Stages Of Age-related Macular Degeneration Research Articles

Geographic atrophy: pathophysiology and current therapeutic strategies.

Geographic atrophy (GA) is an advanced stage of age-related macular degeneration (AMD) that leads to gradual and permanent vision loss. GA is characterized by the loss of photoreceptor cells and retinal pigment epithelium (RPE), leading to distinct atrophic patches in the macula, which tends to increase with time. Patients with geographic atrophy often experience a gradual and painless loss of central vision, resulting in difficulty reading, recognizing faces, or performing activities that require detailed vision. The primary risk factor for the development of geographic atrophy is advanced age; however, other risk factors, such as family history, smoking, and certain genetic variations, are also associated with AMD. Diagnosis is usually based on a comprehensive eye examination, including imaging tests such as fundus photography, optical coherence tomography (OCT), and fluorescein angiography. Numerous clinical trials are underway, targeting identified molecular pathways associated with GA that are promising. Recent approvals of Syfovre and Izervay by the FDA for the treatment of GA provide hope to affected patients. Administration of these drugs resulted in slowing the rate of progression of the disease. Though these products provide treatment benefits to the patients, they do not offer a cure for geographic atrophy and are limited in efficacy. Considering these safety concerns and limited treatment benefits, there is still a significant need for therapeutics with improved efficacy, safety profiles, and better patient compliance. This comprehensive review discusses pathophysiology, currently approved products, their limitations, and potential future treatment strategies for GA.

Micromolded honeycomb scaffold design to support the generation of a bilayered RPE and photoreceptor cell construct.

Age-related macular degeneration (AMD) causes blindness due to loss of retinal pigment epithelium (RPE) and photoreceptors (PRs), which comprise the two outermost layers of the retina. Given the small size of the macula and the importance of direct contact between RPE and PRs, the use of scaffolds for targeted reconstruction of the outer retina in later stage AMD and other macular dystrophies is particularly attractive. We developed microfabricated, honeycomb-patterned, biodegradable poly(glycerol sebacate) (PGS) scaffolds to deliver organized, adjacent layers of RPE and PRs to the subretinal space. Furthermore, an optimized process was developed to photocure PGS, shortening scaffold production time from days to minutes. The resulting scaffolds robustly supported the seeding of human pluripotent stem cell-derived RPE and PRs, either separately or as a dual cell-layered construct. These advanced, economical, and versatile scaffolds can accelerate retinal cell transplantation efforts and benefit patients with AMD and other retinal degenerative diseases.

Automated classification of age-related macular degeneration from optical coherence tomography images using deep learning approach

<p>Early detection of macular diseases can prevent vision loss. Manual screening can be unreliable due to the similarity in the pathological presentations of common retinal illnesses like age-related macular degeneration (AMD). Researchers are becoming more interested in the accurate automated computer-based detection of macular diseases. Using healthy optical coherence tomography (OCT) images, the drusens (early stage) and choroidal neovascularization (CNV) (late stage) of AMD are thus classified using a completely different approach in this paper. The new deep learning (DL) model is proposed for multiple OCT image segmentation of ophthalmological diseases using attention-based nested U-Net (ANU-Net). The flower pollination optimization algorithm (FPOA) is used to optimize the hyperparameters of the network. The SqueezeNet-based classification can be made in the pre-processed images. A dataset from the University of California San Diego (UCSD) is used to evaluate the proposed method. 98.7% accuracy, 99.8% specificity, and 99.7% sensitivity are achieved by the proposed method. The proposed method produces better identification results for automated preliminary diagnosis of macular diseases in hospitals and eye clinics due to the positive classification results.</p>

Effects of Humanin G (HNG) on angiogenesis and neurodegeneration markers in Age-related Macular Degeneration (AMD)

