Panayiota Founti

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.

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.

Association of Sequence Variation in the CX3CR1 Gene with Geographic Atrophy Age-related Macular Degeneration in a Greek Population

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

Association of LOXL1 Polymorphisms With Pseudoexfoliation, Glaucoma, Intraocular Pressure, and Systemic Diseases in a Greek Population. The Thessaloniki Eye Study

PURPOSE To investigate the association of the two single-nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene with pseudoexfoliation syndrome (PEX), pseudoexfoliative glaucoma (PEXG), and primary open-angle glaucoma (POAG) in a Greek population-based setting, from the Thessaloniki Eye study. METHODS A total of 233 subjects with successful DNA extraction, PCR amplification, and genotyping were included in the genetic analysis of G153D and R141L SNPs of LOXL1 gene and classified into four groups: controls (n = 93); subjects with PEX (n = 40); POAG (n = 66); and PEXG (n = 34). Multinomial logistic regression was used to test their association with LOXL1 SNPs with adjustment for covariates. The association of LOXL1 with IOP (in untreated subjects) and with systemic diseases was explored. RESULTS Both LOXL1 SNPs were present in high frequencies in controls and cases. The G153D was strongly associated with both PEX (odds ratio [OR] = 23.2, P = 0.003 for allele G) and PEXG (OR = 24.75, P = 0.003 for allele G) and was not associated with POAG (P = 0.451). In contrast, the R141L was not associated with PEX (P = 0.81), PEXG (P = 0.063), or POAG (P = 0.113). No association of the G153D with either intraocular pressure (IOP) or systemic diseases was found. CONCLUSIONS In the Thessaloniki Eye Study, the G153D SNP of LOXL1 gene was strongly associated with both PEX and PEXG, whereas the R141L was not associated. No association of the LOXL1 with IOP or with systemic diseases was found. These findings further support the hypothesis that the LOXL1 gene contributes to onset of PEXG through PEX. Gene variants of LOXL1 do not help to identify those with PEX at increased risk for glaucoma development.

Agreement among three examiners of colour Doppler imaging retrobulbar blood flow velocity measurements

Purpose:  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.