Early Age-related Macular Degeneration Research Articles

Relative Leukocyte Telomere Length and Genetic Variants in Telomere-Related Genes and Serum Levels Role in Age-Related Macular Degeneration

Our study enrolled 342 patients with AMD and 177 healthy controls. Samples of DNA from peripheral blood leukocytes were extracted by DNA salting-out method. The genotyping of TERT rs2736098, rs401681 in TERT-CLPTM1 locus, TRF1 rs1545827, rs10107605, TNKS2 rs10509637, rs10509639, and TRF2 rs251796 and relative leukocyte telomere length (T/S) measurement were carried out using the real-time polymerase chain reaction method. Serum TERF-1 and TERF2 levels were measured by enzymatic immunoassay (ELISA). We found longer telomeres in early AMD patients compared to the control group. Additionally, we revealed that minor allele C at TRF1 rs10107605 was associated with decreases the odds of both early and exudative AMD. Each minor allele G at TRF2 rs251796 and TRF1 rs1545827 C/T genotype and C/T+T/T genotypes, compared to the C/C genotype, increases the odds of having shorter telomeres. Furthermore, we found elevated TERF1 serum levels in the early AMD group compared to the control group. In conclusion, these results suggest that relative leukocyte telomere length and genetic variants of TRF1 and TRF2 play a role in AMD development. Additionally, TERF1 is likely to be associated with early AMD.

Microglia-Neutrophil Interactions Drive Dry AMD-like Pathology in a Mouse Model.

In dry age-related macular degeneration (AMD), inflammation plays a key role in disease pathogenesis. Innate immune cells such as microglia and neutrophils infiltrate the sub-retinal space (SRS) to induce chronic inflammation and AMD progression. But a major gap in our understanding is how these cells interact with each other in AMD. Here, we report a novel concept of how dynamic interactions between microglia and neutrophils contribute to AMD pathology. Using well-characterized genetically engineered mouse models as tools, we show that in the diseased state, retinal pigmented epithelial (RPE) cells trigger pro-inflammatory (M1) transition in microglia with diminished expression of the homeostatic marker, CX3CR1. Activated microglia localize to the SRS and regulate local neutrophil function, triggering their activation and thereby inducing early RPE changes. Ligand receptor (LR)-loop analysis and cell culture studies revealed that M1 microglia also induce the expression of neutrophil adhesion mediators (integrin β1/α4) through their interaction with CD14 on microglia. Furthermore, microglia-induced neutrophil activation and subsequent neutrophil-mediated RPE alterations were mitigated by inhibiting Akt2 in microglia. These results suggest that the Akt2 pathway in microglia drives M1 microglia-mediated neutrophil activation, thereby triggering early RPE degeneration and is a novel therapeutic target for early AMD, a stage without treatment options.

Exploring the pathogenesis of age-related macular degeneration: A review of the interplay between retinal pigment epithelium dysfunction and the innate immune system.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the older population. Classical hallmarks of early and intermediate AMD are accumulation of drusen, a waste deposit formed under the retina, and pigmentary abnormalities in the retinal pigment epithelium (RPE). When the disease progresses into late AMD, vision is affected due to death of the RPE and the light-sensitive photoreceptors. The RPE is essential to the health of the retina as it forms the outer blood retinal barrier, which establishes ocular immune regulation, and provides support for the photoreceptors. Due to its unique anatomical position, the RPE can communicate with the retinal environment and the systemic immune environment. In AMD, RPE dysfunction and the accumulation of drusen drive the infiltration of retinal and systemic innate immune cells into the outer retina. While recruited endogenous or systemic mononuclear phagocytes (MPs) contribute to the removal of noxious debris, the accumulation of MPs can also result in chronic inflammation and contribute to AMD progression. In addition, direct communication and indirect molecular signaling between MPs and the RPE may promote RPE cell death, choroidal neovascularization and fibrotic scarring that occur in late AMD. In this review, we explore how the RPE and innate immune cells maintain retinal homeostasis, and detail how RPE dysfunction and aberrant immune cell recruitment contribute to AMD pathogenesis. Evidence from AMD patients will be discussed in conjunction with data from preclinical models, to shed light on future therapeutic targets for the treatment of AMD.

