Retinal capillary perfusion heterogeneity in diabetic retinopathy detected by optical coherence tomography angiography.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness and involves retinal capillary damage, microaneurysms, and altered blood flow regulation. Optical coherence tomography angiography (OCTA) is a non-invasive way of visualizing retinal vasculature but has not been used extensively to study blood flow heterogeneity. The purpose of this study is to detect and quantify blood flow heterogeneity utilizing en-face swept source OCTA in patients with DR. METHODS: This is a prospective clinical study which examined patients with either type 1 or 2 diabetes mellitus. Each included eye was graded clinically as no DR, mild DR, or moderate-severe DR. Ten consecutive en face 6 × 6 mm foveal SS-OCTA images were obtained from each eye using a PLEX Elite 9000 (Zeiss Meditec, Dublin, CA). Built-in fixation-tracking, follow-up functions were utilized to reduce motion artifacts and ensure same location imaging in sequential frames. Images of the superficial and deep vascular complexes (SVC and DVC) were arranged in temporal stacks of 10 and registered to a reference frame for segmentation using a deep neural network. The vessel segmentation was then masked onto each stack to calculate the pixel intensity coefficient of variance (PICoV) and map the spatiotemporal perfusion heterogeneity of each stack. RESULTS: Twenty-nine eyes were included: 7 controls, 7 diabetics with no DR, 8 mild DR, and 7 moderate-severe DR. The PICoV correlated significantly and positively with DR severity. In patients with DR, the perfusion heterogeneity was higher in the temporal half of the macula, particularly in areas of capillary dropout. PICoV also correlates as expected with the established OCTA metrics of perfusion density and vessel density. CONCLUSION: PICoV is a novel way to analyze OCTA imaging and quantify perfusion heterogeneity. Retinal capillary perfusion heterogeneity in both the SVC and DVC increased with DR severity. This may be related to the loss of retinal capillary perfusion autoregulation in diabetic retinopathy.

Long-term assessment of internal limiting membrane peeling for full-thickness macular hole using en face adaptive optics and conventional optical coherence tomography.

OBJECTIVE: To evaluate the long-term structural and microvascular retinal effects of internal limiting membrane peeling for full-thickness macular hole (FTMH) using en face adaptive optics optical coherence tomography (AO-OCT), conventional OCT, and OCT angiography (OCTA). DESIGN: Interventional case series. PARTICIPANTS: Patients with FTMH treated with vitrectomy, internal limiting membrane peeling, and gas tamponade. METHODS: Eleven eyes with FTMH that had at least 12 months of postoperative follow-up were enrolled in the study. En face AO-OCT was used to image the superficial retina in the peeled and nonpeeled areas. En face structural OCT was performed to image the inner retinal dimples (IRDs), macular thickness, and retinal nerve fibre layer (RNFL). En face OCTA was used to examine the integrity of the peripapillary nerve fibre layer (NFL) plexus. RESULTS: AO-OCT showed RFNL wrapping around the IRDs, and no obvious peripapillary NFL plexus dropout was seen with OCTA. Scattered hyper-reflective dots were observed on the surface of the peeled retina in all patients imaged with AO-OCT. No significant differences were found in IRD number (91.5 ± 24.4 versus 77.2 ± 14.7; P = 2.07), IRD proportionate area (8.36 ± 3.34 versus 7.53 ± 2.60; P = 0.159), or macular thickness between the 6- and 12-month (or greater) postoperative visits. CONCLUSION: IRDs do not to progress beyond 6 months postoperatively, and no obvious damage to RFNL and peripapillary NFL plexus was detected. Hyper-reflective dots on the surface of the retina suggestive of possible Müller cell reactive gliosis were identified with AO-OCT.

Angiographic biomarkers are significant predictors of treatment response to intravitreal aflibercept in diabetic macular edema.

