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Deep Retinal Capillary Nonperfusion Is Associated With Photoreceptor Disruption in Diabetic Macular Ischemia.

ABSTRACT: PURPOSE:To report outer retinal structural changes associated with macular capillary nonperfusion at the level of deep capillary plexus (DCP) in diabetic patients. DESIGN:Prospective observational cross-sectional study. METHODS:The study included 14 eyes of 10 patients who were diagnosed as having diabetic retinopathy. To study the outer retina and localize areas of capillary nonperfusion at the superficial (SCP) or DCP, we used the spectral-domain optical coherence tomography (SDOCT) device (RTVue-XR Avanti; Optovue Inc, Fremont, California, USA) with split-spectrum amplitude-decorrelation angiography (SSADA) software for optical coherence tomography angiography (OCTA). Two independent masked graders (F.S. and A.A.F.) qualitatively evaluated SDOCT scans as either normal or having outer retina disruption. The angiographic images were examined to define the presence and location of capillary nonperfusion. RESULTS:Eight eyes showed outer retinal disruption on SDOCT that co-localized to areas of enlarged foveal avascular zone, areas of no flow between capillaries, and capillary nonperfusion of the DCP. Six eyes without outer retinal changes on SDOCT showed robust perfusion of the DCP. CONCLUSIONS:Using OCTA, this study shows that macular photoreceptor disruption on SDOCT in patients with diabetic retinopathy corresponds to areas of capillary nonperfusion at the level of the DCP. This is important in highlighting the contribution of the DCP to the oxygen requirements of the photoreceptors as well as the outer retina in diabetic macular ischemia.

SUBMITTER: Scarinci F

PROVIDER: S-EPMC4969199 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Deep Retinal Capillary Nonperfusion Is Associated With Photoreceptor Disruption in Diabetic Macular Ischemia.

Scarinci Fabio F Nesper Peter L PL Fawzi Amani A AA

American journal of ophthalmology 20160510

<h4>Purpose</h4>To report outer retinal structural changes associated with macular capillary nonperfusion at the level of deep capillary plexus (DCP) in diabetic patients.<h4>Design</h4>Prospective observational cross-sectional study.<h4>Methods</h4>The study included 14 eyes of 10 patients who were diagnosed as having diabetic retinopathy. To study the outer retina and localize areas of capillary nonperfusion at the superficial (SCP) or DCP, we used the spectral-domain optical coherence tomogra ...[more]

PMID: 27173374

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Project description:PurposeTo study longitudinal changes in retinal capillary circulation in eyes treated with iodine 125 (I125) plaque brachytherapy for uveal melanoma using OCT angiography (OCTA).DesignLongitudinal prospective study of 21 patients undergoing treatment for uveal melanoma with I125 plaque brachytherapy. Eyes with melanoma were imaged with OCTA before treatment and at 12-month intervals until 2 years after brachytherapy.ParticipantsAfter institutional review board approval, participants were enrolled prospectively from an academic ocular oncology clinic.MethodsPeripapillary (4.5 × 4.5-mm) and macular (3 × 3-mm) OCTA scans were acquired with AngioVue (Optovue, Inc, Fremont, CA).Main outcome measuresThe peripapillary nerve fiber layer plexus capillary density (NFLP_CD), macular superficial vascular complex vessel density (mSVC_VD), and foveal avascular zone (FAZ) area were calculated.ResultsBefore treatment, no significant difference was found in the NFLP_CD, mSVC_VD, or FAZ area between eyes with melanoma and normal fellow eyes. By 24 months, 11 eyes had developed clinical signs of radiation retinopathy, radiation optic neuropathy, or both. In treated eyes, the NFLP_CD (48.4±4.1%) was reduced at 12 months (46.7±5.0%; P = 0.04, Wilcoxon signed-rank test) and 24 months (44.5±6.1%; P < 0.001). Similarly, the mSVC_VD (48.4 2±3.6%) was reduced in treated eyes at 12 months (43.5±5.9%; P = 0.01) and 24 months (37.4±9.1%; P < 0.001). The FAZ area (0.26±0.11 mm2) increased in treated eyes at 12 months (0.35±0.22 mm2; P = 0.009) and 24 months (0.81±1.03 mm2; P = 0.001). When only eyes with clinically evident radiation changes were evaluated, the changes in NFLP_CD, mSVC_VD, and FAZ area were more pronounced. OCT angiography measurements correlated with both radiation dose and visual acuity. The mSVC_VD measured at 12 months was found to predict the development of clinically apparent radiation retinopathy within 1 year.ConclusionsOCT angiography demonstrated early emergence of peripapillary and macular capillary vasculature changes after I125 plaque brachytherapy. OCT angiography provided a quantitative measurement of retinal capillary changes associated with ischemia that correlated with visual acuity and radiation dose and may predict future development of radiation-induced retinal toxicity.

