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1. Recommendations for OCT Angiography Reporting in Retinal Vascular Disease: A Delphi Approach by International Experts.

Author

Munk, MR, Kashani, AH, Tadayoni, R, Korobelnik, J-F, Wolf, S, Pichi, F, Koh, A, Ishibazawa, A, Gaudric, A, Loewenstein, A, Lumbroso, B, Ferrara, D, Sarraf, D, Wong, DT, Skondra, D, Rodriguez, FJ, Staurenghi, G, Pearce, I, Kim, JE, Freund, KB, Parodi, MB, Waheed, NK, Rosen, R, Spaide, RF, Nakao, S, Sadda, S, Vujosevic, S, Wong, TY, Murata, T, Chakravarthy, U, Ogura, Y, Huf, W, Tian, M, Munk, MR, Kashani, AH, Tadayoni, R, Korobelnik, J-F, Wolf, S, Pichi, F, Koh, A, Ishibazawa, A, Gaudric, A, Loewenstein, A, Lumbroso, B, Ferrara, D, Sarraf, D, Wong, DT, Skondra, D, Rodriguez, FJ, Staurenghi, G, Pearce, I, Kim, JE, Freund, KB, Parodi, MB, Waheed, NK, Rosen, R, Spaide, RF, Nakao, S, Sadda, S, Vujosevic, S, Wong, TY, Murata, T, Chakravarthy, U, Ogura, Y, Huf, W, and Tian, M

Abstract

PURPOSE: To develop a consensus nomenclature for reporting OCT angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts. DESIGN: Delphi-based survey. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Twenty-five retinal vascular disease and OCTA imaging experts. METHODS, INTERVENTION, OR TESTING: A Delphi method of consensus development was used, comprising 2 rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The 4 main areas of consensus were: definition of the parameters of "wide-field (WF)" OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study end point was defined by the degree of consensus for each question: "strong consensus" was defined as ≥85% agreement, "consensus" as 80% to 84%, and "near consensus" as 70% to 79%. MAIN OUTCOME MEASURES: Consensus and near consensus on OCTA nomenclature in retinal vascular disease. RESULTS: A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a "large area" of WF-OCTA reduced flow signal should also be defined as ≥30% of the absolute imaged area. The presence of new vessels and intraretinal microvascular abnormalities, the foveal avascular zone parameters, the presence and amount of "no-flow areas," and the assessment of vessel density in various retinal layers should be added for the staging and classification of diabetic retinopathy. Decreased flow ≥30% of the absolute imaged area should define an ischemic central retinal vein occlusion. Several other items did not meet consensus requirements or were

Published
2022

3. Wirksamkeit von intravitrealem Aflibercept, unter Anwendung eines Treat-and-Extend-Regimes, bei Patienten mit Makulaödem nach retinalem Zentralvenenverschluss: Ergebnisse der CENTERA-Studie

Author

Eter, Nicole, Korobelnik, J.-F., Larsen, M., Bailey, C., Wolf, S., Schmelter, T., Allmeier, H., and Chaudhary, V.

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Ziel: Wirksamkeit und Sicherheit von intravitrealem Aflibercept (IVT-AFL), unter Anwendung eines Treat-and-Extend-(T&E-)Regimes bei Patienten mit Makulaödem nach retinalem Zentralvenenverschluss (ZVV). Quelle der Daten CENTERA (NCT02800642) eine 76-wöchige multizentrische, unverblindete,[zum vollständigen Text gelangen Sie über die oben angegebene URL], 33. Jahrestagung der Retinologischen Gesellschaft

Published
2021

4. Evolution of treatment paradigms in neovascular age-related macular degeneration: a review of real-world evidence

Author

Daien, V, Finger, RP, Talks, JS, Mitchell, P, Wong, TY, Sakamoto, T, Eldem, BM, Korobelnik, J-F, Daien, V, Finger, RP, Talks, JS, Mitchell, P, Wong, TY, Sakamoto, T, Eldem, BM, and Korobelnik, J-F

Abstract

The aim of this work was to evaluate the contribution of real-world evidence (RWE) in changing anti-vascular endothelial growth factor (VEGF) therapy treatment practices and improving real-world treatment strategies for neovascular age-related macular degeneration (nAMD).A PubMed literature search was performed to review the large number of English-language studies conducted to investigate the real-world effectiveness of anti-VEGF (aflibercept and ranibizumab) treatment paradigms available for nAMD.The evidence for pro re nata (PRN), treat-and-extend (T&E) and fixed bimonthly dosing regimens for anti-VEGF treatment of nAMD were reviewed and findings are summarised. RWE demonstrated that T&E regimens optimise visual outcomes while reducing burden on patients, clinics and physicians, compared with both fixed-dose and PRN regimens.RWE has helped to develop and improve real-world treatment strategies in nAMD, with the aim of optimising visual outcomes and reducing treatment burden in clinical practice. Of the various regimens, a T&E regimen is most likely to adequately balance clinical outcomes and treatment burden for patients with nAMD.

Published
2021

5. Rationale and Design for the Phase 3 Clinical Trials of Faricimab for Neovascular Age-Related Macular Degeneration

Author

Khanani, AM, Guymer, RH, Basu, K, Boston, H, Heier, JS, Korobelnik, J-F, Kotecha, A, Lin, H, Silverman, D, Swaminathan, B, Willis, JR, Yoon, YH, Quezada-Ruiz, C, Khanani, AM, Guymer, RH, Basu, K, Boston, H, Heier, JS, Korobelnik, J-F, Kotecha, A, Lin, H, Silverman, D, Swaminathan, B, Willis, JR, Yoon, YH, and Quezada-Ruiz, C

Abstract

PURPOSE: To describe the design and rationale of the phase 3 TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) trials that aimed to assess efficacy, safety, and durability of faricimab, the first bispecific antibody for intraocular use, which independently binds and neutralizes both angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A) versus aflibercept in patients with neovascular age-related macular degeneration (nAMD). DESIGN: Identical, global, double-masked, randomized, controlled, phase 3 clinical trials. PARTICIPANTS: Adults with treatment-naïve nAMD. METHODS: These trials were designed to evaluate patients randomized to receive faricimab 6.0 mg up to every 16 weeks after 4 initial every-4-week doses or aflibercept 2.0 mg every 8 weeks after 3 initial every-4-week doses. The initial doses in the faricimab arm were followed by individualized fixed treatment intervals up to week 60, based on disease activity assessment at weeks 20 and 24, guided by central subfield thickness, best-corrected visual acuity (BCVA), and investigator assessment. The primary efficacy end point was BCVA change from baseline averaged over weeks 40, 44, and 48. Secondary end points included the proportion of patients receiving every-8-week, every-12-week, and every-16-week faricimab and anatomic outcomes. Safety outcomes included incidence and severity of ocular and nonocular adverse events. From week 60, faricimab-treated patients followed a personalized treatment interval (PTI), a novel protocol-driven treat-and-extend regimen with interval adjustment from every 8 weeks to every 16 weeks based on individualized treatment response measured by anatomic criteria, functional criteria, and investigator assessment of patients' disease activity. MAIN OUTCOME MEASURES: Rationale for trial design and PTI approach. RESULTS: The TENAYA and LUCERNE trials were the first registrational trials in nAMD to test fixed dosing regime

Published
2021

6. Evolving European guidance on the medical management of neovascular age related macular degeneration

Author

Chakravarthy, U., Soubrane, G., Bandello, F., Chong, V., Creuzot-Garcher, C., Dimitrakos, S.A., II, Korobelnik, J.-F., Larsen, M., Mones, J., Pauleikhoff, D., Pournaras, C.J., Staurenghi, G., Virgili, G., and Wolf, S.