Early Stages of Age-Related Macular Degeneration: Racial/Ethnic Differences and Proposal of a New Classification Incorporating Emerging Concept of Choroidal Pathology

The progression of age-related macular degeneration (AMD) is determined by environmental and genetic factors, and phenotypic or molecular risk factors have been investigated extensively. Interestingly, risk factor profiles for advanced AMD differ among individuals, and one of the causes of variation may be explained by their ethnic background. Recent advances in retinal imaging technology have led to the identification of previously unrecognized risk factors for advanced AMD on optical coherence tomography (OCT) and OCT angiography, which expands the concept of traditional imaging risk factors such as drusen and pigmentary abnormalities visible on color fundus photographs. This OCT imaging modality has identified novel pathognomonic changes for early AMD, including the associated photoreceptor, retinal pigment epithelium, and underlying choroidal changes. Regarding features of multimodal imaging associated with the presence or progression of geographic atrophy, there is an international expert consensus classification system; however, features associated with the progression of macular neovascularization (MNV) are still obscure. To make a consensus towards understanding features associated with the risk of MNV, this review focuses on the early stages of AMD by summarizing imaging characteristics and early signs and classifications in view of advanced multimodal imaging technology. Recent evidence suggests that neovascular AMD is not a single disease entity but a heterogeneous disease characterized by MNV. Besides drusen, OCT features associated with pigment abnormalities, such as shallow irregular RPE elevation (SIRE, also known as double-layer sign), pachychoroid pigment epitheliopathy, and choriocapillaris ischemia, seem to confer a high risk of MNV developing, especially for Asian populations.

Polygenic risk score and biochemical/environmental variables predict a low-risk profile of age-related macular degeneration in Sardinia.

To ascertain the prevalence and clinical and genetic features of age-related macular degeneration (AMD) in subjects living in the Lanusei valley, Central Sardinia, Italy, involved in a study on ageing (SardiNIA project). A total of 814 volunteers aged ≥ 50years, randomly selected from the SardiNIA project dataset, were included. A color fundus (CF) photograph of the 30° central retina of each eye was obtained and graded according to the Age-Related Eye Disease Study system. Life-style choices were investigated using standardized questionnaires. The concentrations of several inflammatory biomarkers (i.e., complement component, fibrinogen, and C-reactive protein) were measured. Polygenic risk score (PRS) was calculated and compared with results obtained from a European cohort. A total of 756 subjects had gradable CF photographs for AMD detection. In 91.3%, no signs of AMD were observed. The prevalence rates of early and late AMDs were 6.9% and 0.6%, respectively. A total of 85% of subjects were physically active; only 13.5% were current smokers. Low concentrations of complement component, fibrinogen, and C-reactive protein were found. We calculated the polygenic risk scores (PRS) using 40 AMD markers distributed on several candidate genes in Europeans and Sardinians. The mean PRS value was significantly lower in Sardinians than in the Europeans (0.21 vs. 0.248, respectively, p = 1.18 × 10-77). In our cohort, most subjects showed no sign of any AMD type and late AMD was a condition rarely observed. Results of genetic, biochemical, and life-style investigation support the hypothesis that Sardinia population may present of a peculiar background with a protective effect against AMD development.

Impact of the Aging Lens and Posterior Capsular Opacification on Quantitative Autofluorescence Imaging in Age-Related Macular Degeneration.

PurposeThe purpose of this study was to investigate quantitative autofluorescence (qAF8) in patients with and without early or intermediate age-related macular degeneration (AMD); to determine the impact of the aged crystalline lens and posterior capsular opacification (PCO).MethodsIn phakic and pseudophakic eyes ≥60 years, AMD status was determined by the Beckman system. PCO presence and severity was extracted from clinical records. qAF8 was calculated using custom FIJI plugins. Differences in qAF8, stratified by lens status, PCO severity, and AMD status, were analyzed using generalized estimating equations.ResultsIn 210 eyes of 115 individuals (mean age = 75.7 ± 6.6 years), qAF8 was lower in intermediate AMD compared to early AMD (P = 0.05). qAF8 did not differ between phakic and pseudophakic eyes (P = 0.8909). In phakic (n = 83) and pseudophakic (n = 127) eyes considered separately, qAF8 did not differ by AMD status (P = 0.0936 and 0.3494, respectively). Qualitative review of qAF images in phakic eyes illustrated high variability. In pseudophakic eyes, qAF8 did not differ with PCO present versus absent (54.5% vs. 45.5%). Review of implanted intraocular lenses (IOLs) revealed that 43.9% were blue-filter IOLs.ConclusionsqAF8 was not associated with AMD status, up to intermediate AMD, considering only pseudophakic eyes to avoid noisy images in phakic eyes. In pseudophakic eyes, qAF8 was not affected by PCO. Because blue-filter IOLs may reduce levels of exciting light for qAF8, future studies investigating qAF in eyes with different IOL types are needed.Translational RelevanceTo reduce variability in observational studies and clinical trials requiring qAF8, pseudophakic participants without blue-filter IOLs or advanced PCO should be preferentially enrolled.

