Ocular surface immune transcriptome and tear cytokines in corneal infection patients.

Background: Microbial keratitis is one of the leading causes of blindness globally. An overactive immune response during an infection can exacerbate damage, causing corneal opacities and vision loss. This study aimed to identify the differentially expressed genes between corneal infection patients and healthy volunteers within the cornea and conjunctiva and elucidate the contributing pathways to these conditions' pathogenesis. Moreover, it compared the corneal and conjunctival transcriptomes in corneal-infected patients to cytokine levels in tears. Methods: Corneal and conjunctival swabs were collected from seven corneal infection patients and three healthy controls under topical anesthesia. RNA from seven corneal infection patients and three healthy volunteers were analyzed by RNA sequencing (RNA-Seq). Tear proteins were extracted from Schirmer strips via acetone precipitation from 38 cases of corneal infection and 14 healthy controls. The cytokines and chemokines IL-1ß, IL-6, CXCL8 (IL-8), CX3CL1, IL-10, IL-12 (p70), IL-17A, and IL-23 were measured using an antibody bead assay. Results: A total of 512 genes were found to be differentially expressed in infected corneas compared to healthy corneas, with 508 being upregulated and four downregulated (fold-change (FC) <-2 or > 2 and adjusted p <0.01). For the conjunctiva, 477 were upregulated, and 3 were downregulated (FC <-3 or ≥ 3 and adjusted p <0.01). There was a significant overlap in cornea and conjunctiva gene expression in patients with corneal infections. The genes were predominantly associated with immune response, regulation of angiogenesis, and apoptotic signaling pathways. The most highly upregulated gene was CXCL8 (which codes for IL-8 protein). In patients with corneal infections, the concentration of IL-8 protein in tears was relatively higher in patients compared to healthy controls but did not show statistical significance. Conclusions: During corneal infection, many genes were upregulated, with most of them being associated with immune response, regulation of angiogenesis, and apoptotic signaling. The findings may facilitate the development of treatments for corneal infections that can dampen specific aspects of the immune response to reduce scarring and preserve sight.

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

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

Refraction and ocular biometric parameters in 3-to 6-year-old preschool children : a large-scale population-based study in Chengdu, China.

PURPOSE: To understand the ocular biometric parameters characteristics and refractive errors in 3-to 6-year-old preschool children in Chengdu, China, and to investigate the prevalence of refractive errors. METHOD: A school-based cross-sectional study was conducted in Chengdu from 2020 to2022 with a total of 666 kindergartens. All children were measured by non-cycloplegic autorefraction and uncorrected visual acuity (UCVA) and ocular biometric parameters. Finally, univariate linear regression models were used to analyze the relationship between ocular biometric parameters and refraction. RESULTS: A total of 108,578 preschool children aged 3-6 underwent examinations, revealing a myopia prevalence of 6.1%. The mean axial length (AL), keratometry (K), corneal radius (CR), axial length/corneal radius (AL/CR) Ratio, central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), and vitreous chamber depth (VCD) were 22.35 ± 0.69 mm, 43.35 ± 1.58 D, 7.80 ± 0.28 mm, 2.87 ± 0.08, 533.31 ± 32.51 µm, 2.70 ± 0.28 mm, 3.91 ± 0.27 mm, and 15.20 ± 0.68 mm, respectively. With increasing age, AL, CR, AL/CR ratio, CCT, ACD, LT, and VCD also increased. Regardless of age, males consistently exhibited longer AL, flatter corneal curvature, shallower ACD, thicker CCT, thinner LT, and longer VCD compared to females. AL, K, CR, LT, and VCD all showed significant linear relationships with SE (all P < 0.001) in univariate linear regression analysis after adjusting for gender and age. CONCLUSION: The prevalence of myopia among preschool children aged 3-6 in Chengdu is relatively low. Ocular biometric parameters affecting refractive errors include AL, K, CR, LT, and VCD. The preschool period serves as a critical phase for myopia prevention and control.

Dual-ROS-scavenging and dual-lingering nanozyme-based eye drops alleviate dry eye disease.

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.

