Stages Of Age-related Macular Degeneration Research Articles

Generative Data Augmentation and ARMD Classification

Abstract: Age Related Macular Degeneration (ARMD) is a type of eye disease which normally have an effect on the central vision of a person. This Disease might sometimes lead to permanent vision loss for some people. It affects the people over the age of 50. So, basically there are 2 different types of ARMD i.e., Dry and Wet. Dry ARMD will generate a tiny amount of protein deposits called drusen, whereas Wet ARMD occurs whenever any abnormal blood vessel is developed under the retina, so sometimes this blood vessels might leak blood fluid, this type of ARMD is very severe and can even lead to permanent central vision loss. Therefore, it is necessary for early detection of the disease. Generative Data Augmentation for ARMD Classification is deep learning based which uses Convolutional Neural Network (CNN) model for generating images to accurately identify the disease. Deep Learning Diagnostic models require expertly graded images from extensive data sets obtained in large scale clinical trials which may not exist. Therefore, (Generative Adversarial Networks) GAN-based generative data augmentation method called Style GAN is used for generating the images. Generative deep learning techniques is used to synthesize new large datasets of artificial retinal images from different stages of ARMD using the images from the already existing datasets. The performance of ARMD diagnostic DCNNs will be trained on the combination of both real and synthetic datasets. Images obtained by using GAN appear to be realistic, and increase the accuracy of the model. It then continues with classifying the retinal images into one of the three classes i.e., dry, wet or normal using CNN model. It also compares the accuracy against the model with traditional augmentation techniques, towards improving the performance of real-world ARMD classification tasks.

Classification Maps: A New Mathematical Tool Supporting the Diagnosis of Age-Related Macular Degeneration.

A new diagnostic graphical tool-classification maps-supporting the detection of Age-Related Macular Degeneration (AMD) has been constructed. The classification maps are constructed using the ordinal regression model. In the ordinal regression model, the ordinal variable (the dependent variable) is the degree of the advancement of AMD. The other variables, such as CRT (Central Retinal Thickness), GCC (Ganglion Cell Complex), MPOD (Macular Pigment Optical Density), ETDRS (Early Treatment Diabetic Retinopathy Study), Snellen and Age have also been used in the analysis and are represented on the axes of the maps. Here, 132 eyes were examined and classified to the AMD advancement level according to the four-point Age-Related Eye Disease Scale (AREDS): AREDS 1, AREDS 2, AREDS 3 and AREDS 4. These data were used for the creation of two-dimensional classification maps for each of the four stages of AMD. The maps allow us to perform the classification of the patient's eyes to particular stages of AMD. The pairs of the variables represented on the axes of the maps can be treated as diagnostic identifiers necessary for the classification to particular stages of AMD.

Vessel density changes in choroid, chorio-capillaries, deep and superficial retinal plexues on OCTA in normal ageing and various stages of age-related macular degeneration.

To study vessel density (VD) on optical coherence tomography angiography at choroid, chorio-capillaries (CC) and various retinal levels in normal population and various stages of dry AMD and how these changes progress with increase in severity of the disease. Prospective, observational, cross-sectional study was done on 252 eyes of 132 patients (males: 61, females: 71) presenting to tertiary-care centre in Central India between February 2021 and January 2022. For study purpose, eyes were divided into five groups according to the size and number of the drusen, viz, Group 1: No AMD (< 50years), Group 2: No AMD (> 50years), Group 3: Early AMD, Group 4: Intermediate AMD and Group 5: Advanced AMD. In all eyes, VD was measured at choroid, CC, deep capillary plexus (DCP) of retina and superficial capillary plexus (SCP) of retina. The mean age in case cohort is 61.90 ± 7.97years. The mean vascular density differed significantly across diagnosis types in all the quadrants (p < 0.05) at choroid, CC and DCP level. At SCP level, the differences were significant across the groups except at the central quadrant. Vessel density was found to be more in early AMD cohort when compared to No AMD (> 50years) cohort at SCP and DCP level, while it showed continuous reduction later in intermediate and advanced AMD cohort. With increase in the severity of disease, significant reduction in VD is also seen in retinal plexuses, along with the changes in choroid and CC. These VD maps may play a role as non-invasive biomarkers for healthy and diseased ageing.

A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing.

