Abstract
Purpose:
The gradings of complete retinal pigment epithelium and outer retinal atrophy (cRORA) and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) on spectral domain optical coherence tomography (SD-OCT) B-scans were compared with the grading of persistent choroidal hypertransmission defects (hyperTDs) on swept-source OCT angiography (SS-OCTA) en face images.
Design:
Comparative diagnostic analysis of prospective study data
Methods:
Patients with late nonexudative AMD underwent same day 6×6 mm macular scans using both SD-OCT (Spectralis® Heidelberg, 512×97, ART:9) and SS-OCTA (PLEX® Elite 9000, Carl Zeiss Meditec, 500×500 angio pattern) instruments. SS-OCTA and SD-OCT en face images were generated from a sub-retinal pigment epithelium slab positioned 64–400 μm below Bruch’s membrane. SD-OCT B-scan gradings, which included an inspection of neighboring B-scans for the diagnosis of cRORA and iRORA, were performed at the Moran Eye Center, while gradings of en face images to identify persistent choroidal hyperTDs were performed at the Bascom Palmer Eye Institute and Tel Aviv Medical Center.
Results:
There was a high degree of agreement (99.6%) between the gradings of cRORA lesions and persistent hyperTDs. However, 27.4% of iRORA lesions were found to be contained within persistent hyperTDs. This discrepancy was due to the finding that 27.5% of iRORA lesions were diagnosed as having a greatest linear horizontal dimension of < 250 μm on B-scans, but on en face images, these B-scan defined iRORA lesions were found to have a greatest linear dimensions in the non-horizontal dimension that were ≥ 250 μm.
Conclusion:
This report demonstrates the benefits of using en face OCT imaging to identify cRORA lesions and highlights the need to acquire dense raster B-scans with the grading neighboring B-scans when identifying iRORA lesions to assess the full extent of the iRORA lesions in the non-horizontal dimension. Even though neighboring B-scans were inspected, 27.5% of iRORA lesions were actually part of larger cRORA lesions when graded using an en face strategy.
Keywords: Age-related macular degeneration, Geographic atrophy, cRORA, iRORA, Grading, hypertransmission defects, OCT
Précis:
Grading of cRORA on SD-OCT B-scans and persistent hyperTDs on en face SS-OCTA scans had a 99.6% agreement, but 27.4% of iRORA graded on B-scans was actually cRORA/hyperTDs when graded on en face images.
INTRODUCTION
Historically, geographic atrophy (GA) was identified using fundus biomicroscopy or color fundus imaging and defined as the late stage of nonexudative age-related macular degeneration (AMD).1 GA is characterized by the degeneration of photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris (CC), and is typically diagnosed as a sharply demarcated area of atrophy that originates in the perifoveal macula and progressively expands to encompass the entire macula.2
The advent of fundus autofluorescence (FAF) imaging largely supplanted color fundus imaging (CFI) for routine identification of macular atrophy in both clinical settings and research trials. However, FAF offers an indirect measure of atrophy, relying on the absence of intrinsic fluorophores that are lost as part of atrophy development.3,4 In contrast, optical coherence tomography (OCT) has emerged as the preferred tool for directly detecting the anatomical changes in the outer retina and RPE that are associated with GA.5–9
In AMD, FAF and OCT imaging each offer unique advantages, with FAF images capturing changes in hypoautofluorescence indicative of atrophy and changes of hyperautofluorescence predictive of disease progression.10 However, OCT offers a detailed structural assessment, providing detailed information about the depth and layer involvement of atrophic regions, especially the earliest anatomic changes that predict the formation of GA.5,11 While FAF and OCT imaging have been shown to be similar when identifying and quantifying established foci of GA, 12–14,15 there have not been many attempts to compare FAF and OCT detection of the earliest anatomic changes that precede the appearance of bona fide GA.16
