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Graefe's Archive For Clinical and... Mar 2020To provide an integrate multimodal imaging characterization of peripheral drusen in the eyes with and without macular signs of age-related macular degeneration (AMD) and...
PURPOSE
To provide an integrate multimodal imaging characterization of peripheral drusen in the eyes with and without macular signs of age-related macular degeneration (AMD) and to analyze their association with macular findings.
METHODS
In this retrospective, cross-sectional study, subjects with peripheral drusen were imaged with the Optos (Optos PLC, Dunfermline, Scotland, UK) and Spectralis devices to obtain referenced spectral domain optical coherence tomography (SD-OCT) images. Two experienced graders independently graded the ultra-widefield (UWF) pseudocolor and fundus autofluorescence (FAF) images for the presence of peripheral drusen and analyzed peripheral druse features using OCT. Main outcome measures included quantitative and qualitative assessment of peripheral drusen.
RESULTS
Fifty-seven eyes (30 subjects) were included in the analysis. Mean ± SD age was 77.6 ± 9.2 years (range 54-97 years). On pseudocolor images, graders identified the presence of drusen in all the enrolled eyes (Cohen's kappa was 1.0). On FAF images, Cohen's kappa was 0.71. In the topographical assessment, peripheral drusen were detected in 23 cases in the temporal region, in 40 cases in the nasal region, in 40 cases in the inferior region, and in 42 cases in the superior region. On SD-OCT images, peripheral drusen had a high reflective core in 97.1% of cases, while remaining drusen were characterized by a low reflective core. The macula was affected by early/intermediate AMD in 23 eyes (43.5%) and late AMD in 6 eyes (10.5%).
CONCLUSIONS
We provided an integrate multimodal imaging assessment of peripheral drusen in the eyes with and without AMD. Peripheral drusen were characterized by distinguished features that may suggest that these lesions constitute a distinct disease, rather than representing an expansion of AMD.
Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Fluorescein Angiography; Fundus Oculi; Humans; Male; Middle Aged; Multimodal Imaging; Reproducibility of Results; Retina; Retinal Drusen; Retrospective Studies; Tomography, Optical Coherence
PubMed: 31900644
DOI: 10.1007/s00417-019-04586-7 -
American Journal of Ophthalmology Sep 2002The accumulation of numerous or confluent drusen, especially in the macula, is a significant risk factor for the development of age-related macular degeneration (AMD).... (Review)
Review
PURPOSE
The accumulation of numerous or confluent drusen, especially in the macula, is a significant risk factor for the development of age-related macular degeneration (AMD). Identifying the origin and molecular composition of these deposits, therefore, has been an important, yet elusive, objective for many decades. Recently, a more complete profile of the molecular composition of drusen has emerged.
DESIGN
In this focused review, we discuss these new findings and their implications for the pathogenic events that give rise to drusen and AMD.
METHODS
Tissue specimens from one or both eyes of more than 400 human donors were examined by light, confocal or electron microscopy, in conjunction with antibodies to specific drusen-associated proteins, to help characterize the transitional events in drusen biogenesis. Quantification of messenger RNA from the retinal pigment epithelium (RPE)/choroid of donor eyes was used to determine if local ocular sources for drusen-associated molecules exist.
RESULTS
The results indicate that cellular remnants and debris derived from degenerate RPE cells become sequestered between the RPE basal lamina and Bruch's membrane. We propose that this cellular debris constitutes a chronic inflammatory stimulus, and a potential "nucleation" site for drusen formation. The entrapped cellular debris then becomes the target of encapsulation by a variety of inflammatory mediators, some of which are contributed by the RPE and, perhaps, other local cell types; and some of which are extravasated from the choroidal circulation.
CONCLUSIONS
The results support a role for local inflammation in drusen biogenesis, and suggest that it is analogous to the process that occurs in other age-related diseases, such as Alzheimer's disease and atherosclerosis, where accumulation of extracellular plaques and deposits elicits a local chronic inflammatory response that exacerbates the effects of primary pathogenic stimuli.
Topics: Aging; Eye Proteins; Humans; Macular Degeneration; Microscopy, Confocal; Pigment Epithelium of Eye; RNA, Messenger; Retinal Drusen; Retinitis
PubMed: 12208254
DOI: 10.1016/s0002-9394(02)01624-0 -
Ophthalmology. Retina Feb 2023To identify the prevalence of extramacular drusen and their role in the progression of age-related macular degeneration (AMD).
PURPOSE
To identify the prevalence of extramacular drusen and their role in the progression of age-related macular degeneration (AMD).