Impact of Obesity and Age on Mouse Corneal Innervation at the Epithelial-Stromal Interface.

Purpose: The corneal epithelium is the most highly innervated structure in the body. Previously, we reported a novel event whereby stromal axons fuse with basal epithelial cells, limiting nerve penetration into the epithelium. Although corneal-epithelial nerves undergo changes in sensitivity and distribution throughout life and in response to an obesogenic diet, it is unknown if neuronal-epithelial cell fusion is altered. Here, we sought to determine if neuronal-epithelial cell fusion frequency correlates with obesogenic diet consumption and age. Methods: Corneas were collected from C57BL/6 mice and evaluated for neuronal-epithelial cell fusion frequency using serial block-face scanning electron microscopy. To assess the correlation between diet-induced obesity and fusion frequency, 6-week-old mice were fed either a normal diet or an obesogenic diet for 10 weeks. To assess changes in fusion frequency between young and adult mice under normal dietary conditions, 9- and 24-week-old mice were used. Results: Mice fed a 10-week obesogenic diet showed 87% of central-cornea stromal nerves engaged in fusion compared with only 54% in age-matched controls (16 weeks old). In 9-week-old normal-diet animals, 48% of central-cornea stromal nerves contained fusing axons and increased to 81% at 24 weeks of age. Corneal sensitivity loss correlated with increased body weight and adiposity regardless of age and diet. Conclusions: Neuronal-epithelial cell fusion positively correlates with age and obesogenic diet consumption, and corneal nerve sensitivity loss correlates with increased body weight and adiposity, regardless of age and diet. As such, neuronal-epithelial cell fusion may play a role in corneal nerve density and sensitivity regulation.

Myopia prevalence and ocular biometry in children and adolescents at different altitudes: a cross-sectional study in Chongqing and Tibet, China.

OBJECTIVE: To investigate the differences in myopia prevalence and ocular biometry in children and adolescents in Chongqing and Tibet, China. DESIGN: Cross-sectional study. SETTING: The study included children and adolescents aged 6-18 years in Chongqing, a low-altitude region, and in Qamdo, a high-altitude region of Tibet. PARTICIPANTS: A total of 448 participants in Qamdo, Tibet, and 748 participants in Chongqing were enrolled in this study. METHODS: All participants underwent uncorrected visual acuity assessment, non-cycloplegic refraction, axial length (AL) measurement, intraocular pressure (IOP) measurement and corneal tomography. And the participants were grouped according to age (6-8, 9-11, 12-14 and 15-18 years group), and altitude of location (primary school students: group A (average altitude: 325 m), group B (average altitude: 2300 m), group C (average altitude: 3250 and 3170 m) and group D (average altitude: 3870 m)). RESULTS: There was no statistical difference in mean age (12.09±3.15 vs 12.2±3.10, p=0.549) and sex distribution (males, 50.4% vs 47.6%, p=0.339) between the two groups. The Tibet group presented greater spherical equivalent (SE, -0.63 (-2.00, 0.13) vs -0.88 (-2.88, -0.13), p<0.001), shorter AL (23.45±1.02 vs 23.92±1.19, p<0.001), lower prevalence of myopia (39.7% vs 47.6%, p=0.008) and flatter mean curvature power of the cornea (Km, 43.06±1.4 vs 43.26±1.36, p=0.014) than the Chongqing group. Further analysis based on age subgroups revealed that the Tibet group had a lower prevalence of myopia and higher SE in the 12-14, and 15-18 years old groups, shorter AL in the 9-11, 12-14 and 15-18 years old groups, and lower AL to corneal radius of curvature ratio (AL/CR) in all age subgroups compared with the Chongqing group, while Km was similar between the two groups in each age subgroup. Simple linear regression analysis showed that SE decreased with age in both the Tibet and Chongqing groups, with the Tibet group exhibiting a slower rate of decrease (p<0.001). AL and AL/CR increased with age in both the Tibet and Chongqing groups, but the rate of increase was slower in the Tibet group (p<0.001 of both). Multiple linear regression analysis revealed that AL had the greatest effect on SE in both groups, followed by Km. In addition, the children and adolescents in Tibet presented thinner corneal thickness (CCT, p<0.001), smaller white to white distance (WTW, p<0.001), lower IOP (p<0.001) and deeper anterior chamber depth (ACD, p=0.015) than in Chongqing. Comparison of altitude subgroups showed that the prevalence of myopia (p=0.002), SE (p=0.031), AL (p=0.001) and AL/CR (p<0.001) of children at different altitudes was statistically different but the Km (p=0.189) were similar. The highest altitude, Tengchen County, exhibited the lowest prevalence of myopia and greatest SE among children, and the mean AL also decreased with increasing altitude. CONCLUSIONS: Myopia prevalence in Tibet was comparable with that in Chongqing for students aged 6-8 and 9-11 years but was lower and myopia progressed more slowly for students aged 12-14 and 15-18 years than in Chongqing, and AL was the main contributor for this difference, which may be related to higher ultraviolet radiation exposure and lower IOP in children and adolescents at high altitude in Tibet. Differences in AL and AL/CR between Tibet and Chongqing children and adolescents manifested earlier than in SE, underscoring the importance of AL measurement in myopia screening.

