Age-related Macular Degeneration Subjects Research Articles

Alterations of the Ganglion Cell Complex in Age-Related Macular Degeneration: an AMISH Eye Study Analysis

To compare the Ganglion Cell Complex (GCC) thickness in eyes with age-related macular degeneration (AMD) versus healthy controls in an elderly Amish population DESIGN: Cross-sectional study METHODS: This is a post hoc analysis of the family-based prospective study of Amish subjects. Study subjects were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec Inc, Dublin, CA) using a macular cube protocol of 512 × 128 scans (128 horizontal B-scans, each compromising 512 A-scans) over a 6 mm x 6 mm region centered on the fovea. The ganglion cell analysis algorithm calculated the GCC thickness by segmenting the outer boundaries of the retinal nerve fiber layer (RNFL) and inner plexiform layer (IPL) in all B-scans of the volume, with the region between these boundaries representing the combined thickness of the GCL and the IPL layer. A number of parameters were used to evaluate the GCC thickness: the average GCC thickness, minimum (lowest GCC thickness at a single meridian crossing the elliptical annulus), and sectoral (within each of six sectoral areas: superior, superotemporal, superonasal, inferior, inferonasal, and inferotemporal). The stage of AMD was graded on color fundus photographs in accordance with the Beckman Initiative for Macular Research classification system. Of 1339 subjects enrolled in the Amish eye study, a total of 1294 eyes of twelve hundred and ninety-four subjects had all required imaging studies of sufficient quality and were included in the final analysis, and of these 798 (62%) were female. Following age adjustment, the average GCC thickness was significantly (p<0.001) thinner in AMD subjects (73.71 ± SD; 13.77 µm) compared to normals (77.97 ± 10.42 µm). Independent t test showed that, early (75.03 ± 12.45 µm), and late AMD (61.64 ± 21.18 µm) groups (among which GA eyes had the lowest thickness of 58.10 ± 20.27 microns) had a statistically significant lower GCC thickness compared to eyes without AMD. There was no significant difference in average GCC thickness between early AMD and intermediate AMD (76.36 ± 9.25 µm) eyes. The GCC thickness in AMD eyes is reduced compared to normal eyes, but the relationship is complex with the greatest reduction in late AMD eyes (particularly GA eyes) but no difference between early and intermediate AMD eyes.

Quantifying cardiac dysfunction and valvular heart disease associated with subretinal drusenoid deposits in age-related macular degeneration.

Demonstrate through objective multidisciplinary imaging that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to both coexistent valvular heart disease (VHD) and reduced systemic perfusion via cardiac index (CI). Post-hoc analysis of cross-sectional study. 200 intermediate AMD (iAMD) subjects were assigned by masked readers to two groups: SDD (with or without drusen) and drusen (only) based on multimodal ophthalmic imaging. 65 transthoracic echocardiograms (TTEs) reports were available for cardiologist evaluation of VHD severity of the four cardiac valves and the presences of precursor lesions of aortic sclerosis (ASc) and mitral annular calcification (MAC). Necessary parameters to calculate CI were also obtained. Univariate testing was performed using Fisher's Exact test and t-test. 82.6% (19/23) of the iAMD subjects with at least one moderate/severe VHD had concurrent SDDs (p = 0.0040). All cases of aortic regurgitation (6/6, p = 0.0370) and mitral regurgitation (13/13, p = 0.0004) were found with coexisting SDDs. Stenotic VHD was not significantly associated with SDDs, however 70.7% of subjects with ASc (29/41, p = 0.0108) and 76.0% of subjects with MAC (19/25, 0.0377) had coexisting SDDs. CI was available in 48 subjects and was significantly below normal levels in the SDD cohort (mean CI SDD 1.95 ± 0.60 L/min/m2, non-SDD 2.71 ± 0.73 L/min/m2, p = 0.0004). Several specific VHDs have been found associated with the SDD form of AMD. Decreased systemic perfusion as measured by CI was also associated with SDDs, which supports a perfusion hypothesis of SDD pathogenesis. Further research is warranted to understand the relationship between cardiovascular disease and SDDs.