Over 30 million people worldwide suffer from untreatable vision loss and blindness associated with childhood-onset and age-related eye diseases caused by photoreceptor (PR), retinal pigment epithelium (RPE), and choriocapillaris (CC) degeneration. Recent work suggests that RPE-based cell therapy may slow down vision loss in late stages of age-related macular degeneration (AMD), a polygenic disease induced by RPE atrophy. However, accelerated development of effective cell therapies is hampered by the lack of large-animal models that allow testing safety and efficacy of clinical doses covering the human macula (20 mm2). We developed a versatile pig model to mimic different types and stages of retinal degeneration. Using an adjustable power micropulse laser, we generated varying degrees of RPE, PR, and CC damage and confirmed the damage by longitudinal analysis of clinically relevant outcomes, including analyses by adaptive optics and optical coherence tomography/angiography, along with automated image analysis. By imparting a tunable yet targeted damage to the porcine CC and visual streak - with a structure similar to the human macula - this model is optimal for testing cell and gene therapies for outer retinal diseases including AMD, retinitis pigmentosa, Stargardt, and choroideremia. The amenability of this model to clinically relevant imaging outcomes will facilitate faster translation to patients.

Systemic Metabolomics in a Framework of Genetics and Lifestyle in Age-Related Macular Degeneration.

Insights into the pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness, point towards a complex interplay of genetic and lifestyle factors triggering various systemic pathways. This study aimed to characterize metabolomic profiles for AMD and to evaluate their position in the trias with genetics and lifestyle. This study included 5923 individuals from five European studies. Blood metabolomics were assessed using a nuclear magnetic resonance platform of 146 metabolites. Associations were studied using regression analyses. A genetic risk score (GRS) was calculated using β-values of 49 AMD variants, a lifestyle risk score (LRS) using smoking and diet data, and a metabolite risk score (MRS) using metabolite values. We identified 61 metabolites associated with early-intermediate AMD, of which 94% were lipid-related, with higher levels of HDL-subparticles and apolipoprotein-A1, and lower levels of VLDL-subparticles, triglycerides, and fatty acids (false discovery rate (FDR) p-value < 1.4 × 10-2). Late AMD was associated with lower levels of the amino acids histidine, leucine, valine, tyrosine, and phenylalanine, and higher levels of the ketone bodies acetoacetate and 3-hydroxybutyrate (FDR p-value < 1.5 × 10-3). A favorable lifestyle characterized by a healthy diet was associated with higher levels of amino acids and lower levels of ketone bodies, while an unfavorable lifestyle, including smoking, showed opposite effects (FDR p-value < 2.7 × 10-2). The MRS mediated 5% of the effect of the GRS and 20% of that of the LRS on late AMD. Our findings show that metabolomic profiles differ between AMD stages and show that blood metabolites mostly reflect lifestyle. The severity-specific profiles spur further interest into the systemic effects related to disease conversion.

Ex Vivo OCT-Based Multimodal Imaging of Human Donor Eyes for Research into Age-Related Macular Degeneration.

A progression sequence for age-related macular degeneration (AMD) learned from optical coherence tomography (OCT)-based multimodal (MMI) clinical imaging could add prognostic value to laboratory findings. In this work, ex vivo OCT and MMI were applied to human donor eyes prior to retinal tissue sectioning. The eyes were recovered from non-diabetic white donors aged ≥80 years old, with a death-to-preservation time (DtoP) of ≤6 h. The globes were recovered on-site, scored with an 18 mm trephine to facilitate cornea removal, and immersed in buffered 4% paraformaldehyde. Color fundus images were acquired after anterior segment removal with a dissecting scope and an SLR camera using trans-, epi-, and flash illumination at three magnifications. The globes were placed in a buffer within a custom-designed chamber with a 60 diopter lens. They were imaged with spectral domain OCT (30° macula cube, 30 µm spacing, averaging = 25), near-infrared reflectance, 488 nm autofluorescence, and 787 nm autofluorescence. The AMD eyes showed a change in the retinal pigment epithelium (RPE), with drusen or subretinal drusenoid deposits (SDDs), with or without neovascularization, and without evidence of other causes. Between June 2016 and September 2017, 94 right eyes and 90 left eyes were recovered (DtoP: 3.9 ± 1.0 h). Of the 184 eyes, 40.2% had AMD, including early intermediate (22.8%), atrophic (7.6%), and neovascular (9.8%) AMD, and 39.7% had unremarkable maculas. Drusen, SDDs, hyper-reflective foci, atrophy, and fibrovascular scars were identified using OCT. Artifacts included tissue opacification, detachments (bacillary, retinal, RPE, choroidal), foveal cystic change, an undulating RPE, and mechanical damage. To guide the cryo-sectioning, OCT volumes were used to find the fovea and optic nerve head landmarks and specific pathologies. The ex vivo volumes were registered with the in vivo volumes by selecting the reference function for eye tracking. The ex vivo visibility of the pathology seen in vivo depends on the preservation quality. Within 16 months, 75 rapid DtoP donor eyes at all stages of AMD were recovered and staged using clinical MMI methods.

