Eleftherios Anastasopoulos

Increasing Prevalence of Myopia in Europe and the Impact of Education

Purpose To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. Design Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E3) Consortium. Participants The E3 Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. Methods Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤−0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. Main Outcome Measures Variation in age-specific myopia prevalence for differing years of birth and educational level. Results There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6–18.1) to 23.5% (95% CI, 23.2–23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0–25.8), 29.1% (CI, 28.8–29.5), and 36.6% (CI, 36.1–37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio–2.43 (CI, 1.26–4.17) and 2.62 (CI, 1.31–5.00), respectively—whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21–6.57). Conclusions Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia.

Risk Factors for Primary Open-Angle Glaucoma and Pseudoexfoliative Glaucoma in the Thessaloniki Eye Study

PURPOSE To investigate risk factors for primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG) in the Thessaloniki Eye Study. DESIGN Cross-sectional, population-based study. METHODS Randomly selected subjects 60 years of age and older (n=2554) participated in the Thessaloniki Eye Study. Glaucomatous damage and presence of pseudoexfoliation (PEX) were defined according to specific criteria. Open-angle glaucoma (OAG) subjects were compared with nonglaucoma subjects (controls), POAG subjects were compared with controls without PEX, and PEXG subjects were compared with controls with PEX for demographic, lifestyle, ophthalmic, and systemic factors. Factors with P < .2 in the univariate analysis were retained for multivariate analyses. RESULTS In multivariate analysis restricted to persons who participated in clinic visits and who had at least 1 phakic eye (n=2078), intraocular pressure (odds ratio [OR], 1.21 per 1 mm Hg; P<.001), PEX (OR, 2.81; P<.001), history of coronary artery bypass or vascular surgery (OR, 1.95; P=.017), and moderate-to-high myopia (≥ -3 diopters; OR, 2.40; P=.009) were associated with higher odds for OAG. In analysis including all clinic visits (n=2261), age became significantly associated (OR, 1.05; P=.004). In multivariate analysis for POAG (n=1840), associations were found for age (OR, 1.04 per year; P=.048), IOP (OR, 1.19 per 1 mm Hg; P<.001), history of coronary artery bypass or vascular surgery (OR, 2.09; P=.01), and history of diabetes treated with insulin (OR, 3.05; P=.045). In multivariate analysis for PEXG (n=238), the latter was associated with increased IOP (OR, 1.25 per 1 mm Hg; P<.001). CONCLUSIONS IOP was the only factor associated with both POAG and PEXG, whereas moderate-to-high myopia showed borderline significance in both. Vascular systemic diseases and their treatment were associated only with POAG. The implications of these differences for the pathogenesis between the 2 common types of OAG should be explored further.

Increased likelihood of glaucoma at the same screening intraocular pressure in subjects with pseudoexfoliation: the Thessaloniki Eye Study.

PURPOSE To compare the clinical characteristics of primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG) identified in the Thessaloniki Eye Study and to evaluate the proportion of subjects with and without pseudoexfoliation (PEX) who have glaucoma by screening intraocular pressure (IOP). DESIGN Cross-sectional, population-based study. METHODS Randomly selected subjects > or =60 years (n = 2,554) participated in the Thessaloniki Eye Study. Subjects were classified as having POAG or PEXG according to specific criteria. POAG and PEXG cases were compared for various clinical characteristics. The proportion with glaucoma among subjects with PEX and the proportion with glaucoma among subjects without PEX were estimated by IOP levels. RESULTS Among the clinic-visit participants (n = 2,261), 94 subjects (4.2%) had POAG and 41 (1.8%) had PEXG. The prevalence of glaucoma among subjects with PEX was 15.2% and the prevalence of glaucoma among subjects without PEX was 4.7%. In subjects without treatment, the mean IOPs were 19.8 mm Hg and 24.3 mm Hg for POAG and PEXG, respectively. For IOP level >20 mm Hg, the proportion with glaucoma among subjects with PEX was higher than that for glaucoma among subjects without PEX (37% vs 15%; P = .004), while no statistically significant difference was found for IOP level < or =20 mm Hg (2.1% vs 2.1%; P = .999), Fisher exact test. CONCLUSIONS In the Thessaloniki Eye Study, for screening IOP </=20 mm Hg the proportion with glaucoma was similar in subjects with and without PEX. For IOP level >20 mm Hg, the proportion with glaucoma increased highly in subjects both with and without PEX, while it was much higher among those with PEX at the same screening IOP.

