Cause Of Visual Impairment Research Articles

Targeted degradation of VEGF with bispecific aptamer-based LYTACs ameliorates pathological retinal angiogenesis.

Rationale: Neovascular ocular diseases (NODs) represent the leading cause of visual impairment globally. Despite significant advances in anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF), persistent challenges remain prevalent. As a proof-of-concept study, we herein demonstrate the effectiveness of targeted degradation of VEGF with bispecific aptamer-based lysosome-targeting chimeras (referred to as VED-LYTACs). Methods: VED-LYTACs were constructed with three distinct modules: a mannose-6-phosphate receptor (M6PR)-binding motif containing an M6PR aptamer, a VEGF-binding module with an aptamer targeting VEGF, and a linker essential for bridging and stabilizing the two-aptamer structure. The degradation efficiency of VED-LYTACs via the autophagy-lysosome system was examined using an enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining. Subsequently, the anti-angiogenic effects of VED-LYTACs were evaluated using in vitro wound healing assay, tube formation assay, three-dimensional sprouting assay, and ex vivo aortic ring sprouting assay. Finally, the potential therapeutic effects of VED-LYTACs on pathological retinal neovascularization and vascular leakage were tested by employing mouse models of NODs. Results: The engineered VED-LYTACs promote the interaction between M6PR and VEGF, consequently facilitating the translocation and degradation of VEGF through the lysosome. Our data show that treatment with VED-LYTACs significantly suppresses VEGF-induced angiogenic activities both in vitro and ex vivo. In addition, intravitreal injection of VED-LYTACs remarkably ameliorates abnormal vascular proliferation and leakage in mouse models of NODs. Conclusion: Our findings present a novel strategy for targeting VEGF degradation with an aptamer-based LYTAC system, effectively ameliorating pathological retinal angiogenesis. These results suggest that VED-LYTACs have potential as therapeutic agents for managing NODs.

The Prevalence of Refractive Errors Among Middle-Class Kids in and Around Dehradun

Background: Children living in countries with moderate income levels, such as India, who are born with untreated refractive abnormalities continue to face significant challenges. Despite the availability of low-cost remedial techniques like eyeglasses, uncorrected refractive defects cause vision loss for many children in India. This persists even though glasses may correct the problem. Aim: The aim of the present study is to investigate whether children from middle-income families exhibit any refractive errors. Materials & methods: The researchers conducted the present study after receiving approval from the institution’s ethics board. The research was carried out at Gautam Budha Chikitsa Mahavidyalaya, Jhajra, Dehradun, India. The study enrolled children from middle-income groups in and around the Dehradun city area. Results & Conclusions: The study revealed that refractive errors are the leading cause of visual impairment among school-age children, particularly those from middle-income families. Given that most refractive defects can be corrected with glasses, there is a need for cost-effective strategies to safeguard children’s eyesight. Such disabilities might impede a child’s development and education. There is compelling evidence supporting this treatable cause of blindness.

Myopia in Tanzania-My Approach

Childhood myopia is now an emerging issue in Tanzania. Today, billions of people around the world are struggling with the condition of myopia. This number is only expected to increase in the future and Africa is no exception. In Tanzania, due to increasing usage of smart phones and Visual Display Units (VDUs) there is an emerging Myopia in children as well as in adults. Data that documents the effects of visual impairment due to refractive error across the country is scant, however. Admittedly there exists a lack of lack of Ophthalmic /Optometry services leading to uncorrected refractive error that is a cause of vision impairment. Increases in life expectancy in Tanzania, and decreases in time spent outdoors, coupled with increased time spent staring at screens each day plays a part as well

On the structure of eye diseases in children leading to blindness or low vision in various countries of the world

The review presents differences in the nosological structure of ophthalmic pathology leading to childhood blindness and low vision in different countries. Worldwide, 1.4 million children are blind, about three quarters of whom live in the poorest regions of Africa or Asia. In lowincome countries, the congenital cataract is one of the leading causes of visual impairment in children, while retinopathy of prematurity is more common in middle-income countries. Uncorrected refractive errors both in children and adults, remain a major cause of visual impairment in all countries. The development of new technologies and quality medical care impacts the structure of blindness and low vision causes, as well as their geographical specificities. The analysis showed that much effort is required from large-scale state programs of prevention, early diagnosis, treatment and rehabilitation of children with socially significant eye diseases.

