retinal drusen

Summary

Summary: Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium.

Top Publications

  1. Anderson D, Mullins R, Hageman G, Johnson L. A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol. 2002;134:411-31 pubmed
    ..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...
  2. Gehrs K, Anderson D, Johnson L, Hageman G. Age-related macular degeneration--emerging pathogenetic and therapeutic concepts. Ann Med. 2006;38:450-71 pubmed
    ..The emergence of this new paradigm of AMD pathogenesis should hasten the development of novel diagnostic and therapeutic approaches for this disease that will dramatically improve the quality of our prolonged lifespan...
  3. Gouras P, Braun K, Ivert L, Neuringer M, Mattison J. Bestrophin detected in the basal membrane of the retinal epithelium and drusen of monkeys with drusenoid maculopathy. Graefes Arch Clin Exp Ophthalmol. 2009;247:1051-6 pubmed publisher
    ..The latter finding provides insight into the pathogenesis of drusen by indicating that segments of the basal membrane of RPE contribute to the material that accumulates within drusen. ..
  4. Roquet W, Roudot Thoraval F, Coscas G, Soubrane G. Clinical features of drusenoid pigment epithelial detachment in age related macular degeneration. Br J Ophthalmol. 2004;88:638-42 pubmed
    ..To analyse clinical features of drusenoid pigment epithelium detachment (PED) in age related macular degeneration...
  5. Luibl V, Isas J, Kayed R, Glabe C, Langen R, Chen J. Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. J Clin Invest. 2006;116:378-85 pubmed
    ..These results suggest that amyloid oligomers may be involved in drusen biogenesis and that similar protein misfolding processes may occur in AMD and amyloid diseases...
  6. An E, Lu X, Flippin J, Devaney J, Halligan B, Hoffman E, et al. Secreted proteome profiling in human RPE cell cultures derived from donors with age related macular degeneration and age matched healthy donors. J Proteome Res. 2006;5:2599-610 pubmed
    ..Overall, these data strongly suggest that RPE cells are involved in the biogenesis of drusen and the pathology of AMD...
  7. Hageman G, Mullins R. Molecular composition of drusen as related to substructural phenotype. Mol Vis. 1999;5:28 pubmed
    ..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...
  8. Yang Z, Camp N, Sun H, Tong Z, Gibbs D, Cameron D, et al. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science. 2006;314:992-3 pubmed
    ..We also found that drusen in the eyes of AMD patients were strongly immunolabeled with HTRA1 antibody. Together, these findings support a key role for HTRA1 in AMD susceptibility and identify a potential new pathway for AMD pathogenesis...
  9. van de Ven J, Boon C, Fauser S, Hoefsloot L, Smailhodzic D, Schoenmaker Koller F, et al. Clinical evaluation of 3 families with basal laminar drusen caused by novel mutations in the complement factor H gene. Arch Ophthalmol. 2012;130:1038-47 pubmed
    ..To identify novel complement factor H (CFH) gene mutations and to specify the clinical characteristics in patients with basal laminar drusen (BLD), a clinical subtype of age-related macular degeneration...

More Information

Publications63

  1. De Jong P. Age-related macular degeneration. N Engl J Med. 2006;355:1474-85 pubmed
  2. Nozaki M, Raisler B, Sakurai E, Sarma J, Barnum S, Lambris J, et al. Drusen complement components C3a and C5a promote choroidal neovascularization. Proc Natl Acad Sci U S A. 2006;103:2328-33 pubmed
    ..Collectively, these findings establish a mechanistic basis for the clinical observation that drusen predispose to CNV, revealing a role for immunological phenomena in angiogenesis and providing therapeutic targets for AMD...
  3. Wang J, Ohno Matsui K, Yoshida T, Kojima A, Shimada N, Nakahama K, et al. Altered function of factor I caused by amyloid beta: implication for pathogenesis of age-related macular degeneration from Drusen. J Immunol. 2008;181:712-20 pubmed
    ..These findings link four factors that have been suggested to be associated with AMD: inflammation, complement activation, Abeta deposition, and drusen...
  4. Davis M, Gangnon R, Lee L, Hubbard L, Klein B, Klein R, et al. The Age-Related Eye Disease Study severity scale for age-related macular degeneration: AREDS Report No. 17. Arch Ophthalmol. 2005;123:1484-98 pubmed
    ..To develop a fundus photographic severity scale for age-related macular degeneration (AMD)...