The Effect of Dietary Supplementations on Delaying the Progression of Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.

Purpose: Age-related macular degeneration (AMD) is a neurodegenerative ophthalmic disease. The purpose of this systematic review (SR) and meta-analysis was to evaluate if dietary supplementation alone or in combinations might delay the progression of any of the stages of AMD. Methods: A SR and meta-analysis identifying cohort studies and randomized controlled trials (RCTs) evaluating the effect of supplements in patients diagnosed with AMD. PubMed, Scopus, Web of Science, CINAHL, and Cochrane were searched through 8th October 2021. Results: Twenty studies, examining 5634 participants ranging from 55 to 80 years, were included in the SR. Eight studies were selected for meta-analysis (414 and 216 subjects in the intervention and control groups). Lutein and zeaxanthin plus n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) supplementation showed significant improvements in best-corrected visual acuity (BCVA) (SMD: −1.99, 95% CI: −3.33, −0.65) compared to the control group. Multifocal electroretinogram results (mfERG) were significantly improved overall (SMD: 4.59, 95% CI: 1.75, 7.43) after lutein plus zeaxanthin supplementation. Conclusions: Combinations of lutein and zeaxanthin with n-3 LC-PUFA might be beneficial in preventing AMD progression and deterioration of visual function. Our results encourage initiating further studies with combinations of n-3 LC-PUFA, lutein, and zeaxanthin especially in early AMD patients.

OCT Risk Factors for Development of Atrophy in Eyes with Intermediate Age-Related Macular Degeneration

To determine the frequency of multiple OCT biomarkers of intermediate age-related macular degeneration (iAMD) and their relationship with the development of complete retinal pigment epithelium and outer retinal atrophy (cRORA) after 2 years. Retrospective cohort study. This retrospective analysis included 330 eyes of 330 consecutive patients with iAMD in ≥ 1 eye who had 24 months of follow-up data. Spectralis OCT volume scans (49 B-scans over 6× 6 mm, automatic real time = 6, fovea-centered) at baseline were evaluated for the previously described iAMD biomarkers, including a high-central drusen volume (DV; ≥ 0.03 mm3), intraretinal hyper-reflective foci (IHRF), subretinal drusenoid deposits (SDDs), hypo-reflective drusen cores (hDCs), and a thin or thick (multilayered) double-layer sign (DLS). The age-related macular degeneration (AMD) status in the fellow eye was also assessed and classified as normal or early AMD, iAMD, exudative macular neovascularization, or cRORA. Incidence of cRORA, odds ratio for demographics, and OCT features. At month 24, 16.36% (54/330) of the iAMD eyes developed cRORA. Several baseline features, including high-central DV, IHRF, SDD, hDC, thin DLS, and cRORA in the fellow eye, were associated with a significantly greater risk for development of cRORA at 2 years. The odds ratio, 95% confidence interval, P value, and baseline frequencies of these biomarkers were DV (6.510, 2.467-17.176, P < 0.001, 49.1%), IHRF (12.763, 4.763-34.202, P < 0.001, 38.8%), SDD (2.307, 1.003-5.304, P= 0.049, 34.2%), hDC (3.012, 1.152-7.873, P= 0.024, 13.0%), thin DLS (4.517, 1.555-13.126, P= 0.006, 11.8%), and cRORA in the fellow eye (7.184, 1.938-26.623, P= 0.003, 8.2%). In addition to the 4 previously reported factors that are present in a significant proportion of iAMD (DV, IHRF, hDC, and SDD), a thin DLS and cRORA in the fellow eye were associated with an increased risk of progression to cRORA over 2 years. These biomarkers may aid in prognostication, risk stratification, and selection of patients for clinical trials.