Research Progress of Diabetic Disease Prediction Model in Deep Learning

Diabetes is a metabolic disease characterized by high blood sugar, which is mostly caused by the defect of insulin secretion or the impairment of its biological function. The persistent high blood sugar in diabetes will damage various tissues, especially the brain, kidney, heart, nerves and so on. Diabetic disease is one of the main causes of visual impairment in diabetic patients. Early classification diagnosis is of great significance for the treatment and control of the disease. Deep learning methods can automatically extract the characteristics of retinopathy and classify them, so they become an important tool for the classification of diabetic retinopathy[1-3]. Firstly, the application of deep learning in the binary classification of diabetic retinopathy was summarized by introducing the commonly used data sets and evaluation indicators of diabetic retinopathy. Secondly, the application of different classical deep learning models in the classification of the severity of diabetic retinopathy was reviewed, with emphasis on the classification and diagnosis methods of convolutional neural network, and a comprehensive comparative analysis of different methods was made. Finally, the challenges facing this field are discussed and the future development direction is prospected.

The m6A reader YTHDC2 maintains visual function and retinal photoreceptor survival through modulating translation of PPEF2 and PDE6B

Inherited retinal dystrophies (IRDs) are major causes of visual impairment and irreversible blindness worldwide, while the precise molecular and genetic mechanisms are still elusive. N6-methyladenosine (m6A) modification is the most prevalent internal modification in eukaryotic mRNA. YTH domain containing 2 (YTHDC2), an m6A reader protein, has recently been identified as a key player in germline development and human cancer. However, its contribution to retinal function remains unknown. Here, we explore the role of YTHDC2 in the visual function of retinal rod photoreceptors by generating rod-specific Ythdc2 knockout mice. Results show that Ythdc2 deficiency in rods causes diminished scotopic ERG responses and progressive retinal degeneration. Multi-omics analysis further identifies Ppef2 and Pde6b as the potential targets of YTHDC2 in the retina. Specifically, via its YTH domain, YTHDC2 recognizes and binds m6A-modified Ppef2 mRNA at the coding sequence and Pde6b mRNA at the 5′-UTR, resulting in enhanced translation efficiency without affecting mRNA levels. Compromised translation efficiency of Ppef2 and Pde6b after YTHDC2 depletion ultimately leads to decreased protein levels in the retina, impaired retinal function, and progressive rod death. Collectively, our finding highlights the importance of YTHDC2 in visual function and photoreceptor survival, which provides an unreported elucidation of IRD pathogenesis via epitranscriptomics.

Characteristics of Myopia in Children at Prof. Dr. I.G.N.G. Ngoerah General Hospital Period 2020/2021

Myopia is the main cause of visual impairment suffered by school-age children in the world. Myopia causes children unable to see clearly at a distance so that if not corrected it can affect children's activities and achievements. This study aims to determine the characteristics of myopia in pediatric patients who came at Eye Polyclinic Prof. Dr. I.G.N.G. Ngoerah in 2020/2021. This study is a descriptive retrospective cross-sectional design with total sampling from secondary medical record which analyzed and processed using SPSS. Based on the study results, it was found that 32 pediatric patients suffered myopia. The results showed that myopia was more common in women (59.4%) with an age range 6-12 years (62.5%). Most of the patients were from Denpasar (62.5%). All cases of myopia were present in both eyes or bilateral (100.0%). The most common classification of myopia found compound myopic astigmatism in right eye (53.1%) and left eye (65.6%). Patients most often experienced moderate visual impairment with visual acuity <6/18 – 6/60 in right eye (46.9%) and left eye (40.6%). The highest degree of myopia was low myopia (40.6%) in right eye with a correction lens <S-3.00 and high myopia in left eye (43.8%) with >S-6.00. Most of patients experienced improvement to normal vision 6/6 – 6/12 after correction in right eye (59.4%) and left eye (65.6%). Amblyopia was found (56.3%) myopia in children. The results of this study are expected to be basis for further research and to realize the importance of preventing and proper management myopia in children.
 Keywords: Myopia, school-age children, visual acuity, degree of myopia, post-correction visual acuity.

