Multimodal imaging of small hard retinal drusen in young healthy adults

BackgroundSmall hard macular drusen can be observed in the retina of adults as young as 18 years of age. Here, we seek to describe the in vivo topography and geometry of these drusen.MethodsRetinal images were acquired in young, healthy adults using colour fundus photography, spectral domain optic coherence tomography (SD-OCT), reflectance flood-illuminated adaptive optic ophthalmoscopy (AO flood) and reflectance adaptive optic scanning light ophthalmoscopy (AOSLO) in both confocal and non-confocal split-detection modalities. Small bright yellow hard drusen within a 10 degree radius from the foveal centre were characterised.ResultsSmall hard drusen were seen on colour photographs in 21 out of 97 participants and 26 drusen in 12 eyes in 11 participants were imaged using the full protocol. Drusen were easily identifiable in all modalities, except a few very small ones, which were not visible on SD-OCT. On AOSLO images, these drusen appeared as round, oval or lobular areas (up to three lobules) of diameter 22–61 µm where cone photoreceptor reflectivity and density was decreased (p=0.049). This was usually associated with discrete thickening of the retinal pigment epithelium (RPE) complex.ConclusionHigh lateral resolution imaging of small lobular hard retinal drusen suggests formation through the confluence of two or more smaller round lesions. The outline and size of these smaller lesions corresponds to 1–4 RPE cells. Prospective longitudinal studies are needed to determine the ultimate fate of small hard drusen and their potential relation to age-related macular degeneration.

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Six-year incidence of age-related macular degeneration and correlation to OCT-derived drusen volume measurements in a Chinese population

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319290 ◽

2021 ◽

pp. bjophthalmol-2021-319290

Author(s):

Anna CS Tan ◽

Miao Li Chee ◽

Beau J Fenner ◽

Paul Mitchell ◽

Yih Chung Tham ◽

...

Keyword(s):

Risk Factors ◽

Macular Degeneration ◽

Systemic Risk ◽

Retinal Pigment ◽

Older Age ◽

Age Related Macular Degeneration ◽

Fundus Photography ◽

Age Related ◽

Systemic Risk Factors ◽

Sd Oct

AimsTo report the 6-year incidence of optical coherence tomography (OCT)-derived age-related changes in drusen volume and related systemic and ocular associations.MethodsChinese adults aged 40 years and older were assessed at baseline and 6 years with colour fundus photography (CFP) and spectral domain (SD) OCT. CFPs were graded for age-related macular degeneration (AMD) features and drusen volume was generated using commercially available automated software.ResultsA total of 4172 eyes of 2580 participants (mean age 58.12±9.03 years; 51.12% women) had baseline and 6-year follow-up CFP for grading, of these, 2130 eyes of 1305 participants had gradable SD-OCT images, available for analysis. Based on CFP grading, 136 (3.39%) participants developed incident early AMD and 10 (0.25%) late AMD. Concurrently, retinal pigment epithelial-Bruch’s membrane (RPE-BrC) volumes decreased, remained stable and increased in 6.8%, 78.5% and 14.7%, respectively, over 6 years. In eyes where RPE-BrC volumes were >0 mm3 at baseline, this was associated with two-fold higher prevalence rate of any AMD at baseline (p<0.001). Multivariable analysis showed that when compared with eyes where RPE-BrC volume was unchanged, volume decrease was significantly associated with older age (OR=1.30; p<0.001), smoking (OR=2.21; p=0.001) and chronic kidney disease (OR=3.4, p=0.008), while increase was associated with older age (OR=1.36; p<0.001) and hypertension (OR=1.43; p=0.016).ConclusionAMD incidence detected at 6 years on CFP and correlated OCT-derived drusen volume measurement change is low. Older age and some systemic risk factors are associated with drusen volume change, and our data provide new insights into relationship between systemic risk factors and outer retinal morphology in Asian eyes.

