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Survey of Ophthalmology 2018A distinction between conventional drusen and pseudodrusen was first made in 1990, and more recently knowledge of pseudodrusen, more accurately called subretinal... (Review)
Review
A distinction between conventional drusen and pseudodrusen was first made in 1990, and more recently knowledge of pseudodrusen, more accurately called subretinal drusenoid deposits (SDDs), has expanded. Pseudodrusen have a bluish-white appearance by biomicroscopy and color fundus photography. Using optical coherence tomography, pseudodrusen were found to be accumulations of material internal to the retinal pigment epithelium that could extend internally through the ellipsoid zone. These deposits are more commonly seen in older eyes with thinner choroids. Histologic evaluation of these deposits revealed aggregations of material in the subretinal space between photoreceptors and retinal pigment epithelium. SDDs contain some proteins in common with soft drusen but differ in lipid composition. Many studies reported that SDDs are strong independent risk factors for late age-related macular degeneration. Geographic atrophy and type 3 neovascularization are particularly associated with SDD. Unlike conventional drusen, eyes with SDD show slow dark adaptation and poor contrast sensitivity. Outer retinal atrophy develops in eyes with regression of SDD, a newly recognized form of late age-related macular degeneration. Advances in imaging technology have enabled many insights into this condition, including associated photoreceptor, retinal pigment epithelium, and underlying choroidal changes.
Topics: Bruch Membrane; Choroidal Neovascularization; Diagnostic Techniques, Ophthalmological; Geographic Atrophy; Humans; Macular Degeneration; Ophthalmoscopy; Retinal Drusen; Retinal Pigment Epithelium; Tomography, Optical Coherence
PubMed: 29859199
DOI: 10.1016/j.survophthal.2018.05.005 -
Eye (London, England) Jan 2021The pachychoroid disease spectrum encompasses seven major retinal conditions including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV),... (Review)
Review
The pachychoroid disease spectrum encompasses seven major retinal conditions including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and pachychoroid neovasculopathy or type I macular neovascularisation (MNV) secondary to chronic persistent thickening and dysfunction of the choroidal vasculature. Drusen are focal yellow-white deposits of extracellular debris, which consist of complement proteins, esterified and nonesterified cholesterol, apolipoproteins, carbohydrates, and trace elements, above the retinal pigment epithelium (RPE) or between the RPE and Bruch's membrane. Although drusen are an essential disease precursor of advanced age-related macular degeneration (AMD), a new entity "pachydrusen" has been identified to be associated with some of the enitites that constitute the pachychoroid spectrum. It remains to be determined what the exact differences are between soft drusen, pseudodrusen, and pachydrusen in terms of phenotype, genotype, and pathogenesis. Improving our knowledge in these areas will inevitably improve our understanding of their clinical significance especially as in disease prediction in AMD and the pachychroid spectrum disorders. It remains controversial whether PCV is a subtype of AMD. Understanding the pathogenesis of different types of drusen may also help in addressing if phenotype and/or genotype of type 1 MNV associated with pachychoroid are similar to type 1 MNV related to AMD. Furthermore, because pachydrusen links two pachychoroid diseases, CSC and PCV, it is also of great interest to investigate if CSC is an early stage or a predictor of PCV in future research. In this review, we share our experience in clinical practice and the latest published evidence-based literature to emphasize the differences and similarities in morphology, pathogenesis, and clinical significance of drusen and pachydrusen, a new member of the pachychoroid spectrum disorders.
Topics: Central Serous Chorioretinopathy; Choroid; Fluorescein Angiography; Humans; Retina; Retinal Drusen
PubMed: 33208847
DOI: 10.1038/s41433-020-01265-4 -
Clinical Ophthalmology (Auckland, N.Z.) 2017Age-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... (Review)
Review
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 associated with late AMD, especially geographic atrophy, type 2 and 3 choroidal neovascularization, which, in turn, are less common in typical AMD. RPD identification is not straightforward at fundus examination, and their identification should employ at least 2 different imaging modalities. In this narrative review, we embrace all aspects of RPD, including history, epidemiology, histology, imaging, functional test, natural history and therapy.
PubMed: 29033536
DOI: 10.2147/OPTH.S130165 -
Scientific Reports Apr 2022This study aimed to describe the clinical characteristics of age-related macular degeneration (AMD) eyes with both cuticular drusen (CD) and reticular pseudodrusen...
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.