Association of Central serous chorioretinopathy with type of personality, anxiety and depression.

Central serous chorioretinopathy (CSCR) a relatively common cause of visual impairment, which is characterized by subretinal fluid accumulation in the macula and is more common in middle-aged males. Various risk factors have been reported in literature, among which substantial role of psychological factors is cited. Our aim was to look for the prevalence and association of the psychiatric factors in CSCR patients and to compare them with other non-chorioretinal ocular pathologies. A cross-sectional correlational study was undertaken involving 91 CSCR patients, along with 91 patients with other non-chorioretinal diseases. Their risk factors, clinical history, ocular examination, and psychiatric assessments were done using standardized tools, and the groups were compared in terms of scoring of Framingham Type A scale (FTAS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HDRS). CSCR patients had a male:female ratio of 8:1. Chronic, bilateral, and recurrent diseases were found in 15%, 20%, and 23% cases, respectively. Anxiety disorder had a prevalence of 40%, followed by major depression with a prevalence of 24%, and these were significantly higher than non-chorioretinal disease patients (odds ratios 14.18 and 5.30, respectively). Also, these psychiatric disorders were significantly associated with an overall lower visual acuity and greater central macular thickness due to subretinal fluid accumulation. Psychiatric comorbidities like Type A personality trait and depression and anxiety disorders were significantly more prevalent in CSCR patients, compared to non-chorioretinal pathologies. Focus on psychological health would certainly benefit these patients in terms of better management of not only CSCR, but their psychiatric morbidity as well.

Age-related macular degeneration and cardiovascular disease in US population: an observational study

Background As far as we know, age-related macular degeneration (AMD) has become one of the predominant causes of visual impairments. Previous studies have revealed that AMD and many cardiovascular diseases (CVDs) share the same pathologic and genotypic factors, making the connection between AMD and CVD a hot topic. However, the conclusions of the available studies on the relationship between them are somewhat divergent. Methods We screened 5523 eligible participants from the National Health and Nutrition Examination Survey (NHANES) database from 2005 through 2008 for an observational clinical study design. Binary logistic regression modelling was used to estimate the relations between AMD and various CVDs with and without adjustment for demographics, health status, and behaviours related to health. Results Binary logistic regression analyses showed that AMD was able to increase the risk of CVDs in patients both unadjusted and after adjusting for confounding variables. Conclusions Within this study, preventing the development of AMD might cut down the incidence of several CVDs, in particular, significantly lowering the stroke risk. These findings indicate that interventions to prevent AMD may also help to prevent CVDs. In general, late AMD has a more severe impact on the risk of CVDs compared with early AMD. These results could help clinical ophthalmology and cardiovascular medicine in their clinical education and interventions.

Requirement of Site-Specific Tyrosine Phosphorylation of Cortactin in Retinal Neovascularization and Vascular Leakage.

Retinal neovascularization is a major cause of vision impairment. Therefore, the purpose of this study is to investigate the mechanisms by which hypoxia triggers the development of abnormal and leaky blood vessels. A variety of cellular and molecular approaches as well as tissue-specific knockout mice were used to investigate the role of Cttn (cortactin) in retinal neovascularization and vascular leakage. We found that VEGFA (vascular endothelial growth factor A) stimulates Cttn phosphorylation at Y421, Y453, and Y470 residues in human retinal microvascular endothelial cells. In addition, we observed that while blockade of Cttn phosphorylation at Y470 inhibited VEGFA-induced human retinal microvascular endothelial cell angiogenic events, suppression of Y421 phosphorylation protected endothelial barrier integrity from disruption by VEGFA. In line with these observations, while blockade of Cttn phosphorylation at Y470 negated oxygen-induced retinopathy-induced retinal neovascularization, interference with Y421 phosphorylation prevented VEGFA/oxygen-induced retinopathy-induced vascular leakage. Mechanistically, while phosphorylation at Y470 was required for its interaction with Arp2/3 and CDC6 facilitating actin polymerization and DNA synthesis, respectively, Cttn phosphorylation at Y421 leads to its dissociation from VE-cadherin, resulting in adherens junction disruption. Furthermore, whereas Cttn phosphorylation at Y470 residue was dependent on Lyn, its phosphorylation at Y421 residue required Syk activation. Accordingly, lentivirus-mediated expression of shRNA targeting Lyn or Syk levels inhibited oxygen-induced retinopathy-induced retinal neovascularization and vascular leakage, respectively. The above observations show for the first time that phosphorylation of Cttn is involved in a site-specific manner in the regulation of retinal neovascularization and vascular leakage. In view of these findings, Cttn could be a novel target for the development of therapeutics against vascular diseases such as retinal neovascularization and vascular leakage.

