Abstract
Purpose: Choriocapillaris (CC) imaging of normal eyes with swept-source optical coherence tomographic angiography (SS-OCTA) was performed, and the percentage of CC flow deficits (FD%) and the average area of CC flow deficits (FDa) were compared within the given macular regions. Design: A prospective, cross-sectional study. Methods: Subjects with normal eyes ranging in age from their 20s through their 80s were imaged with SS-OCTA (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, California, USA) using both 3×3-mm and 6×6-mm macular scan patterns. The CC images were generated using a previously published and validated algorithm. In both 3×3-mm and 6×6-mm scans, the CC FD% and FDa were measured in circular regions centered on the fovea with diameters as 1 mm and 2.5 mm (C1 and C2.5). In 6×6-mm scans, the FD% and FDa were measured within an additional circular region with diameter as 5 mm (C5). The correlations between FD% and FDa from each region were analyzed with Pearson correlation coefficients. Results: A total of 164 eyes were analyzed. There was excellent correlation between CC FDa and FD% measurements from each region. In the 3×3-mm scans, the correlations in the C1 and C2.5 regions were 0.83 and 0.90, respectively. In the 6×6-mm scans, the correlations in C1, C2.5, and C5 regions were 0.90, 0.89, and 0.89, respectively. Conclusions: When measuring CC FDs, we found excellent correlations between FDa and FD% in regions from 3×3-mm and 6×6-mm scans. Further studies are needed to determine if one parameter is more useful when studying diseased eyes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 18-26 |
| Number of pages | 9 |
| Journal | American journal of ophthalmology |
| Volume | 209 |
| DOIs | |
| State | Published - Jan 2020 |
| Externally published | Yes |
ASJC Scopus subject areas
- Ophthalmology
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Correlations Between Different Choriocapillaris Flow Deficit Parameters in Normal Eyes Using Swept Source OCT Angiography. / Shi, Yingying; Zhang, Qinqin; Zheng, Fang; Russell, Jonathan F.; Motulsky, Elie H.; Banta, James T.; Chu, Zhongdi; Zhou, Hao; Patel, Nimesh A.; de Sisternes, Luis; Durbin, Mary K.; Feuer, William; Gregori, Giovanni; Wang, Ruikang K.; Rosenfeld, Philip J.
In: American journal of ophthalmology, Vol. 209, 01.2020, p. 18-26.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Correlations Between Different Choriocapillaris Flow Deficit Parameters in Normal Eyes Using Swept Source OCT Angiography
AU - Shi, Yingying
AU - Zhang, Qinqin
AU - Zheng, Fang
AU - Russell, Jonathan F.
AU - Motulsky, Elie H.
AU - Banta, James T.
AU - Chu, Zhongdi
AU - Zhou, Hao
AU - Patel, Nimesh A.
AU - de Sisternes, Luis
AU - Durbin, Mary K.
AU - Feuer, William
AU - Gregori, Giovanni
AU - Wang, Ruikang K.
AU - Rosenfeld, Philip J.
N1 - Funding Information: The CC FDa measurements were highly correlated with the CC FD% measurements from 164 normal eyes over 7 decades of life. In our previous work, we found that CC FD% increased with age, especially in the central 1-mm area under the fovea. Similar age-related changes were found when using CC FDa to quantify CC. In a given eye, CC FDa measured the average size of the CC flow deficits contained in a specified region. Therefore, FD% is proportional to FDa times the number of flow deficits in the region, and these factors may vary depending on the different regions being considered. Our previous study correlating baseline CC FD measurements with annual ERs of GA showed that the CC FDa measurements had better correlations with ERs of GA compared with CC FD%, which suggested that the average size of the CC FDs may contribute more to GA formation and GA enlargement than the overall percentage of FDs. 27 Future studies will explore the relationship between FD size and the formation and growth of GA, but this relationship seems intuitively more obvious than FD% given the suspicion that GA may form and progress due to the progressive loss of CC perfusion and the size of this perfusion deficit may correlate with localized ischemia and the subsequent loss of the retinal pigment epithelium. Moreover, future studies also need to investigate whether CC flow impairment correlates with other pathologies in AMD, such as drusen and macular neovascularization, and whether differences exist between CC FD% and FDa in these eyes. Combined with our previous study, we now have provided normative data to understand how CC FDa and FD% change in different regions of the macula with normal aging. 4 An increase in CC flow impairment was observed in the central macula during the normal aging process without the development of obvious pathology. This leads to the hypothesis that such an increase in FDs may contribute to the onset and severity of disease in individuals who are at risk for pathologies associated with aging, such as AMD. Moving forward, we hope to leverage this information to better understand the role CC flow impairments plays in different pathologies combined with genetics and the overall health status of the patients. This research represents a work in progress, and our ability to evaluate CC FDs and flow velocity within the CC will improve as SS-OCTA technology evolves. 