title: Reticular Pseudodrusen in Intermediate Age-Related Macular Degeneration: Prevalence, Detection, Clinical, Environmental, and Genetic Associations.
abstract: OBJECTIVE
  To determine the prevalence of reticular pseudodrusen (RPD) and their detection using multimodal imaging in patients with bilateral large drusen, and examine their clinical, demographic, environmental, and genetic associations.
  
  
  METHODS
  Three hundred participants with bilateral large drusen (>125 μm) underwent color fundus photography (CFP), near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT) imaging. Demographic information, smoking, and medical history were recorded, and a blood sample was obtained and genotyped to identify the risk alleles of the CFH and ARMS2 genes.
  
  
  RESULTS
  Reticular pseudodrusen were detected in 28.2% eyes of 29.0% participants using NIR and SD-OCT combined, but CFP and FAF detected only 42% and 89%, respectively, of these eyes with RPD. Participants with RPD were significantly older than those without (P < 0.001), but there was no significant difference in sex distribution, smoking history, cardiovascular factors, and minor allele frequency of the CFH gene (P > 0.173). However, the minor allele frequency of the ARMS2 gene was significantly higher in participants with RPD (P = 0.002). The presence of RPD was also independently associated with the presence of atrophic changes (including nascent geographic atrophy and drusen-associated atrophy detected on SD-OCT; P = 0.043).
  
  
  CONCLUSIONS
  Reticular pseudodrusen were detected on NIR and SD-OCT in more than a quarter of participants with bilateral large drusen, being often overlooked with CFP. Those with RPD had a higher frequency of the ARMS2 risk variant, and eyes with RPD were more likely to have atrophic changes. These findings are important to consider when managing patients with intermediate AMD.
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia 2Ophthalmology, Department of Surgery, The University of Melbourne, Melbourne, Australia.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia 2Ophthalmology, Department of Surgery, The University of Melbourne, Melbourne, Australia.
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Ayton
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia 2Ophthalmology, Department of Surgery, The University of Melbourne, Melbourne, Australia.
authors.forename: Chi D
authors.initials: CD
authors.lastname: Luu
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia 2Ophthalmology, Department of Surgery, The University of Melbourne, Melbourne, Australia.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia 2Ophthalmology, Department of Surgery, The University of Melbourne, Melbourne, Australia.
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D015994:Incidence; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009887:Ophthalmoscopy; D015995:Prevalence; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D015593:Retinal Drusen / Q000453:epidemiology / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D041623:Tomography, Optical Coherence; D014739:Victoria / Q000453:epidemiology
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins; D017242:Complement Factor H; D004247:DNA