Enhanced Detection of Reticular Pseudodrusen on Color Fundus Photos by Image Embossing

Purpose To evaluate whether processing a color fundus photo (CFP) using an image embossing technique can improve the detection of reticular pseudodrusen (RPD). Methods This post-hoc analysis included the eyes of subjects enrolled in the Amish Eye Study with early or intermediate age-related macular degeneration and evidence of RPD. All patients underwent CFP, near-infrared reflectance (NIR), and fundus autofluorescence (FAF) imaging. The ground-truth presence of RPD was established with a combination of NIR and FAF imaging. An embossing processed (EP) image was created by replacing each pixel of the CFP image with a highlight or a shadow representing light and dark boundaries in the original CFP image. The presence of RPD in CFP and EP images was assessed by two graders in a masked fashion and the sensitivity of CFP and EP for detection of RPD was evaluated. Cohen’s kappa (k) was used to test inter-grader agreement for CFP and EP. Results A total of 106 eyes from 62 patients with RPDs were analyzed. The sensitivity for detection of RPD on CFP and EP was 63.2% (95%CI: 52.0%–74.4%) and 91.5% (95%CI: 85.0%–98.0%), respectively. The inter-rater reliabilities of CFP and EP for RPD detection were 0.81 and 0.84, respectively. Conclusions Embossing of CFP can improve the sensitivity for detection of RPD. The embossing technique can be a useful tool for better assessment of the true frequency of RPD in datasets where only CFP images are available.

Characterization and identification of measurable endpoints in a mouse model featuring age-related retinal pathologies: a platform to test therapies

AbstractApolipoprotein B100 (apoB100) is the structural protein of cholesterol carriers including low-density lipoproteins. It is a constituent of sub-retinal pigment epithelial (sub-RPE) deposits and pro-atherogenic plaques, hallmarks of early dry age-related macular degeneration (AMD), an ocular neurodegenerative blinding disease, and cardiovascular disease, respectively. Herein, we characterized the retinal pathology of transgenic mice expressing mouse apoB100 in order to catalog their functional and morphological ocular phenotypes as a function of age and establish measurable endpoints for their use as a mouse model to test potential therapies. ApoB100 mice were found to exhibit an age-related decline in retinal function, as measured by electroretinogram (ERG) recordings of their scotopic a-wave, scotopic b-wave; and c-wave amplitudes. ApoB100 mice also displayed a buildup of the cholesterol carrier, apolipoprotein E (apoE) within and below the supporting extracellular matrix, Bruch's membrane (BrM), along with BrM thickening, and accumulation of thin diffuse electron-dense sub-RPE deposits, the severity of which increased with age. Moreover, the combination of apoB100 and advanced age were found to be associated with RPE morphological changes and the presence of sub-retinal immune cells as visualized in RPE-choroid flatmounts. Finally, aged apoB100 mice showed higher levels of circulating and ocular pro-inflammatory cytokines, supporting a link between age and increased local and systemic inflammation. Collectively, the data support the use of aged apoB100 mice as a platform to evaluate potential therapies for retinal degeneration, specifically drugs intended to target removal of lipids from Bruch's membrane and/or alleviate ocular inflammation.

OCT angiography analysis of choriocapillaris vascular density in different stages of age-related macular degeneration.

To analyze the choriocapillaris vessel density (CVD) of eyes at different stages of Age-related Macular Degeneration (AMD) with Optical Coherence Tomography Angiography (OCTA). This is a prospective observational cross-sectional study on 21 age-matched healthy eyes and 84 eyes with AMD (i.e., early AMD, late AMD, Geographic Atrophy [GA], and disciform scar AMD). OCTA was used to automatically measure the CVD (%), on both the whole macula and the foveal area, in a layer going from 9 µm above to 30 µm below the Bruch's membrane. Furthermore, in the GA subgroup, the extension of the Ellipsoid Zone (EZ) interruption and the area of macular chorio-retinal atrophy was analyzed. Macular CVD was significantly lower in the GA, late AMD and disciform scar AMD-subgroups compared to controls (respectively, p=0.0052; p<0.0001; p=0.0003), whereas it did not significantly vary in the early AMD group (p=0.86). A significant difference between the early AMD and both the late AMD and the disciform scar AMD subgroups was also found (p=0.0009 and 0.0095, respectively). When comparing the foveal CVD of healthy and AMD eyes, a significant difference was found with every AMD subgroup (early AMD, p=0.011; GA, p<0.0001; late AMD, p<0.0001; disciform scar AMD, p<0.0001). Furthermore, in the GA subgroup, the CVD had an inverse correlation with both the extension of the EZ-interruption (p=0.012) and with the calculated chorio-retinal atrophic area (p=0.009). OCTA could play a crucial role in the categorization of AMD, allowing for the evaluation of gradual flow impairment at different stages of the disease. Moreover, the detection of a decreased macular and foveal CVD may shed light on the pathogenesis of AMD.