Advanced stages of Age-related Macular Degeneration (AMD) are characterized by retinal neurodegeneration and aberrant angiogenesis, and mitochondrial dysfunction contributes to the pathogenesis of AMD. In this study, we tested the hypothesis that Humanin G (HNG), a cytoprotective mitochondrial-derived peptide, positively regulates cell proliferation, cell death, and the protein levels of angiogenesis and neurodegeneration markers, in normal (control) and AMD RPE transmitochondrial cybrid cell lines. These normal and AMD RPE transmitochondrial cybrid cell lines had identical nuclei derived from mitochondria-deficient ARPE-19 cell line, but differed in mitochondrial DNA (mtDNA) content that was derived from clinically characterized AMD patients and normal (control) subjects. Cell lysates were extracted from untreated and HNG-treated AMD and normal (control) cybrid cell lines, and the Luminex XMAP multiplex assay was used to examine the protein levels of angiogenesis and neurodegeneration markers. Humanin G reduced Caspase-3/7-mediated apoptosis, improved cell proliferation, and normalized the protein levels of angiogenesis and neurodegeneration markers in AMD RPE cybrid cell lines, thereby suggesting Humanin G's positive regulatory role in AMD.

Evaluation of the state of the blood-retinal barrier during the development of signs of age-related macular degeneration in OXYS rats

Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disease that is becoming the leading cause of irreversible vision loss in people over 55 years of age. The development of the wet form of AMD is associated with impaired permeability of the blood- retinal barrier (BRB). It was believed that the BRB does not change in the dry form of the disease, but recently it was shown that dysfunction of the BRB may also contribute to its development; however, information about the state of the BRB at different stages of AMD, especially preclinical ones, is limited. The purpose of this study was to assess the possible contribution of changes in BRB permeability to the development of signs of AMD in OXYS rats, a model of the dry form of the disease. During the period when clinical signs of AMD in OXYS rats are absent (age 20 days), during their manifestation (~5 months) and progression (at 12 and 18 months), the permeability of the BRB for Evans blue dye and the retinal contents of the tight junction proteins occludin, claudin-5, and zonula occludens-1 (ZO-1) were assessed. Wistar rats of the same age served as controls. In OXYS rats, a decrease in the permeability of the BRB was detected, which may result in a violation of the trophic supply of the retina, as well as an increase in the level of occludin during the progression of signs of AMD. ZO-1 level decreased with age, but no interstrain differences were detected. Analysis of retinal transcriptomes (RNA-seq data) showed that in rats of both strains changes in the expression of genes included (according to KEGG) in the category of tight junctions are maximum in the period from 20 days to 3 months. In OXYS rats, the mRNA levels of the Dlg1, Cd1d1, Map3k5 and Arhgef2 genes at the age of 3 months and the Crb3, F11r, Cgn, Cd1d1 and Rap2c genes the age of 18 months are different compared to Wistar rats. Such changes in gene expression in the retina of OXYS rats as AMD signs develop indicate the activation of compensatory mechanisms.

Patterns of Gene Expression, Splicing, and Allele-Specific Expression Vary among Macular Tissues and Clinical Stages of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness, and elucidating its underlying disease mechanisms is vital to the development of appropriate therapeutics. We identified differentially expressed genes (DEGs) and differentially spliced genes (DSGs) across the clinical stages of AMD in disease-affected tissue, the macular retina pigment epithelium (RPE)/choroid and the macular neural retina within the same eye. We utilized 27 deeply phenotyped donor eyes (recovered within a 6 h postmortem interval time) from Caucasian donors (60-94 years) using a standardized published protocol. Significant findings were then validated in an independent set of well-characterized donor eyes (n = 85). There was limited overlap between DEGs and DSGs, suggesting distinct mechanisms at play in AMD pathophysiology. A greater number of previously reported AMD loci overlapped with DSGs compared to DEGs between disease states, and no DEG overlap with previously reported loci was found in the macular retina between disease states. Additionally, we explored allele-specific expression (ASE) in coding regions of previously reported AMD risk loci, uncovering a significant imbalance in C3 rs2230199 and CFH rs1061170 in the macular RPE/choroid for normal eyes and intermediate AMD (iAMD), and for CFH rs1061147 in the macular RPE/choroid for normal eyes and iAMD, and separately neovascular AMD (NEO). Only significant DEGs/DSGs from the macular RPE/choroid were found to overlap between disease states. STAT1, validated between the iAMD vs. normal comparison, and AGTPBP1, BBS5, CERKL, FGFBP2, KIFC3, RORα, and ZNF292, validated between the NEO vs. normal comparison, revealed an intricate regulatory network with transcription factors and miRNAs identifying potential upstream and downstream regulators. Findings regarding the complement genes C3 and CFH suggest that coding variants at these loci may influence AMD development via an imbalance of gene expression in a tissue-specific manner. Our study provides crucial insights into the multifaceted genomic underpinnings of AMD (i.e., tissue-specific gene expression changes, potential splice variation, and allelic imbalance), which may open new avenues for AMD diagnostics and therapies specific to iAMD and NEO.

