Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium.

Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analysis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (-0.17 mmHg per 10 cm; 95 % CI -0.25, -0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans.Medical Research Council (G1000143), Cancer Research UK (C864/A14136), Research into Ageing (262), Wellcome Trust, Richard Desmond Charitable Trust (via Fight for Sight), National Institute for Health Research, Stichting Lijf en Leven, Krimpen aan de Lek, MD Fonds, Utrecht, Rotterdamse Vereniging Blindenbelangen, Rotterdam, Stichting Oogfonds Nederland, Utrecht, Blindenpenning, Amsterdam, Blindenhulp, The Hague, Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB), Doorn, Landelijke Stichting voor Blinden en Slechtzienden, Utrecht, Swart van Essen, Rotterdam, Stichting Winckel-Sweep, Utrecht, Henkes Stichting, Rotterdam, Lameris Ootech BV, Nieuwegein, Medical Workshop, de Meern, NWO (Graduate Programme 2010 BOO (022.002.023)), Laboratoires Thea (Clermont-Ferrand, France), inter regional grant (PHRC) and the regional Council of Burgundy, European Community’s Seventh Framework Programme (FP7/2007-2013), Rheinland-Pfalz AZ 961-386261/733), Johannes Gutenberg-University of Mainz, Boehringer Ingelheim, PHILIPS Medical Systems, Novartis Pharma, Novartis European Union (European Social Fund—ESF), Greek National Strategic Reference Framework (NSRF) (Research Funding Program: THALES), European Social FundThis is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10654-016-0191-

Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium

Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analysis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (−0.17 mmHg per 10 cm; 95 % CI –0.25, −0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans

Optic disc topography study in a population-based sample with the confocal scanning laser tomography

