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1.
Diabetologia ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977459

RESUMEN

AIMS/HYPOTHESIS: Diabetic retinopathy is characterised by neuroinflammation that drives neuronal and vascular degenerative pathology, which in many individuals can lead to retinal ischaemia and neovascularisation. Infiltrating macrophages and activated retina-resident microglia have been implicated in the progression of diabetic retinopathy, although the distinct roles of these immune cells remain ill-defined. Our aim was to clarify the distinct roles of macrophages/microglia in the pathogenesis of proliferative ischaemic retinopathies. METHODS: Murine oxygen-induced retinopathy is commonly used as a model of ischaemia-induced proliferative diabetic retinopathy (PDR). We evaluated the phenotype macrophages/microglia by immunostaining, quantitative real-time RT-PCR (qRT-PCR), flow cytometry and scRNA-seq analysis. In clinical imaging studies of diabetic retinopathy, we used optical coherence tomography (OCT) and OCT angiography. RESULTS: Immunostaining, qRT-PCR and flow cytometry showed expression levels of M1-like macrophages/microglia markers (CD80, CD68 and nitric oxide synthase 2) and M2-like macrophages/microglia markers (CD206, CD163 and macrophage scavenger receptor 1) were upregulated in areas of retinal ischaemia and around neo-vessels, respectively. scRNA-seq analysis of the ischaemic retina revealed distinct ischaemia-related clusters of macrophages/microglia that express M1 markers as well as C-C chemokine receptor 2. Inhibition of Rho-kinase (ROCK) suppressed CCL2 expression and reduced CCR2-positive M1-like macrophages/microglia in areas of ischaemia. Furthermore, the area of retinal ischaemia was reduced by suppressing blood macrophage infiltration not only by ROCK inhibitor and monocyte chemoattractant protein-1 antibody but also by GdCl3. Clinical imaging studies of diabetic retinopathy using OCT indicated potential involvement of macrophages/microglia represented by hyperreflective foci in areas of reduced perfusion. CONCLUSIONS/INTERPRETATION: These results collectively indicated that heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation in retinal vascular diseases including diabetic retinopathy. This adds important new information that could provide a basis for a more targeted, cell-specific therapeutic approach to prevent progression to sight-threatening PDR.

2.
Ophthalmol Sci ; 2(3): 100181, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36245749

RESUMEN

Purpose: To investigate the detection of slower retinal capillary blood flow using commercial OCT angiography (OCTA) with a longer interscan time in diabetic retinopathy (DR). Design: Observational, prospective, cross-sectional study. Participants: A total of 62 eyes from 39 subjects with diabetes mellitus and 10 eyes from 9 healthy subjects. Methods: Commercial spectral domain-OCT was used to obtain 3 × 3-mm fovea-centered OCTA images of all eyes with 3 different interscan times (4.3, 5.7, and 8.6 ms). For each interscan time, OCTA imaging was performed 5 consecutive times, and a ×5 averaged image was obtained. Capillary flow density and visualization of retinal capillaries in the superficial and deep capillary plexuses (SCPs and DCPs, respectively) were compared between the 3 averaged images from the 3 different interscan times. Main Outcome Measures: Capillary flow density and visualization of foveal capillaries in 3 images with different interscan times. Results: Forty-five eyes of 34 patients were analyzed. There was no significant difference in the flow density of the SCP and DCP between the 3 images with different interscan times in all the DR stages. Some capillaries including microaneurysms that could not be observed at 4.3 ms could be observed at 5.7 or 8.6 ms. There were significantly more capillaries with difference points between the 3 images in the group with DR than in the group without DR (P < 0.01). The morphology of some microaneurysms also changed with longer interscan times. Conclusions: OCTA with longer interscan times revealed slower flow points in capillaries and more accurate visualization and morphology of microaneurysms in DR.

