Prevalence and Significance of Subretinal Drusenoid Deposits (Reticular Pseudodrusen) in Age-Related Macular Degeneration

Zweifel, Sandrine; Imamura, Yutaka; Spaide, Theodore; Fujiwara, Tetsuro; Spaide, Richard F.

doi:10.1016/j.ophtha.2010.01.027

Cited by 289 publications

(239 citation statements)

References 16 publications

Supporting

Mentioning

228

Contrasting

Unclassified

Order By: Relevance

“…Early detection of photoreceptor degeneration in eyes with subretinal drusenoid deposits, another term for reticular pseudodrusen, could be a biomarker prognostic of advanced AMD, including GA development with subsequent visual loss as supported mainly by the use of adaptive optics imaging [50][51][52][53] in addition to older histopathologic findings of drusenoid deposits on the inner RPE in areas surrounding geographic atrophy. 13 Therefore, presence of such lesions in eyes that are treated for wet AMD with anti-VEGF therapy should be noted, not only in the context of future prospective studies, but even in routine clinical practice, where a combination of continuous anti-VEGF administration and pre-existing RPD could increase chances of visual loss due to GA progression.…”

Section: Eyementioning

confidence: 99%

Risk of geographic atrophy in age-related macular degeneration patients treated with intravitreal anti-VEGF agents

Gemenetzi

Lotery

Patel

2016

Eye

104

View full text Add to dashboard Cite

Anti-vascular endothelial growth factor (VEGF) intravitreal agents are the only successful treatment for wet age-related macular degeneration (AMD). However, there are emerging signals that anti-VEGF treatment can potentially increase development of geographic atrophy (GA). Histopathologic, animal, and clinical studies support this hypothesis although direct proof of a relationship between GA and use of anti-VEGF agents in neovascular AMD is not yet established. This review presents current evidence supporting an association between anti-VEGF therapy and progression of geographic atrophy. The need of exploring alternative methods of treating AMD is indirectly but clearly emphasized.

show abstract

Section: Eyementioning

confidence: 99%

Risk of geographic atrophy in age-related macular degeneration patients treated with intravitreal anti-VEGF agents

Gemenetzi

Lotery

Patel

2016

Eye

104

View full text Add to dashboard Cite

show abstract

“…While the appearance of GA has been associated with the disappearance of drusen, GA can also appear in areas without preexisting drusen. 6,7 The exact cause for the appearance and progression of GA remains elusive. Current theories to explain the appearance of GA include nutritional deprivation due to the thickened Bruch's membrane and/or the presence of drusen, oxidative damage to the RPE, the toxic accumulation of lipofuscin within the RPE, inflammatory damage to the retina and/or RPE that may be mediated by the dysregulation of the complement system, and vascular insufficiency of the underlying choroid.…”

Section: Introductionmentioning

confidence: 99%

“…The appearance and progression of GA has been extensively studied using reflectance fundus imaging, 8,9 autofluorescence (AF) imaging, 10 and spectraldomain optical coherence tomography (SD-OCT) imaging. 11 These imaging strategies have provided some clues regarding the appearance and progression of GA. Reflectance imaging has identified drusen, hyperpigmentation, and reticular pseudo-drusen as risk factors for the appearance and progression of GA. 1,6,7,12,13 Autofluorescence imaging has identified different hyperautofluorescence patterns of the RPE, and these patterns have been associated with different growth characteristics of GA.…”

Section: Introductionmentioning

confidence: 99%

Predicting the Progression of Geographic Atrophy in Age-Related Macular Degeneration With SD-OCT En Face Imaging of the Outer Retina

Nunes¹,

Gregori²,

Yehoshua³

et al. 2013

Ophthalmic Surg Lasers Imaging Retina

View full text Add to dashboard Cite

BACKGROUND AND OBJECTIVE: Spectral-domain optical coherence tomography (SD-OCT) en face imaging was used to measure the growth of geographic atrophy (GA) and identify baseline anatomic changes in the outer retina in eyes with nonexudative age-related macular degeneration (AMD). PATIENTS AND METHODS: In this prospective study, eyes were imaged using 200 × 200 and 512 × 128 A-scan raster patterns. Outer retinal anatomy was visualized using en face imaging of a 20-μm thick slab encompassing the inner segment/outer segment (IS/OS) band. RESULTS: En face SD-OCT imaging of the IS/OS region revealed a bilaterally symmetrical pattern of outer retinal disruption extending beyond the borders of GA that accurately predicted the progression of GA over 1 year in 13 of 30 eyes (43.3%). In the remaining cases, the area of disruption was much larger than the area of progression. CONCLUSION: En face imaging of the outer retina can predict the growth of GA in some eyes. Due to the bilateral symmetry of these findings, this imaging strategy may identify a genetic subset of patients in whom photoreceptor loss precedes the progression of GA. These areas with outer retinal disruption should be followed in clinical trials designed to test treatments for dry AMD. [ Ophthalmic Surg Lasers Imaging Retina. 2013;44:344–359.]

show abstract

“…Drusen and subretinal drusenoid deposits (SDD), the two major hallmarks of AMD, contain large amounts of cholesterol (11)(12)(13) and develop below the RPE (14) and at the OS/RPE interface, respectively (15). Accordingly, the OS may be involved in the biogenesis of SDD (15)(16)(17). In SDD, cholesterol is mostly unesterified (13), whereas drusen contain both unesterified cholesterol (UC) and esterified cholesterol (EC) (11,12).…”

mentioning

confidence: 99%

Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and Esterification in Photoreceptor Cells

Saadane

Mast

Dao

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

The process of vision is impossible without the photoreceptor cells, which have a unique structure and specific maintenance of cholesterol. Herein we report on the previously unrecognized cholesterol-related pathway in the retina discovered during follow-up characterizations of Cyp27a1 ؊/؊ Cyp46a1 ؊/؊ mice.These animals have retinal hypercholesterolemia and convert excess retinal cholesterol into cholesterol esters, normally present in the retina in very small amounts. We established that in the Cyp27a1 ؊/؊ Cyp46a1 ؊/؊ retina, cholesterol esters are generated by and accumulate in the photoreceptor outer segments (OS), which is the retinal layer with the lowest cholesterol content. Mouse OS were also found to express the cholesterol-esterifying enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT1), but not lecithin-cholesterol acyltransferase (LCAT), and to differ from humans in retinal expression of ACAT1. Nevertheless, cholesterol esters were discovered to be abundant in human OS. We suggest a mechanism for cholesterol ester accumulation in the OS and that activity impairment of ACAT1 in humans may underlie the development of subretinal drusenoid deposits, a hallmark of age-related macular degeneration, which is a common blinding disease. We generated Cyp27a1؊/؊ mice, characterized their retina by different imaging modalities, and confirmed that unesterified cholesterol does accumulate in their OS and that there is photoreceptor apoptosis and OS degeneration in this line. Our results provide insights into the retinal response to local hypercholesterolemia and the retinal significance of cholesterol esterification, which could be cell-specific and both beneficial and detrimental for retinal structure and function.

show abstract

Prevalence and Significance of Subretinal Drusenoid Deposits (Reticular Pseudodrusen) in Age-Related Macular Degeneration

Cited by 289 publications

References 16 publications

Risk of geographic atrophy in age-related macular degeneration patients treated with intravitreal anti-VEGF agents

Risk of geographic atrophy in age-related macular degeneration patients treated with intravitreal anti-VEGF agents

Predicting the Progression of Geographic Atrophy in Age-Related Macular Degeneration With SD-OCT En Face Imaging of the Outer Retina

Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and Esterification in Photoreceptor Cells

Contact Info

Product

Resources

About