Talisa E. de Carlo

A review of optical coherence tomography angiography (OCTA)

Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging technique that generates volumetric angiography images in a matter of seconds. This is a nascent technology with a potential wide applicability for retinal vascular disease. At present, level 1 evidence of the technology’s clinical applications doesn’t exist. In this paper, we introduce the technology, review the available English language publications regarding OCTA, and compare it with the current angiographic gold standards, fluorescein angiography (FA) and indocyanine green angiography (ICGA). Finally we summarize its potential application to retinal vascular diseases. OCTA is quick and non-invasive, and provides volumetric data with the clinical capability of specifically localizing and delineating pathology along with the ability to show both structural and blood flow information in tandem. Its current limitations include a relatively small field of view, inability to show leakage, and proclivity for image artifact due to patient movement/blinking. Published studies hint at OCTA’s potential efficacy in the evaluation of common ophthalmologic diseases such age related macular degeneration (AMD), diabetic retinopathy, artery and vein occlusions, and glaucoma. OCTA can detect changes in choroidal blood vessel flow and can elucidate the presence of choroidal neovascularization (CNV) in a variety of conditions but especially in AMD. It provides a highly detailed view of the retinal vasculature, which allows for accurate delineation of the foveal avascular zone (FAZ) in diabetic eyes and detection of subtle microvascular abnormalities in diabetic and vascular occlusive eyes. Optic disc perfusion in glaucomatous eyes is notable as well on OCTA. Further studies are needed to more definitively determine OCTA’s utility in the clinical setting and to establish if this technology may offer a non-invasive option of visualizing the retinal vasculature in detail.

Spectral-Domain Optical Coherence Tomography Angiography of Choroidal Neovascularization

PURPOSE To describe the characteristics as well as the sensitivity and specificity of detection of choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA) using spectral-domain optical coherence tomography. DESIGN Observational, retrospective study. PARTICIPANTS Seventy-two eyes of 61 subjects (48 eyes of 43 subjects with CNV, 24 eyes of 18 subjects without CNV). METHODS Patients imaged using the prototype AngioVue OCTA system (Optovue, Inc, Fremont, CA) between August 2014 and October 2014 at New England Eye Center were assessed. Patients in whom CNV was identified on OCTA were evaluated to define characteristics of CNV on OCTA: size using greatest linear dimension (small, <1 mm; medium, 1-2 mm; large, >2 mm), appearance (well-circumscribed, poorly circumscribed), and presence of subretinal and intraretinal fluid. Concurrently, an overlapping second cohort of patients who underwent same-day OCTA and fluorescein angiography (FA) for suspected CNV was evaluated to estimate sensitivity and specificity of OCTA in detecting CNV using FA as ground truth. MAIN OUTCOME MEASURES Choroidal neovascularization appearance, CNV size, and presence of subretinal and intraretinal fluid. RESULTS In 48 eyes, CNV was visualized on OCTA. Thirty-one eyes had CNV associated with neovascular age-related macular degeneration. Size of CNV was small in 23% (7/31), medium in 42% (13/31), and large in 35% (11/31). Poorly circumscribed vessels, subretinal fluid, and intraretinal fluid each were seen in 71% (22/31). Seven eyes had CNV associated with central serous chorioretinopathy. Size of CNV was small in 71% (5/7) and large in 29% (2/7). Seventy-one percent (5/7) had well-circumscribed vessels, 86% (6/7) had subretinal fluid, and 14% (1/7) had intraretinal fluid. Thirty eyes with OCTA and same-day FA were evaluated to determine sensitivity and specificity of CNV detection on OCTA. Sensitivity was 50% (4/8) and specificity was 91% (20/22). CONCLUSIONS Using OCTA allows the clinician to visualize CNV noninvasively and may provide a method for identifying and guiding treatment of CNV. The specificity of CNV detection on OCTA compared with FA seems to be high. Future studies with larger sample sizes are needed to elaborate better on the sensitivity and specificity of CNV detection and to illustrate clinical usefulness.

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.

Association of Choroidal Neovascularization and Central Serous Chorioretinopathy With Optical Coherence Tomography Angiography

