Quantification of Geographic Atrophy Using Spectral Domain OCT in Age-Related Macular Degeneration

Cleland, Spencer C.; Konda, Sri Meghana; Danis, Ronald P.; Huang, Yijun; Myers, Dawn; Blodi, Bárbara A.; Domalpally, Amitha

doi:10.1016/j.oret.2020.07.006

Cited by 26 publications

(15 citation statements)

References 44 publications

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“…We found a significant correlation between circularity at baseline and the rate of GA area progression on univariate analysis, but not in a multivariate model. Such a correlation was also reported by Cleland et al 15 and in a previous study by Domalpally et al involving 593 eyes measured using CFP. 17 In their report, Domalpally et al suggested that low circularity may be associated with a larger lesion perimeter for a given lesion area 17 ; it is worth mentioning that in a recent work by Shen et al, it was shown that the GA perimeter-adjusted growth rate is uncorrelated with circularity.…”

Section: Discussionsupporting

confidence: 87%

“…Interestingly, Cleland et al recently followed 70 eyes with GA using OCT with cRORA criteria for GA, as well as OCT with hyper-transmission criteria alone, FAF, CFP, and infrared imaging. 15 The authors found that the mean annual rate of GA growth was 1.6 mm 2 using the OCT scans with cRORA criteria, which is a bit faster than the rate found in our study. They found no significant difference between GA annotated using cRORA criteria and GA annotated using any of the other imaging modalities.…”

Section: Discussioncontrasting

confidence: 67%

“…In our study, we found a significant correlation between focality at baseline and the rate of GA area progression. Similarly, Cleland et al 15 evaluated GA progression using OCT annotation with cRORA criteria and found a significant correlation between multifocality at baseline and the rate of GA area progression. These findings are also consistent with the results of a meta-analysis of 3489 eyes, which included cases of atrophy imaged using CFP, FAF, and/or OCT. 3 The authors of this study suggested that this correlation between multifocality and GA area progression is related to the proportional increase in the total lesion perimeter being associated with a higher focality index.…”

Section: Discussionmentioning

confidence: 98%

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Progression of cRORA (Complete RPE and Outer Retinal Atrophy) in Dry Age-Related Macular Degeneration Measured Using SD-OCT

Shmueli

Yehuda

Szeskin

et al. 2022

Trans. Vis. Sci. Tech.

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Purpose The purpose of this study was to evaluate the long-term rate of progression and baseline predictors of geographic atrophy (GA) using complete retinal pigment epithelium and outer retinal atrophy (cRORA) annotation criteria. Methods This is a retrospective study. Columns of GA were manually annotated by two graders using a self-developed software on optical coherence tomography (OCT) B-scans and projected onto the infrared images. The primary outcomes were: (1) rate of area progression, (2) rate of square root area progression, and (3) rate of radial progression towards the fovea. The effects of 11 additional baseline predictors on the primary outcomes were analyzed: total area, focality (defined as the number of lesions whose area is >0.05 mm 2 ), circularity, total lesion perimeter, minimum diameter, maximum diameter, minimum distance from the center, sex, age, presence/absence of hypertension, and lens status. Results GA was annotated in 33 pairs of baseline and follow-up OCT scans from 33 eyes of 18 patients with dry age-related macular degeneration (AMD) followed for at least 6 months. The mean rate of area progression was 1.49 ± 0.86 mm 2 /year ( P < 0.0001 vs. baseline), and the mean rate of square root area progression was 0.33 ± 0.15 mm/year ( P < 0.0001 vs. baseline). The mean rate of radial progression toward the fovea was 0.07 ± 0.11 mm/year. A multiple variable linear regression model (adjusted r 2 = 0.522) revealed that baseline focality and female sex were significantly correlated with the rate of GA area progression. Conclusions GA area progression was quantified using OCT as an alternative to conventional measurements performed on fundus autofluorescence images. Baseline focality correlated with GA area progression rate and lesion's minimal distance from the center correlated with GA radial progression rate toward the center. These may be important markers for the assessment of GA activity. Translational Relevance Advanced method linking specific retinal micro-anatomy to GA area progression analysis.

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Section: Discussionsupporting

confidence: 87%

Section: Discussioncontrasting

confidence: 67%

Section: Discussionmentioning

confidence: 98%

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Progression of cRORA (Complete RPE and Outer Retinal Atrophy) in Dry Age-Related Macular Degeneration Measured Using SD-OCT

Shmueli

Yehuda

Szeskin

et al. 2022

Trans. Vis. Sci. Tech.