Correlation between ellipsoid zone thickness and the presence of subretinal drusenoid deposits in age-related macular degeneration

PurposeSubretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are associated with systemic vascular diseases that compromise ocular perfusion. We demonstrate that SDDs are associated with decreased ellipsoid zone (EZ)...

Microglia at sites of atrophy restrict the progression of retinal degeneration via galectin-3 and Trem2.

Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and human AMD. In disease models, conditional deletion of galectin-3 in microglia led to phagocytosis defects and consequent augmented photoreceptor death, RPE damage, and vision loss, indicating protective roles. Mechanistically, Trem2 signaling orchestrated microglial migration to atrophic sites and induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection but in a galectin-3-dependent manner. In elderly human subjects, we identified this highly conserved microglial population that expressed galectin-3 and Trem2. This population was significantly enriched in the macular RPE-choroid of AMD subjects. Collectively, our findings reveal a neuroprotective population of microglia and a potential therapeutic target for mitigating retinal degeneration.

Metagenomic Sequencing Analysis Identifies Cross-Cohort Gut Microbial Signatures Associated With Age-Related Macular Degeneration.

Alterations in the gut microbiota have been associated with age-related macular degeneration (AMD). However, the dysbiosis shared by different ethnicity and geographic groups, which may associate with the disease pathogenesis, remain underexplored. Here, we characterized dysbiosis of the gut microbiota in patients with AMD from Chinese and Swiss cohorts and identified cross-cohort signatures associated with AMD. Shotgun metagenomic sequencing was performed on fecal samples from 30 patients with AMD and 30 healthy subjects. Published datasets with 138 samples from Swiss patients with AMD and healthy subjects were re-analyzed. Comprehensive taxonomic profiling was conducted by matching to the RefSeq genome database, metagenome-assembled genome (MAG) database, and Gut Virome Database (GVD). Functional profiling was performed by reconstruction of the MetaCyc pathways. The α-diversity of the gut microbiota was decreased in patients with AMD according to taxonomic profiles generated using MAG but not RefSeq database as reference. The Firmicutes/Bacteroidetes ratio was also decreased in patients with AMD. Among AMD-associated bacteria shared between Chinese and Swiss cohorts, Ruminococcus callidus, Lactobacillus gasseri, and Prevotellaceae (f) uSGB 2135 were enriched in patients with AMD, whereas Bacteroidaceae (f) uSGB 1825 was depleted in patients with AMD and was negatively associated with hemorrhage size. Bacteroidaceae was one of the major hosts of phages associated with AMD. Three degradation pathways were reduced in AMD. These results demonstrated that dysbiosis of the gut microbiota was associated with AMD. We identified cross-cohort gut microbial signatures involving bacteria, viruses, and metabolic pathways, which potentially serve as promising targets for the prevention or treatment of AMD.

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

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

LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration.

Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD. The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850nm) or sham treatment 3 × per week over 3-4weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500μm). LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p < 0.1) for patients that received all 27 PBM treatments (n = 29 eyes). Approximately 35.3% of PBM-treated eyes showed ≥ 5-letter improvement at 9months. Macular drusen volume was not increased over time in the PBM-treated group but did show increases in the sham-treated group. While PBM and sham groups both showed GA lesion growth in the trial period, there was 20% less growth in the PBM group over 10months, suggesting potential disease-modifying effects. No safety concerns or signs of phototoxicity were observed. These results confirm previous clinical testing of multiwavelength PBM and support treatment with Valeda as a novel therapy with a unique mechanism of action as a potential treatment for non-exudative AMD. Clinicaltrial.Gov Registration Identifier: NCT03878420.