Characteristics of pseudoexfoliation in the Thessaloniki Eye Study.

PurposeTo report on the prevalence of pseudoexfoliation (PEX) and its association with ophthalmic characteristics and systemic diseases in a well-defined population. MethodsThe Thessaloniki Eye study is a cross-sectional population-based study of chronic eye diseases in Thessaloniki, Greece. Participants with PEX were identified by clinical examination and were compared with those without PEX with regards to ophthalmic characteristics and systemic diseases, after adjusting for age and sex. ResultsPEX was found in 11.9% of the 2261 clinic-visit participants. Participants with PEX, compared with those without, had higher intraocular pressure, larger vertical cup-to-disc ratio, and higher percentage with vertical cup-to-disc ratio asymmetry and optic disc damage. The proportion with glaucoma among pseudoexfoliative participants (15.2%) was higher than that for glaucoma among nonpseudoexfoliative participants (4.7%). After excluding glaucoma participants, the only difference was the 0.6 mm Hg higher intraocular pressure in participants with PEX. Compared with nonpseudoexfoliative eyes, the presence of PEX on iris only or on both iris and lens was associated with higher intraocular pressure, whereas the presence of PEX on lens only was not. PEX was not associated with any systemic disease. ConclusionsThe prevalence of PEX in Greece is relatively high compared with other white populations. PEX was associated with higher intraocular pressure and higher percentage with optic disc damage, secondary to the higher proportion with glaucoma among pseudoexfoliative participants than among nonpseudoexfoliative participants. In nonglaucoma participants, eyes with PEX had only slightly higher intraocular pressure, but this was not observed in eyes with PEX on lens only.

Association of Open-angle Glaucoma With Perfusion Pressure Status in the Thessaloniki Eye Study

PURPOSE To investigate the association of open-angle glaucoma (OAG), primary open-angle glaucoma (POAG), and pseudoexfoliative glaucoma (PEXG) with ocular perfusion pressure status (ocular perfusion pressure with or without antihypertensive treatment). DESIGN Cross-sectional, population-based study. METHODS A total of 2554 randomly selected, ≥ 60-year old subjects participated in the Thessaloniki Eye Study. Only clinic-visit participants (n = 2261), who had uniformly collected data, were included in the analyses. A logistic regression model was run for OAG in all clinic-visit participants; covariates included age, sex, diastolic ocular perfusion pressure, antihypertensive treatment, intraocular pressure (IOP), IOP-lowering treatment, pseudoexfoliation, and vascular factors identified as risk factors for glaucoma in a previous analysis. Similar logistic regression models were run separately for POAG and PEXG. In addition, logistic regression models were run for OAG, POAG, and PEXG in subjects with and without antihypertensive treatment. Also, logistic regression models were run to assess the role of systolic ocular perfusion pressure in OAG, POAG, and PEXG. RESULTS Among clinic-visits, 1212 subjects (53.7%) were using antihypertensive treatment. An association of borderline significance was found between low diastolic ocular perfusion pressure and POAG (OR = 0.84 per 10 mm Hg, 95% CI = 0.70-1.01, P = .059). The effect of antihypertensive treatment on POAG was not statistically significant (OR = 1.20, 95% CI = 0.75-1.91, P = .45). In subgroup analyses, diastolic ocular perfusion pressure was significantly associated with POAG in subjects using antihypertensive treatment (OR = 0.78 per 10 mm Hg, 95% CI = 0.62-0.97, P = .028). No association was found between diastolic ocular perfusion pressure and PEXG, regardless of the use of antihypertensive treatment. No associations were found between systolic ocular perfusion pressure and OAG, POAG, or PEXG, regardless of the use of antihypertensive treatment. CONCLUSIONS Low diastolic ocular perfusion pressure may be associated with increased risk for POAG. This association was confirmed in subjects treated for systemic hypertension in subgroup analysis. This may support the hypothesis that the concept of ocular perfusion pressure status may be more relevant to glaucoma pathogenesis than ocular perfusion pressure alone.

