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Ophthalmology Jan 2018To define the range and life cycles of cuticular drusen phenotypes using multimodal imaging and to review the histologic characteristics of cuticular drusen. (Observational Study)
Observational Study
PURPOSE
To define the range and life cycles of cuticular drusen phenotypes using multimodal imaging and to review the histologic characteristics of cuticular drusen.
DESIGN
Retrospective, observational cohort study and experimental laboratory study.
PARTICIPANTS
Two hundred forty eyes of 120 clinic patients with a cuticular drusen phenotype and 4 human donor eyes with cuticular drusen (n = 2), soft drusen (n = 1), and hard drusen (n = 1).
METHODS
We performed a retrospective review of clinical and multimodal imaging data of patients with a cuticular drusen phenotype. Patients had undergone imaging with various combinations of color photography, fluorescein angiography, indocyanine green angiography, near-infrared reflectance, fundus autofluorescence, high-resolution OCT, and ultrawide-field imaging. Human donor eyes underwent processing for high-resolution light and electron microscopy.
MAIN OUTCOME MEASURES
Appearance of cuticular drusen in multimodal imaging and the topography of a cuticular drusen distribution; age-dependent variations in cuticular drusen phenotypes, including the occurrence of retinal pigment epithelium (RPE) abnormalities, choroidal neovascularization, acquired vitelliform lesions (AVLs), and geographic atrophy (GA); and ultrastructural and staining characteristics of druse subtypes.
RESULTS
The mean age of patients at the first visit was 57.9±13.4 years. Drusen and RPE changes were seen in the peripheral retina, anterior to the vortex veins, in 21.8% of eyes. Of eyes with more than 5 years of follow-up, cuticular drusen disappeared from view in 58.3% of eyes, drusen coalescence was seen in 70.8% of eyes, and new RPE pigmentary changes developed in 56.2% of eyes. Retinal pigment epithelium abnormalities, AVLs, neovascularization, and GA occurred at a frequency of 47.5%, 24.2%, 12.5%, and 25%, respectively, and were significantly more common in patients older than 60 years of age (all P < 0.015). Occurrence of GA and neovascularization were important determinants of final visual acuity in eyes with the cuticular drusen phenotype (both P < 0.015). Small cuticular drusen typically demonstrated a homogenous ultrastructural appearance similar to hard drusen, whereas fragmentation of the central and basal contents was seen frequently in larger cuticular drusen.
CONCLUSIONS
Although the ultrastructural characteristics of cuticular drusen appear more similar to those of hard drusen, their lifecycle and macular complications are more comparable with those of soft drusen. Cuticular drusen phenotype may confer a unique risk for the development of GA and neovascularization.
Topics: Adult; Aged; Aged, 80 and over; Bruch Membrane; Eye Diseases, Hereditary; Female; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Male; Middle Aged; Multimodal Imaging; Phenotype; Retinal Drusen; Retinal Pigment Epithelium; Retrospective Studies; Tomography, Optical Coherence; Young Adult
PubMed: 28964580
DOI: 10.1016/j.ophtha.2017.08.033 -
Scientific Reports May 2022Retinal drusen are characteristic of macular degeneration and complement activation, but also occur in C3, lupus and IgA nephropathy. This cross-sectional observational... (Observational Study)
Observational Study
Retinal drusen are characteristic of macular degeneration and complement activation, but also occur in C3, lupus and IgA nephropathy. This cross-sectional observational study compared drusen counts in different forms of glomerulonephritis. Consecutive individuals with glomerulonephritis attending a general renal or transplant clinic underwent retinal imaging with a non-mydriatic camera. Drusen were counted in deidentified images by trained graders, compared with matched hospital patients, and correlated with clinical features. Eighty-four individuals with glomerulonephritis had a mean drusen count of 10 ± 27 compared with 3 ± 8 in hospital controls (p = 0.007). Fourteen individuals with glomerulonephritis (17%) and 4 hospital controls (4/49, 8%) had increased drusen counts (≥ 10) (p = 0.20). Increased drusen counts ≥ 10 were present in 13 (13/63, 21%) of those with glomerulonephritis and immune deposits [membranous (n = 8), antiglomerular basement membrane nephritis (n = 6), FSGS (n = 49)], and one of the 21 (5%) with glomerulonephritis without immune deposits [ANCA-associated (n = 15), minimal change disease (n = 6)]. In antibody-mediated glomerulonephritis (n = 14), mean drusen counts were 2 ± 3 in individuals with normal kidney function, 16 ± 41 with impaired function and 5 ± 7 with kidney failure . Mean counts were 24 ± 56 in individuals with glomerular IgG deposits and 1 ± 1 in those without (p = 0.76), and 23 ± 60 with complement deposits and 4 ± 8 in those without. Drusen counts were also less in immunosuppressed individuals (p = 0.049). The demonstration of retinal drusen in some forms of glomerulonephritis is consistent with systemic complement activation, and suggests that treatment targeting the complement pathways is worthwhile.