3.
Diabetes ; 71(12): 2685-2701, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36203331

RESUMEN

Intraretinal hyperreflective foci (HRF) are significant biomarkers for diabetic macular edema. However, HRF at the vitreoretinal interface (VRI) have not been examined in diabetic retinopathy (DR). A prospective observational clinical study with 162 consecutive eyes using OCT imaging showed significantly increased HRF at the VRI during DR progression (P < 0.01), which was reversed by anti-vascular endothelial growth factor (VEGF) therapy. F4/80+ macrophages increased significantly at the VRI in Kimba (vegfa+/+) or Akimba (Akita × Kimba) mice (both P < 0.01), but not in diabetic Akita (Ins2+/-) mice, indicating macrophage activation was modulated by elevated VEGF rather than the diabetic milieu. Macrophage depletion significantly reduced HRF at the VRI (P < 0.01). Furthermore, BrdU administration in Ccr2rfp/+Cx3cr1gfp/+vegfa+/- mice identified a significant contribution of M2-like tissue-resident macrophages (TRMs) at the VRI. Ki-67+ and CD11b+ cells were observed in preretinal tissues of DR patients, while exposure of vitreal macrophages to vitreous derived from PDR patients induced a significant proliferation response in vitro (P < 0.01). Taken together, the evidence suggests that VEGF drives a local proliferation of vitreous resident macrophages (VRMs) at the VRI during DR. This phenomenon helps to explain the derivation and disease-relevance of the HRF lesions observed through OCT imaging in patients.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Ratones , Animales , Retinopatía Diabética/metabolismo , Factor A de Crecimiento Endotelial Vascular , Macrófagos/metabolismo , Estudios Prospectivos , Tomografía de Coherencia Óptica , Diabetes Mellitus/patología , Receptor 1 de Quimiocinas CX3C/genética
4.
Transl Vis Sci Technol ; 11(9): 21, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36149646

RESUMEN

Purpose: Detecting subtle vitreoretinal interface (VRI) findings, such as a posterior hyaloid membrane, is difficult with conventional retinal imaging. We compared ultra-high-resolution spectral domain optical coherence tomography (UHR-SD-OCT) with standard-resolution OCT (SD-OCT) for the imaging of VRI abnormalities in diabetic retinopathy (DR). Methods: This prospective cross-sectional study included 113 consecutive patients (91 patients with diabetes and 22 healthy controls). The VRI was evaluated, and the results were compared between the conventional SD-OCT and UHR-SD-OCT images. VRI findings were also investigated before and after internal limiting membrane peeling during vitrectomy for proliferative DR. Results: A total of 159 eyes (87.4%) of 91 patients with diabetes were analyzed. UHR-SD-OCT could detect a hyperreflective layer at the VRI, in which en face OCT showed a membrane-like structure, termed the hyperreflective membrane (HRMe). The preoperative HRMe could not be detected in all patients with proliferative DR who underwent internal limiting membrane peeling during vitrectomy. Although the HRMe did not correlate with the DR stage, eyes with diabetic macular edema (DME) (64.5%) showed a significant HRMe with UHR-SD-OCT more frequently than those without DME (35.8%) (P = 0.005). Conclusions: UHR-SD-OCT can detect the HRMe at the VRI in DR eyes, particularly in eyes with DME. The HRMe may present a thickened posterior hyaloid membrane that contributes to DME development. Translational Relevance: UHR-SD-OCT detects slight changes in the VRI in DR eyes. In the future, it may help to elucidate the mechanism of DME formation.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Estudios Transversales , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/diagnóstico por imagen , Humanos , Edema Macular/diagnóstico por imagen , Estudios Prospectivos , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Agudeza Visual
5.
Case Rep Ophthalmol ; 13(2): 385-392, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35811763

RESUMEN

Bullous retinal detachment is a rare complication in the chronic phase of central serous chorioretinopathy (CSC). Only a small subset of eyes with chronic CSC develops into the bullous variant of CSC (bCSC). In patients with bCSC, the elevated concentration of fibrin in the subretinal space leads to persistent retinal detachment and eventually, severe vision loss. We experienced a case of unilateral bCSC with a massive accumulation of subretinal fibrin. Multiple leakage points and dilated choroidal veins were also observed. The patient underwent surgical removal of subretinal fibrin and silicone oil injection followed by photodynamic therapy (PDT). After this treatment, the retina was successfully reattached, and the affected eye was free from recurrent exudative changes for more than 18 months. Massive subretinal fibrin could be surgically removed to prevent the formation of subretinal fibrosis and retinal fold, and PDT under silicone oil can control the underlying exudative changes in bCSC.