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High-Resolution Optical Coherence Tomography Retinal Imaging: A Case Series Illustrating Potential and Limitations

Journal of Ophthalmology ◽

10.1155/2011/764183 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 14

Author(s):

Olena Puzyeyeva ◽

Wai Ching Lam ◽

John G. Flanagan ◽

Michael H. Brent ◽

Robert G. Devenyi ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Macular Degeneration ◽

Retinal Pigment ◽

Central Retinal Artery Occlusion ◽

Case Series ◽

Age Related Macular Degeneration ◽

Fundus Photography ◽

Optical Coherence ◽

Age Related ◽

Sd Oct

Purpose. To present a series of retinal disease cases that were imaged by spectral domain optical coherence tomography (SD-OCT) in order to illustrate the potential and limitations of this new imaging modality.Methods. The series comprised four selected cases (one case each) of age-related macular degeneration (ARMD), diabetic retinopathy (DR), central retinal artery occlusion (CRAO), and branch retinal vein occlusion (BRVO). Patients were imaged using the Heidelberg Spectralis (Heidelberg Engineering, Germany) in SD-OCT mode. Patients also underwent digital fundus photography and clinical assessment.Results. SD-OCT imaging of a case of age-related macular degeneration revealed a subfoveal choroidal neovascular membrane with detachment of the retinal pigment epithelium (RPE) and neurosensory retina. Using SD-OCT, the cases of DR and BRVO both exhibited macular edema with cystoid spaces visible in the outer retina.Conclusions. The ability of SD-OCT to clearly and objectively elucidate subtle morphological changes within the retinal layers provides information that can be used to formulate diagnoses with greater confidence.

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Progressive dysmorphia of retinal pigment epithelium in age related macular degeneration revealed by fluorescence lifetime imaging

10.1101/2021.04.14.21255463 ◽

2021 ◽

Author(s):

Martin Hammer ◽

Juliane Jakob-Girbig ◽

Linda Schwanengel ◽

Christine A. Curcio ◽

Somar Hasan ◽

...

Keyword(s):

Retinal Pigment Epithelium ◽

Macular Degeneration ◽

Fluorescence Lifetime ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Age Related Macular Degeneration ◽

Fundus Photography ◽

Fluorescence Lifetime Imaging ◽

Lifetime Imaging ◽

Age Related

AbstractPurposeTo observe changes of the retinal pigment epithelium (RPE) on the transition from dysmorphia to atrophy in age related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO).MethodsMultimodal imaging including color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, and FLIO was performed in 40 eyes of 37 patients with intermediate AMD and no evidence for geographic atrophy or macular neovascularization) (mean age: 74.2±7.0 years). Twenty-three eyes were followed for 28.3±18.3 months. Seven eyes had a second follow up after 46.6±9.0 months. Thickened RPE on OCT, hyperpigmentation on CFP, and migrated RPE, seen as hyperreflective foci (HRF) on OCT, were identified. Fluorescence lifetimes in two spectral channels (SSC: 500-560 nm, LSC: 560-720 nm) as well as emission spectrum intensity ratio (ESIR) of the lesions were measured by FLIO.ResultsAs hyperpigmented areas form and RPE migrates into the retina, FAF lifetimes lengthen and ESRI of RPE cells increase. Thickened RPE showed lifetimes of 256±49 ps (SSC) and 336±35 ps (LSC) and an ESIR of 0.552±0.079. For hyperpigmentation, these values were 317±68 ps (p<0.001), 377±56 ps (p<0.001), and 0.609±0.081 (p=0.001), respectively, and for HRF 337±79 ps (p<0.001), 414±50 ps (p<0.001), and 0.654±0.075 (p<0.001).ConclusionsIn the process of RPE degeneration, comprising different steps of dysmorphia, hyperpigmentation, and migration, lengthening of FAF lifetimes and a hypsochromic shift of emission spectra can be observed by FLIO. Thus, FLIO might provide early biomarkers for AMD progression and contribute to our understanding of RPE pathology.

