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Graefe's Archive For Clinical and... Mar 2024To examine histological characteristics and differences between drusen beneath the retinal pigment epithelium (small hard drusen) located in the macula and located in...
PURPOSE
To examine histological characteristics and differences between drusen beneath the retinal pigment epithelium (small hard drusen) located in the macula and located in the parapapillary region.
METHODS
We histomorphometrically examined human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma.
RESULTS
The study included 106 eyes (age, 62.6 ± 15.2 years) with macular drusen (n = 7 globes) or parapapillary drusen (n = 29 eyes) and 70 eyes without drusen. In all drusen, periodic-acid-Schiff-positive material was located between the RPE basal membrane and the inner collagenous layer of Bruch's membrane (BM). Macular drusen as compared with parapapillary drusen had lower height (15.2 ± 10.1 µm versus 34.3 ± 19.8 µm; P = 0.003), while both groups did not differ significantly in basal drusen width (74.0 ± 36.3 µm versus 108.7 ± 101.0 µm; P = 0.95). Eyes with macular drusen and eyes without drusen did not differ significantly in BM thickness (2.74 ± 0.44 µm versus 2.55 ± 0.88 µm; P = 0.57) or in RPE cell density (35.4 ± 10.4 cells/480 µm versus 32.8 ± 7.5 cells/480 µm; P = 0.53), neither in the drusen region nor in the drusen vicinity, while BM thickness (4.60 ± 1.490 µm; P < 0.001) and RPE cell density (56.9 ± 26.8 cells/480 µm; P = 0.005) were higher at the parapapillary drusen. Eyes with macular drusen, eyes with parapapillary drusen, and eyes without drusen did not differ significantly in choriocapillaris density (all P > 0.10) and thickness (all P > 0.35). Limitations of the study, among others, were a small number and size of drusen examined, diseases leading to enucleation, lack of serial sections, limited resolution of light microscopy, and enucleation-related and histological preparation-associated artefacts.
CONCLUSIONS
The findings of this study, also taking into account its methodological limitations, suggest that macular drusen and parapapillary drusen shared the morphological feature of periodic-acid-Schiff-positive material between the RPE basal membrane and BM and that they did not vary significantly in choriocapillaris thickness and density. RPE cell density and BM thickness were higher in parapapillary drusen than in macular drusen.
PubMed: 38472430
DOI: 10.1007/s00417-024-06438-5 -
Ophthalmic & Physiological Optics : the... Mar 2020Cones are at great risk in a wide variety of retinal diseases, especially when there is a harsh microenvironment and retinal pigment epithelium is damaged. We provide... (Review)
Review
PURPOSE
Cones are at great risk in a wide variety of retinal diseases, especially when there is a harsh microenvironment and retinal pigment epithelium is damaged. We provide established and new methods for assessing cones and retinal pigment epithelium, together with new results. We investigated conditions under which cones can be imaged and could guide light, despite the proximity of less than ideal retinal pigment epithelium.
RECENT FINDINGS
We used a variety of imaging methods to detect and localise damage to the retinal pigment epithelium. As age-related macular degeneration is a particularly widespread disease, we imaged clinical hallmarks: drusen and hyperpigmentation. Using near infrared light provided improved imaging of the deeper fundus layers. We compared confocal and multiply scattered light images, using both the variation of detection apertures and polarisation analysis. We used optical coherence tomography to examine distances between structures and thickness of retinal layers, as well as identifying damage to the retinal pigment epithelium. We counted cones using adaptive optics scanning laser ophthalmoscopy. We compared the results of five subjects with geographic atrophy to data from a previous normative ageing study. Using near infrared imaging and layer analysis of optical coherence tomography, the widespread aspect of drusen became evident. Both multiply scattered light imaging and analysis of the volume in the retinal pigment epithelial layer from the optical coherence tomography were effective in localising drusen and hyperpigmentation beneath the photoreceptors. Cone photoreceptors in normal older eyes were shorter than in younger eyes. Cone photoreceptors survived in regions of atrophy, but with greatly reduced and highly variable density. Regular arrays of cones were found in some locations, despite abnormal retinal pigment epithelium. For some subjects, the cone density was significantly greater than normative values in some retinal locations outside the atrophy.
SUMMARY
The survival of cones within atrophy is remarkable. The unusually dense packing of cones at some retinal locations outside the atrophy indicates more fluidity in cone distribution than typically thought. Together these findings suggest strategies for therapy that includes preserving cones.