6.
Graefes Arch Clin Exp Ophthalmol ; 260(11): 3517-3523, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35665851

RESUMEN

PURPOSE: To investigate the relevance of microaneurysm morphology in optical coherence tomography angiography (OCTA) image averaging and fluorescein leakage in diabetic retinopathy (DR). METHODS: In 38 consecutive patients with DR, ten consecutive 3- × 3-mm fovea-centered OCTA (HS100, Canon Inc., Tokyo, Japan) and fluorescein angiography (FA) were performed, and averaged OCTA images were created based on the 10 images. After detecting all microaneurysms in FA images, the morphology was classified into four types (focal bulge, saccular/pedunculated, fusiform, and mixed) using averaged OCTA images. The correlation between microaneurysm leakage in FA, retinopathy stage, and microaneurysm morphology was estimated. RESULTS: Thirty-eight eyes (50.0%) of the 33 patients were available for analysis, and 370 (63.5%) of the 583 FA-detected microaneurysms were morphologically classifiable (focal bulge, 46; saccular/pedunculated, 143; fusiform, 29; and mixed, 152) in OCTA. There was a significant correlation between stage and percentage of microaneurysm morphology and between morphology and the presence of leakage (P < 0.0001 and P < 0.01, respectively). The proportion of focal bulges decreased with stage progression, while the other three types increased with stage progression. The percentage of FA leakage for focal bulge, saccular/pedunculated, fusiform, and mixed was 41.3%, 66.4%, 82.8%, and 66.4%, respectively, and the fusiform type showed significant FA leakage. CONCLUSION: Microaneurysm morphology is correlated with the DR stage and FA leakage. Microaneurysm morphology recognition using OCTA image averaging may be useful for the clinical evaluation of DR.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Microaneurisma , Humanos , Retinopatía Diabética/complicaciones , Retinopatía Diabética/diagnóstico , Microaneurisma/diagnóstico , Microaneurisma/etiología , Tomografía de Coherencia Óptica/métodos , Vasos Retinianos , Agudeza Visual , Angiografía con Fluoresceína/métodos , Fóvea Central , Fluoresceínas
7.
Invest Ophthalmol Vis Sci ; 62(13): 17, 2021 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-34673901

RESUMEN

Purpose: No lymphatic vessels have been identified in the retina. This study investigated whether pathological VEGF-A-overexpressing diabetic retina causes lymphangiogenesis. Methods: Three genetic mouse models of diabetic retinopathy (DR) (Akita [Ins2+/-], Kimba [vegfa+/+], and Akimba [Akita × Kimba] mice) were used. Retinas were examined by fundus photography, fluorescence angiography (FA), and immunostaining to detect lymphangiogenesis or angiogenesis. Lyve1-GFP (Lyve1EGFP/Cre) mice were used to examine Lyve1-expressing cells by immunostaining. Lymphatic-related factors were investigated in mouse retina and vitreous fluid from proliferative diabetic retinopathy (PDR) patients by RT-PCR and ELISA, respectively. Aged Kimba and Akimba mice were used to examine the retinal phenotype at the late phase of VEGF overexpression. Results: FA and immunostaining showed retinal neovascularization in Kimba and Akimba mice but not wild-type and Akita mice. Immunohistochemistry showed that lymphangiogenesis was not present in the retinas of Akita, Kimba, or Akimba mice despite the significant upregulation of lymphatic-related factors (Lyve1, podoplanin, VEGF-A, VEGF-C, VEGF-D, VEGFR2, and VEGFR3) in the retinas of Kimba and Akimba mice by RT-PCR (P < 0.005). Furthermore, lymphangiogenesis was not present in aged Kimba or Akimba mice. Significantly increased numbers of Lyve1-positive cells present in the retinas of Kimba and Akimba mice, especially in the peripheral areas, were CD11b positive, indicating a macrophage population (P < 0.005). VEGF-C in PDR vitreous with vitreous hemorrhage (VH) was higher than in PDR without VH or a macular hole. Conclusions: Retinal VEGF-A overexpression did not cause typical lymphangiogenesis despite upregulated lymphatic-related factors and significant Lyve1-positive macrophage infiltration.