Epidemiology of eye diseases: outcomes from a free provincial eye clinic in Papua New Guinea.

To ascertain the prevalence and pattern of eye problems in Madang Province, Papua New Guinea. A six-month retrospective study was performed at Madang Provincial Hospital Eye Clinic. Convenience sampling was used in this study and all patient records from January to June 2020 were included. Data was extracted using Microsoft Excel and the data included gender, age, occupation, district where the patient lived, presenting visual acuity, and diagnosis. It was then analyzed using International Business Machines Corporation's Statistical Package for the Social Sciences version 26. A p-value of ≤0.05 was considered statistically significant. A total of 1,715 patients received services at the eye clinic between January and June 2020, and 1,664 were included in this study. The mean age of the patients was 39.3 ± 20.3 years. There were slightly more males (50.4%) than females. The overall leading ocular morbidities were corneal ulcers and keratitis (20.7%), refractive errors (17.4%), and cataracts (16.8%). More than half of the patients (56.2%) were either visually impaired or blind. Nearly half of the patients (41.8%) traveled long distances to seek services at the eye clinic. There was a significant association between demographic characteristics, diagnosis, and level of visual impairment. There is a high prevalence of potential causes of visual impairment and blindness in Madang Province and these conditions affect all age groups and genders. It is essential to increase accessibility to eye care services in the country.

Shifts in ophthalmic care utilization during the COVID-19 pandemic in the US

BackgroundHealthcare restrictions during the COVID-19 pandemic, particularly in ophthalmology, led to a differential underutilization of care. An analytic approach is needed to characterize pandemic health services usage across many conditions.MethodsA common analytical framework identified pandemic care utilization patterns across 261 ophthalmic diagnoses. Using a United States eye care registry, predictions of utilization expected without the pandemic were established for each diagnosis via models trained on pre-pandemic data. Pandemic effects on utilization were estimated by calculating deviations between observed and expected patient volumes from January 2020 to December 2021, with two sub-periods of focus: the hiatus (March-May 2020) and post-hiatus (June 2020–December 2021). Deviation patterns were analyzed using cluster analyses, data visualizations, and hypothesis testing.ResultsRecords from 44.62 million patients and 2455 practices show lasting reductions in ophthalmic care utilization, including visits for leading causes of visual impairment (age-related macular degeneration, diabetic retinopathy, cataract, glaucoma). Mean deviations among all diagnoses are 67% below expectation during the hiatus peak, and 13% post-hiatus. Less severe conditions experience greater utilization reductions, with heterogeneities across diagnosis categories and pandemic phases. Intense post-hiatus reductions occur among non-vision-threatening conditions or asymptomatic precursors of vision-threatening diseases. Many conditions with above-average post-hiatus utilization pose a risk for irreversible morbidity, such as emergent pediatric, retinal, or uveitic diseases.ConclusionsWe derive high-resolution insights on pandemic care utilization in the US from high-dimensional data using an analytical framework that can be applied to study healthcare disruptions in other settings and inform efforts to pinpoint unmet clinical needs.