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“…The Deep-learning models were developed for each of the constituent OCT features required to define geographic atrophy: RPE loss, overlying photoreceptor degeneration, and hypertransmission. Predictive performances were independently assessed on internal and external validation datasets, in which a wide distribution across all features was observed (appendix pp [7][8][9][10][11][12][13].…”

Section: Resultsmentioning

confidence: 99%

“…3 The Classification of Atrophy Meetings (CAM) group-an international consortium of experts in age-related macular degeneration and retinal imaging-have produced OCTbased definitions of geographic atrophy and its subtypes with histological correlates and clinical validation. 5,6 These standardised definitions enable more accurate measurements, monitoring of disease progression, 7 and identification of early biomarkers. For example, incom plete RPE and outer retinal atrophy (RORA) is a distinct subtype of geographic atrophy that precedes complete RORA-the endpoint of atrophy.…”

Section: Introductionmentioning

confidence: 99%

Clinically relevant deep learning for detection and quantification of geographic atrophy from optical coherence tomography: a model development and external validation study

Zhang

Liefers

et al. 2021

The Lancet Digital Health

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Background Geographic atrophy is a major vision-threatening manifestation of age-related macular degeneration, one of the leading causes of blindness globally. Geographic atrophy has no proven treatment or method for easy detection. Rapid, reliable, and objective detection and quantification of geographic atrophy from optical coherence tomography (OCT) retinal scans is necessary for disease monitoring, prognostic research, and to serve as clinical endpoints for therapy development. To this end, we aimed to develop and validate a fully automated method to detect and quantify geographic atrophy from OCT. Methods We did a deep-learning model development and external validation study on OCT retinal scans at Moorfields Eye Hospital Reading Centre and Clinical AI Hub (London, UK). A modified U-Net architecture was used to develop four distinct deep-learning models for segmentation of geographic atrophy and its constituent retinal features from OCT scans acquired with HeidelbergSpectralis. A manually segmented clinical dataset for model development comprised 5049 B-scans from 984 OCT volumes selected randomly from 399 eyes of 200 patients with geographic atrophy secondary to age-related macular degeneration, enrolled in a prospective, multicentre, phase 2 clinical trial for the treatment of geographic atrophy (FILLY study). Performance was externally validated on an independently recruited dataset from patients receiving routine care at Moorfields Eye Hospital (London, UK). The primary outcome was segmentation and classification agreement between deep-learning model geographic atrophy prediction and consensus of two independent expert graders on the external validation dataset. Findings The external validation cohort included 884 B-scans from 192 OCT volumes taken from 192 eyes of 110 patients as part of real-life clinical care at Moorfields Eye Hospital between Jan 1, 2016, and Dec, 31, 2019 (mean age 78•3 years [SD 11•1], 58 [53%] women). The resultant geographic atrophy deep-learning model produced predictions similar to consensus human specialist grading on the external validation dataset (median Dice similarity coefficient [DSC] 0•96 [IQR 0•10]; intraclass correlation coefficient [ICC] 0•93) and outperformed agreement between human graders (DSC 0•80 [0•28]; ICC 0•79). Similarly, the three independent feature-specific deep-learning models could accurately segment each of the three constituent features of geographic atrophy: retinal pigment epithelium loss (median DSC 0•95 [IQR 0•15]), overlying photoreceptor degeneration (0•96 [0•12]), and hypertransmission (0•97 [0•07]) in the external validation dataset versus consensus grading. Interpretation We present a fully developed and validated deep-learning composite model for segmentation of geographic atrophy and its subtypes that achieves performance at a similar level to manual specialist assessment. Fully automated analysis of retinal OCT from routine clinical practice could provide a promising horizon for diagnosis and prognosis in both research and real-life patien...

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Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months

Fu,

Bagga,

Naik

et al. 2024

JAMA Ophthalmol

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ImportanceDespite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials.ObjectiveTo analyze the association between pegcetacoplan and consensus GA SD-OCT end points.Design, Setting, and ParticipantsThis was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023.InterventionsStudy participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month.Main Outcomes and MeasuresThe primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal).ResultsAmong 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: −0.86 mm2; 95% CI, −1.15 to −0.57; P &lt; .001; pegcetacoplan every other month: −0.69 mm2; 95% CI, −0.98 to −0.39; P &lt; .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: −0.17 mm2; 95% CI, −0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month.Conclusions and RelevanceThese findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors.Trial RegistrationClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613

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Quantification of Geographic Atrophy Using Spectral Domain OCT in Age-Related Macular Degeneration

Cited by 26 publications

References 44 publications

Progression of cRORA (Complete RPE and Outer Retinal Atrophy) in Dry Age-Related Macular Degeneration Measured Using SD-OCT

Progression of cRORA (Complete RPE and Outer Retinal Atrophy) in Dry Age-Related Macular Degeneration Measured Using SD-OCT

Clinically relevant deep learning for detection and quantification of geographic atrophy from optical coherence tomography: a model development and external validation study

Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months

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