Retinal microvascular metrics: The emerging role of swept-source OCT angiography

Bios Ms. Barton is a medical student at Tufts University School of Medicine currently pursuing a research year at the Harvard Retinal Imaging Laboratory under the guidance of Dr. John B. Miller. Mr. Shah is a fourth-year medical student at Dartmouth College engaged in a dedicated research year at the Harvard Retinal Imaging Laboratory. Dr. Chen is a vitreoretinal surgeon at Shanghai General Hospital and the National Clinical Research Center for Eye Diseases, and a postdoctoral research fellow at the Harvard Retinal Imaging Lab, Massachusetts Eye and Ear.  Dr. Miller is an associate professor of ophthalmology at Massachusetts Eye and Ear of Harvard Medical School in Boston and director of the Harvard Retinal Imaging Laboratory. He discloses support by Intalight and Adaptive Sensory Technology and consulting work for Alcon, Allergan, Carl Zeiss, Sunovion, Topcon and Genentech.

Ultrahigh-speed swept-source optical coherence tomography angiography has gained increased attention for its ability to characterize retinal blood flow metrics with high precision. It offers a more non-invasive approach than fluorescein angiography, and faster scan rates compared to spectral-domain OCTA.¹ SS-OCTA has demonstrated utility across a wide range of retinal diseases, including diabetic retinopathy, age-related macular degeneration and retinal vein occlusion. Though primarily limited to larger centers at this time, SS-OCTA offers substantial potential for broader clinical implementation for retinal evaluation.

The field of retinal imaging has rapidly advanced in the past two decades, with ongoing efforts aimed at streamlining image analysis with higher accuracy. We aim to provide a brief overview of retinal microvascular metrics evaluated through ultrahigh-speed SS-OCTA—emphasizing relevant technical specifications, the potential for, and challenges of, clinical application, and potential future advancements.

Technical considerations

In brief, optical coherence tomography angiography is an imaging modality that relies on capturing repeated brightness scan (B-scan) images to quantify changes due to blood flow in comparison to surrounding static tissue, while still evaluating the structural characteristics of traditional OCT.² Early SS-OCTA prototypes were limited by relatively low B-scan acquisition rates, which constrained their ability to perform the repeated scans required for angiographic signal detection. Since the introduction of ultrahigh-speed SS-OCTA by Fujimoto’s group in 2010,^3,4 this imaging modality has been frequently studied for its clinical utility in a variety of retinal diseases. Using a tunable swept laser detected by a photodiode, modern ultrahigh-speed SS-OCTA can achieve scan rates between 100 to 400 kHz. This scan rate offers an improvement over earlier SS-OCTA devices that typically operated between 10 to 50 kHz.³ Ultrahigh-speed SS-OCTA also maintains the longer wavelength of earlier SS-OCTA models (~1050-nm) that contributed to deeper light penetration compared to SD-OCTA (~840-nm).^3,5

Figure 1. Right eye with branch retinal vein occlusion, imaged using expanded-field SS-OCTA (Zeiss PLEX Elite 9000) during routine follow-up. (A) 12 × 12 mm SS-OCTA image acquired at 100 kHz, demonstrating areas of nonperfusion (pink and blue lines indicate the location of the corresponding B-scan). (B) Corresponding B-scan with vascular overlay; yellow dashed lines represent segmentation boundaries.

Visualization of the retinal microvasculature

SS-OCTA can efficiently characterize many retinal microvascular metrics including retinal area and length densities, foveal avascular zone area, various flow areas and signal voids in microvascular networks.⁴ The combination of faster scan speed and increased wavelength offers improved sensitivity roll-off and reduced potential for scattering from the retinal pigment epithelium. Taken together, these factors all contribute to improvements in accuracy. Such improvements are particularly important in evaluating densely vascularized areas such as the optic nerve head, where high precision is necessary to discern structures.⁴ This higher speed is also helpful in visualizing deeper layers such as the deep capillary plexus and choroid, which are particularly susceptible to sensitivity roll-off.^5,6 Furthermore, faster scan speeds lead to reductions in artifacts that may interfere with evaluation.⁷ These characteristics may afford more accurate grading and characterization of retinal pathology.

