Spotlight on reticular pseudodrusen.
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ABSTRACT:
SUBMITTER: Rabiolo A
PROVIDER: S-EPMC5614782 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
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Spotlight on reticular pseudodrusen.
Rabiolo Alessandro A Sacconi Riccardo R Cicinelli Maria Vittoria MV Querques Lea L Bandello Francesco F Querques Giuseppe G
Clinical ophthalmology (Auckland, N.Z.) 20170920
Age-related macular degeneration (AMD) is a leading cause of vision loss in patients >50 years old. The hallmark of the disease is represented by the accumulation of extracellular material between retinal pigment epithelium and the inner collagenous layer of Bruch's membrane, called drusen. Although identified almost 30 years ago, reticular pseudodrusen (RPD) have been recently recognized as a distinctive phenotype. Unlike drusen, they are located in the subretinal space. RPD are strongly associ ...[more]
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Project description:PurposeTo characterize the association of reticular pseudodrusen (RPD) with late-onset retinal degeneration (L-ORD) using multimodal imaging.DesignProspective, 2-center, longitudinal case series.ParticipantsTwenty-nine patients with L-ORD.MethodsAll patients were evaluated within a 3-year interval with near-infrared reflectance, fundus autofluorescence, and spectral-domain OCT. In addition, a subset of patients also underwent indocyanine green angiography, fundus fluorescein angiography, mesopic microperimetry, and multifocal electroretinography.Main outcome measuresPrevalence, topographic distribution, and temporal phenotypic changes of RPD in L-ORD.ResultsA total of 29 patients with molecularly confirmed L-ORD were included in this prospective study. Reticular pseudodrusen was detected in 18 patients (62%) at baseline, 10 of whom were men. The prevalence of RPD varied with age. The mean age of RPD patients was 57.3 ± 7.2 years. Reticular pseudodrusen was not seen in patients younger than the fifth decade of life (n = 3 patients) or in the eighth decade of life (n = 5 patients). Reticular pseudodrusen were found commonly in the macula with relative sparing of the fovea and also were identified in the peripheral retina. The morphologic features of RPD changed with follow-up. Two patients (3 eyes) demonstrated RPD regression.ConclusionsReticular pseudodrusen is found frequently in patients with L-ORD and at a younger age than in individuals with age-related macular degeneration (AMD). Reticular pseudodrusen exhibits quick formation and collapse, change in type and morphologic features with time, and relative foveal sparing and also has a peripheral retinal location in L-ORD.
| S-EPMC8217414 | biostudies-literature
Project description:To investigate genetic, environmental, and systemic risk factors in prospectively identified subjects with the age-related macular degeneration (AMD) phenotypes of (1) reticular pseudodrusen without large soft drusen and (2) large soft drusen without reticular pseudodrusen.Prospective case-case comparison.In a clinical practice setting, patients with AMD were sequentially screened using clinical examination and scanning laser ophthalmoscopy imaging to prospectively identify subjects (n = 73) with the phenotypes of (1) reticular pseudodrusen without large soft drusen (n = 30) or (2) large soft drusen without reticular pseudodrusen (n = 43). Subjects were genotyped for 2 alleles associated with AMD, age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH). A questionnaire was administered to collect history of smoking, hypertension, diabetes, and hyperlipidemia, as well as personal and family history of AMD.The reticular pseudodrusen group was older (median age 87 vs 81 years, P = .04) and had more female subjects (83.3% vs 48.8%, P = .003), later ages of AMD onset (83 vs 70 years, P = .0005), and a greater frequency of hypertension (76.7% vs 55.8%, P = .08). No significant differences were found in the distribution of the ARMS2 risk allele (P = .4) between the reticular pseudodrusen (homozygous = 20.0%; heterozygous = 56.7%) and large soft drusen (homozygous = 19.0%; heterozygous = 42.9%) phenotypes, or in the distribution of the CHF risk allele (P = .7) between the reticular pseudodrusen (homozygous = 26.7%; heterozygous = 56.7%) and large soft drusen (homozygous = 21.4%; heterozygous = 66.7%) phenotypes.The reticular pseudodrusen phenotype was associated with increased age, later age of AMD onset, and female sex.