Association of autoantibody levels with different stages of age-related macular degeneration (AMD): Results from the population-based Gutenberg Health Study (GHS)

PurposeAnti-retinal autoantibodies are assumed to be associated with age-related macular degeneration (AMD). To our knowledge, this is the first evaluation of autoantibodies in human sera of participants with different stages of AMD in a large population-based, observational cohort study in Germany.MethodsThe Gutenberg Health Study (GHS) is a population-based, observational cohort study in Germany, including 15,010 participants aged between 35 and 74. Amongst others, non-mydriatic fundus photography (Visucam PRO NM™, Carl Zeiss Meditec AG, Jena, Germany) was performed. Fundus images of the first 5000 participants were graded based on the Rotterdam Eye Study classification. Sera of participants with AMD (n=541) and sera of age-matched participants without AMD (n=490) were analyzed by antigen-microarrays. Besides descriptive statistics, autoantibody-levels were compared by Mann-Whitney-U test and the associations of level of autoantibodies with AMD were calculated by logistic regression analysis. Likewise, possible associations of the autoantibodies and both clinical and laboratory parameters on AMD subjects were analyzed.ResultsAutoantibodies against transferrin (p<0.001) were significantly downregulated in participants with early AMD and soft, distinct drusen (≥63 μm) or pigmentary abnormalities only compared to Controls. Mitogen-activated protein kinase 3 (p=0.041), glutathione peroxidase 4 (p=0.048), clusterin (p=0.045), lysozyme (p=0.19), protein kinase C substrate 80K-H (p=0.02), heat shock 70 kDa protein 1A (p=0.04) and insulin (p=0.018) show a trend between Control and participants with early AMD and soft, distinct drusen (≥63 μm) or pigmentary abnormalities only.ConclusionsThis study contributes to a growing knowledge of autoantibodies in association with different AMD stages compared to controls in the context of a large population-based study in Germany. Especially autoantibodies against inflammatory proteins were downregulated in participants with early AMD and soft, distinct drusen (≥63 μm) or pigmentary abnormalities only.

Reticular Pseudodrusen: Interreader Agreement of Evaluation on OCT Imaging in Age-Related Macular Degeneration

PurposeTo determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence.DesignInterreader agreement study.ParticipantsTwelve readers from 6 reading centers.MethodsAll readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to ≥ 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image.Main Outcome MeasuresInterreader agreement, as assessed by Gwet’s first-order agreement coefficient (AC1).ResultsWhen evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions, and ≥ 5 definite lesions on en face IR images corresponding to Stage 2 or 3 lesions (AC1 = 0.60–0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions (AC1 = 0.58–0.65) and increasing levels of agreement with increasing RPD stage (AC1 = 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC1 = 0.68), but only fair agreement for this evaluation on selected B-scans (AC1 = 0.30).ConclusionsThere was generally substantial or near-substantial—but not near-perfect—agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading.Financial Disclosure(s)Proprietary or commercial disclosure may be found after the references. To determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence. Interreader agreement study. Twelve readers from 6 reading centers. All readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to ≥ 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image. Interreader agreement, as assessed by Gwet’s first-order agreement coefficient (AC1). When evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions, and ≥ 5 definite lesions on en face IR images corresponding to Stage 2 or 3 lesions (AC1 = 0.60–0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions (AC1 = 0.58–0.65) and increasing levels of agreement with increasing RPD stage (AC1 = 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC1 = 0.68), but only fair agreement for this evaluation on selected B-scans (AC1 = 0.30). There was generally substantial or near-substantial—but not near-perfect—agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading.

Deep survival modeling of longitudinal retinal OCT volumes for predicting the onset of atrophy in patients with intermediate AMD.