BASELINE SATTLER LAYER-CHORIOCAPILLARIS COMPLEX THICKNESS CUTOFFS ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION PROGRESSION.

To assess the relationship between choroidal overall and sublayer thickness and age-related macular degeneration (AMD) stage progression. A prospective, observational case series was performed. Two hundred and sixty-two eyes of 262 patients with different stages of AMD were imaged by optical coherence tomography. Age-related macular degeneration stage, choroidal thickness, Sattler layer-choriocapillaris complex thickness (SLCCT), and Haller layer thickness were determined at the baseline visit, at a 1-year follow-up visit, at a 2-year follow up visit, and at a final visit (performed after a mean of 5 ± 1 year from the baseline visit). Baseline AMD stages were distributed as follows: early AMD (30 eyes; 12%), intermediate AMD (97 eyes; 39%), and late AMD (126 eyes; 49%). At the final follow-up, AMD stages were so distributed: early AMD (14 eyes; 6%), intermediate AMD (83 eyes; 33%), and late AMD (156 eyes; 61%). Each group showed a statistically significant decrease in choroidal thickness values over the entire follow-up ( P < 0.001), and SLCCT reduction was associated with AMD progression ( P < 0.001). Moreover, SLCCT quantitative cutoffs of <20.50 µ m and <10.5 µ m were associated with a moderate and high probability of AMD progression, respectively, and SLCCT quantitative cutoffs of <18.50 µ m and <8.50 µ m implied a moderate and high probability of macular neovascularization onset, respectively. Progressive choroidal impairment contributes to AMD progression. Among choroidal layers, a reduced SLCCT is a promising biomarker of disease worsening, and its quantitative evaluation could help to identify patients at higher risk of stage advancement.

Automated segmentation and feature discovery of age-related macular degeneration and Stargardt disease via self-attended neural networks

Age-related macular degeneration (AMD) and Stargardt disease are the leading causes of blindness for the elderly and young adults respectively. Geographic atrophy (GA) of AMD and Stargardt atrophy are their end-stage outcomes. Efficient methods for segmentation and quantification of these atrophic lesions are critical for clinical research. In this study, we developed a deep convolutional neural network (CNN) with a trainable self-attended mechanism for accurate GA and Stargardt atrophy segmentation. Compared with traditional post-hoc attention mechanisms which can only visualize CNN features, our self-attended mechanism is embedded in a fully convolutional network and directly involved in training the CNN to actively attend key features for enhanced algorithm performance. We applied the self-attended CNN on the segmentation of AMD and Stargardt atrophic lesions on fundus autofluorescence (FAF) images. Compared with a preexisting regular fully convolutional network (the U-Net), our self-attended CNN achieved 10.6% higher Dice coefficient and 17% higher IoU (intersection over union) for AMD GA segmentation, and a 22% higher Dice coefficient and a 32% higher IoU for Stargardt atrophy segmentation. With longitudinal image data having over a longer time, the developed self-attended mechanism can also be applied on the visual discovery of early AMD and Stargardt features.

Mitophagy initiates retrograde mitochondrial-nuclear signaling to guide retinal pigment cell heterogeneity

