Analysis Of Age-related Macular Degeneration Research Articles

Machine Learning Algorithms for the Analysis of Age-Related Macular Degeneration Based on Optical Coherence Tomography: a Systematic Review

Machine Learning Algorithms for the Analysis of Age-Related Macular Degeneration Based on Optical Coherence Tomography: a Systematic Review

Potential gene identification and pathway crosstalk analysis of age-related macular degeneration.

Age-related macular degeneration (AMD), the most prevalent visual disorder among the elderly, is confirmed as a multifactorial disease. Studies demonstrated that genetic factors play an essential role in its pathogenesis. Our study aimed to make a relatively comprehensive study about biological functions of AMD related genes and crosstalk of their enriched pathways. 1691 AMD genetic studies were reviewed, GO enrichment and pathway crosstalk analyses were conducted to elucidate the biological features of these genes and to demonstrate the pathways that these genes participate. Moreover, we identified novel AMD-specific genes using shortest path algorithm in the context of human interactome. We retrieved 176 significantly AMD-related genes. GO results showed that the most significant term in each of these three GO categories was: signaling receptor binding (PBH = 4.835 × 10−7), response to oxygen-containing compound (PBH = 2.764 × 10−21), and extracellular space (PBH = 2.081 × 10−19). The pathway enrichment analysis showed that complement pathway is the most enriched. The pathway crosstalk study showed that the pathways could be divided into two main modules. These two modules were connected by cytokine-cytokine receptor interaction pathway. 42 unique genes potentially participating AMD development were obtained. The aberrant expression of the mRNA of FASN and LRP1 were validated in AMD cell and mouse models. Collectively, our study carried out a comprehensive analysis based on genetic association study of AMD and put forward several evidence-based genes for future study of AMD.

EyeDiseases: an integrated resource for dedicating to genetic variants, gene expression and epigenetic factors of human eye diseases.

Eye diseases are remarkably common and encompass a large and diverse range of morbidities that affect different components of the visual system and visual function. With advances in omics technology of eye disorders, genome-scale datasets have been rapidly accumulated in genetics and epigenetics field. However, the efficient collection and comprehensive analysis of different kinds of omics data are lacking. Herein, we developed EyeDiseases (https://eyediseases.bio-data.cn/), the first database for multi-omics data integration and interpretation of human eyes diseases. It contains 1344 disease-associated genes with genetic variation, 1774 transcription files of bulk cell expression and single-cell RNA-seq, 105 epigenomics data across 185 kinds of human eye diseases. Using EyeDiseases, we investigated SARS-CoV-2 potential tropism in eye infection and found that the SARS-CoV-2 entry factors, ACE2 and TMPRSS2 are highly correlated with cornea and keratoconus, suggest that ocular surface cells are susceptible to infection by SARS-CoV-2. Additionally, integrating analysis of Age-related macular degeneration (AMD) GWAS loci and co-expression data revealed 9 associated genes involved in HIF-1 signaling pathway and voltage-gate potassium channel complex. The EyeDiseases provides a valuable resource for accelerating the discovery and validation of candidate loci and genes contributed to the molecular diagnosis and therapeutic vulnerabilities with various eyes diseases.

A classification tree approach for the modeling of competing risks in discrete time

Cause-specific hazard models are a popular tool for the analysis of competing risks data. The classical modeling approach in discrete time consists of fitting parametric multinomial logit models. A drawback of this method is that the focus is on main effects only, and that higher order interactions are hard to handle. Moreover, the resulting models contain a large number of parameters, which may cause numerical problems when estimating coefficients. To overcome these problems, a tree-based model is proposed that extends the survival tree methodology developed previously for time-to-event models with one single type of event. The performance of the method, compared with several competitors, is investigated in simulations. The usefulness of the proposed approach is demonstrated by an analysis of age-related macular degeneration among elderly people that were monitored by annual study visits.