Asunto(s)
Retinopatía Diabética/genética , Regulación de la Expresión Génica , Linfangiogénesis/genética , Vasos Linfáticos/patología , Retina/metabolismo , Factor C de Crecimiento Endotelial Vascular/genética , Proteínas de Transporte Vesicular/genética , Animales , Diabetes Mellitus Experimental , Retinopatía Diabética/diagnóstico por imagen , Retinopatía Diabética/metabolismo , Angiografía con Fluoresceína/métodos , Vasos Linfáticos/metabolismo , Ratones Endogámicos C57BL , ARN/genética , Retina/patología , Regulación hacia Arriba , Factor C de Crecimiento Endotelial Vascular/biosíntesis , Proteínas de Transporte Vesicular/biosíntesis
9.
Sci Rep ; 11(1): 4185, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33603034

RESUMEN

Our study assessed the influence of vascular permeability on vascular flow density (FD)-correlated retinal sensitivity (RS) in DR. In this cross-sectional, prospective, consecutive study, RS in the extrafoveal macula of DR patient was measured by microperimetry. FD was measured in the total, superficial, and deep capillary plexus layers (TCP, SCP, and DCP) by optical coherence tomography angiography. All measurement points were classified into four categories according to intensity of fluorescein leakage and FD, and the RS reduction was compared. A stratified analysis by retinal thickness (RT) was also performed. Fourteen eyes (14 patients) were enrolled. FDs at 207 RS measurement points were analyzable. For TCP, SCP and DCP, the leakage did not decrease RS at points where FD was maintained. The greater the leakage, the smaller the RS reduction at points with low FD in TCP (P = .020). Points with high leakage showed a significant smaller RS reduction than points with low leakage (P = .001 for TCP, P = .040 for SCP, and P = .046 for DCP) only in areas with low RT and low FD. Our results suggested that vascular hyperpermeability may inhibit the RS reduction in the non-edematous ischemic diabetic retina.


Asunto(s)
Diabetes Mellitus/patología , Retinopatía Diabética/patología , Mácula Lútea/patología , Vasos Retinianos/patología , Estudios Transversales , Femenino , Angiografía con Fluoresceína/métodos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía de Coherencia Óptica/métodos
10.
FASEB J ; 34(6): 8001-8011, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32333612

