Keratoconus Patients Research Articles

Prevalence of Detectable Matrix Metalloproteinase-9 on the Ocular Surface in a Sample of Egyptian Keratoconus Patients

Prevalence of Detectable Matrix Metalloproteinase-9 on the Ocular Surface in a Sample of Egyptian Keratoconus Patients

Integrated analysis of murine cornea identifies JAK/STAT signaling pathway upregulated specifically in female Vitamin A Deficient mice

The Keratoconus (KC) is a corneal ectatic disease with unclear etiology. There are increasing studies that reported its association with a variety of inflammatory mechanisms. Vitamin A(VA) is an important nutrient related to inflammation regulation, and its deficiency may cause abnormalities of the ocular surface. However, the proportion of Vitamin A deficiency(VAD) was found surprisingly high among KC patients in our clinic practice. The aim of this study is to explore the effects of VAD on the transcriptome of corneas with the help of the VAD murine model and transcriptomics techniques. Blood samples of KC patients and non-KC controls (NC) were collected and the serum VA concentrations were measured and analyzed. A total of 52 NC and 39 KC were enrolled and the comparison of serum VA showed that the proportion of VAD in KC patients was 48.7% versus 1.9% in NC group. The further analysis of gender differences showed the proportion of VAD in female KC was 88.9% versus 36.7% in KC male patients. To explore the influence of VAD on cornea, the VAD mice fed with VAD diets were used. The RNA sequencing was employed to compare the corneal transcriptomic characteristics between the VAD female mice, NC female mice, VAD male mice and NC male mice. The transcriptome analysis revealed that the upregulated differential genes were mainly enriched in the immune response related pathways in VAD female mice versus NC female mice, especially the genes of JAK-STAT signaling pathway. The downstream molecules of JAK-STAT pathway were also significant after corneal mechanical scratching in female VAD mice. While, the differential genes between VAD male mice and NC male mice were estrogen signaling pathway instead of JAK-STAT pathway. This study indicates that VAD affects the transcriptomics of murine cornea with gender differences, which specifically affects the inflammatory status of the female murine cornea.

Vision related quality of life among Nepalese patients with keratoconus

Introduction: Keratoconus (KC) is a bilateral progressive noninflammatory disorder characterized by irregular astigmatism and corneal thinning. KC results in a disproportionate impact on major aspects of quality of life (QoL) of a person due to its early onset and chronic nature. This study aims to evaluate vision-related QoL in Nepalese patients with KC. Method: A cross-sectional hospital-based study was carried out for 1 year. A sample of 35 KC subjects and 38 control subjects who met the eligibility criteria were enrolled. All subjects underwent corneal topography and abberometry along with a comprehensive eye examination. Both cases and controls completed the NEI VFQ 25 questionnaire. Visual acuity (high contrast visual acuity and LCVA), CS, color vision, refraction, and scores of all subscales of QoL were measured. The QoL scores were correlated with each of the visual function parameters in KC subjects. Result: The mean scores of all of the subscales of QoL were found significantly less in the KC group than in age and sex matched control group with P<0.001 The mean composite score was found to reduce significantly as the grade of KC increased. The mean composite score for grade 1 KC was 70.79±7.96, grade 2 KC was 60.56±6.49 and for grade 3 KC was 55.99±0.67 with P=0.001 about better eye. There was a highly significant difference in the mean composite score of QoL between these contact lens wearers and spectacle wearers. The mean composite score for spectacle wearer was 67.86±07.99 and that of contact lens wearer was 58.63±04.26 with P=0.004. Conclusion: This study concluded that the QoL of keratoconic individuals was found to reduce gradually as the severity of the disease increased. QoL score in contact lens-wearing Nepalese KC patients is worse than spectacle wearers. By stopping the progression of disease we can maintain functional vision as well as a vision-related QoL. Our study findings suggested that vision and visual function parameters in the better eye is the most important parameter affecting VR-QOL of patients with KC. KC patients should maintain the best vision that they can have.

Intracanalicular Dexamethasone Insert for Post-Corneal Cross-Linking Inflammation and Pain - The LINK Study.