Advanced Optical Coherence Tomography Angiography Analysis of Age-related Macular Degeneration Complicated by Onset of Unilateral Choroidal Neovascularization

To analyze optical coherence tomography angiography (OCTA) quantitative features in patients affected by new-onset choroidal neovascularization (CNV) in 1 eye and early/intermediate age-related macular degeneration (AMD) in the fellow eye. Case-control study. Setting: Clinical practice. Thirty patients and 30 age-matched controls. Both cohorts underwent complete ophthalmologic examination, including best-corrected visual acuity (BCVA) measurement, biomicroscopy, fluorescein angiography (FA) and indocyanine green angiography (ICGA) examination, optical coherence tomography, and OCTA scans. The 1-way a test with Bonferroni correction was used to assess statistical significance and Tau Kendall's correlation analysis was performed. BCVA, choroidal thickness, vessel density, vessel tortuosity, vessel dispersion. and vessel rarefaction. Mean BCVA was 20/32 for CNV eyes and 20/20 for both fellow and control eyes. Choroidal thickness was 190.33 ± 63.98μm for CNV eyes, 216.83 ± 50.31μm for fellow eyes, and 310.52 ± 27.13μm for controls. The quantitative analysis of retinal vessels revealed significant alterations, especially in the deep capillary plexus and radial peripapillary capillaries, both in CNV and in fellow eyes, compared with controls. In particular, decreased vessel density and tortuosity and increased dispersion and rarefaction were found. Several significant correlations were also found among the quantitative parameters adopted. New postprocessing OCTA parameters are able to detect deep retinal vascular alterations quantitatively, in both CNV-affected and fellow eyes of patients with new-onset CNV. Further investigations are warranted in order to explore the validity of these new approaches on follow-up.

A Clinical Analysis of Age-Related Macular Degeneration in Qinghai Plateau

Aim: To investigate the clinically estimated incidence and risk factors for age-related macular degeneration (AMD) in a various nationalities in Tibet and Qinghai plateau. Methods: 185 AMD patients (288 eyes), aged 40 to 86 years and lived in Qinghai-Tibet plateau area (with a sea-level of 1800 m - 4300 m), were enrolled. All patients were assigned into four groups based on their nationalities. The Detached Angiography, Optical Coherence Tomography (OCT), Fundus Photography, Visual Acuity, Slit-Lamp Examination, Intraocular Pressure, Laboratory Blood Test were employed. Results: The data showed that the Qinghai region’s AMD patients in the 70 year old group are 43.25%, accounting for the largest proportion, while the 40 age group is 10.27%. AMD is significantly more prevalent in men than in women. In our 185 cases, the number of binocular cases is higher than that of the monocular. Dry AMD (56.25%) is higher than wet (43.75%). Blind and low vision patients constitute 9.03% and 28.47%, respectively. Vision loss in Tibetan patients is much higher than in Han patients (40.5% vs 28.6%). In the four different concentrations of hemoglobin, the 180 g/L group of AMD patients occupied 83 cases (44.86%). The vision damage is much more serious in exudative SMD than atrophic SMD determined by Fundus fluorescence angiography (FFA). The blood tests showed higher levels of triglycerides, red blood cells deposit, blood sugar, uric acid, and low density lipoprotein cholesterol (LDL-C) but lower levels of high density lipoprotein (HDL-C). Risk factors related to the plateau AMD may include: smoking, angiocardiopathy, hypertension, chronic obstructive pulmonary disease, and diabetes. Conclusion: The chronic hypoxia environment may contribute to systemic changes of the body including retinal macular degeneration. Age, sex, smoking, particularly angiocardiopathy may be the main risk factors associated with AMD in the Qinghai-Tibetan Plateau.

A Clinical Analysis of Age-Related Macular Degeneration in Qinghai Plateau

A Clinical Analysis of Age-Related Macular Degeneration in Qinghai Plateau

Retrospective hospital-based analysis of age-related macular degeneration patterns in India: 5-year follow-up.

