Emily D. Cole

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVEALS CHORIOCAPILLARIS ALTERATIONS IN EYES WITH NASCENT GEOGRAPHIC ATROPHY AND DRUSEN-ASSOCIATED GEOGRAPHIC ATROPHY.

Purpose: To investigate choriocapillaris (CC) alteration in patients with nascent geographic atrophy (nGA) and/or drusen-associated geographic atrophy (DAGA) using swept-source optical coherence tomography angiography (OCTA). Methods: A 1,050-nm wavelength, 400 kHz A-scan rate swept-source optical coherence tomography prototype was used to perform volumetric swept-source optical coherence tomography angiography over 6 mm × 6 mm fields of view in patients with nGA and/or DAGA. The resulting optical coherence tomography (OCT) and OCTA data were analyzed using a combination of en face and cross-sectional techniques. Variable interscan time analysis (VISTA) was used to differentiate CC flow impairment from complete CC atrophy. Results: A total of 7 eyes from 6 patients (mean age: 73.8 ± 5.7 years) were scanned. Seven areas of nGA and three areas of DAGA were identified. Analysis of cross-sectional OCT and OCTA images identified focal alterations of the CC underlying all seven areas of nGA and all three areas of DAGA. En face OCTA analysis of the CC revealed diffuse CC alterations in all eyes. Variable interscan time analysis processing suggested that the observed CC flow alterations predominantly corresponded to flow impairment rather than complete CC atrophy. Conclusion: The OCTA imaging of the CC revealed focal CC flow impairment associated with areas of nGA and DAGA, as well as diffuse CC flow impairment throughout the imaged field. En face OCT analysis should prove useful for understanding the pathogenesis of nGA and DAGA and for identifying the formation of nGA and DAGA as endpoints in therapeutic trials.

Visualizing the Choriocapillaris Under Drusen: Comparing 1050-nm Swept-Source Versus 840-nm Spectral-Domain Optical Coherence Tomography Angiography

Purpose To investigate the appearance of choriocapillaris (CC) flow under drusen by comparing long-wavelength (1050 nm) swept-source optical coherence tomography (SS-OCT) angiography with shorter-wavelength (840 nm) spectral-domain (SD) OCT angiography. Methods Patients with drusen imaged on both devices on the same day were selected and graded. Ambiguous OCT angiography (OCTA) signal loss was defined as low OCTA signal on the en face OCTA CC image that also had low OCT signal in the corresponding area on the en face OCT CC image and OCT B-scans. Unambiguous OCTA signal loss was defined as low OCTA signal on the en face OCTA CC image that did not have low OCT signal in the corresponding area on the en face OCT CC image and OCT B-scans. False-positive flow impairment on SS-OCTA was defined as ambiguous OCTA signal loss on SS-OCTA but no OCTA signal loss on SD-OCTA. False-positive flow impairment on SD-OCTA was defined as ambiguous OCTA signal loss on SD-OCTA but no OCTA signal loss on SS-OCTA. Results Nine eyes from seven patients were enrolled, 23 drusen were analyzed. On 840-nm SD-OCTA, 17 drusen (73.9%) exhibited OCTA signal loss. Fourteen (82.4%) were classified as ambiguous, and three (17.6%) were classified as unambiguous; 10 (58.8%) were classified as having false-positive flow impairment. On 1050-nm SS-OCTA, seven drusen (30.4%) exhibited OCTA signal loss and were classified as unambiguous; none were classified as having false-positive flow impairment. Conclusions Results showed that 1050-nm SS-OCTA appears less prone to producing areas of false-positive flow impairment under drusen.

TOWARD QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: Visualizing Blood Flow Speeds in Ocular Pathology Using Variable Interscan Time Analysis.

