Fundus Autofluorescence Characteristics of Nascent Geographic Atrophy in Age-Related Macular Degeneration

Wu, Zhichao; Luu, Chi D; Ayton, Lauren N; Goh, Jonathan; Lucci, Lúcia Míriam Dumont; Hubbard, William C.; Hageman, Jill L.; Hageman, Gregory S.; Guymer, Robyn H.

doi:10.1167/iovs.14-16211

Cited by 60 publications

(55 citation statements)

References 36 publications

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“…21 Also, as shown by Wu et al, atrophy of the RPE and overlying photoreceptors on SDOCT immediately preceded new onset of drusen-associated GA on CP. 22,23 Briefly, these findings suggested that SDOCT is useful to visualize early indicators of atrophy, rather than neovascularization. 14–21 In an attempt to further clarify the sequence of degenerative events in the atrophic pathway, we focused this report on the A2A SDOCT Study aims pertinent to atrophy and its possible precursors.…”

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confidence: 99%

Optical Coherence Tomography Predictors of Risk for Progression to Non-Neovascular Atrophic Age-Related Macular Degeneration

et al. 2017

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Purpose The appearance of geographic atrophy (GA) on color photography (CP) is preceded by specific features on spectral domain optical coherence tomography (SDOCT). We aimed to build SDOCT-based risk assessment models for 5-year new onset of GA and central GA on CP. Design Prospective longitudinal study. Participants Age-related macular degeneration (AMD) patients with bilateral large drusen and/or non-central GA, and at least one eye without advanced disease (n=317) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT study. Methods For one eye per participant, qualitative and quantitative SDOCT variables were derived, respectively, from standardized grading and semi-automated segmentation at baseline. Up to 7 years later, annual outcomes were extracted and analyzed to fit multivariate logistic regression models and build a risk calculator. Main Outcome Measures New onset of CP-visible GA and central GA. Results Over a follow-up median of 4.0 years and among 292 AMD eyes (without advanced disease at baseline) with complete outcome data, 46 (15.8%) developed central GA. Among a subset of 265 eyes without any GA on baseline CP, 70 (26.4%) developed CP-visible GA. Final multivariate models were adjusted for age. In the model for GA, the independent predicting SDOCT factors (p <0.001 to 0.03) were (1) hyperreflective foci (HF) and (2) retinal pigment epithelium layer atrophy or absence (RPEA), followed by (3) choroidal thickness in absence of subretinal drusenoid deposits, (4) photoreceptor outer segment loss, (5) RPE drusen complex (RPEDC) volume and (6) RPEDC abnormal thinning (RAT) volume. For central GA, the independent predicting SDOCT factors (p<0.001) were (1) RAT volume, (2) intraretinal fluid or cystoid spaces, (3) HF, and (4) RPEA. The models yielded a calculator that computes the probabilities of CP-visible new-onset GA and central GA after 1 through 5 years. Conclusions For AMD eyes with large drusen and no advanced disease, we built a novel risk assessment model – based on age and SDOCT segmentation, drusen characteristics, and retinal pathology – for progression to CP-visible GA over up to 5 years. This calculator may simplify SDOCT grading and, with future validation, have a promising role as a clinical prognostic tool.

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confidence: 99%

Optical Coherence Tomography Predictors of Risk for Progression to Non-Neovascular Atrophic Age-Related Macular Degeneration

et al. 2017

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“…24 Using high-resolution multimodal imaging, in particular spectral-domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy (cSLO) fundus autofluorescence (FAF), the evolution of atrophy has been scrutinized in more detail. 23,[25][26][27][28] Among those observations, ''nascent GA'' as part of the chronological appearance of drusen-associated atrophy development has been analyzed by Wu et al 26 Recently, the Classification of Atrophy Meetings (CAM) group defined OCT-based criteria for complete RPE and outer retinal atrophy (cRORA) as atrophy in AMD. 29 The aim of the current study was to analyze the incidence and development of central atrophy in AMD eyes that were considered at high risk for development of late AMD stages.…”

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confidence: 99%

Multimodal Imaging Patterns for Development of Central Atrophy Secondary to Age-Related Macular Degeneration