Clinical implications

Differentiation in signals based on motion to distinguish blood flow from tissue and generate “decorrelation signals” underpins SS-OCTA. This non-invasive evaluation offers an advantage over dye-based modalities such as FA or indocyanine green angiography.^1,8 Subsequent development of scan speeds provided a marked advancement over earlier generations of SS-OCTA.
These faster acquisition speeds have allowed grading and characterization of a wide array of retinal diseases at depths that were previously difficult to effectively discern with earlier SS-OCTA technologies. For example, SS-OCTA has shown improved depth resolution of the choriocapillaris layer compared to ICGA, and this effect is amplified at faster image acquisition speeds.⁹ At these speeds, SS-OCTA even offers better assessment of choroidal vessels of greater size compared to SD-OCTA.¹⁰

These improvements in image acquisition have led to a number of novel applications, especially in clinical settings. This technology has been applied to detecting changes in CC perfusion among eyes with varying levels of AMD, and there is substantial potential for further evaluation of this relationship.^2,11 SS-OCTA has also demonstrated utility in both the early diagnosis and management of diabetic retinopathy. Compared to SD-OCT, SS-OCTA has superior visualization of the vitreoretinal interface, utility in convenient evaluation of non-perfusion area¹² and improved early detection of retinal microvasculature alterations and CC abnormalities.¹⁰ Other applications of SS-OCTA have included characterizing areas of nonperfusion in eyes with ischemic retinal vein occlusion¹⁰ and evaluating vessel density alterations associated with visual function changes in eyes with retinal artery occlusion.¹³

The ease of use, noninvasiveness and improved resolution of microvasculature may theoretically reduce the threshold to obtain imaging with SS-OCTA—whether it be initial scans to evaluate based on clinical suspicion or subsequent scans for longitudinal follow-up of retinal disease. As more cohorts are followed longitudinally, the findings in SS-OCTA that correspond to disease progression may be further characterized. Such understanding will compound the value of longitudinal retinal microvascular metrics for patients in a clinical setting by offering clues into potential for disease progression.

Challenges in SS-OCTA

Despite the advantages of SS-OCTA, there are still several challenges accompanying efforts to increase the scope of its use. First, though this technology offers improvements in artifact over earlier models with slower scan rates, artifacts still exist. Improvements in tracking can help limit motion artifacts, but manual correction is often required. The time-consuming nature of manual segmentation, which requires repeated adjustment of layer boundaries in areas of distortion, hinders efforts to efficiently analyze images for larger cohorts.¹⁴ Semi-automated algorithms are increasingly being applied to streamline image analysis,¹⁵ alongside current efforts to automate segmentation and correct errors in SS-OCTA images. Such advances would likely increase efficiency of research evaluation of disease complications and progression. Furthermore, automatic segmentation could ease the clinical implementation of SS-OCTA with improved efficiency of image analysis. Such improvements would allow for increased point-of-care utility without the need for manual correction of errors that would be impractical in fast-paced clinical settings.

With various SS-OCTA devices in use spanning different clinics and manufacturers–oftentimes with high inter-device variability in measurements such as vessel density—establishing a consensus of measurement will be critical.¹⁶ Similarly, limiting the variability of inter-device metrics will be critical. Such standardization will likely allow for more accurate longitudinal multicenter evaluation of patient cohorts. Lastly, cost remains a substantial limiting factor in the implementation of ultrahigh-speed SS-OCTA compared to SD-OCTA. This difference in price point is commonly attributed to the need for expensive laser components.¹⁰ Efforts to reduce the cost of this component would likely help improve the accessibility of this device.

Bottom line

Ultrahigh-speed SS-OCTA offers substantial potential for non-invasively quantifying perfusion and vessel areas within retinal microvasculature. This technology has demonstrated utility in determining differences in retinal microvasculature between various stages of disease, such as for AMD and DR. Longitudinal research is ongoing to determine the most predictive metrics of visual function, progression or complications of specific retinal diseases. Challenges involve addressing artifactual errors and increasing consensus regarding accepted measurements. However, with continued work in this area, there is much promise regarding broad clinical implementation of this technology. RS

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