Topics: Complement Activation; Cross-Sectional Studies; Glomerulonephritis; Humans; Kidney; Retinal Drusen
PubMed: 35581312
DOI: 10.1038/s41598-022-12111-w -
Retinal Cases & Brief Reports Jan 2021To report the presence of drusen in infancy, in a patient with Type 1 retinopathy of prematurity and a rare congenital sodium diarrhea secondary to a sporadic GUCY2C...
PURPOSE
To report the presence of drusen in infancy, in a patient with Type 1 retinopathy of prematurity and a rare congenital sodium diarrhea secondary to a sporadic GUCY2C mutation.
METHODS
A case report generated by review of clinical course, with imaging of 1 patient and literature review.
RESULTS
A 1.075-kg infant born at gestation age 27 weeks was admitted to our institution with respiratory distress and secretory diarrhea. During screening for retinopathy of prematurity, peripheral drusen-like subretinal deposits were identified. There were no similar findings in either parent or family history of ocular pathologies. Their distribution is atypical for that seen in other causes of early onset drusen such as autosomal dominant drusen or Sorsby fundus dystrophy. Retinopathy of prematurity was identified, which progressed to Type 1, and was treated with bilateral indirect peripheral retinal photocoagulation at gestational age of 40 weeks. Fluorescein angiography was performed and was consistent with peripheral drusen. Optical coherence tomography of the central macula and an awake electroretinogram at 6 months were normal. Serial examinations confirmed no progression in the drusen-like deposits or in retinopathy of prematurity, with clinically appropriate visual development observed during close follow-up.
CONCLUSION
We identify a unique ocular phenotype of retinal drusen-like deposits in an infant with a rare, sporadic GUCY2C mutation.
Topics: Abnormalities, Multiple; DNA; DNA Mutational Analysis; Diarrhea; Electroretinography; Female; Fluorescein Angiography; Fundus Oculi; Humans; Infant, Newborn; Metabolism, Inborn Errors; Receptors, Enterotoxin; Retina; Retinal Drusen; Retinopathy of Prematurity; Tomography, Optical Coherence
PubMed: 29979251
DOI: 10.1097/ICB.0000000000000748 -
Oman Journal of Ophthalmology 2018Drusen are seen as an end result of various biochemical insults to the retina and have been described in various clinical settings. We would like to report the...
Drusen are seen as an end result of various biochemical insults to the retina and have been described in various clinical settings. We would like to report the histopathology of a case of large drusen, seen associated with chronic retinal detachment in a case of childhood trauma, where the eye was eviscerated for other reasons.
PubMed: 30505122
DOI: 10.4103/0974-620X.244306 -
Retina (Philadelphia, Pa.) Mar 2020To investigate the prevalence of pachydrusen, soft drusen, and subretinal drusenoid deposits in eyes with different neovascular age-related macular degeneration (nAMD)...
PURPOSE
To investigate the prevalence of pachydrusen, soft drusen, and subretinal drusenoid deposits in eyes with different neovascular age-related macular degeneration (nAMD) subtypes, determine the relationship between each drusen type and the choroidal thickness, and analyze the distinct features of each nAMD subtype according to the drusen type.
METHODS
Medical records involving 454 eyes from 454 patients with nAMD were retrospectively reviewed. The prevalence of each drusen type and the choroidal thickness and choroidal characteristics were evaluated according to the nAMD subtype.
