Eric M. Moult

Ultrahigh-Speed Swept-Source OCT Angiography in Exudative AMD

BACKGROUND AND OBJECTIVE To investigate the potential of ultrahigh-speed swept-source optical coherence tomography angiography (OCTA) to visualize retinal and choroidal vascular changes in patients with exudative age-related macular degeneration (AMD). PATIENTS AND METHODS Observational, prospective cross-sectional study. An ultrahigh-speed swept-source prototype was used to perform OCTA of the retinal and choriocapillaris microvasculature in 63 eyes of 32 healthy controls and 19 eyes of 15 patients with exudative AMD. MAIN OUTCOME MEASURE qualitative comparison of the retinal and choriocapillaris microvasculature in the two groups. RESULTS Choroidal neovascularization (CNV) was clearly visualized in 16 of the 19 eyes with exudative AMD, located above regions of severe choriocapillaris alteration. In 14 of these eyes, the CNV lesions were surrounded by regions of choriocapillaris alteration. CONCLUSION OCTA may offer noninvasive monitoring of the retinal and choriocapillaris microvasculature in patients with CNV, which may assist in diagnosis and monitoring.

Ultrahigh-Speed, Swept-Source Optical Coherence Tomography Angiography in Nonexudative Age-Related Macular Degeneration with Geographic Atrophy

PURPOSE To investigate ultrahigh-speed, swept-source optical coherence tomography (SSOCT) angiography for visualizing vascular changes in eyes with nonexudative age-related macular degeneration (AMD) with geographic atrophy (GA). DESIGN Observational, prospective, cross-sectional study. PARTICIPANTS A total of 63 eyes from 32 normal subjects and 12 eyes from 7 patients with nonexudative AMD with GA. METHODS A 1050-nm, 400-kHz A-scan rate SSOCT system was used to perform volumetric optical coherence tomography angiography (OCTA) of the retinal and choriocapillaris (CC) vasculatures in normal subjects and patients with nonexudative AMD with GA. Optical coherence tomography angiography using variable interscan time analysis (VISTA) was performed to assess CC alteration and differentiate varying degrees of CC flow impairment. MAIN OUTCOME MEASURES Qualitative comparison of retinal and CC vasculatures in normal subjects versus those in patients with a clinical diagnosis of nonexudative AMD with GA. RESULTS In all 12 eyes with GA, OCTA showed pronounced CC flow impairment within the region of GA. In 10 of the 12 eyes with GA, OCTA with VISTA showed milder CC flow impairment extending beyond the margin of GA. Of the 5 eyes exhibiting foveal-sparing GA, OCTA showed CC flow within the region of foveal sparing in 4 of the eyes. CONCLUSIONS The ability of ultrahigh-speed, swept-source OCTA to noninvasively visualize alterations in the retinal and CC vasculatures makes it a promising tool for assessing nonexudative AMD with GA. Optical coherence tomography angiography using VISTA can distinguish varying degrees of CC alteration and flow impairment and may be useful for elucidating disease pathogenesis, progression, and response to therapy.

Select Features of Diabetic Retinopathy on Swept-Source Optical Coherence Tomographic Angiography Compared With Fluorescein Angiography and Normal Eyes