To define the earliest changes that precede the appearance of typical GA, the Classification of Atrophy Meeting (CAM) group has advocated for the preferential use of OCT in diagnosing atrophy in AMD. They have developed consensus terminology based on OCT B-scan imaging, introducing the terms incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete retinal pigment epithelium and outer retinal atrophy (cRORA).5,17 iRORA is characterized by three OCT features: photoreceptor degeneration, RPE attenuation or disruption, and increased choroidal signal transmission. In addition, cRORA includes these features but also mandates that the areas of RPE change and choroidal hypertransmission each have a measurement of at least 250 μm on the horizontal OCT B-scan, along with evidence of photoreceptor loss. iRORA is proposed as a precursor to cRORA and was proposed to represent a precursor lesion to GA that would be helpful in monitoring disease onset and progression.18
To define cRORA, the use of the 250 μm horizontal dimension cut-off for the loss or attenuation of RPE and its accompanying choroidal hypertransmission defect (persistent s) was not based on any natural history study, but rather as a dimension that could be reliably and reproducibly measured. 5 This OCT biomarker for the detection of early macular atrophy is primarily reliant on the analysis of B-scans for defining iRORA and cRORA. It is important to acknowledge that the orientation of the B-scan in relation to the size and location of the atrophic area may impose constraints on the consistent and reliable identification of iRORA. This limitation is crucial for interpreting biomarker efficacy and suggests a need for refined methodologies in OCT imaging.19 Furthermore, recent studies suggest that intergrader reliability is lower for evaluating iRORA compared with cRORA on B-scans,18 and 50% of iRORA was found to correspond to cRORA when the lesions were graded in a non-horizontal dimension. 24
Another strategy for detecting OCT lesions that correspond to GA lesions and for detecting early stage OCT changes that precede the formation of GA is to use en face OCT images derived from dense OCT raster scans.11,12,20–25 The use of en face persistent choroidal hyperTDs has been proposed as an alternative to using averaged B-scans for the diagnosis of early-stage lesions.11,21,24,25 This en face strategy using dense volumetric raster B-scans allows for the measurement of hyperTDs in any en face dimension, not just the horizontal dimension. En face OCT detects macular atrophy, including GA, due to the increased choroidal light penetration and reflectivity that results when the highly reflective RPE layer is attenuated or lost, leading to abrupt transition in OCT choroidal reflectivity.12,20–22 These hyperTDs, with a minimum size of 250 μm, have been shown to be persistent and identified as precursors to the formation of typical GA, but diagnosed on en face OCT imaging.21,23,26 Recent studies indicate that hyperTDs can serve as standalone biomarkers for predicting the progression from drusen to atrophy.25,11
With the introduction of OCT B-scan diagnostic definitions of iRORA and cRORA and the introduction of persistent choroidal hyperTD diagnosed on en face OCT images, a lingering question that needed to be addressed is how these different OCT definitions of early atrophy could be reconciled. In their recent study, Corvi et al27. reported that there is significant agreement between the B-scan diagnoses of cRORA when compared with the diagnoses of persistent hyperTDs on en face OCT images. However, they found that about 50% of cases initially diagnosed as iRORA were actually cRORA when assessed in the non-horizontal dimension using en face OCT imaging. Since cRORA indicates a complete loss of photoreceptors, the results by Corvi et al27 indicate that hyperTDs on en face imaging correlates with cRORA, which should correlate with a loss of function.
While Corvi et al27 primarily focused on eyes with established GA, it was reported that the discrepancies between the grading systems mainly occurred in smaller atrophic areas. Given this background and the evidence that the diagnosis of persistent choroidal hyperTDs on en face images from dense OCT raster scans can be easily and reliably graded,28 we wanted to confirm the equivalency between hyperTDs on en face imaging and cRORA on B-scan imaging. We also wanted to improve the diagnosis of iRORA on B-scan imaging by showing that more closely spaced, averaged B-scans were better at distinguishing iRORA from cRORA once neighboring B-scans were graded along with any given B-scan. This would enable graders to identify when conventionally graded iRORA is really cRORA when viewed in a non-horizontal greatest linear dimension (GLD). This report compares the grading of cRORA and iRORA from a dense scan pattern of averaged SD-OCT B-scans against the grading of persistent choroidal hyperTDs from SS-OCTA en face OCT images.