Fitting-Shape-based Strategy for Topography-guided LASIK: A Prospective Study.

PURPOSE: To assess and compare the visual acuity and refractive outcomes of topography-guided laser in situ keratomileusis (LASIK) based on the fitting-shape-based refractive compensated and Phorcides software strategies. METHODS: Consecutive patients who underwent topography-guided LASIK were included in this study. Through double-masked simple randomization, patients were assigned to the Zhang & Zheng Auto-compensate Refraction (ZZ AR) group (the fitting-shape-based refractive compensated strategy using the ZZ AR calculator was used) or the Phorcides group (the topography analysis algorithm in Phorcides software [Phorcides LLC] was used). Only one eye per patient with binocular correction was randomly enrolled. The preoperative and postoperative visual acuities and refraction were analyzed at the 6-month follow-up visit. RESULTS: The ZZ AR and Phorcides groups comprised 156 and 147 eyes, respectively. At the 6-month postoperative follow-up visit, the median (range) absolute residual cylindrical refraction was 0.35 (1.01) and 0.47 (1.63) diopters (D) for the ZZ AR and Phorcides groups, respectively (P < .001). The percentages of patients with residual cylindrical power within 0.25 D were 29.49% and 13.61% for the ZZ AR and Phorcides groups, respectively (P = .001). Based on the percentages of patients with residual cylindrical powers within 0.50 and 1.00 D, the ZZ AR group showed better outcomes (P = .02 and .01). The percentage of patients with visual acuity better than 20/16 was significantly higher for the ZZ AR group than for the Phorcides group (P = .03). CONCLUSIONS: The fitting-shape-based refractive compensated strategy for topography-guided LASIK procedures can better optimize the visual acuity and astigmatic refraction than the Phorcides software strategy. [J Refract Surg. 2024;40(5):e336-e343.].

Comparative Study of Primary SMILE, SMILE Enhancement, and Femtosecond Laser-Assisted LASIK on Higher Order Aberrations and Corneal Densitometry.

PURPOSE: To compare differences in corneal densitometry (CD) and higher order aberrations (HOAs) in eyes that underwent small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for the treatment of myopia and myopic astigmatism at postoperative months 3, 6, and 12, and to evaluate their changes in a separate cohort of eyes after SMILE enhancement. METHODS: In this prospective, randomized, paired-eye clinical trial, consecutive eligible participants were randomized to undergo SMILE or FS-LASIK in either eye. Main outcome measures were CD and HOAs preoperatively and at 3, 6, and 12 months postoperatively. A separate cohort of consecutive patients who had SMILE and underwent enhancement were also included for comparison. RESULTS: For CD, no significant differences were found between SMILE and FS-LASIK up to month 12. For HOA measured by wavefront aberrometry, both SMILE and FS-LASIK had an increase in total root mean square (RMS) HOAs, spherical aberration (SA), and vertical coma up to month 12. SMILE had an additional increase in vertical quatrefoil, and FS-LASIK had an increase in horizontal coma at month 12. FS-LASIK had higher SA than SMILE, whereas SMILE had higher vertical quatrefoil than FS-LASIK at month 12. Central and posterior zone CD had significantly decreased after SMILE enhancement compared to after primary SMILE up to 2 years after enhancement. RMS HOAs, lower order aberrations, and SA were all increased after SMILE enhancement compared to after primary SMILE. CONCLUSIONS: SMILE induced lower SA but higher vertical quatrefoil than FS-LASIK at 1 year. Both SMILE and FS-LASIK had similar increases in RMS HOAs and vertical coma up to 1 year. There were no differences in CD between both groups. SMILE enhancement additionally had decreased central and posterior CD but greater RMS HOAs and SA compared to primary SMILE. [J Refract Surg. 2024;40(5):e291-e303.].