Topics: Aging; Humans; Macular Degeneration; Ophthalmoscopy; Optics and Photonics; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium; Tomography, Optical Coherence; Visual Acuity
PubMed: 32017191
DOI: 10.1111/opo.12670 -
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 -
Retina (Philadelphia, Pa.) Aug 2023To evaluate visual acuity and morphologic changes after photobiomodulation (PBM) for patients affected with large soft drusen and/or drusenoid pigment epithelial...
PURPOSE
To evaluate visual acuity and morphologic changes after photobiomodulation (PBM) for patients affected with large soft drusen and/or drusenoid pigment epithelial detachment associated with dry age-related macular degeneration.
METHOD
Twenty eyes with large soft drusen and/or drusenoid pigment epithelial detachment age-related macular degeneration were included and treated using the LumiThera Valeda Light Delivery System. All patients underwent two treatments per week for 5 weeks. Outcome measures included best-corrected visual acuity, microperimetry-scotopic testing, drusen volume, central drusen thickness, and quality of life score at baseline and month 6 (M6) follow-up. Data of best-corrected visual acuity, drusen volume, and central drusen thickness were also recorded at week 5 (W5).
RESULTS
Best-corrected visual acuity significantly improved at M6 with a mean score gain of 5.5 letters ( P = 0.007). Retinal sensitivity decreased by 0.1 dB ( P = 0.17). The mean fixation stability increased by 0.45% ( P = 0.72). Drusen volume decreased by 0.11 mm 3 ( P = 0.03). Central drusen thickness was reduced by a mean of 17.05 µ m ( P = 0.01). Geographic atrophy area increased by 0.06 mm 2 ( P = 0.01) over a 6-month follow-up, and quality of life score increased by 3,07 points on average ( P = 0.05). One patient presented a drusenoid pigment epithelial detachment rupture at M6 after PBM treatment.
CONCLUSION
The visual and anatomical improvements in our patients support previous reports on PBM. PBM may provide a valid therapeutic option for large soft drusen and drusenoid pigment epithelial detachment age-related macular degeneration and may potentially slow the natural course of the disease.
Topics: Humans; Pilot Projects; Low-Level Light Therapy; Prospective Studies; Quality of Life; Macular Degeneration; Retinal Drusen; Retinal Detachment; Geographic Atrophy; Tomography, Optical Coherence; Follow-Up Studies
PubMed: 37027819
DOI: 10.1097/IAE.0000000000003805 -
Retina (Philadelphia, Pa.) Feb 2023To report the pattern and characteristics of drusen subtypes in Asian populations and the association with choroidal thickness.
PURPOSE
To report the pattern and characteristics of drusen subtypes in Asian populations and the association with choroidal thickness.
METHODS
This is the cross-sectional analysis of the population-based cohort study. Two thousand three hundred and fifty-three eyes of 1,336 Chinese and Indian participants aged older than 50 years, eyes with best-corrected visual acuity better than 20/60, and without other retinal diseases were recruited. Pachydrusen, reticular pseudodrusen, soft and hard drusen were graded on both color fundus photographs, and optical coherence tomography imaging with automated segmentation yielding and measurements of choroidal thickness.
RESULTS
Nine hundred and fifty-five Chinese and 381 Indians were included in the final analysis. The pattern of pachydrusen, soft drusen, hard drusen, and reticular pseudodrusen was 14.0%, 3.7%, 12.5%, and 0.2%, respectively. Mean choroidal thickness was the thickest in eyes with pachydrusen (298.3 μm; 95% confidence interval: 290.5-306.1), then eyes with hard (298.1 μm; 95% confidence interval: 290.6-305.5) and soft drusen (293.7 μm; 95% confidence interval: 281.9-305.4) and thinnest in eyes without drusen (284.6 μm; 95% confidence interval: 280.5-288.7). Systemic associations of the various drusen subtypes also differed.
CONCLUSION
Patterns, characterization and choroidal thickness of drusen subtypes, and their associations provide insights into the Asian phenotypic spectrum of age-related macular degeneration and the underlying pathogenesis.
Topics: Humans; Aged; Cohort Studies; Cross-Sectional Studies; Singapore; East Asian People; Retrospective Studies; Retinal Drusen; Tomography, Optical Coherence; Fluorescein Angiography
PubMed: 36695800
DOI: 10.1097/IAE.0000000000003651 -
PloS One 2022The purpose of this study was to examine the ocular and systemic risk profile of the fundus phenotype ≥ 20 small hard (macular) drusen (< 63 μm in diameter).
