A Longitudinal Comparison of Spectral-Domain Optical Coherence Tomography and Fundus Autofluorescence in Geographic Atrophy

doi:10.1016/j.ajo.2014.05.026

American Journal of Ophthalmology

Volume 158, Issue 3, September 2014, Pages 557-566.e1

https://doi.org/10.1016/j.ajo.2014.05.026 Get rights and content

Purpose

To identify reliable criteria based on spectral-domain optical coherence tomography (SD OCT) to monitor disease progression in geographic atrophy attributable to age-related macular degeneration (AMD) compared with lesion size determination based on fundus autofluorescence (FAF).

Design

Prospective longitudinal observational study.

Methods

setting: Institutional. study population: A total of 48 eyes in 24 patients with geographic atrophy. observation procedures: Eyes with geographic atrophy were included and examined at baseline and at months 3, 6, 9, and 12. At each study visit best-corrected visual acuity (BCVA), FAF, and SD OCT imaging were performed. FAF images were analyzed using the region overlay device. Planimetric measurements in SD OCT, including alterations or loss of outer retinal layers and the RPE, as well as choroidal signal enhancement, were performed with the OCT Toolkit. main outcome measures: Areas of interest in patients with geographic atrophy measured from baseline to month 12 by SD OCT compared with the area of atrophy measured by FAF.

Results

Geographic atrophy lesion size increased from 8.88 mm² to 11.22 mm² based on quantitative FAF evaluation. Linear regression analysis demonstrated that results similar to FAF planimetry for determining lesion progression can be obtained by measuring the areas of outer plexiform layer thinning (adjusted R² = 0.93), external limiting membrane loss (adjusted R² = 0.89), or choroidal signal enhancement (R² = 0.93) by SD OCT.

Conclusions

SD OCT allows morphologic markers of disease progression to be identified in geographic atrophy and may improve understanding of the pathophysiology of atrophic AMD.

Section snippets

Methods

Patients for this prospective longitudinal study were recruited by the Department of Ophthalmology at the Medical University of Vienna. The institutional ethics committee of the Medical University of Vienna approved the study. Written informed consent was obtained from each participant before inclusion in the study. The study protocol and procedures followed the tenets of the Declaration of Helsinki. The study is registered at the Ethics Committee in Vienna (//ethikkommission.meduniwien.ac.at

Clinical Progression of Geographic Atrophy Disease

Forty-eight eyes in 24 patients (13 women, 11 men) were included in this prospective study with a follow-up of 12 months. All participants presented with bilateral geographic atrophy and were followed in quarterly intervals using a standardized protocol. Mean BCVA was 58 letters (20/69 Snellen equivalent) at baseline, and declined to 56.5 letters (20/74) at 3 months, 53 (20/87) at 6 months, 52.5 (20/89) at 9 months, and 50.5 letters (20/98) at 12 months. The difference between BCVA at baseline

Discussion

This study in a cross-sectional patient population based on prespecified SD OCT parameters and comprehensive grading of volume scans offers a systematic analysis of disease progression in atrophic AMD over time using morphologic SD OCT features in comparison to FAF measurements. It is the first prospective longitudinal study aimed at determining the potential of SD OCT for monitoring patients with geographic atrophy during follow-up. The study was designed not only to validate our previous

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Cited by (36)

