporadic keratoconus and their unaffected parents. The variants identified in candidate genes for keratoconus were analyzed using multiple bioinformatics tools. Finally, we identified 7 variants in 5 candidate genes for keratoconus in 5 patients. The c.T464C variant in the IMPDH1 gene was defined as likely pathogenic according to the guidelines of the American College of Medical Genetics and Genomics, and the remaining variants in candidate genes (TRANK1, SLC4A11, CERKL, IFT172) were defined as uncertain significance. Our results expand the genetic spectrum in KC, highlight the genetic heterogeneity of this disease and provide important clues for future functional validation.

Risk Factors for Glaucoma and Ocular Hypertension and Post-Transplant Complications in Keratoconus: A Multivariable Analysis.

Background: The purpose of this study was to investigate the risk factors for glaucoma in patients with keratoconus following keratoplasty and to identify potential factors that could affect post-transplant complications. Methods: A retrospective analysis was conducted on the medical records of 192 keratoconus patients who underwent keratoplasty. Data on treatment history, perioperative information, tissue bank data, postoperative regimens, complications, and infections were collected and analyzed. Statistical analysis was performed to identify risk factors associated with glaucoma and transplant complications. Results: There was a 41.6% incidence of glaucoma (high IOP) (p < 0.001), with the median time to glaucoma development being 314 ± 67 days post-transplant. A significant number of patients required surgical intervention, accounting for 48.05%. Our analysis revealed a 14% graft failure rate. On univariable Cox proportional hazard analysis, the following factors demonstrated statistically significant associations with the risk of glaucoma after transplantation: donor endothelial cell density, the use of a single continuous suture type, and the surgeon (performing the surgery). For many variables, the only factor that remained significant was the surgeon. Among the factors analyzed for risks of failure post-transplantation, significant associations were observed for the donor age, the time from harvest to transplant, and the surgeon. In the multivariable analysis, donor age emerged as a significant predictor of post-transplant complications. Conclusions: Risk factors such as donor endothelial cell density, suture type, surgeon, host and donor size, and host gender were found to increase the risk of developing glaucoma post-keratoplasty. Surgeon type was identified as a significant risk factor, while donor age was predictive of post-transplant complications.

Challenging corneal diseases and miRNA expression: Focus on rare diseases and new therapeutic frontiers.

MicroRNAs (miRNAs) function as posttranscriptional regulators of gene expression by targeting specific messenger RNA (mRNA). This interaction modulates mRNA stability or translational efficiency, ultimately impacting the level of protein production. Emerging evidence suggests that miRNAs act as critical regulators in corneal diseases. These molecules finetune key processes like cell proliferation, differentiation, inflammation, and wound healing. We reviewed the literature to understand the role that miRNAs may play in the development of challenging and poorly understood corneal diseases. We focused on including vernal keratoconjunctivitis, neurotrophic keratitis, keratoconus, Fuchs endothelial corneal dystrophy, and limbal stem cell deficiency. Furthermore, we explored currently studied agonists or antagonists of miRNAs that share similar pathways with ocular diseases and could be employed in ophthalmology in the future. The distinct miRNA expression profiles observed in different ocular surface pathologies, combined with the remarkable stability and relatively easy access of miRNAs sampling in biofluids, present possibilities for the development of non-invasive and highly accurate diagnostic tools. Furthermore, comprehending miRNA's pathophysiological role could open new frontiers to a more comprehensive understanding of the pathophysiology underlying ocular surface diseases, thereby paving the way for the creation of novel therapeutic strategies.

CYR61/CCN1: A novel mediator of redox response in corneal stromal cells of keratoconus.