  5. Umeda S, Suzuki M, Okamoto H, Ono F, Mizota A, Terao K, et al. Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fascicularis). FASEB J. 2005;19:1683-5 pubmed
  6. McAvoy C, Silvestri G. Retinal changes associated with type 2 glomerulonephritis. Eye (Lond). 2005;19:985-9 pubmed
    ..Find out if renal transplantation was linked with visual deterioration. Decide if patients with type 2 MPGN need to be referred for ophthalmological assessment...
  7. Boon C, van de Kar N, Klevering B, Keunen J, Cremers F, Klaver C, et al. The spectrum of phenotypes caused by variants in the CFH gene. Mol Immunol. 2009;46:1573-94 pubmed publisher
    ..The phenotypic outcome of these CFH variants depends on their differential impact on plasma- and surface-bound CFH function. Consequently, distinct genotype-phenotype correlations may be observed...
  8. Chang A, Guyer D, Orlock D, Yannuzzi L. Age-dependent variations in the drusen fluorescence on indocyanine green angiography. Clin Exp Ophthalmol. 2003;31:300-4 pubmed
    ..To examine the fluorescence patterns of macular drusen using indocyanine green (ICG) angiography in human subjects of different ages...
  9. D souza Y, Jones C, Bonshek R. Glycoproteins of drusen and drusen-like lesions. J Mol Histol. 2008;39:77-86 pubmed
    ..As there was no significant difference in the lectin-binding pattern in drusen in different pathologies, a common pathogenesis or at least a final common pathway for the elaboration of carbohydrate components of drusen is suggested...
  10. Malek G, Li C, Guidry C, Medeiros N, Curcio C. Apolipoprotein B in cholesterol-containing drusen and basal deposits of human eyes with age-related maculopathy. Am J Pathol. 2003;162:413-25 pubmed
    ..The combination of apo B mRNA and protein in RPE raises the possibility that intraocular assembly of apo B-containing lipoproteins is a pathway involved in forming cholesterol-enriched lesions in ARM...
  11. Luhmann U, Robbie S, Munro P, Barker S, Duran Y, Luong V, et al. The drusenlike phenotype in aging Ccl2-knockout mice is caused by an accelerated accumulation of swollen autofluorescent subretinal macrophages. Invest Ophthalmol Vis Sci. 2009;50:5934-43 pubmed publisher
    ..Other, previously described features of Ccl2(-/-) mice that are similar to AMD may be the result of aging alone. ..
  12. Gouras P, Ivert L, Neuringer M, Mattison J. Topographic and age-related changes of the retinal epithelium and Bruch's membrane of rhesus monkeys. Graefes Arch Clin Exp Ophthalmol. 2010;248:973-84 pubmed publisher
    ..Therefore lipofuscin toxicity may not be the sole cause of age-related RPE degeneration. ..
  13. Klein R, Klein B, Linton K. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1992;99:933-43 pubmed
    The relationships of retinal drusen, retinal pigmentary abnormalities, and macular degeneration to age and sex were studied in 4926 people between the ages of 43 and 86 years who participated in the Beaver Dam Eye Study.
  14. Ho A, Maguire M, Yoken J, Lee M, Shin D, Javornik N, et al. Laser-induced drusen reduction improves visual function at 1 year. Choroidal Neovascularization Prevention Trial Research Group. Ophthalmology. 1999;106:1367-73; discussion 1374 pubmed
    ..To describe the relationship of laser-induced drusen reduction to change in visual function at 1 year among patients enrolled in the Choroidal Neovascularization Prevention Trial (CNVPT)...
  15. Li C, Clark M, Chimento M, Curcio C. Apolipoprotein localization in isolated drusen and retinal apolipoprotein gene expression. Invest Ophthalmol Vis Sci. 2006;47:3119-28 pubmed
    ..To evaluate apolipoprotein (Apo) gene expression in native human retinal pigment epithelium (RPE) and neurosensory retina and to detect apolipoproteins within age-related, extramacular drusen...