IMPORTANCE Choroidal neovascularization (CNV) is a major cause of vision loss in chronic central serous chorioretinopathy (CSCR). Detecting CNV using fluorescein angiography (FA) may be challenging owing to the coexistence of features related to the primary diagnosis of CSCR. Optical coherence tomography angiography (OCTA) allows noninvasive visualization of retinal and choroidal vasculature via motion contrast and may contribute to the unequivocal diagnosis of CNV in this population. OBJECTIVE To evaluate the sensitivity of spectral-domain OCTA in detecting CNV associated with chronic CSCR. DESIGN, SETTING, AND PARTICIPANTS Observational cross-sectional study including 23 patients (27 eyes) who presented at the New England Eye Center between August 1, 2014, and November 30, 2014, with suspected CNV complicating chronic CSCR and underwent standard assessment for CNV diagnosis, including FA imaging. Participants were prospectively recruited to receive imaging tests using prototype OCTA software on a commercially available spectral-domain OCT. Orthogonal registration and the merging of 2 consecutive image sets were used to obtain 3 × 3-mm and 6 × 6-mm OCT angiograms centered at the macula. Two independent readers masked to other imaging findings performed a qualitative analysis on OCTA depictions of vascular flow representing CNV and the morphologic appearance of CNV. MAIN OUTCOMES AND MEASURES Choroidal neovascularization location as well as retinal pigment epithelial detachment internal reflectivity and the presence of subretinal and intraretinal fluid. Sensitivity and specificity of OCTA in detecting CNV were estimated using FA as the standard examination reference. RESULTS Choroidal neovascularization was diagnosed in 8 of 27 eyes (30%) based on FA imaging analysis. Optical coherence tomography angiography and corresponding OCT B-scans detected 100% (8 of 8) of these CNV lesions and correctly excluded 100% (19 of 19) of eyes with CSCR without CNV. Sensitivity was 100% (95% CI, 0.62-1) and specificity was 100% (95% CI, 0.82-1). Morphologic appearance, location, and position of the CNV relative to the retinal pigment epithelium and Bruch membrane were described using OCTA that combined flow and structural information. CONCLUSIONS AND RELEVANCE This study suggests that OCT alone (OCTA and coregistered OCT B-scans) features sensitivity and specificity comparable with FA for the detection of CNV in eyes with chronic CSCR.

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.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN RETINAL ARTERY OCCLUSION.

Purpose: To describe the retinal microvasculature of the eyes with nonarteritic retinal artery occlusion (RAO) based on optical coherence tomography angiography. Methods: Cross-sectional, prospective, observational study performed from September 2014 through February 2015. En face projection of optical coherence tomography angiography images centered at the macula and optic disk of the eyes presenting with RAO were acquired using the RTVue XR Avanti with AngioVue software. Qualitative analysis of the morphology of the superficial and deep retinal capillary plexuses, and radial peripapillary capillaries was performed. Retinal vasculature images using optical coherence tomography angiography were correlated with fluorescein angiography images. Results: Seven patients (seven eyes) were enrolled in the study, including three eyes with central RAO and four eyes with branch RAO. Distinct differences in the distribution of zones of decreased vascular perfusion between the superficial and deep retinal capillary plexus corresponding to areas of delayed dye perfusion on fluorescein angiography were demonstrated in 6 of 7 (86.5%) eyes. Conclusion: This small series suggests that optical coherence tomography angiography imaging can accurately discern retinal capillary plexuses at different levels in the eyes with RAO and may be sensitive for more precisely characterizing the extent of macular ischemia and monitoring vascular flow changes during the course of the disease.

Retinal Capillary Network and Foveal Avascular Zone in Eyes with Vein Occlusion and Fellow Eyes Analyzed With Optical Coherence Tomography Angiography.

PURPOSE To evaluate the perifoveolar retinal capillary network at different depths and to quantify the foveal avascular zone (FAZ) in eyes with retinal vein occlusion (RVO) compared with their fellow eyes and healthy controls using spectral-domain optical coherence tomography angiography (SD-OCTA). METHODS We prospectively recruited 23 patients with RVO including 15 eyes with central RVO (CRVO) and 8 eyes with branch RVO (BRVO), their fellow eyes, and 8 age-matched healthy controls (8 eyes) for imaging on prototype OCTA software within RTVue-XR Avanti. The 3 × 3 mm and 6 × 6 mm en face angiograms of superficial and deep retinal capillary plexuses were segmented. Perifoveolar retinal capillary network was analyzed and FAZ was quantified. RESULTS Decrease in vascular perfusion at the deep plexus was observed in all eyes with CRVO (8/8, 100%) and BRVO (6/6, 100%) without cystoid macular edema, and in 8 of 15 (53%) and 2 of 8 (25%) of the fellow eyes, respectively. Vascular tortuosity was observed in 13 of 15 (87%) CRVO and 5 of 8 (63%) BRVO eyes. Collaterals were seen in 10 of 15 (67%) CRVO and 5 of 8 (63%) BRVO eyes. Mean FAZ area was larger in eyes with RVO than their fellow eyes (1.13 ± 0.25 mm2 versus 0.58 ± 0.28 mm2; P = 0.007) and controls (1.13 ± 0.25 mm2 versus 0.30 ± 0.09 mm2; P < 0.0001), and in fellow eyes of RVO patients when compared to controls (0.58 ± 0.28 mm2 versus 0.30 ± 0.09 mm2; P = 0.01). CONCLUSIONS Spectral-domain OCTA reveals abnormalities at different levels of perifoveolar retinal capillary network and is able to quantify the FAZ in RVO. Longitudinal studies may be considered to evaluate the clinical utility of OCTA in RVO and other retinal vascular diseases.