Project description:ImportanceMacular ischemia is a key feature of diabetic retinopathy (DR). Quantification of macular ischemia has potential as a biomarker for DR.ObjectiveTo assess the feasibility of automated quantification of capillary nonperfusion as a potential sign of macular ischemia using optical coherence tomography (OCT) angiography.Design, setting, and participantsAn observational study conducted in a tertiary, subspecialty, academic practice evaluated macular nonperfusion with 6 × 6-mm OCT angiography obtained with commercially available 70-kHz OCT and fluorescein angiography (FA). The study was conducted from January 22 to September 18, 2014. Data analysis was performed from October 1, 2014, to April 7, 2015. Participants included 12 individuals with normal vision serving as controls and 12 patients with various levels of DR.Main outcomes and measuresPreplanned primary measures were parafoveal and perifoveal vessel density, total avascular area, and foveal avascular zone as detected with 6 × 6-mm OCT angiography and analyzed using an automated algorithm. Secondary measures included the agreement of the avascular area between the OCT angiogram and FA.ResultsCompared with the 12 healthy controls (11 women; mean [SD] age, 54.2 [14.2] years), the 12 participants with DR (4 women; mean [SD] age, 55.1 [12.1] years) had reduced parafoveal and perifoveal vessel density by 12.6% (95% CI, 7.7%-17.5%; P < .001) and 10.4% (95% CI, 6.8%-14.1%; P < .001), respectively. Total avascular area and foveal avascular zone area were greater in eyes with DR by 0.82 mm2 (95% CI, 0.65-0.99 mm2; P = .02) and 0.16 mm2 (95% CI, 0.05-0.28 mm2; P < .001). The agreement between the vascular areas in the OCT angiogram and FA had a κ value of 0.45 (95% CI, 0.21-0.70; P < .001). Total avascular area in the central 5.5-mm-diameter area distinguished eyes with DR from control eyes with 100% sensitivity and specificity.Conclusions and relevanceAvascular area analysis with an automated algorithm using OCT angiography, although not equivalent to FA, detected DR reliably in this small pilot study. Further study is necessary to determine the usefulness of the automated quantification in clinical practice.

Project description:PurposeTo examine whether deep-learning denoised optical coherence tomography angiography (OCTA) images could enhance automated macular ischemia quantification in branch retinal vein occlusion (BRVO).MethodsThis retrospective, single-center, cross-sectional study enrolled 74 patients with BRVO and 46 age-matched healthy subjects. The severity of macular ischemia was graded as mild, moderate, or severe. Denoised OCTA images were produced using a neural network model. Quantitative parameters derived from denoised images, including vessel density and nonperfusion area, were compared with those derived from the OCTA machine. The main outcome measures were correlations between quantitative parameters, and areas under receiver operating characteristic curves (AUCs) in classifying the severity of the macular ischemia.ResultsThe vessel density and nonperfusion area from denoised images were correlated strongly with the corresponding parameters from machine-derived images in control eyes and BRVO eyes with mild or moderate macular ischemia (all P < 0.001). However, no such correlation was found in eyes with severe macular ischemia. The vessel density and nonperfusion area from denoised images had significantly larger area under receiver operating characteristic curve than those derived from the original images in classifying moderate versus severe macular ischemia (0.927 vs 0.802 [P = 0.042] and 0.946 vs 0.797, [P = 0.022], respectively). There were no significant differences in the areas under receiver operating characteristic curve between the denoised images and the machine-derived parameters in classifying control versus BRVO, and mild versus moderate macular ischemia.ConclusionsA neural network model is useful for removing speckle noise on OCTA images and facilitating the automated grading of macular ischemia in eyes with BRVO.Translational relevanceDeep-learning denoised optical coherence tomography angiography images could enhance automated macular ischemia quantification.

Project description:Extensive effort has been made studying retinal pathology in Alzheimer's disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal vascular changes and their possible relationships with vascular amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APPSWE/PS1ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, vascular amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice (P < 0.0001). This small vessel degeneration reached significance in 8-month-old mice (P = 0.0035), with males more susceptible than females. Degeneration of retinal capillaries also progressively increased with age in healthy mice (P = 0.0145); however, the phenomenon was significantly worse during AD-like progression (P = 0.0001). A substantial vascular PDGFRβ deficiency (~ 50% reduction, P = 0.0017) along with prominent vascular Aβ deposition was further detected in the retina of ADtg mice, which inversely correlated with the extent of degenerated capillaries (Pearson's r = - 0.8, P = 0.0016). Importantly, tight-junction alterations such as claudin-1 downregulation and increased BRB permeability, demonstrated in vivo by retinal fluorescein imaging and ex vivo following injection of FITC-dextran (2000 kD) and Texas Red-dextran (3 kD), were found in ADtg mice. Overall, the identification of age- and Alzheimer's-dependent retinal capillary degeneration and compromised BRB integrity starting at early disease stages in ADtg mice could contribute to the development of novel targets for AD diagnosis and therapy.

Dataset Information

Deep Retinal Capillary Nonperfusion Is Associated With Photoreceptor Disruption in Diabetic Macular Ischemia.

Publications

Deep Retinal Capillary Nonperfusion Is Associated With Photoreceptor Disruption in Diabetic Macular Ischemia.

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