Quantitative Fundus Autofluorescence in Early and Intermediate Age-Related Macular Degeneration

Gliem, Martin; Müller, Philipp L.; Finger, Robert P.; McGuinness, Myra B; Holz, Frank G.; Issa, Peter Charbel

doi:10.1001/jamaophthalmol.2016.1475

Cited by 104 publications

(103 citation statements)

References 27 publications

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“…Fluorescein angiography,10 indocyanine green angiography,11 fundus autofluorescence (FAF)12 and enhanced depth imaging optical coherence tomography (EDI OCT)13 have been all used to quantify stromal changes and vascular alterations in patients with AMD.…”

Section: Introductionmentioning

confidence: 99%

Choroid morphometric analysis in non-neovascular age-related macular degeneration by means of optical coherence tomography angiography

Cicinelli¹,

Rabiolo²,

Marchese³

et al. 2017

Br J Ophthalmol

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Section: Introductionmentioning

confidence: 99%

Choroid morphometric analysis in non-neovascular age-related macular degeneration by means of optical coherence tomography angiography

Cicinelli¹,

Rabiolo²,

Marchese³

et al. 2017

Br J Ophthalmol

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“…A2E accumulation also is thought to contribute to the pathogenesis of age-related macular degeneration (AMD) (11). Moreover, increased fluorescence in the RPE over time is used as a biomarker of progressive retinal disease (12,13). Thus, elucidating the molecular mechanisms of formation and transport of these fluorophores is important both for understanding the cell biology of the retina as well as establishing potential diagnostic markers and devising therapeutic compounds for retinal diseases.…”

mentioning

confidence: 99%

Receptor MER Tyrosine Kinase Proto-oncogene (MERTK) Is Not Required for Transfer of Bis-retinoids to the Retinal Pigmented Epithelium

Palczewska

Maeda

Golczak

et al. 2016

Journal of Biological Chemistry

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Edited by George CarmanAccumulation of bis-retinoids in the retinal pigmented epithelium (RPE) is a hallmark of aging and retinal disorders such as Stargardt disease and age-related macular degeneration. These aberrant fluorescent condensation products, including di-retinoid-pyridinium-ethanolamine (A2E), are thought to be transferred to RPE cells primarily through phagocytosis of the photoreceptor outer segments. However, we observed by twophoton microscopy that mouse retinas incapable of phagocytosis due to a deficiency of the c-Mer proto-oncogene tyrosine kinase (Mertk) nonetheless contained fluorescent retinoid condensation material in their RPE. Primary RPE cells from Mertk ؊/؊ mice also accumulated fluorescent products in vitro.Finally, quantification of A2E demonstrated the acquisition of retinal condensation products in Mertk ؊/؊ mouse RPE prior to retinal degeneration. In these mice, we identified activated microglial cells that likely were recruited to transport A2E-like condensation products to the RPE and dispose of the dying photoreceptor cells. These observations demonstrate a novel transport mechanism between photoreceptor cells and RPE that does not involve canonical Mertk-dependent phagocytosis.Maintaining the health of the vertebrate retina requires a delicate interaction between retinal photoreceptor cells, which collect and transmit visual stimuli, and the adjacent retinal pigmented epithelium (RPE), 4 a cell layer that forms part of the blood-retina barrier (1). Disturbances in this interaction, whether through genetic defects, environmental insults, or trauma can lead to retinal degeneration and ultimate loss of vision (2, 3). The RPE performs many vital functions, including the daily removal of the older distal portions of photoreceptor outer segments (4 -6) and the delivery of both nutrients and the 11-cis-retinal chromophore to rod and cone photoreceptor cells that sustain vision (7). Roughly 10% of each photoreceptor cell outer segment is shed daily throughout an animal's life, distinguishing the RPE as perhaps the most active phagocytic cell layer in the body (5). Although RPE phagocytosis was discovered over 40 years ago (4), the molecular mechanisms underlying this process have not been delineated. However, certain molecular components that support classic phagocytosis have been identified, including the tyrosine receptor kinase Mertk (8, 9). The RPE not only removes toxic photo-oxidation products that accumulate in the retina, but it also recycles usable materials such as proteins, lipids, and small molecules. Retinoid condensation products such as bis-retinoids (di-retinoidpyridinium-ethanolamine (A2E), retinoid dimers, and others) generated in photoreceptors are presumably transported along with photoreceptor membranes to the RPE during phagocytosis. Highly fluorescent A2E accumulation is a pathogenic hallmark of Stargardt disease, the most common juvenile form of human macular degeneration (10). A2E accumulation also is thought to contribute to the pathogenesis of age-related mac...