Subjects
Macular degeneration -- Care and treatment, Neovascularization -- Care and treatment, Choroid -- Diseases, Ophthalmology -- Practice, Medicine -- Practice, Medicine -- Standards, Health
Published
2006

8. The Decreasing Prevalence of Nonrefractive Visual Impairment in Older Europeans: A Meta-analysis of Published and Unpublished Data

Author

Delcourt, C., Le Goff, M., von Hanno, T., Mirshahi, A., Khawaja, A. P., Verhoeven, V. J. M., Hogg, R. E., Anastosopoulos, E., Cachulo, M. L., Hohn, R., Wolfram, C., Bron, A., Miotto, S., Carriere, I., Colijn, J. M., Buitendijk, G. H. S., Evans, J., Nitsch, D., Founti, P., Yip, J. L. Y., Pfeiffer, N., Creuzot-Garcher, C., Silva, R., Piermarocchi, S., Topouzis, F., Bertelsen, G., Foster, P. J., Fletcher, A., Klaver, C. C. W., Korobelnik, J. -F., Acar, N., Azuara-Blanco, A., Berendschot, T., Bergen, A., Binquet, C., Bird, A., Bobak, M., Boon, C., Bretillon, L., Broe, R., Buitendijk, G., Capuano, V., Chakravarthy, U., Chan, M., Chang, P., Colijn, J., Cougnard-Gregoire, A., Cree, A., Cumberland, P., Cunha-Vaz, J., Daien, V., De Jong, E., Deak, G., Delyfer, M. -N., den Hollander, A., Dietzel, M., Erke, M. G., Faria, P., Farinha, C., Fauser, S., Finger, R., Foster, P., Gorgels, T., Grauslund, J., Grus, F., Hammond, C., Hansen, M., Helmer, C., Hense, H. -W., Hermann, M., Hoehn, R., Hogg, R., Holz, F., Hoyng, C., Jansonius, N., Janssen, S., Kersten, E., Khawaja, A., Klaver, C., Lamparter, J., Lechanteur, Y., Lehtimaki, T., Leung, I., Lotery, A., Mauschitz, M., Meester, M., Merle, B., Meyer zu Westrup, V., Midena, E., Mohan-Said, S., Mueller, M., Muldrew, A., Murta, J., Nickels, S., Nunes, S., Owen, C., Peto, T., Prokofyeva, E., Rahi, J., Raitakari, O., Rauscher, F., Ribeiro, L., Rougier, M. -B., Rudnicka, A., Randjvar, Sahel, Salonikiou, A., Sanchez, C., Schmitz-Valckenberg, S., Schouten, J., Schuster, A., Schweitzer, C., Segato, T., Shehata, J., Silvestri, G., Simader, C., Souied, E., Speckauskas, M., Springelkamp, H., Tapp, R., van Leeuwen, E., Verhoeven, V., Verzijden, T., Von Hanno, T., Vujosevic, S., Wiedemann, P., Williams, K., Yip, J., and Zerbib, J.

Subjects
Europe, Aged, Humans, Prevalence, Vision, Low, Visually Impaired Persons, Visual Acuity, Vision, Low
Abstract

TOPIC: To estimate the prevalence of nonrefractive visual impairment and blindness in European persons 55 years of age and older. CLINICAL RELEVANCE: Few visual impairment and blindness prevalence estimates are available for the European population. In addition, many of the data collected in European population-based studies currently are unpublished and have not been included in previous estimates. METHODS: Fourteen European population-based studies participating in the European Eye Epidemiology Consortium (n = 70 723) were included. Each study provided nonrefractive visual impairment and blindness prevalence estimates stratified by age (10-year strata) and gender. Nonrefractive visual impairment and blindness were defined as best-corrected visual acuity worse than 20/60 and 20/400 in the better eye, respectively. Using random effects meta-analysis, prevalence rates were estimated according to age, gender, geographical area, and period (1991-2006 and 2007-2012). Because no data were available for Central and Eastern Europe, population projections for numbers of affected people were estimated using Eurostat population estimates for European high-income countries in 2000 and 2010. RESULTS: The age-standardized prevalence of nonrefractive visual impairment in people 55 years of age or older decreased from 2.22% (95% confidence interval [CI], 1.34-3.10) from 1991 through 2006 to 0.92% (95% CI, 0.42-1.42) from 2007 through 2012. It strongly increased with age in both periods (up to 15.69% and 4.39% in participants 85 years of age or older from 1991 through 2006 and from 2007 through 2012, respectively). Age-standardized prevalence of visual impairment tended to be higher in women than men from 1991 through 2006 (2.67% vs. 1.88%), but not from 2007 through 2012 (0.87% vs. 0.88%). No differences were observed between northern, western, and southern regions of Europe. The projected numbers of affected older inhabitants in European high-income countries decreased from 2.5 million affected individuals in 2000 to 1.2 million in 2010. Of those, 584 000 were blind in 2000, in comparison with 170 000 who were blind in 2010. CONCLUSIONS: Despite the increase in the European older population, our study indicated that the number of visually impaired people has decreased in European high-income countries in the last 20 years. This may be the result of major improvements in eye care and prevention, the decreasing prevalence of eye diseases, or both.

Published
2018

12. Anti-vascular endothelial growth factor in neovascular age-related macular degeneration - a systematic review of the impact of anti-VEGF on patient outcomes and healthcare systems

Author

Finger, RP, Daien, V, Eldem, BM, Talks, JS, Korobelnik, J-F, Mitchell, P, Sakamoto, T, Wong, TY, Pantiri, K, Carrasco, J, Finger, RP, Daien, V, Eldem, BM, Talks, JS, Korobelnik, J-F, Mitchell, P, Sakamoto, T, Wong, TY, Pantiri, K, and Carrasco, J

Abstract

BACKGROUND: Systematically review the evidence describing the impact of anti-vascular endothelial growth factor (anti-VEGF) therapy on neovascular age-related macular degeneration (nAMD) patient outcomes and healthcare resource utilization. METHODS: A systematic literature review was completed using Medline and EMBASE for publications prior to July 2018, and proceedings from major ophthalmology conferences (January 2016 to July 2018). The search strategy combined terms for nAMD with terms for anti-VEGF and study design. The review focused on publications describing the impact of anti-VEGF on blindness, visual impairment, vision-related quality of life (VRQoL), mortality, and costs. The search targeted data collected in epidemiological or observational studies to reflect real-world outcomes but also considered modeling-based approaches. RESULTS: The use of anti-VEGF in clinical practice was associated with significant reduction in the incidence of blindness by nAMD. Population-based analyses reported reduction in incidence among the general population of 47% (9.1 cases/100,000 in 2006 to 4.8 cases/100,000 in 2011). Among patients aged ≥50 years, a reduction of 50% was observed (52.2 cases/100,000 in 2000 to 25.7 cases/100,000 in 2010). In some cases, the odds of decreased vision (defined as decline from normal to moderate, moderate to severe, or severe to blindness) fell by 41% following introduction of anti-VEGF. Patients' VRQoL improved with treatment, with patients reporting a positive impact shortly after treatment was initiated. Change on National Eye Institute 25-Item Visual Function Questionnaire score from baseline to month 12 ranged from 0.7 to 4.4. Although nAMD patients report signs of depression and anxiety, the evidence suggests that there is no association between the use of anti-VEGF and the prevalence or diagnosis of depression. The introduction of anti-VEGF led to increased overall treatment costs due to replacement of existing less frequently admini

Published
2020

13. ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion

Author

Rizzo, Stanislao, Barale, P. -O., Ayello-Scheer, S., Devenyi, R. G., Delyfer, M. -N., Korobelnik, J. -F., Rachitskaya, A., Yuan, A., Jayasundera, K. T., Zacks, D. N., Handa, J. T., Montezuma, S. R., Koozekanani, D., Stanga, P. E., da Cruz, L., Walter, P., Augustin, A. J., Chizzolini, M., Olmos de Koo, L. C., Ho, A. C., Kirchhof, B., Hahn, P., Vajzovic, L., Iezzi, R., Gaucher, D., Arevalo, J. F., Gregori, N. Z., Grisanti, S., Ozmert, E., Yoon, Y. H., Kokame, G. T., Lim, J. I., Szurman, P., de Juan, E., Rezende, F. A., Salzmann, J., Richard, G., Huang, S. S., Merlini, F., Patel, U., Cruz, C., Greenberg, R. J., Justus, S., Cinelli, L., Humayun, M. S., Rizzo S. (ORCID:0000-0001-6302-063X), Rizzo, Stanislao, Barale, P. -O., Ayello-Scheer, S., Devenyi, R. G., Delyfer, M. -N., Korobelnik, J. -F., Rachitskaya, A., Yuan, A., Jayasundera, K. T., Zacks, D. N., Handa, J. T., Montezuma, S. R., Koozekanani, D., Stanga, P. E., da Cruz, L., Walter, P., Augustin, A. J., Chizzolini, M., Olmos de Koo, L. C., Ho, A. C., Kirchhof, B., Hahn, P., Vajzovic, L., Iezzi, R., Gaucher, D., Arevalo, J. F., Gregori, N. Z., Grisanti, S., Ozmert, E., Yoon, Y. H., Kokame, G. T., Lim, J. I., Szurman, P., de Juan, E., Rezende, F. A., Salzmann, J., Richard, G., Huang, S. S., Merlini, F., Patel, U., Cruz, C., Greenberg, R. J., Justus, S., Cinelli, L., Humayun, M. S., and Rizzo S. (ORCID:0000-0001-6302-063X)

