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Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report
  1. Nichole Joachim1,
  2. Johanna Maria Colijn2,3,
  3. Annette Kifley1,
  4. Kristine E Lee4,
  5. Gabriëlle H S Buitendijk2,3,
  6. Barbara E K Klein4,
  7. Chelsea E Myers4,
  8. Stacy M Meuer4,
  9. Ava G Tan1,
  10. Elizabeth G Holliday5,
  11. John Attia5,6,
  12. Gerald Liew1,
  13. Sudha K Iyengar7,
  14. Paulus T V M de Jong8,
  15. Albert Hofman3,9,
  16. Johannes R Vingerling2,3,
  17. Paul Mitchell1,
  18. Caroline C W Klaver2,3,10,
  19. Ronald Klein4,
  20. Jie Jin Wang1
  1. 1 Centre for Vision Research, The Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia
  2. 2 Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands
  3. 3 Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
  4. 4 Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Wisconsin, USA
  5. 5 Centre for Clinical Epidemiology and Biostatistics, and School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
  6. 6 Department of Medicine, John Hunter Hospital and Hunter Medical Research Institute, Newcastle, New South Wales, Australia
  7. 7 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA
  8. 8 Netherlands Institute of Neuroscience of the Royal Netherlands Academy of Arts and Sciences (KNAW), Departments of Ophthalmology AMC, Amsterdam and LUMC, Leiden, The Netherlands
  9. 9 Netherlands Consortium for Healthy Aging, Netherlands Genomics Initiative, The Hague, The Netherlands
  10. 10 Department of Ophthalmology, Radboudumc, Nijmegen, The Netherlands
  1. Correspondence to Professor Jie Jin Wang, Centre for Vision Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW 2145, Australia;{at}


Purpose To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors.

Design Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study.

Methods Retinal photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors.

Results In any 5-year duration, 19–28% of unilateral any AMD cases became bilateral and 27–68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye.

Conclusion One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement.

  • Macula
  • Degeneration
  • Epidemiology

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  • PM, CCWK, RK, JJW are co-senior authors.

  • Contributors All the authors meet the ICMJE recommendations for authorship credit (substantial contributions to the conception or design of the work, or the acquisition, analysis or interpretation of data; drafting the work or revising it critically for important intellectual content; final approval of the version published; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved).

  • Funding This work was supported by the National Health and Medical Research Council (Canberra, Australia) (Project Grant IDs 512423 and 590204 to JJW). The Blue Mountains Eye Study (BMES) was supported by the National Health and Medical Research Council (NHMRC), Canberra, Australia (NHMRC project grant IDs 974159, 211069, 457349, 302068, and Centre for Clinical Research Excellence in Translational Clinical Research in Eye Diseases, CCRE in TCR-Eye, grant ID 529923). The BMES GWAS and genotyping costs was supported by the NHMRC, Canberra, Australia (NHMRC project grant IDs 512423, 475604 and 529912), and the Wellcome Trust, UK as part of Wellcome Trust Case Control Consortium 2 (A Viswanathan, P McGuffin, P Mitchell, F Topouzis, P Foster, grant IDs 085475/B/08/Z and 085475/08/Z). The Beaver Dam Eye Study was supported by National Institutes of Health (NIH) grant EY006594 (BEK Klein and R Klein), an NIH Research Vision Core grant EY016665, and, in part, by an unrestricted grant from Research to Prevent Blindness, New York, NY. The Rotterdam Study (RS) was supported by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. In addition, the RS was supported by Rotterdamse Stichting Blindenbelangen, Rotterdam; Macula Fonds, Utrecht; Henkes Stichting, Rotterdam; Stichting Oogfonds Nederland, Utrecht; and Landelijke Stichting voor Blinden en Slechtzienden, Utrecht. JJW is funded by a NHMRC (Canberra, Australia) Senior Research Fellowship (Grant ID 358702, 2005–2009 and ID 632909, 2010–2015). NHMRC Australia, the NIH and other funding bodies mentioned above had no role in the design or conduct of this research.

  • Competing interests There are no financial disclosures for all authors except for PM and CCWK, who have provided consultancy to Bayer (PM, CCWK), Novartis (PM, CCWK) and Allergan (PM) and received payment and travel/accommodations from these companies for lectures.

  • Ethics approval The University of Sydney and the Sydney West Area Health Service Human Research Ethics Committees; University of Wisconsin-Madison; Erasmus Medical Centre and Ministry of Health, Welfare and Sport of the Netherlands.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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