Automated deep learning-based AMD detection and staging in real-world OCT datasets (PINNACLE study report 5)

Real-world retinal optical coherence tomography (OCT) scans are available in abundance in primary and secondary eye care centres. They contain a wealth of information to be analyzed in retrospective studies. The associated electronic health records alone are often not enough to generate a high-quality dataset for clinical, statistical, and machine learning analysis. We have developed a deep learning-based age-related macular degeneration (AMD) stage classifier, to efficiently identify the first onset of early/intermediate (iAMD), atrophic (GA), and neovascular (nAMD) stage of AMD in retrospective data. We trained a two-stage convolutional neural network to classify macula-centered 3D volumes from Topcon OCT images into 4 classes: Normal, iAMD, GA and nAMD. In the first stage, a 2D ResNet50 is trained to identify the disease categories on the individual OCT B-scans while in the second stage, four smaller models (ResNets) use the concatenated B-scan-wise output from the first stage to classify the entire OCT volume. Classification uncertainty estimates are generated with Monte-Carlo dropout at inference time. The model was trained on a real-world OCT dataset, 3765 scans of 1849 eyes, and extensively evaluated, where it reached an average ROC-AUC of 0.94 in a real-world test set.

Complement factor H Y402H polymorphism results in diminishing CD4+ T cells and increasing C-reactive protein in plasma

Age-related macular degeneration (AMD) is a common cause of visual loss among the elderly. Genetic variants in the gene encoding complement factor H (CFH) have been identified as an AMD susceptibility gene, however, the mechanistic link is debated. Here, we investigated the link between the CFH Y402H genotype and low-grade inflammation. We recruited 153 healthy individuals, 84 participants with dry stages of AMD, and 148 participants with neovascular AMD. All participants were subjected to detailed retinal examination, and interview regarding comorbidities and lifestyle. Blood samples were analyzed for level of C-Reactive Protein (CRP), white blood cell differential count, and stained with fluorescent antibodies to differentiate CD4+ and CD8+ T cells. CFH Y402H genotyping was performed using an allele-specific polymerase chain reaction genotyping assay. Splenocytes from young and aged wild type and Cfh null mutant C57BL/6J mice were examined for CD4+ and CD8+ T cells. Healthy individuals with the CFH Y402H at-risk polymorphism HH had higher levels of CRP and lower proportions of CD4+ T cells compared to persons with the YH or YY polymorphism (P = 0.037, Chi-square). Healthy individuals with the HH polymorphism displayed lower proportions of CD4+ T cells with ageing (P < 0.01, one-way ANOVA), whereas both young and aged Cfh null mutant mice displayed lower proportions of CD4+ T cells (P < 0.001 and P < 0.05; unpaired t test). Participants with dry AMD and the HH polymorphism had similarly lower proportions of CD4+ T cells (P = 0.024, one-way ANOVA), but no difference in CRP-levels. In the neovascular stage of AMD, there was no difference in proportion of CD4+ cells or CRP levels according to genotype. The risk-associated CFH genotype is associated with an age-related decrease in proportion of CD4+ T cells and increased levels of CRP in healthy individuals. This indicates that decreased complement regulation results in extensive changes in innate and adaptive immune compartments that precede development of AMD.

Diagnostic accuracy of community optometrists for age-related macular degeneration using colour fundus photographs: Apilot evaluation.

