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Ophthalmology Jun 2022To determine the prognostic significance and impact on visual function of the cuticular drusen phenotype in a cohort with intermediate age-related macular degeneration... (Observational Study)
Observational Study
PURPOSE
To determine the prognostic significance and impact on visual function of the cuticular drusen phenotype in a cohort with intermediate age-related macular degeneration (AMD).
DESIGN
Longitudinal, observational study.
PARTICIPANTS
Participants aged 50 years or older, with bilateral large conventional drusen, without late AMD.
METHODS
Multimodal imaging (MMI) and microperimetry were performed at baseline and then every 6 months for up to 3 years. Eyes were graded for the MMI-based presence of cuticular drusen at baseline. Color fundus photographs were used to grade for the presence of pigmentary abnormalities. OCT scans were used to calculate drusen volume. The associations between cuticular drusen and progression to MMI-defined late AMD (including OCT signs of atrophy) and the impact on visual sensitivity were examined with and without adjustment for the confounders of baseline age, pigmentary abnormalities, and drusen volume.
MAIN OUTCOME MEASURES
Time to develop MMI-defined late AMD and change in mean visual sensitivity.
RESULTS
A total of 280 eyes from 140 participants were included, with 70 eyes from 35 individuals (25%) having cuticular drusen at baseline. Cuticular drusen were not significantly associated with an increased rate of progression to late AMD with and without adjustment for confounders (P ≥ 0.784 for both). In an adjusted model, cuticular drusen were not associated with lower baseline visual sensitivity (P = 0.758) or a faster rate of visual sensitivity decline (P = 0.196).
CONCLUSIONS
In a cohort with bilateral large conventional drusen, individuals with the cuticular drusen phenotype had neither a higher nor lower risk of developing late AMD over 3 years and were not associated with a difference in rate of visual sensitivity decline compared with those without this phenotype. As such, individuals with this phenotype currently warrant similar monitoring strategies as those with conventional drusen.
Topics: Bruch Membrane; Disease Progression; Eye Diseases, Hereditary; Humans; Macular Degeneration; Retinal Drusen; Tomography, Optical Coherence
PubMed: 35120992
DOI: 10.1016/j.ophtha.2022.01.028 -
Molecular Vision Nov 1999Age-related macular degeneration (AMD) is characterized in part by the deposition of extracellular deposits, including drusen, in the aging macula. A number of clinical... (Review)
Review
Age-related macular degeneration (AMD) is characterized in part by the deposition of extracellular deposits, including drusen, in the aging macula. A number of clinical studies have revealed a strong association between the number, size, and degree of confluency of drusen and AMD. Although a number of distinct morphological classes, or phenotypes, of drusen can be resolved at the ultrastructural level, very little is known about the compositional and etiological relationship between these phenotypes. A number of recent studies have begun to provide insight into the composition of drusen at the light microscopic level of resolution. Out of 33 extracellular matrix proteins evaluated, vitronectin was identified in hard and soft drusen [FASEB J 1999; 13:477-84]. Drusen have also been found to contain carbohydrate moieties which are labeled by wheat germ agglutinin (WGA), and Limax flavus agglutinin (LFA). We have recently extended these histochemical, immunohistochemical, and biochemical investigations to examine the relationship between substructural drusen phenotype and composition. The initial results of these observations, generated from a repository of human donor eyes processed within four hours of death, are reported herein. Five distinct substructural drusen phenotypes were identified in tissue sections from eyes of approximately 400 donors; all five phenotypes were observed in eyes from donors with and without clinically documented AMD. Interestingly, no strict relationship between size (one important discriminator between "hard" and "soft" drusen class) and morphology was noted for four out of the five drusen phenotypes. Sections from the same donors were incubated with antibodies directed against vitronectin and with the lectins WGA and LFA, three probes recently shown to label hard and soft drusen at the light microscopic level of resolution. As anticipated, all of these probes bound to all phenotypes of drusen examined. These data suggest that different phenotypes of drusen, although they may differ significantly with respect to their substructural morphology, may possess a similar complement of extracellular matrix-associated proteins and saccharides. Ongoing investigations are directed toward determining whether there exist specific drusen constituents, not yet identified, that impart phenotypic and/or ontogenic specificity to drusen. It is anticipated that a more complete understanding of drusen composition, as it relates to phenotype, will provide significant new insight into the biology and etiology of various clinically manifested forms of AMD.
Topics: History, 19th Century; Humans; Immunohistochemistry; Macular Degeneration; Microscopy, Electron; Retinal Drusen
PubMed: 10562652
DOI: No ID Found -
Retinal Cases & Brief Reports 2020To report a case of cuticular drusen in an indigenous Australian.
BACKGROUND/PURPOSE
To report a case of cuticular drusen in an indigenous Australian.
METHODS
A 37-year-old indigenous (aboriginal) Australian woman from a remote Western Australian town presented with a 2-month history of vision loss. Clinical history, examination, and multimodal retinal imaging data from spectral domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography were analyzed.
RESULTS
Multimodal imaging confirmed cuticular drusen complicated by a right choroidal neovascularization with pigment epithelial detachment and a left foveal vitelliform lesion. An unusual "negative-staining" pattern was noted on late phase indocyanine green angiography and this spared the regions affected by cuticular drusen.