Abstract

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

Published
2020

14. Hypotony and the Argus II retinal prosthesis: Causes, prevention and management

Author

Rizzo, Stanislao, Barale, P. -O., Ayello-Scheer, S., Devenyi, R. G., Delyfer, M. N., Korobelnik, J. -F., Rachitskaya, A., Yuan, A., Jayasundera, K. T., Zacks, D. N., Handa, J. T., Montezuma, S. R., Koozekanani, D., Stanga, P., Da Cruz, L., Walter, P., Augustin, A. J., Olmos De Koo, L. C., Ho, A. C., Kirchhof, B., Hahn, P., Vajzovic, L., Iezzi, R., Gaucher, D., Arevalo, J. F., Gregori, N. Z., Wiedemann, P., Ozmert, E., Lim, J. I., Rezende, F. A., Huang, S. S., Merlini, F., Patel, U., Greenberg, R. J., Justus, S., Bacherini, D., Cinelli, L., Humayun, M. S., Rizzo S. (ORCID:0000-0001-6302-063X), Rizzo, Stanislao, Barale, P. -O., Ayello-Scheer, S., Devenyi, R. G., Delyfer, M. N., Korobelnik, J. -F., Rachitskaya, A., Yuan, A., Jayasundera, K. T., Zacks, D. N., Handa, J. T., Montezuma, S. R., Koozekanani, D., Stanga, P., Da Cruz, L., Walter, P., Augustin, A. J., Olmos De Koo, L. C., Ho, A. C., Kirchhof, B., Hahn, P., Vajzovic, L., Iezzi, R., Gaucher, D., Arevalo, J. F., Gregori, N. Z., Wiedemann, P., Ozmert, E., Lim, J. I., Rezende, F. A., Huang, S. S., Merlini, F., Patel, U., Greenberg, R. J., Justus, S., Bacherini, D., Cinelli, L., Humayun, M. S., and Rizzo S. (ORCID:0000-0001-6302-063X)

Abstract

NA

Published
2020

15. Real-world data in retinal diseases treated with anti-vascular endothelial growth factor (anti-VEGF) therapy - a systematic approach to identify and characterize data sources.

Author

Daien, V, Eldem, BM, Talks, JS, Korobelnik, J-F, Mitchell, P, Finger, RP, Sakamoto, T, Wong, TY, Evuarherhe, O, Carter, G, Carrasco, J, Daien, V, Eldem, BM, Talks, JS, Korobelnik, J-F, Mitchell, P, Finger, RP, Sakamoto, T, Wong, TY, Evuarherhe, O, Carter, G, and Carrasco, J

Abstract

BACKGROUND: Real-world data (RWD) has been a valuable addition to the scientific literature regarding treatment pathways, clinical outcomes and characteristics of patients with retinal diseases in recent years. Registries, observational studies and patient databases are often used for real-world research. However, there is limited information for each data source on the design, consistency, data captured, limitations and usability for assessing research questions. Using a systematic approach, we identified RWD sources for patients with retinal diseases and assessed them for completeness of data relating to different outcomes. METHODS: A systematic literature review was carried out to identify RWD sources for patients with retinal disease. Potentially relevant articles published between 2006 and 2016 were screened following electronic searches in Embase and MEDLINE. Congress and supplementary searches were undertaken to identify RWD sources that may not be referenced in full publications. For each data source, availability and quantity of data on baseline status, clinical outcomes, treatment and management, safety, and patient-reported and economic burden were assessed using a bespoke completeness assessment tool based on International Consortium for Health Outcomes Measurement guidelines for macular degeneration. Completeness of data for each area of interest in each data source was assessed and rated using a 'good-moderate-poor' rating system based on availability and quantity of available data. Each data source was then given an overall score based on its score for each of the 7 areas of interest. RESULTS: A total of 128 RWD sources from 32 countries were identified. Of the identified sources, 64 sources from 16 countries of interest were analyzed. Most of these sources provided information on baseline status and clinical outcomes and treatment, but few collected data on economic and patient-reported burden. Of the RWD sources analyzed, 10 scored highly in the ove