In patients with age-related macular degeneration (AMD), the risk of progression to late stages is highly heterogeneous, and the prognostic imaging biomarkers remain unclear. We propose a deep survival model to predict the progression towards the late atrophic stage of AMD. The model combines the advantages of survival modelling, accounting for time-to-event and censoring, and the advantages of deep learning, generating prediction from raw 3D OCT scans, without the need for extracting a predefined set of quantitative biomarkers. We demonstrate, in an extensive set of evaluations, based on two large longitudinal datasets with 231 eyes from 121 patients for internal evaluation, and 280 eyes from 140 patients for the external evaluation, that this model improves the risk estimation performance over standard deep learning classification models.

Clinical validation for automated geographic atrophy monitoring on OCT under complement inhibitory treatment

Geographic atrophy (GA) represents a late stage of age-related macular degeneration, which leads to irreversible vision loss. With the first successful therapeutic approach, namely complement inhibition, huge numbers of patients will have to be monitored regularly. Given these perspectives, a strong need for automated GA segmentation has evolved. The main purpose of this study was the clinical validation of an artificial intelligence (AI)-based algorithm to segment a topographic 2D GA area on a 3D optical coherence tomography (OCT) volume, and to evaluate its potential for AI-based monitoring of GA progression under complement-targeted treatment. 100 GA patients from routine clinical care at the Medical University of Vienna for internal validation and 113 patients from the FILLY phase 2 clinical trial for external validation were included. Mean Dice Similarity Coefficient (DSC) was 0.86 ± 0.12 and 0.91 ± 0.05 for total GA area on the internal and external validation, respectively. Mean DSC for the GA growth area at month 12 on the external test set was 0.46 ± 0.16. Importantly, the automated segmentation by the algorithm corresponded to the outcome of the original FILLY trial measured manually on fundus autofluorescence. The proposed AI approach can reliably segment GA area on OCT with high accuracy. The availability of such tools represents an important step towards AI-based monitoring of GA progression under treatment on OCT for clinical management as well as regulatory trials.

Assessment of aggregate index of systemic inflammation and systemic inflammatory response index in dry age-related macular degeneration: a retrospective study.

Inflammation is known to contribute to the development of age-related macular degeneration (AMD). Several inflammatory indices derived from routine complete blood counts have been proposed as biomarkers in multiple disorders. In this study, clinical and laboratory data were retrospectively collected from medical records to assess the aggregate index of systemic inflammation (AISI) and the systemic inflammatory response index (SIRI) as potential biomarkers of systemic inflammation in patients with early diagnosis of dry AMD. The study included 90 patients with dry AMD and 270 age/sex-matched patients with cataracts as a control group. There were no significant differences in the AISI and SIRI results between the cases and controls (p = 0.16 and 0.19, respectively). This suggests that AISI and SIRI may be inadequate metrics for AMD or lack sensitivity in detecting inflammatory changes. Exploring other routine blood markers may help to identify and prevent the early stages of AMD.

A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness, affecting 200 million people worldwide. To identify genes that could be targeted for treatment, we created a molecular atlas at different stages of AMD. Our resource is comprised of RNA sequencing (RNA-seq) and DNA methylation microarrays from bulk macular retinal pigment epithelium (RPE)/choroid of clinically phenotyped normal and AMD donor eyes (n= 85), single-nucleus RNA-seq (164,399 cells), and single-nucleus assay for transposase-accessible chromatin (ATAC)-seq (125,822 cells) from the retina, RPE, and choroid of 6 AMD and 7 control donors. We identified 23 genome-wide significant loci differentially methylated in AMD, over 1,000 differentially expressed genes across different disease stages, and an AMD Müller state distinct from normal or gliosis. Chromatin accessibility peaks in genome-wide association study (GWAS) loci revealed putative causal genes for AMD, including HTRA1 and C6orf223. Our systems biology approach uncovered molecular mechanisms underlying AMD, including regulators of WNT signaling, FRZB and TLE2, as mechanistic players in disease.