ABSTRACT Age-related macular degeneration (AMD), the leading cause of blindness among the elderly, is without treatment for early disease. Degenerative retinal pigment epithelial (RPE) cell heterogeneity is a well-recognized but understudied pathogenic factor. Due to the daily phagocytosis of photoreceptor outer segments, unique photo-oxidative stress, and high metabolism for maintaining vision, the RPE has robust macroautophagy/autophagy, and mitochondrial and antioxidant networks. However, the autophagy subtype, mitophagy, in the RPE and AMD is understudied. Here, we found decreased PINK1 (PTEN induced kinase 1) in perifoveal RPE of early AMD eyes. PINK1-deficient RPE have impaired mitophagy and mitochondrial function that triggers death-resistant epithelial-mesenchymal transition (EMT). This reprogramming is mediated by novel retrograde mitochondrial-nuclear signaling (RMNS) through superoxide, NFE2L2 (NFE2 like bZIP transcription factor 2), TXNRD1 (thioredoxin reductase 1), and phosphoinositide 3-kinase (PI3K)-AKT (AKT serine/threonine kinase) that induced canonical transcription factors ZEB1 (zinc finger E-box binding homeobox 1) and SNAI1 (Snail family transcriptional repressor 1) and an EMT transcriptome. NFE2L2 deficiency disrupted RMNS that paradoxically normalized morphology but decreased function and viability. Thus, RPE heterogeneity is defined by the interaction of two cytoprotective pathways that is triggered by mitophagy function. By neutralizing the consequences of impaired mitophagy, an antioxidant dendrimer tropic for the RPE and mitochondria, EMT (a recognized AMD alteration) was abrogated to offer potential therapy for early AMD, a stage without treatment. Abbreviations: ACTB: actin beta; AKT: AKT serine/threonine kinase; AMD: age-related macular degeneration; CCCP: cyanide m-chlorophenyl hydrazone; CDH1: cadherin 1; DAVID: Database for Annotation, Visualization and Integrated Discovery; DHE: dihydroethidium; D-NAC: N-acetyl-l-cysteine conjugated to a poly(amido amine) dendrimer; ECAR: extracellular acidification rate; EMT: epithelial-mesenchymal transition; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GSEA: Gene Set Enrichment Analysis; HSPD1: heat shock protein family D (Hsp60) member 1; IVT: intravitreal; KD: knockdown; LMNA, lamin A/C; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MMP: mitochondrial membrane potential; NAC: N-acetyl-l-cysteine; NQO1: NAD(P)H quinone dehydrogenase 1; NFE2L2: NFE2 like bZIP transcription factor 2; O2 −: superoxide anion; OCR: oxygen consumption rate; PI3K: phosphoinositide 3-kinase; PINK1: PTEN induced kinase 1; RMNS: retrograde mitochondrial-nuclear signaling; ROS: reactive oxygen species; RPE: retinal pigment epithelium; SNAI1: snail family transcriptional repressor 1; TJP1: tight junction protein 1; TPP-D-NAC: triphenyl phosphinium and N-acetyl-l-cysteine conjugated to a poly(amido amine) dendrimer; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; Trig: trigonelline; TXNRD1: thioredoxin reductase 1; VIM: vimentin; WT: wild-type; ZEB1: zinc finger E-box binding homeobox 1

A Deep Learning Model for Automated Segmentation of Geographic Atrophy Imaged Using Swept-Source OCT

To present a deep learning algorithm for segmentation of geographic atrophy (GA) using en face swept-source OCT (SS-OCT) images that is accurate and reproducible for the assessment of GA growth over time. Retrospective review of images obtained as part of a prospective natural history study. Patients with GA (n= 90), patients with early or intermediate age-related macular degeneration (n= 32), and healthy controls (n= 16). An automated algorithm using scan volume data to generate 3 image inputs characterizing the main OCT features of GA-hypertransmission in subretinal pigment epithelium (sub-RPE) slab, regions of RPE loss, and loss of retinal thickness-was trained using 126 images (93 with GA and 33 without GA, from the same number of eyes) using a fivefold cross-validation method and data augmentation techniques. It was tested in an independent set of one hundred eighty 6× 6-mm2 macular SS-OCT scans consisting of 3 repeated scans of 30 eyes with GA at baseline and follow-up as well as 45 images obtained from 42 eyes without GA. The GA area, enlargement rate of GA area, square root of GA area, and square root of the enlargement rate of GA area measurements were calculated using the automated algorithm and compared with ground truth calculations performed by 2 manual graders. The repeatability of these measurements was determined using intraclass coefficients (ICCs). There were no significant differences in the GA areas, enlargement rates of GA area, square roots of GA area, and square roots of the enlargement rates of GA area between the graders and the automated algorithm. The algorithm showed high repeatability, with ICCs of 0.99 and 0.94 for the GA area measurements and the enlargement rates of GA area, respectively. The repeatability limit for the GA area measurements made by grader 1, grader 2, and the automated algorithm was 0.28, 0.33, and 0.92 mm2, respectively. When compared with manual methods, this proposed deep learning-based automated algorithm for GA segmentation using en face SS-OCT images was able to accurately delineate GA and produce reproducible measurements of the enlargement rates of GA.