Purpose:To provide a detailed analysis of age-related macular degeneration (AMD) with a 5-year follow-up at a Tertiary Eye Care Center in India.Methods:In this retrospective institutional study, 408 eyes of 204 subjects (100 males) with a diagnosis of AMD with minimum 5-year follow-up were included. Data collected included demographics, details of the ocular exam, special investigations performed, treatment offered, complications, and systemic diseases, if any.Results:The median age was 74.24 ± 8.23 years. Median follow-up was 5.77 years. The visual acuity (VA) at baseline and last visit was 0.74 ± 0.12 (Snellen's equivalent 20/100) and 0.54 ± 0.12 logarithm of the minimum angle of resolution (Snellen's equivalent 20/50; P = 0.032) in patients with choroidal neovascular membrane (CNVM). The most common complaint was decreased vision (94.5%). AMD (any stage) was found to be bilateral in 93% of patients at baseline and 197 patients (96.56%) at 5 years. Seventeen eyes had active CNVM (12 of these were occult) at presentation. At baseline, 43 eyes had a disciform scar. Three hundred twenty-one eyes had dry AMD at baseline (geographic atrophy - 12 [3.7%] eyes). Five-year conversion rate into wet AMD and geographic atrophy was 2.87% and 3.12%. Median number of anti-vascular endothelial growth factor injections administered per patient was 2.8 ± 1.2. CNVM bilaterality was low (7.5%).Conclusion:Patients with AMD in India presented later in the course of the disease. Bilateral advanced AMD and geographic atrophy were uncommon. Five-year conversion rate into wet AMD and geographic atrophy was 2.87% and 3.12%.

Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be involved in AMD pathogenesis. We discovered new global biomarkers and gene expression signatures of AMD. These results are consistent with a model whereby cell-based inflammatory responses represent a central feature of AMD etiology, and depending on genetics, environment, or stochastic factors, may give rise to the advanced AMD phenotypes characterized by angiogenesis and/or cell death. Genes regulating these immunological activities, along with numerous other genes identified here, represent promising new targets for AMD-directed therapeutics and diagnostics. Please see related commentary: http://www.biomedcentral.com/1741-7015/10/21/abstract

Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks.

BackgroundAge-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes.MethodsRPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort.ResultsWe identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be involved in AMD pathogenesis.ConclusionsWe discovered new global biomarkers and gene expression signatures of AMD. These results are consistent with a model whereby cell-based inflammatory responses represent a central feature of AMD etiology, and depending on genetics, environment, or stochastic factors, may give rise to the advanced AMD phenotypes characterized by angiogenesis and/or cell death. Genes regulating these immunological activities, along with numerous other genes identified here, represent promising new targets for AMD-directed therapeutics and diagnostics.Please see related commentary: http://www.biomedcentral.com/1741-7015/10/21/abstract

Multilocus analysis of age-related macular degeneration

Age-related macular degeneration (AMD) is a late onset vision disorder. Recent studies demonstrate that alterations in complement cascade genes are associated with AMD. Of the three identified complement loci, variants in complement factor H (CFH) have the highest impact as does an independent locus at 10q26. Our matched case-control study using the Age-Related Eye Disease Study (AREDS) cohort confirms and extends the associations in these loci. Subjects were genotyped for single nucleotide polymorphisms (SNPs) from CFH, complement component 2 (C2), complement component 3 (C3), complement factor B (CFB), age-related maculopathy susceptibility (ARMS2), HtrA serine peptidase 1 (HTRA1), and apolipoprotein E (APOE). Individual SNPs, and haplotypes showed risk trends consistent with those seen in other population studies for CFH, C3, C2, and CFB. SNP rs10490924 on chromosome 10 in exon 1 of the ARMS2 gene showed a highly significant association with an odds ratio (OR) of 3.2 (95% CI 2.4-4.2) for the risk allele and rs11200638 located in the proximal promoter region of HTRA1 showed a higher significant association with an OR of 3.4 (95% CI 2.5-4.6) with our AMD cases. We found that APOE haplotypes were not significantly associated with disease status. Adjustments for other risk factors did not significantly alter the observed associations. This study validates the complement pathway's involvement in AMD and suggests that allelic variants in complement genes have a direct role in disease. These results also support previous findings that variants in the region of 10q26 exert an independent risk for AMD.

