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1.
Optom Vis Sci ; 97(2): 110-120, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32011584

RESUMO

SIGNIFICANCE: Foveal hypoplasia is described clinically by the absence of a foveal pit and subsequent reduction in visual acuity. Optical coherence tomography angiography provides precise segmentation of the retinal vascular supply demonstrating the vascular perfusion in affected patients. Preservation of perfusion is linked to visual acuity and function. PURPOSE: This case report describes a patient with foveal hypoplasia and preservation of visual acuity with preserved retinal capillary density of the superficial and deep capillary plexuses on optical coherence tomography angiography. In addition, the diagnostic findings of foveal hypoplasia as seen on optical coherence tomography angiography will be described. CASE REPORT: A 25-year-old Caucasian female with history of foveal hypoplasia presented to the clinic for evaluation. She had no other visual, ocular, or systemic complaints. Her ocular history included Duane syndrome, accommodative insufficiency, and traumatic brain injury. Her medical history included cardiac ablation secondary to supraventricular tachycardia, gall bladder removal, maxillary sinus cyst, and a history of migraines. Best-corrected visual acuity was 20/15 in the right and left eyes. Funduscopic examination was unremarkable. Spectral domain optical coherence tomography revealed absence of the anatomical foveal pit with normal inner retinal morphology. Optical coherence tomography angiography confirmed a decreased foveal avascular zone; however, a vascular density analysis showed normal perfusion to the inner retinal plexuses. CONCLUSIONS: Optical coherence tomography angiography is a rapid, noninvasive imaging modality that provides excellent insight into the microvasculature supply to the retina and choroid. As such, it allows for an in-depth analysis into the pathophysiology behind certain conditions such as foveal hypoplasia.


Assuntos
Anormalidades do Olho/diagnóstico por imagem , Fóvea Central/anormalidades , Acuidade Visual/fisiologia , Adulto , Capilares/diagnóstico por imagem , Capilares/patologia , Feminino , Angiofluoresceinografia/métodos , Humanos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Transtornos da Visão/fisiopatologia
2.
Invest Ophthalmol Vis Sci ; 61(2): 3, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031575

RESUMO

Purpose: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. ROP occurs as a consequence of postnatal hyperoxia exposure in premature infants, resulting in vasoproliferation in the retina. The tetraspan protein epithelial membrane protein-2 (EMP2) is highly expressed in the retinal pigment epithelium (RPE) in adults, and it controls vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line. We, therefore, hypothesized that Emp2 knockout (Emp2 KO) protects against neovascularization in murine oxygen-induced retinopathy (OIR). Methods: Eyes were obtained from wildtype (WT) and Emp2 KO mouse pups at P7, P12, P17, and P21 after normoxia or hyperoxia (P7-P12) exposure. Following hyperoxia exposure, RNA sequencing was performed using the retina/choroid layers obtained from WT and Emp2 KO at P17. Retinal sections from P7, P12, P17, and P21 were evaluated for Emp2, hypoxia-inducible factor 1α (Hif1α), and VEGF expression. Whole mount images were generated to assess vaso-obliteration at P12 and neovascularization at P17. Results: Emp2 KO OIR mice demonstrated a decrease in pathologic neovascularization at P17 compared with WT OIR mice through evaluation of retinal vascular whole mount images. This protection was accompanied by a decrease in Hif1α at P12 and VEGFA expression at P17 in Emp2 KO animals compared with the WT animals in OIR conditions. Collectively, our results suggest that EMP2 enhances the effects of neovascularization through modulation of angiogenic signaling. Conclusions: The protection of Emp2 KO mice against pathologic neovascularization through attenuation of HIF and VEGF upregulation in OIR suggests that hypoxia-induced upregulation of EMP2 expression in the neuroretina modulates HIF-mediated neuroretinal VEGF expression.