Thiele

Pfau

Larsen

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To evaluate the development of central atrophy in eyes with age-related macular degeneration (AMD).METHODS. Six-year longitudinal multimodal retinal imaging data (MODIAMD study) from 98 eyes of 98 subjects with non-late-stage AMD in the study eye at baseline were analyzed for the presence of central atrophy at each annual follow-up visit. Development, manifestation, and further progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) by multimodal imaging data were compared with atrophy detection based on color fundus photography only.RESULTS. Seventeen study eyes with development of central cRORA within 6 years (cumulative rate: 17.4%) were identified based on multimodal imaging. In 10 (60%) of these eyes, presence of central manifest atrophy was initially not detectable by color fundus photography. In six (35%) eyes, central cRORA occurred by the spread of existing paracentral atrophy toward the fovea. Drusen-associated atrophy development was noted in eight eyes. In two eyes, atrophy development was associated with refractile deposits, while only pigmentary changes in absence of large drusen or refractile deposits were detectable before atrophy occurrence in one eye.CONCLUSIONS. The earlier and more precise detection of central cRORA by multimodal imaging as compared to atrophy detection solely based on color fundus photography allows for more accurate detection and identification of different pathways for atrophy development. In accordance with previous clinical and histopathologic reports, the results confirm that different precursor lesions may independently proceed to central cRORA in AMD.

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“…15 It is also recognized that subtle changes in microstructural features occur in the early stages of AMD, despite not easily appreciated on clinical examination or on CFPs. 16,17 Such changes can be visualized and quantified on high-resolution imaging modalities such as SD-OCT, including changes to the extent and morphology of drusen, 4,8,9,[18][19][20][21] pigmentary abnoriovs.arvojournals.org j ISSN: 1552-5783 malities, 6 atrophic changes (including nascent GA [nGA] 7,22 and drusen-associated atrophy) and the integrity of the photoreceptor inner-segment ellipsoid (ISe) band. 19 Previous studies have also observed that changes in some of these microstructural features are strongly associated with changes in mesopic microperimetric sensitivity, although it is not possible to conclude whether any of these parameters represent the underlying pathologic changes that are contributing to the decreased visual sensitivity.…”

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confidence: 99%

“…This study, therefore, examined the associations between visual function changes on mesopic microperimetry and longitudinal changes in SD-OCT microstructural parameters, including drusen volume, pigmentary changes (visualized on SD-OCT as hyperreflective foci [HF] 28 ) and its inner retinal migration and proliferation, 6 and atrophic changes (including nGA and drusen-associated atrophy detected on SD-OCT 7,22 ) in participants with the early stages of AMD. All these parameters have been observed to be significantly associated with the future development of advanced AMD, [6][7][8][9] and may therefore be independently associated with the longitudinal rate of change in microperimetric sensitivity.…”

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confidence: 99%

Longitudinal Associations Between Microstructural Changes and Microperimetry in the Early Stages of Age-Related Macular Degeneration

Cunefare

Chiu

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To determine whether longitudinal changes in mesopic visual function on microperimetry occurred independent of its associations with microstructural parameters on spectral-domain optical coherence tomography (SD-OCT) in the early stages of AMD.METHODS. Forty-one AMD eyes underwent microperimetry testing and SD-OCT scans over a 12-month period at 6-month intervals. Microstructural parameters analyzed include the retinal pigment epithelium-drusen complex (RPEDC) layer thickness, number of hyperreflective foci (HF) and their inner retinal migration (represented by a weighted axial distribution score; AxD), and the number of atrophic areas.RESULTS. Microperimetric sensitivity was 0.29 dB (95% confidence interval [CI] ¼ À0.38 to À0.20 dB, P < 0.001) and 0.13 dB (95% CI ¼ À0.22 to À0.03 dB, P ¼ 0.008) lower in each sector for every 10-lm higher RPEDC layer thickness and 1-HF present, but was not associated with the AxD score or the number of atrophic areas present (P 0.464). However, each 10-lm greater RPEDC layer thickness and 1-HF present was not independently associated with a further decline in sensitivity (À0.08 dB/year, 95% CI ¼ À0.24 to 0.07 dB/year, P ¼ 0.288 and 0.09 dB/year, 95% CI ¼ À0.06 to 0.24 dB/year, P ¼ 0.242, respectively) over time when accounting for the association between RPEDC layer thickness and number of HF with microperimetric sensitivity. CONCLUSIONS.Longitudinal changes in mesopic visual function measured on microperimetry paralleled changes in the microstructural changes over a 12-month time frame, without any changes occurring independent of the associations between structure and function alone.

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Fundus Autofluorescence Characteristics of Nascent Geographic Atrophy in Age-Related Macular Degeneration

Cited by 60 publications

References 36 publications

Optical Coherence Tomography Predictors of Risk for Progression to Non-Neovascular Atrophic Age-Related Macular Degeneration

Optical Coherence Tomography Predictors of Risk for Progression to Non-Neovascular Atrophic Age-Related Macular Degeneration

Multimodal Imaging Patterns for Development of Central Atrophy Secondary to Age-Related Macular Degeneration

Longitudinal Associations Between Microstructural Changes and Microperimetry in the Early Stages of Age-Related Macular Degeneration

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