35-37 Given the intrinsic difficulties in imaging and quantifying CC features, and the fact that a number of studies have recently appeared in the literature using different instruments, algorithms, and terminologies that may yield disparate conclusions, we believe it is important at this time to reflect on the best strategies for measuring CC flow impairment. We recommend that whatever instrument is used, the researchers should only employ an algorithm that has been validated. The validation of CC algorithm should focus on both qualitative CC visualization and quantitative CC analysis. As a first step to provide qualitatively CC en face flow image, a segmentation strategy should be adopted that is parallel and under the BM rather than a segmentation strategy that follows the retinal pigment epithelium, especially in pathologic eyes with elevations of the retinal pigment epithelium such as drusen in which the light-scattering properties of the retinal pigment epithelium and the signal attenuation of the drusen may cause variability in the appearance of the CC. 33 To be consistent with histologic findings, the generated CC en face images should be able to show the lobular pattern of the CC, especially in the peripheral regions, because the CC vessels cannot be visualized in the central macula as these capillaris are beyond the resolution of current commercial OCTA instruments. 3 , 33 Furthermore, the CC flow appearance should be consistent in the same region when using different scan patterns and should also be consistent between averaged scans when using the same scan pattern. 33 , 38 As the first step for CC quantitative analysis, proper terminologies to describe FDs should be used, and there are certain parameters that should be avoided. Vessel parameters such as perfusion density, vessel length density, and vessel diameter index have been used to quantify CC changes with age, 8 , 9 , 20 , 21 but these measurements cannot be meaningfully computed from CC images because of the limitations of current OCTA technologies, as the CC vessels within the macula are typically below the lateral resolution of the instruments. Similarly, parameters like gray value, 8 defined as the mean, grayscale intensity value of all pixels in the region of interest are problematic because the grayscale intensity produced by OCTA technologies is influenced by a number of factors such as flow velocity, wavelength, interscan times, projection artifacts from the retina, focusing, and anatomic alterations overlying the CC. 5 , 7 , 39-41 Very small FDs, with diameters below the transverse resolution of the particular instrument and/or scanning pattern, should be viewed with suspicion and removed from the analyses. Previously, the term of flow voids, which was used to describe an area without detectable flow, is a misnomer. 20 Just because the flow was not detectable does not mean it represents a true flow void. Moreover, CC analysis using different OCTA instruments should consider the limitation of SD-OCTA instrument for CC visualization compared with SS-OCTA. 20 , 42 SD-OCTA operates at 840 nm wavelength, which is heavily scattered by the retinal pigment epithelial complex, and thus affects the ability to visualize CC. However, SS-OCTA operates at a wavelength of approximately 1,060 nm, which results in less scattering by the retinal pigment epithelium and less sensitivity roll-off for choroidal imaging compared with SD-OCT imaging. Moreover, SS-OCTA instruments have faster scanning rates and denser scan patterns, which results in better CC images compared with SD-OCTA instruments. Sacconi and associates investigated CC in 72 normal eyes using SS-OCTA. 9 Although they found that CC perfusion density decreased with aging and this decrease was greater in the foveal region compared to parafoveal region, the repeatability and reproducibility of their algorithm were not analyzed. Although they reported the CC perfusion density was significantly decreased in the foveal region compared with the parafoveal regions in subjects, they showed differences in significance between their 3×3-mm and 6×6-mm scans, and they found inconsistent changes when comparing different age groups, particularly those in their 30s and 50s compared with other decades of life. 9 We did not observe these internal inconsistencies, and their internal discrepancies, as well as their differences compared with our results, most likely arise from their use of an algorithm that was not validated. Using the same instrument, we found that CC flow impairments increase with age in normal eyes, especially within the C 1 region, and the results were consistent when using different scan patterns (3×3-mm and 6×6-mm scans) and different parameters (FD% and FDa), and these results support the strengths of our approach. The usefulness of a validated algorithm become even more important when analyzing eyes with different pathologies. In our current study, the CC FDa measured in the 3×3-mm scans were correlated with CC FDa from the 6×6-mm scans, but the value of CC FDa from the 3×3-mm scans tended to be smaller than the values from 6×6-mm scans. This was primarily due to the different scanning parameters of different patterns. The 3×3-mm scans have a spacing distance of 10 μm between A scans and B scans whereas the 6×6-mm scans have a spacing of 12 μm. In addition, the B scans are repeated 4 times in the 3×3-mm scans and repeated twice in the 6×6-mm scans. Thus, the 6×6-mm scan has less averaging and greater separation, which, we hypothesize, results in greater average FD size measurements. As scanning speeds increase and denser scan patterns are achieved, the measurement differences between different scan patterns should become less apparent. One of the limitations