Archimidis Koskosas

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 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.

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.

Overdiagnosis of open-angle glaucoma in the general population: the Thessaloniki Eye Study

To assess the overdiagnosis of open‐angle glaucoma (OAG) and to investigate associated factors.

Structure-Function Correlation Using Confocal Laser Ophthalmoscope in Primary Open-Angle Glaucoma and Pseudoexfoliative Glaucoma.

Purpose:To compare Heidelberg Retina Tomograph (HRT) optic disc parameters and structure-function correlation between primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG). Design:Prospective, observation case series. Patients and Methods:A total of 54 POAG and 33 PEXG cases, consecutively recruited from a University Glaucoma Service, underwent a comprehensive ophthalmic examination, including HRT optic disc imaging. Glaucoma definition required the presence of both structural and functional damage. One eye per subject was included in the analysis. T test, Mann-Whitney U test, and analysis of covariance were used to compare HRT parameters between POAG and PEXG, adjusting for age, mean deviation (MD) in the visual field, intraocular pressure, and disc area. The correlation between HRT and MD was assessed in each group. Results:Cup area (P=0.048), height variation contour (P=0.016), and cup/disc area ratio (P=0.023) were higher in POAG, whereas the mean retinal nerve fiber layer thickness (P=0.048), retinal nerve fiber layer cross-section area (P=0.044), and rim area (P=0.048) were lower in POAG, compared with PEXG. The correlation of HRT parameters with MD was significant only in the POAG group. Conclusions:At a similar level of functional damage, POAG subjects presented with more pronounced structural damage than PEXG subjects. The correlation between HRT and visual field parameters was more evident in POAG, compared with PEXG.