Repeatability and Reproducibility of Photoreceptor Density Measurement in the Macula Using the Spectralis High Magnification Module.

PURPOSE: To evaluate the repeatability and reproducibility of photoreceptor density assessment with manual cell counting in healthy participants imaged with the Heidelberg Spectralis High Magnification Module (HMM). DESIGN: Precision study, evaluation of diagnostic test or technology. PARTICIPANTS: Eleven eyes of 8 participants. METHODS: Images were acquired using the Spectralis HMM by a single operator during 2 separate imaging sessions. The 3 highest-quality images of each eye from each session were selected for analysis and coregistered. For a subset of participants, a second operator acquired images in 1 session, and images with the best quality were selected for analysis. Photoreceptor densities were obtained by manual counts in squares of 0.0625 mm2 located in the parafovea. Repeatability (intragrader and intrasession) and reproducibility (interoperator, intergrader, and intersession) were assessed by calculating the intraclass correlation coefficient (ICC) from linear mixed effects models. Bland-Altman plots, coefficients of repeatability, and Pearson correlation results were reported. MAIN OUTCOME MEASURES: Intragrader, intrasession, intersession, interoperator, and intergrader ICC estimates and their 95% confidence intervals for photoreceptor density measurements in the parafovea. RESULTS: Twenty-four eyes of 13 healthy participants were imaged initially. Of these, 11 eyes (45.83%) of 8 participants that had at least 3 acceptable images in each session were included in this study. Mean parafoveal photoreceptor density was 14 988 cells/mm2 (standard deviation, 1403.15 cells/mm2). Intragrader ICC was 0.84 (95% confidence interval, 0.57-0.95), intrasession ICC was 0.69 (95% confidence interval, 0.17-0.86), intersession ICC was 0.88 (95% confidence interval, 0.53-0.96), interoperator ICC was 0.70 (95% confidence interval, 0-0.95), and intergrader ICC was 0.22 (95% confidence interval, 0-0.71). CONCLUSIONS: Images obtained with the HMM allow for photoreceptor mosaic visualization in the macular area, mainly in the parafovea. Although densities obtained are in accordance with other reported methods in the literature, variability within and between images of the apparent cell mosaic were observed, and this study did not demonstrate high repeatability or reproducibility for quantitative assessments using the manual counting method.

Optical coherence tomography angiography artifacts in retinal pigment epithelial detachment.

OBJECTIVE: To describe optical coherence tomography angiography (OCTA) reflectance artifacts secondary to retinal pigment epithelial detachment (RPED). DESIGN: Retrospective review. METHODS: Four eyes from 4 subjects were included. Three presented with RPED and 1 eye was a normal control. Two eyes diagnosed with RPED and the normal eye were evaluated using en face OCTA centred at the fovea acquired using the RTVue XR Avanti (Optovue Inc). In the third eye with RPED, OCTA imaging was performed using a CIRRUS 5000 prototype modified to do OCTA imaging on a spectral domain OCT platform provided by Carl Zeiss Meditec, Inc. The segmented OCTA angiograms were overlaid to determine if the flow patterns seen at the edge of the RPEDs were due to reflectance from the inner retinal vessels, also known as "decorrelation tails." RESULTS: OCTA projection artifacts were noted when segmentation lines intersected with the boundary of the RPED. The overlaid segmented OCTA from the 3 RPED eyes imaged using each system revealed the same vasculature pattern at the edges of the RPED as that of the inner retina, demonstrating the "decorrelation tails" artifact, which caused the RPED to appear as a bright ring on the segmented OCTA. CONCLUSIONS: OCTA images are susceptible to various known artifacts. This series describes the impact of the projection artifact seen at the edges of an RPED that simulates appearance of flow but is actually due to reflectance of the inner retinal vasculature on the RPED.

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.

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.

Choroidal Neovascularization Analyzed on Ultrahigh-Speed Swept-Source Optical Coherence Tomography Angiography Compared to Spectral-Domain Optical Coherence Tomography Angiography.

PURPOSE: To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) using an ultrahigh-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype vs a spectral-domain (SD) OCTA device. DESIGN: Comparative analysis of diagnostic instruments. METHODS: Patients were prospectively recruited to be imaged on SD OCT and SS OCT devices on the same day. The SD OCT device employed is the RTVue Avanti (Optovue, Inc, Fremont, California, USA), which operates at ∼840 nm wavelength and 70 000 A-scans/second. The SS OCT device used is an ultrahigh-speed long-wavelength prototype that operates at ∼1050 nm wavelength and 400 000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the 2 devices. The nonparametric Wilcoxon signed rank test was used to compare area measurements and P values of <.05 were considered statistically significant. RESULTS: Fourteen eyes from 13 patients were enrolled. The CNV in 11 eyes (78.6%) were classified as type 1, 2 eyes (14.3%) as type 2, and 1 eye (7.1%) as mixed type. Total CNV area measured using SS OCT and SD OCT 3 mm × 3 mm OCTA were 0.949 ± 1.168 mm(2) and 0.340 ± 0.301 mm(2), respectively (P = .001). For the 6 mm × 6 mm OCTA the total CNV area using SS OCT and SD OCT were 1.218 ± 1.284 mm(2) and 0.604 ± 0.597 mm(2), respectively (P = .0019). The field of view did not significantly affect the measured CNV area (P = .19 and P = .18 for SS OCT and SD OCT, respectively). CONCLUSION: SS OCTA yielded significantly larger CNV areas than SD OCTA. It is possible that SS OCTA is better able to demarcate the full extent of CNV vasculature.

DETECTION OF MICROVASCULAR CHANGES IN EYES OF PATIENTS WITH DIABETES BUT NOT CLINICAL DIABETIC RETINOPATHY USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To evaluate the ability of optical coherence tomography angiography to detect early microvascular changes in eyes of diabetic individuals without clinical retinopathy. METHODS: Prospective observational study of 61 eyes of 39 patients with diabetes mellitus and 28 control eyes of 22 age-matched healthy subjects that received imaging using optical coherence tomography angiography between August 2014 and March 2015. Eyes with concomitant retinal, optic nerve, and vitreoretinal interface diseases and/or poor-quality images were excluded. Foveal avascular zone size and irregularity, vessel beading and tortuosity, capillary nonperfusion, and microaneurysm were evaluated. RESULTS: Foveal avascular zone size measured 0.348 mm² (0.1085-0.671) in diabetic eyes and 0.288 mm² (0.07-0.434) in control eyes (P = 0.04). Foveal avascular zone remodeling was seen more often in diabetic than control eyes (36% and 11%, respectively; P = 0.01). Capillary nonperfusion was noted in 21% of diabetic eyes and 4% of control eyes (P = 0.03). Microaneurysms and venous beading were noted in less than 10% of both diabetic and control eyes. Both diabetic and healthy control eyes demonstrated tortuous vessels in 21% and 25% of eyes, respectively. CONCLUSION: Optical coherence tomography angiography was able to image foveal microvascular changes that were not detected by clinical examination in diabetic eyes. Changes to the foveal avascular zone and capillary nonperfusion were more prevalent in diabetic eyes, whereas vessel tortuosity was observed with a similar frequency in normal and diabetic eyes. Optical coherence tomography angiography may be able to detect diabetic eyes at risk of developing retinopathy and to screen for diabetes quickly and noninvasively before the systemic diagnosis is made.

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.