Deep learning innovations in diagnosing diabetic retinopathy: The potential of transfer learning and the DiaCNN model

Diabetic retinopathy (DR) is a significant cause of vision impairment, emphasizing the critical need for early detection and timely intervention to avert visual deterioration. Diagnosing DR is inherently complex, as it necessitates the meticulous examination of intricate retinal images by experienced specialists. This makes the early diagnosis of DR essential for effective treatment and prevention of eventual blindness. Traditional diagnostic methods, relying on human interpretation of medical images, face challenges in terms of accuracy and efficiency. In the present research, we introduce a novel method that offers superior precision in DR diagnosis, compared to traditional methods, by employing advanced deep learning techniques. Central to this approach is the concept of transfer learning. This entails the utilization of pre-existing, well-established models, specifically InceptionResNetv2 and Inceptionv3, to extract features and fine-tune selected layers to cater to the unique requirements of this specific diagnostic task. Concurrently, we also present a newly devised model, DiaCNN, which is tailored for the classification of eye diseases. To prove the efficacy of the proposed methodology, we leveraged the Ocular Disease Intelligent Recognition (ODIR) dataset, which comprises eight different eye disease categories. The results are promising. The InceptionResNetv2 model, incorporating transfer learning, registered an impressive 97.5% accuracy in both the training and testing phases. Its counterpart, the Inceptionv3 model, achieved an even more commendable 99.7% accuracy during training, and 97.5% during testing. Remarkably, the DiaCNN model showcased unparalleled precision, achieving 100% accuracy in training and 98.3% in testing. These figures represent a significant leap in classification accuracy when juxtaposed with existing state-of-the-art diagnostic methods. Such advancements hold immense promise for the future, emphasizing the potential of our proposed technique to revolutionize the accuracy of DR and other eye disease diagnoses. By facilitating earlier detection and more timely interventions, this approach stands poised to significantly reduce the incidence of blindness associated with DR, thus heralding a new era of improved patient outcomes. Therefore, this work, through its novel approach and stellar results, not only pushes the boundaries of DR diagnostic accuracy but also promises a transformative impact in early detection and intervention, aiming to substantially diminish DR-induced blindness and champion enhanced patient care.

Exploring the involvement of the alternative complement pathway in non-infectious uveitis pathogenesis.

Non-infectious uveitis is a complex disease characterized by intraocular inflammation of the uveal area and the leading cause of vision impairment and blindness in young people globally. However, what triggers inflammation and contributes to its recurrence remains unclear. The complement system has been linked to various immunological and inflammatory conditions. In the present study, we have systematically evaluated the role of the alternative complement pathway in the pathogenesis of non-infectious uveitis. Quantitative PCR was done in the peripheral leukocytes to study the expression of genes and regulatory miRNA in both anterior and posterior uveitis (n=28 in each category). Multiplex ELISA was performed to measure alternative pathway complement components, such as C3b, factor B, and CFH, and aqueous humor of infectious and non-infectious uveitis patients and non-inflammatory controls (n=10 each). Western blotting was done to validate the ELISA findings in a subset of patients and controls. Downregulation of C3 and CFH mRNA in the peripheral blood was shown by quantitative PCR in the group of anterior uveiits (AU), while the opposite result was found in the group of posterior uveitis (PU). ELISA levels of C3b and CFH proteins were significantly higher in aqueous humor of infectious and non-infectious uveitis (*p = 0.03 and **p = 0.0007 respectively) as compared to the control group. Western blotting further validated (VitH) the activation of the complement cascade in the aqueous (AH) and vitreous humor of patients with non-infectious uveitis, with an increased level of C3b (n=6) and CFH (n=4) in aqueous humor. C3b level was significantly increased while CFH was reduced relative to controls in the vitreous humor (VitH) of posterior uveitis patients compared to controls (n=27 in each category). A C3b to CFH ratio was computed to assess the regulation of complement activation and this index was several folds higher in both anterior and posterior uveitis (n=10 each). The expression of miRNA-hsa-miR-146a and miRNA-hsa-miR-155-5p that regulates CFH was downregulated and nicely correlated with the increased complement proteins in both anterior and posterior uveitis (n=10 each). Our results demonstrate a clear role of CFH and the activation of the alternative complement pathway in the pathogenesis of non-infectious uveitis; however, its therapeutic potential warrants further investigations.

Pathologic vs. protective roles of hypoxia-inducible factor 1 in RPE and photoreceptors in wet vs. dry age-related macular degeneration.