Published
2019

17. Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Author

Colijn, J.M. (Johanna), Buitendijk, G.H.S. (Gabrielle), Prokofyeva, E. (Elena), Alves, D. (Dalila), Cachulo, M.L. (Maria L.), Khawaja, A.P. (Anthony), Cougnard-Grégoire, A. (Audrey), Merle, B.M.J. (Bénédicte M.J.), Korb, C. (Christina), Erke, M.G. (Maja Gran), Bron, A. (Alain), Anastasopoulos, E. (Eleftherios), Meester-Smoor, M.A. (Magda), Segato, T. (Tatiana), Piermarocchi, S. (Stefano), Jong, P.T.V.M. (Paulus) de, Vingerling, J.R. (Hans), Topouzis, F. (Fotis), Creuzot-Garcher, C. (Catherine), Bertelsen, G. (Geir), Pfeiffer, A.F.H. (Andreas), Fletcher, A.E. (Astrid E.), Foster, P.J. (Paul), Silva, R. (Rufino), Korobelnik, J.-F. (Jean-François), Delcourt, C. (Cécile), Klaver, C.C.W. (Caroline), Ajana, S. (Soufiane), Arango-Gonzalez, B. (Blanca), Arndt, V. (Verena), Bhatia, V. (Vaibhav), Bhattacharya, S.S. (Shomi S.), Biarnés, M. (Marc), Borrell, A. (Anna), Bühren, S. (Sebastian), Calado, S.M. (Sofia M.), Colijn, J.M. (Johanna M.), Dammeier, S. (Sascha), Jong, E.K. (Eiko) de, De la Cerda, B. (Berta), den Hollander, A.I. (Anneke I.), Diaz-Corrales, F.J. (Francisco J.), Diether, S. (Sigrid), Emri, E. (Eszter), Endermann, T. (Tanja), Ferraro, L.L. (Lucia L.), Garcia, M. (Míriam), Heesterbeek, T.J. (Thomas J.), Honisch, S. (Sabina), Hoyng, C.B. (Carel B.), Kersten, E. (Eveline), Kilger, E. (Ellen), Klaver, C.C.W. (Caroline C.W.), Langen, H. (Hanno), Lengyel, I. (Imre), Luthert, P. (Phil), Maugeais, C. (Cyrille), Meester-Smoor, M. (Magda), Monés, J. (Jordi), Nogoceke, E. (Everson), Peto, T. (Tunde), Pool, F.M. (Frances M.), Rodríguez, E. (Eduardo), Ueffing, M. (Marius), Ulrich Bartz-Schmidt, K.U. (Karl U.), van Leeuwen, E.M. (Elisabeth M.), Verzijden, T. (Timo), Zumbansen, M. (Markus), Acar, N. (Niyazi), Anastosopoulos, E. (Eleftherios), Azuara-Blanco, A. (Augusto), Bergen, A.A.B. (Arthur), Binquet, C. (Christine), Bird, A.C. (Alan), Bretillon, L. (Lionel), Buitendijk, G. (Gabrielle), Cachulo, M.L. (Maria Luz), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chang, P. (Petrus), Colijn, J. (Johanna), Cumberland, P. (Phillippa), Cunha-Vaz, J. (José), Daien, V. (Vincent), Deak, G. (Gabor), Delyfer, M.-N. (Marie-Noëlle), Hollander, A.I. (Anneke), Dietzel, M. (Martha), Fauser, S. (Sascha), Finger, R. (Robert), Fletcher, A. (Astrid), Foster, P.J. (Paul J.), Founti, P. (Panayiota), Göbel, A. (Arno), Gorgels, T.G.M.F. (Theo), Grauslund, J. (Jakob), Grus, F. (Franz), Hammond, C.J. (Christopher), Helmer, C. (Catherine), Hense, H.-W. (Hans-Werner), Hermann, M. (Manuel), Hoehn, R. (René), Hogg, R. (Ruth), Holz, F.G. (Frank), Hoyng, C.B. (Carel), Jansonius, N.M. (Nomdo), Janssen, S.F. (Sarah), Khawaja, A. (Anthony), Lamparter, J. (Julia), Le Goff, M. (Mélanie), Leal, S. (Sergio), Lechanteur, Y.T.E. (Yara T. E.), Lehtimäki, T. (Terho), Lotery, A.J. (Andrew), Leung, I. (Irene), Mauschitz, M. (Matthias), Merle, B. (Bénédicte), Meyer zu Westrup, V. (Verena), Midena, E. (Edoardo), Miotto, S. (Stefania), Mirshahi, A. (Alireza), Mohan-Saïd, S. (Sadek), Mueller, M. (Michael), Muldrew, A. (Alyson), Nunes, S. (Sandrina), Oexle, K. (Konrad), Peto, T. (Tünde), Rahi, J. (Jugnoo), Raitakari, O. (Olli), Ribeiro, L. (Luisa), Rougier, M.-B. (Marie-Bénédicte), Sahel, J.-A. (José-Alain), Salonikiou, A. (Aggeliki), Sanchez, C. (Clarisa), Schmitz-Valckenberg, S. (Steffen), Schweitzer, C.M.C. (C. M C), Shehata, J. (Jasmin), Silvestri, G. (Giuliana), Simader, C. (Christian), Souied, E.H. (Eric), Springelkamp, H. (Henriët), Tapp, R. (Robyn), Verhoeven, V. (Virginie), Von Hanno, T. (Therese), Vujosevic, S. (Stela), Williams, K. (Katie), Wolfram, C. (Christian), Yip, J. (Jennifer), Zerbib, J. (Jennyfer), Zwiener, I. (Isabella), Colijn, J.M. (Johanna), Buitendijk, G.H.S. (Gabrielle), Prokofyeva, E. (Elena), Alves, D. (Dalila), Cachulo, M.L. (Maria L.), Khawaja, A.P. (Anthony), Cougnard-Grégoire, A. (Audrey), Merle, B.M.J. (Bénédicte M.J.), Korb, C. (Christina), Erke, M.G. (Maja Gran), Bron, A. (Alain), Anastasopoulos, E. (Eleftherios), Meester-Smoor, M.A. (Magda), Segato, T. (Tatiana), Piermarocchi, S. (Stefano), Jong, P.T.V.M. (Paulus) de, Vingerling, J.R. (Hans), Topouzis, F. (Fotis), Creuzot-Garcher, C. (Catherine), Bertelsen, G. (Geir), Pfeiffer, A.F.H. (Andreas), Fletcher, A.E. (Astrid E.), Foster, P.J. (Paul), Silva, R. (Rufino), Korobelnik, J.-F. (Jean-François), Delcourt, C. (Cécile), Klaver, C.C.W. (Caroline), Ajana, S. (Soufiane), Arango-Gonzalez, B. (Blanca), Arndt, V. (Verena), Bhatia, V. (Vaibhav), Bhattacharya, S.S. (Shomi S.), Biarnés, M. (Marc), Borrell, A. (Anna), Bühren, S. (Sebastian), Calado, S.M. (Sofia M.), Colijn, J.M. (Johanna M.), Dammeier, S. (Sascha), Jong, E.K. (Eiko) de, De la Cerda, B. (Berta), den Hollander, A.I. (Anneke I.), Diaz-Corrales, F.J. (Francisco J.), Diether, S. (Sigrid), Emri, E. (Eszter), Endermann, T. (Tanja), Ferraro, L.L. (Lucia L.), Garcia, M. (Míriam), Heesterbeek, T.J. (Thomas J.), Honisch, S. (Sabina), Hoyng, C.B. (Carel B.), Kersten, E. (Eveline), Kilger, E. (Ellen), Klaver, C.C.W. (Caroline C.W.), Langen, H. (Hanno), Lengyel, I. (Imre), Luthert, P. (Phil), Maugeais, C. (Cyrille), Meester-Smoor, M. (Magda), Monés, J. (Jordi), Nogoceke, E. (Everson), Peto, T. (Tunde), Pool, F.M. (Frances M.), Rodríguez, E. (Eduardo), Ueffing, M. (Marius), Ulrich Bartz-Schmidt, K.U. (Karl U.), van Leeuwen, E.M. (Elisabeth M.), Verzijden, T. (Timo), Zumbansen, M. (Markus), Acar, N. (Niyazi), Anastosopoulos, E. (Eleftherios), Azuara-Blanco, A. (Augusto), Bergen, A.A.B. (Arthur), Binquet, C. (Christine), Bird, A.C. (Alan), Bretillon, L. (Lionel), Buitendijk, G. (Gabrielle), Cachulo, M.L. (Maria Luz), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chang, P. (Petrus), Colijn, J. (Johanna), Cumberland, P. (Phillippa), Cunha-Vaz, J. (José), Daien, V. (Vincent), Deak, G. (Gabor), Delyfer, M.-N. (Marie-Noëlle), Hollander, A.I. (Anneke), Dietzel, M. (Martha), Fauser, S. (Sascha), Finger, R. (Robert), Fletcher, A. (Astrid), Foster, P.J. (Paul J.), Founti, P. (Panayiota), Göbel, A. (Arno), Gorgels, T.G.M.F. (Theo), Grauslund, J. (Jakob), Grus, F. (Franz), Hammond, C.J. (Christopher), Helmer, C. (Catherine), Hense, H.-W. (Hans-Werner), Hermann, M. (Manuel), Hoehn, R. (René), Hogg, R. (Ruth), Holz, F.G. (Frank), Hoyng, C.B. (Carel), Jansonius, N.M. (Nomdo), Janssen, S.F. (Sarah), Khawaja, A. (Anthony), Lamparter, J. (Julia), Le Goff, M. (Mélanie), Leal, S. (Sergio), Lechanteur, Y.T.E. (Yara T. E.), Lehtimäki, T. (Terho), Lotery, A.J. (Andrew), Leung, I. (Irene), Mauschitz, M. (Matthias), Merle, B. (Bénédicte), Meyer zu Westrup, V. (Verena), Midena, E. (Edoardo), Miotto, S. (Stefania), Mirshahi, A. (Alireza), Mohan-Saïd, S. (Sadek), Mueller, M. (Michael), Muldrew, A. (Alyson), Nunes, S. (Sandrina), Oexle, K. (Konrad), Peto, T. (Tünde), Rahi, J. (Jugnoo), Raitakari, O. (Olli), Ribeiro, L. (Luisa), Rougier, M.-B. (Marie-Bénédicte), Sahel, J.-A. (José-Alain), Salonikiou, A. (Aggeliki), Sanchez, C. (Clarisa), Schmitz-Valckenberg, S. (Steffen), Schweitzer, C.M.C. (C. M C), Shehata, J. (Jasmin), Silvestri, G. (Giuliana), Simader, C. (Christian), Souied, E.H. (Eric), Springelkamp, H. (Henriët), Tapp, R. (Robyn), Verhoeven, V. (Virginie), Von Hanno, T. (Therese), Vujosevic, S. (Stela), Williams, K. (Katie), Wolfram, C. (Christian), Yip, J. (Jennifer), Zerbib, J. (Jennyfer), and Zwiener, I. (Isabella)

Abstract

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95% C

Published
2017
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18. Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium

Author

Khawaja, A.P. (Anthony), Springelkamp, H. (Henriët), Creuzot-Garcher, C. (Catherine), Delcourt, C. (Cécile), Hofman, A. (Albert), Höhn, R. (René), Iglesias González, A.I. (Adriana), Wolfs, R.C.W. (Roger), Korobelnik, J.-F. (Jean-François), Silva, R. (Rufino), Topouzis, F. (Fotis), Williams, K.M. (Katie M.), Bron, A. (Alain), Buitendijk, G.H.S. (Gabrielle), Cachulo, M.L. (Maria da Luz), Cougnard-Grégoire, A. (Audrey), Dartigues, J.-F., Hammond, C.J. (Christopher J.), Pfeiffer, A.F.H. (Andreas), Salonikiou, A. (Angeliki), van Duijn, C.M. (Cornelia M.), Vingerling, J.R. (Hans), Luben, R.N. (Robert), Mirshahi, A. (Alireza), Lamparter, J. (Julia), Klaver, C.C.W. (Caroline), Jansonius, N.M. (Nomdo M.), Foster, P.J. (Paul), Khawaja, A.P. (Anthony), Springelkamp, H. (Henriët), Creuzot-Garcher, C. (Catherine), Delcourt, C. (Cécile), Hofman, A. (Albert), Höhn, R. (René), Iglesias González, A.I. (Adriana), Wolfs, R.C.W. (Roger), Korobelnik, J.-F. (Jean-François), Silva, R. (Rufino), Topouzis, F. (Fotis), Williams, K.M. (Katie M.), Bron, A. (Alain), Buitendijk, G.H.S. (Gabrielle), Cachulo, M.L. (Maria da Luz), Cougnard-Grégoire, A. (Audrey), Dartigues, J.-F., Hammond, C.J. (Christopher J.), Pfeiffer, A.F.H. (Andreas), Salonikiou, A. (Angeliki), van Duijn, C.M. (Cornelia M.), Vingerling, J.R. (Hans), Luben, R.N. (Robert), Mirshahi, A. (Alireza), Lamparter, J. (Julia), Klaver, C.C.W. (Caroline), Jansonius, N.M. (Nomdo M.), and Foster, P.J. (Paul)

Abstract

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.

