PurposeTo achieve reproducible imaging of the choriocapillaris and associated flow voids using swept-source OCT angiography (SS-OCTA).MethodsSubjects were enrolled and SS-OCTA was performed using the 3 × 3 mm scan pattern. Blood flow was identified using the complex optical microangiography (OMAG) algorithm. The choriocapillaris was defined as a slab from the outer boundary of Bruch's membrane (BM) to approximately 20 μm below BM. Compensation for the shadowing effect caused by the RPE and BM complex on the choriocapillaris angiogram was achieved by using the structural information from the same slab. A thresholding method to calculate the percentage of flow voids from a region was developed based on a normal database.ResultsTwenty normal subjects and 12 subjects with drusen were enrolled. SS-OCTA identified the choriocapillaris in normal subjects as a lobular plexus of capillaries in the central macula and the lobular arrangement became more evident toward the periphery. In all eyes, signal compensation resulted in fewer choriocapillaris flow voids with improved repeatability of measurements. The best repeatability for the measurement was achieved by using 1 standard deviation (SD) for the thresholding strategy.ConclusionsSS-OCTA can image the choriocapillaris in vivo, and the repeatability of flow void measurements is high in the presence of drusen. The ability to image the choriocapillaris and associated flow voids should prove useful in understanding disease onset, progression, and response to therapies.

Quantitative assessment of the retinal microvasculature using optical coherence tomography angiography," J. Biomed. Opt. 21(6), 066008 (2016), doi: 10.1117/1.JBO.21.6.066008.

Patients with AD had less density of retinal microvascular networks than controls. Our findings suggest the presence of retinal microvascular dysfunction in AD.

Purpose To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). Design Prospective, double-masked, randomized clinical trial. Participants Patients with GA measuring from 1.25 to 18 mm2 based on spectral-domain optical coherence tomography imaging. Methods Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and lowluminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores. Main Outcome Measures Change in area of GA at 26 weeks. Results Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55±0.94 and 2.02±0.74 mm in the eculizumab and placebo groups,respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19±0.12 and 0.18±0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37±0.22 mm in the eculizumab-treated eyes and by a mean of 0.37±0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified. Conclusions Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly. However, there was a statistically significant correlation between the lowluminance deficit at baseline and the progression of GA over 6 months.Ophthalmology 2014;121:693-701 © 2014 by the American Academy of Ophthalmology.

Purpose-To determine the area and enlargement rate (ER) of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) using the spectral-domain optical coherence tomography (SDOCT) fundus image. Design-Prospective longitudinal natural history studyParticipants-Eighty-six eyes of 64 patients with at least 6 months follow-up.Methods-Patients with GA secondary to AMD were enrolled in this study. Macular scans were performed using the Cirrus SDOCT (Carl Zeiss Meditec, Dublin CA). The areas of GA identified on the SDOCT fundus images were quantified using a digitizing tablet. Reproducibility of these measurements was assessed and the ER of GA was calculated. The usefulness of performing square root transformations of the lesion area measurements was explored.Main Outcome Measure-Enlargement rate of GA Results-At baseline, 27% of eyes had a single area of GA. The mean total area at baseline was 4.59mm 2 (1.8 disc areas (DA)). The mean follow up time was 1.24 years. Reproducibility, as assessed with the intraclass correlation coefficient (ICC), was excellent on both the original area scale (ICC = 0.995) and the square-root scale (ICC=0.996). Inter-grader differences were not an important source of variability in lesion size measurement (ICC=0.999, 0.997). On average, the ER of GA per year was 1.2 mm 2 (0.47 DA; range [0.01 -3.61 mm 2 /year]. The ER correlated with the initial area of GA (r=0.45, p<0.001), but there were variable growth rates for any given baseline area. When the square root transformation of the lesion area measurements was used as a measure of lesion size, the enlargement rate (0.28 mm/yr) was not correlated with baseline size Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptOphthalmology. Author manuscript; available in PMC 2012 April 1. r=-0.09,p=0.40). In this cohort of lesions, no correlation was found between ER and length of follow-up. Square root transformation of the data helped facilitate sample size estimates for controlled clinical trials involving GA.Conclusions-The SDOCT fundus image can be used to visualize and quantify GA. Advantages of this approach include the convenience and assurance of using a single imaging technique that permits simultaneous visualization of GA along with the loss of photoreceptors and the retinal pigment epithelium which should correlate with the loss of visual function.

