Clinical and Genetic Characteristics of Japanese Patients with Age-Related Macular Degeneration and Pseudodrusen

Elfandi, Sufian; Ooto, Sotaro; Ueda-Arakawa, Naoko; Takahashi, Ayako; Yoshikawa, Munemitsu; Nakanishi, Hideo; Tamura, Hiroshi; Oishi, Akio; Yamashiro, Kenji; Yoshimura, Nagahisa

doi:10.1016/j.ophtha.2016.06.052

Cited by 14 publications

(3 citation statements)

References 33 publications

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“…33 Japan. 26,54,55 We found several factors associated with SDD, such as increasing age, female gender, higher stage of early AMD, subfoveal confluent soft drusen, disruption of ellipsoid zone, and thinner subfoveal choroidal thickness. The association with other factors such as lipid-lowering drugs deserves further investigation.…”

Section: Discussionmentioning

confidence: 89%

Subretinal Drusenoid Deposits in the Elderly in a Population-Based Study (the Montrachet Study)

Gabrielle

Seydou

Arnould

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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The aim of this study was to investigate the prevalence of subretinal drusenoid deposits (SDD) and to identify associated factors in an elderly population. METHODS. The participants of the population-based Montrachet study underwent an exhaustive ophthalmologic examination, including color fundus photography and macular spectral domain-optical coherence tomography (SD-OCT), coupled with infrared reflectance imaging. The presence of SDD and other age-related macular degeneration lesions, according to the European Eye Epidemiology SD-OCT classification of macular diseases, and subfoveal choroidal thickness were recorded. Moreover, the association of SDD and both clinical and demographic factors as well as plasma levels of vitamin E and lutein/zeaxanthin (L/Z) were analyzed. RESULTS. The mean age of patients was 82.3 6 3.8 years and 62.7% were female. The prevalence of SDD was 18.1% (n ¼ 205) in the subjects with at least one eye interpretable (n ¼ 1135). In multivariate analysis, SDD was positively associated with increasing age (OR, 4.6; 95% CI, 2.8-7.7; P < 0.001 for subjects aged >85 years), female sex (OR, 1.7; 95% CI, 1.2-2.4; P ¼ 0.005), and plasma L/Z level (OR, 1.2; 95% CI, 1.0-1.5; P ¼ 0.039), and negatively associated with lipid-lowering drugs use (OR, 0.5; 95% CI, 0.3-0.9; P ¼ 0.014 for statin medications) and subfoveal choroidal thickness (OR, 0.8; 95% CI, 0.7-0.9; P ¼ 0.002). CONCLUSIONS. The prevalence of SDD was high in subjects older than 75 years, more frequent in women, and was associated with a thinner choroid. The association with lipid-lowering drugs deserves further investigation.

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Section: Discussionmentioning

confidence: 89%

Subretinal Drusenoid Deposits in the Elderly in a Population-Based Study (the Montrachet Study)

Gabrielle

Seydou

Arnould

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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“…2 We found that dot pseudodrusen were associated with neovascular AMD, whereas confluent pseudodrusen were associated with geographic atrophy. 2 Elfandi et al 14 found no association for both ARMS2 and CFH Y402H with dot-dominant pseudodrusen vs dot-reticular pseudodrusen but found CFH I62V was more common in patients with dot-dominant pseudodrusen. Shijo et al 15 did not find any association between subtypes of pseudodrusen with CFH I62V or ARMS2.…”

Section: Resultsmentioning

confidence: 98%

Association of Single-Nucleotide Polymorphisms in Age-Related Macular Degeneration With Pseudodrusen