PURPOSE
The purpose of this study was to examine the ocular and systemic risk profile of the fundus phenotype ≥ 20 small hard (macular) drusen (< 63 μm in diameter).
METHODS
This single-center, cross-sectional study of 176 same-sex twin pairs aged 30 to 80 (median 60) years was a component of a framework study of the transition from not having age-related macular degeneration to having early AMD. Drusen categories assessed using fundus photography and optical coherence tomography included small hard drusen (diameter < 63 μm), intermediate soft drusen (63-125 μm), and large soft drusen (> 125 μm), of which the soft drusen are compatible with a diagnosis of AMD.
RESULTS
Having ≥ 20 small hard drusen within or outside the macula was associated with increasing age, lower body mass index, shorter axial length, hyperopia, female sex, increasing high-density lipoprotein (HDL), high alcohol consumption, and with the presence of soft drusen.
CONCLUSIONS
Having ≥ 20 small hard drusen was associated with some AMD-related risk factors, but not with smoking, increasing body mass index, and higher blood pressure. Having ≥ 20 small hard drusen was also associated with soft drusen, in agreement with previous studies. These findings suggest that small hard drusen are not an early manifestation of AMD but the product of a distinct process of tissue alteration that promotes the development of AMD or some subtype thereof.
Topics: Female; Humans; Cross-Sectional Studies; Retinal Drusen; Macular Degeneration; Retina; Risk Factors; Tomography, Optical Coherence
PubMed: 36548342
DOI: 10.1371/journal.pone.0279279 -
Investigative Ophthalmology & Visual... Mar 2024A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and... (Review)
Review
A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and eye-tracked clinical imaging. This narrative review proposes to supplement the Early Treatment of Diabetic Retinopathy Study (sETDRS) grid with a ring to capture high rod densities. Published photoreceptor and retinal pigment epithelium (RPE) densities in flat mounted aged-normal donor eyes were recomputed for sETDRS rings including near-periphery rich in rods and cumulatively for circular fovea-centered regions. Literature was reviewed for tissue-level studies of aging outer retina, population-level epidemiology studies regionally assessing risk, vision studies regionally assessing rod-mediated dark adaptation (RMDA), and impact of atrophy on photopic visual acuity. The 3 mm-diameter xanthophyll-rich macula lutea is rod-dominant and loses rods in aging whereas cone and RPE numbers are relatively stable. Across layers, the largest aging effects are accumulation of lipids prominent in drusen, loss of choriocapillary coverage of Bruch's membrane, and loss of rods. Epidemiology shows maximal risk for drusen-related progression in the central subfield with only one third of this risk level in the inner ring. RMDA studies report greatest slowing at the perimeter of this high-risk area. Vision declines precipitously when the cone-rich central subfield is invaded by geographic atrophy. Lifelong sustenance of foveal cone vision within the macula lutea leads to vulnerability in late adulthood that especially impacts rods at its perimeter. Adherence to an sETDRS grid and outer retinal cell populations within it will help dissect mechanisms, prioritize research, and assist in selecting patients for emerging treatments.
Topics: Humans; Adult; Aged; Macular Degeneration; Retina; Macula Lutea; Geographic Atrophy; Retinal Cone Photoreceptor Cells
PubMed: 38466281
DOI: 10.1167/iovs.65.3.4 -
Frontiers in Immunology 2023Inherited retinal dystrophies (IRDs) as well as genetically complex retinal phenotypes represent a heterogenous group of ocular diseases, both on account of their... (Review)
Review
Inherited retinal dystrophies (IRDs) as well as genetically complex retinal phenotypes represent a heterogenous group of ocular diseases, both on account of their phenotypic and genotypic characteristics. Therefore, overlaps in clinical features often complicate or even impede their correct clinical diagnosis. Deciphering the molecular basis of retinal diseases has not only aided in their disease classification but also helped in our understanding of how different molecular pathologies may share common pathomechanisms. In particular, these relate to dysregulation of two key processes that contribute to cellular integrity, namely extracellular matrix (ECM) homeostasis and inflammation. Pathological changes in the ECM of Bruch's membrane have been described in both monogenic IRDs, such as Sorsby fundus dystrophy (SFD) and Doyne honeycomb retinal dystrophy (DHRD), as well as in the genetically complex age-related macular degeneration (AMD) or diabetic retinopathy (DR). Additionally, complement system dysfunction and distorted immune regulation may also represent a common connection between some IRDs and complex retinal degenerations. Through highlighting such overlaps in molecular pathology, this review aims to illuminate how inflammatory processes and ECM homeostasis are linked in the healthy retina and how their interplay may be disturbed in aging as well as in disease.