In Vivo Corneal Biomechanical Response to Three Different Laser Corneal Refractive Surgeries.

PURPOSE: To compare the effects of three common refractive surgeries on corneal biomechanics. METHODS: Two hundred seven patients who had refractive surgery were included in this study, of whom 65 received transepithelial photorefractive keratectomy (tPRK), 73 received femtosecond laser-assisted laser in situ keratomileusis (FSLASIK), and 69 received small incision lenticule extraction (SMILE). Each patient had biomechanical measurements using the Corvis ST (Oculus Optikgeräte GmbH) preoperatively and at 3 and 6 months postoperatively. The measurements included five parameters expected to be associated with corneal biomechanics: deformation amplitude ratio at 2 mm (DAR2), integrated inverse radius (IIR), stiffness parameter at first applanation (SP-A1), highest concavity time (HCT), and the updated stress-strain index (SSIv2). The variations in these parameters postoperatively among the three surgeries, and their relationship with corneal thickness (CCT) and intraocular pressure measured by the Dynamic Contour Tonometer (DCT-IOP) were analyzed. RESULTS: SP-A1 decreased significantly from preoperatively to 3 months postoperatively in all three groups, whereas DAR2 and IIR increased significantly, all indicating stiffness losses. Between 3 and 6 months postoperatively, the results were inconsistent, with DAR2 decreasing (indicating stiffness increases) and IIR increasing (denoting stiffness decreases) in the FS-LASIK and SMILE groups. The decrease in SSIv2 (the only measure of corneal material stiffness) postoperatively was comparatively less pronounced at both 3 and 6 months postoperatively. On the other hand, HCT remained generally stable after all three surgeries. Unlike DAR2, IIR, and SP-A1, the changes postoperatively in stiffness parameters HCT and SSIv2 were independent of the corresponding changes in both DCT-IOP and CCT. CONCLUSIONS: Among the stiffness parameters considered, SSIv2 was not correlated with CCT or DCT-IOP, and holds promise for representing the corneal material stiffness and how it remains largely unaffected by refractive surgeries. Overall, FS-LASIK had the most significant impact on corneal stiffness, followed by SMILE, and finally tPRK. [J Refract Surg. 2024;40(5):e344-e352.].

[ARTIFICIAL CORNEA: FROM THE BEGINNING TO THE FUTURE].

INTRODUCTION: Corneal disease is among the leading reversible causes of blindness worldwide. Corneal transplantation is a successful and curative treatment for most of these cases. However, in certain indications it is not amendable for standard corneal transplantation, the only available option to restore functional vision is keratoprosthesis (KPro) implantation. KPros may also offer an alternative to the global shortage of donor corneas, limiting the access to transplantations. However, current KPros face many challenges, including surgical complexity that requires skilled surgeons and vast resources as well as unique surgical and post-operative complications. Although several artificial corneas have been proposed over the years, two implants are mostly used in the clinical setting today. The first, the Boston KPro, consists of a front plate with an optical stem and a back plate snapped together with donor corneal tissue in-between, which is then sutured to the patient's cornea. The second, the Osteo-odonto-keratoprosthesis (OOKP), uses biological tissue of the alveolar bone to support an optical cylinder within the eye. The indications, surgical techniques, and complication profile of the two procedures are different and will be discussed in this review. Extensive research continues to improve the accessibility and technological developments of KPros in the search for a potential breakthrough in the treatment of these difficult cases.