Inhibition of AIF-1 alleviates laser-induced macular neovascularization by inhibiting endothelial cell proliferation via restrained p44/42 MAPK signaling pathway

Age-related macular degeneration (AMD) is a leading blinding disease worldwide, and macular neovascularization (MNV) is a common complication encountered in the advanced stages of AMD. While the underlying causes of MNV remain elusive, aberrant multiplication of choroidal endothelial cells (CECs) and increased vascular endothelial growth factor (VEGF) are thought to play significant roles in the occurrence and development of MNV. Allograft inflammatory factor-1(AIF-1) is a crucial regulatory factor of vascular tubular structure formation and growth, involving the proliferation and migration of vascular endothelial cells and various tumor cells. This study aimed to understand how AIF-1 effects the proliferation of CECs and the subsequent progression of MNV. To study this, a mouse MNV model was established through laser injury, and the AIF-1 expression levels were then measured using western blot and immunohistochemistry. AIF-1 siRNA was intravitreally injected to silence AIF-1 gene expression. Western blot and choroidal flat mount were performed to measure the progression of MNV and proliferation of the CECs. These results showed that the protein expression of AIF-1 was significantly elevated in the laser-induced mouse MNV model, and the expression trend was consistent with VEGF. The protein level of AIF-1 was significantly decreased after the intravitreal injection of AIF-1 siRNA, the damage range of laser lesions was significantly reduced, and the proliferation of endothelial cells was inhibited. Knockdown of the AIF-1 gene significantly inhibited the expression of mitogen-activated protein kinase p44/42 in MNV lesions. In summary, this research demonstrates that AIF-1 promoted MNV progression by promoting the proliferation of CECs and that silencing AIF-1 significantly ameliorates MNV progression in mouse models, which may act through the p44/42 MAPK signaling pathway. AIF-1 could be a new potential molecular target for MNV.

Vision-related quality of life is selectively affected by comorbidities in patients with geographic atrophy

BackgroundThe atrophic late stage of age-related macular degeneration (AMD) is termed geographic atrophy (GA), and affects visual acuity (VA) as well as quality of life (QoL). Previous studies have found that best-corrected VA (BCVA), the standard vision assessment often underrepresents functional deficits. Therefore, the purpose of this study was to evaluate the correlation between atrophic lesion size, VA and QoL measured with the National Eye Institute Visual Function Questionnaire (VFQ-39) in a Danish population. Moreover, we wanted to evaluate the correlation between comorbidities, behavioural factors, and QoL.MethodsThis was prospective clinical study of 51 patients with GA in one or both eyes, of these 45 patients had bilateral GA. Patients were consecutively included between April 2021 and February 2022. All patients filled in the VFQ-39 questionnaire except the subscales “ocular pain” and “peripheral vision.” Lesion size was measured from fundus autoflourescense images, and BCVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol.ResultsWe found an overall low score in each VFQ-39 subscale scores reflected by GA. Lesion size and VA were both significantly associated with all VFQ-39 subscale scores except for “general health.” VA showed a larger effect on QoL than lesion size. Chronic obstructive pulmonary disease (COPD) was associated with a lower score in the subscale score “general health” but none of the other subscale scores were affected. Cardiovascular disease (CVD) was associated with a lower BCVA as well as in QoL reflected in the subscale scores “poor general vision,” “near activities,” and “dependency” of VFQ-39.ConclusionBoth atrophic lesion size and visual acuity affects QoL in Danish patients with GA, who reports an overall poor QoL. CVD seems to have a negative effect on disease, as well as in VFQ-39 in several subscales, whereas COPD did not affect disease severity or vision-related subscales in VFQ-39.

Abstract 4273: Integration with benchmark data of paired bulk and single-cell RNA sequencing data substantially improves the accuracy of bulk tissue deconvolution