Published
2016
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19. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author

Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), Makela, K.M. (Kari Matti), Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), and Makela, K.M. (Kari Matti)

Abstract

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10-5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

Published
2016
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20. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Author

Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), Vatavuk, Z. (Zoran), Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), and Vatavuk, Z. (Zoran)

Abstract

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).

Published
2016
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21. Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium.

Author

Khawaja, AP, Springelkamp, H, Creuzot-Garcher, C, Delcourt, C, Hofman, A, Höhn, R, Iglesias, AI, Wolfs, RCW, Korobelnik, J-F, Silva, R, Topouzis, F, Williams, KM, Bron, AM, Buitendijk, GHS, Cachulo, MDL, Cougnard-Grégoire, A, Dartigues, J-F, Hammond, CJ, Pfeiffer, N, Salonikiou, A, van Duijn, CM, Vingerling, JR, Luben, RN, Mirshahi, A, Lamparter, J, Klaver, CCW, Jansonius, NM, Foster, PJ, European Eye Epidemiology (E³) Consortium, Khawaja, AP, Springelkamp, H, Creuzot-Garcher, C, Delcourt, C, Hofman, A, Höhn, R, Iglesias, AI, Wolfs, RCW, Korobelnik, J-F, Silva, R, Topouzis, F, Williams, KM, Bron, AM, Buitendijk, GHS, Cachulo, MDL, Cougnard-Grégoire, A, Dartigues, J-F, Hammond, CJ, Pfeiffer, N, Salonikiou, A, van Duijn, CM, Vingerling, JR, Luben, RN, Mirshahi, A, Lamparter, J, Klaver, CCW, Jansonius, NM, Foster, PJ, and European Eye Epidemiology (E³) Consortium

Abstract

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.

Published
2016

22. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author

Fan, Q, Verhoeven, VJM, Wojciechowski, R, Barathi, VA, Hysi, PG, Guggenheim, JA, Hoehn, R, Vitart, V, Khawaja, AP, Yamashiro, K, Hosseini, SM, Lehtimaki, T, Lu, Y, Haller, T, Xie, J, Delcourt, C, Pirastu, M, Wedenoja, J, Gharahkhani, P, Venturini, C, Miyake, M, Hewitt, AW, Guo, X, Mazur, J, Huffman, JE, Williams, KM, Polasek, O, Campbell, H, Rudan, I, Vatavuk, Z, Wilson, JF, Joshi, PK, McMahon, G, St Pourcain, B, Evans, DM, Simpson, CL, Schwantes-An, T-H, Igo, RP, Mirshahi, A, Cougnard-Gregoire, A, Bellenguez, C, Blettner, M, Raitakari, O, Kaehoenen, M, Seppala, I, Zeller, T, Meitinger, T, Ried, JS, Gieger, C, Portas, L, van Leeuwen, EM, Amin, N, Uitterlinden, AG, Rivadeneira, F, Hofman, A, Vingerling, JR, Wang, YX, Wang, X, Boh, ET-H, Ikram, MK, Sabanayagam, C, Gupta, P, Tan, V, Zhou, L, Ho, CEH, Lim, W, Beuerman, RW, Siantar, R, Tai, E-S, Vithana, E, Mihailov, E, Khor, C-C, Hayward, C, Luben, RN, Foster, PJ, Klein, BEK, Klein, R, Wong, H-S, Mitchell, P, Metspalu, A, Aung, T, Young, TL, He, M, Paerssinen, O, van Duijn, CM, Wang, JJ, Williams, C, Jonas, JB, Teo, Y-Y, David, AMM, Oexle, K, Yoshimura, N, Paterson, AD, Pfeiffer, N, Wong, T-Y, Baird, PN, Stambolian, D, Bailey-Wilson, JE, Cheng, C-Y, Hammond, CJ, Klaver, CCW, Saw, S-M, Rahi, JS, Korobelnik, J-F, Kemp, JP, Timpson, NJ, Smith, GD, Craig, JE, Burdon, KP, Fogarty, RD, Iyengar, SK, Chew, E, Janmahasatian, S, Martin, NG, MacGregor, S, Xu, L, Schache, M, Nangia, V, Panda-Jonas, S, Wright, AF, Fondran, JR, Lass, JH, Feng, S, Zhao, JH, Khaw, K-T, Wareham, NJ, Rantanen, T, Kaprio, J, Pang, CP, Chen, LJ, Tam, PO, Jhanji, V, Young, AL, Doering, A, Raffel, LJ, Cotch, M-F, Li, X, Yip, SP, Yap, MKH, Biino, G, Vaccargiu, S, Fossarello, M, Fleck, B, Yazar, S, Tideman, JWL, Tedja, M, Deangelis, MM, Morrison, M, Farrer, L, Zhou, X, Chen, W, Mizuki, N, Meguro, A, Makela, KM, Fan, Q, Verhoeven, VJM, Wojciechowski, R, Barathi, VA, Hysi, PG, Guggenheim, JA, Hoehn, R, Vitart, V, Khawaja, AP, Yamashiro, K, Hosseini, SM, Lehtimaki, T, Lu, Y, Haller, T, Xie, J, Delcourt, C, Pirastu, M, Wedenoja, J, Gharahkhani, P, Venturini, C, Miyake, M, Hewitt, AW, Guo, X, Mazur, J, Huffman, JE, Williams, KM, Polasek, O, Campbell, H, Rudan, I, Vatavuk, Z, Wilson, JF, Joshi, PK, McMahon, G, St Pourcain, B, Evans, DM, Simpson, CL, Schwantes-An, T-H, Igo, RP, Mirshahi, A, Cougnard-Gregoire, A, Bellenguez, C, Blettner, M, Raitakari, O, Kaehoenen, M, Seppala, I, Zeller, T, Meitinger, T, Ried, JS, Gieger, C, Portas, L, van Leeuwen, EM, Amin, N, Uitterlinden, AG, Rivadeneira, F, Hofman, A, Vingerling, JR, Wang, YX, Wang, X, Boh, ET-H, Ikram, MK, Sabanayagam, C, Gupta, P, Tan, V, Zhou, L, Ho, CEH, Lim, W, Beuerman, RW, Siantar, R, Tai, E-S, Vithana, E, Mihailov, E, Khor, C-C, Hayward, C, Luben, RN, Foster, PJ, Klein, BEK, Klein, R, Wong, H-S, Mitchell, P, Metspalu, A, Aung, T, Young, TL, He, M, Paerssinen, O, van Duijn, CM, Wang, JJ, Williams, C, Jonas, JB, Teo, Y-Y, David, AMM, Oexle, K, Yoshimura, N, Paterson, AD, Pfeiffer, N, Wong, T-Y, Baird, PN, Stambolian, D, Bailey-Wilson, JE, Cheng, C-Y, Hammond, CJ, Klaver, CCW, Saw, S-M, Rahi, JS, Korobelnik, J-F, Kemp, JP, Timpson, NJ, Smith, GD, Craig, JE, Burdon, KP, Fogarty, RD, Iyengar, SK, Chew, E, Janmahasatian, S, Martin, NG, MacGregor, S, Xu, L, Schache, M, Nangia, V, Panda-Jonas, S, Wright, AF, Fondran, JR, Lass, JH, Feng, S, Zhao, JH, Khaw, K-T, Wareham, NJ, Rantanen, T, Kaprio, J, Pang, CP, Chen, LJ, Tam, PO, Jhanji, V, Young, AL, Doering, A, Raffel, LJ, Cotch, M-F, Li, X, Yip, SP, Yap, MKH, Biino, G, Vaccargiu, S, Fossarello, M, Fleck, B, Yazar, S, Tideman, JWL, Tedja, M, Deangelis, MM, Morrison, M, Farrer, L, Zhou, X, Chen, W, Mizuki, N, Meguro, A, and Makela, KM