There is no standard-of-care treatment regimen for post-corneal crosslinking (CXL) inflammation & pain. This study compared efficacy of intracanalicular dexamethasone insert to tapered topical steroid over 28 days post-CXL. Single-private practice, outpatient setting. Prospective, observational, randomized study. This prospective, randomized study investigated the efficacy of a dexamethasone intracanalicular insert on post-CXL pain and inflammation in progressive keratoconus patients. Twenty patients (40 eyes) were enrolled; half were randomized to the dexamethasone intracanalicular insert group; half were prescribed a 28-day topical tapering steroid regimen. All patients were evaluated for pain scores, rate of re-epithelialization, ease of post-CXL regimen & need for rescue pain medication following standard bilateral epithelium-off CXL on postoperative day (POD) 1, POD-3, POD4-7, postoperative week (POW)-1, POW2, POW3 and POW4. Twenty patients (40 eyes) underwent standard-of-care epithelium-off bilateral CXL for progressive keratoconus. Ten patients were randomized to receive prednisolone eye drops on a tapering schedule post-CXL; 10 patients received dexamethasone intracanalicular inserts at the time of CXL. Regardless of postoperative steroid regimen, there was no significant difference in rate of re-epithelialization or use of rescue pain medication between groups. There was a nominal, however statistical difference in pain scores between groups, favoring prednisolone eye drops. Both groups stated no difficulty in following postoperative regimens. There were no adverse events noted in relation to treatment or CXL procedure. Utilizing a dexamethasone insert to alleviate pain and inflammation can be considered as a safe and efficacious part of a post-CXL regimen.

New keratoconus staging system based on OCT.

To establish a numerical spectral-domain optical coherence tomography (SD-OCT)-based keratoconus (KC) staging system and compare it with existing KC staging systems. Eye Hospital of Wenzhou Medical University, Wenzhou, China. Retrospective case-control study. Scheimpflug tomography, air-puff tonometry, and SD-OCT were performed on 236 normal and 331 KC eyes. All SD-OCT-derived parameters of the corneal epithelium and stroma were evaluated based on their receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity to discriminate between normal and KC eyes. The best performing parameters were subsequently used to create an OCT-based staging system, which was compared with existing tomographic and biomechanical staging systems. 236 eyes from 236 normal patients and 331 eyes from 331 KC patients of different stages were included. The highest ranked AUC ROC SD-OCT parameters, derived from stroma and epithelium, were stroma overall minimum thickness (ST: AUC 0.836, sensitivity 90%, specificity 67%) and epithelium overall SD (EP: AUC 0.835, sensitivity 75%, specificity 78%). A numerical SD-OCT staging system called STEP including 2 parameters-"ST" and "EP"-with 5 stages was proposed. The new SD-OCT-based KC staging system is the first to take the epithelium with its sublayer stroma information into account, showing a strong agreement to the existing staging systems. This system could be incorporated into daily practice, potentially leading to an overall improvement in KC treatment and follow-up management.

Impact on quality of life of keratoconus patients treated with accelerated "epi-on" corneal collagen crosslinking technique: results from the NEI VFQ-25 Questionnaire in a Romanian population.

Objective: The main objective of this study was to describe vision-related quality of life (VRQoL) in a Romanian population of patients with keratoconus who underwent the accelerated "epi-on" corneal collagen crosslinking procedure and to evaluate the association with demographic data of age, gender and civil status (married, cohabitants or non-cohabitants). Method: The National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) was administered to 72 patients with keratoconus who had undergone a minimally invasive procedure. Descriptive statistics and bivariate analysis were used to determine the distribution of demographic parameters and a possible association between this parameter and the scores obtained on the NEI VFQ-25 questionnaire. Results: Based on the answers to the questionnaire we calculated the mean (SD) VFQ-25 total score, which was 73,97 (15,11), whilst scores for the subscales varied from 49.93 to 84,23. No significant difference was observed between the demographic parameters and the NEI VFQ-25 items, except for one item (being with others) when comparing paired and non-paired participants. Conclusion: In a Romanian population with keratoconus being treated with accelerated "epi-on" corneal collagen crosslinking procedure, VRQoL was reported at a high baseline level. The value of this information is significant when discussing patients' expectations during treatment. The VRQoL was not affected by age or civil status.