CONCLUSION
To the best of our knowledge, this is the first published report of cuticular drusen in an indigenous Australian. We hypothesize that this may be secondary to ancestral mixing of the gene pool. An unusual staining pattern witnessed on indocyanine green angiography suggests widespread disturbance of lipoprotein deposition in the Bruch membrane.
Topics: Adult; Australia; Bruch Membrane; Eye Diseases, Hereditary; Female; Fluorescein Angiography; Fundus Oculi; Humans; Indigenous Peoples; Retinal Drusen; Retinal Pigment Epithelium; Tomography, Optical Coherence
PubMed: 29219932
DOI: 10.1097/ICB.0000000000000684 -
BMC Ophthalmology Sep 2020Type 2 macular neovascularization (MNV) is supposed to be a rare condition in age-related macular degeneration (AMD). The main purpose of this study was to assess...
BACKGROUND
Type 2 macular neovascularization (MNV) is supposed to be a rare condition in age-related macular degeneration (AMD). The main purpose of this study was to assess accompanying factors of type 2 MNV in AMD.
METHODS
Retrospective data analysis of eyes previously diagnosed with neovascular AMD in a tertiary eye care center (Medical Retina Unit, Rudolf Foundation Hospital, Vienna, Austria) between June 2008 and December 2017. Drusen subtypes, fibrosis, atrophy and subfoveal choroidal thickness (SFCT) of both eyes in patients with type 2 MNV lesions were categorized based on multimodal imaging.
RESULTS
Type 2 MNV was diagnosed in 27 (3.2%) of 835 eyes (749 patients). Drusen characteristics in type 2 MNV were observed as followed: drusen < 63 μm in 2 eyes (7.4%), drusen ≥63 μm in 10 eyes (37%), subretinal drusenoid deposits (SDD) in 8 eyes (29.6%), cuticular drusen in 2 eye (7.4%) and no drusen were evident in 10 eyes (37%). Drusen distribution in 23 fellow eyes was detected as followed: drusen < 63 μm in 2 eyes (8.7%), drusen ≥63 μm in 9 eyes (39.1%), SDD in 5 eyes (21.7%), cuticular drusen in 1 eye (4.3%) and no drusen were evident in 9 eyes (39.1%). Mean SFCT was 140 ± 49 μm in affected eyes and 152 ± 41 μm in the fellow eyes. Patients with drusen or SDD were significantly younger (mean 70.88 ± 6.85, p = 0.04) than patients without deposits (mean 77.40 ± 5.74).
CONCLUSIONS
Type 2 MNV remains a rare entity in AMD. It was frequently seen in the absence of drusen, a hallmark of AMD. These findings contribute to the heterogeneity of phenotypes related to pure type 2 lesions.
Topics: Angiogenesis Inhibitors; Choroidal Neovascularization; Fluorescein Angiography; Humans; Retina; Retinal Drusen; Retrospective Studies; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration
PubMed: 32977799
DOI: 10.1186/s12886-020-01651-2 -
Retina (Philadelphia, Pa.) Mar 2021To correlate drusen morphology and outer retinal status with autofluorescence (AF) imaging in patients with intermediate age-related macular degeneration.
PURPOSE
To correlate drusen morphology and outer retinal status with autofluorescence (AF) imaging in patients with intermediate age-related macular degeneration.
METHODS
Drusen type and morphology were analyzed using color fundus photography and spectral-domain optic coherence tomography, whereas fundus AF was used for drusen AF evaluation. Additional structural changes on spectral-domain optic coherence tomography, such as disruption of external limiting membrane, ellipsoid zone, and retinal pigment epithelium/Bruch membrane complex, as well as the presence of choroidal hypertransmission at correspondent locations were also evaluated and correlated with fundus AF findings. Spearman's correlation coefficient was used to analyze the correlation between spectral-domain optic coherence tomography morphological characteristics of drusen and AF appearance of the corresponding drusen. Strength of correlation was calculated (r), and a P value < 0.05 was considered statistically significant.
RESULTS
Two hundred and twenty-eight drusen from 53 eyes of 53 patients were analyzed, 130 soft drusen (57.02%) and 98 cuticular drusen (42.98%). Sixty percent of the drusen were isoautofluorescent (n = 136), 35% hyperautofluorescent (n = 80), and 5% hypoautofluorescent (n = 12). We found positive correlation between drusen AF and hyperreflective foci (r = 0.4). Outer retinal layers morphology (external limiting membrane and ellipsoid zone status and hypertransmission) also correlates with autofluorescent findings (r = 0.3).
CONCLUSION
Multimodal imaging reveals a broad spectrum of ultrastructural changes, which may reflect different stages in the evolution of drusen. Our results suggest that drusen morphological characteristics and autofluorescent findings are correlated but other factors or cofactors may be involved. The described correlations will help us understand new progression biomarkers of nonexudative age-related macular degeneration.