Abstract

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

Published
2016

25. Prevalence of refractive error in Europe: the European Eye Epidemiology (E3) Consortium

Author

Williams, K.M. (Katie M.), Verhoeven, V.J.M. (Virginie), Cumberland, P. (Phillippa), Bertelsen, G. (Geir), Wolfram, C. (Christian), Buitendijk, G.H.S. (Gabrielle), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Vingerling, J.R. (Hans), Kuijpers, R.W.A.M. (Robert), Höhn, R. (René), Mirshahi, A. (Alireza), Khawaja, A.P. (Anthony P.), Luben, R.N. (Robert N.), Erke, M.G. (Maja Gran), Von Hanno, T. (Therese), Mahroo, O. (Omar), Hogg, R. (Ruth), Gieger, C. (Christian), Cougnard-Grégoire, A. (Audrey), Anastasopoulos, E. (Eleftherios), Bron, A. (Alain), Dartigues, J.-F., Korobelnik, J.-F. (Jean-François), Creuzot-Garcher, C. (Catherine), Topouzis, F. (Fotis), Delcourt, C. (Cécile), Rahi, J.S. (Jugnoo), Meitinger, T. (Thomas), Fletcher, A. (Astrid), Foster, P.J. (Paul J.), Pfeiffer, N. (Norbert), Klaver, C.C.W. (Caroline), Hammond, C.J. (Christopher), Williams, K.M. (Katie M.), Verhoeven, V.J.M. (Virginie), Cumberland, P. (Phillippa), Bertelsen, G. (Geir), Wolfram, C. (Christian), Buitendijk, G.H.S. (Gabrielle), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Vingerling, J.R. (Hans), Kuijpers, R.W.A.M. (Robert), Höhn, R. (René), Mirshahi, A. (Alireza), Khawaja, A.P. (Anthony P.), Luben, R.N. (Robert N.), Erke, M.G. (Maja Gran), Von Hanno, T. (Therese), Mahroo, O. (Omar), Hogg, R. (Ruth), Gieger, C. (Christian), Cougnard-Grégoire, A. (Audrey), Anastasopoulos, E. (Eleftherios), Bron, A. (Alain), Dartigues, J.-F., Korobelnik, J.-F. (Jean-François), Creuzot-Garcher, C. (Catherine), Topouzis, F. (Fotis), Delcourt, C. (Cécile), Rahi, J.S. (Jugnoo), Meitinger, T. (Thomas), Fletcher, A. (Astrid), Foster, P.J. (Paul J.), Pfeiffer, N. (Norbert), Klaver, C.C.W. (Caroline), and Hammond, C.J. (Christopher)

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 combined 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 prevalence were obtained including the following classifications: myopia ≤−0.75 diopters (D), high myopia ≤−6D, hyperopia ≥1D and astigmatism ≥1D. Meta-analysis of refractive error was performed for 61,946 individuals from fifteen studies with median age ranging from 44 to 81 and minimal ethnic variation (98 % European ancestry). The age-standardised prevalences (using the 2010 European Standard Population, limited to those ≥25 and <90 years old) were: myopia 30.6 % [95 % confidence interval (CI) 30.4–30.9], high myopia 2.7 % (95 % CI 2.69–2.73), hyperopia 25.2 % (95 % CI 25.0–25.4) and astigmatism 23.9 % (95 % CI 23.7–24.1). Age-specific estimates revealed a high prevalence of myopia in younger participants [47.2 % (CI 41.8–52.5) in 25–29 years-olds]. Refractive error affects just over a half of European adults. The greatest burden of refractive error is due to myopia, with high prevalence rates in young adults. Using the 2010 European population estimates, we estimate there are 227.2 million people with myopia across Europe.

Published
2015
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26. Increasing Prevalence of Myopia in Europe and the Impact of Education

Author

Williams, K.M. (Katie M.), Bertelsen, G. (Geir), Cumberland, P. (Phillippa), Wolfram, C. (Christian), Verhoeven, V.J.M. (Virginie), Anastasopoulos, E. (Eleftherios), Buitendijk, G.H.S. (Gabrielle), Cougnard-Grégoire, A. (Audrey), Creuzot-Garcher, C. (Catherine), Erke, M.G. (Maja Gran), Hogg, R. (Ruth), Höhn, R. (René), Hysi, P.G. (Pirro), Khawaja, A.P. (Anthony P.), Korobelnik, J.-F. (Jean-François), Ried, J.S. (Janina), Vingerling, J.R. (Hans), Bron, A. (Alain), Dartigues, J.-F. (Jean-François), Fletcher, A. (Astrid), Hofman, A. (Albert), Kuijpers, R.W.A.M. (Robert), Luben, R.N. (Robert N.), Oxele, K. (Konrad), Topouzis, F. (Fotis), Von Hanno, T. (Therese), Mirshahi, A. (Alireza), Foster, P.J. (Paul J.), Duijn, C.M. (Cornelia) van, Pfeiffer, A.F.H. (Andreas), Delcourt, C. (Cécile), Klaver, C.C.W. (Caroline), Rahi, J.S. (Jugnoo), Hammond, C.J. (Christopher), Williams, K.M. (Katie M.), Bertelsen, G. (Geir), Cumberland, P. (Phillippa), Wolfram, C. (Christian), Verhoeven, V.J.M. (Virginie), Anastasopoulos, E. (Eleftherios), Buitendijk, G.H.S. (Gabrielle), Cougnard-Grégoire, A. (Audrey), Creuzot-Garcher, C. (Catherine), Erke, M.G. (Maja Gran), Hogg, R. (Ruth), Höhn, R. (René), Hysi, P.G. (Pirro), Khawaja, A.P. (Anthony P.), Korobelnik, J.-F. (Jean-François), Ried, J.S. (Janina), Vingerling, J.R. (Hans), Bron, A. (Alain), Dartigues, J.-F. (Jean-François), Fletcher, A. (Astrid), Hofman, A. (Albert), Kuijpers, R.W.A.M. (Robert), Luben, R.N. (Robert N.), Oxele, K. (Konrad), Topouzis, F. (Fotis), Von Hanno, T. (Therese), Mirshahi, A. (Alireza), Foster, P.J. (Paul J.), Duijn, C.M. (Cornelia) van, Pfeiffer, A.F.H. (Andreas), Delcourt, C. (Cécile), Klaver, C.C.W. (Caroline), Rahi, J.S. (Jugnoo), and Hammond, C.J. (Christopher)

Abstract

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

Published
2015
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33. Genetic association study of mitochondrial polymorphisms in neovascular age-related macular degeneration

Author

Tilleul, J., Richard, F., Puche, N., Zerbib, J., Leveziel, N., José-Alain Sahel, Cohen, S. Y., Korobelnik, J. F., Feingold, J., Munnich, A., Kaplan, J., Rozet, J. M., and Souied, E. H.

Subjects
Male, Polymorphism, Genetic, genetic structures, DNA, Mitochondrial, eye diseases, Choroidal Neovascularization, Mitochondria, Macular Degeneration, Case-Control Studies, Odds Ratio, Humans, Female, sense organs, Genetic Association Studies, Research Article, Aged, Demography
Abstract

Purpose Age-related macular degeneration (AMD) is a multifactorial disease involving genetic and environmental factors. Most of the genetic factors identified so far involve the nuclear genome. Recently, two studies in North America and Australia reported an association between advanced AMD and the mitochondrial T2 haplogroup. Our purpose was to assess this association in a large French population. Methods This case control study included 1,224 patients with neovascular AMD and 559 controls with normal fundus. Mitochondrial DNA polymorphisms at and around nucleotides 4917, 11,812, and 14,233 were determined using PCR amplification and direct sequencing of mitochondrial DNA. Results No association was found between the mitochondrial T2 haplogroup and neovascular AMD in the French population: 94/1,152 patients with neovascular AMD had the T2 haplogroup (8.2%) versus 34/482 controls (7.1%; odds ratio=0.9 [0.5–1.5], p=0.66). Conclusions An association between AMD and the T2 haplogroup, previously described in North American and Australian populations, was not confirmed in a large French population.

