Ophthalmic Diseases Research Articles

Generation of Anterior Segment of the Eye Cells from hiPSCs in Microfluidic Platforms.

Ophthalmic diseases affect many people, causing partial or total loss of vision and a reduced quality of life. The anterior segment of the eye accounts for nearly half of all visual impairment that can lead to blindness. Therefore, there is a growing demand for ocular research and regenerative medicine that specifically targets the anterior segment to improve vision quality. This study aims to generate a microfluidic platform for investigating the formation of the anterior segment of the eye derived from human induced pluripotent stem cells (hiPSC) under various spatial-mechanoresponsive conditions. Microfluidic platforms are developed to examine the effects of dynamic conditions on the generation of hiPSCs-derived ocular organoids. The differentiation protocol is validated, and mechanoresponsive genes are identified through transcriptomic analysis. Several culture strategies is implemented for the anterior segment of eye cells in a microfluidic chip. hiPSC-derived cells showed anterior eye cell characteristics in mRNA and protein expression levels under dynamic culture conditions. The expression levels of yes-associated protein and transcriptional coactivator PDZ binding motif (YAP/TAZ) and PIEZO1, varied depending on the differentiation and growth conditions of the cells, as well as the metabolomic profiles under dynamic culture conditions.

RVS-FDSC: A retinal vessel segmentation method with four-directional strip convolution to enhance feature extraction

Retinal vessel segmentation is important to assist ophthalmologists in the diagnosis and treatment of ophthalmic diseases. However, traditional convolutional neural networks (CNNs) are constrained by using square convolution kernels for retinal vessel feature extraction, thereby overlooking the structural characteristics of retinal vessels, which to some extent limits model performance. Consequently, we propose a retinal vessel segmentation method with four-directional strip convolution to enhance feature extraction (RVS-FDSC). Firstly, due to the shape structure of retinal vessels which have branching paths and appear locally as strips, we have constructed a residual strip convolution (RSC) module by using strip convolutions in four different directions: horizontal, vertical, antidiagonal, and main diagonal. These four directions can roughly simulate the branching directions of vessels, making it possible to better extract vessel features. Furthermore, to more comprehensively understand and utilize both local details and global context, RVS-FDSC introduces a multi-scale pooling feature fusion (MSPF2) module. Finally, to better focus on important features and reduce the attention to unimportant or redundant information, RVS-FDSC introduces a residual parallel dual attention (RPDA) module. We conduct experiments on three retinal vessel segmentation datasets: DRIVE, CHASE-DB1, and STARE. RVS-FDSC achieves excellent results on these three public datasets, with AUC of 0.9856, 0.9867, and 0.9808, Acc of 0.9692, 0.9743, and 0.9718, and Spe of 0.9878, 0.9856 and 0.9882, respectively. These results indicate the superior performance of RVS-FDSC compared to other state-of-the-art methods.

Validation of an enzyme-linked immunosorbent assay test-system for bevacizumab concentration determing in biological fluids

Introduction. One of the reasons for the development of many diseases primarily malignant is the increased expression of Vascular Endothelial Growth Factor (VEGF). Bevacizumab is a drug that neutralizes the biological activity of VEGF. The molecular structure of bevacizumab is a recombinant humanized antibody. Its use reduces vascularization in the foci of increased VEGF expression which slows down tumor growth and also helps restore vision in a number of ophthalmic diseases. To determine the concentration of bevacizumab in human biological fluids a test system based on Enzyme-linked Immunosorbent Assay (ELISA) is presented.Aim. Aim of this study is the validation of this test system.Materials and methods. Blank sera of volunteers, bevacizumab solution, enzyme-linked immunosorbent assay, solid-phase sandwich ELISA kit, microplate photometer.Results and discussion. The following characteristics of the test system were determined: the lower limit of quantification is 2.0 mcg/ml, the upper calibration range is up to 200 mcg/ml, the accuracy and precision within one series and between series does not exceed 20 %, and the total error of the method – 30 %, short-term stability for samples at room temperature – 6 hours, long-term stability – 14 days at –20 °C, the ability to freeze/thaw of samples is up to three times, the ability to determine samples with a concentration above the upper calibrator after diluting in 2 times.Conclusion. The results obtained fully comply with international acceptance criteria and allow the use of the ELISA test system manufactured by LLC "Probiotek" for use in the field of clinical laboratory diagnostics.