It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular degeneration (AMD), a leading cause of visual impairment among the elderly. Nonetheless, how oxidative stress contributes to the development of choroidal neovascularization (CNV) in some AMD patients and geographic atrophy (GA) in others is poorly understood. Here, we provide evidence demonstrating that oxidative stress cooperates with hypoxia to synergistically stimulate the accumulation of hypoxia-inducible factor (HIF)-1α in the retinal pigment epithelium (RPE), resulting in increased expression of the HIF-1-dependent angiogenic mediators that promote CNV. HIF-1 inhibition blocked the expression of these angiogenic mediators and prevented CNV development in an animal model of ocular oxidative stress, demonstrating the pathological role of HIF-1 in response to oxidative stress stimulation in neovascular AMD. While human-induced pluripotent stem cell (hiPSC)-derived RPE monolayers exposed to chemical oxidants resulted in disorganization and disruption of their normal architecture, RPE cells proved remarkably resistant to oxidative stress. Conversely, equivalent doses of chemical oxidants resulted in apoptosis of hiPSC-derived retinal photoreceptors. Pharmacologic inhibition of HIF-1 in the mouse retina enhanced-while HIF-1 augmentation reduced-photoreceptor apoptosis in two mouse models for oxidative stress, consistent with a protective role for HIF-1 in photoreceptors in patients with advanced dry AMD. Collectively, these results suggest that in patients with AMD, increased expression of HIF-1α in RPE exposed to oxidative stress promotes the development of CNV, but inadequate HIF-1α expression in photoreceptors contributes to the development of GA.

BAFF deficiency aggravated optic nerve crush-induced retinal ganglion cells damage by regulating apoptosis and neuroinflammation via NF-κB-IκBα signaling

Loss of retinal ganglion cells (RGCs) is a primary cause of visual impairment in glaucoma, the pathological process is closely related to neuroinflammation and apoptosis. B-cell activating factor (BAFF) is a fundamental survival factor mainly expressed in the B cell lineage. Evidence suggests its neuroprotective effect, but the expression and role in the retina have not yet been investigated. In this study, we adopt optic nerve crush (ONC) as an in vivo model and oxygen-glucose deprivation/reoxygenation (OGD/R) of RGCs as an in vitro model to investigate the expression and function of BAFF. We found that BAFF and its receptors were abundantly expressed in the retina and BAFF inhibition exacerbated the caspase 3-mediated RGCs apoptosis, glial cell activation and pro-inflammatory cytokines expression, which may be caused by the activation of the NF-κB pathway in vivo. In addition, we found that BAFF treatment could alleviate RGCs apoptosis, pro-inflammatory cytokines expression and NF-κB pathway activation, which could be reversed the effect by blockade of the NF-κB pathway in vitro. Meanwhile, we found that microglia induced to overexpress BAFF in the inflammatory microenvironment in a time-dependent manner. Taken together, our results indicated that BAFF deficiency promoted RGCs apoptosis and neuroinflammation through activation of NF-κB pathway in ONC retinas, suggesting that BAFF may serve as a promising therapeutic target for the treatment of glaucoma.

Comparing the Robustness of ResNet, Swin-Transformer, and MLP-Mixer under Unique Distribution Shifts in Fundus Images.

Diabetic retinopathy (DR) is the leading cause of visual impairment and blindness. Consequently, numerous deep learning models have been developed for the early detection of DR. Safety-critical applications employed in medical diagnosis must be robust to distribution shifts. Previous studies have focused on model performance under distribution shifts using natural image datasets such as ImageNet, CIFAR-10, and SVHN. However, there is a lack of research specifically investigating the performance using medical image datasets. To address this gap, we investigated trends under distribution shifts using fundus image datasets. We used the EyePACS dataset for DR diagnosis, introduced noise specific to fundus images, and evaluated the performance of ResNet, Swin-Transformer, and MLP-Mixer models under a distribution shift. The discriminative ability was evaluated using the Area Under the Receiver Operating Characteristic curve (ROC-AUC), while the calibration ability was evaluated using the monotonic sweep calibration error (ECE sweep). Swin-Transformer exhibited a higher ROC-AUC than ResNet under all types of noise and displayed a smaller reduction in the ROC-AUC due to noise. ECE sweep did not show a consistent trend across different model architectures. Swin-Transformer consistently demonstrated superior discrimination compared to ResNet. This trend persisted even under unique distribution shifts in the fundus images.