METHODS
Study Design and Ethical Approval
This retrospective analysis of a prospective, observational study used two different OCT imaging techniques to investigate early atrophic lesions in nonexudative AMD. The study was a collaboration between the Moran Eye Center, Bascom Palmer Eye Institute, and Tel Aviv Medical Center. Ethical clearance was obtained from the University of Tel Aviv’s ethics committee, and all subjects were enrolled at the Tel Aviv Medical Center. The study was conducted in strict adherence to the principles outlined in the Declaration of Helsinki and was compliant with the Health Insurance Portability and Accountability Act (HIPAA) of 1996. All participants provided informed consent prior to enrollment.
Study Period and Participant Selection
The study was conducted from 2022 to 2023. Consecutive patients presenting to the Macula Center within the Ophthalmology Department at Tel Aviv Medical Center were included if they had at least one eye affected by GA secondary to nonexudative AMD. The diagnosis was confirmed through standard structural OCT imaging.
Exclusion Criteria
Patients were excluded from the study if they had a history of other retinal pathologies, including but not limited to diabetic retinopathy, retinal vein occlusion, and central serous chorioretinopathy. Additionally, patients were ruled out if there was any evidence of exudation, which was defined as the presence of subretinal or intraretinal fluid as observed on structural OCT B-scans or retinal thickness maps.
Imaging Protocols
All enrolled participants underwent 6×6 mm macular scans using both the Spectralis SD-OCT (Heidelberg, 512×97, ART:9) and the SS-OCTA (PLEX® Elite 9000, Carl Zeiss, Meditec Inc., Dublin, CA, 500×500 angio pattern) instruments on the same day. The Spectralis SD-OCT operated at a central wavelength of 880 nm and had a scanning rate of 85,000 A-scans per second. The scanning pattern for the SD-OCT imaging included a 20-degree field of view with 512 A-scans per B-scan and utilized the high-speed raster scan pattern consisting of 97 B-scans with an automatic real-time-tracking (ART) setting of 9 per volume resulting in a B-scan interval of 62 μm. The SS-OCTA device operated at a central wavelength of 1050 nm and had a scanning rate of 100,000 A-scans per second. The scanning pattern consisted of 500 A-scans per B-scan, with each B-scan acquired twice at the same position. The study exclusively included 6×6-mm scans centered on the fovea, resulting in a uniform 12 μm spacing between A-scans and B-scans. All acquired images underwent a quality assessment. Scans with evident motion artifacts or with a signal strength rating below 7 out of 10 on the device’s scale were excluded from the subsequent analysis.
Image Processing
En face SS-OCTA images were created from a sub-RPE slab with segmentation boundaries between 64–400 μm beneath Bruch’s membrane and referred to as a subRPE slab. HyperTDs with a GLD of at least 250 μm were graded and tracked across multiple visits. For the SS-OCTA scans, the grading of en face images to identify hyperTDs at least 250 μm in GLD was conducted collaboratively by the University of Washington and Bascom Palmer Eye Institute. A previously developed artificial intelligence (AI)-assisted algorithm9,29 was used to facilitate the identification of hyperTDs using SS-OCT. The semi-automated algorithm integrated data from OCT structural information, optical attenuation coefficients (OAC) signals, and drusen elevation to enhance the segmentation of hyperTDs. The software excluded all lesions with a GLD of less than 250 μm from the final hyperTDs mask. Additionally, the software calculated and recorded the area of each individual hyperTD and the cumulative area of all lesions. Two independent graders meticulously reviewed and manually graded the en face hyperTDs and the corresponding choroidal hyperTDs on the B-scans for the grading. A consensus outline from these evaluators was adopted for subsequent analyses as illustrated in Figure 1F. In cases where agreement could not be reached, a senior evaluator was consulted (PJR).