The frequency of early age-related macular degeneration and its relationship with dietary pattern in Hunan, China: a cross-sectional study

PurposeTo estimate the frequency of age-related macular degeneration (AMD) among people who underwent health examination in Hunan, China and to determine the relationship between dietary pattern and the risk of AMD.MethodsThe Questionnaire was used to collect dietary data from 56,775 study participants of ≥ 50 years old who underwent health examination at the Department of Health Management, the Third Xiangya Hospital of Central South University between January 2017 and December 2019. The diagnosis of AMD was based on the results of color fundus photography (CFP), spectral-domain optical coherence tomography (OCT) and multispectral imaging (MSI). After excluding participants with incomplete records or other ocular disease that may affect the results of fundus examination, a total of 43,672 study participants were included. The univariate and multivariate logistic regression analyses were used to determine the relationship between dietary pattern and the frequency of AMD.ResultsAmong the 43,672 study participants, 1080 (2.5%) had early AMD: the frequencies were 2.6% (n = 674) in men and 2.3% (n = 406) in women; the frequencies were 1.0% (n = 289), 3.6% (n = 401), 9.1% (n = 390) in 50–59, 60–69, ≥ 70 years old, respectively. And the age-standard frequency was 6.6% over the 60 years old in Hunan China. The high-salt intake increased the risk of early AMD [odds ratio (OR) = 1.61, 95% confidence interval (CI) = 1.54–1.68], whereas the intake of meat decreased the risk (OR = 0.90, 95% CI = 0.81–0.99).ConclusionIn Hunan China, there was a high frequency of early AMD detected through health examination over the 60 years old. And high-salt intake increases the risk of early AMD, whereas intake of meat decreases the risk. Modulating the dietary pattern and reducing the salt intake as an AMD prevention strategy warrant further study.

Effects of smoking on the retina of patients with dry age-related macular degeneration by optical coherence tomography angiography

BackgroundThe macula of the retina is analysed using optical coherence tomography angiography (OCTA) to provide clinical basis and explain the mechanism of smoking as a risk factor in dry age-related macular degeneration (AMD).MethodsThis cross-sectional study included 49 normal control nonsmokers, 12 normal control smokers, 38 dry AMD nonsmokers and 35 dry AMD smokers. The foveal avascular zone (FAZ), foveal density (FD) in a 300 μm region around FAZ, vessel densities of the superficial (SCP) and deep (DCP) capillary plexuses and central fovea retinal thickness (FRT) were compared using OCTA. The bivariate correlation analysis was used to evaluate the effect of pack–year history on retina-related indices.ResultsThe vessel densities of whole, foveal and parafoveal of SCP and whole and parafoveal of DCP in the control nonsmoking group were all significantly higher than those in the dry AMD nonsmoking group (all P < 0.05), whereas the whole vessel density of SCP in the normal smoking group was higher than that in the dry AMD smoking group (P = 0.04). The thickness values of the inner and full-layer FRT in the normal nonsmoking group were significantly thicker than those in the dry AMD nonsmoking group (all P < 0.01). The pack–year history was negatively correlated with the parafoveal vessel density of DCP (r = − 0.224, P < 0.01).ConclusionsFD, SCP, DCP and FRT are sensitive indices for the detection of early and intermediate dry AMD. DCP is a sensitive indicator that reflects the effects of smoking on the retina. Considerable changes are observed in retinal vessels, suggesting that dry AMD may affect the retinal tissue to a certain extent.

How Vision Is Impaired From Aging to Early and Intermediate Age-Related Macular Degeneration: Insights From ALSTAR2 Baseline.

PurposeWe hypothesize the first visual dysfunction in transitioning to early and intermediate age-related macular degeneration (AMD) is delayed rod-mediated dark adaptation (RMDA), owing to impaired photoreceptor sustenance from the circulation. This analysis from the Alabama Study on Early Age-related Macular Degeneration 2 provides insight on our framework's validity, comparing RMDA and other visual tests among older normal, early, and intermediate AMD eyes.MethodsAMD disease severity was determined via fundus photos using the Age-Related Eye Disease Study nine-step system. Visual functions evaluated were RMDA 5°, acuity, contrast sensitivity (photopic, mesopic), and light sensitivity for a macular grid (scotopic, mesopic, photopic). Presence versus absence of subretinal drusenoid deposits (SDD) was identified through multimodal imaging.ResultsOne eye from each of 481 persons (mean age, 72 years) was evaluated. All visual functions were significantly worse with increasing AMD disease severity. Using z-scores to standardize visual function measures across groups, the greatest difference in probability density functions between older normal and intermediate AMD was for RMDA. Early and intermediate AMD eyes with SDD present had longer rod intercept times than eyes with SDD absent. SDD absent eyes also exhibited delayed RMDA and wide probability density functions relative to normal eyes.ConclusionsAmong the visual functions evaluated, RMDA best discriminates among normal, early AMD, and intermediate AMD eyes. The Alabama Study on Early Age-related Macular Degeneration 2 will evaluate whether AMD's natural history confirms our hypothesis at the 3-year follow-up.Translational RelevanceResults support a sequence of visual function impairments in aging and AMD, suggesting RMDA as a promising outcome for evaluating interventions in early disease.