Cross-Sectional Study of Cone Function in Age-Related Macular Degeneration Subjects With Non-foveal Nascent Geographic Atrophy

To determine photoreceptor function in subjects with drusen only and non-foveal nascent geographic atrophy (nGA) intermediate age-related macular degeneration. In this cross-sectional study, 60 eyes from 33 subjects, 30 with drusen only and 30 with non-foveal nGA determined by spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) underwent testing for best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), and qCSF algorithm (area under log contrast sensitivity function [AULCSF]) under both standard photopic and low-luminance (LL AULCSF) conditions. Areas of nGA-associated hypo-autofluorescence (hypo-AF) were graded. In the drusen group, visual acuity (VA)=81 letters ± 3 (mean ± SD), LLVA=65 letters ± 4, AULCSF=0.99 ± 0.0.5, and LL AULCSF=0.38 ± 0.04, whereas in the nGA group, VA=77 ± 4 letters, LLVA=61± 4, AULCSF=0.87 ± 0.09, and LL AULCSF=0.28 ± 0.06. Multivariate analysis of variance among the LLVA, AULCSF, and LL AULCSF did not demonstrate a statistical difference (P=.167), whereas LL AULCSF analyzed by analysis of variance demonstrated a significant difference between the 2 groups (P=.037). Linear regressions demonstrated significant relationships between BCVA and AULCSF in both the drusen and nGA groups (r=0.83, P < 10-9 and r=0.61, P=.0004) but did not correlate with AULCSF under low-luminance conditions (r=2.9, P=.13) in the nGA group. The total area of hypo-AF was negatively associated with poorer visual functions. The use of LL AULCSF and certain features of FAF should be considered in clinical trials of intermediate age-related macular degeneration. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Subretinal drusenoid deposits are strongly associated with coexistent high-risk vascular diseases

Background/aimsDemonstrate that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to coexistent high-risk vascular diseases (HRVDs).MethodsCross-sectional study. Two hundred AMD subjects (aged 51–100 years; 121 women, 79...

Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting.

Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. ‘Wet’ AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage. Gold standard anti-vascular endothelial growth factor (VEGF) treatment is an effective therapy, but the long-term prevention of visual decline has not been as successful. This warrants the need to elucidate potential VEGF-independent pathways. We generated blood out-growth endothelial cells (BOECs) from wet AMD and normal control subjects, then induced angiogenic sprouting of BOECs using a fibrin gel bead assay. To deconvolute endothelial heterogeneity, we performed single-cell transcriptomic analysis on the sprouting BOECs, revealing a spectrum of cell states. Our wet AMD BOECs share common pathways with choroidal neovascularization such as extracellular matrix remodeling that promoted proangiogenic phenotype, and our ‘activated’ BOEC subpopulation demonstrated proinflammatory hallmarks, resembling the tip-like cells in vivo. We uncovered new molecular insights that pathological angiogenesis in wet AMD BOECs could also be driven by interleukin signaling and amino acid metabolism. A web-based visualization of the sprouting BOEC single-cell transcriptome has been created to facilitate further discovery research.

Association of Human Plasma Metabolomics with Delayed Dark Adaptation in Age-Related Macular Degeneration.

The purpose of this study was to analyze the association between plasma metabolite levels and dark adaptation (DA) in age-related macular degeneration (AMD). This was a cross-sectional study including patients with AMD (early, intermediate, and late) and control subjects older than 50 years without any vitreoretinal disease. Fasting blood samples were collected and used for metabolomic profiling with ultra-performance liquid chromatography–mass spectrometry (LC-MS). Patients were also tested with the AdaptDx (MacuLogix, Middletown, PA, USA) DA extended protocol (20 min). Two measures of dark adaptation were calculated and used: rod-intercept time (RIT) and area under the dark adaptation curve (AUDAC). Associations between dark adaption and metabolite levels were tested using multilevel mixed-effects linear modelling, adjusting for age, gender, body mass index (BMI), smoking, race, AMD stage, and Age-Related Eye Disease Study (AREDS) formulation supplementation. We included a total of 71 subjects: 53 with AMD (13 early AMD, 31 intermediate AMD, and 9 late AMD) and 18 controls. Our results revealed that fatty acid-related lipids and amino acids related to glutamate and leucine, isoleucine and valine metabolism were associated with RIT (p < 0.01). Similar results were found when AUDAC was used as the outcome. Fatty acid-related lipids and amino acids are associated with DA, thus suggesting that oxidative stress and mitochondrial dysfunction likely play a role in AMD and visual impairment in this condition.

