Reticular macular lesions: a review of the phenotypic hallmarks and their clinical significance

Saade, Celine; Rjh, Smith

doi:10.1111/ceo.12353

Cited by 20 publications

(16 citation statements)

References 58 publications

(244 reference statements)

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“…46 Similar to previous studies, we found pseudodrusen were more prevalent in women 7,8,10,14,21,22 and in older subjects. 10,11,14,47 However, smoking was not associated with pseudodrusen, likely because of the selective CATT participants with a high percentage of former smokers (51%) or current smokers (9%).…”

Section: Discussionsupporting

confidence: 91%

Pseudodrusen and Incidence of Late Age-Related Macular Degeneration in Fellow Eyes in the Comparison of Age-Related Macular Degeneration Treatments Trials

et al. 2016

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Purpose To evaluate the association between pseudodrusen and incidence of late age-related macular degeneration (AMD) in fellow eyes of patients with unilateral neovascular AMD (nAMD). Design Cohort study within the Comparison of AMD Treatments Trials (CATT). Participants Patients with neither nAMD nor geographic atrophy (GA) in the fellow eye at baseline. Methods Presence and type (dot, reticular, or confluent) of baseline pseudodrusen were assessed using digital color fundus photography (CFP) viewed under full color, green channel, and blue channel; red-free images; and fluorescein angiography (FA). Incidence of nAMD was based on monthly clinical examination and reading center evaluation of images at years 1 and 2. Incidence of GA was based on reading center evaluation of CFP and FA images at years 1 and 2. Associations of baseline pseudodrusen with incident nAMD and GA were summarized with adjusted risk ratios (aRRs) and their 95% confidence intervals (CIs) from multivariate Cox models, with adjustment of covariates identified through backward stepwise selection. Main Outcome Measures Incident nAMD and GA. Results Among 620 fellow eyes, 176 (28.4%) had baseline pseudodrusen (55% dot, 82% reticular, 35% confluent). Within 2 years, nAMD occurred in 54 eyes (30.7%) with pseudodrusen and in 72 eyes (16.2%) without pseudodrusen (aRR, 2.05; 95% CI, 1.43–2.93); GA occurred in 27 eyes (15.3%) with pseudodrusen and in 37 eyes (8.3%) without pseudodrusen (aRR, 1.89; 95% CI, 1.13–3.17); late AMD occurred in 73 eyes (41.5%) with pseudodrusen and in 101 eyes (22.8%) without pseudodrusen (aRR, 2.07; 95% CI, 1.51–2.83). Dot pseudodrusen were associated independently with nAMD (aRR, 2.53; 95% CI, 1.60–4.00), whereas confluent pseudodrusen were associated independently with GA (aRR, 4.35; 95% CI, 1.69–11.2). Eyes with pseudodrusen had increased incidence of late AMD regardless of whether the Age-Related Eye Diseases Study (AREDS) severity score was 2 (28.7% vs. 10.3%), 3 (34.9% vs. 13.7%), or 4 (50.5% vs. 32.0%). Conclusions In fellow eyes of CATT participants, pseudodrusen were associated independently with a higher incidence of both nAMD and GA. Dot pseudodrusen were associated with nAMD, whereas confluent pseudodrusen were associated with GA. Pseudodrusen should be considered along with the AREDS severity score for predicting late AMD.

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Section: Discussionsupporting

confidence: 91%

Pseudodrusen and Incidence of Late Age-Related Macular Degeneration in Fellow Eyes in the Comparison of Age-Related Macular Degeneration Treatments Trials

et al. 2016

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“…First, human ACAT1 or SOAT1 gene (Mendelian Inheritance in Man database 102642) is highly polymorphic and has frequent mRNA-and proteinaltering variants, for which the functional significance is currently unknown. Second, SDD are associated with increased mortality rate, which could be a manifestation of a systemic condition (25,70). If humans indeed have only limited ability to esterify cholesterol in the OS by ACAT1, then the polymorphism-determined impairment in ACAT1 activity could have a significant effect on cholesterol homeostasis in human OS.…”

Section: Cyp46a1mentioning

confidence: 99%

Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and Esterification in Photoreceptor Cells

Saadane

Mast

Dao

et al. 2016

Journal of Biological Chemistry

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The process of vision is impossible without the photoreceptor cells, which have a unique structure and specific maintenance of cholesterol. Herein we report on the previously unrecognized cholesterol-related pathway in the retina discovered during follow-up characterizations of Cyp27a1 ؊/؊ Cyp46a1 ؊/؊ mice.These animals have retinal hypercholesterolemia and convert excess retinal cholesterol into cholesterol esters, normally present in the retina in very small amounts. We established that in the Cyp27a1 ؊/؊ Cyp46a1 ؊/؊ retina, cholesterol esters are generated by and accumulate in the photoreceptor outer segments (OS), which is the retinal layer with the lowest cholesterol content. Mouse OS were also found to express the cholesterol-esterifying enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT1), but not lecithin-cholesterol acyltransferase (LCAT), and to differ from humans in retinal expression of ACAT1. Nevertheless, cholesterol esters were discovered to be abundant in human OS. We suggest a mechanism for cholesterol ester accumulation in the OS and that activity impairment of ACAT1 in humans may underlie the development of subretinal drusenoid deposits, a hallmark of age-related macular degeneration, which is a common blinding disease. We generated Cyp27a1؊/؊ mice, characterized their retina by different imaging modalities, and confirmed that unesterified cholesterol does accumulate in their OS and that there is photoreceptor apoptosis and OS degeneration in this line. Our results provide insights into the retinal response to local hypercholesterolemia and the retinal significance of cholesterol esterification, which could be cell-specific and both beneficial and detrimental for retinal structure and function.

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“…Many authors recommend using SD-OCT because it allows visualization of hyperreflective material in the subretinal space and infrared reflectance (IR) for screening over a wide area of macula. 32 Others also used fundus autofluorescence (FAF), red-free light, channel-separated color fundus photographs (CFP), and indocyanine green angiography. 26, 33 …”

Section: Introductionmentioning

confidence: 99%

Prevalence of Subretinal Drusenoid Deposits in Older Persons with and without Age-Related Macular Degeneration, by Multimodal Imaging

et al. 2016

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Purpose To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. Design Cross-sectional study. Participants A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. Methods Subjects were imaged using spectral domain optical coherence tomography (SD-OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the AREDS 9-step scale. Criteria for SDD presence were identification on ≥1 en-face modality plus SD-OCT or on ≥2 en-face modalities if absent on SD-OCT. SDD were considered present at the person-level if present in 1 or both eyes. Main outcomes measures Prevalence of SDD in participants with and without AMD. Results Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, p =0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (p<0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4x more likely to have AMD than those without SDD (95% CI 2.3–4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD-OCT and confirmed by at least one en-face modality 47% (89/190) were detected exclusively on the ONH SD-OCT volume. Conclusion SDD are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its retinal topography including peripapillary involvement resembles that of rod photoreceptors. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance.

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Reticular macular lesions: a review of the phenotypic hallmarks and their clinical significance

Cited by 20 publications

References 58 publications

Pseudodrusen and Incidence of Late Age-Related Macular Degeneration in Fellow Eyes in the Comparison of Age-Related Macular Degeneration Treatments Trials

Pseudodrusen and Incidence of Late Age-Related Macular Degeneration in Fellow Eyes in the Comparison of Age-Related Macular Degeneration Treatments Trials

Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and Esterification in Photoreceptor Cells

Prevalence of Subretinal Drusenoid Deposits in Older Persons with and without Age-Related Macular Degeneration, by Multimodal Imaging

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