Figure 1.
Identification of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete RORA (cRORA) in a representative eye using SD-OCT and SS-OCT instruments. (A) SD-OCT B-scan with blue lines denoting cRORA. The position of this B-scan is shown by the yellow dashed line in (B). (B) En face image of the sub-retinal pigment epithelium (subRPE) slab obtained from the SD-OCT scan. Persistent choroidal hypertransmission defects (hyperTDs) are visible across the entire scan area with the overlay of lines corresponding to cRORA (blue lines) and iRORA (red lines). (C) An en face cRORA mask was generated based on B-scan gradings on SD-OCT. (D) An en face iRORA mask was generated based on its B-scan gradings on SD-OCT. (E) SS-OCT B-scans displays the hyperTD lesions with the yellow line indicating the segmentation of subRPE slab. The position of this B-scan is shown by the green dashed line in (F). (F) The en face view of the sub-RPE slab from the SS-OCT, featuring superimposed grading marks for hyperTDs. (G) Binary images of persistent hyperTD lesions from the SS-OCT system, automatically identified by a validated and automated algorithm calculation, with a greatest linear dimension (GLD) ≥ 250 μm. (H) The binary en face mask of hyperTDs from the SS-OCT system, including the SD-OCT B-scan gradings of cRORA (blue lines) and iRORA (red lines), registered and overlaid.
For the SD-OCT B-scans, en face images were also created from the subRPE slab. Raw OCT cubes were extracted from the e2e files using the Heidelberg OCT review software. Inter-frame registration and intensity normalization were conducted to compensate the eye motion and uneven illumination. A contrast-limited adaptive histogram equalization filter was applied to the en face image to enhance the contrast of the image.
Using SD-OCT B-scans, a masked grader (MF) at the Moran Eye Center identified cRORA and iRORA lesions. The review software within the SD-OCT machine was used by graders to identify choroidal hyperTDs, outer retinal changes, and RPE attenuation. cRORA was labeled when the hyperTDs in the B-scan plane met one of the following criteria: 1) lesion size was at least 250 μm; or 2) lesion was connected to another lesion that was at least 250 μm in size; or 3) lesion was linked to more than four adjacent lesions on OCT B-scans, resulting in a GLD exceeding 250 μm along the slow scan direction. Similarly, hyperTDs were categorized as iRORA when their size was smaller than 250 μm in both the fast and slow scan directions. Once the grading was complete, the masks of cRORA and iRORA were projected and superimposed onto the subRPE slab of the SD-OCT scans as shown in Figure 1 A and 1B. The resulting masks and their respective areas were calculated for further analysis as depicted in Figure 1C and 1D.
The iRORA/cRORA mask created from the SD-OCT images was manually registered to the SS-OCT images to minimize the distortion and lesion mismatch between the OCT systems (see Figure 1H). The number of iRORA/cRORA lesions that overlaped with the persistent hyperTDs on en face SS-OCTA images were recorded based on the registered image.
Statistical Analyses
The total area of the cRORA and the hyperTDs were compared by paired-samples t test. Statistical analyses were conducted using MATLAB R2021. The data were summarized with mean and standard deviation, if applicable. A two-sided P value less than 0.05 was considered statistically significant.
RESULTS
Study Population and Analysis of SD-OCT and SS-OCTA Scans
A retrospective analysis identified 19 eyes from 15 patients diagnosed with nonexudative AMD and exhibiting persistent choroidal hyperTDs on SS-OCTA en face images. These patients had undergone same day SD-OCT and SS-OCTA imaging between the years 2022 and 2023. Within the collected dataset, 558 SD-OCT B-scans exhibited cRORA, while 142 B-scans were categorized as having iRORA. The mean area of single hyperTD lesion measured on the en face image was 0.64 ± 1.28 mm2, with a maximum of 5.16 mm2 and a minimum of 0.02 mm2. The mean GLD of a single hyperTD lesion was 0.81 ± 0.83 mm, with a maximum of 3.30 mm and a minimum of 0.25mm.