Development of a Web-Based Algorithm for Understanding the Intraocular Lens-Based Surgery in Stable and Progressing Keratoconus for Non-Specialist Ophthalmologists

Purpose To propose an algorithm to facilitate lens-based surgery in keratoconus. Methods A literature review was performed to prepare a software algorithm based on cone location, stability, best spectacle-corrected distance visual acuity (BSCVA) level and whether there is a clear or cataractous lens. The software usability was assessed through a 10-question questionnaire and two hypothetical keratoconus case histories (moderately simple and moderately complex) given to 15 trainees. The usability questionnaires were graded on a Likert scale (1 = strongly disagree to 5 = strongly agree) and two case histories (1 = very difficult to 7 = very easy). Results The algorithm can be found at https://www.sussexeyelaserclinic.co.uk/keratoconus/. Thirteen trainees completed the questionnaire. 91.9% would frequently use it; for 100%, it was easy to use independently without technical support; for 63.7%, it was strongly integrated; for 100%, it was consistent; 100% thought that most people would learn to use it quickly, 91.9% found the system not cumbersome to use, felt very confident to use it and need not learn a lot to use it. The first case was found easy by 63.7% and the second by 45%. Conclusion We present an algorithm as a guide for lens-based surgery in stable and progressing keratoconus, which is classified based on cone location. This algorithm will help trainee and “non-specialist” ophthalmic surgeons understand the pre-operative planning for the surgery and referral to the “specialist” corneal surgeon, considering factors such as progression, BSCVA, keratometry, topography and apex location of the cone in keratoconus patients.

A high body mass index strengthens the association between the time of eye rubbing and keratoconus in a Chinese population: a case control study

BackgroundAlthough body mass index (BMI) and eye rubbing are linked to an increased risk of keratoconus (KC), the interactive effect of eye rubbing and BMI on KC is largely unknown. This study aimed to evaluate the independent and interactive effects of BMI and eye rubbing on KC and to further explore the role of environmental factors on the occurrence of KC.MethodsA total of 621 individuals (291 KC patients and 330 control individuals) were enrolled in this hospital‑based study on KC patients in Central China after individuals missing BMI data were excluded. BMI was calculated as weight in kilograms divided by the square of height in meters. Data on eye rubbing was recorded through face-to-face interviews. Generalized linear regression models were used to analyze associations among BMI, eye rubbing and KC. Interaction plots were used to describe the interactive effects of BMI and eye rubbing on KC.ResultsThe β and 95% confidence interval (CI) were 0.923 (0.112, 1.733) (p = 0.026) and 3.356 (1.953, 4.759) (p < 0.001), respectively, for the effect of each 10 kg/m2 increase in BMI and each 1 min increase in eye rubbing on KC. The interaction of BMI and eye rubbing were positively correlated with KC (p < 0.001).ConclusionThese findings suggested that a high BMI aggravated the negative effect of eye rubbing on KC, implying that individuals with a high BMI may be more susceptible to exposure to eye rubbing, which is related to an increased risk of KC.

The application of corneal biomechanical interocular asymmetry for the diagnosis of keratoconus and subclinical keratoconus.

Purpose: To evaluate the interocular consistency of biomechanical properties in normal, keratoconus (KC) and subclinical keratoconus (SKC) populations and explore the application of interocular asymmetry values in KC and SKC diagnoses. Methods: This was a retrospective chart-review study of 331 ametropic subjects (control group) and 207KC patients (KC group, including 94 SKC patients). Interocular consistency was evaluated using the intraclass correlation coefficient (ICC). Interocular asymmetry was compared between the control and KC groups and its correlation with disease severity was analyzed. Three logistic models were constructed using biomechanical monocular parameters and interocular asymmetry values. The diagnostic ability of interocular asymmetry values and the newly established models were evaluated using receiver operating characteristic curves and calibration curves. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were also estimated. Results: The interocular consistency significantly decreased and the interocular asymmetry values increased in KC patients compared with those in control individuals. In addition, the interocular asymmetry values increased with respect to the severity of KC. The binocular assisted biomechanical index (BaBI) had an area under the curve (AUC) of 0.998 (97.8% sensitivity, 99.2% specificity; cutoff 0.401), which was statistically higher than that of the Corvis biomechanical index [CBI; AUC = 0.935, p < 0.001 (DeLong's test), 85.6% sensitivity]. The optimized cutoff of 0.163 provided an AUC of 0.996 for SKC with 97.8% sensitivity, which was higher than that of CBI [AUC = 0.925, p < 0.001 (DeLong's test), 82.8% sensitivity]. Conclusion: Biomechanical interocular asymmetry values can reduce the false-negative rate and improve the performance in KC and SKC diagnoses.

