Assessment of Neutrophil-Lymphocyte Ratios in Patients with Dry Age-related Macular Degeneration

Abstract Purpose: To assess the significance of neutrophil-lymphocyte ratio (NLR) as an inflammatory indicator in patients with dry age-related macular degeneration (AMD). Study design: A retrospective case-control study.Methods: Clinical diagnosis along with complete blood count (CBC) results were extracted from hospital and laboratory information systems for patients with dry-AMD and age/gender-matched controls attending the ophthalmology clinic at King Abdulaziz medical city, Jeddah, Saudi Arabia, between 2018-2020. NLR was calculated by dividing the neutrophil by the lymphocyte count. Results: This study captured 90 patients diagnosed with dry-AMD and 270 control subjects without AMD. The mean of ages 70 and 71 years old for cases and controls, respectively. In univariate analysis, there were no significant differences in CBC results between cases and control. In NLR, dry-AMD patients have a slightly higher mean than the control group; however, this increase was not statistically significant (P-value 0.8). In the NLR model, age and gender were statistically significant factors affecting the NLR values in dry-AMD (P-value 0.03, 0.01 respectively). Conclusion: as a systemic inflammatory biomarker, NLR alone could not predict dry-AMD. However, the slight increase in the NLR values may be helpful if augmented with other laboratory measurements to aid in early disease prediction.

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THE HOMING TRIAL: A RETROSPECTIVE PILOT STUDY ON THE EFFICACY OF PERSONALIZED BIOIDENTICAL HORMONE, DIETARY SUPPLEMENT AND NUTRITION CARE PLANS FOR AGE-RELATED MACULAR DEGENERATION (AMD)

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v5i4.1886 ◽

2021 ◽

Vol 5 (4) ◽

Author(s):

George W. Rozakis ◽

Brian A. Bakke

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Visual Acuity ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Control Group ◽

Care Plans ◽

Age Related ◽

Dry Amd ◽

Wet Amd

The objective of the Hormones, Oxidative stress, Methylation, Inflammation and Gene expression (HOMING) trial was to assess the efficacy of personalized bio identical hormone, dietary supplement and nutritional care plans on dry and wet Age-related Macular Degeneration (AMD) outcomes. We evaluated 220 Age-related Macular Degeneration (AMD) patients that followed a personalized clinical care plan for up to 9 months. The care plans consisted of bio identical hormones, dietary supplements and nutrition recommendations with the objective to improve lab and clinical measurements linked to oxidative stress, inflammation and gene expression. Serum concentrations of CRP, HbA1c and homocysteine responded favorably to the HOMING protocol with full program compliance. Sixty percent (42/70) of wet AMD patients reported improvement in visual acuity and/or a reduction in the frequency of anti-VEGF injections during the study period. Forty eight percent (44/92) of dry AMD patients reported improvement in visual acuity during the study period. Nine percent (4/45) patients reported improvement in visual acuity in the dry AMD control group and no (0/13) wet AMD patients in the control group reported improvement. Six percent (4/70) of wet AMD patients reported that their vision declined and/or that their F frequency increased during the study period. Five percent (4/92) of dry AMD patients reported that their vision was worse. Keywords: Bio identical Hormones, Oxidative stress, Methylation, Inflammation, Gene Expression, Nutrition and AMD.

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Comparison of Serum Biochemical and Haematological Analyses in Patients with Age-Related Macular Degeneration and Diabetic Retinopathy

Journal of Molecular Biology Research ◽

10.5539/jmbr.v9n1p41 ◽

2019 ◽

Vol 9 (1) ◽

pp. 41

Author(s):

Muberra Akdogan ◽

Yasemin Ustundag ◽

M. Cem Sabaner ◽

Mustafa Dogan

Keyword(s):