RESULTS
Pachydrusen were prevalent in the typical nAMD (40.4%) and polypoidal choroidal vasculopathy (47.8%) groups and were not detected in the retinal angiomatous proliferation group. No significant drusen were detected in 24.3% of typical nAMD, 43.3% of polypoidal choroidal vasculopathy, and 0% of retinal angiomatous proliferation groups. Regardless of the nAMD subtype, pachydrusen, soft drusen, and subretinal drusenoid deposits were associated with a thick, moderately thick, and thin choroid, respectively. For eyes with typical nAMD, the prevalence of choroidal vascular hyperpermeability and extrafoveal neovascularization was significantly higher in the pachydrusen group than in the other groups. By contrast, the prevalence of Type 2 neovascularization was significantly lower in the pachydrusen group than in the subretinal drusenoid deposit group (P < 0.001 for all).
CONCLUSION
The prevalence of various drusen differed according to the nAMD subtypes, and each drusen type was strongly associated with the choroidal thickness. Typical nAMD showed distinct features according to the accompanying drusen type.
Topics: Aged; Aged, 80 and over; Choroid; Female; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Incidence; Male; Middle Aged; Republic of Korea; Retina; Retinal Drusen; Retrospective Studies; Tomography, Optical Coherence; Visual Acuity; Wet Macular Degeneration
PubMed: 30550531
DOI: 10.1097/IAE.0000000000002419 -
Medicine Dec 2022Drusen are precursor lesions to advanced age-related macular degeneration. Although cuticular drusen are located between the retinal pigment epithelium and Bruch's...
RATIONALE
Drusen are precursor lesions to advanced age-related macular degeneration. Although cuticular drusen are located between the retinal pigment epithelium and Bruch's membrane, as are conventional drusen, they possess unique characteristics that are distinct from those of conventional drusen on clinical presentations. Central serous chorioretinopathy (CSC) is a rare complication in eyes with cuticular drusen.
PATIENT CONCERN
A 58-years-old man was referred to our institute for the treatment of persistent subretinal fluid (SRF) in both eyes. Spectral-domain optical coherence tomography revealed focal SRF that did not involve the central macula of the right eye and SRF in the central macula of the left eye. Fluorescein angiography exhibited focal leakage corresponding to SRF and hyperfluorescence resembling a "stars in the sky" appearance in both eyes. On initial presentation, the best-corrected visual acuity values were 1.2 and 0.9 in the right and left eye decimal formats, respectively.
DIAGNOSIS
Cuticular drusen presenting with CSC in both eyes.
INTERVENTIONS
No treatment was administered for CSC in the right eye, whereas photodynamic therapy was administered for CSC in the left eye.
OUTCOMES
At the 6-month visit, extrafoveal SRF persisted in the right eye and resolved in the left eye. Best-corrected visual acuity improved from 0.9 to 1.2 in the decimal format in the left eye.
LESSONS
Although cuticular drusen presenting with CSC are rare, physicians should be aware of the possibility of CSC development in eyes with cuticular drusen.
Topics: Humans; Middle Aged; Bruch Membrane; Central Serous Chorioretinopathy
PubMed: 36482569
DOI: 10.1097/MD.0000000000032032 -
Scientific Reports Oct 2022Drusen are retinal deposits comprising cell debris, immune material and complement that are characteristic of macular degeneration but also found in glomerulonephritis....
Drusen are retinal deposits comprising cell debris, immune material and complement that are characteristic of macular degeneration but also found in glomerulonephritis. This was a pilot cross-sectional study to determine how often drusen occurred in IgA glomerulonephritis and their clinical significance. Study participants underwent non-mydriatic retinal photography, and their deidentified retinal images were examined for drusen by two trained graders, who compared central drusen counts, counts ≥ 10 and drusen size with those of matched controls. The cohort comprised 122 individuals with IgA glomerulonephritis including 89 males (73%), 49 individuals (40%) of East Asian or Southern European ancestry, with an overall median age of 54 years (34-64), and median disease duration of 9 years (4-17). Thirty-nine (33%) had an eGFR < 60 ml/min/1.73 m and 72 had previously reached kidney failure (61%). Overall mean drusen counts were higher in IgA glomerulonephritis (9 ± 27) than controls (2 ± 7, p < 0.001). Central counts ≥ 10 were also more common (OR = 3.31 (1.42-7.73, p = 0.006), and were associated with longer disease duration (p = 0.03) but not kidney failure (p = 0.31). Larger drusen were associated with more mesangial IgA staining (p = 0.004). Increased drusen counts were also present in IgA glomerulonephritis secondary to Crohn's disease but not with Henoch-Schonlein purpura. The finding of retinal drusen in IgA glomerulonephritis is consistent with complement activation and represents a model for better understanding glomerular immune deposition and a supporting argument for treatment with anti-complement therapies.