A novel multi-ingredient supplement significantly improves ocular symptom severity and tear production in patients with dry eye disease: results from a randomized, placebo-controlled clinical trial.

Dry eye disease (DED) is multifactorial and characterized by a loss of tear film homeostasis that causes a cycle of tear film instability, tear hyperosmolarity, and inflammation. While artificial tears are the traditional mainstay of treatment, addressing the underlying pathophysiology could relieve symptoms and prevent progression. Increasing evidence indicates a role for oral nutritional supplementation in multiple ophthalmic diseases, including DED. Lutein, zeaxanthin, curcumin, and vitamin D3 have demonstrated protective and anti-inflammatory properties in ocular models. This prospective, randomized, double-blind, parallel, placebo-controlled study evaluated the efficacy and safety of a proprietary blend of lutein, zeaxanthin isomers, curcumin, and vitamin D3 (LCD) as a daily supplement in adult participants with DED. Participants were randomized to receive one LCD supplement capsule (lutein 20 mg, zeaxanthin isomers 4 mg, curcumin 200 mg curcuminoids, and vitamin D3 600 IU) or placebo per day for 8 weeks (LCD, n=77; placebo, n=78). Primary outcomes were changes in tear volume (Schirmer's test) and ocular symptoms (Ocular Surface Disease Index [OSDI]). The study met its primary endpoints: the LCD group demonstrated significantly better Schirmer's test scores and improvement in overall OSDI score, versus placebo, at Day 56 (p<0.001 for both). Scores for total OSDI, and symptoms and vision domains, significantly improved by Day 14 for LCD versus placebo, (p<0.05 for all) and were maintained to Day 56 (p<0.001). In addition, the LCD group demonstrated significantly improved tear film break-up time (TBUT) and tear film osmolarity, versus placebo, by Day 56 (p<0.001), along with significant improvements in corneal and conjunctival staining (p<0.001 for both), and inflammation (matrix metalloproteinase-9; p<0.001 for each eye). Total Standard Patient Evaluation of Eye Dryness (SPEED) score, and scores for the frequency and severity domains, were significantly improved by Day 14 for LCD versus placebo (p<0.05 for all) and maintained to Day 56 (p<0.001). There was no difference between groups for artificial tear usage. The supplement was well-tolerated. Once-daily LCD supplementation significantly improved tear production, stability and quality, reduced ocular surface damage and inflammation, and improved participants' symptoms. LCD supplementation could offer a useful adjunct to artificial tears for patients with DED (NCT05481450).

Genetic correlation between circulating cytokines and risk of three ophthalmic diseases: a bidirectional two-sample Mendelian randomization study.

Pathogenesis and the associated risk factors of cataracts, glaucoma, and age-related macular degeneration (AMD) remain unclear. We aimed to investigate causal relationships between circulating cytokine levels and the development of these diseases. Genetic instrumental variables for circulating cytokines were derived from a genome-wide association study of 8293 European participants. Summary-level data for AMD, glaucoma, and senile cataract were obtained from the FinnGen database. The inverse variance weighted (IVW) was the main Mendelian randomization (MR) analysis method. The Cochran's Q, MR-Egger regression, and MR pleiotropy residual sum and outlier test were used for sensitivity analysis. Based on the IVW method, MR analysis demonstrated five circulating cytokines suggestively associated with AMD (SCGF-β, 1.099 [95%CI, 1.037-1.166], P = 0.002; SCF, 1.155 [95%CI, 1.015-1.315], P = 0.029; MCP-1, 1.103 [95%CI, 1.012-1.202], P = 0.026; IL-10, 1.102 [95%CI, 1.012-1.200], P = 0.025; eotaxin, 1.086 [95%CI, 1.002-1.176], P = 0.044), five suggestively linked with glaucoma (MCP-1, 0.945 [95%CI, 0.894-0.999], P = 0.047; IL1ra, 0.886 [95%CI, 0.809-0.969], P = 0.008; IL-1β, 0.866 [95%CI, 0.762-0.983], P = 0.027; IL-9, 0.908 [95%CI, 0.841-0.980], P = 0.014; IL2ra, 1.065 [95%CI, 1.004-1.130], P = 0.035), and four suggestively associated with senile cataract (TRAIL, 1.043 [95%CI, 1.009-1.077], P = 0.011; IL-16, 1.032 [95%CI, 1.001-1.064], P = 0.046; IL1ra, 0.942 [95%CI, 0.887-0.999], P = 0.047; FGF-basic, 1.144 [95%CI, 1.052-1.244], P = 0.002). Furthermore, sensitivity analysis results supported the above associations. This study highlights the involvement of several circulating cytokines in the development ophthalmic diseases and holds potential as viable pharmacological targets for these diseases.

