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Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population
  1. Emma Connolly1,
  2. Maedbh Rhatigan1,
  3. Aisling M O’Halloran2,
  4. Katherine Alyson Muldrew3,
  5. Usha Chakravarthy3,
  6. Mark Cahill4,
  7. Rose Anne Kenny2,
  8. Sarah L Doyle1
  1. 1Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland
  2. 2Department of Medical Gerontology, The Irish Longitudinal Study on Ageing (TILDA), School of Medicine, Trinity College Dublin, Dublin, Ireland
  3. 3Centre for Public Health, Queens University of Belfast, Belfast, UK
  4. 4Royal Victoria Eye and Ear Hospital, Dublin, Ireland
  1. Correspondence to Dr Sarah L Doyle, Dept. Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland; doyles8{at}


Background/aims Age-related macular degeneration (AMD) is estimated to affect 196 million people >50 years old globally. Prevalence of AMD-associated genetic risk factors and rate of disease progression are unknown in Ireland.

Methods Prevalence of AMD-associated genetic risk variants, complement factor H (CFH) rs1061170, age-related maculopathy susceptibility 2 (ARMS2) rs10490924, component 3 (C3) rs2230199, complement factor B (CFB) rs641153 and superkiller viralicidic activity 2-like (SKIV2L) rs429608 and 4-year progression data in a population-representative cohort (The Irish Longitudinal study on Ageing (TILDA)) were assessed. 4473 participants ≥50 years were assessed. 4173 had no disease n=1843; 44% male and n=2330; 56% female, mean age 60±9.0, 300 had AMD n=136; 45% male and n=164; 55% female, mean age 64±9.0. A 4-year follow-up was undertaken with 66% of AMD cases attending. Progression and regression from early to late AMD were measured. Genetic association as indicators of disease and as predictors of progression were assessed by multinomial logistic regression.

Results Older age and the presence of CFH and ARMS2 risk alleles are two main risk factors associated with the prevalence of AMD in the TILDA cohort. 23% progressed to a higher grade of AMD. Carriers of CFH risk allele showed a strong association for disease progression. Heterozygosity for ARMS2 risk allele predicted progression to late AMD. 75% of those who progressed from early to late disease had soft drusen and hyperpigmentation at baseline.

Conclusions The prevalence of risk-associated genes and 4-year progression rates of AMD in this Ireland cohort are comparable with other Caucasian populations. CFH Y402H is associated with disease progression, with soft drusen and hyperpigmentation as high-risk features.

  • degeneration
  • epidemiology
  • genetics
  • macula
  • public health

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  • EC and MR contributed equally.

  • Contributors SLD and RAK conceived the research questions. EC and SLD analysed the data. EC, MR and SLD wrote the manuscript. AMOH and RAK provided access to TILDA cohort and contributed to data analysis. KAM and UC trained MR in grading funds photographs and edited manuscript. MC second graded fundus photographs.

  • Funding This work was supported by Health Research Board Ireland grant number HRB HRA/2013.290, Science Foundation Ireland SFI 15/TIDA/2920; SFI 15/CDA/3497 and the RVEEH.

  • Competing interests None declared.

  • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval Ethics Board, School of Medicine, Trinity College Dublin.

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

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