Directional Reflectivity of the Ellipsoid Zone in Dry Age-Related Macular Degeneration.

Ellipsoid zone (EZ) reflectivity on optical coherence tomography (OCT) is affected by the orientation of the scanning beam. The authors sought to determine how directional reflectivity changes in dry age-related macular degeneration (AMD). Retrospective image analysis included 17 control and 20 dry AMD subjects. Directional OCT (D-OCT) was performed using multiple displaced pupil entrance positions. EZ pixel values and apparent incidence angles were measured. EZ reflectivity decreased in off-axis scans in controls (P < .001), AMD areas between drusen (P < .001), and AMD areas overlying drusen (P < .001). The magnitude of decrement in EZ reflectivity was significantly higher when incidence angles exceeded 10° in controls than in AMD areas between drusen (P = .024). EZ reflectivity in dry AMD may vary by incident angle of light less than in controls, possibly indicating alteration of photoreceptor orientation or integrity. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:145-152.].

Possible Association of Periodontal Disease and Macular Degeneration: A Case-Control Study.

Oral pathogens have been identified in bioptic specimens from Age-Related Macular Degeneration (ARMD) patients, and alveolar bone loss has been related to ARMD. Therefore, the possible association between ARMD and periodontal disease was investigated in the present case-control study, evaluating clinical and radiographic periodontal parameters, primarily, in cases vs. controls and, secondarily, in relation to ARMD risk factors, in cases, to highlight a possible pathogenic link between the disorders. Forty ARMD cases and 40 non-ARMD controls, matched for age (±3 years) and gender and homogeneous for ARMD risk factors, therefore comparable, underwent full-mouth periodontal charting, panoramic radiograph, and medical data, including ARMD risk factors, collection. Statistical analysis was conducted using the language R. Comparisons between groups were made using both traditional t-tests and Yuen’s test with bootstrap calibration. Enrolled subjects were ≥55 years old, and 50 females and 30 males were equally distributed among the two groups. No statistically significant difference was found in clinical and radiographic periodontal parameters in cases vs. controls. In the case group, no differences were found when relating the periodontal parameters to ARMD risk factors, except for Clinical Attachment Level values that were statistically significantly higher in hypertensive ARMD subjects. A possible association between periodontal disease and ARMD may be hypothesized in hypertensive ARMD subjects, with hypertension as a possible pathogenic link between the disorders.

Biomechanical properties of the cornea following intravitreal ranibizumab injection.

To evaluate intraocular pressure (IOP) and corneal biomechanical properties changes after intravitreal ranibizumab injection (IVRI). One hundred twenty eyes of 120 patients who underwent IVRI between January and March 2018 in Adnan Menderes University Ophthalmology Clinic were included in study. Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc) were measured by Ocular Response Analyzer (ORA) by the same specialist preoperatively (preop), postoperative 1st (postop-1st), postoperative 3rd (postop-3rd), and postoperative 24th hours (postop-24th) after single-dose IVRI. Among the 120 wet age-related macular degeneration subjects, 58 (48.3%) were female and 62 (51.7%) were male. The mean age was 64.8 ± 10.4years. Postop-1st hour IOP cc and IOPg measurements were statistically different from all other measurements (p < 0.001). Postop-1st hour CH measurements were statistically different from preop and postop-3rd (p = 0.022 and p = 0.008, respectively). After intravitreal injection, IOP pressures significantly increased. But, CH and CRF values were significantly decreased. All these changes were temporary.