Topics: Aged; Aged, 80 and over; Female; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Male; Middle Aged; Ophthalmoscopy; Optical Imaging; Prospective Studies; Retinal Drusen; Retinal Pigment Epithelium; Tomography, Optical Coherence
PubMed: 32604342
DOI: 10.1097/IAE.0000000000002881 -
Journal Francais D'ophtalmologie Mar 2020
Topics: Calcinosis; Fundus Oculi; Humans; Male; Middle Aged; Optic Disk Drusen; Visual Fields
PubMed: 31987679
DOI: 10.1016/j.jfo.2019.07.027 -
Investigative Ophthalmology & Visual... Oct 2022To determine if increasing drusen height correlates with predictive optical coherence tomography (OCT) biomarkers of atrophy.
PURPOSE
To determine if increasing drusen height correlates with predictive optical coherence tomography (OCT) biomarkers of atrophy.
METHODS
Retrospective cross-sectional study that enrolled patients with drusen associated with intermediate AMD. Macular drusen were classified as small, intermediate, large, or very large based on OCT quartile measurement of height. Drusen diameter was also tabulated. The presence and localization of the OCT biomarkers of atrophy were assessed: disruption of the external limiting membrane and ellipsoid zone, intraretinal hyper-reflective foci, RPE disruption, choroidal hypertransmission, and presence of hyporeflective cores. Predictive OCT biomarkers of atrophy were correlated with drusen height.
RESULTS
A total of 155 eyes from 104 patients met the inclusion and exclusion criteria. The mean age was 75.7 ± 8.7 years, and patients were predominantly female (74.0%). The mean visual acuity was logMAR 0.2 ± 0.2 (Snellen equivalent 20/32). The average drusen height was 134.6 ± 107.5 µm and the greatest horizontal diameter was 970.7 ± 867.4 µm. Disruption of the external limiting membrane and ellipsoid zone, RPE thickening or thinning, intraretinal hyper-reflective foci, choroidal hypertransmission, and presence of hyporeflective cores (P < 0.05) were more common in eyes with large drusen and very large drusen versus small or intermediate drusen. All biomarkers were positively correlated with drusen height. OCT biomarkers of atrophy were predominantly located at the apex of the drusen.
CONCLUSIONS
Predictive OCT biomarkers of atrophy, specifically signs of RPE breakdown and disruption, occur more commonly in large or very large drusen, especially in drusen with greater height and separation of the RPE from the underlying choroid.
Topics: Humans; Female; Aged; Aged, 80 and over; Male; Tomography, Optical Coherence; Fluorescein Angiography; Retrospective Studies; Macular Degeneration; Retinal Pigment Epithelium; Cross-Sectional Studies; Retinal Drusen; Atrophy; Calcinosis; Biomarkers
PubMed: 36306145
DOI: 10.1167/iovs.63.11.24 -
Journal Francais D'ophtalmologie May 2021
Topics: Hemorrhage; Humans; Optic Disk; Optic Disk Drusen; Visual Fields
PubMed: 33455814
DOI: 10.1016/j.jfo.2020.06.027 -
Retina (Philadelphia, Pa.) Sep 2010
Topics: Extracellular Space; Humans; Macular Degeneration; Retinal Drusen; Risk Factors
PubMed: 20827136
DOI: 10.1097/IAE.0b013e3181ed8d05 -
Acta Ophthalmologica Dec 2022To study age- and sex-adjusted heritability of small hard drusen and early age-related macular degeneration (AMD) in a population-based twin cohort.
PURPOSE
To study age- and sex-adjusted heritability of small hard drusen and early age-related macular degeneration (AMD) in a population-based twin cohort.
METHODS
This was a single-centre, cross-sectional, classical twin study with ophthalmic examination including refraction, biometry, best-corrected visual acuity assessment, colour and autofluorescence fundus photography, and fundus optical coherence tomography. Grading and categorization of drusen was by diameter and location.
RESULTS
The study enrolled 176 same-sex pairs of twins of mean (SD) age 58.6 (9.9) years. The prevalence of the four phenotypes ≥20 small hard macular drusen (largest diameter < 63 μm), ≥20 small hard extramacular drusen, intermediate drusen (63-125 μm) anywhere, and large drusen (>125 μm) anywhere was 12.4%, 36.4%, 5.8%, and 8.4%, respectively, and the respective heritabilities, adjusted for age and sex, were 78.2% [73.5-82.9], 69.1% [62.3-75.9], 30.1% [4.1-56.1], and 65.6% [26.4-100]. Age trajectory analysis supported a gradual transition to larger numbers of small hard drusen with increasing age. The heritability of ≥20 small hard drusen was markedly lower than the 99% found in the 40% overlapping twin cohort that was seen 20 years earlier.
CONCLUSION
Numerous (≥20) small hard drusen and larger drusen that fit the definition of dry AMD were highly heritable. Small hard drusen counts increased with age. Decreasing heritability with increasing age suggests that the impact of behavioural and environmental factors on the development of small hard drusen increases with age.
Topics: Humans; Retinal Drusen; Cross-Sectional Studies; Macular Degeneration; Geographic Atrophy; Twins, Monozygotic; Tomography, Optical Coherence
PubMed: 35322936
DOI: 10.1111/aos.15136