Association of diabetes with age-related macular degeneration in the EUREYE study

Objective: To examine the association between self-reported diabetes history and early or late age-related macular degeneration (AMD) in the European population. Methods: Participants aged 65 years and over in the cross-sectional population-based EUREYE study underwent an eye examination including digital retinal photography. The images were graded at a single centre. A structured questionnaire was administered by trained field workers for putative risk factors for AMD including history of diabetes mellitus. Logistic regression models were used to examine the association between diabetes and stages of AMD, taking account of potential demographic, behavioural, dietary and medical (history of cardiovascular disease) confounders. Main outcome measures: Photographic images were graded according to the modified International Classification System for AMD and stratified into five exclusive stages from no signs of AMD (AMD stage 0), early AMD (Stages 1–3) and late AMD (Stage 4). Late AMD was subdivided in neovascular AMD (NV-AMD) or geographic atrophy (GA). Results: Data on diabetes history and potential confounders were available in 2117 control subjects without AMD, 2182 with early AMD, 49 with GA and 101 with NV-AMD. Of all participants, 13.1% reported a history of diabetes. After adjusting for potential confounders, subjects with neovascular AMD compared with controls had increased odds for diabetes (odds ratio 1.81; 95% confidence interval, 1.10 to 2.98, p = 0.02). Subjects with AMD grades 1 to 3 or GA had no increased odds for diabetes compared with those without AMD. Conclusions: In the EUREYE study, after multiple adjustments, positive association of diabetes mellitus with neovascular AMD was found. The hypothesis that diabetes is associated with neovascular AMD but not with geographic atrophy may suggest a different pathogenesis of the two advanced forms of the disease and needs to be further evaluated.

Update on pseudoexfoliation syndrome pathogenesis and associations with intraocular pressure, glaucoma and systemic diseases.

Purpose of review Pseudoexfoliation (PEX) syndrome is a common age-related disorder affecting intraocular and extraocular tissues. This review focuses on recent publications related with the pathogenesis and associations of PEX syndrome with intraocular pressure (IOP), glaucoma and systemic diseases. Recent findings In PEX tissues, expression of lysyl oxidase-like 1 (LOXL1) was found to be markedly dysregulated. This may adversely affect elastin metabolism and lead to elastotic alteration in tissues such as lamina cribrosa. There is increasing evidence that cellular stress conditions and low-grade chronic inflammatory processes are involved in the pathogenesis of PEX. Although there is an increased risk for glaucoma development in patients with PEX and ocular hypertension as compared with non-PEX patients with ocular hypertension, LOXL1 single nucleotide polymorphisms were not associated with intraocular pressure (IOP) differences. Lack of association of PEX with all-cause mortality or dementia has been reported recently. The association with vascular diseases is not consistent among different studies. Summary Despite the high prevalence of the LOXL1 variants in the general population, a much lower proportion of the population develops PEX, suggesting that in addition to LOXL1, other genetic, epigenetic and environmental factors may contribute to the development of PEX. Also, LOXL1 cannot help to identify those with PEX at increased risk for glaucoma development. Increased risk for glaucoma development in PEX patients who present with increased IOP may be related to other factors beyond IOP, contributing to increased vulnerability of the optic nerve to glaucoma development in the presence of PEX.

Association of the optic disc structure with the use of antihypertensive medications: the thessaloniki eye study.