Assuntos
Glicoproteínas de Membrana/fisiologia , Neovascularização Retiniana/patologia , Retinopatia da Prematuridade/patologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Animais , Animais Recém-Nascidos , Linhagem Celular , Hiperóxia/fisiopatologia , Hipóxia/fisiopatologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Patológica/patologia , Oxigênio/toxicidade , Epitélio Pigmentado da Retina/metabolismo , Vasos Retinianos/patologia , Regulação para Cima/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
Invest Ophthalmol Vis Sci ; 61(2): 5, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031577

RESUMO

Purpose: To investigate characteristics of the foveal pit and the foveal avascular zone (FAZ) in patients with Alport syndrome (AS), a rare monogenetic disease due to mutations in genes encoding for collagen type IV. Methods: Twenty-eight eyes of nine patients with AS, and five autosomal-recessive carriers and 15 eyes from 15 age-similar healthy control subjects were examined using optical coherence tomography (OCT) and OCT-angiography (OCT-A). Foveal configuration and FAZ measures including the FAZ area, circularity, and vessel density in the central 1° and 3° were correlated. Results: Foveal hypoplasia was found in 10 eyes from seven patients with either genotype. In contrast, a staircase foveopathy was found in seven eyes of four X-linked AS patients. The average FAZ area did not differ significantly between AS patients and control subjects (mean ± SD 0.24 ± 0.24 mm2 vs. 0.21 ± 0.09 mm2; P = 0.64). Five eyes showed absence or severe anomalies of the FAZ with crossing macular capillaries that was linked to the degree of foveal hypoplasia on OCT images leading to a significant inverse correlation of FAZ area and foveal thickness (r = -0.88; P < 0.001). In contrary, female patients with X-linked mutations exhibited a significantly greater FAZ area (0.48 ± 0.30 mm2 vs. 0.21 ± 0.09 mm2; P = 0.007), in line with OCT findings of a staircase foveopathy. Conclusions: The foveal phenotypic spectrum in AS ranges from foveal hypoplasia and absence of a FAZ to staircase foveopathy with an enlarged FAZ. Because the development of the FAZ and foveal pit are closely related, these findings suggest an important role for collagen type IV in foveal development and maturation.


Assuntos
Fóvea Central/anormalidades , Nefrite Hereditária/patologia , Doenças Retinianas/patologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Colágeno Tipo IV/genética , Estudos Transversais , Feminino , Angiofluoresceinografia , Fóvea Central/crescimento & desenvolvimento , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Nefrite Hereditária/genética , Nefrite Hereditária/fisiopatologia , Fenótipo , Estudos Prospectivos , Doenças Retinianas/genética , Doenças Retinianas/fisiopatologia , Vasos Retinianos/patologia , Tomografia de Coerência Óptica , Acuidade Visual , Adulto Jovem
4.
Invest Ophthalmol Vis Sci ; 61(2): 35, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32084264

RESUMO

Purpose: To compare postvitrectomy retinal and choroidal vessel density (VD) and retinal layer thickness between eyes with macula-off and macula-on rhegmatogenous retinal detachment (RRD) using swept-source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (OCTA) and to identify OCTA factors associated with visual outcomes. Methods: We retrospectively reviewed 31 eyes that underwent pars plana vitrectomy for primary RRD. Eyes with macula-off and macula-on RRD were compared with healthy fellow eyes. Both OCT and OCTA were performed 6 months after surgery, and the macula-off RRD group was divided into two subgroups according to the presence of an outer retinal defect. The correlations between postoperative best-corrected visual acuity (BCVA) at 6 months and SS-OCT and OCTA measurements were analyzed. Results: Twenty eyes with macula-off RRD and 11 eyes with macula-on RRD were included. In the macula-off RRD group, the central retinal thickness was significantly decreased 6 months postoperatively compared with the fellow eyes (228.9 ± 29.7 µm and 253.6 ± 27.7 µm, P = 0.009). In the outer retinal defect group, the choriocapillaris plexus (CCP) VD was significantly decreased compared with the fellow eyes (56.4% ± 4.8% and 60.2% ± 4.0%, P = 0.026). In the macula-off RRD group, the postoperative BCVA at 6 months correlated significantly with the ratio of the center CCP VD of the detached eyes to that of the fellow eyes (R2 = 0.207, P = 0.025). Conclusions: The CCP VD could be related to the anatomical restoration of the outer retinal layer in macula-off RRD. The CCP VD as determined by OCTA could be an indicator of the visual outcome after surgery in macula-off RRD.