DESIGN
Retrospective analysis of a prospective cohort study.
PARTICIPANTS
The study was conducted in 4168 eyes (2998 participants) with intermediate AMD in one or both eyes enrolled in the Age-Related Eye Disease Study 2 (AREDS2), a 5-year multicenter study of nutritional supplements.
METHODS
Baseline 3-field 30-degree color photographs were evaluated for drusen characteristics outside the macular grid, including size, area, and location. The characteristics of extramacular drusen were compared with those of drusen within the macula.
MAIN OUTCOME MEASURES
Progression rates to late AMD.
RESULTS
Although extramacular drusen were observed in 3624 (86.9%) eyes, they represented a small area (< 0.5 mm) in 50.3% of eyes, with only 17.5% exhibiting an area of > 1 disc area. Eyes with extramacular drusen exhibited larger macular drusen size and area than eyes without extramacular drusen (P < 0.001). Extramacular drusen were not associated with progression to late AMD. The hazard ratio adjusted for baseline age, sex, smoking, AMD severity level, and reticular pseudodrusen for 4043 eyes at risk of developing late AMD over 5 years was 1.17 (95% confidence interval [CI], 0.88-1.54; P = 0.27) for geographic atrophy and 0.96 (95% CI, 0.76-1.2; P = 0.7) for neovascular AMD.
CONCLUSIONS
Extramacular drusen are commonly observed in eyes with AMD and are more frequent with an increasing drusen burden within the macula. In eyes with intermediate AMD, extramacular drusen do not confer additional risk to previously identified risk factors in progression to late AMD.
Topics: Humans; Angiogenesis Inhibitors; Prospective Studies; Retinal Drusen; Retrospective Studies; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration; Macular Degeneration
PubMed: 35940477
DOI: 10.1016/j.oret.2022.08.001 -
Current Alzheimer Research 2018Recent work on Alzheimer's disease (AD) diagnosis focuses on neuroimaging modalities; however, these methods are expensive, invasive, and not available to all patients....
BACKGROUND
Recent work on Alzheimer's disease (AD) diagnosis focuses on neuroimaging modalities; however, these methods are expensive, invasive, and not available to all patients. Ocular imaging of biomarkers, such as drusen in the peripheral retina, could provide an alternative method to diagnose AD.
OBJECTIVE
This study compares macular and peripheral drusen load in control and AD eyes.
METHODS
Postmortem eye tissues were obtained from donors with a neuropathological diagnosis of AD. Retina from normal donors were processed and categorized into younger (<55 years) and older (>55 years) groups. After fixation and dissection, 3-6 mm punches of RPE/choroid were taken in macular and peripheral (temporal, superior, and inferior) retinal regions. Oil red O positive drusen were counted and grouped into two size categories: small (<63 μm) and intermediate (63-125 μm).
RESULTS
There was a significant increase in the total number of macular and peripheral hard drusen in older, compared to younger, normal eyes (p<0.05). Intermediate hard drusen were more commonly found in the temporal region of AD eyes compared to older normal eyes, even after controlling for age (p<0.05). Among the brain and eye tissues from AD donors, there was a significant relationship between cerebral amyloid angiopathy (CAA) severity and number of temporal intermediate hard drusen (r=0.78, p<0.05).
CONCLUSION
Imaging temporal drusen in the eye may have benefit for diagnosing and monitoring progression of AD. Our results on CAA severity and temporal intermediate drusen in the AD eye are novel. Future studies are needed to further understand the interactions among CAA and drusen formation.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Biomarkers; Female; Humans; Male; Middle Aged; Retina; Retinal Drusen
PubMed: 29359670
DOI: 10.2174/1567205015666180123122637 -
The Cochrane Database of Systematic... Jul 2009Drusen are amorphous yellowish deposits beneath the sensory retina. People with drusen, particularly large drusen, are at higher risk of developing age-related macular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Drusen are amorphous yellowish deposits beneath the sensory retina. People with drusen, particularly large drusen, are at higher risk of developing age-related macular degeneration (AMD). The most common complication in AMD is choroidal neovascularisation (CNV), the growth of new blood vessels in the centre of the macula. The risk of CNV is higher among patients who are already affected by CNV in one eye.It has been observed clinically that laser photocoagulation of drusen leads to their disappearance and may prevent the occurrence of advanced disease (CNV or geographic atrophy) associated with visual loss.
OBJECTIVES
To examine the effectiveness and adverse effects of laser photocoagulation of drusen in AMD.