Ocular Surface Microbiota in Naïve Keratoconus: A Multicenter Validation Study.

In the field of Ophthalmology, the mNGS 16S rRNA sequencing method of studying the microbiota and ocular microbiome is gaining more and more weight in the scientific community. This study aims to characterize the ocular microbiota of patients diagnosed with keratoconus who have not undergone any prior surgical treatment using the mNGS 16S rRNA sequencing method. Samples of naïve keratoconus patients were collected with an eNAT with 1 mL of Liquid Amies Medium (Copan Brescia, Italy), and DNA was extracted and analyzed with 16S NGS. The microbiota analysis showed a relative abundance of microorganisms at the phylum level in each sample collected from 38 patients with KC and 167 healthy controls. A comparison between healthy control and keratoconus samples identified two genera unique to keratoconus, Pelomonas and Ralstonia. Our findings suggest that alterations in the microbiota may play a role in the complex scenario of KC development.

Enhanced morphological assessment based on interocular asymmetry analysis for keratoconus detection.

To clarify the interocular asymmetry of corneal morphological descriptors and evaluate its discriminant ability of keratoconus (KC). This retrospective study recruited 344 normal participants and 290 KC patients, randomized to training and validation datasets. Interocular correlation and agreement were evaluated on 44 corneal morphological descriptors derived from Schiempflug tomography. Logistic regression models were constructed using binocular data and of which diagnostic performance was evaluated using the area under receiver operating characteristics curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Interocular agreement of corneal descriptors is better in the normal than in KC except for dimensions of cornea and anterior chamber. The interocular asymmetry increases along with the severity of KC. Interocular asymmetry in maximum anterior keratometry, mean anterior keratometry and higher-order aberrations of anterior surface show high AUC above 0.950. Binocular logistic regression index reaches an AUC of 0.963 with high specificity (95.2%) and brings gain to monocular parameters in distinguishing the normal eyes from KC (NRI = 0.080 (0.042 ~ 0.118), P < 0.001) and IDI = 0.071 (0.049 ~ 0.092), P < 0.001). Interocular asymmetry benefits even more in subclinical keratoconus (SKC) detection reflected by NRI (0.4784 (0.2703-0.6865), P < 0.001) and IDI (0.2680 (0.1495-0.3866), P < 0.001) measures. Interocular asymmetry is a well-characterized feature of KC and related to the severity. It is feasible to apply the interocular asymmetry in diagnosis of KC and SKC as a replenishment of monocular parameters and in progression tracking.

A Cross-Sectional Analysis to Assess the Role of Atopy in Keratoconus Among Saudi Population.

In cases of atopy, IgE antibodies are formed in reaction to certain environmental factors like house dust mites, pollen, or even food allergens. Some studies have shown an association between atopic diseases and keratoconus. This study aims to determine the prevalence of atopy and its associated factors among keratoconus patients. A cross-sectional study was conducted among the Jazan population attending ophthalmology clinics regardless of their sex. Data collection started in August 2020 and finished in mid-June 2021. The sample was selected using the convenience sampling technique, and the total sample size was 83 participants. Data were collected via a questionnaire-based interview that contained 46 questions in the Arabic language. The data collected were analyzed using SPSS software. Family history is the leading predisposing factor for keratoconus (P < 0.001). Also, eye rubbing was a significant (P < 0.015) trigger for keratoconus. However, other factors, including demographic factors such as gender and atopic conditions, did not have any significant association. A combination of genetic and environmental factors is the leading cause of the development of keratoconus; however, family history is the most influential factor, followed by eye rubbing.