et al. 2018

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IMPORTANCE Previous studies investigating the association of single-nucleotide polymorphisms (SNPs) that confer increased risk of age-related macular degeneration (AMD) with pseudodrusen have yielded conflicting results and have not evaluated other AMD SNPs or pseudodrusen subtypes.OBJECTIVE To determine the association of SNPs in the complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), HtrA serine peptidase 1 (HTRA1), complement C2 (C2), complement C3 (C3), lipase C (LIPC), and complement factor B (CFB) genes with the presence of pseudodrusen and pseudodrusen subtypes (ie, dot, reticular, and confluent). DESIGN, SETTING, AND PARTICIPANTSIn this post hoc analysis of cross-sectional data from US participants in the Comparison of AMD Treatments Trials, genotyping was performed in 835 participants with TaqMan assays for the SNPs rs1061170 (Y402H variant in CFH), rs800292 (I62V variant in CFH), rs10490924 (A69S variant in ARMS2), rs11200638 (HTRA1), rs547154 (C2), rs2230199 (R102G variant in C3), rs10468017 (LIPC), and rs4151667 (L9H variant in CFB). MAIN OUTCOMES AND MEASURESPresence and subtype of baseline pseudodrusen in either eye determined using color fundus photography, red-free images, and fluorescein angiograms. RESULTS Among 835 participants enrolled for genotyping, 755 (90.4%) were evaluated for pseudodrusen. Of these, 471 (62.4%) were female and 750 (99.3%) were white, and the mean (SD) age was 78.3 (7.5) years. A total of 213 of 755 participants (28.2%) had pseudodrusen (107 [14.2%] had dot pseudodrusen, 180 [23.8%] had reticular pseudodrusen, and 102 [13.5%] had confluent pseudodrusen). After adjusting for age, sex, and smoking status, the ARMS2 risk allele T was associated with higher risk of pseudodrusen (odds ratio [OR], 1.93; 95% CI, 1.19-3.12) for TT vs GG (P = .04). A similar association was found for HTRA1 (OR, 2.04; 95% CI, 1.26-3.31) for AA vs GG (P = .03). The CFH Y402H risk allele C was associated with lower risk of pseudodrusen (OR, 0.61; 95% CI, 0.38-0.97) for CC vs TT but was not statistically significant after correcting for multiple comparison (P = .20). CFH Y402H, ARMS2, HTRA1, and C3 were significantly associated with reticular pseudodrusen.CONCLUSIONS AND RELEVANCE Among patients with neovascular AMD, the AMD risk alleles ARMS2 and HTRA1 were associated with an increased risk of pseudodrusen and the risk allele CFH Y402H was associated with lower risk of pseudodrusen, supporting findings from previous studies. Understanding the role of these SNPs in the development of pseudodrusen might improve our understanding of the pathogenesis of AMD and help develop future therapies.

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“…This is in line with previous literature that reported partly contradicting results about the association of SDD with AMD risk genes [ 3 ]. While some studies report an association with polymorphisms in the gene for CFH [ 30 , 31 ] and the ARMS2 gene [ 32 , 33 ], other studies could not find any association [ 34 – 36 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence and determinants of subretinal drusenoid deposits in patients’ first-degree relatives

Mauschitz,

Hochbein,

Klinkhammer

et al. 2023

Graefes Arch Clin Exp Ophthalmol

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Purpose Subretinal drusenoid deposits (SDDs) are distinct extracellular alteration anterior to the retinal pigment epithelium (RPE). Given their commonly uniform phenotype, a hereditary predisposition seems likely. Hence, we aim to investigate prevalence and determinants in patients’ first-degree relatives. Methods We recruited SDD outpatients at their visits to our clinic and invited their relatives. We performed a full ophthalmic examination including spectral domain–optical coherence tomography (SD-OCT) and graded presence, disease stage of SDD as well as percentage of infrared (IR) en face area affected by SDD. Moreover, we performed genetic sequencing and calculated a polygenic risk score (PRS) for AMD. We conducted multivariable regression models to assess potential determinants of SDD and associations of SDD with PRS. Results We included 195 participants, 123 patients (mean age 81.4 ± 7.2 years) and 72 relatives (mean age 52.2 ± 14.2 years), of which 7 presented SDD, resulting in a prevalence of 9.7%. We found older age to be associated with SDD presence and area in the total cohort and a borderline association of higher body mass index (BMI) with SDD presence in the relatives. Individuals with SDD tended to have a higher PRS, which, however, was not statistically significant in the multivariable regression. Conclusion Our study indicates a potential hereditary aspect of SDD and confirms the strong association with age. Based on our results, relatives of SDD patients ought to be closely monitored for retinal alterations, particularly at an older age. Further longitudinal studies with larger sample size and older relatives are needed to confirm or refute our findings.

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Clinical and Genetic Characteristics of Japanese Patients with Age-Related Macular Degeneration and Pseudodrusen

Abstract: Patients with pseudodrusen can be classified with dot-dominant or dot-ribbon type, and these subtypes usually are the same in both eyes. The distribution of CFH I62V polymorphisms may have an association with pseudodrusen subtypes.

Cited by 14 publications

References 33 publications

Subretinal Drusenoid Deposits in the Elderly in a Population-Based Study (the Montrachet Study)

Subretinal Drusenoid Deposits in the Elderly in a Population-Based Study (the Montrachet Study)

Association of Single-Nucleotide Polymorphisms in Age-Related Macular Degeneration With Pseudodrusen

Prevalence and determinants of subretinal drusenoid deposits in patients’ first-degree relatives

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