Diabetic Retinopathy ◽

Macular Degeneration ◽

Complete Blood Count ◽

Fasting Glucose ◽

Serum Levels ◽

Age Related Macular Degeneration ◽

Retrospective Case ◽

Urine Albumin ◽

Age Related ◽

Serum Biochemical

We evaluated biochemical analysis results with the aim of discovering serum levels that have possible effects and differences on age-related macular degeneration (AMD) and diabetic retinopathy (DRP). A retrospective case-control study was conducted between January 2017 and January 2018 on a total of 114 patients (84 DRP, 30 AMD) and 24 age and sex-matched control individuals. Four groups were created; 52 patients with proliferative DRP (PDR), 32 patients with nonproliferative PDR (non-PDR), 30 patients with wet AMD and 24 control individuals. Serum biochemical (HbA1C, fasting glucose, AST, ALT, C-reactive protein, albumin, total protein, uric acid, triglyceride, HDL, LDL, total cholesterol, Na, K, urine albumin) and complete blood count (CBC) analyses were performed at the time of diagnosis. Descriptive statistics, one-way ANOVA and Kruskal-Wallis tests were performed using SPSS to analyse data (Version 22.0). The mean age of patients was 63.3 years ± 6.4 (49-91year), and that of control individuals was 65.3 years ± 9.3 (50-88 year). Post hoc analysis showed statistically significant differences in HbA1c and fasting glucose levels among PDR-AMD, PDR-control, non-PDR-AMD, and non-PDR-control groups (whole, P

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Photoreceptor alteration in intermediate age-related macular degeneration

Scientific Reports ◽

10.1038/s41598-020-78201-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Enrico Borrelli ◽

Riccardo Sacconi ◽

Biancamaria Zuccaro ◽

Michele Cavalleri ◽

Alessandro Bordato ◽

...

Keyword(s):

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Control Group ◽

Early Event ◽

Retrospective Case ◽

Swept Source ◽

Flow Signal ◽

Signal Density ◽

Age Related ◽

Free Region

AbstractThe aim of this study was to analyze photoreceptor alterations occurring in eyes with intermediate age-related macular degeneration (AMD) and to investigate their associations with choriocapillaris (CC) flow. In this retrospective case–control study, we collected data from 35 eyes with intermediate AMD from 35 patients who had swept source optical coherence tomography structural and angiography imaging obtained. A control group of 35 eyes from 35 healthy subjects was included for comparison. Our main outcome measure for comparison between groups was the normalized reflectivity of en face image segmented at the ellipsoid zone (EZ) level, which was calculated to quantify the photoreceptor damage. OCTA metrics to quantify CC flow signal were also computed. These metrics were measured in a circle centered on the fovea and with a diameter of 5 mm. In intermediate AMD eyes, the macular area occupied by drusen was identified. Therefore, the EZ reflectivity and CC flow signal were separately measured in regions without drusen (“drusen-free” region). Measurements were generated using previously published algorithms. Mean ± SD age was 74.1 ± 6.8 years in the intermediate AMD group and 72.1 ± 6.0 years in the control group (p = 0.206). The normalized EZ reflectivity was 0.76 ± 0.10 in the intermediate AMD group and 0.85 ± 0.08 in the control group (p < .0001). In the “drusen-free” region, the normalized EZ reflectivity was 0.77 ± 0.10 (p < .0001 vs. healthy controls) and was positively correlated with the CC flow signal density (ρ = − 0.340 and p = 0.020). In conclusion, eyes with intermediate AMD exhibit a diffuse reduced EZ normalized reflectivity, and this reduction is correlated with CC flow signal in the regions without drusen. This study supports the concept of the damage of the unit comprised of photoreceptor, CC, and intervening tissues as an early event in AMD.