Atypical optic neuritis in a keratoconus patient and literature review

Myelin oligodendrocyte glycoprotein antibody disease-optic neuritis (MOGAD-ON) is an uncommon form of demyelinating optic neuritis, which may be potentially blinding. Keratoconus (KC) is a noninflammatory, progressive ectatic corneal disorder often affecting young adults, leading to visual dysfunction. A singular account of the coexistence of unilateral KC with bilateral (BL) MOGAD-ON has been reported before. Our report narrates the experience of managing the visual deficit due to BL MOGAD-ON in a patient with BL KC, an association hitherto unreported so far. The emphasis is on highlighting the diagnostic approach and stressing the refined principles of management of optic neuritis in conjunction with the neurology team.

Differences in Axial Length and Anterior Chamber Depth among Keratoconic, Myopic and Emmetropic Eyes

Purpose: To report variation of the axial length (AL) and anterior chamber depth (ACD) among keratoconic (KC) eyes compared to myopic and emmetropic eyes in an African population sample. Study Design: Cross sectional observational. Place and Duration of Study: Al-Faisal Eye Hospital at Khartoum state of Sudanfrom January 2022 to September 2022. Methods: One-hundred and twenty-four eyes of 62 patients were divided into KC group (n =17, eyes=34), myopic group (n=28, eyes=56), and an age/gender matched emmetropic group (n=17, eyes =34). Central corneal thickness (CCT) was measured using ultrasonic pachymeter, AL, ACD and keratometry readings (K-reading) were recorded for each patient using non-contact partial coherence interferometry with an IOL Master. Results: Mean age of the sample population was 22.27± 6.05 (range; 10 – 40 years). KC patients had the highest spherical equivalent of refraction (SER) (-6.19±3.91 dioptres), highest k-reading (48.98±5.68 dioptres) and the thinnest CCT. Myopic participants had a longer AL compared to other refractive error groups (AL=24.99±2.39, p&lt;0.001). KC patients exhibited a larger ACD in comparison to emmetropes and myopes (ACD=3.6?9±0.26, p&lt;0.001). Among all participants, SER exhibited the highest correlation with AL (r=-0.71, p&lt;0.001) followed by a weaker correlation with ACD (r=-0.26, p=0.003). However, among KC patients, SER exhibited a weaker correlation with AL compared to myopes (r=-0.55, p=0.001), and a higher correlation with ACD compared to myopes (r=-0.38, p=0.03). Conclusion: ACD and corneal curvature were the most significantly detrimental parameters in KC. KC participants demonstrated a lower correlation between SER and AL and higher correlation between SER and ACD.

Novel deep learning approach to estimate rigid gas permeable contact lens base curve for keratoconus fitting

IntroductionRigid gas permeable contact lenses (RGP) are the most efficient means of providing optimal vision in keratoconus. RGP fitting can be challenging and time-consuming for ophthalmologists and patients. Deep learning predictive models could simplify this process. ObjectiveTo develop a deep learning model to predict the base curve (R0) of rigid gas permeable contact lenses for keratoconus patients. MethodsWe conducted a retrospective study at the Rothschild Foundation Hospital between June 2012 and April 2021. We included all keratoconus patients fitted with Menicon Rose K2® lenses. The data was divided into a training set to develop the model and a test set to evaluate the model's performance. We used a U-net architecture. The raw matrix of anterior axial curvature in millimeters was extracted from Scheimpflug examinations for each patient and used as input for the model. The mean absolute error (MAE) between the prediction and the prescribed R0 was calculated. Univariate and multivariate analyses were conducted to assess the model's errors. ResultsThree hundred fifty-eight eyes from 202 patients were included: 287 eyes were included in the training dataset, and 71 were included in the testing dataset. Our model's Pearson coefficient of determination (R2) was calculated at 0.83, compared to 0.75 for the manufacturer's recommendation (mean keratometry, Km). The mean square error of our model was calculated at 0.04, compared to 0.11 for Km. The predicted R0 MAE (0.16 ± 0.13) was statistically significantly different from the Km MAE (0.23 ± 0.23) (p = 0.02). In multivariate analysis, an apex center outside the central 5 mm region was the only factor significantly increasing the prediction absolute error. ConclusionOur deep learning approach demonstrated superior precision in predicting rigid gas permeable contact lens base curves for keratoconus patients compared to the manufacturer's recommendation. This approach has the potential to be particularly beneficial in complex fitting cases and can help reduce the time spent by ophthalmologists and patients during the process.