Development of LuxIA, a Cloud-Based AI Diabetic Retinopathy Screening Tool Using a Single Color Fundus Image.

Diabetic retinopathy (DR) is the leading cause of vision impairment in working-age adults. Automated screening can increase DR detection at early stages at relatively low costs. We developed and evaluated a cloud-based screening tool that uses artificial intelligence (AI), the LuxIA algorithm, to detect DR from a single fundus image. Color fundus images that were previously graded by expert readers were collected from the Canarian Health Service (Retisalud) and used to train LuxIA, a deep-learning-based algorithm for the detection of more than mild DR. The algorithm was deployed in the Discovery cloud platform to evaluate each test set. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve were computed using a bootstrapping method to evaluate the algorithm performance and compared through different publicly available datasets. A usability test was performed to assess the integration into a clinical tool. Three separate datasets, Messidor-2, APTOS, and a holdout set from Retisalud were evaluated. Mean sensitivity and specificity with 95% confidence intervals (CIs) reached for these three datasets were 0.901 (0.901-0.902) and 0.955 (0.955-0.956), 0.995 (0.995-0.995) and 0.821 (0.821-0.823), and 0.911 (0.907-0.912) and 0.880 (0.879-0.880), respectively. The usability test confirmed the successful integration of LuxIA into Discovery. Clinical data were used to train the deep-learning-based algorithm LuxIA to an expert-level performance. The whole process (image uploading and analysis) was integrated into the cloud-based platform Discovery, allowing more patients to have access to expert-level screening tools. Using the cloud-based LuxIA tool as part of a screening program may give diabetic patients greater access to specialist-level decisions, without the need for consultation.

Microbiological Profile of Infectious Keratitis in a Tertiary Care Hospital

Abstract Background: Microbial keratitis is a major preventable cause of visual impairment. In developed countries viral infections are the leading cause of corneal ulcer whereas bacteria and fungi attributes to maximum number of cases in the developing countries. There is paucity of recent data, risk factors and demographic distribution of patients for all three leading etiological agents of keratitis. Material and Methods: This study included all clinically diagnosed cases of infective keratitis from 01 Jan 2021 to 01 Jan 2022. In brief, four sets of corneal scrapings were taken from patients of infectious keratitis and processed for bacterial and fungal culture, microscopy and RTPCR of viral agents. Results: It was observed that rural elderly males were the most predisposed to occurrence of infectious keratitis and trauma being the leading cause. Out of total 151 samples processed, 49(32%) samples were found to have definitive evidence of bacterial, fungal and viral pathogens. Fungi were found to be the most common 37 (24%) etiological agent leading to keratitis followed by bacterial 7(5%) and viral agents 5(3%). Conclusion: Clinical signs alone are not sufficient to diagnose infectious keratitis, the importance of microbiology in the identification of pathogen and aiming at definitive therapy of infectious keratitis helps in rescuing the eye from this reversible cause of blindness.

Inhibition of Ferroptosis Ameliorates Photoreceptor Degeneration in Experimental Diabetic Mice

Diabetic retinopathy (DR) is a leading cause of vision impairment in the working-age population worldwide. Various modes of photoreceptor cell death contribute to the development of DR, including apoptosis and autophagy. However, whether ferroptosis is involved in the pathogenesis of photoreceptor degeneration in DR is still unclear. High-glucose (HG)-stimulated 661W cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. The levels of intracellular iron, glutathione (GSH), reactive oxygen species (ROS), lipid peroxidation (MDA), and ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, FTH1, and NCOA4) were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. Our data showed the levels of iron, ROS, and MDA were enhanced and GSH concentration was reduced in HG-induced 661W cells and diabetic retinas. The expression of GPX4 and SLC7A11 was downregulated, while the expression of ACSL4, FTH1, and NCOA4 was upregulated in the 661W cells cultured under HG conditions and in the photoreceptor cells in diabetic mice. Furthermore, the administration of the ferroptosis inhibitor ferrostatin-1 (Fer-1) obviously alleviated ferroptosis-related changes in HG-cultured 661W cells and in retinal photoreceptor cells in diabetic mice. Taken together, our findings suggest that ferroptosis is involved in photoreceptor degeneration in the development of the early stages of DR.