The accurate diagnosis of age-related macular degeneration (AMD) represents an important step in delaying and preventing vision loss and achieving optimal patient care. Therefore, this pilot study aimed to estimate the diagnostic accuracy of community optometrists for identifying AMD using colour fundus photographs (CFPs) to support sample size calculations for subsequent definitive studies. Five practising community optometrists were invited to classify a total of 1023 CFPs for the (1) presence of AMD, and, if applicable, (2) stage of AMD (early/intermediate/late geographic atrophy/late neovascular AMD). Diagnosis by referral centre clinicians formed the reference standard. Diagnostic accuracy was assessed by the area under the receiver operating characteristic curve (aROC). Sensitivity, specificity, positive and negative predictive values were also calculated. Of the 1023 CFPs included in the study, 226 images were of AMD and 797 images were of other ocular conditions or no abnormal findings. Participating community optometrists had a mean (SD) age of 30.2 (8.9) years, 60.0% (3/5) were female and the mean number of years practising in primary eye care was 5.4 (5.4) years. Community optometrists demonstrated excellent performance for diagnosing AMD, with an aROC of 0.86 (95% CI 0.83 to 0.89), sensitivity of 84.5% (95% CI 79.1 to 89.0) and specificity of 88.0% (95% CI 85.5 to 90.1). The aROC (95% CI) for diagnosing early, intermediate, late geographic atrophy and late neovascular AMD was 0.82 (0.73 to 0.91), 0.76 (0.72 to 0.81), 0.69 (0.49 to 0.90) and 0.55 (0.34 to 0.75), respectively. These results justify the need for an appropriately powered definitive study to assess community clinicians' diagnostic accuracy for AMD.

Prevalence and Associations of Keratoconus Among Children, Adults, and Elderly in the Population-Based Ural Eye Studies.

To estimate prevalence and associations of keratoconus in populations in Russia with an age from childhood to seniority. The study population consisted of the cohorts of 3 population-based studies performed in urban and rural areas within the same geographical region in Bashkortostan/Russia: the Ural Children Eye Study (UCES; age = 6-18 y; n = 4890), the Ural Eye and Medical Study (UEMS; age = >40 y; n = 5314), and the Ural Very Old Study (UVOS; age = >85 y; n = 651). Based on Scheimflug imaging, keratoconus was defined by a keratometric reading of ≥48 diopters (D) in any eye. The mean maximal and minimal corneal refractive power increased from the UCES (43.58 ± 1.50 D and 42.70 ± 1.42 D, respectively) to the UEMS (44.26 ± 1.70 D and 43.61 ± 1.76 D, respectively) and to the UVOS (45.1 ± 1.72 D and 43.98 ± 1.68 D, respectively). Correspondingly, keratoconus prevalence increased from the UCES (42/4890; 0.086%; 95% CI = 0.060, 0.112) to the UEMS (112/5314; 2.11%; 95% CI = 1.72, 2.49) and to the UVOS (42/651; 6.45%; 95% CI = 4.56, 8.34). In the UCES, higher keratoconus prevalence was associated (multivariable analysis) with higher birth order [odds ratio (OR) = 2.34; 95% CI = 1.32, 4.15; P = 0.004], lower birth weight (OR = 0.99; 95% CI = 0.99, 0.99; P < 0.001), and shorter axial length (OR = 0.15; 95% CI = 0.08, 0.30; P < 0.001). In the UEMS, keratoconus prevalence correlated with shorter axial length (OR = 0.15; 95% CI = 0.10, 0.23; P < 0.001), larger corneal volume (OR = 1.17; 95% CI = 1.09, 1.25; P = 0.001), thicker lens (OR = 2.27; 95% CI = 1.06, 5.28; P = 0.04), cortical cataract degree (OR = 1.02; 95% CI = 1.01, 1.04; P = 0.01), and higher stage of age-related macular degeneration (OR = 1.65; 95% CI = 1.09, 2.51; P = 0.02). In the UVOS, keratoconus prevalence correlated with lower educational level (OR = 0.84; 95% CI = 0.71, 0.99; P = 0.04) and lower dynamometric handgrip force (OR = 0.92; 95% CI = 0.88, 0.97; P = 0.003). In this study on multiethnic groups from Russia, keratoconus prevalence increased from the pediatric group (0.09%) to the adult group (2.11%) and seniority group (6.45%), correlated mostly with biometric ocular parameters and was in all age groups statistically independent of most systemic parameters.

Robust AMD Stage Grading with Exclusively OCTA Modality Leveraging 3D Volume.

Age-related Macular Degeneration (AMD) is a degenerative eye disease that causes central vision loss. Optical Coherence Tomography Angiography (OCTA) is an emerging imaging modality that aids in the diagnosis of AMD by displaying the pathogenic vessels in the subretinal space. In this paper, we investigate the effectiveness of OCTA from the view of deep classifiers. To the best of our knowledge, this is the first study that solely uses OCTA for AMD stage grading. By developing a 2D classifier based on OCTA projections, we identify that segmentation errors in retinal layers significantly affect the accuracy of classification. To address this issue, we propose analyzing 3D OCTA volumes directly using a 2D convolutional neural network trained with additional projection supervision. Our experimental results show that we achieve over 80% accuracy on a four-stage grading task on both error-free and error-prone test sets, which is significantly higher than 60%, the accuracy of human experts. This demonstrates that OCTA provides sufficient information for AMD stage grading and the proposed 3D volume analyzer is more robust when dealing with OCTA data with segmentation errors.