Purpose: Currently available optical coherence tomography angiography systems provide information about blood flux but only limited information about blood flow speed. The authors develop a method for mapping the previously proposed variable interscan time analysis (VISTA) algorithm into a color display that encodes relative blood flow speed. Methods: Optical coherence tomography angiography was performed with a 1,050 nm, 400 kHz A-scan rate, swept source optical coherence tomography system using a 5 repeated B-scan protocol. Variable interscan time analysis was used to compute the optical coherence tomography angiography signal from B-scan pairs having 1.5 millisecond and 3.0 milliseconds interscan times. The resulting VISTA data were then mapped to a color space for display. Results: The authors evaluated the VISTA visualization algorithm in normal eyes (n = 2), nonproliferative diabetic retinopathy eyes (n = 6), proliferative diabetic retinopathy eyes (n = 3), geographic atrophy eyes (n = 4), and exudative age-related macular degeneration eyes (n = 2). All eyes showed blood flow speed variations, and all eyes with pathology showed abnormal blood flow speeds compared with controls. Conclusion: The authors developed a novel method for mapping VISTA into a color display, allowing visualization of relative blood flow speeds. The method was found useful, in a small case series, for visualizing blood flow speeds in a variety of ocular diseases and serves as a step toward quantitative optical coherence tomography angiography.

AN AUTOMATIC, INTERCAPILLARY AREA-BASED ALGORITHM FOR QUANTIFYING DIABETES-RELATED CAPILLARY DROPOUT USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE To develop a robust, sensitive, and fully automatic algorithm to quantify diabetes-related capillary dropout using optical coherence tomography (OCT) angiography (OCTA). METHODS A 1,050-nm wavelength, 400 kHz A-scan rate swept-source optical coherence tomography prototype was used to perform volumetric optical coherence tomography angiography imaging over 3 mm × 3 mm fields in normal controls (n = 5), patients with diabetes without diabetic retinopathy (DR) (n = 7), patients with nonproliferative diabetic retinopathy (NPDR) (n = 9), and patients with proliferative diabetic retinopathy (PDR) (n = 5); for each patient, one eye was imaged. A fully automatic algorithm to quantify intercapillary areas was developed. RESULTS Of the 26 evaluated eyes, the segmentation was successful in 22 eyes (85%). The mean values of the 10 and 20 largest intercapillary areas, either including or excluding the foveal avascular zone, showed a consistent trend of increasing size from normal control eyes, to eyes with diabetic retinopathy but without diabetic retinopathy, to nonproliferative diabetic retinopathy eyes, and finally to PDR eyes. CONCLUSION Optical coherence tomography angiography-based screening and monitoring of patients with diabetic retinopathy is critically dependent on automated vessel analysis. The algorithm presented was able to automatically extract an intercapillary area-based metric in patients having various stages of diabetic retinopathy. Intercapillary area-based approaches are likely more sensitive to early stage capillary dropout than vascular density-based methods.Purpose: To develop a robust, sensitive, and fully automatic algorithm to quantify diabetes-related capillary dropout using optical coherence tomography (OCT) angiography (OCTA). Methods: A 1,050-nm wavelength, 400 kHz A-scan rate swept-source optical coherence tomography prototype was used to perform volumetric optical coherence tomography angiography imaging over 3 mm × 3 mm fields in normal controls (n = 5), patients with diabetes without diabetic retinopathy (DR) (n = 7), patients with nonproliferative diabetic retinopathy (NPDR) (n = 9), and patients with proliferative diabetic retinopathy (PDR) (n = 5); for each patient, one eye was imaged. A fully automatic algorithm to quantify intercapillary areas was developed. Results: Of the 26 evaluated eyes, the segmentation was successful in 22 eyes (85%). The mean values of the 10 and 20 largest intercapillary areas, either including or excluding the foveal avascular zone, showed a consistent trend of increasing size from normal control eyes, to eyes with diabetic retinopathy but without diabetic retinopathy, to nonproliferative diabetic retinopathy eyes, and finally to PDR eyes. Conclusion: Optical coherence tomography angiography-based screening and monitoring of patients with diabetic retinopathy is critically dependent on automated vessel analysis. The algorithm presented was able to automatically extract an intercapillary area-based metric in patients having various stages of diabetic retinopathy. Intercapillary area-based approaches are likely more sensitive to early stage capillary dropout than vascular density-based methods.

