Torcato Santos

Quantification of Retinal Microvascular Density in Optical Coherence Tomographic Angiography Images in Diabetic Retinopathy

Importance Quantitative measurements based on optical coherence tomographic angiography (OCTA) may have value in managing diabetic retinopathy (DR), but there is limited information on the ability of OCTA to distinguish eyes with DR. Objective To evaluate the ability of measurements of retinal microvasculature using OCTA to distinguish healthy eyes from eyes with DR. Design, Setting, and Participants In this prospective cross-sectional study, OCTA was used to examine the eyes of participants with type 2 diabetes with or without DR and the eyes of participants without diabetes from September 17, 2015, to April 6, 2016. Density maps based on superficial retinal layer (SRL) and deeper retinal layer (DRL) images were generated after a method to remove decorrelation tails was applied to the DRL images. Exposures Both eyes of each participant were examined by means of a 3-mm OCTA scan and 7-field fundus photography using the Diabetic Retinopathy Severity Scale. Main Outcomes and Measures Two measures were examined: perfusion density, based on the area of vessels, and vessel density, based on a map with vessels of 1-pixel width. The size of the foveal avascular zone was also calculated automatically, and so was the area under the receiver operating characteristic curve. Results A total of 50 eyes from 26 participants with diabetes (10 women and 16 men; mean [SD] age, 64.9 [7.5] years) and 50 healthy eyes from 25 participants without diabetes (14 women and 11 men; mean [SD] age, 64.0 [7.1] years) were imaged. All participants were white. Vessel density measured in the SRL had the highest area under the receiver operating characteristic curve (0.893 [95% CI, 0.827-0.959]), compared with perfusion density in the SRL (0.794 [95% CI, 0.707-0.881]), foveal avascular zone area (0.472 [95% CI, 0.356-0.588]), and vessel density in the DRL (0.703 [95% CI, 0.601-0.805]). Vessel density in the SRL negatively correlated with best-corrected visual acuity (r = –0.28; P = .05) and severity of DR (r = –0.46; P = .001). Density metrics correlated with age. No correlation was detected between vascular density or foveal avascular zone metrics and hemoglobin A1C or duration of diabetes. Conclusions and Relevance Vessel density measured by OCTA provides a quantitative metric of capillary closure that correlates with severity of DR and may allow staging, diagnosis, and monitoring that do not require subjective evaluation of fundus images.

Retinal Layer Location of Increased Retinal Thickness in Eyes with Subclinical and Clinical Macular Edema in Diabetes Type 2

Purpose: To identify the retinal layer predominantly affected in eyes with subclinical and clinical macular edema in diabetes type 2. Methods: A cohort of 194 type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20/35) were examined with Cirrus spectral-domain optical coherence tomography (OCT) at the baseline visit (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers of the eyes with subclinical and clinical macular edema was compared with a sample of 31 eyes from diabetic patients with normal OCT and an age-matched control group of 58 healthy eyes. Results: From the 194 eyes in the study, 62 had subclinical macular edema and 12 had clinical macular edema. The highest increases in retinal thickness (RT) were found in the inner nuclear layer (INL; 33.6% in subclinical macular edema and 81.8% in clinical macular edema). Increases were also found in the neighboring layers. Thinning of the retina was registered in the retinal nerve fiber, ganglion cells and inner plexiform layers in the diabetic eyes without macular edema. Conclusions: The increase in RT occurring in diabetic eyes with macular edema is predominantly located in the INL but extends to neighboring retinal layers indicating that it may be due to extracellular fluid accumulation.

Noninvasive Evaluation of Retinal Leakage Using Optical Coherence Tomography

Purpose: To demonstrate the association between changes in the blood-retinal barrier (BRB) identified by fluorescein leakage and those in the optical properties of the human retina determined by optical coherence tomography (OCT) and show how these changes can be quantified and their location identified within the retina. Methods: Two imaging techniques were applied: the retinal leakage analyzer, to map BRB function into intact or disrupted regions, and OCT, to measure refractive index changes along the light path within the human ocular fundus. Results: A total of 140 comparisons were made, 77 between areas of regions receiving the same classification (intact or disrupted BRB) and 63 between areas of regions receiving distinct classifications, from 4 pathological cases: 2 eyes with nonproliferative diabetic retinopathy and 2 eyes with wet age-related macular degeneration. In all cases, the distribution of OCT data between regions of intact and regions of disrupted BRB, identified by the retinal leakage analyzer, was quantified and was statistically significantly different (p < 0.001). In addition, it was found that the differences could be localized in the retina to specific structural sequences. Conclusions: Using a novel method to analyze OCT data, we showed that it may be possible to quantify differences in the extracellular compartment in eyes with retinal disease and alterations of the BRB. Based on quantitative techniques, our findings demonstrate the presence of indirect information on the BRB status within noninvasive OCT data.