| S-EPMC4115805 | biostudies-literature
Project description:ImportanceAlthough retinal multimodal imaging is needed for diagnosing reticular pseudodrusen (RPD), the incidence of RPD in the general population typically has been assessed only using fundus photographs, which may underestimate their incidence.ObjectivesTo describe the incidence of RPD using retinal color photographs, spectral-domain optical coherence tomography scans, fundus autofluorescence, and near-infrared reflectance images among individuals 77 years of age or older and to analyze the associated risk factors of RPD.Design, setting, and participantsThe ALIENOR (Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires) Study is a cohort of French individuals 77 years of age or older. Data for this study were collected between February 22, 2011, and February 15, 2017, with a mean (SD) follow-up of 3.7 (1.0) years (range, 1.2-5.6 years). At baseline, 501 individuals were eligible to participate. Of 1002 eyes, 197 had prevalent RPD, advanced age-related macular degeneration, or ungradable images. Of the remaining 805 eyes, 333 were missing follow-up data; therefore, the statistical analyses included data from 472 eyes. Data management and statistical analyses were performed between March 15, 2017, and April 5, 2019.Main outcomes and measuresReticular pseudodrusen were considered as present if detected by at least 2 of the following imaging methods: color fundus photographs, fundus autofluorescence, near-infrared reflectance, and spectral-domain optical coherence tomography images.ResultsOf the 472 eyes analyzed, 263 (55.7%) were from female participants, and the mean (SD) age was 81.9 (3.2) years. Forty-three eyes developed RPD, corresponding to an annual incidence rate of 2.9% (95% CI, 1.9%-4.4%) per participant and an estimated 5-year risk of 13.5%. In multivariable analysis, 4 risk factors of incident RPD were identified: subfoveal choroidal thinning (hazard ratio [HR], 0.99; 95% CI, 0.99-1.00 per 10-?m decrease in thickness; P?=?.02) and the presence of the minor allelic variants rs10490924 for ARMS2 (HR, 3.57; 95% CI, 1.80-7.10; P?<?.001), rs1061170 for CFH (HR, 2.12; 95% CI, 1.02-4.41; P?=?.04), and rs10468017 for LIPC (HR, 2.57; 95% CI, 1.37-4.82; P?=?.003). Lipophilic statin therapy was associated with a lower incidence of RPD (HR, 0.13; 95% CI, 0.02-0.74; P?=?.02).Conclusions and relevanceWith the use of multimodal imaging, the RPD incidence rate was higher than previously reported in other population-based studies using fundus color images. Individuals with subfoveal choroidal thinning or carrying minor allelic variants for ARMS2, CFH, or LIPC had an increased risk for RPD, whereas lipophilic statin therapy was associated with a lower incidence.
| S-EPMC7068673 | biostudies-literature
Project description:Reticular pseudodrusen (RPD) could be present not only in the posterior pole but extramacular area also as a confluent morphological pattern. Thus RPD can be classified by the fundus distribution for the assessment of visual prognosis. The electrophysiological function in eyes with reticular pseudodrusen (RPD), showing various fundus distribution were evaluated using full-field electroretinogram (ERG). Retinal distribution of RPD was divided into three types (localized, intermediate, and diffuse) according to the extent of involvement of retinal areas by fundus photograph montages. RPD were present with the diffuse type in 21 eyes (25.6%), with the intermediate type in 30 eyes (36.6%), and with the localized type in 31 eyes (37.8%). The average age was 74.76 ± 4.52 (range, 65-81) years in the diffuse type, 72.47 ± 9.13 (range, 55-91) years in the intermediate type, and 70.26 ± 7.77 (range, 61-89) years in the localized type. The mean amplitudes of the scotopic rod response, scotopic maximal combined response, oscillatory potentials (OP), photopic cone response, and 30Hz cone flicker response were more decreased in the diffuse, intermediate, and localized types in order, except for the photopic cone a-wave response. The diffuse type showed reduced amplitudes of ERG responses than the normal control group under all testing conditions except for the photopic a-wave response, and differences were statistically significant with the age restriction and adjustment methods (Bonferroni-corrected P < 0.05). The mean implicit times of ERG responses were significantly delayed in the diffuse type in the photopic b-wave. (Bonferroni-corrected P < 0.05). Extensive retinal involvement of RPD correlates with severely reduced electrophysiological retinal function. This acquired form of decreased electrophysiological function should be regarded as different from those of hereditary retinal degeneration.
