The Onion Sign in Neovascular Age-Related Macular Degeneration Represents Cholesterol Crystals

Ophthalmology

Volumn 122, Issue 11, 2015, Pages 2316-2326

  Pang, Claudine E ^a   Messinger, Jeffrey D ^c   Zanzottera, Emma C ^c,d   Freund, K Bailey ^a,b,e   Curcio, Christine A ^c  

^a VITREOUS RETINA MACULA CONSULTANTS OF NEW YORK   (United States)

^b Manhattan Eye   (United States)

^c UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^d UNIVERSITY OF MILAN   (Italy)

^e NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; HYPOCHOLESTEROLEMIC AGENT;

AGE RELATED MACULAR DEGENERATION; AGED; AQUEOUS HUMOR; ARTICLE; CHOLESTEROL CRYSTAL; COHORT ANALYSIS; DISORDERS OF CHOLESTEROL METABOLISM; DRUSEN; EX VIVO STUDY; EYE FUNDUS; FEMALE; FOLLOW UP; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; HYPERCHOLESTEROLEMIA; HYPERPIGMENTATION; LABORATORY TEST; MAJOR CLINICAL STUDY; MALE; MEDICAL RECORD REVIEW; MULTIMODAL IMAGING; NEAR INFRARED REFLECTANCE SPECTROSCOPY; OBSERVATIONAL STUDY; ONION SIGN; OUTCOME ASSESSMENT; PIGMENT EPITHELIUM; PRECIPITATION; PRIORITY JOURNAL; QUALITATIVE ANALYSIS; RETINA DETACHMENT; RETINA EXUDATE; RETROSPECTIVE STUDY; SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY; SUBRETINAL NEOVASCULARIZATION; VERY ELDERLY; CRYSTALLIZATION; DONOR; FLUORESCENCE ANGIOGRAPHY; GRANULOMA, FOREIGN-BODY; OPTICAL COHERENCE TOMOGRAPHY; PATHOLOGY; RETINAL PIGMENT EPITHELIUM; WET MACULAR DEGENERATION;

AGED; AGED, 80 AND OVER; ANTICHOLESTEREMIC AGENTS; CHOLESTEROL; CRYSTALLIZATION; FEMALE; FLUORESCEIN ANGIOGRAPHY; FOLLOW-UP STUDIES; GRANULOMA, FOREIGN-BODY; HUMANS; MALE; MULTIMODAL IMAGING; RETINAL PIGMENT EPITHELIUM; RETROSPECTIVE STUDIES; TISSUE DONORS; TOMOGRAPHY, OPTICAL COHERENCE; WET MACULAR DEGENERATION;

EID: 84955208213     PISSN: 01616420     EISSN: 15494713     Source Type: Journal    
DOI: 10.1016/j.ophtha.2015.07.008     Document Type: Article

References (61)