Polarized Desmosome and Hemidesmosome Shedding via Small Extracellular Vesicles is an Early Indicator of Outer Blood-Retina Barrier Dysfunction.

The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age-related macular degeneration (AMD), the leading cause of vision loss among the elderly in industrialized nations. A major responsibility of the RPE is to process photoreceptor outer segments, which relies on the proper functioning of its endocytic pathways and endosomal trafficking. Exosomes and other extracellular vesicles (EVs) from RPE are an essential part of these pathways and may be early indicators of cellular stress. To test the role of small EVs (sEVs) including exosomes, that may underlie the early stages of AMD, we used a polarized primary RPE cell culture model under chronic subtoxic oxidative stress. Unbiased proteomic analyses of highly purified basolateral sEVs from oxidatively stressed RPE cultures revealed changes in proteins involved in epithelial barrier integrity. There were also significant changes in proteins accumulating in the basal-side sub-RPE extracellular matrix during oxidative stress, that could be prevented with an inhibitor of sEV release. Thus, chronic subtoxic oxidative stress in primary RPE cultures induces changes in sEV content, including basal-side specific desmosome and hemidesmosome shedding via sEVs. These findings provide novel biomarkers of early cellular dysfunction and opportunity for therapeutic intervention in age-related retinal diseases (e.g., AMD).

Traditional Chinese medicine for age-related macular degeneration: A clinical evidence map between 2000 and 2022

Abstract Background We systematically searched and summarized clinical studies on traditional Chinese medicine (TCM) for age-related macular degeneration (AMD) with the method of evidence map. We aimed to provide evidence and research direction for the prevention or treatment of AMD with TCM in the future. Materials and methods We searched PubMed, Web of Science, EMBASE, and Chinese databases including CNKI (Chinese National Knowledge Infrastructure), WanFang and VIP, Clinical Trials.gov, and Chinese Clinical Trial Registry Center studies on the prevention or treatment of TCM for AMD from January 2000 to November 2022. We showed distribution features of these studies in the form of text description, graphs, and tables. Results The final 258 articles included 245 clinical studies, 9 systematic reviews or meta-analyses, and 4 guidelines, expert consensus, or clinical pathway. After analyzing the articles with a focus on the stage of AMD, study type, sample size, intervention measures, outcome indicators, and the quality of evidence, we found that the studies were increasing, most of which were wet AMD, the main study type was randomized controlled trials, and the sample size was mostly fewer than 100 cases. Different interventions of TCM, such as Chinese medicine, Chinese patent medicine, or acupuncture, showed the potential benefits of improving vision, reducing fundus lesions, and alleviating some uncomfortable symptoms. However, the sample size of these studies was small. The outcome indicators were not unified, and the stage of AMD was unclear. The quality of articles was lower, and there were few studies on early AMD. The advantages of TCM for the prevention or treatment of AMD remained unclear. Conclusions Early intervention will be the focus and direction of AMD in the prevention or treatment of TCM, and more standardized clinical studies of TCM for early AMD need to be designed and carried out in the future.

Genetic Risk Score Analysis Supports a Joint View of TwoClassification Systems for Age-Related Macular Degeneration.