Topics: Male; Humans; Adult; Middle Aged; Retinal Drusen; Glomerulonephritis, IGA; Cross-Sectional Studies; Complement Activation; IgA Vasculitis; Glomerulonephritis; Immunoglobulin A
PubMed: 36316518
DOI: 10.1038/s41598-022-21386-y -
Progress in Retinal and Eye Research Nov 2001Age-related macular degeneration (AMD) is a blinding disease that afflicts millions of adults in the Western world. Although it has been proposed that a threshold event... (Review)
Review
An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration.
Age-related macular degeneration (AMD) is a blinding disease that afflicts millions of adults in the Western world. Although it has been proposed that a threshold event occurs during normal aging which leads to AMD, the sequelae of biochemical, cellular, and/or molecular events leading to the development of AMD are poorly understood. Although available data provide strong evidence that a significant proportion of AMD has a genetic basis, no gene(s) has yet been identified that causes a significant proportion of AMD. Moreover, no major molecular pathways involved in the etiology of this disease have been elucidated.Drusen, pathological deposits that form between the retinal pigmented epithelium (RPE) and Bruch's membrane, are significant risk factors for the development of AMD. In our view, the development of testable new hypotheses of drusen origins has been hindered significantly by the absence of a comprehensive profile of their molecular composition. In this review, we describe an integrated ultrastructural, histochemical, molecular biological, and biochemical approach to identify specific molecular pathways associated with drusen biogenesis. The implicit assumption underlying these recent investigations has been that a thorough understanding of the composition of drusen and source(s) of drusen-associated material is likely to provide fresh insight into the pathobiology underlying AMD. Significantly, these studies have revealed that proteins associated with inflammation and immune-mediated processes are prevalent among drusen-associated constituents. Transcripts that encode a number of these molecules have been detected in retinal, RPE, and choroidal cells. These data have also lead to the observations that dendritic cells, potent antigen-presenting cells, are intimately associated with drusen development and that complement activation is a key pathway that is active both within drusen and along the RPE-choroid interface. We propose herein a unifying hypothesis of drusen biogenesis that attempts to incorporate a large body of new and previously published structural, histochemical, and molecular data pertaining to drusen composition and development. This theory is put forth with the acknowledgment that numerous AMD genotypes may exist. Thus, only some aspects of the proposed hypothesis may be involved in any given AMD genotype. Importantly, this hypothesis invokes, for the first time, the potential for a direct role of cell- and immune-mediated processes in drusen biogenesis. We acknowledge that the proposed hypothesis clearly represents a paradigm shift in our conceptualization pertaining to pathways that participate in the development of drusen and age-related macular degeneration. It is our hope that other investigators will test, validate and/or refute various aspects of this hypothesis, and in so doing, increase our overall understanding of the biological pathways associated with early AMD.
Topics: Aging; Biomarkers; Bruch Membrane; Dendritic Cells; Eye Proteins; Humans; Immune System; Macular Degeneration; Philosophy; Pigment Epithelium of Eye; Retinal Drusen
PubMed: 11587915
DOI: 10.1016/s1350-9462(01)00010-6 -
Journal Francais D'ophtalmologie Jun 2023
Topics: Humans; Retinal Drusen; Choroidal Neovascularization; Bruch Membrane; Eye Diseases, Hereditary; Fluorescein Angiography; Tomography, Optical Coherence
PubMed: 37076393
DOI: 10.1016/j.jfo.2022.10.015 -
Ophthalmology Jan 2018
Topics: Humans; Macular Degeneration; Optic Disk Drusen; Retina; Retinal Drusen
PubMed: 29268869
DOI: 10.1016/j.ophtha.2017.09.007