1. S.K. Mukkamala, R.A. Costa, A. Fung, and et al. Optical coherence tomographic imaging of sub-retinal pigment epithelium lipid Arch Ophthalmol 130 2012 1 7
2. L.H. Lima, K.B. Freund, J.M. Klancnik Jr., and R.F. Spaide Intraretinal crystalline deposits in neovascular age-related macular degeneration Retina 30 2010 542 547
3. G. Coscas Optical Coherence Tomography in Age-Related Macular Degeneration 2009 Springer Berlin
4. G. Querques, A. Georges, N. Ben Moussa, and et al. Appearance of regressing drusen on optical coherence tomography in age-related macular degeneration Ophthalmology 121 2014 173 179
5. C. Bonnet, G. Querques, J. Zerbib, and et al. Hyperreflective pyramidal structures on optical coherence tomography in geographic atrophy areas Retina 34 2014 1524 1530
6. C. Christakopoulos, A. Pryds, and M. Larsen Subretinal lamellar bodies in polypoidal choroidal vasculopathy Acta Ophthalmol 91 2013 e248 e249
7. L. Liu, J.A. Gardecki, S.K. Nadkarni, and et al. Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography Nat Med 17 2011 1010 1014
8. G.J. Tearney, I.K. Jang, and B.E. Bouma Optical coherence tomography for imaging the vulnerable plaque J Biomed Opt 11 2006 021002
9. T. Yonetsu, B.E. Bouma, K. Kato, and et al. Optical coherence tomography: 15 years in cardiology Circ J 77 2013 1933 1940
10. G.S. Abela, and K. Aziz Cholesterol crystals rupture biological membranes and human plaques during acute cardiovascular events - a novel insight into plaque rupture by scanning electron microscopy Scanning 28 2006 1 10
11. W.R. Green, and S.N. Key 3rd Senile macular degeneration: a histopathologic study Trans Am Ophthalmol Soc 75 1977 180 254
12. C.A. Curcio, J.B. Presley, C.L. Millican, and N.E. Medeiros Basal deposits and drusen in eyes with age-related maculopathy: evidence for solid lipid particles Exp Eye Res 80 2005 761 775
13. K.M. Litts, J.D. Messinger, K. Dellatorre, and et al. Clinicopathological correlation of outer retinal tubulation in age-related macular degeneration JAMA Ophthalmol 133 2015 609 612
14. C.A. Curcio, J.D. Messinger, A.M. Mitra, and et al. Human chorioretinal layer thicknesses measured using macula-wide high resolution histological sections Invest Ophthalmol Vis Sci 52 2011 3943 3954
15. C.A. Curcio, N.E. Medeiros, and C.L. Millican The Alabama Age-Related Macular Degeneration Grading System for donor eyes Invest Ophthalmol Vis Sci 39 1998 1085 1096
16. G. Staurenghi, S. Sadda, U. Chakravarthy, and R.F. Spaide Proposed lexicon for anatomic landmarks in normal posterior segment spectral-domain optical coherence tomography: The IN∗OCT Consensus Ophthalmology 121 2014 1572 1578
17. E.C. Zanzottera, J.D. Messinger, T. Ach, and et al. The Project MACULA retinal pigment epithelium grading system for histology and optical coherence tomography in age-related macular degeneration Invest Ophthalmol Vis Sci 56 2015 3253 3268
18. E.S. Ford, C. Li, W.S. Pearson, and et al. Trends in hypercholesterolemia, treatment and control among United States adults Int J Cardiol 140 2010 226 235
19. D.J. Wilson, R.G. Weleber, M.L. Klein, and et al. Bietti's crystalline dystrophy. A clinicopathologic correlative study Arch Ophthalmol 107 1989 213 221
20. A.I. Ramírez, J.J. Salazar, R. De Hoz, and et al. Macroglial and retinal changes in hypercholesterolemic rabbits after normalization of cholesterol levels Exp Eye Res 83 2006 1423 1438
21. J.J. Salazar, A.I. Ramírez, R. de Hoz, and et al. Alterations in the choroid in hypercholesterolemic rabbits: reversibility after normalization of cholesterol levels Exp Eye Res 84 2006 412 422
22. D.M. Monson, J.R. Smith, M.L. Klein, and D.J. Wilson Clinicopathologic correlation of retinal angiomatous proliferation Arch Ophthalmol 126 2008 1664 1668
23. A. Nagiel, D. Sarraf, S.R. Sadda, and et al. Type 3 neovascularization: evolution, association with pigment epithelial detachment, and treatment response as revealed by spectral domain optical coherence tomography Retina 35 2015 638 647
24. G.S. Abela Cholesterol crystals piercing the arterial plaque and intima trigger local and systemic inflammation J Clin Lipidol 4 2010 156 164
25. D.M. Small George Lyman Duff Memorial Lecture. Progression and regression of atherosclerotic lesions. Insights from lipid physical biochemistry Arteriosclerosis 8 1988 103 129
26. A. Vedre, D.R. Pathak, M. Crimp, and et al. Physical factors that trigger cholesterol crystallization leading to plaque rupture Atherosclerosis 203 2009 89 96
27. V. Uskokovic Insights into morphological nature of precipitation of cholesterol Steroids 73 2008 356 369
28. R. Virmani, F.D. Kolodgie, A.P. Burke, and et al. Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage Arterioscler Thromb Vasc Biol 25 2005 2054 2061
29. P. Duewell, H. Kono, K.J. Rayner, and et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals Nature 464 2010 1357 1361
30. C.A. Curcio, M. Johnson, J.-D. Huang, and M. Rudolf Aging, age-related macular degeneration, and the response-to-Retention of apolipoprotein B-containing lipoproteins Prog Ret Eye Res 28 2009 393 422
31. M.C. Killingsworth, J.P. Sarks, and S.H. Sarks Macrophages related to Bruch's membrane in age-related macular degeneration Eye 4 1990 613 621