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A study on plasma homocysteine level in age-related macular degeneration

Nepalese Journal of Ophthalmology ◽

10.3126/nepjoph.v5i2.8728 ◽

2013 ◽

Vol 5 (2) ◽

pp. 195-200 ◽

Cited By ~ 12

Author(s):

Sourav Ghosh ◽

M Saha ◽

D Das

Keyword(s):

Macular Degeneration ◽

Homocysteine Level ◽

Plasma Homocysteine ◽

Age Related Macular Degeneration ◽

Control Group ◽

Plasma Homocysteine Level ◽

Blood Samples ◽

Age Related ◽

Dry Amd ◽

Wet Amd

Introduction: Age-related macular degeneration (AMD) related to adverse vascular changes is the most frequent cause of irreversible visual impairment in the elderly. Elevated plasma concentrations of serum homocysteine have been shown to increase the risk of vascular disease. Objective: To assess the relationship between plasma homocysteine level and age related macular degeneration. Materials and methods: A case control study was conducted in a tertiary eye care hospital with 32 diagnosed AMD patients. The patients were compared for plasma homocysteine levels with a control group of 32 patients without AMD. A 1.5 ml of fasting venous blood sample was obtained from each participant. Plasma homocysteine level was measured by high performance liquid chromatography. The main outcome measure was hyperhomocysteinemia, defined as a plasma homocysteine level above 15 μmol/l. Results: Hyperhomocysteinemia was found in 10 blood samples (83.3 %) of patients in the wet AMD group, in 16 (80 %) blood samples in the dry AMD group, and in 12 blood samples (37%) of controls. The mean ± SD homocysteine level in the AMD group was 16.86 ± 3.52 μmol/L, while in the non-AMD control group it was 14.53 ± 4.08 μmol/L. This difference was statistically significant (p-value = 0.0186). In the individual analysis, it was also found out that the homocysteine level differed significantly between cases and controls in only the wet variety of AMD. Conclusion: Hyperhomocysteinemia was significantly associated with the wet AMD variety but not with the dry AMD. Thus, homocysteine by oxidative stress and vascular dysfunction can be an important risk factor in the pathogenesis of AMD. Nepal J Ophthalmol 2013; 5(10): 195-200 DOI: http://dx.doi.org/10.3126/nepjoph.v5i2.8728

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Outer retinal tubulation formation and clinical course of advanced age-related macular degeneration

Scientific Reports ◽

10.1038/s41598-021-94310-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alessandro Arrigo ◽

Emanuela Aragona ◽

Ottavia Battaglia ◽

Andrea Saladino ◽

Alessia Amato ◽

...

Keyword(s):

Macular Degeneration ◽

Müller Cells ◽

Geographic Atrophy ◽

Age Related Macular Degeneration ◽

Advanced Age ◽

Age Related ◽

Dry Amd ◽

Foveal Sparing ◽

Wet Amd

AbstractOuter retinal tubulations (ORT) are a relatively new finding characterizing outer retinal atrophy. The main aim of the present study was to describe ORT development in advanced age-related macular degeneration (AMD) and to assess its relationship with disease’s severity. Patients with advanced AMD characterized either by macular neovascularization or geographic atrophy, showing signs of outer retinal disruption or retinal pigment epithelium atrophy on structural optical coherence tomography (OCT) at the inclusion examination were prospectively recruited. All the patients underwent complete ophthalmologic evaluation, structural OCT scans and fundus autofluorescence imaging. The planned follow-up was of 3-years. Main outcome measures were ORT prevalence, mechanism of ORT formation, mean time needed for complete ORT formation, best-corrected visual acuity (BCVA), definitely decreased autofluorescence (DDAF) area, questionably decreased autofluorescence (QDAF) area, retinal layer thickness, foveal sparing, number of intravitreal injections. We also assessed the possible role of external limiting membrane (ELM) and Müller cells in ORT pathogenesis. Seventy eyes (70 patients) were included; 43 showed dry AMD evolving to geographic atrophy, while 27 displayed the features of wet AMD. Baseline BCVA was 0.5 ± 0.5 LogMAR, decreasing to 0.9 ± 0.5 LogMAR at the 3-year follow-up (p < 0.01). We detected completely formed ORT in 26/70 eyes (37%), subdivided as follows: 20 eyes (77%) wet AMD and 6 eyes (23%) dry AMD (p < 0.01). ORT took 18 ± 8 months (range 3–35 months) to develop fully. We described the steps leading to ORT development, characterized by progressive involvement of, and damage to the photoreceptors, the ELM and the RPE. Eyes displaying ORT were associated with a smaller QDAF area, less retinal layers damage and lower rate of foveal sparing than eyes free of ORT (p < 0.01). We also described pigment accumulations simulating ORT, which were detected in 16/70 eyes (23%), associated with a greater loss of foveal sparing, increased DDAF area and smaller QDAF area at the 3-year follow-up (p < 0.01). In conclusion, this study provided a description of the steps leading to ORT development in AMD. ELM and Müller cells showed a role in ORT pathogenesis. Furthermore, we described a subtype of pigment hypertrophy mimicking ORT, evaluating its clinical utility.