Topics: Choroid; Female; Fluorescein Angiography; Humans; Macular Degeneration; Retina; Retinal Drusen; Tomography, Optical Coherence
PubMed: 35383241
DOI: 10.1038/s41598-022-09608-9 -
Scientific Reports Apr 2021The natural history and clinical significance of pachydrusen is unclear. This study aims to compare the longitudinal changes of eyes with pachydrusen and soft drusen and...
The natural history and clinical significance of pachydrusen is unclear. This study aims to compare the longitudinal changes of eyes with pachydrusen and soft drusen and progression to exudative macular neovascularisation (MNV). Patients with a diagnosis of MNV in one eye only and the fellow eye was selected as the study eye. Study eyes were required to have pachydrusen or soft drusen on fundus photographs and follow up of at least 2 years or until exudative MNV occurred. Systematic grading was performed at baseline and change in drusen area and onset of exudative MNV recorded over the period of follow up. A total of 75 eyes from 75 patients (29 with pachydrusen and 46 with soft drusen) were included. There was no difference in the rate of progression to exudative MNV in the soft and pachydrusen groups (13.3% versus 24.1%, p = 0.38). Pachydrusen, as compared to soft drusen, was associated with polypoidal choroidal vasculopathy subtype (85.7% versus 16.7%, p < 0.01) and the location of exudation was co-localised with soft drusen but not with pachydrusen. There was a higher rate of increase in soft drusen area compared to pachydrusen area (27.7 ± 31.9%/year versus 8.7 ± 12.4%/year respectively, p < 0.01). We found no difference in the proportion of eyes that developed exudative MNV in this study however characterisation of drusen evolution patterns revealed a strong association with exudative MNV subtype.
Topics: Aged; Choroidal Neovascularization; Disease Progression; Female; Humans; Macular Degeneration; Male; Retinal Drusen; Tomography, Optical Coherence
PubMed: 33820941
DOI: 10.1038/s41598-021-87083-4 -
Eye (London, England) May 2018The first descriptions of ageing macula disorder (AMD), be it under other names, appeared in 1855 and 1868. The earliest accounts of AMD linked the presence of drusen... (Review)
Review
The first descriptions of ageing macula disorder (AMD), be it under other names, appeared in 1855 and 1868. The earliest accounts of AMD linked the presence of drusen with visual loss. It took a century before these connections between drusen and AMD were generally accepted by medical science and in clinical articles. The first signs of AMD appear in the region of the choriocapillaris, Bruch's membrane and the retinal pigment epithelium. The pathogenesis of drusen and of AMD is still uncertain. This is reflected in the wide variation in nomenclature of both, since the first publications.
Topics: History, 19th Century; History, 20th Century; History, 21st Century; Humans; Macular Degeneration; Retinal Drusen; Terminology as Topic
PubMed: 29424832
DOI: 10.1038/eye.2017.298 -
The British Journal of Ophthalmology Sep 2022To provide a comprehensive multimodal retinal imaging characterisation of patients with North Carolina macular dystrophy (NCMD).
BACKGROUND/AIM
To provide a comprehensive multimodal retinal imaging characterisation of patients with North Carolina macular dystrophy (NCMD).
METHODS
Clinical evaluation and retinal imaging in six families.
RESULTS
Twenty-one subjects showed phenotypic characteristics of NCMD . Small drusen-like deposits were found in all affected individuals, either tightly grouped in the macula, or surrounding atrophic or fibrotic macular alterations. These small subretinal lesions showed an increased fundus autofluorescence and were associated with only mild irregularities on optical coherence tomography imaging. Similar drusen-like deposits were regularly seen in the peripheral fundus, predominantly temporally and often with a radial distribution. Two patients showed a bilateral chorioretinal atrophy and two had a macular neovascularisation (MNV). Findings from follow-up examinations were available from 11 patients. The retinal phenotype remained overall stable, except for two patients: one patient with atrophy showed a distinct growth of the atrophic lesions on longitudinal AF imaging over a review period of 14 years. One patient with MNV showed a unilateral decline of best-corrected visual acuity. Genetic testing identified the single nucleotide variant chr6:100040987G>C upstream of the gene in all family members with NCMD phenotype.
CONCLUSION
Patients with NCMD show a characteristic retinal phenotype and distribution of drusen that differ from drusen in patients with age-related macular degeneration. Although the prognosis of this developmental condition is overall better than for other macular diseases with drusen, patients may be at risk of developing MNV or enlargement of pre-existing atrophy.