RESUMEN

Macrophages are the main infiltrating immune cells in choroidal neovascularization (CNV), a hallmark of the human wet, or neovascular age-related macular degeneration (AMD). Due to their plasticity and ability to adapt to the local microenvironment in a tissue-dependent manner, macrophages display polar functional phenotypes characterized by their cell surface markers and their cytokine profiles. We found accumulation of hemoglobin-scavenging cluster of differentiation 163 (CD163)(+) macrophages in laser-induced CNV lesions and higher expression of CD163(+) monocytes in the peripheral blood on day 7 post injury in mice. In comparison, CD80(+) macrophages did not differ with laser-injury in young or aged mice and did not significantly change in the peripheral blood of CNV mice. We examined the percentages of CD163(+), CD206(+), and CD80(+) monocytes in the peripheral blood of patients with wet AMD, patients with dry AMD, and in age-matched individuals without AMD as controls. Percentages of peripheral blood CD163(+) monocytes in both dry AMD (P < .001) and wet AMD (P < .05) were higher than in age-matched non-AMD controls, while there was no difference between the groups in the percentages of peripheral CD206(+) and CD80(+) monocytes. Further, serum level of soluble CD163 (sCD163) was elevated only in patients with wet AMD (P < .05). An examination of 40 cytokine levels across the study groups revealed that anti-VEGF treated patients with wet AMD, who showed no exudative signs on the day of blood drawing had a cytokine profile that was similar to that of non-AMD individuals. These results indicate that CD163 could be further evaluated for its potential as a useful marker of disease activity in patients with neovascular AMD. Future studies will address the origin and potential mechanistic role of CD163(+) macrophages in wet AMD pathologies of angiogenesis and leakage of blood components.


Asunto(s)
Antígenos CD/sangre , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/sangre , Antígenos de Diferenciación Mielomonocítica/metabolismo , Monocitos/metabolismo , Receptores de Superficie Celular/sangre , Receptores de Superficie Celular/metabolismo , Degeneración Macular Húmeda/sangre , Degeneración Macular Húmeda/metabolismo , Anciano , Inhibidores de la Angiogénesis/farmacología , Animales , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Neovascularización Coroidal/sangre , Neovascularización Coroidal/metabolismo , Femenino , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Monocitos/efectos de los fármacos , Retina/efectos de los fármacos , Retina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Agudeza Visual/efectos de los fármacos , Agudeza Visual/fisiología , Degeneración Macular Húmeda/tratamiento farmacológico
11.
Diabetes ; 69(5): 981-999, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32139595

RESUMEN

Approximately 40% of patients with diabetic macular edema (DME) are resistant to anti-vascular endothelial growth factor (VEGF) therapy (rDME). Here, we demonstrate that significant correlations between inflammatory cytokines and VEGF, as observed in naive DME, are lost in patients with rDME. VEGF overexpression in the mouse retina caused delayed inflammatory cytokine upregulation, monocyte/macrophage infiltration (CD11b+ Ly6C+ CCR2+ cells), macrophage/microglia activation (CD11b+ CD80+ cells), and blood-retinal barrier disruption due to claudin-5 redistribution, which did not recover with VEGF blockade alone. Phosphorylated protein analysis of VEGF-overexpressed retinas revealed rho-associated coiled-coil-containing protein kinase (ROCK) activation. Administration of ripasudil, a selective ROCK inhibitor, attenuated retinal inflammation and claudin-5 redistribution. Ripasudil also contributed to the stability of claudin-5 expression by both transcriptional enhancement and degradation suppression in inflammatory cytokine-stimulated endothelium. Notably, the anti-VEGF agent and the ROCK inhibitor were synergic in suppressing cytokine upregulation, monocyte/macrophage infiltration, macrophage/microglia activation, and claudin-5 redistribution. Furthermore, in vitro analysis confirmed that claudin-5 redistribution depends on ROCK2 but not on ROCK1. This synergistic effect was also confirmed in human rDME cases. Our results suggest that ROCK-mediated claudin-5 redistribution by inflammation is a key mechanism in the anti-VEGF resistance of DME.


Asunto(s)
Claudina-5/metabolismo , Complicaciones de la Diabetes , Diabetes Mellitus Experimental/complicaciones , Inflamación/metabolismo , Edema Macular/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/uso terapéutico , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Bevacizumab/uso terapéutico , Línea Celular , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Células Endoteliales/efectos de los fármacos , Eliminación de Gen , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Humanos , Edema Macular/etiología , Ratones Endogámicos C57BL , Ranibizumab/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Retina/patología , Quinasas Asociadas a rho/genética , Quinasas Asociadas a rho/metabolismo
12.
Ophthalmol Retina ; 4(2): 175-186, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31753811