An exploratory study to evaluate visual function endpoints in non-advanced age-related macular degeneration

BackgroundTo prevent irreversible vision loss in age-related macular degeneration (AMD), it is critical to detect retinal dysfunction before permanent structural loss occurs. In the current study we evaluated a series of visual function tests to identify potential endpoints to detect visual dysfunction in non-advanced AMD.MethodsA series of visual function tests were performed on 23 non-advanced AMD subjects (AREDS grade 1–4 on simplified scale) and 34 age-matched normals (AREDS grade 0). Tests included some commonly used endpoints such as ETDRS visual acuity (VA), low luminance (LL) 2.0ND ETDRS VA, MNREAD as well as newly developed tests such as the Ora-VCF™ test, Ora-tablet reading test, color sensitivity etc. Differences between the two groups were compared for each test. Test-retest repeatability and reproducibility was assessed on a subset of subjects and percent agreement was calculated.ResultsThere was no difference in standard ETDRS VA between non-advanced AMD (0.06 ± 0.02 logMAR) and normal groups (0.04 ± 0.02 logMAR) (p = 0.57). LL 2.0 ETDRS VA and MNREAD showed no difference between the groups (p > 0.05). Ora-VCF™ test was significantly worse in the non-advanced AMD group compared to normals (0.67 ± 0.07 in AMD; 0.45 ± 0.04 in normals, p = 0.005). Non-advanced AMD subjects also had significantly worse reading performance using the Ora-tablet with LL 2.0ND (114.55 ± 11.22 wpm in AMD; 145.17 ± 9.55 wpm in normals p = 0.049). No significant difference between the groups was noted using other tests. Repeatability was 82% for Ora-VCF™ test and 92% for Ora-tablet LL 2.0ND reading. Reproducibility was 89% for both Ora-VCF™ test and Ora-tablet LL 2.0ND reading.ConclusionWhile there was no significant difference between non-advanced AMD and normal groups using some current common endpoints such as ETDRS VA, LL 2.0 ETDRS VA or MNREAD, Ora-VCF™ test and Ora-tablet LL 2.0ND reading tests were able to identify significant visual dysfunction in non-advanced AMD subjects. These tests show promise as endpoints for AMD studies.

Differential effects of risuteganib and bevacizumab on AMD cybrid cells

PurposeIntravitreal injections of anti-vascular endothelial growth factor (VEGF) treatments are currently used to treat wet age-related macular degeneration (AMD), diabetic retinopathy, and macular edema. Chronic, repetitive treatments with anti-VEGF may have unintended consequences beyond the inhibition of angiogenesis. Most recently, clinical trials have been conducted with risuteganib (RSG, Luminate®), which is anti-angiogenic and has neuroprotective and anti-inflammatory properties. Mitochondrial damage and dysfunction play a major role in development of AMD. Transmitochondrial cybrids are cell lines established by fusing human retinal pigment epithelial (RPE) cells that are Rho0 (lacking mtDNA) with platelets isolated from AMD subjects or age-matched normal subjects. Cybrid cell lines have identical nuclei but mitochondria from different subjects, enabling investigation of the functional consequences of damaged AMD mitochondria. The present study compares the responses of AMD cybrids treated with bevacizumab (Bmab, Avastin®) versus risuteganib (RSG, Luminate®). MethodsCybrids were created by fusing mtDNA depleted ARPE-19 cells with platelets from AMD or age-matched normal patients. AMD (n = 5) and normal (n = 3) cybrids were treated for 48 h with or without 1x clinical dose of 1.25 mg/50 μl (25,000 μg/ml) of Bmab or 1.0 mg/50 μl (20,000 μg/ml) of RSG. Cultures were analyzed for levels of cleaved caspase 3/7 and NucLight Rapid Red staining (IncuCyte® Live Cell Imager), mitochondrial membrane potential (ΔΨm, JC1 assay) or reactive oxygen species (ROS, H2DCFDA assay). Expression levels of genes related to the following pathways were analyzed with qRT-PCR: Apoptosis (BAX, BCL2L13, CASP-3, -7, -9); angiogenesis (VEGFA, HIF1α, PDGF); integrins (ITGB-1, -3, -5, ITGA-3, -5, -V); mitochondrial biogenesis (PGC1α, POLG); oxidative stress (SOD2, GPX3, NOX4); inflammation (IL-6, -18, -1β, IFN-β1); and signaling (P3KCA, PI3KR1). Statistical analyses were performed using GraphPad Prism software. ResultsThe untreated AMD cybrids had significantly higher levels of cleaved caspase 3/7 compared to the untreated normal cybrids. The Bmab-treated AMD cybrids showed elevated levels of cleaved caspase 3/7 compared to untreated AMD or RSG-treated AMD cybrids. The Bmab-treated cybrids had lower ΔΨm compared to untreated AMD or RSG-treated AMD cybrids. The ROS levels were not changed with Bmab or RSG treatment. Results showed that Bmab-treated cybrids had higher expression levels of inflammatory (IL-6, IL1-β), oxidative stress (NOX4) and angiogenesis (VEGFA) genes compared to untreated AMD, while RSG-treated cybrids had lower expression levels of apoptosis (BAX), angiogenesis (VEGFA) and integrin (ITGB1) genes. ConclusionsThese data suggest that the mechanism(s) of action of RSG, an integrin regulator, and Bmab, a recombinant monoclonal antibody, affect the AMD RPE cybrid cells differently, with the former having more anti-apoptosis properties, which may be desirable in treating degenerative ocular diseases.