Topics: Atrophy; Corneal Dystrophies, Hereditary; Fluorescein Angiography; Humans; Pedigree; Phenotype; Retinal Drusen; Tomography, Optical Coherence
PubMed: 33785507
DOI: 10.1136/bjophthalmol-2021-318815 -
Retina (Philadelphia, Pa.) Feb 2024To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography.
PURPOSE
To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography.
METHOD
From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy.
RESULTS
From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy.
CONCLUSION
The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.
Topics: Humans; Macular Degeneration; Retina; Retinal Drusen; Retinal Pigment Epithelium; Tomography, Optical Coherence; Fluorescein Angiography; Atrophy; Retrospective Studies
PubMed: 37756671
DOI: 10.1097/IAE.0000000000003945 -
Japanese Journal of Ophthalmology Jan 2023Drusen are extracellular material considered a precursor lesion to advanced age-related macular degeneration (AMD), located either on the retinal pigment epithelium... (Review)
Review
Drusen are extracellular material considered a precursor lesion to advanced age-related macular degeneration (AMD), located either on the retinal pigment epithelium (RPE) or the sub-RPE; they contain various proteins associated with inflammation and lipids. Previous studies suggest that the lifecycle of drusen varies depending on drusen type and size. In general, conventional drusen grow and aggregate/coalesce in the first stage, and in the second stage, they regress with or without showing RPE atrophy. The risk of advanced AMD also varies depending on the drusen and drusenoid deposit types' along with their size and RPE abnormalities. In eyes with macular neovascularization (MNV), specific drusen/drusenoid deposits are closely associated with the MNV subtype. Recently, pachychoroid-associated drusen (pachydrusen) were proposed and clinical findings regarding this entity have been accumulating, as more attention is focused on drusen as well as pachychoroid diseases. With the advance in imaging modalities, various modalities can show specific characteristics depending on drusen types. To assess the risk of advanced AMD, it is essential for physicians to have accurate clinical knowledge about each druse/drusenoid lesion and correctly evaluate its imaging characteristics using multimodal imaging. This review summarizes the latest clinical knowledge about each druse/drusenoid lesions and documents their imaging characteristics on multimodal imaging, allowing clinicians to better manage patients and stratify the risk of developing advanced AMD. The most representative cases are illustrated, which can be helpful in the differential diagnosis of drusen and drusenoid deposits.
Topics: Humans; Macular Degeneration; Retinal Drusen; Tomography, Optical Coherence; Retinal Pigment Epithelium; Multimodal Imaging; Fluorescein Angiography
PubMed: 36477878
DOI: 10.1007/s10384-022-00943-y -
Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies.Investigative Ophthalmology & Visual... Mar 2018AMD is a major cause of legal blindness in older adults approachable through multidisciplinary research involving human tissues and patients. AMD is a... (Review)
Review
AMD is a major cause of legal blindness in older adults approachable through multidisciplinary research involving human tissues and patients. AMD is a vascular-metabolic-inflammatory disease, in which two sets of extracellular deposits, soft drusen/basal linear deposit (BLinD) and subretinal drusenoid deposit (SDD), confer risk for end-stages of atrophy and neovascularization. Understanding how deposits form can lead to insights for new preventions and therapy. The topographic correspondence of BLinD and SDD with cones and rods, respectively, suggest newly realized exchange pathways among outer retinal cells and across Bruch's membrane and the subretinal space, in service of highly evolved, eye-specific physiology. This review focuses on soft drusen/BLinD, summarizing evidence that a major ultrastructural component is large apolipoprotein B,E-containing, cholesterol-rich lipoproteins secreted by the retinal pigment epithelium (RPE) that offload unneeded lipids of dietary and outer segment origin to create an atherosclerosis-like progression in the subRPE-basal lamina space. Clinical observations and an RPE cell culture system combine to suggest that soft drusen/BLinD form when secretions of functional RPE back up in the subRPE-basal lamina space by impaired egress across aged Bruch's membrane-choriocapillary endothelium. The soft drusen lifecycle includes growth, anterior migration of RPE atop drusen, then collapse, and atrophy. Proof-of-concept studies in humans and animal models suggest that targeting the "Oil Spill in Bruch's membrane" offers promise of treating a process in early AMD that underlies progression to both end-stages. A companion article addresses the antecedents of soft drusen within the biology of the macula.
Topics: Apolipoproteins B; Apolipoproteins E; Humans; Macular Degeneration; Retinal Drusen; Retinal Pigment Epithelium
PubMed: 30357336
DOI: 10.1167/iovs.18-24882