Purpose: To study optic disc topography in a randomly selected sample of the Greek population and to create a normative database. Also, to study diagnostic ability of HRT parameters as well as that of new parameters created by our research team based on optic disc cupping contour, and to study the correlation of various factors with those with the best diagnostic ability. Finally, to assess the diagnostic ability of HRT algorithms Moorfields Regression Analysis (MRA) και Glaucoma Probability Score (GPS).Methods: We used HRT data from 1620 consecutive participants of the population-based study Thessaloniki Eye Study. Assessment of HRT parameters was done with the creation of receiver operation characteristics (ROC) curves, calculation of the area under the curve (AUC) and of the best sum of sensitivity and specificity for each parameter. Glaucoma suspects were grouped with normal, and in a second analysis they were excluded. Study of the association of HRT parameters with various factors was done first with a univariate and then with a multivariable model. Results: Among 1620 participants examined with HRT, data from 1337 were finally available for analysis. We calculated distribution of HRT parameters for normal and glaucomatous subjects, while the 97.5% percentile for vertical cup-to-disc ratio (VCDR) was 0.74. HRT parameters showing the best diagnostic ability were cup-to-disc area ratio (CDARATIO), rim-to-disc area ratio (RDARATIO), cup volume (CUPV), cup area (CUPA) and VCDR. The univariate analysis showed association of HRT parameters with height, weight, body mass index, diastolic blood pressure, intraocular pressure (IOP), age, sex, smoking, insulin intake, hormone intake, history of diabetes, cardiovascular disease and heart attack. The multivariable model in the population showed association of disc area with all selected HRT parameters (p<0.0001). IOP showed positive correlation with CDARATIO (p=0.014), LCDR (p=0.038), CUPA (p=0.039) and negative with RDARATIO (p=0.014). Finally, diabetes and female sex were negatively correlated with CUPV (p=0.033 and p=0.028 respectively). Analysis with females only showed association of smoking with increased VCDR (p=0.026) and CUPV (p=0.043), insulin intake with decreased CUPA (p=0.048), while an association of low diastolic pressure under treatment with increased VCDR was not confirmed. Disc area was positively correlated with all new HRT parameters while IOP and older ages were associated with some of them. AUC for MRA was 0.773 (suspects grouped with normals and borderline results with normal), while AUC for GPS was 0.855. Results: The morphology of the optic disc as measured with the HRT was studied in detail for the first time in a random sample of the Greek population. According to a published glaucoma classification system based on the 97.5% percentile for VCDR in the normal population, more than half of glaucomatous patients in our population would remain undiagnosed due to their small VCDR. Disc area, IOP, diabetes and female sex were associated with HRT parameters, while there were some differences in such associations when females were studied separately. Finally, diagnostic accuracy of MRA and GPS was not sufficiently high in order for them to be used for glaucoma screening.Σκοπός: Μελέτη της τοπογραφίας του οπτικού δίσκου σε τυχαίο δείγμα του Ελληνικού πληθυσμού και δημιουργία βάσης δεδομένων. Επίσης, μελέτη της διαγνωστικής ικανότητας των HRT παραμέτρων καθώς και νέων παραμέτρων που δημιουργήθηκαν με βάση τις λήψεις του HRT και περιγράφουν το περίγραμμα της κοίλανσης, και μελέτη της επίδρασης διαφόρων παραγόντων σ’ αυτές με τη μεγαλύτερη διαγνωστική ικανότητα. Τέλος, εκτίμηση της διαγνωστικής ικανότητας των αλγορίθμων Moorfields Regression Analysis (MRA) και Glaucoma Probability Score (GPS). Υλικό και μέθοδος: Αξιοποιήθηκαν δεδομένα του HRT από 1620 διαδοχικούς συμμετέχοντες της πληθυσμιακής μελέτης Thessaloniki Eye Study. Η αξιολόγηση των HRT παραμέτρων έγινε με τη δημιουργία των καμπυλών αντιστοιχίας ευαισθησίας-ειδικότητας, την επιφάνεια κάτω από την καμπύλη (AUC) και το μέγιστο άθροισμα ευαισθησίας-ειδικότητας για καθεμία. Οι ύποπτοι για γλαύκωμα αρχικά ομαδοποιήθηκαν με τους φυσιολογικούς και στη συνέχεια εξαιρέθηκαν. Η μελέτη συσχέτισης με παράγοντες έγινε με μονοπαραγοντική ανάλυση και στη συνέχεια με πολυπαραγοντικό μοντέλο. Αποτελέσματα: Από το σύνολο των 1620 ατόμων που εξετάστηκαν με το HRT Ι, δεδομένα από 1337 άτομα ήταν διαθέσιμα για τις αναλύσεις με το HRT3. Υπολογίστηκε η κατανομή των τιμών για τον φυσιολογικό πληθυσμό, ενώ η 97.5% εκατοστιαία θέση για το VCDR ήταν 0.74. Οι HRT παράμετροι που έδειξαν μεγαλύτερη διαγνωστική ικανότητα ήταν: επιφάνεια κοίλανσης/επιφάνεια οπτικού δίσκου (CDARATIO), νευροαμφιβληστροειδικός ιστός/επιφάνεια οπτικού δίσκου (RDARATIO), όγκος και επιφάνεια κοίλανσης (CUPV και CUPA), κάθετη διαμέτρος κοίλανσης/διάμετρο δίσκου (VCDR) και τετραγωνική ρίζα αυτής σταθμισμένη για την επιφάνεια δίσκου (LCDR). Η μονοπαραγοντική ανάλυση ανέδειξε συσχέτιση των HRT παραμέτρων με ύψος, βάρος, δείκτη μάζας σώματος, διαστολική αρτηριακή πίεση, ενδοφθάλμια πίεση (ΕΟΠ), ηλικία, φύλο, κάπνισμα, λήψη ινσουλίνης, λήψη ορμονών, ιστορικό διαβήτη, καρδιαγγειακής νόσου και καρδιακής προσβολής. Τα αποτελέσματα του πολυπαραγοντικού μοντέλου στο σύνολο των συμμετεχόντων έδειξαν συσχέτιση της επιφάνειας του δίσκου με όλες τις επιλεγμένες HRT παραμέτρους (p<0.0001). Η ΕΟΠ σχετίστηκε θετικά με CDARATIO (p=0.014), LCDR (p=0.038), CUPA (p=0.039) και αρνητικά με RDARATIO (p=0.014). Τέλος, διαβήτης και θήλυ φύλο σχετίστηκαν με μειωμένο CUPV (p=0.033 και p=0.028 αντίστοιχα). Η ανάλυση στο γυναικείο πληθυσμό ανέδειξε συσχέτιση του καπνίσματος με αύξηση του VCDR (p=0.026) και του CUPV (p=0.043), η λήψη ινσουλίνης σχετίστηκε με ελαττωμένη CUPA (p=0.048), ενώ δεν επιβεβαιώθηκε η συσχέτιση της χαμηλής διαστολικής πίεσης υπό αγωγή με αυξημένο VCDR. Η επιφάνεια του οπτικού δίσκου έδειξε θετική συσχέτιση με όλες τις νέες HRT παραμέτρους ενώ η ΕΟΠ και οι μεγάλες ηλικίες σχετίστηκαν με ορισμένες από αυτές. Η AUC του MRA ήταν 0.773 (ομαδοποίηση ύποπτων+φυσιολογικών και αποτελεσμάτων “οριακών”+“φυσιολογικών”), ενώ του GPS ήταν 0.855. Συμπεράσματα: Για πρώτη φορά μελετήθηκαν τα χαρακτηριστικά του οπτικού δίσκου φυσιολογικών ατόμων σε τυχαίο δείγμα του ελληνικού πληθυσμού με βάση το HRT. Σύμφωνα με διεθνές σύστημα κατάταξης του γλαυκώματος με βάση την 97.5% εκατοστιαία θέση του VCDR, πάνω από τους μισούς γλαυκωματικούς στον πληθυσμό μας θα παρέμεναν αδιάγνωστοι λόγω χαμηλού VCDR. Η επιφάνεια δίσκου, η ΕΟΠ, ο διαβήτης και το θήλυ φύλο σχετίστηκαν με ορισμένες HRT παραμέτρους, ενώ διαπιστώθηκαν κάποιες διαφορές στην επίδραση παραγόντων όταν οι γυναίκες μελετώνται χωριστά. Τέλος, οι αλγόριθμοι MRA και GPS δεν έδειξαν ικανοποιητική διαγνωστική ικανότητα ως εργαλεία μαζικού ελέγχου του πληθυσμού για γλαύκωμα