SEARCH STRATEGY
We searched CENTRAL, MEDLINE and EMBASE on 14 November 2008.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of laser treatment of drusen in AMD in which laser treatment had been compared with no intervention or sham treatment. Two types of trials were included. Some trials studied one eye of each patient (unilateral studies); other studies recruited patients with bilateral drusen and randomised one eye to photocoagulation or control and the fellow eye to the other group.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data. We pooled data from unilateral and bilateral studies using a random-effects model. For the bilateral studies, we estimated the within-patient correlation coefficient from one study and assumed it was valid for the others.
MAIN RESULTS
We found nine studies which randomised 2216 people: four unilateral trials, three bilateral trials and two trials that included both a unilateral and a bilateral study arm.Overall, the studies were of moderate quality. Only half of the trials reported adequate allocation sequence generation, allocation concealment and masking of visual acuity outcome assessors.Although two (of the nine) studies reported significant drusen disappearance at two years, photocoagulation did not appear to affect the development of CNV at two years follow up (nine studies, 1767 people followed up, odds ratio (OR) 1.04, 95% CI 0.71 to 1.51) or the loss of three or more lines of visual acuity (six studies, 1628 people followed up, OR 1.17, 95% CI 0.75 to 1.82).
AUTHORS' CONCLUSIONS
The trials included in this review confirm the clinical observation that laser photocoagulation of drusen leads to their disappearance. However, there is no evidence that this subsequently results in a reduction in the risk of developing CNV, geographic atrophy or visual acuity loss.
Topics: Humans; Laser Coagulation; Macular Degeneration; Randomized Controlled Trials as Topic; Retinal Drusen
PubMed: 19588397
DOI: 10.1002/14651858.CD006537.pub2 -
Der Ophthalmologe : Zeitschrift Der... Oct 1992The drusen found in Bruch's membrane represent precursors for the development of age-related macular degeneration. The pathogenetic concepts are summarized: 1. As a... (Review)
Review
The drusen found in Bruch's membrane represent precursors for the development of age-related macular degeneration. The pathogenetic concepts are summarized: 1. As a result of aging changes in the metabolism of the pigment epithelium with age, the normal structure of Bruch's membrane is destroyed. This process is associated with lipid accumulation and the development of drusen. The lipids deposited are predominantly phospholipids or neutral lipids. 2. The clinical appearance of drusen can also vary from one person to another, but individually a significant symmetry of drusen characteristics can be seen, demonstrating that drusen are the results of specific metabolic dysfunctions rather than non-specific aging products. 3. The development of specific forms of age-related macular degeneration corresponds with different drusen. Larger, more confluent and hypofluorescent drusen are associated with the development of pigment epithelium detachments. In eyes with smaller, scattered and hyperfluorescent drusen, choroidal neovascularizations are more likely. 4. Histochemically, larger, hypofluorescent drusen contain predominantly neutral lipids. In contrast, smaller, hyperfluorescent drusen consist predominantly of phospholipids. 5. The accumulation of neutral lipids in Bruch's membrane is therefore associated with Pigment epithelium detachments. These apolar lipids may produce a hydrophobic barrier in Bruch's membrane for the water transport from the retina towards the choroid. A pigment epithelium detachment can develop. 6. The deposition of polar phospholipids predisposes to the development of choroidal neovascularization. These lipids in association with the changed structure of Bruch's membrane may induce an inflammation--like reaction, resulting in the in-growth of choroidal capillaries under the pigment epithelium. The analysis of the relationship between subclinical aging changes in Bruch's membrane and different forms of age-related macular degeneration may help to identify specific risk factors and to predict the future outcome in individual eyes. This may result in differentiated treatment concepts adapted to the specific aging changes in each person.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Bruch Membrane; Child; Female; Humans; Macular Degeneration; Male; Middle Aged; Phospholipids; Pigment Epithelium of Eye; Retinal Drusen; Risk Factors
PubMed: 1304217
DOI: No ID Found -
Kidney International Reports Apr 2022Complement has been implicated in systemic lupus erythematosus (SLE) pathogenesis on the basis of the associations with inherited complement defects and genome-wide...
INTRODUCTION
Complement has been implicated in systemic lupus erythematosus (SLE) pathogenesis on the basis of the associations with inherited complement defects and genome-wide association study risk alleles, glomerular deposits, reduced serum levels, and occasional reports of retinal drusen. This study examined drusen in SLE and their clinical significance.
METHODS
This cross-sectional observational study compared individuals with SLE recruited from renal and rheumatology clinics with hospital controls. Participants were reviewed for clinical features and underwent imaging with a nonmydriatic retinal camera. Deidentified images were examined by 2 trained graders for drusen number and size using a grid overlay.