A Comparison Between Optical Coherence Tomography Angiography and Fluorescein Angiography for the Imaging of Type 1 Neovascularization

PURPOSE To determine the sensitivity of the combination of optical coherence tomography angiography (OCTA) and structural optical coherence tomography (OCT) for detecting type 1 neovascularization (NV) and to determine significant factors that preclude visualization of type 1 NV using OCTA. METHODS Multicenter, retrospective cohort study of 115 eyes from 100 patients with type 1 NV. A retrospective review of fluorescein (FA), OCT, and OCTA imaging was performed on a consecutive series of eyes with type 1 NV from five institutions. Unmasked graders utilized FA and structural OCT data to determine the diagnosis of type 1 NV. Masked graders evaluated FA data alone, en face OCTA data alone and combined en face OCTA and structural OCT data to determine the presence of type 1 NV. Sensitivity analyses were performed using combined FA and OCT data as the reference standard. RESULTS A total of 105 eyes were diagnosed with type 1 NV using the reference. Of these, 90 (85.7%) could be detected using en face OCTA and structural OCT. The sensitivities of FA data alone and en face OCTA data alone for visualizing type 1 NV were the same (66.7%). Significant factors that precluded visualization of NV using en face OCTA included the height of pigment epithelial detachment, low signal strength, and treatment-naïve disease (P < 0.05, respectively). CONCLUSIONS En face OCTA and structural OCT showed better detection of type 1 NV than either FA alone or en face OCTA alone. Combining en face OCTA and structural OCT information may therefore be a useful way to noninvasively diagnose and monitor the treatment of type 1 NV.

RETINAL AND CHOROIDAL VASCULATURE IN BIRDSHOT CHORIORETINOPATHY ANALYZED USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Purpose: To describe retinal and choroidal vascular changes in eyes with birdshot chorioretinopathy using optical coherence tomography angiography. Methods: Patients underwent imaging using the AngioVue prototype software of the RTVue XR spectral domain optical coherence tomography device (Optovue, Inc) between September and December 2014. Two trained patients evaluated the optical coherence tomography angiography images for changes in the retinal and choroidal vasculature in the posterior pole. Results: Four of eight eyes (50%) had birdshot lesions in the posterior pole as demonstrated on fundus photography. All of these eyes demonstrated the areas of decreased choroidal blood flow below the disrupted retinal pigment epithelium. Larger choroidal vessels bordered the birdshot lesions. All eyes analyzed showed retinal thinning, telangiectatic vessels, and an increased intercapillary space. Capillary dilatations and loops were each seen in 7 of 8 eyes (88%). Conclusion: Optical coherence tomography angiography provides precise microvascular detail of the retinal vasculature and choriocapillaris that allows for the noninvasive visualization of the birdshot lesions and changes in the inner retina. The optical coherence tomography angiography images delineated widespread retinal vascular findings not previously described in the literature. In the future, optical coherence tomography angiography could be a useful tool to evaluate the natural history of birdshot chorioretinopathy, its progression, and the effect of treatment in these patients.

Vascularization of Irregular Retinal Pigment Epithelial Detachments in Chronic Central Serous Chorioretinopathy Evaluated With OCT Angiography

BACKGROUND AND OBJECTIVE To assess eyes with flat, irregular retinal pigment epithelial detachments (RPEDs) associated with central serous chorioretinopathy (CSCR) for choroidal neovascularization (CNV) using optical coherence tomography angiography (OCTA). MATERIALS AND METHODS Retrospective review of OCTA images of chronic CSCR eyes with irregular RPED (group 1) and regular RPED (controls, group 2) for presence of CNV, subretinal fluid, and intraretinal fluid. Fluorescein angiography was also evaluated for CNV. RESULTS CNV was detected using OCTA in 13 of 31 eyes (41.9%) in group 1 and in one of 18 eyes (5.6%) in group 2 (P = .007). Irregular RPED was a risk factor for CNV (odds ratio [OR] = 12.28; 95% CI, 1.45-104.3). There was no significant difference between detection by OCTA and FA (P = 1.0). Sensitivity and specificity of detection by OCTA were 85.7% and 95.7%, respectively. CONCLUSIONS Irregular RPEDs in chronic CSCR eyes may harbor neovascularization more often than previously thought, which has implications on therapy.