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Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Biology ◽

10.3390/biology10070622 ◽

2021 ◽

Vol 10 (7) ◽

pp. 622

Author(s):

Iswariyaraja Sridevi Gurubaran ◽

Hanna Heloterä ◽

Stephen Marry ◽

Ali Koskela ◽

Juha M. T. Hyttinen ◽

...

Keyword(s):

Oxidative Stress ◽

Mouse Model ◽

Macular Degeneration ◽

Complement Component ◽

Factor H ◽

Age Related Macular Degeneration ◽

Related Factor ◽

Complement Factor ◽

Age Related ◽

Dry Amd

Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.

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A Review of the Role of the Intestinal Microbiota in Age-Related Macular Degeneration

Journal of Clinical Medicine ◽

10.3390/jcm10102072 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2072

Author(s):

Phoebe Lin ◽

Scott M. McClintic ◽

Urooba Nadeem ◽

Dimitra Skondra

Keyword(s):

Macular Degeneration ◽

Intestinal Microbiota ◽

Retinal Disease ◽

Age Related Macular Degeneration ◽

Intestinal Microbiome ◽

Age Related ◽

Intestinal Dysbiosis ◽

Apo E ◽

Dry Amd

Blindness from age-related macular degeneration (AMD) is an escalating problem, yet AMD pathogenesis is incompletely understood and treatments are limited. The intestinal microbiota is highly influential in ocular and extraocular diseases with inflammatory components, such as AMD. This article reviews data supporting the role of the intestinal microbiota in AMD pathogenesis. Multiple groups have found an intestinal dysbiosis in advanced AMD. There is growing evidence that environmental factors associated with AMD progression potentially work through the intestinal microbiota. A high-fat diet in apo-E-/- mice exacerbated wet and dry AMD features, presumably through changes in the intestinal microbiome, though other independent mechanisms related to lipid metabolism are also likely at play. AREDS supplementation reversed some adverse intestinal microbial changes in AMD patients. Part of the mechanism of intestinal microbial effects on retinal disease progression is via microbiota-induced microglial activation. The microbiota are at the intersection of genetics and AMD. Higher genetic risk was associated with lower intestinal bacterial diversity in AMD. Microbiota-induced metabolite production and gene expression occur in pathways important in AMD pathogenesis. These studies suggest a crucial link between the intestinal microbiota and AMD pathogenesis, thus providing a novel potential therapeutic target. Thus, the need for large longitudinal studies in patients and germ-free or gnotobiotic animal models has never been more pressing.

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Introduction to the multi-author review on macular degeneration

Cellular and Molecular Life Sciences ◽

10.1007/s00018-019-03418-5 ◽

2020 ◽

Vol 77 (5) ◽

pp. 779-780 ◽

Cited By ~ 1

Author(s):

Anu Kauppinen

Keyword(s):