RESUMEN

PURPOSE: In diabetic retinopathy (DR), OCT angiography (OCTA) could not image all fluorescein angiography (FA)-detected microaneurysms. We investigated whether multiple image averaging could enhance the microaneurysm detection capability of OCTA in patients with DR. DESIGN: Prospective and cross-sectional observational study. PARTICIPANTS: Consecutive 31 patients (n = 62 eyes) with DR. METHODS: All eyes underwent FA and 3 × 3 mm fovea-centered OCTA images were obtained using 2 devices: RTVue XR Avanti (Optovue Inc, Fremont, CA) and OCT HS-100 (Canon Inc, Toyko, Japan). OCTA imaging (HS-100) was performed 10 consecutive times. Microaneurysm detection capability was compared among 5 OCTA images (single image, ×3, ×5, and ×10 averaged images and single scan image with the RTVue XR Avanti device). MAIN OUTCOME MEASURES: Microaneurysm detection capability and the correlation between microaneurysm clinical characteristics or morphology and the extent of image averaging required for OCTA detection. RESULTS: A total of 415 microaneurysms could be analyzed in 31 eyes from 25 patients. Microaneurysms detected on single image, ×3, ×5, and ×10 averaged OCTA images were 144 (34.7%), 227 (54.7%), 285 (68.7%), and 306 (73.7%), respectively. Microaneurysm detection capability was significantly increased with increased image averaging. Microaneurysm detection with OCTA was not correlated with retinal thickness, FA leakiness, and indocyanine green angiogram detection or the number of averaged images, whereas there was significant correlation between microaneurysm morphology and microaneurysm visibility by the image-averaging process for 4 morphologies, particular the focal bulge types (P < 0.01). CONCLUSIONS: In DR, multiple image averaging is useful for increasing the microaneurysm detection capability of OCTA, especially for focal bulge-type microaneurysms.


Asunto(s)
Angiografía con Fluoresceína/métodos , Fóvea Central/patología , Microaneurisma/diagnóstico , Vasos Retinianos/patología , Tomografía de Coherencia Óptica/métodos , Estudios Transversales , Femenino , Fóvea Central/irrigación sanguínea , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
13.
Am J Ophthalmol Case Rep ; 16: 100549, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31508535

RESUMEN

PURPOSE: In this study, we report a case of branch retinal artery occlusion (BRAO) in the contralateral eye the day after aflibercept treatment during systemic heparin administration. OBSERVATIONS: A 63-year-old woman with diabetic macular edema underwent repeated intravitreal injection of anti-VEGF drugs (0.5mg ranibizumab or 2mg aflibercept) for her left eye. The day after intravitreal injection of aflibercept, she presented with sudden painless blurred vision that was limited to the inferior visual field defect in the contralateral eye (right eye) during hemodialysis with the anti-coagulant heparin. Optical coherence tomography angiography (OCTA) showed decreased artery perfusion and the patient was diagnosed with contralateral BRAO. CONCLUSIONS: Previous in vitro and in vivo studies have reported that the Fc portion of anti-VEGF drugs activates platelets with heparin. Therefore, careful anti-VEGF drug selection may be necessary in cases with concomitant heparin treatment.

14.
Sci Rep ; 9(1): 8668, 2019 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-31209251

RESUMEN

Our study evaluated the diagnostic capability of flow density (FD) in OCT angiography (OCTA) for diabetic retinopathy (DR) detection in diabetic patients. We studied 93 eyes of 68 diabetic patients who underwent OCTA (36 and 57 eyes without and with DR, respectively). Retinal capillary FD of a 2.6 × 2.6 mm2 area and four divided areas at the superficial (SCP) and deep capillary plexus (DCP) were measured. Predictions were evaluated using the area under the receiver operating characteristic curve (AUC). The diagnostic capabilities of the FDs in discriminating between eyes without DR and eyes with total or early DR were compared. Furthermore, predictions with foveal avascular zone (FAZ) area, hemoglobin A1c (HbA1c), and DM duration were also compared with FD. Prediction using FD AUC in the temporal side in the DCP (0.83) was the highest and significantly better than all other AUCs examined (P < 0.05), including discriminating between eyes without DR and with early DR (P < 0.01). Prediction using this particular AUC was also significantly better than that by FAZ area and HbA1c (P < 0.001 and <0.001, respectively). Area-divided FD in OCTA may be valuable for diagnosing retinopathy in diabetic patients.