Comparison of diabetic retinopathy classification using fluorescein angiography and optical coherence tomography angiography

Purpose To analyse and compare the classification of eyes with diabetic retinopathy using fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) performed either with AngioPlex or AngioVue. Methods This was an observational cross-sectional study of 50 eyes from 26 diabetic subjects. Two independent graders classified the FA angiograms, to assess the presence and severity of several characteristics according to the ETDRS Report 11, and a similar evaluation was performed for each 3×3 mm OCTA image from the superficial retinal layer and for the full retina slab. Results Percentages of non-gradable images for the outline of foveal avascular zone (FAZ) in the central subfield (CSF) were 29.0% for FA, 12.0% for AngioVue and 3.0% for AngioPlex. For capillary loss, percentages of non-gradable images in the CSF were 25.0% for FA, 11% for AngioVue and 0.0% for AngioPlex. For the inner ring (IR), percentages of non-gradable images were 12.5% for FA, 11.5% for AngioVue and 0.5% for AngioPlex. Agreement between graders was substantial for outline of FAZ. For capillary loss, the agreement was fair for the CSF, and moderate for the IR. Conclusions The OCTA allows better discrimination of the CSF and parafoveal macular microvasculature than FA, especially for FAZ disruption and capillary dropout, without the need of an intravenous injection of fluorescein. In addition, FA had also a higher number of non-gradable images. The OCTA can replace with advantage the FA, as a non-invasive and more sensitive procedure for detailed morphological evaluation of central macular vascular changes. Trial registration number NCT02391558, Pre-results.

Increased-Resolution OCT Thickness Mapping of the Human Macula: A Statistically Based Registration

PURPOSE To describe the development of a technique that enhances spatial resolution of retinal thickness maps of the Stratus OCT (Carl Zeiss Meditec, Inc., Dublin, CA). A retinal thickness atlas (RT-atlas) template was calculated, and a macular coordinate system was established, to pursue this objective. METHODS The RT-atlas was developed from principal component analysis of retinal thickness analyzer (RTA) maps acquired from healthy volunteers. The Stratus OCT radial thickness measurements were registered on the RT-atlas, from which an improved macular thickness map was calculated. Thereafter, Stratus OCT circular scans were registered on the previously calculated map to enhance spatial resolution. RESULTS The developed technique was applied to Stratus OCT thickness data from healthy volunteers and from patients with diabetic retinopathy (DR) or age-related macular degeneration (AMD). Results showed that for normal, or close to normal, macular thickness maps from healthy volunteers and patients with DR, this technique can be an important aid in determining retinal thickness. Efforts are under way to improve the registration of retinal thickness data in patients with AMD. CONCLUSIONS The developed technique enhances the evaluation of data acquired by the Stratus OCT, helping the detection of early retinal thickness abnormalities. Moreover, a normative database of retinal thickness measurements gained from this technique, as referenced to the macular coordinate system, can be created without errors induced by missed fixation and eye tilt.

OCT-Leakage: A New Method to Identify and Locate Abnormal Fluid Accumulation in Diabetic Retinal Edema

Purpose To identify retinal extracellular fluid changes and their correlation with increased retinal thickness (RT) in eyes with subclinical and clinical macular edema in diabetes type 2. Methods A cohort of 48 eyes from 48 type 2 diabetic patients with mild or moderate nonproliferative diabetic retinopathy (Early Treatment Diabetic Retinopathy Study levels 20/35) were classified as having normal RT (10), subclinical macular edema (30), or clinical macular edema (8). They were examined with Cirrus spectral-domain optical coherence tomography (OCT) at baseline visits (ClinicalTrials.gov number, NCT01145599) in the Coimbra center. Results from automated analysis of the retinal extracellular space, using our OCT-Leakage algorithm to identify sites of low optical reflectivity, were compared with those from a control group of 25 healthy eyes. Results The highest increases in RT in the eyes with subclinical and clinical macular edema were found in the inner nuclear layer (INL). These increases were, on average, 49.9% in subclinical macular edema and 104.7% in clinical macular edema. Extracellular space increases in the INL that were identified with the OCT-Leakage algorithm showed a strong positive correlation with the increases in RT in the central subfield (r = 0.71, P < 0.001). Conclusions Increases in number of sites with lower optical reflectivity positively correlate with the increase in RT in the initial stages of macular edema in diabetes type 2. Diabetic macular edema is represented mainly by extracellular fluid accumulation that preferentially involves the INL of the retina.

