Elsevier

Ophthalmology

Volume 123, Issue 3, March 2016, Pages 599-608
Ophthalmology

Original article
Reticular Pseudodrusen and Their Association with Age-Related Macular Degeneration: The Melbourne Collaborative Cohort Study

https://doi.org/10.1016/j.ophtha.2015.10.029Get rights and content

Purpose

To determine the prevalence of reticular pseudodrusen (RPD) and its association with age-related macular degeneration (AMD) and AMD risk factors in a large sample.

Design

Community-based cohort study in Melbourne, Victoria, Australia.

Participants

A total of 21130 participants 48 to 86 years of age available for ophthalmic assessment at follow-up from 2003 through 2007.

Methods

Lifestyle, diet, and anthropometric measurements were obtained at baseline and follow-up. At follow-up, digital macular color photographs were graded for early, intermediate, and late AMD as well as the presence of RPD. Data were analyzed using multinomial logistic regression controlling for age, gender, smoking, country of birth, and diet.

Main Outcome Measures

Detection of RPD based on color fundus photographs.

Results

Prevalence of RPD was 0.41% (87 of 21130 participants), with 51% having bilateral RPD. Patients with RPD were older compared with patients with large drusen (>125 μm; 76±4 vs. 68±9 years; P < 0.001). Increasing age, female gender, being a current smoker, as well as focal pigmentary abnormalities and large drusen (>125 μm) were associated with a higher prevalence of RPD. Presence of geographic atrophy (GA) was associated with the highest odds of having RPD (odds ratio [OR], 153; 95% confidence interval [CI], 53–442), followed by choroidal neovascularization (CNV; OR, 90; 95% CI, 26–310), intermediate AMD (OR, 33; 95% CI, 14–77), and early AMD (OR, 12; 95% CI, 5–31) compared with those with no AMD. The ARMS2 single nucleotide polymorphism (SNP) rs10490924, HTRA1 SNPs rs11200638 and rs3793917, and CFH SNPs rs393955, rs1061170, and rs2274700 were associated with increased prevalence of RPD (all P < 0.05).

Conclusions

Reticular pseudodrusen are highly concurrent with AMD and have similar associations with known AMD risk factors such as age, gender, smoking, and genetic risk factors. Reticular pseudodrusen are associated more strongly with GA than with CNV. Although RPD are not specific to AMD, they are likely to be a strong risk factor for progression to late-stage AMD, similar to focal pigmentary abnormalities and large drusen.

Section snippets

Study Sample

The MCCS is a prospective, community-based cohort study of 41 514 people (24 469 women) living in Melbourne, Australia.8 Almost all participants (99.3%) were between 40 and 69 years of age at recruitment (1990–1994). At baseline, participants attended clinics where demographic, lifestyle, and dietary data were collected and anthropometric measurements were performed. The follow-up study was conducted between 2003 and 2007, when demographic information and anthropometric measurements were

Results

The prevalence of definite RPD was 0.41% (87 of 21 130 participants), with 51% having bilateral RPD. When all RPD cases were included (including those with <80% certainty of RPD), the prevalence increased to 0.78% (Table 2, available at www.aaojournal.org). Demographic characteristics of all participants included in this study by definite RPD and AMD status can be found in Table 3 (available at www.aaojournal.org). The median age of cases was 77 years (interquartile range, 74.6–79.6 years).

Discussion

In this study, we have shown that definite RPD are associated highly with all stages of AMD as well as focal pigmentary abnormalities and large drusen. Reticular pseudodrusen seem to occur later in life compared with large drusen and are associated highly with late AMD. Age-related macular degeneration and RPD share risk factors such as increasing age, female gender, and smoking, as well as the common AMD risk genotypes. When adjusted for focal pigmentary abnormalities and large drusen, the

Acknowledgments

The authors thank members of the community who volunteered their time to participate in this study.

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    Supplemental material is available at www.aaojournal.org.

    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    Supported by the National Health & Medical Research Council of Australia (program grant no.: 209057, capacity building grant no.: 251533, and enabling grant no.: 396414); VicHealth and Cancer Council Victoria (cohort recruitment); Ophthalmic Research Institute of Australia; American Health Assistance Foundation (grant no.: M2008-082); Jack Brockhoff Foundation; John Reid Charitable Trust; Perpetual Trustees; the Charles Viertel Charitable Foundation; the Lloyd and Kathleen Ansell Ophthalmology Foundation; and the Mankiewicz-Zelkin Fellowship of the University of Melbourne, Melbourne, Australis (R.P.F.); the Victorian Centre for Biostatistics (Australian Postgraduate Award and studentship funded by National Health & Medical Research Council of Australia Centre of Research Excellence grant no.: 1035261 [M.B.M.]). The Centre for Eye Research Australia is supported by the National Health & Medical Research Council of Australia (Centre of Clinical Research Excellence grant no.: 529923) and the Victorian Government (operational infrastructure support). All sponsors are located in Australia except the American Health Assistance Foundation which is located in the United States. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    Author Contributions:

    Conception and design: Finger, Chong, Robman, Giles, Guymer

    Analysis and interpretation: Finger, Chong, McGuiness, Baird, Guymer

    Data collection: Chong, Robman, Aung, Guymer

    Obtained funding: none

    Overall responsibility: Finger, Chong, McGuiness, Robman, Aung, Giles, Baird, Guymer

    Both Robert P. Finger, MD, PhD, and Elaine Chong, MBBS, PhD, contributed equally as first authors.

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