34. AFLIBERCEPT AFTER RANIBIZUMAB INTRAVITREAL INJECTIONS IN EXUDATIVE AGE–RELATED MACULAR DEGENERATION

Author

Maddalena Quaranta-ElMaftouhi, Eric H. Souied, Stéphane Béchet, Florence Coscas, Camille Jung, Jean-François Korobelnik, José Sahel, Joel Uzzan, Giuseppe Querques, Rocio Blanco-Garavito, Blanco-Garavito, R., Jung, C., Uzzan, J., Quaranta-Elmaftouhi, M., Coscas, F., Sahel, J., Korobelnik, J. -F., Bechet, S., Querques, G., and Souied, E. H.

Subjects
Male, Vascular Endothelial Growth Factor A, Time Factors, Visual acuity, genetic structures, pigment epithelial detachment, Visual Acuity, Angiogenesis Inhibitors, Retinal Pigment Epithelium, 0302 clinical medicine, Pro re nata, Medicine, Original Study, Macula Lutea, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Aflibercept, Aged, 80 and over, Drug Substitution, aflibercept, Retinal detachment, General Medicine, Diabetic retinopathy, Middle Aged, wet age-related macular degeneration, 3. Good health, Treatment Outcome, Intravitreal Injections, Female, medicine.symptom, Tomography, Optical Coherence, medicine.drug, medicine.medical_specialty, switch therapy, Recombinant Fusion Proteins, 03 medical and health sciences, Ranibizumab, Ophthalmology, Humans, ranibizumab, Aged, business.industry, Retinal Detachment, Macular degeneration, medicine.disease, Receptors, Vascular Endothelial Growth Factor, wet age–related macular degeneration, Wet Macular Degeneration, 030221 ophthalmology & optometry, anti-VEGF therapy, business, Follow-Up Studies
Abstract

Treatment-resistant pigment epithelial detachments can be effectively treated with aflibercept switch therapy. Patients were treated with 3 monthly intravitreal injections and then a Q6 regimen. Mean pigment epithelial detachment height and volume were statistically reduced after the switch at primary endpoint (12 weeks), and best-corrected visual acuity also improved steadily throughout the duration of the study., Purpose: To analyze the efficacy of aflibercept switch treatment for regression of pigment epithelial detachment (PED) in patients previously treated with ranibizumab. Methods: Multicenter, prospective, nonrandomized clinical trial. One eye of patients presenting neovascular age–related macular degeneration with PED of more than 250 μm in height, with persistent fluid, was included. Patients had to have received at least six ranibizumab intravitreal injections during the 12 months before enrollment. Patients were switched from ranibizumab pro re nata to aflibercept (fixed regimen, 3 monthly intravitreal injections, and then Q6). Main outcome measure was change in PED height from baseline to Week 12 after switch. Secondary outcomes were best-corrected visual acuity and PED volume changes. Results: Eighty four patients were included. Mean delay between last ranibizumab intravitreal injection and switch was 44.7 days. Mean maximal PED height at baseline visit was 347 μm (±109) and reduced to a mean of 266 μm (±114) at Week 12 (P < 0.001) and 288.2 μm at Week 32 (P < 0.001). Mean PED volume was reduced from 1.3 mm3 to 0.98 mm3 at Week 12 (P < 0.001). Best-corrected visual acuity improved by 3.3 Early Treatment Diabetic Retinopathy Study letters at Week 32 (P = 0.003). Conclusion: Aflibercept switch therapy seems to be effective on large PED in patients previously treated with pro re nata ranibizumab.

Published
2018
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35. Fundamental principles of an effective diabetic retinopathy screening program

Author

Lanzetta, Paolo, Sarao, Valentina, Scanlon, Peter H, Barratt, Jane, Porta, Massimo, Bandello, Francesco, Loewenstein, Anat, Eldem, Bora, Hunyor, Alex, Joussen, Antonia, Koh, Adrian, Korobelnik, Jean-François, Lövestam-Adrian, Monica, Navarro, Rafael, Okada, Annabelle A., Pearce, Ian, Rodríguez, Francisco J., Staurenghi, Giovanni, Wolf, Sebastian, Wong, David T., Lanzetta, P., Sarao, V., Scanlon, P. H., Barratt, J., Porta, M., Bandello, F., Loewenstein, A., Eldem, B., Hunyor, A., Joussen, A., Koh, A., Korobelnik, J. -F., Lovestam-Adrian, M., Navarro, R., Okada, A. A., Pearce, I., Rodriguez, F. J., Staurenghi, G., Wolf, S., and Wong, D. T.

Subjects
Adult, Male, Telemedicine, Consensus, Endocrinology, Diabetes and Metabolism, Diabetic macular edema, Early detection, 030209 endocrinology & metabolism, Macular Edema, Diabetic retinopathy screening, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Evidence-based recommendations, Internal Medicine, medicine, Diabetes Mellitus, Humans, Mass Screening, Grading (education), Referral and Consultation, Accreditation, Diabetic Retinopathy, business.industry, General Medicine, Diabetic retinopathy, Middle Aged, medicine.disease, RA645.D54, Systematic review, Practice Guidelines as Topic, 030221 ophthalmology & optometry, RE, Female, Medical emergency, business, Program Evaluation
Abstract

Background Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults worldwide. Early detection and treatment are necessary to forestall vision loss from DR. Methods A working group of ophthalmic and diabetes experts was established to develop a consensus on the key principles of an effective DR screening program. Recommendations are based on analysis of a structured literature review. Results The recommendations for implementing an effective DR screening program are: (1) Examination methods must be suitable for the screening region, and DR classification/grading systems must be systematic and uniformly applied. Two-field retinal imaging is sufficient for DR screening and is preferable to seven-field imaging, and referable DR should be well defined and reliably identifiable by qualified screening staff; (2) in many countries/regions, screening can and should take place outside the ophthalmology clinic; (3) screening staff should be accredited and show evidence of ongoing training; (4) screening programs should adhere to relevant national quality assurance standards; (5) studies that use uniform definitions of risk to determine optimum risk-based screening intervals are required; (6) technology infrastructure should be in place to ensure that high-quality images can be stored securely to protect patient information; (7) although screening for diabetic macular edema (DME) in conjunction with DR evaluations may have merit, there is currently insufficient evidence to support implementation of programs solely for DME screening. Conclusion Use of these recommendations may yield more effective DR screening programs that reduce the risk of vision loss worldwide.

Published
2020

36. Endophthalmitis after intravitreal injections: incidence, presentation, management, and visual outcome

Author

Julien Pérol, Catherine Français, Carole Burillon, Jean-François Korobelnik, Stéphanie Baillif, Laurent Berthon, Giuseppe Querques, M. Boissonnot, Jean-Paul Berrod, Catherine Creuzot-Garcher, Christiane Besse Ramahefasolo, Florence Coscas, Olivier Chevreaud, Christophe Chiquet, Maher Saleh, G Chaine, Pierre-Jean Pisella, Morgane Straub, John Conrath, Jean-François Girmens, Laurent Kodjikian, Joel Uzzan, Franck Fajnkuchen, Salomon Y. Cohen, Alain M. Bron, Yannick Le Mer, Marie-Noëlle Delyfer, Typhaine Grenet, Eric H Souied, Denis Dossarps, Bernard Delbosc, David Gaucher, Philippe Koehrer, Ludwig S. Aho-Glélé, Cécile Musson, Marc Muraine, Amina Bakhti, Quaranta-El Maftouhi, Audrey Giocanti, Nicolas Leveziel, Vincent Fortoul, Sam Razavi, Marie-Laure Le Lez, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Recherche Agronomique (INRA), Ministry of Health (PHRC inter-regional), Dijon, France, Dossarps, D., Bron, A. M., Koehrer, P., Aho-Glele, L. S., Creuzot-Garcher, C., Berthon, L., Maftouhi, Q. -E., Bakhti, A., Conrath, J., Le Mer, Y., Ramahefasolo, C. B., Coscas, F., Francais, C., Grenet, T., Cohen, S. Y., Uzzan, J., Razavi, S., Saleh, M., Delbosc, B., Chaine, G., Fajnkuchen, F., Giocanti, A., Delyfer, M. -N., Korobelnik, J. -F., Querques, G., Chevreaud, O., Souied, E., Musson, C., Chiquet, C., Fortoul, V., Kodjikian, L., Straub, M., Burillon, C., Berrod, J. -P., Baillif, S., Girmens, J. -F., Perol, J., Leveziel, N., Boissonnot, M., Muraine, M., Gaucher, D., Le Lez, M. -L., Pisella, P. -J., and ProdInra, Archive Ouverte