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Origins of Ghost Drusen: A follow-up Analysis

Ophthalmology Point of Care ◽

10.5301/oapoc.0000011 ◽

2017 ◽

Vol 1 (1) ◽

pp. oapoc.0000011

Author(s):

Caroline Bottin ◽

Olivia Zambrowski ◽

Giuseppe Querques ◽

Salomon Yves Cohen ◽

Mayer Srour ◽

...

Keyword(s):

Pigment Epithelium ◽

Retinal Pigment ◽

Geographic Atrophy ◽

Primary Lesion ◽

Age Related Macular Degeneration ◽

Age Related ◽

Soft Drusen ◽

Initial Lesions ◽

Sd Oct

Purpose Ghost drusen (GD) are pyramidal or dome-shaped retinal pigment epithelium elevations observed in some geographic atrophy (GA) areas in the context of age-related macular degeneration (AMD). The purpose was to investigate the first morphologic features preceding GD on spectral-domain optical coherence tomography (SD-OCT) on patients with GA associated with AMD. Methods A retrospective observational study was performed on a series of patients with GA that had at least 3 years of follow-up. Using the follow-up tool of SD-OCT, we tracked the initial lesions that could lead to GD. Results Among 442 patients with GA, 37 had well defined GD (8%). We included the 17/37 patients (31 eyes) with at least 3 years of follow-up for analysis, which led to a total of 582 counted GD. Most GD were already present at the first visit, and remained stable. However, on 13 of the 582 analyzed GD (2.2%), soft drusen were shown as the initial lesion, which progressively turned into GD. Conclusions GD were observed in less than 10% of eyes with GA. None of the ghost drusen turned into another shaped lesion, suggesting that GD is a possible final stage of evolution. In a few cases, large drusen were shown as the primary lesion that progressed into GD.

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Low-Reflectivity Drusen With Overlying RPE Damage Revealed by Spectral-Domain OCT: Hint for the Development of Age-Related Macular Degeneration

Frontiers in Medicine ◽

10.3389/fmed.2021.706502 ◽

2021 ◽

Vol 8 ◽

Author(s):

Shasha Yang ◽

Zongyin Gao ◽

Haijiang Qiu ◽

Chengguo Zuo ◽

Lan Mi ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Macular Degeneration ◽

Retinal Pigment ◽

Morphological Characteristics ◽

Age Related Macular Degeneration ◽

Spectral Domain ◽

Optical Coherence ◽

Age Related ◽

Sd Oct

Purpose: To observe the relationship between the characteristic changes in the drusen morphology revealed by the spectral-domain optical coherence tomography (SD-OCT) and the progression of age-related macular degeneration (AMD).Methods: A total of 380 drusen in 45 eyes in 35 patients with the intermediate drusen were longitudinally followed up every 6 months by SD-OCT for a period of 24 months. The drusen were divided into the dynamic group and stable group according to the following parameters: number, volume, concurrent retinal pigment epithelium (RPE)/ellipsoid zone (EZ) damage, and the development of advanced AMD. The morphological characteristics of the progressive or stable drusen were further analyzed. Odds ratios (ORs) and the risk for the drusen progression were calculated.Results: The level of interobserver and intraobserver agreement for each drusen tomographic morphological parameters ranged from 82.7 to 90%. At the end of an average follow-up of 15.92 ± 6.99 months, six patients developed choroidal neovascularization and no patients developed geographic atrophy. Finally, 139 drusen changed and 241 drusen remained stable. The drusen with low reflectivity (p < 0.001; OR: 5.26; 95% CI: 2.24–12.36), non-homogeneity without a core (p < 0.001; OR: 4.31; 95% CI: 2.08–8.92), RPE damage (p < 0.001; OR: 28.12; 95% CI: 9.43–83.85), and the EZ damage (p < 0.001; OR: 14.01; 95% CI: 5.28–37.18) were significantly associated with active change; the drusen with low reflectivity (p = 0.01; OR: 2.95; 95% CI: 1.29–6.75) and decreased overlying RPE reflectivity (p < 0.001; OR: 21.67; 95% CI: 9.20–51.02) were the independent predictors for progression. The drusen with high reflectivity were significantly associated with stabilization (p = 0.03; OR: 0.17; 95% CI: 0.04–0.84).Conclusion: Spectral-domain optical coherence tomography is an optimized, accurate, and efficient method to follow-up the drusen. The intermediate non-exudative AMD prognosis of the patient was most strongly correlated with the drusen reflectivity and disruption of the overlying RPE layer. The drusen with low reflectivity and overlying RPE damage were more likely to progress and required frequent follow-up.