Imaging of Age-Related Macular Degeneration by Adaptive Optics Scanning Laser Ophthalmoscopy in Eyes With Aged Lenses or Intraocular Lenses.

PurposeTo assess the performance of adaptive optics scanning laser ophthalmoscopy (AOSLO) in a large sample of eyes with or without age-related macular degeneration (AMD) and with cataracts or intraocular lenses (IOLs).MethodsPatients with various degrees of AMD and age-similar normal subjects underwent fundus photography. Cataract severity and IOL clarity were assessed by fundus reflex photographs. In phakic eyes, lenticular opacity was graded as nuclear, cortical, or posterior subcapsular cataract. In eyes with IOLs, lens clarity was assessed by posterior capsule opacification (PCO). Quality of AOSLO images of the macular photoreceptor mosaic was classified as good, adequate or inadequate by human graders in a subjective assessment of cone visibility.ResultsA total of 159 eyes in 80 subjects (41 males, 39 females, aged 72.5 ± 11.5 years, 16 normals) were examined. Seventy-nine eyes had IOLs, and 80 eyes were phakic. AOSLO produced good images in 91 eyes (57%), adequate images in eight eyes (5%), and inadequate images in 27 eyes (17%). AOSLO did not acquire images in 33 eyes (21%), because of dense lenticular opacity, widespread PCO, or problems specific to individual subjects.ConclusionsAOSLO images considered at least Adequate or better for visualizing cone photoreceptors were acquired from 62% of study eyes.Translational RelevanceAOSLO can be used as an additional imaging modality to investigate the structure of cone photoreceptors in research on visual function in AMD and in clinical trials involving older patients.

Levels of self-reported and objective physical activity in individuals with age-related macular degeneration

