Eleftherios Anastasopoulos - Academia.edu (original) (raw)

Papers by Eleftherios Anastasopoulos

Investigative Ophthalmology & Visual Science, 2003

US Ophthalmic Review, 2007

Glaucoma-The Importance of Early Detection and Early Treatment An Increasing Global Concern Glauc... more Glaucoma-The Importance of Early Detection and Early Treatment An Increasing Global Concern Glaucoma is a major global health problem, and all types of the disease combined are the second leading cause of blindness worldwide, with approximately 6.7 million people being blinded as a result of the disease. 1 With the predicted increase in life expectancy, the anticipated number of people becoming blind from the disease will rise substantially in the near future. Despite increasing public health awareness and the availability of advancedtechnology diagnostic tests in developed countries, a high proportion of glaucoma cases remain undiagnosed in the community. Improved strategies for achieving earlier and more accurate diagnosis of glaucoma will facilitate the prompt implementation of effective treatment options, and subsequently will minimize the anticipated rising burden of the disease in the near future. The Problem of Early Detection of Glaucoma Various population-based epidemiological studies have reported that more than 50% of glaucoma cases remain undiagnosed, even in developed countries. 2-5 High prevalence estimates of undiagnosed glaucoma are consistent with the lack of cost-effective screening methods for glaucoma. Despite being a major risk factor for glaucoma, elevated intraocular pressure (IOP) lacks sensitivity and specificity in glaucoma diagnosis since it is not present in a high proportion of affected patients at the time of diagnosis, while many people without glaucoma present with elevated IOP. Also, possible reasons for the high prevalence of undiagnosed glaucoma include the fact that glaucoma is a silent, asymptomatic disease. Visual function may not deteriorate significantly until advanced stages of the disease. However, even in the advanced stages of the disease glaucoma can remain undiagnosed due to lack of regular visits to an ophthalmologist or lack of thoroughness at the eye examination. In a

Integrative Ophthalmology, 2019

Helicobacter pylori (HP) is a microaerophilic gram-negative helicobacter that parasitizes between... more Helicobacter pylori (HP) is a microaerophilic gram-negative helicobacter that parasitizes between the surface of gastric mucosa and the mucus layer and contains several virulence factors. Glaucoma is a characteristic group of optic neuropathies with elevated intraocular pressure as the main risk factor. It is in essence the apoptosis of retinal ganglion cells. HP and glaucoma belong to two different systems. In the past, eye doctors regarded the gastrointestinal diseases, as far as they are concerned, as a stress reaction that only occurs during the period of rapid IOP elevation in glaucoma. And physicians usually regard the acute angle-closure glaucoma as a candidate condition for differential diagnosis for the symptom of internal medical acute pain. However, if we try to understand the two conditions from the perspective of holistic integrative medicine, we will find that HP is a microaerobe whose antigenicity and invasiveness will lead to complex pathological immune responses in multiple sites, while the apoptosis of retinal ganglion cells in glaucoma, on the other hand, requires the participation of autoimmune system. Taking into consideration also the latest research progress in subspecialties, we can find that there are similarities between the two seemingly unrelated diseases on different levels: (1) correlation between them in the pathogenesis on the molecular, cellular and biological level; (2) correlation between them in ecology on the level of epidemiology studies; (3) correlation between them in immunology in case–control trials; (4) correlation between eradication of HP and the glaucomatous damage to vision in clinical trials; and (5) they are both psychosomatic diseases. Though it is still unclear whether the correlation is concomitant or causal due to limited current understanding of them, their mysterious correlation is going to be revealed in the near future with the development and integration of various subspecialties.

Investigative Ophthalmology & Visual Science, 2009

Investigative Ophthalmology & Visual Science, 2006

Investigative Ophthalmology & Visual Science, 2016

Ophthalmic Genetics, 2018

Background: Pseudoexfoliation syndrome (PEX) and glaucoma (pseudoexfoliative glaucoma; PEXG, prim... more Background: Pseudoexfoliation syndrome (PEX) and glaucoma (pseudoexfoliative glaucoma; PEXG, primary open-angle glaucoma; POAG) have mainly been studied for their associations with genes' polymorphisms. The purpose of this exploratory study was to investigate the role of polymorphisms in genes encoding for micro RNAs (miRNAs) and in genes related to miRNA biogenesis. Material and Methods: In the present genetic association study, ninety-two polymorphisms were investigated for their contribution to PEX (n = 203), PEXG (n = 38), and POAG (n = 40) pathogenesis compared to a control group (n = 188). The next generation sequencing (NGS) genotypic analysis revealed data for additional 28 variants. Results: A protective association was found between PEX and polymorphism 11382316 (mir-3161) [odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.47-0.86, p = 0.003], rs2155248 (mir-1304) [OR = 0.66, 95%CI: 0.47-0.94, p = 0.019], and rs28635903 (mir-1268a) [OR = 0.30, 95%CI: 0.10-0.94, p = 0.029]. Polymorphism rs113297757 (mir-3196) was associated with an increased risk of POAG [OR = 7.75, 95%CI: 2.13-28.76, p = 3 × 10 −4 ]. Polymorphism rs1057035 (DICER) and rs55671916 (XPO5) in the 3ʹ-UTR of genes related to miRNA biogenesis was associated with decreased risk of PEX [OR = 0.65, 95%CI: 0.46-0.92, p = 0.014] and increased risk of PEXG [OR = 2.84, 95%CI: 1.02-7.94, p = 0.038], respectively. The aforementioned associations according to the allelic model were further supported by the genotypic models of statistical analyses. Conclusions: This is the first study to report distinct associations of PEX, PEXG, and POAG in the same population with variants of genes involved in miRNA biogenesis and with miRNA genes' polymorphisms. Further studies in larger groups of patients of various origins are needed to confirm the reported preliminary results.