Objective To correlate images from swept source optical coherence tomography microangiography (SS-OMAG) with images from fluorescein angiography (FA) and indocyanine green angiography (ICGA) performed on asymptomatic eyes with intermediate age-related macular degeneration. Study Design and Methods A retrospective, observational, consecutive case series of patients with asymptomatic, intermediate AMD in one eye and neovascular AMD in their fellow eye. The patients underwent SS-OMAG, FA, and ICGA, and the images obtained from these three angiographic techniques were compared. Results Three patients were identified with intermediate AMD in one eye and symptomatic, neovascular AMD in their fellow eye. The three asymptomatic eyes had drusen and pigmentary abnormalities in the central macula and no evidence of macular fluid on OCT imaging. One patient presented with minimal leakage on FA from the asymptomatic eye. ICGA revealed the presence of central macular plaques, and SS-OMAG revealed type 1 neovascularization corresponding to the plaques. The type 1 neovascularization was visualized using en face slabs that extended from the border of the outer retina to the choriocapillaris (CC), 8 μm beneath Bruch’s membrane. Conclusions SS-OMAG identified type 1 neovascularization within ICGA plaques. The ability of OCTA to provide non-invasive, fast, detailed, depth-resolved identification of non-exudative neovascular lesions in eyes with intermediate AMD suggests the need for new terminology that distinguishes between non-exudative intermediate AMD and non-exudative, neovascular intermediate AMD. This distinction should prove useful for managing AMD patients at risk for conversion to late, exudative AMD once natural history studies are performed to better understand disease progression.

Purpose To investigate the changes of the retinal microvascular network and microcirculation in high myopia. Design A cross-sectional, matched, comparative clinical study. Participants Twenty eyes of twenty subjects with non-pathological high myopia (28 ± 5 Years) with a refractive error of −6.31 ± 1.23 Diopters (mean ± standard deviation) and twenty eyes of twenty age- and gender-matched control subjects (30 ± 6 years) with a refractive error of −1.40 ± 1.00 Diopters were recruited. Methods Optical coherence tomography angiography (OCTA) was used to image the retinal microvascular network, which was later quantified by fractal analysis (box counting, Dbox, representing vessel density) in both superficial and deep vascular plexuses. The retinal function imager (RFI) was used to image the retinal microvessel blood flow velocity (BFV). The BFV and microvascular density in the myopia group were corrected for ocular magnification using Bennett’s formula. Results The density of both superficial and deep microvascular plexuses was significantly decreased in the myopia group in comparison to the controls (P < 0.05). The decrease of the microvessel density of the annular zone (0.6 – 2.5 mm), measured as Dbox, was 2.1% and 2.9% in superficial and deep vascular plexuses, respectively. The microvessel density reached a plateau from 0.5 mm to 1.25 mm from the fovea in both groups, but that in myopic group was about 3% lower than the control group. No significant differences were detected between the groups in retinal microvascular BFV in either arterioles or venules (P > 0.05). Microvascular densities in both superficial (r = −0.45, P = 0.047) and deep (r = −0.54, P = 0.01) vascular plexuses were negatively correlated with the axial lengths in the myopic eye. No correlations were observed between BFV and vessel density (P > 0.05). Conclusions Retinal microvascular decrease was observed in the high myopia subjects, whereas the retinal microvessel BFV remained unchanged. The retinal microvascular network alteration may be attributed to ocular elongation that occurs with the progression of myopia. The novel quantitative analyses of the retinal microvasculature may help to characterize the underlying pathophysiology of myopia and enable early detection and prevention of myopic retinopathy.

ZEISS Angioplex™ optical coherence tomography (OCT) angiography generates high-resolution three-dimensional maps of the retinal and choroidal microvasculature while retaining all of the capabilities of the existing CIRRUS™ HD-OCT Model 5000 instrument. Angioplex™ OCT angiographic imaging on the CIRRUS™ HD-OCT platform was made possible by increasing the scanning rate to 68,000 A-scans per second and introducing improved tracking software known as FastTrac™ retinal-tracking technology. The generation of en face microvascular flow images with Angioplex™ OCT uses an algorithm known as OCT microangiography-complex, which incorporates differences in both the phase and intensity information contained within sequential B-scans performed at the same position. Current scanning patterns for en face angiographic visualization include a 3 × 3 and a 6 × 6 mm scan pattern on the retina. A volumetric dataset showing erythrocyte flow information can then be displayed as a color-coded retinal depth map in which the microvasculature of the superficial, deep, and avascular layers of the retina are displayed together with the colors red, representing the superficial microvasculature; green, representing the deep retinal vasculature; and blue, representing any vessels present in the normally avascular outer retina. Each retinal layer can be viewed separately, and the microvascular layers representing the choriocapillaris and the remaining choroid can be viewed separately as well. In addition, readjusting the contours of the slabs to target different layers of interest can generate custom en face flow images. Moreover, each en face flow image is accompanied by an en face intensity image to help with the interpretation of the flow results. Current clinical experience with this technology would suggest that OCT angiography should replace fluorescein angiography for retinovascular diseases involving any area of the retina that can be currently scanned with the CIRRUS™ HD-OCT instrument and may replace fluorescein angiography and indocyanine green angiography for some choroidal vascular diseases.