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Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration

Science Translational Medicine ◽

10.1126/scitranslmed.aat4544 ◽

2018 ◽

Vol 10 (466) ◽

pp. eaat4544 ◽

Cited By ~ 34

Author(s):

Anna C. S. Tan ◽

Matthew G. Pilgrim ◽

Sarah Fearn ◽

Sergio Bertazzo ◽

Elena Tsolaki ◽

...

Keyword(s):

Macular Degeneration ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Age Related Macular Degeneration ◽

Human Eye ◽

Age Related ◽

Increased Risk ◽

Risk Of Progression ◽

Retinal Drusen ◽

Independent Cohort

Drusen are lipid-, mineral-, and protein-containing extracellular deposits that accumulate between the basal lamina of the retinal pigment epithelium (RPE) and Bruch’s membrane (BrM) of the human eye. They are a defining feature of age-related macular degeneration (AMD), a common sight-threatening disease of older adults. The appearance of heterogeneous internal reflectivity within drusen (HIRD) on optical coherence tomography (OCT) images has been suggested to indicate an increased risk of progression to advanced AMD. Here, in a cohort of patients with AMD and drusen, we show that HIRD indicated an increased risk of developing advanced AMD within 1 year. Using multimodal imaging in an independent cohort, we demonstrate that progression to AMD was associated with increasing degeneration of the RPE overlying HIRD. Morphological analysis of clinically imaged cadaveric human eye samples revealed that HIRD was formed by multilobular nodules. Nanoanalytical methods showed that nodules were composed of hydroxyapatite and that they differed from spherules and BrM plaques, other refractile features also found in the retinas of patients with AMD. These findings suggest that hydroxyapatite nodules may be indicators of progression to advanced AMD and that using multimodal clinical imaging to determine the composition of macular calcifications may help to direct therapeutic strategies and outcome measures in AMD.

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POLYPOIDAL CHOROIDAL VASCULOPATHY IN CAUCASIANS: MORPHOLOGICAL FINDINGS FROM MULTIMODAL RETINAL IMAGING

Ophthalmologica ◽

10.1159/000515295 ◽

2021 ◽

Author(s):

Jorge M. Simão ◽

Cláudia V. Farinha ◽

João P. Marques ◽

Sandrina Nunes ◽

Isabel M. Pires ◽

...

Keyword(s):