The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD) Consortium Severity Scale (3CACSS) for classification of AMD. In two independent cross-sectional datasets of our population-based AugUR study (Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg), we graded AMD via color fundus images applying two established classification systems (CC and 3CACSS). We calculated the genetic risk score (GRS) across 50 previously identified variants for late AMD, its association via logistic regression, and area under the curve (AUC) for each AMD stage. We analyzed 2188 persons aged 70 to 95 years. When comparing the two classification systems, we found a distinct pattern: CC "age-related changes" and CC "early AMD" distinguished individuals with 3CACSS "no AMD"; 3CACSS "mild/moderate/severe early AMD" stages, and distinguished CC "intermediate AMD". This suggested a 7-step scale combining the 2 systems: (i) "no AMD", (ii) "age-related changes", (iii) "very early AMD", (i.e. CC "early"), (iv) "mild early AMD", (v) "moderate early AMD", (vi) "severe early AMD", and (vii) "late AMD". GRS association and diagnostic accuracy increased stepwise by increased AMD severity in the 7-step scale and by increased restriction of controls (e.g. for CC "no AMD without age-related changes": AUC = 55.1%, 95% confidence interval [CI] = 51.6, 58.6, AUC = 62.3%, 95% CI=59.1, 65.6, AUC = 63.8%, 95% CI=59.3, 68.3, AUC=78.1%, 95% CI=73.6, 82.5, AUC = 82.2%, 95% CI = 78.4, 86.0, and AUC = 79.2%, 95% CI = 75.4, 83.0). A stepwise increase was also observed by increased drusen size and area. The utility of a 7-step scale is supported by our clinical and GRS data. This harmonization and full data integration provides an immediate simplification over using either CC or 3CACSS and helps to sharpen the control group.

Comparative mechanistic study of RPE cell death induced by different oxidative stresses

Oxidative stress is hypothesized to drive the progression of age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cell layer is important for supporting the function of retina and is particularly susceptible to oxidative stress-induced cell death. How RPE cells die in AMD, especially in geographic atrophy (GA), a late stage of dry AMD, is still controversial. The goal of this study is to compare the features and mechanisms of RPE cell death induced by different oxidative stresses, to identify potential universal therapeutic targets for GA. RPE cell death was induced both in vitro and ex vivo by 4-Hydroxynonenal (4-HNE), a major product of lipid peroxidation, sodium iodate (NaIO3) that has been widely used to model RPE cell death in dry AMD, a ferroptosis inducer RAS-selective lethal 3 (RSL3) or a necroptosis inducer shikonin. We found that RPE necroptosis and ferroptosis show common and distinct features. Common features include receptor-interacting protein kinase (RIPK)1/RIPK3 activation and lipid reactive oxygen species (ROS) accumulation, although lipid ROS accumulation is much milder during necroptosis. This supports cross talk between RPE ferroptosis and necroptosis pathways and is consistent with the rescue of RPE necroptosis and ferroptosis by RIPK1 inhibitor Necrostatin-1 (Nec-1) or in Ripk3−/− RPE explants. Distinct feature includes activated mixed lineage kinase domain like pseudokinase (MLKL) that is translocated to the cell membrane during necroptosis, which is not happening in ferroptosis. This is consistent with the failure to rescue RPE ferroptosis by MLKL inhibitor necrosulfonamide (NSA) or in Mlkl−/− RPE explants. Using this framework, we found that 4-HNE and NaIO3 induced RPE cell death likely through necroptosis based on the molecular features and the rescuing effect by multiple inhibitors. Our studies suggest that multiple markers and inhibitors are required to distinguish RPE necroptosis and ferroptosis, and that necroptosis inhibitor Nec-1 could be a potential therapeutic compound for GA since it inhibits RIPK1/RIPK3 activation and lipid ROS accumulation occurred in both necroptosis and ferroptosis pathways.

Subclinical Angioid Streaks with Pseudodrusen: A New Phenotype of Age-Related Macular Degeneration.

To describe subclinical angioid streaks (AS) as a frequent, peculiar age-related macular degeneration (AMD) phenotype, comparing features of eyes with subclinical AS with those of eyes with AMD without AS. This was a retrospective, observational study. Among a patient cohort with AMD, we selected patients without known causes for AS whose eyes showed signs of angioid streaks (AS) on structural optical coherence tomography (OCT) but not on fundus examination. Selected OCT features of AS were Bruch's membrane (BM) breaks and large BM dehiscences. Among 543 eyes of 274 patients with AMD (mean ± standard deviation: 82 ± 7years), 73 eyes of 46 patients (81 ± 7years; p = 0.432) showed AS features on OCT (OCT AS) that were not visible on fundus examination. Estimated prevalence of subclinical age-related AS was 13.4% (95% confidence interval 10.3-16.3%) in this AMD population. Fifty-three eyes (73%) with AS features were affected by peripapillary atrophy, often with a "petaloid-like" pattern, similar to typical features of AS disease. Almost all cases (97%) presented reticular pseudodrusen (RPD), with (41%) or without (59%) drusen showing a significant difference in RPD prevalence in OCT AS eyes in comparison to AMD eyes without subclinical AS using generalized estimating equations (P < 0.001). Among the 73 subclinical AS cases, 71 were affected by late AMD (57 with macular neovascularization, 14 with geographic atrophy), showing a more advanced AMD stage in comparison with AMD eyes without subclinical AS (P < 0.001). The following OCT features were disclosed: BM breaks in 100% of cases and BM dehiscences in 37%. Subclinical AS in eyes with AMD is a peculiar phenotype of the disease, with features suggesting a primary involvement of Bruch's membrane and clinical similarities with mild, late-onset pseudoxanthoma elasticum.