Abstract The accuracy of current deconvolution methods largely relies on the quality of cell-type expression references. However, single-cell (sc) and single-nuclei (sn) RNA-seq data used for building the reference are usually generated from independent studies that are distinct from the bulk RNA-seq data to be deconvolved. This study design inherently introduces technical confounding factors as unwanted variations, which is not fully addressed by current methods. To evaluate the impact of this variation on deconvolution accuracy, we generated a benchmark dataset where bulk and snRNA-seq profiling were performed from the same aliquot of single-nuclei that were extracted from 24 healthy retina samples. All donor eye samples were collected within six hours post-mortem and were absent of any disease. This study design guarantees the matched sequencing data to present the same cell-type compositions, so that cross-platform technical artifacts become the remaining confounding factor. We used the benchmark dataset to evaluate the performance of seven current deconvolution methods and found they performed much worse in matched real-bulk data than in matched pseudo-bulks that were summations of the single-cell data. This finding suggests that none of these methods have fully addressed the major technical artifacts between bulk and single-cell sequencing platforms. We therefore propose DeMix.SC, a new deconvolution framework that optimizes deconvolution parameters using a small set of matched bulk and sc/snRNA-seq data from the same tissue type. DeMix.SC includes two major steps. First, we measure the technical variations across genes and across platforms using the benchmark data. Second, we introduce a new weight function for each gene that produces a ranking order that accounts for both the platform-specific technical variations and cell-type specific expressions at gene level. Using the benchmark data for retina, we applied DeMix.SC to previously published human retinal RNA-seq data from 523 individuals with different stages of age-related macular degeneration (AMD). We observed that DeMix.SC can accurately capture the cell-type composition shifts in the AMD retina. DeMix.SC revealed a significant drop of rod cells as well as increased astrocytes, bipolar cells, and Müller cells in the AMD retina compared to the non-AMD group. The proportion changes of the later three minor cell types were not identified by other methods, while DeMix.SC could reveal such tendency. In summary, DeMix.SC integrates benchmark data to improve the deconvolution accuracy in retina samples. Our method is generic and can be applied to other disease conditions, such as deciphering the cell-type heterogeneity in cancer. We expect DeMix.SC will help revolutionize the downstream cell-type specific analysis of bulk RNA-seq data and identify cellular targets of human diseases. Citation Format: Shuai Guo, Xuesen Cheng, Andrew Koval, Shuangxi Ji, Qingnan Liang, Yumei Li, Leah A. Owen, Ivana K. Kim, John Weinstein, Scott Kopetz, John Paul Shen, Margaret M. DeAngelis, Rui Chen, Wenyi Wang. Integration with benchmark data of paired bulk and single-cell RNA sequencing data substantially improves the accuracy of bulk tissue deconvolution. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4273.

Symmetry of Macular Fundus Features in Age-Related Macular Degeneration

The symmetry of major macular fundus features in both eyes of the same patient with age-related macular degeneration (AMD) was investigated using swept-source(SS)-OCT. Retrospective review of a prospective study. Patients with AMD. Grading was performed on the first SS-OCT images obtained on the patients. Two graders diagnosed the presence of drusen, geographic atrophy (GA), and exudative AMD (eAMD) in each eye. Medical records were reviewed to assess prior exudation. To assess symmetry, 1 eye of each patient was randomly selected as the index eye and compared with the fellow eye. The kappa statistic (κ) was used to assess the symmetry of diagnosis. The intraclass correlation coefficient (ICC) was used to assess the symmetry of drusen area and volume. Interocular symmetry of the AMD stages: drusen, GA, and eAMD. A total of 1310 patients with AMD were included. The average age was 78 years (range, 50-102; 60% women). Of the 1310 subjects, 54% (701) presented with symmetric disease: 20% with bilateral drusen, 11% with bilateral GA, and 22% with bilateral eAMD. Only 0.5% of the subjects had both GA and eAMD in both eyes. Of the randomly selected index eyes, 825 (47%) were right eyes. Overall, limited interocular agreement was observed between the index and fellow eyes (54%; κ= 0.29). Kappa coefficients were poor (< 0.4) for index eyes diagnosed with drusen (κ= 0.27), eAMD (κ= 0.17), and mixed disease (κ= 0.03). There was moderate agreement between the index and fellow eyes for GA (κ= 0.50). Of the 265 patients with bilateral drusen, the symmetry of drusen area measurements had moderate ICC values of 0.70, 0.71, and 0.70 in the 3- and 5-mm diameter foveal-centered circles and in the total scan area, respectively. The ICC values for the drusen volumes were 0.65, 0.66, and 0.64, respectively. Interocular symmetry was poor for eyes with drusen, eAMD, and mixed disease, but moderate for GA. Although the diagnosis of drusen was not very symmetric between eyes, when present in both eyes, the drusen area and volume measurements were moderately symmetric. Proprietary or commercial disclosure may be found after the references.