Polypoidal Choroidal Vasculopathy ◽

Retinal Pigment ◽

Subretinal Fluid ◽

Morphological Features ◽

Age Related Macular Degeneration ◽

Fundus Photography ◽

Soft Drusen ◽

The Mean ◽

Choroidal Vasculopathy ◽

Sd Oct

Purpose: To characterize the morphological features of polypoidal choroidal vasculopathy (PCV) in a large Caucasian population. Methods: A multicenter, cross-sectional study of treatment-naïve patients with PCV. Baseline fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein and indocyanine green angiography (FA,ICGA) were assessed by trained medical graders. Typical PCV features were explored, and retinal and choroidal thickness (RT,CT) measurements were performed. Results: Seventy-nine eyes of 73 patients (mean age,72.6±11.9 years) were included. ICGA identified macular polyps in 89.9% of cases. SD-OCT revealed mostly subretinal fluid (93.6%) and a retinal pigment epithelium (RPE) detachment in 91.4%, with sharp protrusion in 67.0%. Polyp-like structures were seen in 74.3%, mostly adherent to an elevated RPE (69.6%). Type 1 neovascularization (NV) was identified in 74.7%, while 16.5% had a mixed NV. The mean macular CT was 220.9±83.2 µm (range,67.9-403.6). Diffuse and focal pachychoroid were observed in 26.6% and 30.4%. Soft drusen were reported in 62.0%, but retinal hemorrhage occurred in only 19.0%. Conclusion: The morphological features of PCV in Caucasians are similar to those reported in Asians. Pachychoroid signs were found in nearly half of our cohort. However, the mean age at presentation, high prevalence of soft drusen, and low prevalence of large subretinal hemorrhages make PCV closer to age-related macular degeneration in this ethnic group.

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Quantification of Early and Intermediate Age-related Macular Degeneration Using OCT “en face” Presentation

Klinische Monatsblätter für Augenheilkunde ◽

10.1055/a-1327-3633 ◽

2021 ◽

Author(s):

Frauke Jürgens ◽

Kai Rothaus ◽

Henrik Faatz ◽

Britta Heimes-Bussmann ◽

Daniel Pauleikhoff ◽

...

Keyword(s):

Clinical Trials ◽

Macular Degeneration ◽

Retinal Pigment ◽

Age Related Macular Degeneration ◽

Fundus Photography ◽

Slice Thickness ◽

Age Related ◽

En Face Oct ◽

En Face ◽

The Impact

Abstract Background Early and intermediate age-related macular degeneration (AMD) results in drusen deposits under the retinal pigment epithelium (RPE). These early stages of AMD exhibit different risks of progressing to late AMD. To date, early AMD has been classified and quantified by fundus photography. This does not appear to be sensitive enough for clinical trials studying the impact on drusen. SD-OCT with two-dimensional rendering of the segmented slices analysed allows for en face imaging of the drusen. The present trial studied the potential of quantifying early and intermediate AMD by en-face optical coherence tomography (OCT). Material and Methods Thirty-one eyes of 29 patients in different stages of early and intermediate AMD were studied. To this end, fundus photographs (Kowa VX-10i, Kowa, Tokyo, Japan) and en-face OCT images (RTVue XR Avanti, Optovue, Inc., Fremont, CA, USA) were taken. First, different segmentation levels (6 µm underneath the RPE, on the RPE, 6 µm and 9 µm above the RPE) and different layer thicknesses (5 µm, 10 µm, 20 µm and 30 µm) were analysed to determine the best segmentation for visualising drusen. Drusen were marked manually and their number and surface area calculated. This analysis was then compared with the standardised drusen analyses on fundus photography. Additional changes in early and intermediate AMD such as pigment epithelial detachments (PEDs) and subretinal drusenoid deposits (SDD) as well as small atrophies were also documented and compared. Outcomes The best segmentation for delineating the drusen on the en-face OCT images was found to be a segmentation 6 µm underneath the RPE with a slice thickness of 20 µm. Comparison of drusen quantification on en-face OCT images with the standardised drusen analysis on fundus photography revealed particularly good similarity. Other changes in early and intermediate AMD, such as PEDs, SDD and small atrophies, were easier to assess on the en-face OCT images. Conclusions The analysis and quantification of drusen from en-face OCT images with 20 µm segmentation at 6 µm underneath the RPE allows differentiated quantification of various drusen characteristics. Moreover, other changes in early and intermediate AMD can also be analysed. In future observational and clinical trials, this could help quantify drusen.