Visual Functioning and Mortality of Age-Related Macular Degeneration Patients in a Colorado Cohort

To investigate the relationship between visual functioning as measured by the National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) and mortality in patients with various stages of age-related macular degeneration (AMD). Observational cohort study. Patients with AMD enrolled in the University of Colorado AMD Registry between July 9, 2014 and December 31, 2021 were included. Age-related macular degeneration cases were classified into early AMD, intermediate AMD, geographic atrophy, neovascular AMD, or both advanced types of AMD (neovasuclar and geographic atrophy both present) using multimodal imaging and the Beckman and Classification of Atrophy Meetings criteria. Visual Function Questionnaire-25 composite and subscale scores at the time of study enrollment were calculated. Cox proportional hazards modeling was used to assess time to event for mortality utilizing univariate and multivariable models, which adjusted for all variables significantly associated with mortality. The measures of association were hazard ratios (HRs) and 95% confidence intervals (CIs). All-cause mortality statistics were obtained through a collaborative agreement with the Colorado Department of Public Health and Environment. Death rates through October 19, 2022 were compared by demographics and potential confounders. Analysis was completed on a cohort of 876 patients, of which 180 (20.6%) died during the follow-up period. Average follow-up time for this cohort was 52.5 (standard deviation: 26.6) months. In univariate analysis, composite VFQ-25 score and all subscale scores aside from ocular pain were significantly associated with time to mortality. Additionally, age, AMD category, marital status, history of smoking, and multiple chronic comorbid conditions were significantly associated with time to mortality. In multivariable analysis, for each 10-point increase in a patient's VFQ-25 scores for general health and driving, the risk of death decreased with HR of 0.85 (95% CI: 0.80, 0.91; P < 0.0001) and 0.92 (95% CI: 0.87, 0.97; P= 0.005), respectively. Composite and other subscale scores were not significantly associated with mortality after adjusting for confounding variables. This cohort of AMD patients had a 20% rate of death in the 52.5-month average follow-up time. Better general health and ability to drive, as measured by the VFQ-25, were each separately associated with significantly lower risk of death among individuals with AMD. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Efficacy of low-vision devices in elderly population with age-related macular degeneration.

Age-related macular degeneration (AMD) is a common cause of blindness, residual damage to macular area in spite of treatment necessitates visual rehabilitation by means of low-vision aids (LVAs). Thirty patients suffering from different stages of AMD requiring LVAs were included in this prospective study. Patients with nonprogressive, adequately treated AMD were enrolled over a 12-month period, prescribed requisite LVAs and followed-up for a minimum 1-month period. Before and after provision of LVAs, near work efficiencies were evaluated by calculating reading speed as words per minute (wpm) under both photopic and mesopic light conditions, and impact of poor vision on activities of daily living (ADL) was quantified by modified standard questionnaire based on Nhung X et al. questionnaire. Of the 30 patients mean studied with mean age of 68 ± 10 years, 20 patients (66.7%) had dry AMD in better eye and 10 (33.3%) had wet AMD. Post-LVA, near visual acuity improved significantly and all cases were able to read some letters on near vision chart with an average improvement of 2.4 ± 0.96 lines. The different LVAs prescribed were high plus reading spectacles (up to 10 D) in 23.3%, hand-held magnifiers in 53.3%, base in prisms in 10%, stand held magnifiers in 6.7%, and bar and dome magnifiers in 3.3%. LVAs are effective in visual rehabilitation in patients with AMD. Self-reported reduction in visual dependency and improvement in vision-related quality of life post use of aids corroborated perceived benefit.

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.