| S-EPMC6114915 | biostudies-literature
Project description:There is a lack of treatment aimed at the regression of reticular pseudodrusen (RPD) secondary to age-related macular degeneration (AMD). The aim of this prospective, pilot study is to evaluate the safety and short-term efficacy of subthreshold laser treatment (SLT) in patients affected by RPD secondary to dry AMD (dAMD). Twenty eyes of 20 patients (mean age 78.4 ± 6.8 years) with RPD secondary to dAMD were prospectively enrolled. All patients were treated in an extrafoveal area of 1.27 mm2 using end-point management yellow subthreshold laser and followed for 3 months. Best-corrected visual acuity was 0.140 ± 0.09 LogMAR at the baseline and no changes were observed during the follow-up (p = 0.232). No significant worsening was disclosed before and after the treatment analyzing the macular sensitivity of the treated area (p = 0.152). No topical and/or systemic side effects were disclosed during the 3-month follow-up. The distribution among the RPD stages changed after the treatment (p < 0.001). In detail, in the treated area, we observed a significant increase in the number of Stage 1 RPD during the follow-up (p = 0.002), associated with a significant decrease of Stage 3 RPD (p = 0.020). Outer nuclear layer (ONL) thickness analysis showed a significant increase after the treatment associated with RPD regression (p = 0.001). End-point management SLT appears a safe treatment for RPD secondary to dAMD, showing short-term safety outcomes. Our results suggest that SLT could be effective in inducing a RPD regression in terms of RPD stage and ONL thickening.
| S-EPMC7838261 | biostudies-literature
Project description:PurposeThe purpose of this study was to analyze genetic and nongenetic associations with reticular pseudodrusen (RPD) in patients with and without age-related macular degeneration (AMD).MethodsThis case-control study included 2,719 consecutive subjects from the prospective multicenter European Genetic Database (EUGENDA). Color fundus photographs and optical coherence tomography (OCT) scans were evaluated for the presence of AMD and RPD. Association of RPD with 39 known AMD polymorphisms and various nongenetic risk factors was evaluated. Stepwise backward variable selection via generalized linear models (GLMs) was performed based on models including the following: a) age, sex, and genetic factors and b) all predictors. Receiver operating characteristic (ROC) curves and the areas under the curve (AUCs) were determined.ResultsRPD were present in 262 cases (no AMD, n = 9 [0.7%; early/intermediate AMD, n = 75 [12.4%]; late AMD, n = 178 [23.8%]). ROC analysis of the genetic model including age, APOE rs2075650, ARMS2 rs10490924, CFH rs800292, CFH rs12144939, CFI rs10033900, COL8A1 rs13081855, COL10A1 rs3812111, GLI3 rs2049622, and SKIV2L rs4296082 revealed an AUC of 0.871. Considering all possible predictors, backward selection revealed a slightly different set of genetic factors, as well as the following nongenetic risk factors: smoking, rheumatoid arthritis, steroids, antiglaucomatous drugs, and past sunlight exposure; the results showed an AUC of 0.886.ConclusionsRPD share a variety of genetic and nongenetic risk factors with AMD. Future AMD grading systems should integrate RPD as an important risk phenotype.
| S-EPMC8763662 | biostudies-literature
Project description:This study aimed to describe the clinical characteristics of age-related macular degeneration (AMD) eyes with both cuticular drusen (CD) and reticular pseudodrusen (RPD). Clinical records of patients diagnosed with CD or RPD with multimodal imaging was reviewed for patients diagnosed with both CD and RPD. The distribution patterns of CD (macular and diffuse type) and RPD (localized, intermediate, and diffuse type), presence of soft drusen, large drusen (> 200 µm), variant subretinal drusenoid deposits, and macular complications were investigated. Of the 220 eyes of 110 patients diagnosed with CD and 926 eyes of 463 patients diagnosed with RPD, 13 eyes of seven patients met the diagnostic criteria for both CD and RPD. The mean age at initial presentation was 71.4 ± 8.8 years and six patients were female. The mean subfoveal choroidal thickness was 143.8 ± 25.1 µm. The distribution of CD was of the macular type in all eyes. Distribution of RPD was localized in 11 eyes (84.6%) and intermediate in two eyes (15.4%). Soft drusen, large drusen, and variant subretinal drusenoid deposits were present in 13 (100%), 12 (92.3%) and, seven (53.8%) eyes, respectively. Macular neovascularization was observed in two eyes (15.4%). CD and RPD can coexist in eyes with AMD. Multimodal imaging should be used for AMD eyes with features suggestive of CD and RPD, considering the high likelihood of developing late AMD.
| S-EPMC8983695 | biostudies-literature
Project description:PurposeTo study choriocapillaris blood flow in age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA) and study its correlation to visual acuity (VA) in eyes with reticular pseudodrusen (RPD) vs those with drusen without RPD (drusen).DesignCross-sectional study.MethodsPatients with either drusen or RPD in early AMD underwent OCTA imaging of the superior, inferior, and/or nasal macula. We quantified "percent choriocapillaris area of nonperfusion" (PCAN) in eyes with RPD vs those with drusen. We assessed the repeatability of PCAN and its correlations with VA.ResultsTwenty-nine eyes of 26 patients with RPD and 21 eyes of 16 age-matched AMD patients with drusen were included. Qualitatively, the choriocapillaris in areas with RPD showed focal dark regions without flow signal on OCTA (nonperfusion). The repeatability coefficient of PCAN was 0.49%. Eyes with RPD had significantly greater PCAN compared with eyes with drusen (7.31% and 3.88%, respectively; P < .001). We found a significant correlation between PCAN and VA for the entire dataset (r = 0.394, P = .005). When considering eyes with RPD separately, this correlation was stronger (r = 0.474, P = .009) but lost significance when considering eyes with drusen separately (r = 0.175, P = .45).ConclusionsEyes with RPD have significantly larger areas of choriocapillaris nonperfusion compared with eyes with drusen and no RPD. The correlation between PCAN and VA in this RPD population provides a potential mechanistic explanation for vision compromise in RPD compared with other forms of drusen in AMD.