Subjects
Male, Visual acuity, factor agents, Visual Acuity, Angiogenesis Inhibitors, Eye Infections, Bacterial, Endophthalmitis, Antiseptic, Risk Factors, causative organisms, risk-factors, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Incidence (epidemiology), Incidence, Middle Aged, Anti-Bacterial Agents, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Intravitreal Injections, Female, France, Presentation (obstetrics), medicine.symptom, metaanalysis, Adult, medicine.medical_specialty, macular degeneration, medicine.drug_class, Retinal Diseases, medicine, Humans, ranibizumab, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Glucocorticoids, Aged, Retrospective Studies, ocular surface, Bacteria, business.industry, Retrospective cohort study, antibiotic-prophylaxis, Eye infection, medicine.disease, Confidence interval, Surgery, Vitreous Body, Ophthalmology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, operating-room, endothelial growth-factor
Abstract

Purpose To report the incidence and characteristics of endophthalmitis after intravitreal injections of anti–vascular endothelial growth factor agents or corticosteroids and to describe the clinical and bacteriologic characteristics, management, and outcome of these eyes with acute endophthalmitis in France. Design Retrospective, nationwide multicenter case series. Methods From January 2, 2008 to June 30, 2013, a total of 316 576 intravitreal injections from 25 French ophthalmic centers were included. For each center, the number of intravitreal injections was determined using billing codes and the injection protocol was recorded. A registry and hospital records were reviewed to identify patients treated for endophthalmitis after injection during the same time period. The main outcome measures were the incidence of clinical endophthalmitis and visual acuity of endophthalmitis cases. Results During the study period, 65 cases of presumed endophthalmitis were found, giving an overall incidence of 0.021% (2.1 in 10 000 injections) (95% confidence interval [CI], 0.016%–0.026%). The median number of days from injection to presentation was 4 [1–26] days. The most common symptom was vision loss. Bacterial identification was achieved in 43.4%. The most frequent pathogens were gram-positive bacteria (91.3%), including coagulase-negative Staphylococcus in 78.3%. Neither the interval between injection and presentation for endophthalmitis nor the clinical signs differentiated culture-positive from culture-negative cases. In multivariate analysis, the use of a disposable conjunctival mould assist device and the use of prophylaxis with an antibiotic or antiseptic were significantly associated with an increased incidence of endophthalmitis ( P = .001). The majority of patients had worse visual acuity after 3 months of follow-up when compared with acuity before endophthalmitis. Conclusions The incidence of presumed endophthalmitis after intravitreal injections of anti–vascular endothelial growth factors or corticosteroids was low and the prognosis poor. Prevention and management remain challenging. It remains to be determined whether the findings of this study are relevant for other countries using different techniques for intravitreal injections.

Published
2015
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37. Sight-threatening phenylketonuric encephalopathy in a young adult, reversed by diet.

Author

Rubin S, Piffer AL, Rougier MB, Delyfer MN, Korobelnik JF, Redonnet-Vernhet I, Marchal C, Goizet C, Mesli S, Gonzalez C, Gin H, and Rigalleau V

Abstract

Phenylketonuria (PKU) leads to severe neurological disorders in childhood, shunned by the diet. The long-term prognosis after diet diversification at adolescence is uncertain. We report a case of cortical blindness in a young patient regressive 1 month after the diet was resumed.Mr M., 25 years old, had PKU detected at birth. He maintained good serum levels of Phenylalanine (Phe) (120-300 μmol/L) during childhood and got a normal intellectual development. During adolescence he diversified his diet but maintained low meat and fish intake; Phe was ~1,200 μmol/L with no symptoms. In 2009, the patient stopped the low-Phe amino acid substitutes due to weariness. On June 27, 2011, he consulted for a decrease of visual acuity progressing for 6 months. Ophthalmologic examination found that visual acuity was 2/10 in two eyes associated to a central visual field defect. The visual evoked potentials were altered. MRI showed bilateral and symmetric occipital FLAIR hyperintensities. On admission in the Nutrional Unit on June 29, 2011, blood pressure was 120/70 mmHg, there was no other neurological abnormality. Phe was at 1,512 μmol/L, and not responsive to BH4. He was then treated with a very low-Phe diet with an amino acid substitute, and he obtained Phe between 120 and 300 μmol/L. Visual acuity was suddenly restored on August 1, 2011, with a dramatic attenuation of the MRI hyperintensities.Our observation shows that the withdrawal of the diet and substitutes exposes to serious neurological complications in adults that may reverse with a fast nutritional support.

Published
2013
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38. Scleral and episcleral histological changes related to encircling explants in 20 eyes.

Author

D'Hermies F, Korobelnik JF, Chauvaud D, Pouliquen Y, Parel JM, and Renard G

Subjects
Adult, Aged, Aged, 80 and over, Biocompatible Materials adverse effects, Catgut adverse effects, Female, Fibrosis, Follow-Up Studies, Granuloma, Foreign-Body etiology, Humans, Hydrogel, Polyethylene Glycol Dimethacrylate adverse effects, Male, Middle Aged, Retinal Detachment surgery, Retrospective Studies, Scleral Diseases etiology, Silicone Elastomers adverse effects, Granuloma, Foreign-Body pathology, Sclera pathology, Scleral Buckling adverse effects, Scleral Diseases pathology
Abstract

Purpose: To investigate scleral and episcleral histological alterations induced by encircling explants used in scleral buckling procedures., Methods: We performed a histopathological study of 20 enucleated eyes after failure of retinal detachment surgery including encircling scleral buckle., Results: Nonabsorbable materials were encapsulated and often gave rise to a limited scleral invagination. The inner capsular surface was regular in 10 silicone explants, it was partially covered with hydrogel fragments and a granulomatous foreign body giant cell reaction in 8 hydrogel explants. One Arruga thread was encased in fibrosis and a catgut circle showed no encapsulation. Other changes were mostly related to the long-standing retinal detachment: peripheral anterior synechiae, anterior uveal effusion, persistent retinal detachment, retinal gliosis, retinal atrophy, retinal breaks, and silicone oil droplets., Conclusion: All nonabsorbable explants underwent encapsulation and prompted scleral invagination. A granulomatous reaction accompanied hydrogel fragmentation. The long term fragmentation impact on implanted eyes remains unknown.

Published
1999
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39. Pseudouveitis as a manifestation of hyperlipidaemia.

Author

Thanh HX, Hannouche D, Robin H, Van Der Donk M, and Korobelnik JF

Subjects
Adult, Diabetic Retinopathy complications, Humans, Male, Visual Acuity, Hyperlipidemias complications, Uveitis, Anterior etiology
Published
1998

40. Choroidal neovascularization complicating epiretinal membrane removal.

Author

Korobelnik JF, Dureau P, Sarfati A, Chauvaud D, and Hoang-Xuan T

Subjects
Adult, Basement Membrane pathology, Basement Membrane surgery, Choroid surgery, Female, Fluorescein Angiography, Follow-Up Studies, Fundus Oculi, Humans, Neovascularization, Pathologic surgery, Retinal Neovascularization pathology, Visual Acuity, Choroid blood supply, Laser Coagulation adverse effects, Neovascularization, Pathologic etiology, Postoperative Complications, Retinal Neovascularization surgery
Abstract

Purpose: Surgical removal of epiretinal membranes generally leads to anatomic and functional improvement. Main complications include cataract, retinal breaks and detachment. We describe the onset of a juxtafoveal choroidal neovascularization 2 years after surgery of an epiretinal membrane., Methods: The neovascular membrane was treated by argon laser photocoagulation., Results: Complete obliteration of the neovascularization was obtained resulting in functional improvement., Conclusions: Although rare, choroidal neovascularization as a complication of epiretinal membrane surgery must be suspected in case of poor visual outcome or relapse of symptoms.

Published
1997
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