Asunto(s)
Diabetes Mellitus Tipo 1/diagnóstico por imagen , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Retinopatía Diabética/diagnóstico por imagen , Retina/diagnóstico por imagen , Vasos Retinianos/diagnóstico por imagen , Adulto , Anciano , Área Bajo la Curva , Estudios Transversales , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Flujo Sanguíneo Regional/fisiología , Retina/metabolismo , Retina/patología , Vasos Retinianos/metabolismo , Vasos Retinianos/patología , Tomografía de Coherencia Óptica
16.
Graefes Arch Clin Exp Ophthalmol ; 256(12): 2275-2282, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30191299

RESUMEN

PURPOSE: Fluorescein angiography (FA) has been conventionally used for detection of retinal nonperfused area (NPA) in diabetic retinopathy (DR) in spite of its qualitative evaluation. Optical coherence tomography angiography (OCTA) has been recently reported to be useful for the quantification of retinal vascular disorder in DR. In this study, we examined whether retinal flow density (FD) measurement in OCTA was useful for NPA detection in DR. METHODS: The study included 41 eyes from 29 patients with DR who underwent FA and OCTA. Regions surrounded by arteries or veins were extracted in the OCTA image, and the FDs in each region were measured by Image J. Furthermore, each region was classified as NPA or perfused area (PA) in FA. The receiver operating characteristic (ROC) curve was prepared by logistic regression analysis of the FD. The AUC (area under the ROC curve) and cutoff value of FD were also calculated. RESULTS: Two hundred fifty-two regions were analyzed and classified into 38 NPA regions and 214 PA regions using FA. FD of each capillary plexus in NPA was significantly smaller than in PA (p < 0.0001). The AUC of total capillary plexus layers (TCP), superficial capillary plexus layer (SCP), and deep capillary plexus layer (DCP) was 0.975, 0.974, and 0.971, respectively. All areas, where the FD was more than the cutoff value (0.07 in TCP), were diagnosed with PA. Three areas with intraretinal microvascular abnormalities (IRMA) were diagnosed as PA despite being below the cutoff value. CONCLUSIONS: FD measurement in OCTA is useful for NPA detection in DR.


Asunto(s)
Retinopatía Diabética/diagnóstico , Angiografía con Fluoresceína/métodos , Flujo Sanguíneo Regional/fisiología , Vasos Retinianos/fisiopatología , Tomografía de Coherencia Óptica/métodos , Adulto , Anciano , Anciano de 80 o más Años , Capilares/fisiopatología , Estudios Transversales , Retinopatía Diabética/fisiopatología , Femenino , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Vasos Retinianos/diagnóstico por imagen
18.
Invest Ophthalmol Vis Sci ; 58(11): 4889-4897, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28973335

RESUMEN

Purpose: Our purpose is to evaluate the spatial bias of macular capillary dropout accompanying diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). Methods: This study included 47 patients with diabetes and 29 healthy individuals who underwent OCTA. Retinal capillary flow density (FD) of 2.6 × 2.6 or 5.2 × 5.2 mm foveal area as well as the four divided areas (superior, inferior, temporal, nasal) without a foveal avascular zone (FAZ) at the superficial capillary plexus and deep capillary plexus (DCP) were measured respectively using ImageJ and NI Vision. Spatial biases of FD (orientation bias ratio and hierarchical bias ratio) and the correlation between FAZ and FD were examined. Results: OCTA showed focal capillary dropout in DR patients. The orientation bias of FD was significantly higher in NPDR compared to NDR in the DCP (P = 0.03). The hierarchical bias of FD was significantly shifted to a DCP dominance with progression of DR (P < 0.01). In addition, the FD and FAZ area were significantly inversely correlated in both plexus in DR patients but not in healthy subjects (P < 0.01). Conclusions: Area-divided OCTA quantification shows the appearance of spatial biases of macular capillary dropout with the onset of DR, suggesting that DR-related macular capillary dropout occurs locally and randomly. Future studies are necessary to determine the clinical relevance of the spatial pattern of capillary dropout in DR.