32. C.A. Curcio, M. Johnson, M. Rudolf, and J.-D. Huang The oil spill in ageing Bruch's membrane Br J Ophthalmol 95 2011 1638 1645
33. I. Pikuleva, and C.A. Curcio Cholesterol in the retina: the best is yet to come Prog Ret Eye Res 41 2014 64 89
34. C.A. Curcio, M. Johnson, J.-D. Huang, and M. Rudolf Apolipoprotein B-containing lipoproteins in retinal aging and age-related maculopathy J Lipid Res 51 2010 451 467
35. M.E. Pennesi, and R.G. Weleber High-resolution optical coherence tomography shows new aspects of Bietti crystalline retinopathy Retina 30 2010 531 532
36. M.T. Dotti, A. Rufa, and A. Federico Cerebrotendinous xanthomatosis: heterogeneity of clinical phenotype with evidence of previously undescribed ophthalmological findings J Inherit Metab Dis 24 2001 696 706
37. F.B. Sallo, I. Leung, M. Chung, and et al. Retinal crystals in type 2 idiopathic macular telangiectasia Ophthalmology 118 2011 2461 2467
38. D. Sarraf, N. Vyas, A. Jain, and et al. Triamcinolone-associated crystalline maculopathy Arch Ophthalmol 128 2010 685 690
39. M. Suzuki, C.A. Curcio, R.F. Mullins, and R.F. Spaide Refractile drusen: clinical imaging and candidate histology Retina 35 2015 859 865
40. R.B. Thompson, V. Reffatto, J.G. Bundy, and et al. Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye Proc Natl Acad Sci U S A 112 2015 1565 1570
41. M. Fleckenstein, P. Charbel Issa, H.M. Helb, and et al. High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration Invest Ophthalmol Vis Sci 49 2008 4137 4144
42. K. Moussa, J.Y. Lee, S.S. Stinnett, and G.J. Jaffe Spectral domain optical coherence tomography-determined morphologic predictors of age-related macular degeneration-associated geographic atrophy progression Retina 33 2013 1590 1599
43. S.H. Sarks Ageing and degeneration in the macular region: a clinico-pathological study Br J Ophthalmol 60 1976 324 341
44. T.L. van der Schaft, C.M. Mooy, W.C. de Bruijn, and et al. Histologic features of the early stages of age-related macular degeneration Ophthalmology 99 1992 278 286
45. W.R. Green, and C. Enger Age-related macular degeneration histopathologic studies: the 1992 Lorenz E. Zimmerman Lecture Ophthalmology 100 1993 1519 1535
46. S. Sarks, S. Cherepanoff, M. Killingsworth, and J. Sarks Relationship of basal laminar deposit and membranous debris to the clinical presentation of early age-related macular degeneration Invest Ophthalmol Vis Sci 48 2007 968 977
47. C.A. Curcio, J.D. Messinger, K.R. Sloan, and et al. Subretinal drusenoid deposits in non-neovascular age-related macular degeneration: morphology, prevalence, topography, and biogenesis model Retina 33 2013 265 276
48. E. Buschini, A. Piras, R. Nuzzi, and A. Vercelli Age related macular degeneration and drusen: neuroinflammation in the retina Prog Neurobiol 95 2011 14 25
49. K. Gocho, V. Sarda, S. Falah, and et al. Adaptive optics imaging of geographic atrophy Invest Ophthalmol Vis Sci 54 2013 3673 3680
50. J.N. Leuschen, S.G. Schuman, K.P. Winter, and et al. Spectral-domain optical coherence tomography characteristics of intermediate age-related macular degeneration Ophthalmology 120 2013 140 150
51. G. Coscas, U. De Benedetto, F. Coscas, and et al. Hyperreflective dots: a new spectral-domain optical coherence tomography entity for follow-up and prognosis in exudative age-related macular degeneration Ophthalmologica 229 2013 32 37
52. H. Xu, M. Chen, A. Manivannan, and et al. Age-dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice Aging Cell 7 2008 58 68
53. M. Karlstetter, R. Scholz, M. Rutar, and et al. Retinal microglia: just bystander or target for therapy? Prog Retin Eye Res 45 2015 30 57
54. I.R. Rodriguez, M.E. Clark, J.W. Lee, and C.A. Curcio 7-ketocholesterol accumulates in ocular tissues as a consequence of aging and is present in high levels in drusen Exp Eye Res 128 2014 151 155
55. M. Indaram, W. Ma, L. Zhao, and et al. 7-ketocholesterol increases retinal microglial migration, activation, and angiogenicity: a potential pathogenic mechanism underlying age-related macular degeneration Sci Rep 5 2015 9144
56. J. Lammer, M. Bolz, B. Baumann, and et al. Detection and analysis of hard exudates by polarization-sensitive optical coherence tomography in patients with diabetic maculopathy Invest Ophthalmol Vis Sci 55 2014 1564 1571
57. N.G. Ghazi, C. Dibernardo, H. Ying, and et al. Optical coherence tomography of peripheral retinal lesions in enucleated human eye specimens with histologic correlation Am J Ophthalmol 141 2006 740 742
58. N.H. Brown, A.F. Koreishi, M. McCall, and et al. Developing SDOCT to assess donor human eyes prior to tissue sectioning for research Graefes Arch Clin Exp Ophthalmol 247 2009 1069 1080
59. N. Bagheri, B.A. Bell, V.L. Bonilha, and J.G. Hollyfield Imaging human postmortem eyes with SLO and OCT Adv Exp Med Biol 723 2012 479 488
60. M.L. Klein, and D.J. Wilson Clinicopathologic correlation of choroidal and retinal neovascular lesions in age-related macular degeneration Am J Ophthalmol 151 2011 161 169
61. E. Friedman, and T.R. Smith Clinical and pathological study of choroidal lipid globules Arch Ophthalmol 75 1966 334 336