Identification and Analysis of Primary Cilia in the Corneal Endothelial Cells of Patients with Bullous Keratopathy

Purpose To identify primary cilia in human corneal endothelial cells (CECs) obtained from patients with bullous keratopathy (BK). Methods This study involved CEC specimens obtained from 10 eyes of 10 consecutive patients (three males and seven females; mean age: 74.5 years, range: 68–90 years) with BK who underwent Descemet’s stripping automated endothelial keratoplasty at Baptist Eye Institute, Kyoto, Japan between August 2019 and September 2020. Three corneal buttons obtained from 3 patients who underwent penetrating keratoplasty for keratoconus were used as 'non-BK' controls. All specimens were evaluated with immunofluorescence staining using an antibody against acetylated α-tubulin. Results Ciliary expression was observed in six of the 10 CEC specimens; i.e. in two specimens obtained from BK patients after glaucoma surgery (trabeculectomy), in two specimens obtained from patients with Fuchs endothelial corneal dystrophy, and in two specimens obtained from a patient with BK after laser iridotomy for primary angle closure. There was acetylated α-tubulin staining but no hair-like structures in two specimens, and ciliary expression was unknown in two specimens due to the absence of cells. The length of the primary cilia varied between all specimens. In contrast, no primary cilia were observed in the corneal buttons obtained from the three keratoconus patients. Conclusion The findings in this study clearly demonstrate the expression of primary cilia in the CECs of patients afflicted with BK.

Phakic intraocular Lens implantation in keratoconus patients.

Both the anterior chamber and posterior chamber phakic intraocular lenses (pIOLs) implantation are acceptable refractive surgical approaches in keratoconus patients with high anisometropia, contact lens intolerance, or who prefer spectacle and contact lens independent. They are beneficial for correcting anisometropia in stable keratoconus cases or following corneal procedures such as intrastromal corneal ring segments (ICRS), collagen cross-linking (CXL), and keratoplasty. They are suitable for eyes without advanced keratoconus with acceptable best-corrected distance visual acuity (BCDVA) or without highly irregular astigmatism, high comma, and higher-order aberrations (HOAs). Combined procedures for irregular astigmatism reduction and corneal regularization with either ICRS or topography/wavefront-guided transepithelial PRK (with or without CXL) can be associated in advance with pIOLs implantation to improve BCDVA in these cases. To study and report the evidence regarding the safety and efficacy of pIOLs for KC patients' visual and refractive rehabilitation, we have analyzed the scientific evidence published within the last 10 years (from 2012 onwards). No randomized controlled trials but only eleven retrospective case series and two prospective case series were identified. Satisfactory visual rehabilitation was achieved regarding uncorrected and corrected distance visual acuity (CDVA) and predictability of the refractive correction. Both types of pIOL (iris claw and posterior chamber pIOLs) offer very good results in terms of safety and efficacy with indexes close to or even exceeding 1. pIOLs implantation is a valid refractive therapeutic approach for correcting stable keratoconus with moderate-to-high refractive errors, especially anisometropia associated with regular or mildly irregular astigmatism, and good CDVA.

Ocular condition prognosis in Keratoconus patients after corneal ring implantation using artificial neural networks

The common disorder, Keratoconus (KC), is distinguished by cumulative corneal slimming and steepening. The corneal ring implantation has become a successful surgical procedure to correct the KC patient’s vision. The determination of suitable patients for the surgery alternative is among the paramount concerns of ophthalmologists. To reduce the burden on them and enhance the treatment, this research aims to previse the ocular condition of KC patients after the corneal ring implantation. It focuses on predicting post-surgical corneal topographic indices and visual characteristics. This study applied an efficacious artificial neural network approach to foretell the aforementioned ocular features of KC subjects 6 and 12 months after implanting KeraRing and MyoRing based on the accumulated data. The datasets are composed of sufficient numbers of corneal topographic maps and visual characteristics recorded from KC patients before and after implanting the rings. The visual characteristics under study are uncorrected visual acuity (UCVA), sphere (SPH), astigmatism (Ast), astigmatism orientation (Axe), and best corrected visual acuity (BCVA). In addition, the statistical data of multiple KC subjects were registered, including three effective indices of corneal topography (i.e., Ast, K-reading, and pachymetry) pre- and post-ring embedding. The outcomes represent the contribution of practical training of the introduced models to the estimation of ocular features of KC subjects following the implantation. The corneal topographic indices and visual characteristics were estimated with mean errors of 7.29% and 8.60%, respectively. Further, the errors of 6.82% and 7.65% were respectively realized for the visual characteristics and corneal topographic indices while assessing the predictions by the leave-one-out cross-validation (LOOCV) procedure. The results confirm the great potential of neural networks to guide ophthalmologists in choosing appropriate surgical candidates and their specific intracorneal rings by predicting post-implantation ocular features.