Comparison of Fundus Autofluorescence Versus Optical Coherence Tomography–based Evaluation of the Therapeutic Response to Pegcetacoplan in Geographic Atrophy
2022, American Journal of Ophthalmology
To perform an optical coherence tomography (OCT)-based analysis of geographic atrophy (GA) progression in patients treated with pegcetacoplan.
Post hoc analysis of a phase 2 multicenter, randomized, sham-controlled trial.
Manual annotation of retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) loss was performed on OCT volumes from baseline and month 12 from the phase 2 FILLY trial of intravitreal pegcetacoplan for the treatment of GA secondary to age-related macular degeneration.
Correlation of GA areas measured on fundus autofluorescence and OCT. Difference in square root transformed growth rates of RPE, EZ, and ELM loss between treatment groups (monthly injection [AM], injection every other month [AEOM], and sham [SM]).
OCT volumes from 113 eyes of 113 patients (38 AM, 36 AEOM, and 39 SM) were included, resulting in 11 074 B-scans. The median growth of RPE loss was significantly slower in the AM group (0.158 [0.057-0.296]) than the SM group (0.255 [0.188-0.359], P = .014). Importantly, the growth of EZ loss was also significantly slower in the AM group (0.127 [0.041-0.247]) than the SM group (0.232 [0.130-0.349], P = .017). There was no significant difference in the growth of ELM loss between the treatment groups (P = .114).
OCT imaging provided consistent results for GA growth compared with fundus autofluorescence. In addition to slower RPE atrophy progression in patients treated with pegcetacoplan, a significant reduction in EZ impairment was also identified by OCT, suggesting the use of OCT as a potentially more sensitive monitoring tool in GA therapy.
Role of Deep Learning–Quantified Hyperreflective Foci for the Prediction of Geographic Atrophy Progression
2020, American Journal of Ophthalmology
Citation Excerpt :
Patients with geographic atrophy (GA) secondary to AMD aged 50 years and over were included in a reported10,33,40–46 prospective observational cohort study after giving written informed consent.
To quantitatively measure hyperreflective foci (HRF) during the progression of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) using deep learning (DL) and investigate the association with local and global growth of GA.
Eyes with GA were prospectively included. Spectral-domain optical coherence tomography (SDOCT) and fundus autofluorescence images were acquired every 6 months. A 500-μm-wide junctional zone adjacent to the GA border was delineated and HRF were quantified using a validated DL algorithm. HRF concentrations in progressing and nonprogressing areas, as well as correlations between HRF quantifications and global and local GA progression, were assessed.
A total of 491 SDOCT volumes from 87 eyes of 54 patients were assessed with a median follow-up of 28 months. Two-thirds of HRF were localized within a millimeter adjacent to the GA border. HRF concentration was positively correlated with GA progression in unifocal and multifocal GA (all P < .001) and de novo GA development (P = .037). Local progression speed correlated positively with local increase of HRF (P value range <.001-.004). Global progression speed, however, did not correlate with HRF concentrations (P > .05). Changes in HRF over time did not have an impact on the growth in GA (P > .05).
Advanced artificial intelligence (AI) methods in high-resolution retinal imaging allows to identify, localize, and quantify biomarkers such as HRF. Increased HRF concentrations in the junctional zone and future macular atrophy may represent progressive migration and loss of retinal pigment epithelium. AI-based biomarker monitoring may pave the way into the era of individualized risk assessment and objective decision-making processes. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
Outer Retinal Thickness and Fundus Autofluorescence in Geographic Atrophy
2019, Ophthalmology Retina
Citation Excerpt :
Such precision is necessary to study multiple, varied pathologies that change at a small scale, especially within the transition zones. Likewise, in a study in which careful co-registration was applied, the area of atrophy measured by FAF was larger than any area graded by SD-OCT,26 emphasizing the care needed in comparing multiple modalities. The recently published Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT5 has also stated that it remains unclear at the moment whether severely reduced FAF would be correlated exclusively with a single category of OCT-defined atrophy or if certain variations might be present.