Declines in Arrestin and Rhodopsin in the Macula with Progression of Age-Related Macular Degeneration

Biochemical analysis of age-related macular degeneration (AMD) at distinct stages of the disease will help further understanding of the molecular events associated with disease progression. This study was conducted to determine the ability of a new grading system for eye bank eyes, the Minnesota Grading System (MGS), to discern distinct stages of AMD so that retinal region-specific changes in rod photoreceptor protein expression from donors could be determined. Donor eyes were assigned to a specific level of AMD by using the MGS. Expression of the rod photoreceptor proteins rhodopsin and arrestin was evaluated by Western immunoblot analysis in the macular and peripheral regions of the neurosensory retina from donors at different stages of AMD. A significant linear decline in both arrestin and rhodopsin content correlated with progressive MGS levels in the macula. In contrast, the peripheral region showed no significant correlation between MGS level and the content of either protein. The statistically significant relationship between decreasing macular rod photoreceptor proteins and progressive MGS levels of AMD demonstrates the utility of the clinically based MGS to correspond with specific protein changes found at known, progressive stages of degeneration. Future biochemical analysis of clinically characterized donor eyes will further understanding of the pathobiochemistry of AMD.

A comparison of stereoscopic fluorescein angiography with indocyanine green videoangiography in age-related macular degeneration

Purpose To correlate features of indocyanine green (ICG) videoangiography with stereo film fluorescein angiography (FA) in the analysis of age-related macular degeneration (AMD). Design A retrospective study with concurrent comparison of two methods of assessment on one set of patients with AMD undergoing sequential FA-ICG videoangiography. Methods One hundred four patients with AMD who had undergone immediately sequential FA-ICG videoangiography were selected in a consecutive fashion from the photographic files of the Casey Eye Institute. Three interpreters independently graded in an unbiased fashion the FA features of AMD. These were compared with ICG videoangiography features of hypocyanescence (ICG videoangiography hypofluorescence), moderate or intense hypercyanescence (ICG videoangiography hyperfluorescence), or absence of fluorescence over background (ICG videoangiography isocyanescence). We also assessed ICG videoangiography features in the opposite eye of those with choroidal neovascularization (CNV) by FA in one eye by examining an additional 96 FA-ICG videoangiography scans. Main outcome measures Outcomes were the ICG videoangiography characteristics of classic and occult CNV, serous pigment epithelial detachments (SPEDs) both with and without CNV, macular hemorrhage, and the comparative size of these features. Results There were 25 eyes that had significant macular hemorrhage by FA. Of these, the FA revealed CNV in its entirety under or near the hemorrhage in 11. The ICG examination revealed all 11 plus an additional 12 hypercyanescent features that were not visible by FA. Although 26 of 32 SPEDs had CNV by FA analysis, 31 of 32 had well-defined hypercyanescence under or at the SPED edge by ICG videoangiography. Eighty-seven percent of eyes with classic choroidal neovascular membranes (CCNV; 20 of 23) and 93% of eyes with fibrovascular pigment epithelial detachments (FVPED; 66 of 71) were hypercyanescent with distinct edges. Fifty percent of eyes with only late leakage of undetermined source (LLUS) were hypercyanescent, whereas 50% were isocyanescent on ICG videoangiography. There were four of 104 eyes in which ICG videoangiography revealed poorly defined hypercyanescent areas when, by FA, there were only drusen or elevated blocked fluorescence. Indocyanine green videoangiography revealed only three eyes with poorly defined hypercyanescence of 200 fellow eyes in patients with unilateral AMD. Conclusions Indocyanine green videoangiography correlated fairly well with stereoscopic FA for the presence of CCNV or FVPED, but correlated poorly when LLUS was present. In certain cases where CNV was associated with SPED or macular hemorrhage, ICG videoangiography demonstrated features not apparent on FA.