Topics: Humans; Macular Degeneration; Retina; Optic Disk Drusen; Inflammation
PubMed: 36936905
DOI: 10.3389/fimmu.2023.1147037 -
Japanese Journal of Ophthalmology Jul 2020Pachychoroid, or the structural and functional abnormalities of the choroid, is one of the most important causes of exudative maculopathies. The purpose of this article... (Review)
Review
BACKGROUND
Pachychoroid, or the structural and functional abnormalities of the choroid, is one of the most important causes of exudative maculopathies. The purpose of this article is to review the current definitions of pachychoroid and their potential consequences. Most publications are from Asian countries. Although no consensus diagnosis has been reached, pachychoroid is defined by thickened choroid and choroidal vascular hyperpermeability, pachyvessels with inner choroidal attenuation; it is closely linked to pachydrusen. Although some studies suggest choroidal congestion may play a role in its pathogenesis, the exact causes of this condition are still unknown. Pachychoroid is associated with exudative maculopathies including central serous chorioretinopathy, pachychoroid neovasculopathy and polypoidal choroidal vasculopathy (PCV). It is widely accepted that macular neovascular membranes may develop secondary to pachychoroid. Recent clinical observations illustrate the importance of pachychoroid in the etiology of macular neovascularization including neovascular age-related macular degeneration (nAMD).
CONCLUSION
Pachychoroid is an important cause of exudative maculopathies. Both drusen and pachychoroid are increasingly recognized as important causes of macular neovascularization, and eyes formally categorized as typical nAMD or PCV can be further sub-categorized based on the presence or absence of pachychoroid and drusen. There is a need to develop a consensus definition, which will greatly enhance our understanding of pachychoroid and facilitate the development of individual interventions in pachychoroid diseases.
Topics: Central Serous Chorioretinopathy; Choroid Diseases; Choroidal Neovascularization; Consensus; Exudates and Transudates; Humans; Macular Degeneration; Polyps
PubMed: 32318919
DOI: 10.1007/s10384-020-00740-5 -
Investigative Ophthalmology & Visual... Feb 2021To refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated... (Observational Study)
Observational Study
PURPOSE
To refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated topographic distribution and growth rates of drusen by optical coherence tomography (OCT). We compared results to retinal features with similar topographies (cone density and macular pigment) in healthy eyes.
METHODS
In a prospective study, distribution and growth rates of soft drusen in eyes with AMD were identified by human observers in OCT volumes and analyzed with computer-assistance. Published histologic data for macular cone densities (n = 12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n = 31; 62 paired eyes, averaged) were revisited. All values were normalized to Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas.
RESULTS
Sixty-two eyes of 44 patients were imaged for periods up to 78 months. Soft drusen volume per unit volume at baseline is 24.6-fold and 2.3-fold higher in the central ETDRS subfield than in outer and inner rings, respectively, and grows most prominently there. Corresponding ratios (central versus inner and central versus outer) for cone density in donor eyes is 13.3-fold and 5.1-fold and for MPOD, 24.6 and 23.9-fold, and 3.6 and 3.6-fold.
CONCLUSIONS
Normalized soft drusen volume in AMD eyes as assessed by OCT is ≥ 20-fold higher in central ETDRS subfields than in outer rings, paralleling MPOD distribution in healthy eyes. Data on drusen volume support this metric for AMD risk assessment and clinical trial outcome measure. Alignment of different data modalities support the ETDRS grid for standardizing retinal topography in mechanistic studies of drusen biogenesis.
Topics: Aged; Aged, 80 and over; Disease Progression; Female; Fluorescein Angiography; Follow-Up Studies; Fovea Centralis; Fundus Oculi; Humans; Macular Degeneration; Male; Middle Aged; Prospective Studies; Retinal Drusen; Retinal Pigment Epithelium; Tomography, Optical Coherence
PubMed: 33605982
DOI: 10.1167/iovs.62.2.26