Most studies of fundus autofluorescence (FAF) in geographic atrophy (GA) have been nonquantitative, with inadequate registration of image modalities. Furthermore, as pointed out in the recent Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT, it is unclear whether decreased FAF would be correlated exclusively with a single category of OCT-defined atrophy. We sought to determine how FAF intensity in eyes with GA correlates with structural changes of the outer retina and choroid as seen on co-registered spectral domain OCT (SD-OCT) images.
Retrospective cross-sectional.
Twenty eyes of 11 patients with GA secondary to non-neovascular age-related macular degeneration (AMD).
Spectral domain OCT and FAF images for each eye were co-registered using MATLAB (MathWorks Inc, Natick, MA). On B-scans, the choroid, retinal pigment epithelium (RPE), photoreceptor (PR) layer, and outer nuclear layer (ONL) were segmented. Regions of interest (ROIs) including all atrophic and border regions were selected manually on the FAF scans. Regions of interest were subdivided into quartiles of FAF level to correlate with retinal thickness measurements taken along the B-scans. Mean choroid, RPE, PR, and ONL thicknesses were compared across quartiles using an analysis of variance factorial design testing for interaction effects, adjusted for repeated measures (on both eyes) with a within-subjects factor.
Seventeen eyes of 10 patients were selected for analysis. The mean choroidal thicknesses were not significantly different across FAF quartiles, but the overall differences in mean RPE, PR layer, and ONL thicknesses across quartiles were statistically significant (analysis of variance, P < 0.001, P < 0.001, and P = 0.015, respectively). Post hoc analysis demonstrated significant differences in thickness among quartiles 1, 2, and 3 for the RPE and PR layers (Tukey, P < 0.01 in each case). The FAF quartiles within GA did not correlate exclusively with single categories of Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration–defined atrophy.
Not only RPE but also PR layer thickness on SD-OCT varies significantly with FAF levels in GA. This suggests that although the RPE cells are losing thickness and function, evidenced by decreased FAF from fluorophores, delicate PR cells also succumb early in the disease process. These relationships should be pursued as a possibly better-detailed mechanism in GA.
Geographic atrophy segmentation in SD-OCT images using synthesized fundus autofluorescence imaging
2019, Computer Methods and Programs in Biomedicine
Accurate assessment of geographic atrophy (GA) is critical for diagnosis and therapy of non-exudative age-related macular degeneration (AMD). Herein, we propose a novel GA segmentation framework for spectral-domain optical coherence tomography (SD-OCT) images that employs synthesized fundus autofluorescence (FAF) images.
An en-face OCT image is created via the restricted sub-volume projection of three-dimensional OCT data. A GA region-aware conditional generative adversarial network is employed to generate a plausible FAF image from the en-face OCT image. The network balances the consistency between the entire synthesize FAF image and the lesion. We use a fully convolutional deep network architecture to segment the GA region using the multimodal images, where the features of the en-face OCT and synthesized FAF images are fused on the front-end of the network.
Experimental results for 56 SD-OCT scans with GA indicate that our synthesis algorithm can generate high-quality synthesized FAF images and that the proposed segmentation network achieves a dice similarity coefficient, an overlap ratio, and an absolute area difference of 87.2%, 77.9%, and 11.0%, respectively.
We report an automatic GA segmentation method utilizing synthesized FAF images.
Our method is effective for multimodal segmentation of the GA region and can improve AMD treatment.
The Border of Macular Atrophy in Age-Related Macular Degeneration: A Clinicopathologic Correlation
2018, American Journal of Ophthalmology
To correlate in vivo imaging to histology in an eye with macular atrophy owing to age-related macular degeneration (AMD; complete retinal pigment epithelium [RPE] and outer retinal atrophy [cRORA]) to evaluate the utility of new optical coherence tomography (OCT) suggested by previous histology.
Case study with clinicopathologic correlation.
In vivo eye-tracked cross-sectional OCT scans at 13 and 8 months before death were compared to postmortem histopathology. On OCT, the atrophy border was identified as either the descent of the external limiting membrane (ELM) toward the Bruch membrane (BrM) (representing gliosis) or the presence of choroidal hypertransmission (representing lack of shadowing by RPE). Thicknesses of RPE, basal laminar deposit (BLamD), and BrM were measured at 500 and 100 μm on the nonatrophic and atrophic sides of these borders, on in vivo eye-tracked OCT and histology matched to the same location.