Antioxidant Carbon Dots Nanozyme Loaded in Thermosensitive in situ Hydrogel System for Efficient Dry Eye Disease Treatment.

Purpose: Dry eye disease (DED) is a multifactorial ocular surface disease with a rising incidence. Therefore, it is urgent to construct a reliable and efficient drug delivery system for DED treatment. Methods: In this work, we loaded C-dots nanozyme into a thermosensitive in situ gel to create C-dots@Gel, presenting a promising composite ocular drug delivery system to manage DED. Results: This composite ocular drug delivery system (C-dots@Gel) demonstrated the ability to enhance adherence to the corneal surface and extend the ocular surface retention time, thereby enhancing bioavailability. Furthermore, no discernible ocular surface irritation or systemic toxicity was observed. In the DED mouse model induced by benzalkonium chloride (BAC), it was verified that C-dots@Gel effectively mitigated DED by stabilizing the tear film, prolonging tear secretion, repairing corneal surface damage, and augmenting the population of conjunctival goblet cells. Conclusion: Compared to conventional dosage forms (C-dots), the C-dots@Gel could prolong exhibited enhanced retention time on the ocular surface and increased bioavailability, resulting in a satisfactory therapeutic outcome for DED.

Optical coherence elastography under homolateral parallel acoustic radiation force excitation for ocular elasticity quantification.

Alteration in the elastic properties of biological tissues may indicate changes in the structure and components. Acoustic radiation force optical coherence elastography (ARF-OCE) can assess the elastic properties of the ocular tissues non-invasively. However, coupling the ultrasound beam and the optical beam remains challenging. In this Letter, we proposed an OCE method incorporating homolateral parallel ARF excitation for measuring the elasticity of the ocular tissues. An acoustic-optic coupling unit was established to reflect the ultrasound beam while transmitting the light beam. The ARF excited the ocular tissue in the direction parallel to the light beam from the same side of the light beam. We demonstrated the method on the agar phantoms, the porcine cornea, and the porcine retina. The results show that the ARF-OCE method can measure the elasticity of the cornea and the retina, resulting in higher detection sensitivity and a more extensive scanning range.

Comprehensive dry eye therapy: overcoming ocular surface barrier and combating inflammation, oxidation, and mitochondrial damage.

BACKGROUND: Dry Eye Disease (DED) is a prevalent multifactorial ocular disease characterized by a vicious cycle of inflammation, oxidative stress, and mitochondrial dysfunction on the ocular surface, all of which lead to DED deterioration and impair the patients' quality of life and social functioning. Currently, anti-inflammatory drugs have shown promising efficacy in treating DED; however, such drugs are associated with side effects. The bioavailability of ocular drugs is less than 5% owing to factors such as rapid tear turnover and the presence of the corneal barrier. This calls for investigations to overcome these challenges associated with ocular drug administration. RESULTS: A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study. In terms of delivery, PHP-DPS@INS nanoparticles (NPs) overcame the ocular surface transport barrier by adopting the strategy of "ocular surface electrostatic adhesion-lysosomal site-directed escape". In terms of therapy, PHP-DPS@INS achieved mitochondrial targeting and antioxidant effects through SS-31 peptide, and exerted an anti-inflammatory effect by loading insulin to reduce mitochondrial inflammatory metabolites. Ultimately, the synergistic action of "anti-inflammation-antioxidation-mitochondrial function restoration" breaks the vicious cycle associated with DED. The PHP-DPS@INS demonstrated remarkable cellular uptake, lysosomal escape, and mitochondrial targeting in vitro. Targeted metabolomics analysis revealed that PHP-DPS@INS effectively normalized the elevated level of mitochondrial proinflammatory metabolite fumarate in an in vitro hypertonic model of DED, thereby reducing the levels of key inflammatory factors (IL-1ß, IL-6, and TNF-α). Additionally, PHP-DPS@INS strongly inhibited reactive oxygen species (ROS) production and facilitated mitochondrial structural repair. In vivo, the PHP-DPS@INS treatment significantly enhanced the adhesion duration and corneal permeability of the ocular surface in DED mice, thereby improving insulin bioavailability. It also restored tear secretion, suppressed ocular surface damage, and reduced inflammation in DED mice. Moreover, it demonstrated favorable safety profiles both in vitro and in vivo. CONCLUSION: In summary, this study successfully developed a comprehensive DED management nanosystem that overcame the ocular surface transmission barrier and disrupted the vicious cycle that lead to dry eye pathogenesis. Additionally, it pioneered the regulation of mitochondrial metabolites as an anti-inflammatory treatment for ocular conditions, presenting a safe, efficient, and innovative therapeutic strategy for DED and other inflammatory diseases.