IMPORTANCE Optical coherence tomographic angiography (OCTA) is a recently developed noninvasive imaging technique that can visualize the retinal and choroidal microvasculature without the injection of exogenous dyes. OBJECTIVE To evaluate the potential clinical utility of OCTA using a prototype swept-source OCT (SS-OCT) device and compare it with fluorescein angiography (FA) for analysis of the retinal microvasculature in diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS Prospective, observational cross-sectional study conducted at a tertiary care academic retina practice from November 2013 through November 2014. A cohort of diabetic and normal control eyes were imaged with a prototype SS-OCT system. The stage of diabetic retinopathy was determined by clinical examination. Imaging was performed using angiographic 3 × 3-mm and 6 × 6-mm SS-OCT scans to generate 3-dimensional en-face OCT angiograms for each eye. Two trained Boston Image Reading Center readers reviewed and graded FA and OCTA images independently. MAIN OUTCOMES AND MEASURES The size of the foveal nonflow zone and the perifoveal intercapillary area on OCTA were measured in both normal and diabetic eyes using Boston Image Reading Center image analysis software. RESULTS The study included 30 patients with diabetes (mean [SD] age, 55.7 [10] years) and 6 control individuals (mean [SD] age, 55.1 [6.4] years). A total of 43 diabetic and 11 normal control eyes were evaluated with OCTA. Fluorescein angiography was performed in 17 of 43 diabetic eyes within 8 weeks of the OCTA. Optical coherence tomographic angiography was able to identify a mean (SD) of 6.4 (4.0) microaneurysms (95% CI, 4.4-8.5), while FA identified a mean (SD) of 10 (6.9) microaneurysms (95% CI, 6.4-13.5). The exact intraretinal depth of microaneurysms on OCTA was localized in all cases (100%). The sensitivity of OCTA in detecting microaneuryms when compared with FA was 85% (95% CI, 53-97), while the specificity was 75% (95% CI, 21-98). The positive predictive value and the negative predictive value were 91% (95% CI, 59-99) and 60% (95% CI, 17-92), respectively. CONCLUSIONS AND RELEVANCE Optical coherence tomographic angiography enables noninvasive visualization of macular microvascular pathology in eyes with diabetic retinopathy. It identified fewer microaneurysms than FA, but located their exact intraretinal depth. Optical coherence tomographic angiography also allowed the precise and reproducible delineation of the foveal nonflow zone and perifoveal intercapillary area. Evaluation of OCTA may be of clinical utility in the evaluation and grading of diabetic eye disease.

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.

Optical Coherence Tomography Angiography of Dry Age-Related Macular Degeneration

Optical coherence tomography angiography (OCTA) can be used to visualize alterations in the choriocapillaris of patients with dry age-related macular degeneration (AMD). These changes seem to be present during all stages of the disease. Earlier stages are associated with patchy thinning of the choriocapillaris, while geographic atrophy is associated with loss of choriocapillaris lying under the area of geographic atrophy and asymmetric alteration of choriocapillaris at the margins of the geographic atrophy. The use of high-speed, long-wave-length swept-source OCT for angiography, with its better penetration into the choroid and high acquisition speeds, enable OCTA with scaled slowest detectable flow and fastest distinguishable flow. This will enable us to better investigate choriocapillaris changes in patients with dry AMD. The ability to image the choriocapillaris structure and flow impairments may be useful in the future for detecting and monitoring the progression of dry AMD and for monitoring treatment responses in clinical trials to therapies that target disease progression in dry AMD.

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.

ULTRAHIGH SPEED SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL AND CHORIOCAPILLARIS ALTERATIONS IN DIABETIC PATIENTS WITH AND WITHOUT RETINOPATHY.

Purpose: To investigate the utility of ultrahigh speed, swept source optical coherence tomography angiography in visualizing retinal microvascular and choriocapillaris (CC) changes in diabetic patients. Methods: The study was prospective and cross-sectional. 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 of the retinal and CC vasculatures in diabetic patients and normal subjects. Sixty-three eyes from 32 normal subjects, 9 eyes from 7 patients with proliferative diabetic retinopathy, 29 eyes from 16 patients with nonproliferative diabetic retinopathy, and 51 eyes from 28 diabetic patients without retinopathy were imaged. Results: Retinal and CC microvascular abnormalities were observed in all stages of diabetic retinopathy. In nonproliferative diabetic retinopathy and proliferative diabetic retinopathy, optical coherence tomography angiography visualized a variety of vascular abnormalities, including clustered capillaries, dilated capillary segments, tortuous capillaries, regions of capillary dropout, reduced capillary density, abnormal capillary loops, and foveal avascular zone enlargement. In proliferative diabetic retinopathy, retinal neovascularization above the inner limiting membrane was visualized. Regions of CC flow impairment in patients with proliferative diabetic retinopathy and nonproliferative diabetic retinopathy were also observed. In 18 of the 51 of eyes from diabetic patients without retinopathy, retinal mircrovascular abnormalities were observed and CC flow impairment was found in 24 of the 51 diabetic eyes without retinopathy. Conclusion: The ability of optical coherence tomography angiography to visualize retinal and CC microvascular abnormalities suggests it may be a useful tool for understanding pathogenesis, evaluating treatment response, and earlier detection of vascular abnormalities in patients with diabetes.

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.

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.