Keratoconus (KC) is a progressive, multifactorial and ectatic corneal disorder that characterized by steepening thinning of the cornea. It was previously demonstrated that oxidative stress has a strong link with KC progression. However, the molecular mechanism underlying oxidative stress response in KC remains unclear. Hence, the present study analyzed the heterogeneity of response of corneal stromal cells (CSCs) to oxidative stress in order to further illustrate how oxidative shape the pathophysiology of KC. Single-cell transcriptomics analysis revealed that CSCs demonstrated significant higher oxidative stress score in the KC group compared to the Ctrl group. The expression of oxidative markers verified by experiments illustrated elevated oxidative stress levels and insufficient antioxidant levels in CSCs of KC. In further single-cell transcriptomics analysis, we identified CYR61 to distinguish different subgroups of CSCs responding to oxidative stress. The cornea stroma cells in KC could be differentiated into CYR61high cells and CYR61low cells. Of note, the CYR61high cells showed lower score in collagen production process and higher score in collagen catabolic process. Further experiments illustrated that CYR61 was elevated in KC and associated with collagen production.

Assessment of OCT and Angio-OCT Parameters in Keratoconus Patients with and without Penetrating Keratoplasty.

Background/Objectives: Keratoconus (KC) is a bilateral eye disease characterized by corneal thinning and cone-like deformation, leading to visual impairment. This study evaluated the radial peripapillary capillaries (RPCs) in keratoconus patients with and without penetrating keratoplasty (PKP) using OCT and angio-OCT, comparing the results to a control group. Methods: This retrospective study included 149 eyes, 97 from patients who underwent PKP between January 2018 and February 2023 and 52 from patients who did not undergo PKP. The control group comprised 72 patients (144 eyes) who were healthy volunteers. Measurements included the best corrected visual acuity (BCVA), the intraocular pressure (IOP), slit-lamp biomicroscopy, a fundus examination, and corneal topography, as well as OCT and angio-OCT assessments of the RPCs, retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), and central retinal thickness (CRT). Statistical analyses were performed using Student's t-test and Pearson's correlation coefficient. Results: The RNFL was significantly thinner in KC eyes after PKP compared to control eyes (p < 0.001), and the CRT was significantly thicker in KC eyes after PKP compared to control eyes (p = 0.003). However, the GCC was similar across the groups (p = 0.0885). Additionally, RPCs inside the disc were significantly reduced in KC eyes after PKP compared to control eyes (p < 0.0001). A significant positive correlation was found between RPC whole vessel density and RNFL thickness as measured via angio-OCT (r = 0.308, p < 0.0001). Conclusions: This study found that the RPC density inside the disc is significantly reduced in keratoconus patients after penetrating keratoplasty, highlighting RPCs inside the disc as a potential diagnostic tool for further assessment of keratoconus.

Neural adaptation to the eye's optics through phase compensation.

How does the brain achieve a seemingly veridical and 'in-focus' perception of the world, knowing how severely corrupted visual information is by the eye's optics? Optical blur degrades retinal image quality by reducing the contrast and disrupting the phase of transmitted signals. Neural adaptation can attenuate the impact of blur on image contrast, yet vision rather relies on perceptually-relevant information contained within the phase structure of natural images. Here we show that neural adaptation can compensate for the impact of optical aberrations on phase congruency. We used adaptive optics to fully control optical factors and test the impact of specific optical aberrations on the perceived phase of compound gratings. We assessed blur-induced changes in perceived phase over three distinct exposure spans. Under brief blur exposure, perceived phase shifts matched optical theory predictions. During short-term (~1h) exposure, we found a reduction in blur-induced phase shifts over time, followed by after-effects in the opposite direction-a hallmark of adaptation. Finally, patients with chronic exposure to poor optical quality showed altered phase perception when tested under fully-corrected optical quality, suggesting long-term neural compensatory adjustments to phase spectra. These findings reveal that neural adaptation to optical aberrations compensates for alterations in phase congruency, helping restore perceptual quality over time.

Scheimpflug Tomographic Indices for Classifying Normal, Down Syndrome and Clinical Keratoconus in Pediatric Patients.