  16. Haimovici R, Gantz D, Rumelt S, Freddo T, Small D. The lipid composition of drusen, Bruch's membrane, and sclera by hot stage polarizing light microscopy. Invest Ophthalmol Vis Sci. 2001;42:1592-9 pubmed
  17. Guigui B, Leveziel N, Martinet V, Massamba N, Sterkers M, Coscas G, et al. Angiography features of early onset drusen. Br J Ophthalmol. 2011;95:238-44 pubmed publisher
    ..Our purpose was to classify the phenotype of EOD on the basis of fundus examination, and fluorescein angiography (FA) and indocyanine green angiography (ICGA) features...
  18. Wang L, Clark M, Crossman D, Kojima K, Messinger J, Mobley J, et al. Abundant lipid and protein components of drusen. PLoS ONE. 2010;5:e10329 pubmed publisher
  19. Johnson L, Leitner W, Staples M, Anderson D. Complement activation and inflammatory processes in Drusen formation and age related macular degeneration. Exp Eye Res. 2001;73:887-96 pubmed
    ..Thus, the process of drusen biogenesis may be envisaged as a secondary manifestation of primary RPE pathology that is exacerbated by consequences of local inflammatory processes...
  20. Curcio C, Presley J, Malek G, Medeiros N, Avery D, Kruth H. Esterified and unesterified cholesterol in drusen and basal deposits of eyes with age-related maculopathy. Exp Eye Res. 2005;81:731-41 pubmed
    ..UC in sub-RPE deposits cannot be derived directly from OS without considerable intracellular processing within RPE, additional cholesterol sources, or both...
  21. Smith R, Chan J, Nagasaki T, Sparrow J, Barbazetto I. A method of drusen measurement based on reconstruction of fundus background reflectance. Br J Ophthalmol. 2005;89:87-91 pubmed
    ..Current manual methods of drusen segmentation and quantification are laborious and subjective. The authors introduced a digital method and tested it for accuracy and reliability...
  22. Klein R, Klein B, Tomany S, Meuer S, Huang G. Ten-year incidence and progression of age-related maculopathy: The Beaver Dam eye study. Ophthalmology. 2002;109:1767-79 pubmed
    The aim of the study was to describe the 10-year incidence and progression of retinal drusen, retinal pigmentary abnormalities, and signs of late age-related maculopathy.
  23. Rapantzikos K, Zervakis M, Balas K. Detection and segmentation of drusen deposits on human retina: potential in the diagnosis of age-related macular degeneration. Med Image Anal. 2003;7:95-108 pubmed
    ..The performance of the algorithm is established through statistical analysis of the results. This analysis indicates that the proposed drusen detector gives reliable detection accuracy in both position and mass size...
  24. Seddon J, Reynolds R, Rosner B. Peripheral retinal drusen and reticular pigment: association with CFHY402H and CFHrs1410996 genotypes in family and twin studies. Invest Ophthalmol Vis Sci. 2009;50:586-91 pubmed publisher
    To evaluate the relationship between peripheral retinal drusen and reticular pigment changes and genotypes associated with age-related macular degeneration (AMD).
  25. Wang A, Lukas T, Yuan M, Du N, Tso M, Neufeld A. Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration. PLoS ONE. 2009;4:e4160 pubmed publisher
    ..Molecular and cellular changes in the old RPE may underlie susceptibility to genetic mutations that are found in AMD patients and may be associated with the pathogenesis of AMD in the elderly. ..
  26. Wang J, Ohno Matsui K, Yoshida T, Shimada N, Ichinose S, Sato T, et al. Amyloid-beta up-regulates complement factor B in retinal pigment epithelial cells through cytokines released from recruited macrophages/microglia: Another mechanism of complement activation in age-related macular degeneration. J Cell Physiol. 2009;220:119-28 pubmed publisher
  27. Mullins R, Johnson M, Faidley E, Skeie J, Huang J. Choriocapillaris vascular dropout related to density of drusen in human eyes with early age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011;52:1606-12 pubmed publisher
    ..Choroidal vascular changes have also been noted in AMD. This study examined the relationship between the choroidal vasculature and extent of drusen and other sub-RPE deposits, the key pathologic landmarks of AMD...
  28. Johnson L, Forest D, Banna C, Radeke C, Maloney M, Hu J, et al. Cell culture model that mimics drusen formation and triggers complement activation associated with age-related macular degeneration. Proc Natl Acad Sci U S A. 2011;108:18277-82 pubmed publisher
    ..This model system will facilitate the analysis of molecular and cellular aspects of AMD pathogenesis, and the testing of new therapeutic agents for its treatment...