| S-EPMC5253325 | biostudies-literature
Project description:ObjectiveSystemic activation of the complement system in intermediate age-related macular degeneration (AMD) is understudied. Moreover, links between the presence of reticular pseudodrusen (RPD) and systemic complement dysregulation have not been studied. The aim of this study was to determine if there is a difference in plasma complement factor levels in intermediate AMD compared with controls, and if complement levels are related to the presence of RPD.Methods and analysisLevels of complement factors C1q (µg/mL), C4 (µg/mL), C2 (µg/mL), Mannose Binding Lectin (ng/mL), C4b (µg/mL), C3 (µg/mL), factor B (µg/mL), factor D (µg/mL), properdin (µg/mL), C3a (ng/mL), iC3b/C3b (ng/mL), Ba (ng/mL), factor H (µg/mL), factor I (µg/mL), C5 (µg/mL), C5a (pg/mL) and SC5b-9 (ng/mL) were measured in plasma.Results109 cases and 65 controls were included in the study. Thirty-nine (36%) cases had RPD. Significantly lower systemic levels of: C1q (OR 0.96, 95% CI 0.94 to 0.98), factor B (OR 0.98, 95% CI 0.96 to 0.99), iC3b/C3b (OR 0.97, 95% CI 0.95 to 0.98), factor H (OR 0.99, 95% CI 0.98 to 0.99), factor I (OR 0.83, 95% CI 0.77 to 0.89) and C5 (OR 0.94, 95% CI 0.90 to 0.98) were found in cases versus controls. Significantly elevated levels of: C2 (OR 1.29, 95% CI 1.07 to 1.59), C3a (OR 1.03, 95% CI 1.01 to 1.05) Ba (OR 1.03, 95% CI 1.01 to 1.05) and C5a (OR 1.04, 95% CI 1.02 to 1.07) were found in cases versus controls. Systemic levels of complement factors measured were not related to the presence of RPD.ConclusionsLevels of several systemic complement pathway factors were found to be altered in intermediate AMD. Systemic levels of complement factors were not related to RPD.
| S-EPMC7254108 | biostudies-literature
Project description:PurposeWe investigate whether ocular and person-based characteristics were associated with dark adaptation (DA).DesignCross-sectional, single-center, observational study.ParticipantsOne hundred sixteen participants older than 50 years of age with a range of age-related macular degeneration (AMD) severity.MethodsParticipants underwent best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination, and multimodal imaging. Presence of reticular pseudodrusen (RPD) was assessed by masked grading of fundus images and was confirmed with optical coherence tomography. Eyes also were graded for AMD features (drusen, pigmentary changes, late AMD) to generate person-based AMD severity groups. One eye was designated the study eye for DA testing. Nonparametric statistical testing was performed on all comparisons.Main outcome measuresThe primary outcome of this study was the rod intercept time (RIT), which is defined as the time for a participant's visual sensitivity to recover to a stimulus intensity of 5×10(-3) cd/m(2) (a decrease of 3 log units), or until a maximum test duration of 40 minutes was reached.ResultsA total of 116 study eyes from 116 participants (mean age, 75.4±9.4 years; 58% female) were analyzed. Increased RIT was associated significantly with increasing AMD severity, increasing age (r = 0.34; P = 0.0002), decreasing BCVA (r = -0.54; P < 0.0001), pseudophakia (P = 0.03), and decreasing subfoveal choroidal thickness (r = -0.27; P = 0.003). Study eyes with RPD (15/116 [13%]) had a significantly greater mean RIT compared with eyes without RPD in any AMD severity group (P < 0.02 for all comparisons), with 80% reaching the DA test ceiling.ConclusionsImpairments in DA increased with age, worse visual acuity, presence of RPD, AMD severity, and decreased subfoveal choroidal thickness. Analysis of covariance found the multivariate model that best fit the data included age, AMD group, and presence of RPD (R(2) = 0.56), with the presence of RPD conferring the largest parameter estimate.
| S-EPMC4836058 | biostudies-literature