Congenital Corneal Staphyloma: A Comprehensive Histopathologic Assessment Including Associated Anterior Segment Abnormalities.

Congenital corneal staphyloma is a rare congenital malformation with guarded visual potential. The cornea is opaque, markedly ectatic, and lined by uveal tissue with a variety of associated anterior segment abnormalities. In this case report, the detailed histopathology of this condition is highlighted with an unusual finding of the malformed lens. [J Pediatr Ophthalmol Strabismus. 2024;61(3):e28-e32.].

Association of Novel Loci With Keratoconus Susceptibility in a Chinese Genome-Wide Association Study.

Purpose: Keratoconus (KC) is a progressive corneal disease that can lead to corneal blindness if not properly managed. The purpose of this study was to identify genetic associations with KC in China and to investigate whether these genetic variants are associated with corneal thickness and corneal curvature in KC cases. Methods: A genome-wide association study was conducted on 853 patients with KC and 6248 controls. The KC cases were genotyped with the Illumina Infinium Human Asian Screening Array BeadChip, and the controls were genotyped with the Illumina Infinium Human Global Screening Array BeadChip. Genetic associations with KC, as well as correlations between the positive variants and corneal parameters including central corneal thickness (CCT) and mean keratometry (Km), were compared using PLINK version 1.90. Results: Our present study identified four single-nucleotide polymorphisms (SNPs) within four risk loci (PTGER3: rs2300163, EYA1: rs1077435, ASS1: rs141365191, and CHTF8: rs3743680) associated with KC in Chinese patients that reached genome-wide significance. Among the identified SNPs with P < 1.00 × 10-4, seven SNPs (FOSL2-PLB1: rs12622211, RXRA-COL5A1: rs3118515, rs3132306, rs1536482, rs3118520, KAT6B: rs192187772, RAP2A-IPO5: rs41361245) were observed to be associated with CCT, and one SNP (USP13: rs6767552) was found to be associated with Km. Conclusions: In the first genome-wide association study of KC with a relatively large study population in China, we identified four SNPs in four risk loci associated with the disease. The findings enriched the understanding of genetic susceptibility to KC and provided new insights into the genetic etiology of the disease.

Macular corneal dystrophy with iridofundal coloboma in the same patient: a unique combination.

A young a presented with painless, progressive diminution of vision in both eyes (BE). Slit lamp examination revealed the presence of a single central corneal opacity in the right eye and multiple corneal opacities of varying sizes in the left eye (LE), limited to the anterior-mid corneal stroma. Microcornea with reduced central corneal thickness and complete inferonasal iris coloboma along with inferior fundal coloboma, sparing both the disc and macula, were noted in BE. A diagnosis of BE macular corneal dystrophy (MCD) and iridofundal coloboma (IFC) was made. The patient underwent LE sutureless anterior lamellar therapeutic keratoplasty. On histopathological examination, the excised corneal tissue revealed stromal lamellar disarray with positive colloidal iron staining, strongly suggestive of MCD. Whole-exome sequencing revealed the presence of a likely pathogenic carbohydrate sulfotransferase 6 (CHST6) mutation, confirming the diagnosis of MCD. This concurrent presence of IFC with a corneal stromal dystrophy is previously unreported in the literature, to the best of our knowledge.