Purpose:To investigate the association of antihypertensive medications with optic disc structure by blood pressure (BP) level, in nonglaucoma subjects. Design:Cross-sectional, population-based study. Methods:A subset of Thessaloniki Eye Study participants was included in this study. Subjects were interviewed for medical history and underwent extensive ophthalmic examination, BP measurement, and optic disc imaging with the Heidelberg retinal tomograph. Subjects treated for hypertension were grouped in the following groups: (1) angiotensin-converting enzyme inhibitors and/or angiotensin-receptor blockers; (2) beta blockers and/or calcium-channel blockers; (3) diuretics alone or combined with others; and (4) other combinations. Cup size and cup-to-disc (C/D) ratio in the above groups were compared with the untreated group, using regression models. Analyses were rerun for subjects with systolic BP (SBP)<140 mm Hg, SBP≥140 mm Hg, diastolic BP (DBP)<90 mm Hg, and DBP≥90 mm Hg. Results:Among 232 subjects, 131 were receiving antihypertensive medications. In subjects with DBP<90 mm Hg, all medications groups were associated with larger cup size and higher C/D ratio compared with the untreated group. Results were similar in subjects with SBP<140 mm Hg, with the exception of the beta blockers and/or calcium-channel blockers group. None of the medications groups were associated with the Heidelberg retinal tomograph parameters in those with DBP≥90 mm Hg or SBP≥140 mm Hg. Conclusions:All classes of antihypertensive medications were associated with larger cup size and higher C/D ratio in subjects with either DBP<90 mm Hg or SBP<140 mm Hg. These results suggest that there is no specific medication-related effect on optic disc structure, and the associations found are mediated through the hypotensive effect of antihypertensive medications.

Ethnicity‐Based Differences in the Association of LOXL1 Polymorphisms with Pseudoexfoliation/Pseudoexfoliative Glaucoma: A Meta‐Analysis

Pseudoexfoliation (PEX) is an age‐related disorder of the extracellular matrix; it is strongly associated with glaucoma, the leading cause of irreversible blindness worldwide. We conducted an ethnic‐based meta‐analysis of the association of LOXL1 polymorphisms with PEX/pseudoexfoliative glaucoma (PEXG). Association studies were retrieved systematically from PubMed, EMBASE, and Web of Knowledge. Allelic and genotype frequencies of rs3825942, rs1048661, and rs2165241 were compared between PEX/PEXG and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random effects model. Overall, 39 independent cohorts were included. Rs3825942 (G) was an at risk allele for PEX/PEXG in Caucasians, Japanese, Koreans, Chinese, South Asians, and Middle Easterners, but protective in Black South Africans (OR = 0.10, 95%CI:0.06–0.16). Rs1048661 (G) was an at risk allele for PEX/PEXG in Caucasians, South Asians, Middle Easterners and Black South Africans, but was protective in Japanese (OR = 0.03, 95%CI:0.02–0.06) and Koreans (OR = 0.10, 95%CI:0.05–0.22). These associations we‐re confirmed for the genotypic recessive models. Rs2165241 (C) was a protective allele for PEX/PEXG in Caucasians, but was an at risk allele in Japanese (OR = 7.49, 95%CI:3.22–17.41) and Koreans (OR = 6.63, 95%CI:2.60–16.90). This was confirmed for the genotypic dominant model. Other genetic and/or environmental factors may modify the effect of LOXL1 polymorphisms in certain ethnic groups.

Inter-examiner reproducibility of Ocular Response Analyzer using the waveform score quality index in healthy subjects.

Purpose:To evaluate the inter-examiner reproducibility of Ocular Response Analyzer (ORA) parameters in healthy subjects using the waveform score (WS) for quality control of acquisition. Patients and Methods:Fifteen healthy subjects had their intraocular pressure (IOP) measured with ORA by 2 masked examiners. An acquisition protocol that aimed at obtaining 4 reliable measurements in each eye with WS≥6 and with as few repeated measurements as possible was employed, whereas a maximum of 8 measurements per eye was allowed. Additional good quality criteria included symmetrical force-in and force-out applanation signal peaks on the ORA waveform and few or no distortions of the applanation signal curve. Only the right eyes were included in the analysis. Examiners were trained but not experienced. The inter-examiner reproducibility of ORA parameters was assessed using the intraclass correlation coefficient (ICC). Mean values of the best 4 measurements were considered in analysis. Results:ICC including the best 4 measurements per eye was high for all ORA parameters. Specifically, ICC for Goldmann-correlated IOP was 0.961, for corneal-compensated IOP was 0.962, for corneal resistance factor was 0.987, and for corneal hysteresis was 0.988. Similar reproducibility was found when only the 3 best measurements per eye were included in the analysis. Conclusions:The protocol for IOP measurement with ORA using the WS ≥6 as quality index achieved high inter-examiner reproducibility for all ORA parameters. High reproducibility was obtained even by inexperienced examiners when considering the mean of the best 3 measurements per eye.