Advances in artificial intelligence in thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO), also referred to as Graves' ophthalmopathy, is a medical condition wherein ocular complications arise due to autoimmune thyroid illness. The diagnosis of TAO, reliant on imaging, typical ocular symptoms, and abnormalities in thyroid function or thyroid-associated antibodies, is generally graded and staged. In recent years, Artificial intelligence(AI), particularly deep learning(DL) technology, has gained widespread use in the diagnosis and treatment of ophthalmic diseases. This paper presents a discussion on specific studies involving AI, specifically DL, in the context of TAO, highlighting their applications in TAO diagnosis, staging, grading, and treatment decisions. Additionally, it addresses certain limitations in AI research on TAO and potential future directions for the field.

Bi-directional ConvLSTM residual U-Net retinal vessel segmentation algorithm with improved focal loss function

Accurate blood vessel segmentation on retinal blood vessel images is helpful for the early detection of ophthalmic diseases such as diabetes, hypertension, cardiovascular and cerebrovascular diseases, and inhibits the deterioration of the disease. In current research within the field of retinal blood vessel segmentation, significant challenges exist in accurately segmenting small blood vessels and maintaining blood vessel continuity. The segmentation algorithm proposed in this article offers substantial improvements to address these issues. To enhance the segmentation performance of retinal blood vessels and facilitate more accurate diagnosis of fundus diseases by ophthalmologists, this paper introduces a novel bidirectional convolutional long short-term memory (LSTM) residual U-Net segmentation algorithm, incorporating improvements to the Focal loss function. Firstly, in the encoding part of U-Net, the multi-scale convolution kernels and Bi-ConvLSTM were adopted to improve the residual structure, obtain richer blood vessel features and enhance the detection ability of micro vessels and the continuity of blood vessel characteristics. At the same time, the class balanced cross entropy loss function was improved and the proportional modulation factor is introduced to enhance the learning ability of the network for difficult samples. By adding the Bi-ConvLSTM to the residual structure and introducing the proportional modulation coefficient to the loss function, the network structure realizes better feature information detection and greatly enhances the detection ability of small blood vessels. The experimental analysis on the DRIVE and CHASE_DB1 data sets showed that the sensitivity, specificity, accuracy and AUC reached 0.7961, 0.9796, 0.9563, 0.9792; 0.8344, 0.9665, 0.9547, 0.9758, respectively. The experimental results fully show that the Bi-ConvLSTM residual U-Net segmentation algorithm based on the improved Focal loss function enhances the detection ability of small blood vessel features, improves the continuity of blood vessel features and the network segmentation performance, and is superior to U-Net algorithm and some current mainstream retinal blood vessel segmentation algorithms.

Regulatory role of Echinochrome A in cancer-associated fibroblast-mediated lung cancer cell migration.