Assuntos
Retina/patologia , Descolamento Retiniano/cirurgia , Vasos Retinianos/patologia , Vitrectomia , Adulto , Idoso , Feminino , Humanos , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/patologia , Descolamento Retiniano/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologia , Vitrectomia/métodos
5.
Invest Ophthalmol Vis Sci ; 61(2): 34, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32084269

RESUMO

Purpose: We aimed to observe longitudinal changes in retinal blood flow (RBF) and structural transformations in capillaries using Doppler optical coherence tomography (DOCT) and optical coherence tomography angiography (OCTA) in a feline retinal blood occlusion (RVO) model. Methods: RVO was induced by argon green laser photocoagulation (PC) in six eyes of six cats. RBF was measured at a first-order retinal artery and vein by a DOCT flowmeter, and structural changes in the capillaries around the occluded vessels (12 × 12 and 3 × 3 mm) were assessed by OCTA before (at baseline); immediately after PC; and on days 1, 4, 7, and 14 thereafter. Systemic and ocular parameters were monitored during the observation period. Results: There were no significant differences in any systemic or ocular parameters before and after PC. Arterial RBF increased significantly on day 1 (160.6 ± 8.6% vs. baseline, P < 0.001) and decreased below baseline after day 1 through 14. Venous RBF decreased immediately after PC (17.4 ± 9.6% vs. baseline, P = 0.001) and then gradually increased afterwards, but did not return to baseline. OCTA showed dilatation of retinal venules immediately after PC to day 1. Collateral vessels began to form on day 4, had matured by day 7, and were pruned on day 14, which formed as mature as normal retinal venule diameters. Conclusions: With increasing arterial RBF within 1 day after inducing RVO, venules gradually expanded to form collateral vessels, suggesting that collateral vessels originate from existing capillary networks, not neovascularization.


Assuntos
Fluxo Sanguíneo Regional/fisiologia , Oclusão da Veia Retiniana/fisiopatologia , Vasos Retinianos , Animais , Capilares/patologia , Gatos , Angiofluoresceinografia/métodos , Retina/fisiopatologia , Oclusão da Veia Retiniana/patologia , Vasos Retinianos/patologia , Vasos Retinianos/fisiopatologia , Tomografia de Coerência Óptica/métodos
6.
Invest Ophthalmol Vis Sci ; 61(2): 39, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32097476

RESUMO

Purpose: Familial exudative vitreoretinopathy (FEVR) is an inherited retinal disease in which the retinal vasculature is affected. Patients with FEVR typically lack or have abnormal vasculature in the peripheral retina, the outcome of which can range from mild visual impairment to complete blindness. A missense mutation (p.His455Tyr) in ZNF408 was identified in an autosomal dominant FEVR family. Little, however, is known about the molecular role of ZNF408 and how its defect leads to the clinical features of FEVR. Methods: Using CRISPR/Cas9 technology, two homozygous mutant zebrafish models with truncated znf408 were generated, as well as one heterozygous and one homozygous missense znf408 model in which the human p.His455Tyr mutation is mimicked. Results: Intriguingly, all three znf408-mutant zebrafish strains demonstrated progressive retinal vascular pathology, initially characterized by a deficient hyaloid vessel development at 5 days postfertilization (dpf) leading to vascular insufficiency in the retina. The generation of stable mutant lines allowed long-term follow up studies, which showed ectopic retinal vascular hyper-sprouting at 90 dpf and extensive vascular leakage at 180 dpf. Conclusions: Together, our data demonstrate an important role for znf408 in the development and maintenance of the vascular system within the retina.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Vitreorretinopatias Exsudativas Familiares , Vasos Retinianos/patologia , Animais , Proteínas de Ligação a DNA/genética , Vitreorretinopatias Exsudativas Familiares/genética , Vitreorretinopatias Exsudativas Familiares/fisiopatologia , Mutação de Sentido Incorreto , Peixe-Zebra
7.
Invest Ophthalmol Vis Sci ; 61(2): 43, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32106290

RESUMO

Purpose: Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness worldwide in the working-age population, and the incidence is rising. Until now it has been difficult to define initiating events and disease progression at the molecular level, as available diabetic rodent models do not present the full spectrum of neural and vascular pathologies. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor pdx1 were previously shown to display a diabetic phenotype from larval stages through adulthood. In this study, pdx1 mutants were examined for retinal vascular and neuronal pathology to demonstrate suitability of these fish for modeling DR. Methods: Vessel morphology was examined in pdx1 mutant and control fish expressing the fli1a:EGFP transgene. We further characterized vascular and retinal phenotypes in mutants and controls using immunohistochemistry, histology, and electron microscopy. Retinal function was assessed using electroretinography. Results: Pdx1 mutants exhibit clear vascular phenotypes at 2 months of age, and disease progression, including arterial vasculopenia, capillary tortuosity, and hypersprouting, could be detected at stages extending over more than 1 year. Neural-retinal pathologies are consistent with photoreceptor dysfunction and loss, but do not progress to blindness. Conclusions: This study highlights pdx1 mutant zebrafish as a valuable complement to rodent and other mammalian models of DR, in particular for research into the mechanistic interplay of diabetes with vascular and neuroretinal disease. They are furthermore suited for molecular studies to identify new targets for treatment of early as well as late DR.