CLINICAL TRIAL ENDPOINTS FOR OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

Purpose: To describe qualitative and quantitative optical coherence tomography (OCT) angiography (OCTA) parameters for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and their applicability as potential clinical trial endpoints. Methods: A review of current literature related to the topic of OCTA and AMD. Results: There are a number of promising OCTA parameters that can be used to diagnose the presence of CNV and to monitor the activity and progression of the lesion, pre- and post-treatment morphological characteristics, CNV dimensions, and automated quantitative parameters such as vessel density. Conclusion: The OCTA parameters described in this review have promise for the future development of clinical trial endpoints, but require further validation before they can be widely used.

Contemporary retinal imaging techniques in diabetic retinopathy: a review

Over the last decade, there has been an expansion of imaging modalities available to clinicians to diagnose and monitor the treatment and progression of diabetic retinopathy. Recently, advances in image technologies related to OCT and OCT angiography have enabled improved visualization and understanding of this disease. In this review, we will describe the use of imaging techniques such as colour fundus photography, fundus autofluorescence, fluorescein angiography, infrared reflectance imaging, OCT, OCT‐Angiography and techniques in adaptive optics and hyperspectral imaging in the diagnosis and management of diabetic retinopathy.

Optical Coherence Tomography Angiography in Nonarteritic Anterior Ischemic Optic Neuropathy.

Background: Optical coherence tomography angiography (OCTA) has demonstrated good utility in qualitative analysis of retinal and choroidal vasculature and therefore may be relevant in the diagnostic and treatment efforts surrounding nonarteritic anterior ischemic optic neuropathy (NAION). Methods: Retrospective, cross-sectional study of 10 eyes of 9 patients with a previous or new diagnosis of NAION that received imaging with OCTA between November 2015 and February 2016. Two independent readers qualitatively analyzed the retinal peripapillary capillaries (RPC) and peripapillary choriocapillaris (PCC) for flow impairment. Findings were compared with automated visual field and structural optical coherence tomography (OCT) studies. Results: Flow impairment seen on OCTA in the RPC corresponded to structural OCT deficits of the retinal nerve fiber layer (RNFL) and ganglion cell layer complex (GCC) in 80% and 100% of eyes, respectively, and to automated visual field deficits in 90% of eyes. Flow impairment seen on OCTA in the PCC corresponded to structural OCT deficits of the RNFL and GCC in 70% and 80% of eyes, respectively, and to visual field deficits in 60%–80% of eyes. Conclusions: OCTA can noninvasively visualize microvascular flow impairment in patients with NAION.

The Definition, Rationale, and Effects of Thresholding in OCT Angiography

PURPOSE To examine the definition, rationale, and effects of thresholding in OCT angiography (OCTA). DESIGN A theoretical description of OCTA thresholding in combination with qualitative and quantitative analysis of the effects of OCTA thresholding in eyes from a retrospective case series. PARTICIPANTS Four eyes were qualitatively examined: 1 from a 27-year-old control, 1 from a 78-year-old exudative age-related macular degeneration (AMD) patient, 1 from a 58-year-old myopic patient, and 1 from a 77-year-old nonexudative AMD patient with geographic atrophy (GA). One eye from a 75-year-old nonexudative AMD patient with GA was quantitatively analyzed. MAIN OUTCOME MEASURES A theoretical thresholding model and a qualitative and quantitative description of the dependency of OCTA on thresholding level. RESULTS Due to the presence of system noise, OCTA thresholding is a necessary step in forming OCTA images; however, thresholding can complicate the relationship between blood flow and OCTA signal. CONCLUSIONS Thresholding in OCTA can cause significant artifacts, which should be considered when interpreting and quantifying OCTA images.