The Association Between Diabetic Retinopathy and the Prevalence of Age-Related Macular Degeneration-The Kailuan Eye Study.

This study aimed to investigate the prevalence of age-related macular degeneration (AMD) in patients with diabetes mellitus (DM) and diabetic retinopathy (DR) and analyze whether DR is a risk factor for AMD. This population-based epidemiological study included 14,440 people from the Kailuan Eye Study in 2016, of whom 1,618 were patients with type 2 DM aged over 50 years, and 409 had DM with DR. We analyzed whether there were differences in the prevalence of AMD between DM with DR and DM without DR, and conducted a hierarchical statistical analysis according to different stages of DR. Using variable regression analysis, we explored whether DR constituted a risk factor for AMD. In the DM population, the prevalence of wet AMD in patients with DM with and without DR was 0. 3 and 0.2%, respectively, with no significant difference (P = 0.607). Meanwhile, the prevalence of dry AMD in patients with DM with and without DR was 20.8 and 16.0%, respectively, with a significant difference. In the subgroup analysis of dry AMD, the prevalence of early, middle, and late dry AMD in DM with DR was 14.4, 5.9, and 0.5%, respectively. In DM without DR, the prevalence of early, middle, and late dry AMD was 10.5, 4.8, and 0.7%, respectively (P = 0.031). In the subgroup analysis of DR staging, statistical analysis could not be performed because of the limited number of patients with PDR. In the variable regression analysis of risk factors for dry AMD, after adjusting for age, sex, body mass index, hypertension, and dyslipidemia, DR constituted the risk factor for dry AMD. In conclusion, DM did not constitute a risk factor for AMD, and the prevalence of wet AMD and dry AMD in patients with DM and DR was higher than that in patients with DM without DR (among which dry AMD was statistically significant). Multivariate regression analysis confirmed that DR is an independent risk factor for dry AMD. Reasonable control of DM and slowing down the occurrence and development of DR may effectively reduce the prevalence of AMD in patients with DM.

Chorioretinal thickness and retinal pigment epithelial degeneration of fellow eyes in patients with unilateral neovascular age-related macular degeneration with subretinal drusenoid deposits

BackgroundWe sought to investigate the chorioretinal thickness and retinal pigment epithelial (RPE) degenerative features of eyes with early age-related macular degeneration (AMD) and subretinal drusenoid deposits (SDDs) according to the presence of macular neovascularization (MNV) in the fellow eyes.MethodsWe classified 70 eyes into two groups of 47 eyes with non-neovascular AMD and 23 eyes with neovascular AMD, respectively, according to the presence of MNV in the fellow eyes. The mean macular retinal, ganglion cell–inner plexiform layer (GCIPL), and choroidal thickness values and RPE features of the 6-mm-diameter zone were compared. RPE degeneration was defined as a lesion with an incomplete RPE and outer retinal atrophy (iRORA) or attenuated RPE reflectivity with diffuse basal laminar deposits, which was defined as when the eye showed an attenuated RPE line with granular features and mixed reflectivity in combination with sub-RPE deposits with a lesion ≥ 1,000 µm in length.ResultsMean retinal, GCIPL, and choroidal thickness values (286.69 ± 15.02 µm, 64.36 ± 4.21 µm, and 156.11 ± 33.10 µm) of the neovascular AMD group were greater than those (278.61 ± 13.96 µm, 61.44 ± 4.63 µm, and 133.59 ± 34.33 µm) of the non-neovascular AMD group (all P < 0.05). RPE degeneration was more prevalent in the neovascular AMD group (65.2%) than the non-neovascular AMD group (38.3%; P = 0.034). Greater mean GCIPL and choroidal thickness values and the presence of RPE degeneration were associated with type 3 MNV in fellow eyes (all P < 0.05).ConclusionsDifferent degenerative features according to MNV in fellow eyes of patients with AMD and SDDs suggest that variable degenerative features might be present during disease progression and have an association with the phenotype.