Echinochrome A (Ech A), a marine biosubstance isolated from sea urchins, is a strong antioxidant, and its clinical form, histochrome, is being used to treat several diseases, such as ophthalmic, cardiovascular, and metabolic diseases. Cancer-associated fibroblasts (CAFs) are a component of the tumor stroma and induce phenotypes related to tumor malignancy, including epithelial-mesenchymal transition (EMT) and cancer stemness, through reciprocal interactions with cancer cells. Here, we investigated whether Ech A modulates the properties of CAFs and alleviates CAF-induced lung cancer cell migration. First, we observed that the expression levels of CAF markers, Vimentin and fibroblast-activating protein (FAP), were decreased in Ech A-treated CAF-like MRC5 cells. The mRNA transcriptome analysis revealed that in MRC5 cells, the expression of genes associated with cell migration was largely modulated after Ech A treatment. In particular, the expression and secretion of cytokine and chemokine, such as IL6 and CCL2, stimulating cancer cell metastasis was reduced through the inactivation of STAT3 and Akt in MRC5 cells treated with Ech A compared to untreated MRC5 cells. Moreover, while conditioned medium from MRC5 cells enhanced the migration of non-small cell lung cancer cells, conditioned medium from MRC5 cells treated with Ech A suppressed cancer cell migration. In conclusion, we suggest that Ech A might be a potent adjuvant that increases the efficacy of cancer treatments to mitigate lung cancer progression.

FNeXter: A Multi-Scale Feature Fusion Network Based on ConvNeXt and Transformer for Retinal OCT Fluid Segmentation.

The accurate segmentation and quantification of retinal fluid in Optical Coherence Tomography (OCT) images are crucial for the diagnosis and treatment of ophthalmic diseases such as age-related macular degeneration. However, the accurate segmentation of retinal fluid is challenging due to significant variations in the size, position, and shape of fluid, as well as their complex, curved boundaries. To address these challenges, we propose a novel multi-scale feature fusion attention network (FNeXter), based on ConvNeXt and Transformer, for OCT fluid segmentation. In FNeXter, we introduce a novel global multi-scale hybrid encoder module that integrates ConvNeXt, Transformer, and region-aware spatial attention. This module can capture long-range dependencies and non-local similarities while also focusing on local features. Moreover, this module possesses the spatial region-aware capabilities, enabling it to adaptively focus on the lesions regions. Additionally, we propose a novel self-adaptive multi-scale feature fusion attention module to enhance the skip connections between the encoder and the decoder. The inclusion of this module elevates the model's capacity to learn global features and multi-scale contextual information effectively. Finally, we conduct comprehensive experiments to evaluate the performance of the proposed FNeXter. Experimental results demonstrate that our proposed approach outperforms other state-of-the-art methods in the task of fluid segmentation.

Nationwide Screening Practices for Tamoxifen Retinal Toxicity in South Korea: A Population-Based Cohort Study.

(1) Background/Objectives: To investigate the nationwide screening practices and trends in tamoxifen retinal toxicity (tamoxifen retinopathy) in South Korea using national health insurance claims data. (2) Methods: A total of 43,848 patients who started tamoxifen therapy between 2015 and 2020 and had no prior ophthalmic diseases or other conditions requiring screening for retinopathy were included. The annual numbers of tamoxifen users and new initiators of tamoxifen therapy were assessed. The screening examinations were separated into baseline (first ophthalmic examination after tamoxifen administration) and subsequent monitoring examinations. The timing and modalities for the baseline and subsequent monitoring examinations performed between 2015 and 2021 were assessed in tamoxifen users. (3) Results: The annual number of tamoxifen users increased over the study period from 54,056 in 2015 to 81,720 in 2021. The number of patients who underwent ophthalmic examination after tamoxifen administration was 8961 (20.4%). Baseline screening was performed in 6.5% of patients within 1 year of use, and subsequent monitoring was performed in 27.8% of patients who underwent baseline screening. Funduscopy or fundus photography was performed most commonly for baseline screening and subsequent monitoring (99.0% and 98.6%, respectively), while optical coherence tomography was performed only in 21.9% and 29.6% of baseline and monitoring examinations, respectively. The average number of monitoring examinations per year was 0.68 ± 0.45. Although the annual percentage of patients receiving a baseline examination within 1 year gradually increased over time, the percentage of those with subsequent monitoring performed within 1 year was similar over the study period. (4) Conclusions: Our finding, appropriate screening in a small proportion of patients receiving tamoxifen, suggests the need to promote awareness among healthcare professionals and develop a standardized approach for screening for tamoxifen retinopathy.