Consensus Grading and Overlap Analysis
Consensus iRORA/cRORA gradings and the en face hyperTD gradings were performed by the designated evaluators. There was a near-perfect overlap between SD-OCT cRORA lesions and SS-OCTA persistent hyperTDs. Specifically, 556 out of the 558 cRORA lesions identified through SD-OCT imaging were also detected as persistent hyperTDs with a GLD of at least 250 μm in GLD on SS-OCTA en face images (556/558; 99.6%). To further elucidate the correlation between cRORA and hyperTD lesions, area measurements from the cRORA mask obtained from the SD-OCT scans were compared with the en face images of the hyperTDs from the SS-OCTA scans as shown in Figure 3. The average area per scan for cRORA was 1.98 ± 1.77 mm2, while hyperTDs had a slightly larger mean area of 2.14 ± 1.87 mm2. A strong correlation (R2 = 0.938) was noted between the two sets of area measurements and the difference in measurements was not statistically significant (P= 0.148). In Figure 3, the dashed diagonal line represents the line of unity (slope=1) and shows the correlation between area measurements of the cRORA on SD-OCT and hyperTD on SS-OCT imaging. A representative case was pointed out by the green arrow in Figure 3 and was shown in (C-D), while an outlier case was indicated by the red arrow and shown in Figure 3 (E-F).
Figure 3.
Comparison of total area measurements for cRORA on SD-OCT scans and persistent choroidal hyperTDs on SS-OCTA scans. (A) Correlation plot illustrating the relationship between area measurements of cRORA and hyperTDs. The dash diagonal line represents the line of unity (slope=1), indicating a strong correlation between the two measurements (r2=0.938 (B) The box plot compares the areas of cRORA and hyperTDs, with a mean area of 1.98 mm2 for cRORA and 2.14 mm2 for hyperTDs. The p-value for the comparison of the areas of inner retinal outer retinal atrophy (iRORA) and cRORA is 0.148. (C-D) The representative case indicated by the green arrow. (C) The subRPE slab of the SD-OCT. (D) The hyperTD mask of SS-OCT overlay by the grading of cRORA and iRORA. (E-F) The outlier case as shown by the red arrow in panel (A). (E) shows the subRPE slab of the SD-OCT, while (F) displays the hyperTD mask of SS-OCT overlay with the grading of cRORA and iRORA.
Additional Observations
Interestingly, 72.5% of iRORA lesions (103/142) were not accompanied by any persistent hyperTDs on en face images, but this would be expected since iRORA lesions measure less than 250 μm even when neighboring B-scans are included. A lesion with a hyperTD measuring less than 250 μm in GLD would not be considered a persistent hyperTD. Conversely, 27.4% of iRORA lesions (39/142) were classified as persistent hyperTDs when they were part of larger lesions. Among 39 iRORA lesions that classified as hyperTDs, the average length measured on B-scans was 179.1 ± 48.7um. These observations are illustrated in four representative cases shown in Figure 2. In Case 1, if we define cRORA as a lesion that measures 250 μm or greater in any GLD and iRORA as a lesion that measures less than 250 in any GLD, then cRORA was accurately identified in 100% of the gradings (34/34), while iRORA was correctly identified in 71% of the gradings (20/28). In Case 2, cRORA was identified accurately in all gradings (11/11; 100%), and iRORA was correctly identified in 100% of the gradings (2/2). In Case 3, none of the iRORA lesions were correctly identified (0%, 0/5). In Case 4, iRORA was correctly identified in 50% of the gradings (3/6).
Figure 2.