Оценка эффективности вторичной профилактики пациентов с ранней стадией возрастной макулярной дегенерации

Age-related macular degeneration (AMD) is one of the leading medical and social problems worldwide. The purpose of this study was to evaluate the effectiveness of drug prevention in patients with early-stage AMD lutein-zeaxanthin containing vitamin and mineral complex. Material and methods. The clinical study included 50 patients of the main group who took lutein-zeaxanthin containing a vitamin and mineral complex 1 capsule 1 time a day for 3 months 2 times a year, for 3 consecutive years, and 50 patients of the control group who did not receive drug therapy. Results. In the main group of patients, there was an increase in visual acuity, an improvement in indicators according to OCT data, and an improvement in the subjective perception of their own visual functions. At the same time, the patients of the control group had a deterioration in visual acuity, the progression of the disease according to OCT, which was manifested by the transition to the next stage of AMD. Conclusion. Drug therapy of early-stage AMD has a preventive effect on the progression of the pathological process in the macular zone. Keywords: age-related macular degeneration, vitamins, minerals, lutein, zeaxanthin

Serum 25-Hydroxyvitamin D Is Differentially Associated with Early and Late Age-Related Macular Degeneration in the United States Population.

Age-related macular degeneration (AMD) has been the leading cause of irreversible blindness in industrialized countries. Emerging data suggest that serum vitamin D levels may be associated with AMD but show mixed results. National-level population data on the relationship between vitamin D and AMD severities are still lacking. We used data from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2008. Retinal photographs were taken and graded for AMD stage. The odds ratio (OR) of AMD and its subtype was calculated after adjusting for confounding factors. Restricted cubic spline (RCS) analyses were used to explore potential non-linear relations. A total of 5041 participants with a mean age of 59.6 years were included. After adjusting for covariates, participants with higher level of serum 25-hydroxyvitamin D [25(OH)D] had significantly greater odds of early AMD (OR, 1.65; 95% CI, 1.08-2.51) and decreased risk of late AMD (OR, 0.29; 95% CI, 0.09-0.88). When stratified by age, a positive association between the level of serum 25(OH)D and early AMD was present in the <60 years group (OR, 2.79; 95% CI, 1.08-7.29), whereas a negative relation between the level of serum 25(OH)D and late AMD was detected in the ≥60 years group (OR, 0.24; 95% CI, 0.08-0.76). A higher level of serum 25(OH)D was related to increased risk of early AMD in those <60 years and decreased risk of late AMD in those ≥60 years.

MicroRNAs as potential biomarkers and therapeutic targets in age-related macular degeneration.

Age-related macular degeneration (AMD) involves degenerative and neovascular alteration in the macular region of the retina resulting in central vision loss. AMD can be classified into dry (dAMD) and wet AMD (wAMD). There is no established treatment for dAMD, and therapies available for wAMD have limited success. Diagnosis in early AMD stages is difficult due to the absence of clinical symptoms. Currently, imaging tests are used in the diagnosis of AMD, but cannot predict the clinical course. The clinical limitations to establishing a diagnosis of AMD have led to exploration for innovative and more sensitive tests to support the diagnosis and prognosis of the disease. MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that negatively regulate genes by post-transcriptional gene silencing. Because these molecules are dysregulated in various processes implicated in the pathogenesis of AMD, they could contribute to the early detection of the disease and monitoring of its progression. Studies of miRNA profiling have indicated several miRNAs as potential diagnostic biomarkers of AMD, but no approved biomarker is available at present for early AMD detection. Thus, understanding the function of miRNAs in AMD and their use as potential biomarkers may lead to future advances in diagnosis and treatment. Here we present a brief review of some of the miRNAs involved in regulating pathological processes associated with AMD and discuss several candidate miRNAs proposed as biomarkers or therapeutic targets for AMD.

Retinal Pigment Epithelium Cell Development: Extrapolating Basic Biology to Stem Cell Research

The retinal pigment epithelium (RPE) forms an important cellular monolayer, which contributes to the normal physiology of the eye. Damage to the RPE leads to the development of degenerative diseases, such as age-related macular degeneration (AMD). Apart from acting as a physical barrier between the retina and choroidal blood vessels, the RPE is crucial in maintaining photoreceptor (PR) and visual functions. Current clinical intervention to treat early stages of AMD includes stem cell-derived RPE transplantation, which is still in its early stages of evolution. Therefore, it becomes essential to derive RPEs which are functional and exhibit features as observed in native human RPE cells. The conventional strategy is to use the knowledge obtained from developmental studies using various animal models and stem cell-based exploratory studies to understand RPE biogenies and developmental trajectory. This article emphasises such studies and aims to present a comprehensive understanding of the basic biology, including the genetics and molecular pathways of RPE development. It encompasses basic developmental biology and stem cell-based developmental studies to uncover RPE differentiation. Knowledge of the in utero developmental cues provides an inclusive methodology required for deriving RPEs using stem cells.