En Face Doppler Optical Coherence Tomography Measurement of Total Retinal Blood Flow in Diabetic Retinopathy and Diabetic Macular Edema

Importance Alterations in ocular blood flow play an important role in the pathogenesis and progression of diabetic retinopathy (DR). However, the measurement of retinal blood flow in clinical studies has been challenging. En face Doppler optical coherence tomography (OCT) provides an effective method for measuring total retinal blood flow (TRBF) in the clinic. Objective To investigate TRBF in eyes with DR of varying severity, with or without diabetic macular edema (DME), using en face Doppler OCT. Design, Setting, and Participants This was a cross-sectional study conducted from May 23, 2014, to January 11, 2016, which analyzed 41 eyes with DR from 31 diabetic patients, 20 eyes without DR from 11 diabetic patients, and 16 eyes from 12 healthy age-matched controls, all at the New England Eye Center in Boston, Massachusetts. Main Outcomes and Measures Participants were imaged with a high-speed, swept-source OCT prototype at 1050-nm wavelength using repeated en face Doppler OCT raster scans, comprising 600 × 80 axial scans and covering a 1.5 × 2-mm2 area centered at the optic disc. The TRBF was automatically calculated using custom Matlab software. Results This study included 41 eyes with DR from 31 diabetic patients (mean [SD] age, 62.8 [13.4] years; 12 were female patients), 20 eyes without DR from 11 diabetic patients (mean [SD] age, 58.8 [10.1] years; 5 were female patients), and 16 eyes from 12 healthy age-matched controls (mean [SD] age, 57.9 [8.1] years; 8 were female participants). The mean (SD) TRBF was 28.0 (8.5) µL/min in the eyes with DME, 48.8 (13.4) µL/min in the eyes with DR but without DME, 40.1 (7.7) µL/min in the diabetic eyes without retinopathy, and 44.4 (8.3) µL/min in age-matched healthy eyes. A difference in TRBF between the eyes with DME that were treated and the eyes with DME that were not treated was not identified. The TRBF was consistently low in the eyes with DME regardless of DR severity. The eyes with moderate nonproliferative DR but without DME exhibited a wide range of TRBF from 31.1 to 75.0 µL/min, with the distribution being highly skewed. Conclusions and Relevance High-speed en face Doppler OCT can measure TRBF in healthy and diabetic eyes. Diabetic eyes with DME exhibited lower TRBF than healthy eyes (P ⩽ .001). Further longitudinal studies of TRBF in eyes with DR would be helpful to determine whether reduced TRBF is a risk factor for DME.

Visualization of Changes in the Choriocapillaris, Choroidal Vessels, and Retinal Morphology After Focal Laser Photocoagulation Using OCT Angiography

PURPOSE To utilize optical coherence tomography (OCT) and OCT angiography (OCTA) to describe alterations in the retinal and choriocapillaris vasculature following remote laser photocoagulation. Lesions are classified on the basis of choriocapillaris alteration as evaluated on en face OCTA. METHODS This was a retrospective, cross-sectional study analyzing 28 laser photocoagulation scars from 8 patients treated for diabetic macular edema. All eyes were analyzed using a combination of OCTA, en face and cross-sectional OCT, and fundus photography. Two masked readers scored images for alterations at the level of the retinal pigment epithelium (RPE), choroid, and choriocapillaris. Laser photocoagulation lesions were classified as deep if choriocapillaris alteration was present on OCTA; lesions were classified as superficial if no choriocapillaris alteration was present on OCTA. RESULTS Optical coherence tomography angiography was found to be useful for evaluation of choriocapillaris alteration underlying regions of laser scarring. Of the 28 analyzed laser scars, 13 were classified as superficial and 15 were classified as deep. CONCLUSIONS Optical coherence tomography angiography can be used to visualize choriocapillaris alterations associated with focal laser photocoagulation treatment.