Asunto(s)
Capilares/patología , Retinopatía Diabética/patología , Mácula Lútea/patología , Vasos Retinianos/patología , Adulto , Anciano , Capilares/fisiopatología , Estudios de Casos y Controles , Estudios Transversales , Retinopatía Diabética/fisiopatología , Femenino , Angiografía con Fluoresceína , Humanos , Mácula Lútea/fisiopatología , Masculino , Persona de Mediana Edad , Vasos Retinianos/fisiopatología , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos
19.
Transl Vis Sci Technol ; 6(5): 2, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28875064

RESUMEN

PURPOSE: Retinal vascular networks are observed as a layered structure residing in a nerve fiber layer and an inner nuclear layer of the retina. This study aimed to evaluate reflectance confocal adaptive optics scanning laser ophthalmoscopy (AO-SLO) for imaging of the layered retinal vascular networks. METHODS: This study included 16 eyes of 16 healthy cases. On the fovea, 2.8- and 3.0 mm2-areas were imaged using a prototype AO-SLO and optical coherence tomography angiography (OCTA), respectively. AO-SLO images focused on the nerve fiber and photoreceptor layers were recorded in the area. Two different vessel images (capillary networks in the superficial layer and in all layers) were generated to examine if the deep capillary network could be distinguished. We compared AO-SLO with OCTA in imaging of the layered retinal vascular networks. RESULTS: Sufficient images of capillary networks for analysis could be generated when the motion contrast was enhanced with AO-SLO movies in seven cases (43.8%). The deep capillary network could be distinguished in the merged image. Vascular depiction performance in AO-SLO was significantly better than in OCTA at both 0.5- and 1.0-mm areas from the fovea (P < 0.05). CONCLUSIONS: Retinal vascular imaging using AO-SLO might be a useful adjunct to OCTA as a supportive method to evaluate the retina in healthy patients and patients with disease. TRANSLATIONAL RELEVANCE: In cases requiring accurate and detailed retinal vasculature observation, AO-SLO might be useful for evaluating retinal vascular lesions as a supportive imaging method of OCTA.

20.
Ophthalmologica ; 238 Suppl 1: 21-27, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28693011

RESUMEN

Objetivo: Comparar la efectividad de ranibizumab intravítreo (RIV) para el tratamiento del edema macular diabético (EMD) en ojos con y sin vitrectomía previa. Procedimientos: Evaluamos de manera prospectiva la mejor agudeza visual corregida (MAVC) y el grosor macular central (GMC) tras el tratamiento con RIV durante 6 meses. Resultados: No se observaron diferencias significativas en la MAVC o GMC inicial en ninguno de los dos grupos. En el grupo no vitrectomizado (n = 15), los cambios medios en la MAVC y GMC hasta el sexto mes de tratamiento con respecto al valor inicial resultaron significativos (p < 0,01). En el grupo vitrectomizado (n = 10), se observó una mejora más lenta, y la mejora media en la MAVC no resultó significativa (p = 0,5), aunque la media en la disminución del GMC sí que lo fue (p < 0,05). No se observaron diferencias significativas en los cambios medios en la MAVC y el GMC entre ambos grupos a los 6 meses del tratamiento. Conclusiones: La diferencia en la efectividad de RIV entre ambos grupos no resultó significativa. Ranibizumab intravítreo puede ser una opción de tratamiento incluso en pacientes vitrectomizados con EMD.

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