[Current possibilities for the diagnosis and treatment of pterygium]. / Sovremennye vozmozhnosti diagnostiki i lecheniya pterigiuma.

Pterygium is a common inflammatory-proliferative disease characterized by the invasion of degeneratively altered fibrovascular tissue into the cornea. This literature review analyzes the etiological factors and pathogenetic concepts of its development, describes modern methods of diagnostics and surgical treatment of pterygium, and pays particular attention to the assessment of structural and functional changes in the cornea occurring during the growth of pterygium and after its excision.

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

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

Establishing Standardization Guidelines For Finite-Element Optomechanical Simulations of Refractive Laser Surgeries: An Application to Photorefractive Keratectomy.

Purpose: Computational models can help clinicians plan surgeries by accounting for factors such as mechanical imbalances or testing different surgical techniques beforehand. Different levels of modeling complexity are found in the literature, and it is still not clear what aspects should be included to obtain accurate results in finite-element (FE) corneal models. This work presents a methodology to narrow down minimal requirements of modeling features to report clinical data for a refractive intervention such as PRK. Methods: A pipeline to create FE models of a refractive surgery is presented: It tests different geometries, boundary conditions, loading, and mesh size on the optomechanical simulation output. The mechanical model for the corneal tissue accounts for the collagen fiber distribution in human corneas. Both mechanical and optical outcome are analyzed for the different models. Finally, the methodology is applied to five patient-specific models to ensure accuracy. Results: To simulate the postsurgical corneal optomechanics, our results suggest that the most precise outcome is obtained with patient-specific models with a 100 µm mesh size, sliding boundary condition at the limbus, and intraocular pressure enforced as a distributed load. Conclusions: A methodology for laser surgery simulation has been developed that is able to reproduce the optical target of the laser intervention while also analyzing the mechanical outcome. Translational Relevance: The lack of standardization in modeling refractive interventions leads to different simulation strategies, making difficult to compare them against other publications. This work establishes the standardization guidelines to be followed when performing optomechanical simulations of refractive interventions.

[Influence of corneal curvature and peripheral thickness on tonometry readings]. / Vliyanie krivizny i perifericheskoi tolshchiny rogovitsy na rezul'tat tonometrii.

PURPOSE: This study investigates the influence of peripheral corneal thickness (PCT) and its curvature on tonometry readings. MATERIAL AND METHODS: The study included 49 patients (49 eyes) who were indicated for glaucoma surgery. Using bidirectional applanation tonometry, the following parameters were obtained: IOPcc, IOPg - intraocular pressure (IOP) corrected for corneal compensation, taken as the most reliable indicator; IOP converted to Goldmann measurement, taken as the result of applanation tonometry, ΔIOP (IOPcc-IOPg), CH and CRF (corneal hysteresis and corneal resistance factor). During corneal topography, the corneal thickness was studied in the center, PCT at 1.5; 2, 3, 4 and 5 mm from the center in four meridians, as well as ΔPCT (PCT 3 mm - PCT 1.5 mm), the curvature of the anterior and posterior surfaces of the cornea and the depth of the anterior chamber. Aberrometry was used to obtain refractometry data and the curvature of the anterior surface of the cornea. The influence of the studied parameters on ΔIOP was evaluated. RESULTS: ΔIOP correlated with CRF (r= -0.652), CH (r= -0.873), central corneal thickness (r= -0.293), PCT at all distances except 5 mm (r= -0.297; -0.287; -0.302; -0.303), with the strong and weak meridians of the anterior surface of the cornea (r=0.328; r=0.315), with the strong and weak meridians of the posterior surface, as well as the average curvature of the posterior surface (r=0.307; r=0.332; r=0.328). After step-by-step selection of the above parameters for creating a linear regression model for ΔIOP calculation, CH, CRF and PCT1.5mm remained in the model. The model describes ΔIOP with high accuracy (R2=0.974). CONCLUSION: Biomechanical parameters of the cornea are the leading factor of applanation tonometry error. Individual linear dimensions of the cornea (thickness, curvature) have a lesser effect.