BackgroundSelf-report in people with age-related macular degeneration (AMD) shows that they lead less active lifestyles. Physical activity is important as it has been shown to improve quality of life, reduce co-morbidity and also slow down the progression of AMD. Self-reported measures of physical activity are prone to subjective biases and therefore less accurate in quantifying physical activity. This study compared self-reported and objective (accelerometer-based) physical activity levels and patterns in older adults with AMD.MethodsData were collected in 11 AMD subjects with binocular vision loss (aged 76 ± 7 years), 10 AMD subjects with good binocular vision (aged 76 ± 7 years), and 11 controls (aged 70 ± 4 years). Binocular vision was established using visual acuity score. Contrast sensitivity and visual fields were also measured. Self-reported sedentary behaviour and moderate-to-vigorous physical activity (MVPA) was assessed using the Global Physical Activity Questionnaire. Objective measurements were obtained with an Actigraph GT3X accelerometer being worn for seven consecutive days on the hip. The objective physical activity measures were sedentary behaviour, light physical activity, MVPA, and step count.ResultsObjectively measured MVPA was 33–34% higher for controls compared to both AMD groups (p < 0.05). There were no group differences for any of the other objectively measured physical activity variables and self-reported physical activity variables were also not significantly different (all p > 0.05). Comparing the objective with the self-report physical activity measure showed that all groups under-reported their sedentary behaviour and MVPA, but controls under-reported their MVPA more than both AMD groups (p < 0.05). Weak to moderate correlations were observed between the severity of vision loss and objective physical activity measures (all − 0.413 ≥ r ≤ 0.443), while correlations for self-reported physical activity measures were less strong (all − 0.303 ≥ r ≤ 0.114).ConclusionsPeople with AMD, irrespective of whether they were vision impaired, were better able to estimate the time spent in MVPA compared to controls. However, objectively measured MVPA, was higher in controls than AMD subjects. Although clinicians may use self-report to monitor the compliance of AMD subjects with any prescribed exercise programs, they should be aware that a valid comparison with healthy controls can only be made when MVPA is objectively measured.

Measurement of Enzymatic and Nonenzymatic Polyunsaturated Fatty Acid Oxidation Products in Plasma and Urine of Macular Degeneration Using LC-QTOF-MS/MS.

Oxidized polyunsaturated fatty acids (PUFA) are associated to pathogenesis of diseases including cardiovascular and neurodegeneration. The novel products are not only biomarkers but also lipid mediators in gene regulation and signaling pathways. Herein, simultaneous quantitation of 28 products derived from nonenzymatic and enzymatic oxidation of PUFA i.e. 5-, 15-F2t -isoprostanes, 7-, 17-F2t -dihomo-isoprostanes, 7-, 17-F2t -dihomo-isofurans, 5-, 8-, 18-F3t -isoprostanes, 4-, 10-, 13-, 14-, 20-F4t -neuroprostanes, 5-, 8-, 9-, 11-,12-, 15-, 20-HETE, 4-, 7-, 11-, 14-, 17-HDHA, RvE1, and NPD1 using LC-(ESI)-QTOF-MS/MS was developed. These products were measurable in a single sample and the analytical time was relative short (~15 min). Furthermore, we showed that the use of internal standards is a requisite to normalize matrix effects and preparation loss for the quantitation. Validation assays indicated the method to be robust for plasma and mid-stream urine sample analysis in particular from those of age-related macular degeneration subjects, where the accuracy of quantitation displayed good repeatability.

Classification of dry age‐related macular degeneration and diabetic macular oedema from optical coherence tomography images using dictionary learning

Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME) are the major causes of vision loss in developed countries. Alteration of retinal layer structure and appearance of exudates are the most significant signs of these diseases. In this paper, with the aim of automatic classification of DME, AMD, and normal subjects using Optical Coherence Tomography (OCT) images, a dictionary-learning based classification is proposed. The two important issues intended in this approach are avoiding retinal layer segmentation and attempting to mimic the authors' understanding based on normal and abnormal region identifications, considering that the signs of diseases appear in a small fraction of B-Scans. The histogram of oriented gradients feature descriptor was utilized to characterize the distribution of local intensity gradients and edge directions. To capture the structure of extracted features, different dictionary learning-based classifiers are employed. The dataset consists of 45 subjects: 15 patients with AMD, 15 patients with DME, and 15 normal subjects. The proposed classifier leads to an accuracy of 95.13, 100.00, and 100.00% for DME, AMD, and normal OCT images, respectively, only by considering 4% of all B-Scans of a volume, which outperforms the state-of-the-art methods.