This prospective single-center study aims to identify biomarkers that predict improvement in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6 months, in 76 eyes with diabetic macular edema (DME) treated monthly with intravitreal aflibercept. At baseline, all patients underwent standardized imaging with color photography, optical coherence tomography (OCT), fluorescein angiography (FA) and OCT angiography (OCTA). Glycosylated hemoglobin, renal function, dyslipidemia, hypertension, cardiovascular disease and smoking were recorded. Retinal images were graded in a masked fashion. Baseline imaging, systemic and demographic variables were investigated to detect associations to BCVA and CRT change post aflibercept. Predictors of BCVA improvement included greater macular vessel density quantified using OCTA (p = 0.001) and low-density lipoprotein (LDL) ≥ 2.6 mmol/L (p = 0.017). Lower macular vessel density eyes showed a significant reduction in CRT but no BCVA improvement. Predictors of CRT reduction included peripheral non-perfusion seen on ultrawide-field FA (p = 0.005) and LDL ≥ 2.6 mmol/L (p < 0.001). Retinal angiographic biomarkers derived from OCTA and ultrawide-field FA may help predict functional and anatomic response to anti-vascular endothelial growth factor (VEGF) therapy in patients with DME. Elevated LDL is associated with treatment response in DME. These results may be used to better-select patients who will benefit from intravitreal aflibercept for treatment of DME.

ADAPTIVE OPTICS OPTICAL COHERENCE TOMOGRAPHY IN A CASE OF ACUTE ZONAL OCCULT OUTER RETINOPATHY.

PURPOSE: To report a case of acute zonal occult outer retinopathy in which adaptive optics (AO) facilitated visualization of abnormal photoreceptors previously thought to be in an area of normal retina on conventional optical coherence tomography (OCT). METHODS: Case report. RESULTS: A 51-year-old woman presents with 11-month history of photopsias and scotoma in the temporal visual field of her left eye. Ocular imaging including fluorescein angiography, fundus autofluorescence and OCT suggested the diagnosis of acute zonal occult outer retinopathy in the left eye. Adaptive optics optical coherence tomography (AO-OCT) revealed photoreceptor abnormalities not previously identified in conventional OCT, in areas apparently normal on multimodal imaging. On enface and cross-sectional AO-OCT, round and evenly spaced hyperreflectivity corresponding to normal cone mosaic (Pattern 1) was adjacent to unevenly and disrupted cone hyperreflectivity (Pattern 2) and areas with hyporeflectivity or no cone reflectivity (Pattern 3). Cross-sectional AO-OCT of Patterns 2 and 3 also revealed attenuation of ellipsoid zone with loss of interdigitation zone. CONCLUSION: Adaptive optics OCT documented cone photoreceptors in finer details than conventional OCT and revealed early changes in a patient with acute zonal occult outer retinopathy, in an area of the retina thought to be normal on conventional multimodal imaging. These findings may provide important insight into pathogenesis and progression of the disease.

Use of the Retinal Vascular Histology to Validate an Optical Coherence Tomography Angiography Technique.

Purpose: To determine the fidelity of optical coherence tomography angiography (OCTA) techniques by direct comparison of the retinal capillary network images obtained from the same region as imaged by OCTA and high-resolution confocal microscope. Method: Ten porcine eyes were perfused with red blood cells for OCTA image acquisition from the area centralis and then perfusion-fixed, and the vessels were labeled for confocal imaging. Two approaches involving post-processing of two-dimensional projection images and vessel tracking on three dimensional image stacks were used to obtain quantitative measurements. Data collected include vessel density, length of visible vessel track, count of visible branch points, vessel track depth, vessel diameter, angle of vessel descent, and angle of dive for comparison and analysis. Results: Comparing vascular images acquired from OCTA and confocal microscopy, we found (1) a good representation of the larger caliber retinal vessels, (2) an underrepresentation of retinal microvessels smaller than 10 µm and branch points in all four retinal vascular plexuses, particularly the intermediate capillary plexus, (3) reduced visibility associated with an increase in the angle of descent, (4) a tendency to loss visibility of vessel track at a branch point or during a sharp dive, and (5) a reduction in visibility with increase in retinal depth on OCTA images. Conclusions: Current OCTA techniques can visualize the retinal capillary network, but some types of capillaries cannot be detected by OCTA, particularly in the middle to deeper layers. Translational Relevance: The information indicates the limitation in clinical use and scopes for improvement in the current OCTA technologies.