  29. Rudolf M, Clark M, Chimento M, Li C, Medeiros N, Curcio C. Prevalence and morphology of druse types in the macula and periphery of eyes with age-related maculopathy. Invest Ophthalmol Vis Sci. 2008;49:1200-9 pubmed publisher
    ..The present study was conducted to determine regional differences in morphology that contribute to the higher vulnerability of the macula to advanced disease...
  30. Boon C, Klevering B, Hoyng C, Zonneveld Vrieling M, Nabuurs S, Blokland E, et al. Basal laminar drusen caused by compound heterozygous variants in the CFH gene. Am J Hum Genet. 2008;82:516-23 pubmed publisher
    ..Our findings strongly suggest that monogenic inheritance of CFH variants can result in basal laminar drusen in young adults, and this can progress to maculopathy and severe vision loss later in life...
  31. Killingsworth M, Sarks J, Sarks S. Macrophages related to Bruch's membrane in age-related macular degeneration. Eye (Lond). 1990;4 ( Pt 4):613-21 pubmed
    ..It is suggested that the widespread accumulation of phospholipid-containing membranes together with the focal concentration of lipid in hard drusen attract macrophages...
  32. Anderson D, Ozaki S, Nealon M, Neitz J, Mullins R, Hageman G, et al. Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium: implications for the process of drusen formation. Am J Ophthalmol. 2001;131:767-81 pubmed
    ..Accordingly, we assessed the potential biosynthetic contribution of local ocular cell types to the apolipoprotein E found in drusen...
  33. Smith R, Nagasaki T, Sparrow J, Barbazetto I, Klaver C, Chan J. A method of drusen measurement based on the geometry of fundus reflectance. Biomed Eng Online. 2003;2:10 pubmed
    ..Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method...
  34. Ferris F, Davis M, Clemons T, Lee L, Chew E, Lindblad A, et al. A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. Arch Ophthalmol. 2005;123:1570-4 pubmed
    ..To develop a simplified clinical scale defining risk categories for development of advanced age-related macular degeneration (AMD)...
  35. Curcio C, Presley J, Millican C, Medeiros N. Basal deposits and drusen in eyes with age-related maculopathy: evidence for solid lipid particles. Exp Eye Res. 2005;80:761-75 pubmed
    ..These results are consistent with recent evidence implicating lipoprotein particles of intra-ocular origin as a potential source of neutral lipids, including esterified cholesterol, in the specific lesions of ARM...
  36. Lengyel I, Tufail A, Hosaini H, Luthert P, Bird A, Jeffery G. Association of drusen deposition with choroidal intercapillary pillars in the aging human eye. Invest Ophthalmol Vis Sci. 2004;45:2886-92 pubmed
    ..To determine the pattern of drusen accumulation with age and to investigate the initial sites of deposition and their relationship to choroidal capillaries in human donor eyes from the eye bank of Moorfields Eye Hospital...
  37. Anderson D, Talaga K, Rivest A, Barron E, Hageman G, Johnson L. Characterization of beta amyloid assemblies in drusen: the deposits associated with aging and age-related macular degeneration. Exp Eye Res. 2004;78:243-56 pubmed
    ..We characterized the ultrastructural organization and histochemical staining properties of these Abeta-containing elements in order to further assess their significance in drusen formation and AMD pathogenesis...
  38. Johnson L, Ozaki S, Staples M, Erickson P, Anderson D. A potential role for immune complex pathogenesis in drusen formation. Exp Eye Res. 2000;70:441-9 pubmed
  39. Mullins R, Aptsiauri N, Hageman G. Structure and composition of drusen associated with glomerulonephritis: implications for the role of complement activation in drusen biogenesis. Eye (Lond). 2001;15:390-5 pubmed
    ..These features were compared with those of drusen from patients with clinically documented AMD...
  40. Hageman G, Luthert P, Victor Chong N, Johnson L, Anderson D, Mullins R. 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. Prog Retin Eye Res. 2001;20:705-32 pubmed
    ..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...
  41. Isas J, Luibl V, Johnson L, Kayed R, Wetzel R, Glabe C, et al. Soluble and mature amyloid fibrils in drusen deposits. Invest Ophthalmol Vis Sci. 2010;51:1304-10 pubmed publisher
    ..In previous study, a conformational-specific antibody showed drusen to contain nonfibrillar amyloid structures. The current study was undertaken to assess the presence of additional amyloid structures in drusen...