Comparison of veterinarians and a deep learning tool in the diagnosis of equine ophthalmic diseases.

The aim was to compare ophthalmic diagnoses made by veterinarians to a deep learning (artificial intelligence) software tool which was developed to aid in the diagnosis of equine ophthalmic diseases. As equine ophthalmology is a very specialised field in equine medicine, the tool may be able to help in diagnosing equine ophthalmic emergencies such as uveitis. In silico tool development and assessment of diagnostic performance. A deep learning tool which was developed and trained for classification of equine ophthalmic diseases was tested with 40 photographs displaying various equine ophthalmic diseases. The same data set was shown to different groups of veterinarians (equine, small animal, mixed practice, other) using an opinion poll to compare the results and evaluate the performance of the programme. Convolutional Neural Networks (CNN) were trained on 2346 photographs of equine eyes, which were augmented to 9384 images. Two hundred and sixty-one separate unmodified images were used to evaluate the trained network. The trained deep learning tool was used on 40 photographs of equine eyes (10 healthy, 12 uveitis, 18 other diseases). An opinion poll was used to evaluate the diagnostic performance of 148 veterinarians in comparison to the software tool. The probability for the correct answer was 93% for the AI programme. Equine veterinarians answered correctly in 76%, whereas other veterinarians reached 67% probability for the correct diagnosis. Diagnosis was solely based on images of equine eyes without the possibility to evaluate the inner eye. The deep learning tool proved to be at least equivalent to veterinarians in assessing ophthalmic diseases in photographs. We therefore conclude that the software tool may be useful in detecting potential emergency cases. In this context, blindness in horses may be prevented as the horse can receive accurate treatment or can be sent to an equine hospital. Furthermore, the tool gives less experienced veterinarians the opportunity to differentiate between uveitis and other ocular anterior segment disease and to support them in their decision-making regarding treatment.

Dynamics of Structural and Functional Changes of Patients with Dry Form Age-related Macular Degeneration after Double Filtration Plasmapheresis

Actuality. One of the significant ophthalmic diseases is a dry form age-related macular degeneration (dAMD). The issues of etiology and pathogenesis are not completely cleared nowadays and they signify the subject of discussion. There are risk factors of dAMD (age, heredity, lifestyle etc.) which can cause metabolic disorders, changes hemorheological parameters which promote activation of druseogenesis and as a result an angiogenesis. Mostly an outcome of dAMD is geographical atrophy and decrease of central visual acuity. At the same time, it is known that similar metabolic and rheological disorders detected in other diseases are effectively corrected by extracorporeal rheoaferesis, in particular, using double filtration plasmapheresis. Thus, using of extracorporeal rheoaferesis with dAMD patients is pathogenetically well-reasoned, but in the available literature, a correct analysis of the effectiveness and safety of double filtration plasmapheresis in patients with intermediate stage of dAMD is presented poorly.Objective. To study along with data of OCT, OCT angiography, visometry, microperimetry and electroretinography structural and functional changes in the macular zone in patients with a dry form of age-related macular degeneration after the using of double filtration plasmapheresis.Patients and methods. The study included 63 patients (94 eyes) with an intermediate stage of dAMD. The patients were separated into two groups randomly. The first (main) group included 34 patients (52 eyes) who were performed double filtration plasmapheresis (DFPP) on an OctoNova device using a Plasmaflo plasma filter and a Cascadeflo EC40 fractionator in the amount of 4 procedures with a frequency of 1 time per week for 1 month. The second group (control) included 29 patients (42 eyes) who did not receive any specific treatment. In the main group of patients, OCT, OCT angiography, microperimetry and electroretinography were additionally performed in addition to standard ophthalmological examination before the DFPP course, after the DFPP course (1 month after the start of follow-up), 6 and 12 months later. Patients in the control group also underwent a similar examination at the specified time — 1, 6, 12 months after the start of follow-up.Results. In this study we found according to optical coherence tomography, optical coherence tomography-angiography, visometry, microperimetry and electroretinography, positive dynamics of structural and functional parameters of the macular retina is observed in patients with a dry form of age-related macular degeneration with using double filtration plasmapheresis. At the same time, a statistically significant difference between the two groups begins at 1 month and persists for 12 months of follow-up, which points to stabilization of the pathological process during the specified period.Conclusions. This study showed that after applying the double filtration plasmapheresis in patients with dry form of age-related macular degeneration, there is an improvement in structural and functional parameters of the macular zone, consisting in a decrease volume DOPES and stabilization of retinal light sensitivity.