Optimizing 3D retinal vasculature imaging in diabetic retinopathy using registration and averaging of OCT-A.

High resolution visualization of optical coherence tomography (OCT) and OCT angiography (OCT-A) data is required to fully take advantage of the imaging modality's three-dimensional nature. However, artifacts induced by patient motion often degrade OCT-A data quality. This is especially true for patients with deteriorated focal vision, such as those with diabetic retinopathy (DR). We propose a novel methodology for software-based OCT-A motion correction achieved through serial acquisition, volumetric registration, and averaging. Motion artifacts are removed via a multi-step 3D registration process, and visibility is significantly enhanced through volumetric averaging. We demonstrate that this method permits clear 3D visualization of retinal pathologies and their surrounding features, 3D visualization of inner retinal capillary connections, as well as reliable visualization of the choriocapillaris layer.

Sensorless adaptive-optics optical coherence tomographic angiography.

Optical coherence tomographic angiography (OCTA) can image the retinal blood flow but visualization of the capillary caliber is limited by the low lateral resolution. Adaptive optics (AO) can be used to compensate ocular aberrations when using high numerical aperture (NA), and thus improve image resolution. However, previously reported AO-OCTA instruments were large and complex, and have a small sub-millimeter field of view (FOV) that hinders the extraction of biomarkers with clinical relevance. In this manuscript, we developed a sensorless AO-OCTA prototype with an intermediate numerical aperture to produce depth-resolved angiograms with high resolution and signal-to-noise ratio over a 2 × 2 mm FOV, with a focal spot diameter of 6 µm, which is about 3 times finer than typical commercial OCT systems. We believe these parameters may represent a better tradeoff between resolution and FOV compared to large-NA AO systems, since the spot size matches better that of capillaries. The prototype corrects defocus, astigmatism, and coma using a figure of merit based on the mean reflectance projection of a slab defined with real-time segmentation of retinal layers. AO correction with the ability to optimize focusing in arbitrary retinal depths - particularly the plexuses in the inner retina - could be achieved in 1.35 seconds. The AO-OCTA images showed greater flow signal, signal-to-noise ratio, and finer capillary caliber compared to commercial OCTA. Projection artifacts were also reduced in the intermediate and deep capillary plexuses. The instrument reported here improves OCTA image quality without excessive sacrifice in FOV and device complexity, and thus may have potential for clinical translation.

Effective bidirectional scanning pattern for optical coherence tomography angiography.

We demonstrate the utility of a novel scanning method for optical coherence tomography angiography (OCTA). Although raster scanning is commonly used for OCTA imaging, a bidirectional approach would lessen the distortion caused by galvanometer-based scanners as sources continue to increase sweep rates. As shown, a unidirectional raster scan approach has a lower effective scanning time than bidirectional approaches; however, a strictly bidirectional approach causes contrast variation along the B-scan direction due to the non-uniform time interval between B-scans. Therefore, a stepped bidirectional approach is introduced and successfully applied to retinal imaging in normal controls and in a pathological subject with diabetic retinopathy.

Automated identification of cone photoreceptors in adaptive optics optical coherence tomography images using transfer learning.

Automated measurements of the human cone mosaic requires the identification of individual cone photoreceptors. The current gold standard, manual labeling, is a tedious process and can not be done in a clinically useful timeframe. As such, we present an automated algorithm for identifying cone photoreceptors in adaptive optics optical coherence tomography (AO-OCT) images. Our approach fine-tunes a pre-trained convolutional neural network originally trained on AO scanning laser ophthalmoscope (AO-SLO) images, to work on previously unseen data from a different imaging modality. On average, the automated method correctly identified 94% of manually labeled cones when compared to manual raters, from twenty different AO-OCT images acquired from five normal subjects. Voronoi analysis confirmed the general hexagonal-packing structure of the cone mosaic as well as the general cone density variability across portions of the retina. The consistency of our measurements demonstrates the high reliability and practical utility of having an automated solution to this problem.