Screening and identification of genes related to ferroptosis in keratoconus

Corneal keratoconus (KC) is a dilated (ectatic) corneal disease characterized by a central thinning of the cornea, which causes protrusion into a conical shape that seriously affects vision. However, due to the complex etiology of keratoconus, its entire mechanism remains unclear and there is no mechanism-directed treatment method. Ferroptosis is a novel programmed cell death mechanism related to lipid peroxidation, stress, and amino acid metabolism, which plays a crucial role in various diseases. This study aimed to explore the relationship between keratoconus and ferroptosis, to provide new insights into the mechanism of keratoconus development, and potential treatment options based on further elucidation of this mechanism. The corresponding mRNA microarray expression matrix data of KC patients were obtained from GEO database (GSE204791). Weighted co-expression network analysis (WGCNA) and support vector machine recursive feature elimination (SVM-RFE) were selected to screen hub genes, which were overlapped with ferroptosis genes (FRGs) from FerrDb. GO and GSEA were performed to analyze differential pathways, ssGSEA was used to determine immune status, and then, feasible drugs were predicted by gene-drug network. Additionally, we predicted the miRNA and IncRNA of hub genes to identify the underlying mechanism of disease so as to predict treatment for the disease. The epithelial transcriptome from keratoconus tissue mRNA microarray data (GSE204791) was extracted for the main analysis, including eight epithelial cells and eight epithelial control cells. The differential genes that were overlapped by WGCAN, SVM-RFE and FRGs were mainly related to oxidative stress, immune regulation, cellular inflammation, and metal ion transport. Through further analysis, aldo–keto reductase family 1 member C3 (AKR1C3) was selected, and negatively correlated with mature CD56 natural killer (NK) cells and macrophages. Then, gene-drug interaction network analysis and miRNA prediction were performed through the website. It was concluded that four immune-related drugs (INDOMETHACIN, DAUNORUBICIN, DOXORUBICIN, DOCETAXEL) and a miRNA (has-miR-184) were screened to predict potential drugs and targets for disease treatment. To our knowledge, this was the first report of KC being associated with ferroptosis and prompted search for differential genes to predict drug targets of gene immunotherapy. Our findings provided insight and a solid basis for the analysis and treatment of KC.

Novel Multivariable Evolutionary Algorithm-Based Method for Modal Reconstruction of the Corneal Surface from Sparse and Incomplete Point Clouds.

Three-dimensional reconstruction of the corneal surface provides a powerful tool for managing corneal diseases. This study proposes a novel method for reconstructing the corneal surface from elevation point clouds, using modal schemes capable of reproducing corneal shapes using surface polynomial functions. The multivariable polynomial fitting was performed using a non-dominated sorting multivariable genetic algorithm (NS-MVGA). Standard reconstruction methods using least-squares discrete fitting (LSQ) and sequential quadratic programming (SQP) were compared with the evolutionary algorithm-based approach. The study included 270 corneal surfaces of 135 eyes of 102 patients (ages 11-63) sorted in two groups: control (66 eyes of 33 patients) and keratoconus (KC) (69 eyes of 69 patients). Tomographic information (Sirius, Costruzione Strumenti Oftalmici, Italy) was processed using Matlab. The goodness of fit for each method was evaluated using mean squared error (MSE), measured at the same nodes where the elevation data were collected. Polynomial fitting based on NS-MVGA improves MSE values by 86% compared to LSQ-based methods in healthy patients. Moreover, this new method improves aberrated surface reconstruction by an average value of 56% if compared with LSQ-based methods in keratoconus patients. Finally, significant improvements were also found in morpho-geometric parameters, such as asphericity and corneal curvature radii.