in our current study is that we did not stratify patients based on their systemic diseases other than excluding patients with diabetes and uncontrolled hypertension. Future studies are needed to investigate how cardiovascular disease, hypertension, and other systemic disease affect the CC perfusion over time. Future studies should explore how the duration of systemic diseases, the number and duration of medications, and the types of interventional procedures affect CC flow impairment. Another limitation is that our compensation strategy, although superior to other strategies for processing CC images, is not always successful in completely restoring the OCT signal in areas where overlying retinal structures significantly attenuate the light source. Although it is not possible to restore a signal in some areas where the signal is completely attenuated, we are now developing and testing other compensation and thresholding strategies that should improve our ability to provide better CC images. These approaches could be extremely useful in studying a wide range of eye diseases, especially AMD in eyes with drusen, neovascularization, or GA. Our algorithm provides CC images showing a morphology similar to histologic findings. In addition, our previous work demonstrated qualitative and quantitative similarities between different scan patterns, repeated scans, and different studies. 4 , 33 , 34 Nevertheless, improvements in OCTA technology will help us further understand the CC in vivo and approach the results given by histology or OCT with adaptive optics. 35 In summary, we used SS-OCTA to investigate CC FDa changes with age in normal eyes, and our results were consistent with previously reported age-related CC FD% changes. Although both parameters are strongly correlated with each other, CC FDa and FD% represent different features of CC flow impairment. Studies are ongoing to investigate how these 2 parameters correlate with the onset, severity, and progression of various retinal and macular diseases. Funding/Support: Research supported by grants from Carl Zeiss Meditec, Inc. (Dublin, CA), the National Eye Institute ( R01EY024158 , R01EY028753 ), the Salah Foundation , an unrestricted grant from the Research to Prevent Blindness , Inc, New York, NY, and the National Eye Institute Center Core Grant ( P30EY014801 ) to the Department of Ophthalmology, University of Miami Miller School of Medicine . The funding organization had no role in the design or conduct of this research. Financial Disclosures: Drs Gregori, Wang, and Rosenfeld received research support from Carl Zeiss Meditec , Inc. Dr Gregori and the University of Miami co-own a patent that is licensed to Carl Zeiss Meditec, Inc. Dr Rosenfeld is a consultant for Apellis, Boehringer-Ingelheim, Carl Zeiss Meditec, Chengdu Kanghong Biotech, Healios K.K., Hemera Biosciences, F. Hoffmann-La Roche Ltd, Isarna Pharmaceuticals, Lin Bioscience, NGM Biopharmaceuticals, Ocunexus Therapeutics, Ocudyne, and Unity Biotechnology. Dr Rosenfeld has equity interest in Apellis, Verana Health, and Ocudyne. Dr Wang discloses intellectual property owned by the Oregon Health and Science University and the University of Washington related to OCT angiography, and licensed to commercial entities, which are related to the technology and analysis methods described in parts of this manuscript. Dr Wang also receives research support from Tasso Inc. He is a consultant to Insight Photonic Solutions, and Kowa. Drs de Sisternes and Durbin are employed by Carl Zeiss Meditec, Inc. Drs Shi, Zhang, Zheng, Russell, Motulsky, Banta, Chu, Zhou, and Patel have no disclosures. Mr Feuer have no disclosures. All authors attest that they meet the current ICMJE criteria for authorship. Funding Information: Funding/Support: Research supported by grants from Carl Zeiss Meditec, Inc. (Dublin, CA), the National Eye Institute (R01EY024158, R01EY028753), the Salah Foundation, an unrestricted grant from the Research to Prevent Blindness, Inc, New York, NY, and the National Eye Institute Center Core Grant (P30EY014801) to the Department of Ophthalmology, University of Miami Miller School of Medicine. The funding organization had no role in the design or conduct of this research. Financial Disclosures: Drs Gregori, Wang, and Rosenfeld received research support from Carl Zeiss Meditec, Inc. Dr Gregori and the University of Miami co-own a patent that is licensed to Carl Zeiss Meditec, Inc. Dr Rosenfeld is a consultant for Apellis, Boehringer-Ingelheim, Carl Zeiss Meditec, Chengdu Kanghong Biotech, Healios K.K. Hemera Biosciences, F. Hoffmann-La Roche Ltd, Isarna Pharmaceuticals, Lin Bioscience, NGM Biopharmaceuticals, Ocunexus Therapeutics, Ocudyne, and Unity Biotechnology. Dr Rosenfeld has equity interest in Apellis, Verana Health, and Ocudyne. Dr Wang discloses intellectual property owned by the Oregon Health and Science University and the University of Washington related to OCT angiography, and licensed to commercial entities, which are related to the technology and analysis methods described in parts of this manuscript. Dr Wang also receives research support from Tasso Inc. He is a consultant to Insight Photonic Solutions, and Kowa. Drs de Sisternes and Durbin are employed by Carl Zeiss Meditec, Inc. Drs Shi, Zhang, Zheng, Russell, Motulsky, Banta, Chu, Zhou, and Patel have no disclosures. Mr Feuer have no disclosures. All authors attest that they meet the current ICMJE criteria for authorship. Publisher Copyright: © 2019 Elsevier Inc.