  42. Kochounian H, Johnson L, Fong H. Accumulation of extracellular RGR-d in Bruch's membrane and close association with drusen at intercapillary regions. Exp Eye Res. 2009;88:1129-36 pubmed publisher
    ..Intensely immunostained RGR-d loci can be found at the base of early-stage drusen mounds in the older donors and may precede the formation of these drusen...
  43. Li C, Clark M, Rudolf M, Curcio C. Distribution and composition of esterified and unesterified cholesterol in extra-macular drusen. Exp Eye Res. 2007;85:192-201 pubmed
    ..The relative sizes of sub-domains defined by cholesterol composition are compared to sub-domains detected in drusen by in vivo imaging methods...
  44. Smith R, Chan J, Nagasaki T, Ahmad U, Barbazetto I, Sparrow J, et al. Automated detection of macular drusen using geometric background leveling and threshold selection. Arch Ophthalmol. 2005;123:200-6 pubmed
    ..Age-related macular degeneration (ARMD) is the most prevalent cause of visual loss in patients older than 60 years in the United States. Observation of drusen is the hallmark finding in the clinical evaluation of ARMD...
  45. Jager R, Mieler W, Miller J. Age-related macular degeneration. N Engl J Med. 2008;358:2606-17 pubmed publisher
  46. Raoul W, Feumi C, Keller N, Lavalette S, Houssier M, Behar Cohen F, et al. Lipid-bloated subretinal microglial cells are at the origin of drusen appearance in CX3CR1-deficient mice. Ophthalmic Res. 2008;40:115-9 pubmed publisher
  47. Klein R, Klein B, Knudtson M, Meuer S, Swift M, Gangnon R. Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology. 2007;114:253-62 pubmed
    ..To describe the 15-year cumulative incidence of signs of early and late age-related macular degeneration (AMD)...
  48. Lengyel I, Flinn J, Peto T, Linkous D, Cano K, Bird A, et al. High concentration of zinc in sub-retinal pigment epithelial deposits. Exp Eye Res. 2007;84:772-80 pubmed
    ..Based on the evidence provided here we suggest that zinc plays a role in sub-RPE deposit formation in the aging human eye and possibly also in the development and/or progression of AMD...
  49. Curcio C, Millican C. Basal linear deposit and large drusen are specific for early age-related maculopathy. Arch Ophthalmol. 1999;117:329-39 pubmed
    ..To determine the distributions of basal laminar and basal linear deposits in Bruch membrane (BM) with respect to age and early age-related maculopathy (ARM)...
  50. Russell S, Mullins R, Schneider B, Hageman G. Location, substructure, and composition of basal laminar drusen compared with drusen associated with aging and age-related macular degeneration. Am J Ophthalmol. 2000;129:205-14 pubmed
    ..To determine whether basal laminar drusen differ in their location, ultrastructure, or composition from drusen associated with aging and age-related macular degeneration...
  51. Dentchev T, Milam A, Lee V, Trojanowski J, Dunaief J. Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas. Mol Vis. 2003;9:184-90 pubmed
    ..The goal of this study was to characterize the distribution and frequency of Abeta deposits in drusen from AMD and normal post mortem human retinas to gain additional insight about the potential role of Abeta in AMD patho genesis...
  52. Grassi M, Folk J, Scheetz T, Taylor C, Sheffield V, Stone E. Complement factor H polymorphism p.Tyr402His and cuticular Drusen. Arch Ophthalmol. 2007;125:93-7 pubmed
    ..To determine the histidine frequency in patients with the cuticular drusen phenotype of age-related macular degeneration (AMD)...
  53. Erke M, Bertelsen G, Peto T, Sjølie A, Lindekleiv H, Njølstad I. Lactation, female hormones and age-related macular degeneration: the Tromsø Study. Br J Ophthalmol. 2013;97:1036-9 pubmed publisher
    ..Longer duration of lactation was associated with lower frequency of maternal late AMD when controlled for confounders. Other reproductive factors and hormone replacement therapy were not significantly associated with AMD. ..
  54. Bucheli P, Vidal K, Shen L, Gu Z, Zhang C, Miller L, et al. Goji berry effects on macular characteristics and plasma antioxidant levels. Optom Vis Sci. 2011;88:257-62 pubmed publisher