The study aimed to evaluate the precision of different Pentacam indices in diagnosing keratoconus (KC) in pediatric patients with and without Down Syndrome (DS) and determine suitable cutoff values. This prospective multicenter cross-sectional study evaluated 216 eyes of 131 patients aged 6-18 years (mean age 12.5 ± 3.2 years) using Pentacam. Patients were categorized into four groups: KC, forme fruste keratoconus (FK), DS, and control, excluding DS patients with topographic KC. Receiver operating characteristic curves were generated to determine the optimal cutoff points and compare the accuracy in identifying KC and FK in patients with and without DS. In DS patients, corneal morphology resembled KC features. The most effective indices for distinguishing KC in DS patients were the average pachymetric progression index (AUC = 0.961), higher-order aberration of the anterior cornea (AUC = 0.953), anterior elevation (AUC = 0.946), posterior elevation (AUC = 0.947), index of vertical asymmetry (AUC = 0.943), and Belin/Ambrosio enhanced ectasia total derivation value (AUC = 0.941). None of the indices showed good accuracy for distinguishing FK in DS patients. The thresholds of these indices differed significantly from non-DS patients. The results highlighted the need for DS-specific cutoff values to avoid false-positive or false-negative diagnoses in this population.

Corneal Cross-Linking for Pediatric Keratoconus.

AIM: The aim of this study was to evaluate corneal cross-linking (CXL) for keratoconus in pediatric patients. MATERIALS AND METHODS: After keratometric qualification according to the Amsler-Krumeich system, corneal collagen cross-linking was performed using ultraviolet light and photosensitizing riboflavin drops in 111 eyes of 74 children with a mean age of 15 ± 1.67 years. None of the children studied wore contact lenses before the procedure. Visual acuity, intraocular pressure, keratometry, and pachymetry parameters were analyzed before and after corneal cross-linking. RESULTS: Visual acuity was 0.64 ± 0.31 and 0.66 ± 0.29 before CXL and at the end of the follow-up, respectively; the difference was not statistically significant. The mean intraocular pressure before CXL was 14.48 ± 3.13 mmHg, while the mean value at the end of the follow-up was 14.23 ± 3.03 mmHg; no statistically significant difference was found. Pre- and post-CXL astigmatism was 3.98 ± 2.34 Dcyl and 3.63 ± 1.86 Dcyl, respectively; the difference was not statistically significant. The mean keratometry before CXL was 47.99 ± 3.96 D; the mean post-follow-up value was 47.74 ± 3.63 D. The mean corneal thickness (pachymetry) at the apex of the keratoconus-the thinnest zone of the cornea-before CXL was 492.16 ± 38.75 µm, while the mean value at the end of the follow-up was 479.99 ± 39.71 µm; the difference was statistically significant. CONCLUSIONS: Corneal cross-linking is an effective method for preventing keratoconus progression in children. However, further and detailed ophthalmic follow-up of patients who underwent CXL before the age of 18 is highly advisable.

A genetic investigation in five Chinese families with keratoconus.

Background: This study investigated the genetic characteristics of five Chinese families with keratoconus (KC). Methods: In the five families affected by KC, medical records, clinical observations, and blood samples were collected from all individuals. All KC family members (n = 20) underwent both whole exome sequencing of genomic DNA and Sanger sequencing to confirm the variants. Online software was utilized to analyze all variants, and the online server I-TASSER was employed for in silico predictions of the three-dimensional protein structures of the variants. The newly discovered variants and single nucleotide polymorphisms were further examined in 322 sporadic KC patients. Results: The Pentacam tomographic composite index in those affected first-degree family members of the probands showed a pathological change. Five new variants were detected in the five probands and other affected members in their families: a heterozygous missense variant g.19043832C>T (p.Ser145Asn) in the homer scaffolding protein 3 (HOMER3) gene; a heterozygous missense variant g.99452113G>A (p.Gly483Arg) in the insulin-like growth factor 1 receptor (IGF1R) gene; a heterozygous missense variant g.55118280G>T (p.Trp843Leu) in the echinoderm microtubule-associated protein like 6 (EML6) gene; a heterozygous frameshift variant c. 1226_1227del (p.Gln410Glufs*17) in the DOP1 leucine zipper-like protein B (DOP1B) gene; and a heterozygous splice-site variant c.7776+2T>A in the neurobeachin-like protein 2 (NBEAL2) gene. These variations were predicted to be potentially pathogenic and associated with KC. Conclusion: Five novel variants in HOMER3, IGF1R, EML6, DOP1B, and NBEAL2 genes were identified in this study and may be associated with the pathogenesis of KC. This study provides new information about the gene variants and their protein changes in KC patients. The findings should be explored further and could potentially be applied to the early diagnosis of KC before clinical onset.