PY - 2020/1
Y1 - 2020/1
N2 - Purpose: Choriocapillaris (CC) imaging of normal eyes with swept-source optical coherence tomographic angiography (SS-OCTA) was performed, and the percentage of CC flow deficits (FD%) and the average area of CC flow deficits (FDa) were compared within the given macular regions. Design: A prospective, cross-sectional study. Methods: Subjects with normal eyes ranging in age from their 20s through their 80s were imaged with SS-OCTA (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, California, USA) using both 3×3-mm and 6×6-mm macular scan patterns. The CC images were generated using a previously published and validated algorithm. In both 3×3-mm and 6×6-mm scans, the CC FD% and FDa were measured in circular regions centered on the fovea with diameters as 1 mm and 2.5 mm (C1 and C2.5). In 6×6-mm scans, the FD% and FDa were measured within an additional circular region with diameter as 5 mm (C5). The correlations between FD% and FDa from each region were analyzed with Pearson correlation coefficients. Results: A total of 164 eyes were analyzed. There was excellent correlation between CC FDa and FD% measurements from each region. In the 3×3-mm scans, the correlations in the C1 and C2.5 regions were 0.83 and 0.90, respectively. In the 6×6-mm scans, the correlations in C1, C2.5, and C5 regions were 0.90, 0.89, and 0.89, respectively. Conclusions: When measuring CC FDs, we found excellent correlations between FDa and FD% in regions from 3×3-mm and 6×6-mm scans. Further studies are needed to determine if one parameter is more useful when studying diseased eyes.
AB - Purpose: Choriocapillaris (CC) imaging of normal eyes with swept-source optical coherence tomographic angiography (SS-OCTA) was performed, and the percentage of CC flow deficits (FD%) and the average area of CC flow deficits (FDa) were compared within the given macular regions. Design: A prospective, cross-sectional study. Methods: Subjects with normal eyes ranging in age from their 20s through their 80s were imaged with SS-OCTA (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, California, USA) using both 3×3-mm and 6×6-mm macular scan patterns. The CC images were generated using a previously published and validated algorithm. In both 3×3-mm and 6×6-mm scans, the CC FD% and FDa were measured in circular regions centered on the fovea with diameters as 1 mm and 2.5 mm (C1 and C2.5). In 6×6-mm scans, the FD% and FDa were measured within an additional circular region with diameter as 5 mm (C5). The correlations between FD% and FDa from each region were analyzed with Pearson correlation coefficients. Results: A total of 164 eyes were analyzed. There was excellent correlation between CC FDa and FD% measurements from each region. In the 3×3-mm scans, the correlations in the C1 and C2.5 regions were 0.83 and 0.90, respectively. In the 6×6-mm scans, the correlations in C1, C2.5, and C5 regions were 0.90, 0.89, and 0.89, respectively. Conclusions: When measuring CC FDs, we found excellent correlations between FDa and FD% in regions from 3×3-mm and 6×6-mm scans. Further studies are needed to determine if one parameter is more useful when studying diseased eyes.
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U2 - 10.1016/j.ajo.2019.09.017
DO - 10.1016/j.ajo.2019.09.017
M3 - Article
C2 - 31562858
AN - SCOPUS:85075369726
VL - 209
SP - 18
EP - 26
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
SN - 0002-9394
ER -