Assuntos
Retinopatia Diabética/patologia , Células Fotorreceptoras/patologia , Degeneração Retiniana/patologia , Vasos Retinianos/patologia , Análise de Variância , Animais , Diabetes Mellitus Experimental , Retinopatia Diabética/fisiopatologia , Eletrorretinografia , Degeneração Retiniana/fisiopatologia , Vasos Retinianos/fisiopatologia , Peixe-Zebra
8.
PLoS One ; 15(2): e0229213, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32078656

RESUMO

PURPOSE: Von Hippel-Lindau (VHL) disease is a hereditary disorder that can lead to ophthalmic manifestations, including retinal capillary hemangioma (RCH). The diagnosis of RCH is often guided by wide-field fluorescein angiography. In some cases, optical coherence tomography angiography (OCT-A) serves as a non-invasive alternative to FA. Herein, we used OCT-A to examine the macular microvasculature in patients with VHL disease. SUBJECTS: Subjects were selected from patients with a diagnosis of VHL. The control group included eyes without retinal diagnosis from patients with an episode of unilateral retinal detachment or trauma and age ≤ 50 years old. METHODS: Subjects were scanned on the Optovue RTVue-XR device to acquire 3mm x 3mm OCT-A images of the superficial (SCP) and deep capillary plexus (DCP). SCP and DCP vessel density (VD) were calculated after the images were binarized. Furthermore, for subjects with RCH, each OCT-A image was divided equally into four quadrants. SCP and DCP VD of quadrants with RCH were compared to those without RCH. T-tests were performed for statistical analysis. RESULTS: 67 eyes with a history of VHL disease were included as study subjects, while 16 eyes were included as controls. Significant increases in VD were found in patients with VHL disease for both the SCP (p = 0.0441) and DCP (p = 0.0344). When comparing quadrants with associated RCH development to those without, we found no significant difference in SCP VD (p = 0.160) or DCP VD (p = 0.484). CONCLUSIONS: OCT-A can detect changes in the retinal microvasculature in the macula of patients with VHL disease. OCT-A imaging may be an additional tool for screening and early detection of patients at risk of developing ocular complications of VHL disease. Future studies should explore subtle progression on OCT-A associated with the pathogenesis and development of RCH, particularly with larger scan patterns.


Assuntos
Angiofluoresceinografia/métodos , Doenças Retinianas/diagnóstico , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Doença de von Hippel-Lindau/complicações , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Doenças Retinianas/etiologia , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Acuidade Visual , Doença de von Hippel-Lindau/diagnóstico por imagem
9.
PLoS One ; 15(2): e0229388, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101581

RESUMO

Treatment of neovascular age-related macular degeneration (nAMD) with VEGF can be performed with several posologies. The purpose of our cross-sectional study was to analyze retinal vessel density by quantitative OCT-angiography (OCT-A) and to compare treat-and-extend (T&E) and fixed treatment protocols to a control group with dry AMD. Altogether 48 patients were enrolled: 13 eyes with T&E protocol ranibizumab treatment (group A) and 17 eyes with fixed regimen aflibercept therapy (group B), the control group comprised 18 eyes with dry AMD (group C). One year after the start of the treatment, quantitative OCT-A (AngioVue-Optovue, Fermont, USA) was performed: superficial and deep retinal vessel densities were analyzed in the foveal and parafoveal regions. Our results show, that the density of retinal superficial vasculature in the fovea was not different between the treatment groups (A: 25.9±9.1%; B: 24.3%±8.9), neither from group C (25.6±4.8%). Superficial parafoveal vascular density of the retina, however, was decreased in both treated groups (A: 46.7±9.1%, B: 42.9±6.1%, C: 49.7±4.9%). In the deep retinal plexus, vascular density was lower in both treatment groups compared to that of in controls in both the foveal and parafoveal area (A: 29.8±6.3%, B: 32.5±6.9%, C: 36.4±1.7% and A: 46.3±3.8%, B: 47.1±5.3%, C: 49.7±4.9%, foveal and parafoveal respectively). Our data suggest, that after one year of anti-VEGF treatment, reduced macular vessel density in three of the four examined vascular regions can be found independent of the treatment regimen.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Degeneração Macular/patologia , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Vasos Retinianos/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Fóvea Central/efeitos dos fármacos , Fóvea Central/patologia , Humanos , Degeneração Macular/tratamento farmacológico , Masculino , Estudos Prospectivos , Vasos Retinianos/efeitos dos fármacos , Retratamento , Fatores de Tempo
10.
Eur J Endocrinol ; 182(3): 293-302, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31917679