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FTO alleviates Aβ1-40 induced retinal pigment epithelium degeneration via PKA/CREB signaling pathway

10.21203/rs.3.rs-30549/v1 ◽

2020 ◽

Author(s):

YiFan Hu ◽

JieQiong Chen ◽

JunRan Sun ◽

YuWei Wang ◽

PeiRong Huang ◽

...

Keyword(s):

Retinal Pigment Epithelium ◽

Signaling Pathway ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Amyloid Β ◽

Age Related Macular Degeneration ◽

Fundus Photography ◽

Molecular Characteristics ◽

Cell Degeneration ◽

Age Related

Abstract Background Amyloid-β (Aβ), a component of age-related macular degeneration (AMD) hallmark drusen, induces retinal pigment epithelium (RPE) cell degeneration and promotes the progress of AMD. Evidence shows that epigenetics mechanism is involved in the regulation of AMD. In this study, we aimed to investigate the roles of N6-methyladenosine (m6A) and its demethylase the fat mass and obesity-associated gene (FTO) in Aβ-mediated degeneration. Methods The molecular characteristics and morphology of FTO were examined by quantitative Real-Time PCR (qRT-PCR), Western blot and immunofluorescence. Inhibition of FTO was conducted to analyze its function on cell survival. Ocular Coherence Tomography and Fundus Photography was performed to evaluate the fundus of animal models. m6A-mRNA Epi-transcriptomic microarray, bioinformatics analysis and experimental verification were used to explore the potential molecular mechanism and signaling pathway. Results We found overexpression of FTO in Aβ model and demonstrated that inhibition of FTO by the sodium form of Meclofenamic acid (MA1) aggravated RPE impairment. Mechanistically, we identified protein kinase A (PKA) as FTO’s mediating target and found that FTO epigenetically demethylated PKA mRNA and decreased PKA expression, leading to suppressed PKA/ cyclin AMP-responsive element binding (CREB) signaling pathway. Moreover, inhibition of FTO promoted PKA/CREB signaling pathway inducing greater RPE degeneration and death. Conclusions These data demonstrated the functional significance of FTO in Aβ-induced RPE degeneration and the regulatory mechanism of PKA/CREB signaling pathway, implying FTO as a potentially therapeutic target for AMD.

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Spectral-domain Optical Coherence Tomography Imaging of Age-related Macular Degeneration

European Ophthalmic Review ◽

10.17925/eor.2011.05.02.98 ◽

2011 ◽

Vol 05 (02) ◽

pp. 98

Author(s):

Carlos Alexandre de Amorim Garcia Filho ◽

Philip J Rosenfeld ◽

Zohar Yehoshua ◽

Giovanni Gregori ◽

◽

...

Keyword(s):

Optical Coherence Tomography ◽

High Resolution ◽

Macular Degeneration ◽

High Speed ◽

Retinal Pigment ◽

Age Related Macular Degeneration ◽

High Resolution Imaging ◽

Age Related ◽

Resolution Imaging ◽

Sd Oct

Spectral-domain optical coherence tomography (SD-OCT) high-speed, high-resolution imaging of the macula has become an essential tool for evaluating dry and wet age-related macular degeneration (AMD). This high-speed, high-resolution imaging strategy, combined with new innovative algorithms, permits reproducible measurements of the anatomical changes associated with AMD, which include drusen, geographic atrophy (GA) and choroidal neovascularisation (CNV). To visualise drusen and larger retinal pigment epithelial detachments, an algorithm was developed for Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) to detect elevations in the retinal pigment epithelium (RPE). To visualise GA, an algorithm was developed to provide en face visualisation of the macula, which easily identifies and measures areas where the RPE has been lost. To visualise CNV and the associated macular fluid, an algorithm was developed to measure the retinal thickness between the internal limiting membrane and the RPE. No other imaging modality is capable of qualitatively and quantitatively following patients at all stages of AMD, which makes SD-OCT the ideal instrument for following disease progression and the effect of therapies.

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