Four representative cases used to grade iRORA, cRORA, and persistent choroidal hyperTDs. (A.1-A.4) SD-OCT B-Scans (512×97) with grading of cRORA (blue) and iRORA (red) (B.1-B.4) SD-OCT en face subRPE slab with the yellow dashed line representing the location of the B-scan in panel (A). (C.1-C.4) SS-OCT subRPE slabs with scan size 500×500 overlay with corresponding SD-OCT B-Scan projected gradings (D.1-D.4). HyperTD algorithm mask overlays with b-scan gradings. In case 1, cRORA was correctly identified in 100% (34/34) of gradings, while iRORA was correctly identified in 71.3% (20/28) of gradings. In case 2, cRORA was correctly identified in 100% (11/11) of gradings and iRORA was correctly identified in 100% (2/2) of gradings. In case 3, iRORA was not identified correctly in any of the gradings (0%, 0/5). In case 4, iRORA was correctly identified in 50% (3/6) of gradings.
DISCUSSION
We compared the grading of cRORA and iRORA on B-scans with the grading of persistent hyperTDs observed on en face images. The results of this grading exercise indicated that cRORA grading on B-scans was almost identical to the grading of persistent hyperTDs on en face images. This is to be expected since persistent choroidal hyperTDs on en face imaging have a GLD of at least 250 μm so this would include all cRORA lesions graded on horizontal B-scans. However, grading of iRORA based solely on horizontal B-scans, even when considering the neighboring B-scans, does not fully distinguish iRORA from what is actually cRORA when the GLD of choroidal hypertransmission is larger than 250 μm in a non-horizontal dimension. Upon examination in a non-horizontal dimension, it was discovered that 27% of iRORA lesions detected on B-scans were actually cRORA lesions. These iRORA lesions would likely have been recognized correctly as persistent hyperTDs on en face images since they were situated within a larger lesion that would be diagnosed as cRORA when viewed non-horizontally.
En face OCT imaging offers several advantages over B-scan evaluation for diagnosing cRORA and identifying when iRORA lesions are really cRORA lesions. The ability to inspect a single en face image for the presence of persistent hyperTDs considerably expedites the assessment process, providing a fast overview of the entire scan area as compared with meticulous scrolling through each of the 97 B-scans from a raster volume scan. Moreover, en face imaging provides valuable insights into the topographic correlation of atrophic lesions with other anatomic features that are related to AMD progression such as the location of drusen and hyperreflective foci (HRF). 30,31
Our results also suggest that iRORA lesions can be correctly classified as cRORA when closely spaced neighboring B-scans are considered. A retrospective, cross-sectional study that evaluated the correlation between FAF and en face SD-OCT measurements of GA area associated with AMD showed a robust correlation between FAF and en face SD-OCT measurements of GA area (r = 0.98; P < 0.001), particularly after manual correction of SD-OCT segmentation errors.14 However, when Corvi et al 19 compared B-scan diagnoses of cRORA and iRORA with en face OCT images, they found that approximately 50% of iRORA lesions were actually cRORA lesions on en face images, but they did not include neighboring B-scans when grading iRORA. In our current study, the B-scan grader specifically included neighboring B-scans when grading iRORA and cRORA, and even with the inclusion of these neighboring B-scans, 27.4% of iRORA lesions were actually cRORA lesions on en face images. In an analysis from our current dataset in which neighboring B-scans were not considered when grading iRORA lesion, we found that approximately 50% of the iRORA lesions were found to be cRORA lesions. These findings further support the potential of en face OCT imaging in identifying lesions as they progress to typical GA. The application of en face imaging is not only useful for clinical research and clinical trials, but also a valuable tool for assessing disease severity and treatment outcomes in clinical practice in which a single OCT can be used to follow both exudative and nonexudative AMD.
Our study, which specifically uses a SD-OCT instrument capable of producing averaged OCT B-scans, takes advantage of an enhanced ability to detect iRORA lesions compared with an instrument that does not produce averaged B-scans, as previously described by Corvi et al. in which they evaluated the detection of iRORA between two such devices.19
Limitations of this investigation include the small sample size; however, it is unlikely that the inclusion of additional eyes would significantly alter the observed similarities between hyperTDs and cRORA detection or the limitations in iRORA detection and the need to grade neighboring B-scans when grading iRORA. Additionally, the current hyperTD detection algorithm is specifically designed for dense SD-OCTA and SS-OCTA scans, and our results also support the need for a dense scanning pattern when grading cRORA and iRORA lesions on all OCT instruments. However, as suggested here, subRPE en face images can be generated as long as a dense SD-OCT scan pattern can be performed, and we recommend a minimum of 97 B-scans over a 6X6 mm field-of-view.