RESUMO

Objective: Excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as in acromegaly, is associated with increased risk of diabetes, but whether retinal vessels are altered is unknown. The aim of this study was to evaluate retinal vessel morphology in patients with acromegaly at diagnosis and after treatment and to describe the prevalence of diabetic retinopathy in patients with long-standing acromegaly and diabetes. Design: Two independent observational studies, one being prospective and the other retrospective and cross-sectional. Methods: Retinal vessel morphology of 26 patients with acromegaly was examined at diagnosis and 1 year after treatment and compared to 13 healthy controls. Cross-sectional evaluation of 39 patients with long-standing acromegaly and diabetes was performed. Fundus photographs were digitally analyzed for vessel morphology. Results: Patients with acromegaly had a median (interquartile range) of 34.3 (30.0-39.0) vessel branching points compared to 27.0 (24.0-29.0) for healthy controls (P < 0.001). Tortuosity of arterioles and venules remained unchanged. Vessel morphology did not change significantly after treatment. Patients with acromegaly and diabetes for a median of 14 years also had a high number of branching points (34.2 (32.5-35.6)), but the prevalence of diabetic retinopathy was not higher than expected in diabetic patients without acromegaly. Conclusions: Patients with acromegaly have an increased number of vascular branching points in the retina without an alteration of macroscopic vessel morphology. This is consistent with an angiogenic effect of GH/IGF-1 in humans. The prevalence of diabetic retinopathy was not increased in patients with acromegaly and diabetes.


Assuntos
Acromegalia/patologia , Vasos Retinianos/patologia , Acromegalia/complicações , Acromegalia/terapia , Adolescente , Adulto , Idoso , Arteríolas/patologia , Estudos de Casos e Controles , Estudos Transversais , Complicações do Diabetes/patologia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/etiologia , Neovascularização Patológica/patologia , Prevalência , Estudos Retrospectivos , Vênulas/patologia , Adulto Jovem
11.
Eur J Ophthalmol ; 30(3): 411-416, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31928211

RESUMO

Diabetic retinopathy is a common diabetes complication representing a heavy burden in terms of visual impairment and heath expenditure. Optical coherence tomography angiography is a relatively new imaging method and has proven to be a powerful tool in the analysis of diabetic retinopathy common features, including microaneurysms, intraretinal microvascular abnormalities, or neovascularization, as well as in research field, challenging the gold standard of fluorescein angiography. Many studies underlined the vascular impairment observed through optical coherence tomography angiography and its typical parameters such as vessel length density, foveal avascular zone, and fractal dimension. Choriocapillaris involvement in the pathogenesis of diabetic retinopathy is an interesting point, derived from the analysis of this plexus using optical coherence tomography angiography. In conclusion, optical coherence tomography angiography, which is not free of limitations, such as motion artifacts or segmentation errors, has become an indispensable technique in adding more information to our understanding of diabetic retinopathy.


Assuntos
Retinopatia Diabética/diagnóstico , Angiofluoresceinografia , Tomografia de Coerência Óptica , Corioide/irrigação sanguínea , Retinopatia Diabética/fisiopatologia , Humanos , Macula Lutea/fisiopatologia , Disco Óptico/irrigação sanguínea , Vasos Retinianos/patologia
12.
PLoS One ; 15(1): e0227175, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923188