Macular Degeneration ◽

Vision Loss ◽

The Elderly ◽

Developed Countries ◽

Age Related Macular Degeneration ◽

Age Related ◽

Severe Vision Loss ◽

Author Review ◽

Dry Amd ◽

Endothelial Growth Factor

AbstractProlonged life expectancies contribute to the increasing prevalence of age-related macular degeneration (AMD) that is already the leading cause of severe vision loss among the elderly in developed countries. In dry AMD, the disease culminates into vast retinal atrophy, whereas the wet form is characterized by retinal edema and sudden vision loss due to neovascularization originating from the choroid beneath the Bruch’s membrane. There is no treatment for dry AMD and despite intravitreal injections of anti-vascular endothelial growth factor (VEGF) that suppress the neovessel formation, also wet AMD needs new therapies to prevent the disease progression and to serve patients lacking of positive response to current medicines. Knowledge on disease mechanisms is a prerequisite for the drug development, which is hindered by the multifactorial nature of AMD. Numerous distinguished publications have revealed AMD mechanisms at the cellular and molecular level and in this multi-author review, we take a bit broader look at the topic with some novel aspects.

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Epidemiology Prevalence and Incidence in Dry-Form (Non-Neovascular) Age-Related Macular Degeneration

Güncel Retina Dergisi (Current Retina Journal) ◽

10.37783/crj-0016 ◽

2017 ◽

pp. 97-99

Keyword(s):

Macular Degeneration ◽

Elderly Population ◽

The Elderly ◽

Epidemiologic Studies ◽

Age Related Macular Degeneration ◽

Neovascular Amd ◽

Age Related ◽

Dry Amd ◽

Degenerative Disorder ◽

Definition Of

Age-related macular degeneration (AMD) is a degenerative disorder of the central retina and represents the leading cause of severe visual impairment in the elderly population of industrialized societies. It is known that it currently exists between 30 and 50 million people around the world and is estimated that will have doubled by the end of the coming decade. Several large epidemiologic studies have evaluated the prevalence of non-neovascular or so-called dry AMD. There is some variation in the prevalence of non-neovascular AMD depending on the exact definition of AMD. All of them report a higher prevalence of early AMD and an increasing prevalence with age. It is seen most in Caucasians and least in people with Africans and it is not related to gender.

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Therapeutic Effect of Garcinia cambogia Extract and Hydroxycitric Acid Inhibiting Hypoxia-Inducible Factor in a Murine Model of Age-Related Macular Degeneration

International Journal of Molecular Sciences ◽

10.3390/ijms20205049 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5049 ◽

Cited By ~ 4

Author(s):

Ibuki ◽

Shoda ◽

Miwa ◽

Ishida ◽

Tsubota ◽

...

Keyword(s):

Macular Degeneration ◽

Hypoxia Inducible Factor ◽

Age Related Macular Degeneration ◽

Luciferase Assay ◽

Inhibitory Effects ◽

Garcinia Cambogia ◽

Food Ingredients ◽

Age Related ◽

Dry Amd ◽

Wet Amd

Background: Age-related macular degeneration (AMD) is the leading cause of blindness and can be classified into two types called atrophic AMD (dry AMD) and neovascular AMD (wet AMD). Dry AMD is characterized by cellular degeneration of the retinal pigment epithelium, choriocapillaris, and photoreceptors. Wet AMD is characterized by the invasion of abnormal vessels from the choroid. Although anti-vascular endothelial growth factor (VEGF) therapy has a potent therapeutic effect against the disease, there is a possibility of chorio-retinal atrophy and adverse systemic events due to long-term robust VEGF antagonism. We focused on hypoxia-inducible factor (HIF) regulation of VEGF transcription, and report the suppressive effects of HIF inhibition against ocular phenotypes in animal models. Many of the known HIF inhibitors are categorized as anti-cancer drugs, and their systemic side effects are cause for concern in clinical use. In this study, we explored food ingredients that have HIF inhibitory effects and verified their effects in an animal model of AMD. Methods: Food ingredients were screened using a luciferase assay. C57BL6/J mice were administered the Garcinia cambogia extract (Garcinia extract) and hydroxycitric acid (HCA). Choroidal neovascularization (CNV) was induced by laser irradiation. Results: Garcinia extract and HCA showed inhibitory effects on HIF in the luciferase assay. The laser CNV model mice showed significant reduction of CNV volume by administering Garcinia extract and HCA. Conclusions: Garcinia extract and HCA showed therapeutic effects in a murine AMD model.

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