Vision, 2022

Purpose: The present study evaluates the differences in the prevalence of the signs and symptoms ... more Purpose: The present study evaluates the differences in the prevalence of the signs and symptoms of ocular surface disease (OSD) in patients with PEX glaucoma (PEXG), compared to other glaucoma types (non-PEXG). Methods: Patients with non-PEXG and PEXG were prospectively examined for the presence and severity of OSD signs and questioned for symptoms using the OSDI (ocular surface disease index) questionnaire. Results: 116 patients were prospectively enrolled (58 non-PEXG and 58 PEXG). PEXG subjects who were older, had lower central corneal thickness (CCT) values, at a more advanced glaucoma stage and required more IOP lowering drops. OSD signs were prevalent in both groups: conjunctival hyperemia (74.5% non-PEXG vs. 94.8% PEXG), eyelid redness (70.7% vs. 96.6%), conjunctival (74.1% vs. 93.1%) and corneal fluorescein staining (81% vs. 93.1%) and abnormal TFBUT (82.8% vs. 87.9%). When adjusted for potential confounders, (older age, thinner CCT, more advanced glaucoma in PEXG) eyelid r...

Journal of Glaucoma

PRECIS In the Thessaloniki Eye Study incidence phase population, frequent dietary salt intake was... more PRECIS In the Thessaloniki Eye Study incidence phase population, frequent dietary salt intake was potentially associated with increased risk of open-angle glaucoma in antihypertensive users. PURPOSE To examine the association between dietary salt intake and glaucoma by antihypertensive use in the Thessaloniki Eye Study (TES) population. METHODS The study population included TES incidence phase participants. Dietary salt intake frequency was assessed by self-report. Outcomes included prevalence of any open angle glaucoma (OAG), primary open angle glaucoma (POAG), and pseudoexfoliation (PEX). Covariates included demographics, cardiovascular disease, migraines, diabetes, steroid use, smoking, history of cataract surgery, central corneal thickness, intraocular pressure, blood pressure, and antihypertensive use. Logistic regression was used to examine associations between frequency of salt intake and glaucoma, controlling for covariates and stratified by antihypertensive use. RESULTS The study included 1076 participants 80.5±4.4 years old, of whom 518 were female. There were 89/1076 (8.3%) participants with any OAG, 46/789 (5.8%) with POAG, and 287/1030 (27.9%) with PEX. In participants with antihypertensive use, frequent versus never salt intake was associated with increased risk of any OAG (adjusted odds ratio [aOR]=2.65, 95% confidence interval [CI]=1.12, 6.28; n=784) and POAG (aOR=3.59, 95% CI=1.16, 11.11; n=578) overall, and additionally in participants with diastolic blood pressure <90▒mmHg (aOR=2.42, 95% CI=1.00, 5.84; n=735) for OAG. There were no statistically significant adjusted associations between salt intake and PEX, or in participants without antihypertensive use. CONCLUSIONS In TES participants assessed for OAG in the prevalence and incidence phases, frequent salt intake may be associated with increased OAG in those who take antihypertensive medication. Further investigation is needed of salt intake and glaucoma in hypertensive individuals.

$Research paper thumbnail of OPHTHALMIC EPIDEMIOLOGY Prevalence of refractive error in Europe: the European Eye Epidemiology (E3) Consortium$

The Author(s) 2015. This article is published with open access at Springerlink.com Abstract To es... more The Author(s) 2015. This article is published with open access at Springerlink.com Abstract To estimate the prevalence of refractive error in adults across Europe. Refractive data (mean spherical equivalent) collected between 1990 and 2013 from fifteen population-based cohort and cross-sectional studies of the European Eye Epidemiology (E3) Consortium were com-bined in a random effects meta-analysis stratified by 5-year age intervals and gender. Participants were excluded if they were identified as having had cataract surgery, retinal detachment, refractive surgery or other factors that might influence refraction. Estimates of refractive error preva-lence were obtained including the following classifications: myopia B-0.75 diopters (D), high myopia B-6D, hy-peropia C1D and astigmatism C1D. Meta-analysis of re-fractive error was performed for 61,946 individuals from