Survival of Visual Function in Patients with Advanced Glaucoma after Standard Guarded Trabeculectomy with MMC

Surgical intervention in patients with severe glaucoma remains controversial, especially in unilateral cases with a minimally affected fellow eye. Many question the benefit of trabeculectomy in such cases due to high complication rates and prolonged recovery. In this retrospective, non-comparative, interventional case series we aimed to determine the effect of trabeculectomy or combined phaco-trabeculectomy on the visual function of advanced glaucoma patients. Consecutive cases with perimetric mean deviation loss worse than −20 dB were included. Survival of visual function according to five predetermined visual acuity and perimetric criteria was set as the primary outcome. Qualified surgical success utilizing two different sets of criteria commonly used in the literature constituted secondary outcomes. Forty eyes with average baseline visual field mean deviation −26.3 ± 4.1 dB were identified. The average pre-operative intraocular pressure was 26.5 ± 11.4 mmHg and decreased to 11.4 ± 4.0 mmHg (p < 0.001) after an average follow-up of 23.3 ± 15.5 months. Visual function was preserved at two years in 77% or 66% of eyes respectively according to two different sets of visual acuity and perimetric criteria. Qualified surgical success was 89%, 72% at 1 and 3 years respectively. Trabeculectomy and/or phaco-trabeculectomy is associated with meaningful visual outcomes in patients with uncontrolled advanced glaucoma

Association of LOXL1 polymorphisms with pseudoexfoliation, glaucoma, intraocular pressure, and systemic diseases in a Greek population. The Thessaloniki eye study.

PurposeTo 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.MethodsA 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.ResultsBoth 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.ConclusionsIn 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

Association of LOXL1 polymorphisms with pseudoexfoliation, glaucoma, intraocular pressure, and systemic diseases in a Greek population. The Thessaloniki eye study.

PurposeTo 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.MethodsA 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.ResultsBoth 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.ConclusionsIn 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