In conclusion, our research highlights the critical importance of thoroughly evaluating choroidal hyperTDs in all neighboring B-scans when classifying iRORA lesions using a dense OCT B-scan imaging pattern to determine when iRORA lesions are really cRORA lesions. In contrast, en face OCT imaging facilitates the detection of persistent hyperTDs, which are equivalent to cRORA lesions. To ensure accurate differentiation between iRORA and cRORA when grading B-scans, it is essential to examine adjacent B-scans for a comprehensive understanding of the extent of choroidal hyperTDs and the accompanying changes in the RPE and outer retina. Most notably, detection of persistent hyperTDs on en face images is much easier than scrolling through 97 or more B-scans to identify these lesions. Additionally, the use of automated algorithms to identify persistent hyperTDs improves the efficiency of lesion detection, streamlining the diagnostic process.
Financial Disclosures:
Research is supported in part by an unrestricted grant from the Research to Prevent Blindness, Inc. (New York, NY), Carl Zeiss Meditec Inc, the National Institutes of Health (P30EY014801, R01EY028753, R01AG060942, R01EY033365, and R01EY034965), the National Institutes of Health Core Grant EY014800. The funding organizations had no role in the design or conduct of the present research.
Conflicts of Interest:
Dr. Marc Steffen Schmitz-Valckenberg: Grants or contracts from AlphaRET, Apellis, Bayer, Formycon, Carl Zeiss MediTec, eyeDNA Therapeutics, Galimedix, Katairo, Kubota Vision, Novartis, Perceive Therapeutics, Pixium, Roche/Genentech, SparingVision; Consulting fees from Apellis, Roche/Genentech; and nonfinancial support from Carl Zeiss Meditec and Heidelberg Engineering, outside the submitted work. Dr. Ruikang Wang discloses intellectual property owned by the Oregon Health and Science University and the University of Washington. Dr. Wang also receives research support from Carl Zeiss Meditec Inc, Colgate Palmolive Company and Estee Lauder Inc. He is a consultant to Carl Zeiss Meditec and Cyberdontics. Dr. Philip Rosenfeld and Dr. Giovanni Gregori receive research support from Carl Zeiss Meditec, Inc. and the University of Miami co-own a patent that is licensed to Carl Zeiss Meditec, Inc. Dr. Philip Rosenfeld also received research funding from Gyroscope Therapeutics. He is also a consultant for Abbvie, Annexon, Apellis, Bayer Pharmaceuticals, Boehringer-Ingelheim, Carl Zeiss Meditec, Genentech/Roche, InflammX Therapeutics, Ocudyne, Regeneron Pharmaceuticals, and Unity Biotechnology. He also has equity interest in Apellis, InflammX, Ocudyne, and Valitor. The other authors have no disclosures.
Abbreviations:
- SS-OCT
swept source OCT
- SD-OCT
spectral domain optical coherence tomography
- OCTA
OCT angiography
- AMD
age-related macular degeneration
- GA
geographic atrophy
- iRORA
incomplete retinal pigment epithelium and outer retinal atrophy
- cRORA
complete retinal pigment epithelium and outer retinal atrophy
- hyperTDs
hypertransmission defects
- RPE
retinal pigment epithelium
- CC
choriocapillaris
- CCFDs
CC flow deficits
- FAF
fundus autofluorescence
- CFI
color fundus imaging
- CAM
Classification of Atrophy Meeting
- OAC
optical attenuation coefficients
- HRF
hyperreflective foci
- subRPE
sub-retinal pigment epithelium
- GLD
greatest linear dimension
Footnotes
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