RESULTS
The cohort with SLE ( 65) comprised 55 women (85%) and 10 men (15%) with a median age of 47 years (interquartile range 35-59), where 23 (35%) were of southern European or Asian ancestry, and 32 (49%) had biopsy-proven lupus nephritis. Individuals with SLE had higher mean drusen numbers than controls (27 ± 60, 3 ± 9, respectively, = 0.001), more drusen counts ≥10 (31, 48% and 3, 5%, respectively, < 0.001), and more medium-large drusen (14, 22% and 3, 5%, respectively, < 0.001). In SLE, mean drusen counts were higher, and drusen were larger, with an estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m ( = 0.02, = 0.02, respectively) or class IV nephritis ( = 0.03, = 0.02).
CONCLUSION
Drusen composition resembles that of glomerular immune deposits. CFH controls complement activation in the extracellular matrix and risk variants are shared by drusen in macular degeneration and by SLE. CFH represents a possible treatment target for SLE especially with renal impairment.
PubMed: 35497809
DOI: 10.1016/j.ekir.2022.01.1063 -
Scientific Reports Oct 2022Retinal sensitivity may vary by subtypes of cuticular drusen. This retrospective study included 52 eyes of 32 patients with cuticular drusen. All the patients underwent...
Retinal sensitivity may vary by subtypes of cuticular drusen. This retrospective study included 52 eyes of 32 patients with cuticular drusen. All the patients underwent assessment of best-corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT), color fundus photography, fluorescein angiography, fundus autofluorescence, and microperimetry. The area occupied by drusen was counted using microperimetry. The cuticular drusen subtype was classified into 3 groups based on the SD-OCT findings. Age, BCVA, pattern standard deviation, area occupied by drusen, pupil size, and the false-positive rate were not significantly different (p > 0.05) according to the cuticular drusen type. The mean retinal sensitivity (MRS) (p = 0.063) and mean deviation (MD) (p = 0.098) showed marginally significant differences among the groups. In the subgroup analyses, type 1 and type 3 cuticular drusen showed significant differences in the MD (- 1.8 ± 2.1 vs - 5.1 ± 5.3; p = 0.011) and MRS (25.1 ± 2.2 vs 21.3 ± 5.7; p = 0.016) without differences in age, BCVA, or the area occupied by drusen (p > 0.05). The results indicate that depending on the subtypes of cuticular drusen type, the deterioration of retinal sensitivity is more likely to occur than decreased vision.
Topics: Humans; Visual Field Tests; Retrospective Studies; Retinal Drusen; Bruch Membrane; Fluorescein Angiography; Tomography, Optical Coherence
PubMed: 36266529
DOI: 10.1038/s41598-022-22513-5 -
Journal of Neuro-ophthalmology : the... Jun 2014Optic nerve head drusen (ONHD) are calcific deposits buried or at the surface of the optic disc. Although ONHD may be associated with progressive visual field defects,... (Review)
Review
BACKGROUND
Optic nerve head drusen (ONHD) are calcific deposits buried or at the surface of the optic disc. Although ONHD may be associated with progressive visual field defects, the mechanism of drusen-related field loss is poorly understood. Methods for detecting and imaging disc drusen include B-scan ultrasonography, fundus autofluorescence, and optical coherence tomography (OCT). These modalities are useful for drusen detection but are limited by low resolution or poor penetration of deep structures. This review was designed to assess the potential role of new OCT technologies in imaging ONHD.
EVIDENCE ACQUISITION
Critical appraisal of published literature and comparison of new imaging devices to established technology.
RESULTS
The new imaging modalities of enhanced depth imaging optical coherence tomography (EDI-OCT) and swept source optical coherence tomography (SS-OCT) are able to provide unprecedented in vivo detail of ONHD. Using these devices it is now possible to quantify optic disc drusen dimensions and assess integrity of neighboring retinal structures, including the retinal nerve fiber layer.
CONCLUSIONS
EDI-OCT and SS-OCT have the potential to allow better detection of longitudinal changes in drusen and neural retina and improve our understanding of drusen-related visual field loss.
Topics: Diagnostic Imaging; Humans; Optic Disk Drusen; Perceptual Disorders; Tomography, Optical Coherence; Visual Fields
PubMed: 24662838
DOI: 10.1097/WNO.0000000000000115 -
Canadian Journal of Ophthalmology.... Aug 2023
Topics: Humans; Optic Disk Drusen; Hemorrhage; Optic Disk; Retina
PubMed: 36803931
DOI: 10.1016/j.jcjo.2023.01.018