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

Purpose To identify the origin and significance of discordance between blue-light autofluorescence (BL-AF; 488nm) and near-infrared autofluorescence (NI-AF; 787nm) in patients with age-related macular degeneration (AMD). Methods A total of 86 eyes of 59 patients with a diagnosis of AMD were included in this cross-sectional study conducted between March 9, 2015 and May 1, 2015. A masked observer examined the BL-AF, NI-AF, and spectral-domain optical coherence tomography (OCT) images. Areas with discordance of autofluorescence patterns between NI-AF and BL-AF images were correlated with structural findings at the corresponding location in OCT scans. Results 79 eyes had discordance between BL-AF and NI-AF. The most common OCT finding accounting for these discrepancies was pigment migration accounting for 35 lesions in 21 eyes. The most clinically relevant finding was geographic atrophy missed on BL-AF in seven eyes. Conclusions Our findings indicate that variations in the distribution of lipofuscin, melanin and melanolipofuscin account for the majority of discordance between BL-AF and NI-AF. Given our finding of missed geographic atrophy lesions on BL-AF in 24% of eyes with geographic atrophy (7/29 eyes), clinicians should consider multimodal imaging, including NI-AF and OCT, especially in clinical trials of geographic atrophy.

Section: Discussionmentioning

confidence: 99%

Discordance Between Blue-Light Autofluorescence and Near-Infrared Autofluorescence in Age-Related Macular Degeneration

Heiferman

Fawzi

2016

“…Maculopathy was further checked at the time of histologic preparation (2011–2013) using ex vivo multimodal imaging including SDOCT and FAF (Spectralis, Heidelberg Engineering, Heidelberg, Germany). 34 Atrophy in one nvAMD eye used for cross-sectional analysis, revealed by ex vivo color photography and FAF imaging, is shown in Figure 1A–C.…”

Section: Methodsmentioning

confidence: 99%

Visualizing Retinal Pigment Epithelium Phenotypes in the Transition to Atrophy in Neovascular Age-Related Macular Degeneration

Zanzottera

Ach

Huisingh

et al. 2016

Self Cite

Purpose To enable future studies of retinal pigment epithelium (RPE) fate in the macular atrophy occurring in eyes with neovascular AMD (nvAMD), we determined how RPE morphology changes across the transition from health to atrophy in donor eyes with nvAMD. Method In RPE-Bruch’s membrane flat mounts of 5 nvAMD eyes the terminations of organized RPE cytoskeleton and autofluorescent material were compared. In high-resolution histological sections of 27 nvAMD eyes, RPE phenotypes were assessed at ±500 and ±100 µm from the descent of the external limiting membrane (ELM) towards Bruch’s membrane. Thicknesses of RPE, basal laminar deposit (BLamD), and RPE+BLamD were determined. Shapes of the ELM descent were recorded. Results Approaching the ELM descent, the percentage of different RPE phenotypes (Zanzottera, IOVS 2015) and the thickness of RPE, BLamD, and RPE + BLamD each stayed roughly constant. When compared to a separately described cohort of eyes with geographic atrophy, eyes with nvAMD were more likely to have RPE dysmorphia that did not worsen towards the atrophy border, thinner BLamD overall (3.25 ± 3.46 µm vs 7.99 ± 7.49 µm for geographic atrophy), and a higher proportion of oblique ELM descents (47.9% vs 31.9%). Conclusion The distribution of RPE phenotypes at the transition to macular atrophy in eyes with nvAMD differs from that in primary geographic atrophy, likely reflecting greater photoreceptor loss and the effects of exudation in nvAMD. This distribution, the shape of ELM descents, and thickness profiles may be useful metrics in clinical studies of macular atrophy utilizing optical coherence tomography and fundus autofluorescence.

“…These newly described migratory cells of apparent RPE origin play an as-yet undefined role in AMD progression. Remarkably, most RPE phenotypes are visible by SDOCT, 8, 20, 21 suggesting that an accurate timeline of RPE degeneration is attainable through clinical imaging.…”

Section: Introductionmentioning

confidence: 99%

Visualizing Retinal Pigment Epithelium Phenotypes in the Transition to Geographic Atrophy in Age-Related Macular Degeneration

Zanzottera

Ach

Huisingh

et al. 2016

Self Cite

136

Purpose To inform the interpretation of clinical optical coherence tomography and fundus autofluorescence?imaging in geographic atrophy (GA) of age-related macular degeneration (AMD) by determining the distribution of retinal pigment epithelium (RPE) phenotypes in the transition from health to atrophy (GA) in donor eyes. Method In RPE-Bruch’s membrane flat mounts of 2 GA eyes the terminations of organized RPE cytoskeleton and autofluorescent material were compared. In high-resolution histological sections of 13 GA eyes, RPE phenotypes were assessed at ±500 and ±100 µm from the descent of the external limiting membrane (ELM) towards Bruch’s membrane. The ELM descent was defined as curved, reflected, or oblique in shape. Thicknesses of RPE, basal laminar deposit (BLamD), and RPE+BLamD were measured. Results A border of atrophy that can be precisely delimited is the ELM descent, as opposed to the termination of the RPE layer itself, because of dissociated RPE in the atrophic area. Approaching the ELM descent, the percentage of abnormal RPE morphologies increases, the percentage of age-normal cells decreases, overall RPE thickens, and BLamD does not thin. The combination of RPE plus BLamD is 19.7% thicker at −100 µm from the ELM descent than at −500 µm (23.1 ± 10.7 vs 19.3 ± 8.2 µm; p=0.05). Conclusion The distribution of RPE phenotypes at the GA transition support the idea that these morphologies represent defined stages of a degeneration sequence. The idea RPE dysmorphia including rounding and stacking helps explain variable autofluorescence patterns in GA 14 is reinforced. The ELM descent and RPE+BLamD thickness profile may have utility as SDOCT metrics in clinical trials.