Investigative Ophthalmology & Visual Science, 2007

Investigative Ophthalmology & Visual Science, 2014

Investigative Ophthalmology & Visual Science, 2002

Investigative Ophthalmology & Visual Science, 2008

JAMA, 2021

The Genetics of Exfoliation Syndrome Partnership IMPORTANCE Exfoliation syndrome is a systemic di... more The Genetics of Exfoliation Syndrome Partnership IMPORTANCE Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. OBJECTIVE To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. DESIGN, SETTING, AND PARTICIPANTS A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. EXPOSURES Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. MAIN OUTCOMES AND MEASURES The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10 −6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. RESULTS The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10 −7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. CONCLUSIONS AND RELEVANCE In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

British Journal of Ophthalmology, 2017

AimsTo provide population-based data on the maximum tolerable rate of progression to avoid visual... more AimsTo provide population-based data on the maximum tolerable rate of progression to avoid visual impairment (maxTRoP_VI) and blindness (maxTRoP_BL) from open-angle glaucoma (OAG).MethodsParticipants with OAG in the Thessaloniki Eye Study (cross-sectional, population-based study in a European population) were included in the analysis. Visual impairment was defined as mean deviation (MD) equal to or worse than −12dB and blindness as MD equal to or worse than −24dB. Additional thresholds for visual impairment were tested. For each participant maxTRoP_VI was defined as the rate of progression which would not lead to visual impairment during expected lifetime. MaxTRoP_BL was defined accordingly. Both parameters were calculated for each OAG subject using age, sex, MD and life expectancy data. The eye with the better MD per subject was included in the analysis.ResultsAmong 135 subjects with OAG, 123 had reliable visual fields and were included in the analysis. The mean age was 73±6 years ...

Nature genetics, Jan 23, 2015

Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide... more Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: ORA allele = 9.87, P = 2.13 × 10(-217); non-Japanese: ORA allele = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.

Current Eye Research, 2012

To explore the association of two single nucleotide polymorphisms (SNPs) in the CX3CR1 gene with ... more To explore the association of two single nucleotide polymorphisms (SNPs) in the CX3CR1 gene with grades of age-related macular degeneration (AMD) in a population-based setting. The Thessaloniki Eye study is a cross-sectional population-based epidemiologic study of chronic eye diseases in Thessaloniki, Greece. A total of 371 subjects were included and classified according to their AMD status. Subjects with AMD Grades 0-1 (n = 188) were compared to those with AMD Grades 2-3 (n = 138), to those with AMD Grade 4 (geographic atrophy) (n = 20) and to those with AMD Grade 5 (neovascular AMD) (n = 25) with regard to the presence of CX3CR1 polymorphisms (V249I and T280M). Polychotomous logistic regression analysis adjusted for age, gender, and smoking was conducted and the log-additive allelic model was preferred. Participants with AMD Grade 4 were approximately three times more likely to carry the VI249 and nine times more likely to carry the II249 alleles, compared to those with AMD Grades 0-1, whereas those with AMD Grades 2-3 or Grade 5 did not differ. The T280M polymorphism was not associated with either AMD Grades 2-3 or AMD Grades 4 or 5. In this Greek population, after adjusting for known risk factors, increased risk of geographic atrophy (GA) AMD among the carriers of the V249I polymorphism in the CX3CR1 gene was found. Our study failed to reveal any association with the T280M polymorphism reported in previous studies. Additional studies in different ethnic populations using standardized methodology are needed in order to confirm this association.

American Journal of Ophthalmology, 2008

Acta Ophthalmologica, 2011

To assess the agreement among three masked examiners on central retinal artery (CRA) and ophthalm... more To assess the agreement among three masked examiners on central retinal artery (CRA) and ophthalmic artery (OA) blood flow velocity measurements performed with colour Doppler imaging (CDI) in healthy volunteers. The study included 30 eyes of 15 healthy volunteers. Prior to the study, all examiners underwent intensive CDI training by an expert to facilitate uniformity in performing measurements according to a specific protocol. Following the eligibility visit, three masked examiners performed CDI measurements assessing the CRA and OA in both eyes of all subjects. All CDI images were analysed by a masked grader. Intraclass correlation coefficients (ICC) were calculated for peak systolic velocity (PSV) and end diastolic velocity (EDV) in the CRA and OA among the examiners. p-values &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05 were considered statistically significant. The study included seven men and eight women (mean age 30.9 ± 4.5 years). In right eyes, ICCs for PSV and EDV in the CRA ranged from 0.917 to 0.961 and from 0.937 to 0.980, respectively. ICCs for PSV and EDV in the OA ranged from 0.802 to 0.926 and from 0.611 to 0.891, respectively. In left eyes, all ICCs for PSV and EDV were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.9, both in the CRA and the OA. All p-values calculated for ICCs were statistically significant. Expert training and execution of a specific protocol for CDI of ocular blood flow velocity measurements provide highly reproducible results in healthy volunteers. This is important for long-term studies assessing ocular hemodynamics, where multiple examiners may be involved.