In all OCT scans, the ELM descent was visible. The RPE-BLamD band significantly thickened toward it (P < .005), over time (P = .015 and P = .043, at 500 and 100 μm, respectively). On OCT, the ELM descent delineated a smaller atrophic area than did hypertransmission. RPE-BLamD thicknesses manually measured on OCT overestimated histologic thicknesses. BrM visibility varied with RPE status.
Visible on OCT, the ELM descent is a histopathologic atrophy border supporting new terminology of cRORA, whereas hypertransmission reveals RPE degeneration. RPE-BLamD thickening across the macula, toward the atrophy and over time is confirmed. The presence of gliosis and thick RPE-BLamD suggests that macular atrophy is a late stage in disease progression, encouraging anatomic endpoints at earlier AMD stages than atrophy enlargement.
The Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration
2018, Ophthalmology
Citation Excerpt :
For example, “nascent GA,” a drusen-associated atrophy preceding development of complete outer retinal atrophy, was identified on OCT by subsidence of the outer plexiform layer and inner nuclear layer, and a wedge-shaped band within the outer plexiform layer.33 The GA lesion boundaries on OCT have been defined by an abrupt increase in choroidal reflectivity below Bruch's membrane from loss of absorbing outer retinal structures and RPE (choroidal hypertransmission); RPE, photoreceptor, and choriocapillaris layer loss; and external limiting membrane absence/descent.12,14,34,35 In addition to resolving fine retinal details, spectral-domain OCT is widely available and comfortable for patients, whereas newer swept-source OCT devices have faster acquisition and use longer wavelengths with better tissue penetration.15
Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible loss of visual function. Geographic atrophy is defined by the presence of sharply demarcated atrophic lesions of the outer retina, resulting from loss of photoreceptors, retinal pigment epithelium (RPE), and underlying choriocapillaris. These lesions typically appear first in the perifoveal macula, initially sparing the foveal center, and over time often expand and coalesce to include the fovea. Although the kinetics of GA progression are highly variable among individual patients, a growing body of evidence suggests that specific characteristics may be important in predicting disease progression and outcomes. This review synthesizes current understanding of GA progression in AMD and the factors known or postulated to be relevant to GA lesion enlargement, including both affected and fellow eye characteristics. In addition, the roles of genetic, environmental, and demographic factors in GA lesion enlargement are discussed. Overall, GA progression rates reported in the literature for total study populations range from 0.53 to 2.6 mm²/year (median, ∼1.78 mm²/year), assessed primarily by color fundus photography or fundus autofluorescence (FAF) imaging. Several factors that could inform an individual's disease prognosis have been replicated in multiple cohorts: baseline lesion size, lesion location, multifocality, FAF patterns, and fellow eye status. Because best-corrected visual acuity does not correspond directly to GA lesion enlargement due to possible foveal sparing, alternative assessments are being explored to capture the relationship between anatomic progression and visual function decline, including microperimetry, low-luminance visual acuity, reading speed assessments, and patient-reported outcomes. Understanding GA progression and its individual variability is critical in the design of clinical studies, in the interpretation and application of clinical trial results, and for counseling patients on how disease progression may affect their individual prognosis.

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Original articleA Longitudinal Comparison of Spectral-Domain Optical Coherence Tomography and Fundus Autofluorescence in Geographic Atrophy

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Clinical Progression of Geographic Atrophy Disease

Discussion

Surv Ophthalmol

Surv Ophthalmol

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

2002 global update of available data on visual impairment: a compilation of population-based prevalence studies

Ophthalmic Epidemiol

Global data on visual impairment in the year 2002

Bull World Health Organ

The natural history of geographic atrophy, the advanced atrophic form of age-related macular degeneration

Mol Vis

Three-dimensional ultrahigh-resolution optical coherence tomography of macular diseases

Invest Ophthalmol Vis Sci

Original article
A Longitudinal Comparison of Spectral-Domain Optical Coherence Tomography and Fundus Autofluorescence in Geographic Atrophy