Brillouin microscopic imaging of ex-vivo porcine eye using VIPA-CMOS-based spectrometer

The research on non-invasive ophthalmic imaging has become a hot topic in diagnosing ophthalmic diseases, especially assessment of corneal biomechanics has been an unmet clinical need in ophthalmology for many years. The Brillouin microscopy technique based on spontaneous Brillouin scattering has emerged as a unique elastography method due to its advantages of non-contact, label-free, and high-resolution biomechanical imaging of biological tissues. Here, we developed a three-dimensional (3D) optical microscope system for ex-vivo porcine cornea Brillouin imaging. To do this, we designed and experimentally demonstrated a setup with double-stage VIPA etalons and CMOS camera that integrate to a fully parallel dispersive Brillouin spectrometer. The designed spectrometer exhibits a smaller dispersion rate to enhance the spectral sampling rate and downsizes the size of the double-stage-based system. Using the optical microscope system, we measured and mapped the Brillouin frequency shifts of the cornea and crystalline lens in ex-vivo porcine eyes at micron-scale spatial resolution, and a spectral accuracy of < 50 MHz can be achieved without interpolating the spectra. This work is essential for future applications of Brillouin microscopy in clinical diagnosis and treatment of ophthalmic diseases.

The role of oxidative stress in the pathogenesis of ocular diseases: an overview.

Dysregulation of oxidative stress serves as a pivotal predisposing or exacerbating factor in the intricate development of numerous pathological processes and diseases. In recent years, substantial evidence has illuminated the crucial role of reactive oxygen species (ROS) in many fundamental cellular functions, including proliferation, inflammation, apoptosis, and gene expression. Notably, producing free radicals within ROS profoundly impacts a wide range of biomolecules, such as proteins and DNA, instigating cellular damage and impairing vital cellular functions. Consequently, oxidative stress emerges as a closely intertwined factor across diverse disease spectra. Remarkably, the pathogenesis of several eye diseases, including age-related macular degeneration, glaucoma, and diabetic retinopathy, manifests an intrinsic association with oxidative stress. In this comprehensive review, we briefly summarize the recent progress in elucidating the intricate role of oxidative stress in the development of ophthalmic diseases, shedding light on potential therapeutic avenues and future research directions.

The 6-Item Vision-Related Quality of Life and Limitations Questionnaire: Evaluation of Psychometric Properties.

We developed the Vision-related Quality of life and Limitations Questionnaire (VQL-6), a screening instrument to signal a need for additional care resulting from reduced vision-related quality of life in patients with chronic ophthalmic diseases. The aim of the present study was to evaluate psychometric properties. A Dutch population-based sample of 2032 participants (mean age, 55 ± 19 years) completed the VQL-6 and other questionnaires on vision-related quality of life, executive functioning, attention, mental health, and symptom validity. In addition, we recruited a sample of 208 ophthalmic patients (mean age, 72 ± 12 years) and 98 age and gender similar controls (mean age, 69 ± 11 years) who completed the VQL-6 and the National Eye Institute Visual Function Questionnaire-25. We studied the factor structure, internal consistency, convergent and divergent validity, and known-groups validity. For the factor analyses, the population-based sample was split randomly in two subsamples. Exploratory factor analysis on the first subsample suggested a two-factor model (visual limitations and general health and quality of life), which was supported by confirmatory factor analyses on the second subsample, and on the patients. The VQL-6 demonstrated good internal consistency within each factor (0.78-0.89), sufficient convergent (r2= 55%) and divergent validity (r2 = 11%-24%), and good known-groups validity (Cohen's r = 0.57; P < 0.001). The VQL-6 has a robust two-factor structure and seems to be a valid tool to assess vision-related quality of life. Additional validation is needed in patients with chronic ophthalmic diseases. Future research is needed to determine if the VQL-6 can be used to identify patients with chronic ophthalmic diseases who are in need of additional care.