Evaluation of Blood-Retinal Barrier Function from Fourier Domain High-Definition Optical Coherence Tomography

The aim of the work presented in this paper is to demonstrate the possibility of using a non-invasive imaging technique, the high-definition optical coherence tomography, as a surrogate detector of blood-retinal barrier breakdown. The retinal leakage analyzer is currently the only available technique to map the blood-retinal barrier function, a structure affected by diabetes, one of the most frequent cases in clinical practice.Nevertheless, it requires dedicated instrumentation and skilled personnel and is used only in the clinical research environment. Recently launched optical coherence devices, of the spectral or Fourier domain type, are able to scan the human retina at high rates and with high depth resolution providing users with unprecedented detailed retinal structure images. Besides this structural information, in this work we demonstrate that information on blood-retinal barrier function is also present, opening the perspective of using these non-invasive high-definition imaging devices to access it.

Synthetic OCT data for image processing performance testing

The use of synthetic images is needed for testing the performance of image processing methods in order to establish a ground truth to test performance metrics. However, these synthetic images do not represent real applications. The aim of this paper is to build a mathematical model to obtain a synthetic noise-free image mimicking a real Optical Coherence Tomography (OCT) B-scan or volume from the human retina, in order to establish a ground truth for filtering performance metrics in this context. Moreover we also suggest a method to add speckle noise to this image based on the speckle noise of the given OCT volume. In this way we establish a repli-cable method to obtain a ground truth for image processing performance metrics that actually mimics a real case.

One-Year Progression of Diabetic Subclinical Macular Edema in Eyes with Mild Nonproliferative Diabetic Retinopathy: Location of the Increase in Retinal Thickness

Purpose: To characterize the 1-year progression of retinal thickness (RT) increase occurring in eyes with subclinical macular edema in type 2 diabetes. Methods: Forty-eight type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (NPDR; levels 20 and 35 in the Early Treatment Diabetic Retinopathy Study) classified as presenting subclinical macular edema at baseline completed the 1-year follow-up period, from a sample of 194 followed in a 12-month observational and prospective study (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers in these eyes was performed, followed by verification and correction by a human grader. Results: The highest increase in RT over the 1-year follow-up period for the 48 eyes/patients with subclinical macular edema was found in the inner nuclear layer (INL). Progression to clinical macular edema was also associated with increased thickening of other retinal layers aside from the INL. The microvascular disease activity shown by microaneurysm (MA) turnover ≥6 was associated with progression from subclinical to clinical macular edema. Conclusions: Increases in RT occurring over a period of 1 year in diabetic eyes with mild NPDR and subclinical macular edema occur mainly in the INL. The development of clinical macular edema appears to be associated with increased thickening of other retinal layers and microvascular disease activity.

Optical coherence tomography: automatic retina classification through support vector machines

Optical coherence tomography (OCT) is becoming one of the most important imaging modalities in ophthalmology due to its non-invasiveness and by allowing the visualisation the human retina structure in detail. It was recently proposed that OCT data embeds functional information from the human retina. Specifically, it was proposed that blood–retinal barrier status information is present within OCT data from the human retina. Besides this ability, the authors present data supporting the idea of having the OCT data encoding the ageing of the retina in addition to the disease (diabetes) condition from the healthy status. The methodology followed makes use of a supervised classification procedure, the support vector machine (SVM) classifier – based solely on the statistics of the distribution of OCT data from the human retina (i.e. OCT data between the inner limiting membrane and the retinal pigment epithelium). Results achieved suggest that information on both the healthy status of the blood–retinal barrier and on the ageing process co-exist encoded within the optical properties of the human retina.