Mendelian randomization analysis does not reveal a causal influence between keratoconus and three major mental disorders.

Background: Observational studies have suggested at a possible link between keratoconus (KC) and various mental disorders, but the exact direction of causation in these associations remains unclear. This study aims to investigate the potential causal link between KC and three prominent mental conditions: Anxiety, Depression, and Schizophrenia. Methods: Using instrumental variables identified from Genome-wide association study (GWAS) data of European individuals, we conducted bidirectional two-sample Mendelian Randomization (MR) analyses to explore potential causal relationships between KC and the three major mental disorders. We primarily employed the Inverse-Variance Weighted (IVW) method to evaluate causality. In addition, we performed four supplementary MR methods (MR-Egger, Weighted Median, Simple Mode, and Weighted Mode). Furthermore, we conducted various sensitivity analyses to assess heterogeneity, horizontal pleiotropy, and result stability. Results: Our findings did not reveal any concrete evidence of a causal link between KC and the three major mental disorders, namely anxiety, depression, and schizophrenia [anxiety: odds ratio (OR)=0.997, 95% confidence interval (CI)=0.988-1.008, p = 0.621; depression: OR=1.008, 95% CI=0.999-1.017, p = 0.084; schizophrenia: OR=1.002, 95% CI= 0.984-1.020, p = 0.840]. Similarly, the three major mental disorders were not caustically associated with KC [anxiety: OR=1.014, 95% CI=0.635-1.620, p = 0.953; depression: OR=1.109, 95% CI= 0.749-1.643, p = 0.604; schizophrenia: OR= 0.969, 95% CI= 0.884-1.062, p = 0.497]. The sensitivity analyses indicated that the results remained robust, with no signs of pleiotropy or heterogeneity. Conclusions: Our study does not support a genetically determined significant causal connection between KC and the three major mental disorders. The increased occurrence of mental disorders observed in KC patients in observational reports likely arises from factors that can be modified. Further research is warranted to unveil the underlying mechanisms behind the associations observed in observational studies.

Clinical Outcomes of Iris-Supported Phakic Toric Intraocular Lenses in Corneal Ectasia.

INTRODUCTION: Our aim was to evaluate the visual and refractive outcomes of iris-fixated phakic toric intraocular lenses (IOLs) for visual rehabilitation in eyes with stable corneal ectasia. METHODS: We conducted a study looking at the clinical outcomes of iris-fixated toric IOLs (Artisan) in 33 eyes of 27 patients diagnosed with mild-to-moderate corneal ectasia at a single center (Queen Victoria Hospital, East Grinstead, UK). The main outcome measures were functional improvement [accuracy of post-operative spherical equivalent (SE), astigmatic correction, topographic parameters, uncorrected and corrected distance visual acuity (UCVA, CDVA)] and safety of the procedure: endothelial cell count and intra- and post-operative complications. RESULTS: Eighteen males and nine females of mean age 38.85 were included in the study with a mean follow-up of 18 months. All patients had ectasia due to keratoconus except one with post-refractive laser ectasia. Twelve patients had crosslinking, eight had intracorneal rings, and eight had previous keratoplasties. Mean pre-operative logMAR UCVA was 0.75 ± 0.35 improving to 0.02 ± 0.17 (p = 0.000). Mean pre-operative logMAR CDVA was 0.16 ± 0.17 improving to 0.02 ± 0.17 (p = 0.000). Mean pre-operative (SE) was - 3.5 ± 3.9 improving to - 2.75 ± 1.39 (p = 0.000) with up to 36-42 months of follow-up. The mean value of endothelial cell density in the overall sample was 2252.54 ± 473.24 cells/mm2 pre-operatively and 2126.75 ± 365.21 cells/mm2 at 24-36 months of follow-up visit. Two patients have intra-operative hyphemia secondary to iris prolapse. CONCLUSIONS: Implantation of iris-fixated phakic toric IOLs has shown high efficacy and safety in patients with mild-to-moderate astigmatism in corneal ectasia.