PrimPol Variant V102A with Altered Primase and Polymerase Activities

PrimPol is a human DNA primase-polymerase which restarts DNA synthesis beyond DNA lesions and non-B DNA structures blocking replication. Disfunction of PrimPol in cells leads to slowing of DNA replication rates in mitochondria and nucleus, accumulation of chromosome aberrations, cell cycle delay, and elevated sensitivity to DNA-damaging agents. A defective PrimPol has been suggested to be associated with the development of ophthalmic diseases, elevated mitochondrial toxicity of antiviral drugs and increased cell resistance to chemotherapy. Here, we describe a rare missense PrimPol variant V102A with altered biochemical properties identified in patients suffering from ovarian and cervical cancer. The Val102 to Ala substitution dramatically reduced both the primase and DNA polymerase activities of PrimPol as well as specifically decreased its ability to incorporate ribonucleotides. Structural analysis indicates that the V102A substitution can destabilize the hydrophobic pocket adjacent to the active site, affecting dNTP binding and catalysis.

PGKD-Net: Prior-guided and Knowledge Diffusive Network for Choroid Segmentation

The thickness of the choroid is considered to be an important indicator of clinical diagnosis. Therefore, accurate choroid segmentation in retinal OCT images is crucial for monitoring various ophthalmic diseases. However, this is still challenging due to the blurry boundaries and interference from other lesions. To address these issues, we propose a novel prior-guided and knowledge diffusive network (PGKD-Net) to fully utilize retinal structural information to highlight choroidal region features and boost segmentation performance. Specifically, it is composed of two parts: a Prior-mask Guided Network (PG-Net) for coarse segmentation and a Knowledge Diffusive Network (KD-Net) for fine segmentation. In addition, we design two novel feature enhancement modules, Multi-Scale Context Aggregation (MSCA) and Multi-Level Feature Fusion (MLFF). The MSCA module captures the long-distance dependencies between features from different receptive fields and improves the model’s ability to learn global context. The MLFF module integrates the cascaded context knowledge learned from PG-Net to benefit fine-level segmentation. Comprehensive experiments are conducted to evaluate the performance of the proposed PGKD-Net. Experimental results show that our proposed method achieves superior segmentation accuracy over other state-of-the-art methods. Our code is made up publicly available at: https://github.com/yzh-hdu/choroid-segmentation.

A bird’s eye view on the use of whole exome sequencing in rare congenital ophthalmic diseases

Phenotypic and genotypic heterogeneity in congenital ocular diseases, especially in anterior segment dysgenesis (ASD), have created challenges for proper diagnosis and classification of diseases. Over the last decade, genomic research has indeed boosted our understanding in the molecular basis of ASD and genes associated with both autosomal dominant and recessive patterns of inheritance have been described with a wide range of expressivity. Here we describe the molecular characterization of a cohort of 162 patients displaying isolated or syndromic congenital ocular dysgenesis. Samples were analyzed with diverse techniques, such as direct sequencing, multiplex ligation-dependent probe amplification, and whole exome sequencing (WES), over 20 years. Our data reiterate the notion that PAX6 alterations are primarily associated with ASD, mostly aniridia, since the majority of the cohort (66.7%) has a pathogenic or likely pathogenic variant in the PAX6 locus. Unexpectedly, a high fraction of positive samples (20.3%) displayed deletions involving the 11p13 locus, either partially/totally involving PAX6 coding region or abolishing its critical regulatory region, underlying its significance. Most importantly, the use of WES has allowed us to both assess variants in known ASD genes (i.e., CYP1B1, ITPR1, MAB21L1, PXDN, and PITX2) and to identify rarer phenotypes (i.e., MIDAS, oculogastrointestinal-neurodevelopmental syndrome and Jacobsen syndrome). Our data clearly suggest that WES allows expanding the analytical portfolio of ocular dysgenesis, both isolated and syndromic, and that is pivotal for the differential diagnosis of those conditions in which there may be phenotypic overlaps and in general in ASD.