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“…[55][56][57][58][59]61,64 In contrast, AMD reveals different FAF patterns and low to low-normal FAF intensity. 61,65 While good diagnostic separability is given for STGD1 and AMD based on FAF imaging and genetic testing, the study presented here outlines a framework that may now be used for subphenotype analysis within disease entities. For example, choroidal insufficiency has been previously implicated in the pathogenesis of subphenotypes within the spectrum of AMD including ''reticular macular disease'' and ''diffuse-trickling geographic atrophy'' based on indocyanine green and fluorescein angiography findings, pronounced choroidal thinning, and cardiovascular comorbidity.…”

Section: Discussionmentioning

confidence: 99%

Choroidal Flow Signal in Late-Onset Stargardt Disease and Age-Related Macular Degeneration: An OCT-Angiography Study

Müller

Pfau

Möller

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To investigate the choroidal blood flow in areas within and adjacent to retinal pigment epithelium (RPE) atrophy secondary to late-onset Stargardt disease (STGD1) and agerelated macular degeneration (AMD). METHODS.A total of 43 eyes (23 STGD1 and 20 AMD) of patients with RPE atrophy and 25 eyes of healthy controls without ocular pathology underwent multimodal imaging including optical coherence tomography angiography (OCT-A; PLEX Elite 9000 Swept-Source OCT). Using an exploratory approach, choriocapillaris and deeper choroid OCT-A slabs were evaluated in order to detect differences between STGD1 and AMD. The magnitude of absenceof-flow signal (AFS) was investigated in terms of area-fraction and size-frequency distribution. RESULTS.Qualitative and quantitative analysis of areas of RPE atrophy revealed more pronounced rarefaction of the choriocapillaris flow signal in STGD1 as compared to AMD (AFS area fraction: 33.15% 6 6.86% vs. 31.68% 6 8.39%; P ¼ 0.517), while outside RPE atrophy rarefaction was less pronounced in STGD1 (AFS area fraction: 17.41% 6 5.67% vs. 21.59% 6 6.90%; P < 0.001), to the level of nonsignificance compared to controls (13.27% 6 2.99%, P ¼ 0.368). Given this discrepancy, the ratio of the AFS area fraction within/outside of RPE atrophy could be used to differentiate between STGD1 and AMD with 65.0% sensitivity and 92.3% specificity. CONCLUSIONS.Using OCT-A, comparison of choroidal flow signal within and outside the area of RPE atrophy revealed distinct differences between STGD1 and AMD, potentially implicating a differential role of the choroid in the pathogenesis of RPE atrophy in these two diseases.

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Quantitative Fundus Autofluorescence in Early and Intermediate Age-Related Macular Degeneration

Cited by 104 publications

References 27 publications

Choroid morphometric analysis in non-neovascular age-related macular degeneration by means of optical coherence tomography angiography

Choroid morphometric analysis in non-neovascular age-related macular degeneration by means of optical coherence tomography angiography

Receptor MER Tyrosine Kinase Proto-oncogene (MERTK) Is Not Required for Transfer of Bis-retinoids to the Retinal Pigmented Epithelium

Choroidal Flow Signal in Late-Onset Stargardt Disease and Age-Related Macular Degeneration: An OCT-Angiography Study

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