Incidence and Clinical Characteristics of COVID-19 Ophthalmopathy Following the Termination of Dynamic Zero COVID-19 Strategy in China

ABSTRACT Ocular involvement is not uncommon in patients with COVID-19. However, the incidence of COVID-19 ophthalmopathy in COVID-19 patients is still not clear. In this prospective case series study, we recruited 2445 consecutive cases presenting at Neuro-ophthalmology clinic of our Eye Center during the last resurgence of SARS-CoV-2 infection from 8 December 2022 to 15 March 2023 in China, 149 cases were diagnosed as COVID-19 ophthalmopathy, 87 cases were female, with a mean age of 43.2 years, and the mean follow-up time was 15.4 weeks. One hundred and twenty of 149 cases suffered from systemic symptoms mostly manifesting as fever, cough and muscle pain prior to or soon after ocular involvement. The most common COVID-19 ophthalmopathy was optic neuritis (51/149), followed by acute zonal occult outer retinopathy complex disease (31/149), uveitis (17/149), ocular mobility disorder-related (third, fourth, or sixth) cranial nerve neuritis (15/149), anterior ischaemic optic neuropathy (9/149), retinal artery occlusion (8/149), retinal microangiopathy including retinal haemorrhage and cotton wool spot (8/149), viral conjunctivitis (7/149), retinal vein occlusion (3/149), viral keratitis (2/149), ptosis (2/149), and other rare ocular diseases. Except 5 cases with central retinal artery occlusion, other 144 COVID-19 ophthalmopathy cases showed good response to steroid therapy. Our study revealed an incidence of 6.09% for COVID-19 ophthalmopathy in outpatients at our Neuro-ophthalmology clinic during last resurgence of COVID-19 in China, and demonstrated that SARS-CoV-2 infection could induce an initial onset or a relapse of ophthalmic diseases, and that ocular involvement might manifest as the initial or even the only presentation of COVID-19.

Актуальные проблемы эпидемиологии офтальмологической заболеваемости среди молодежи России и Центрального федерального округа.

Indicators of primary morbidity of the eyes and their appendages in adolescents aged 15–17 years and young people, in particular among students of higher educational institutions, increase annually due to increased visual stress as risk factors. The purpose of the work is to identify current problems in the epidemiology of ophthalmological morbidity among young people in the Russian Federation and the Central Federal District. Materials and methods. A theoretical analysis of the literature on the epidemiology of ophthalmic diseases in young people and a search for statistical data on the epidemiology of ophthalmic diseases was carried out. To assess the dynamics of epidemiological indicators, an increase calculation was carried out. Results. The increase in the incidence of visual organs in adolescents per 100 thousand children aged 15–17 years from 2000 to 2021 was +47.9%, and from 2018 to 2019 the increase in the incidence of myopia was +9.2%. In the structure of diseases for adolescents, it is pathologies of the visual organs that lead, and 40% of students have visual impairments, the detection of which increases by 3–7% annually, while the severity of myopia grows every year by 5–7%. The increase in morbidity of the eyes and adnexa in the Central Federal District for 2019–2021 was +57.5%, however, morbidity statistics do not consider the age distribution of diseases and their structure. The largest (+296.0 +110.1%) increase per 100 thousand population is observed for the Vladimir, Voronezh, Lipetsk, Ivanovo and Kaluga regions. It was revealed that in 2017, the incidence rate of eyes and their appendages in the Voronezh region over 10 years increased from 64.8 to 94.8 per 1000 students, 45.6% of students had impaired visual acuity. In the region, there is a staff shortage of ophthalmologists, insufficient coverage of preventive examinations and a low level of detection of patients at an early stage of disease. Conclusion. The epidemiology of eye diseases on the territory of the Russian Federation and its constituent entities in the young population has not been sufficiently studied. Improving regional analysis tools will help identify factors of variability in the epidemiology of eye diseases across the country’s regions. In regions with a high increase in ophthalmic morbidity, it is necessary to study in more detail the epidemiology of vision diseases in young people.