RESUMO

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with an increased risk of myocardial infarction and stroke but it remains unclear how to identify microvascular changes in this population. OBJECTIVES: We hypothesized that simple non-mydriatic retinal photography is feasible and can be used to assess microvascular damage in COPD. METHODS: Novel Vascular Manifestations of COPD was a prospective study comparing smokers with and without COPD, matched for age. Non-mydriatic, retinal fundus photographs were assessed using semi-automated software. RESULTS: Retinal images from 24 COPD and 22 control participants were compared. Cases were of similar age to controls (65.2 vs. 63.1 years, p = 0.38), had significantly lower Forced Expiratory Volume in one second (FEV1) (53.4 vs 100.1% predicted; p < 0.001) and smoked more than controls (41.7 vs. 29.6 pack years; p = 0.04). COPD participants had wider mean arteriolar (155.6 ±15 uM vs. controls [142.2 ± 12 uM]; p = 0.002) and venular diameters (216.8 ±20.7 uM vs. [201.3± 19.1 uM]; p = 0.012). Differences in retinal vessel caliber were independent of confounders, odds ratios (OR) = 1.08 (95% confidence intervals [CI] = 1.02, 1.13; p = 0.007) and OR = 1.05 (CI = 1.01, 1.09; p = 0.011) per uM increase in arteriolar and venular diameter respectively. FEV1 remained significantly associated with retinal vessel dilatation r = -0.39 (p = 0.02). CONCLUSIONS: Non-mydriatic retinal imaging is easily facilitated. We found significant arteriole and venous dilation in COPD compared to age-matched smokers without COPD associated with lung function independent of standard cardiovascular risk factors. Retinal microvascular changes are known to be strongly associated with future vascular events and retinal photography offers potential to identify this risk. TRIAL REGISTRATION: clinicaltrials.gov NCT02060292.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Microvasos/diagnóstico por imagem , Fotomicrografia/métodos , Doença Pulmonar Obstrutiva Crônica/complicações , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/etiologia , Vasos Retinianos/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Viabilidade , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vasos Retinianos/patologia , Fumantes , Fumar/efeitos adversos
13.
J Ethnopharmacol ; 247: 112275, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31589966

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic retinopathy (DR) is a terrible microvascular disorder causing blindness. Retinal inflammation is the early stage in DR, which is believed to play a crucial role in the development of it. Shengpuhuang-tang (ST), a traditional herbal formula, which has effective treatment of fundus bleeding disorder. ST exerts protective effects against DR in rats, but its underlying mechanism of this efficacy remains unknown. Thus, the objective of this study is to examine the mechanism and the efficacy of ST on retinal inflammation in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: The administration of ST was initiated at 4 weeks after diabetes induction and continued for 12 weeks. Retinal vessel permeability was evaluated by using FITC-dextran and Evans blue. Retinal leukostasis was evaluated with FITC-coupled concanavalin A lectin (ConA). Moreover, western blotting was performed to detect TNF-α, ICAM-1 and the relative expression levels of IκBα, IKKß, and p65 in vivo. RESULTS: The results showed that the retinal inflammation in streptozotocin-induced diabetic rats was significantly decreased by ST. ST could decreased the expression levels of TNF-α, ICAM-1 and inhibited the expression of p-IKKß, p-p65 and IκBα. It could also inhibited the nuclear transfer of p65. CONCLUSIONS: In conclusion, these data suggested that ST may have potential treatment strategies against early stage of diabetic retinopathy through NF-κB pathway.


Assuntos
Diabetes Mellitus Experimental/complicações , Retinopatia Diabética/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Leucostasia/tratamento farmacológico , Vasos Retinianos/efeitos dos fármacos , Administração Oral , Animais , Capilares/efeitos dos fármacos , Capilares/metabolismo , Capilares/patologia , Permeabilidade Capilar/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Retinopatia Diabética/etiologia , Retinopatia Diabética/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Leucostasia/etiologia , Masculino , NF-kappa B/imunologia , NF-kappa B/metabolismo , Ratos , Vasos Retinianos/metabolismo , Vasos Retinianos/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Estreptozocina/toxicidade
14.
Am J Ophthalmol ; 209: 99-106, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31472160

RESUMO

PURPOSE: To correlate fractal dimension (FD) of the retinal vasculature with the extent of retinal nonperfusion area in diabetic retinopathy (DR) on ultrawide-field fluorescein angiography (FA). DESIGN: Cross-sectional study. METHODS: Baseline Optos 200Tx ultrawide-field FA images of 80 eyes with DR from the DAVE (NCT01552408) and RECOVERY (NCT02863354) studies were stereographically projected at the Doheny Image Reading Center. The retinal vasculature was extracted from an early-phase FA frame by exploiting the elongated nature of the vessels and then skeletonized for calculation of FD using a box-counting method. The nonperfusion area was delineated by 2 independent, reading center-certified graders who were masked to the study groups and who were using a standardized protocol and then computed in millimeters squared. RESULTS: While no difference in FD was observed for the entire retina in DR compared with normal control subjects, a significantly smaller FD was found in the far-periphery of the DR eyes (P < .001). FD for the entire retina was negatively associated with global nonperfusion area (R = -0.44; P < .001), and this relationship was also present within the 3 concentric retinal zones (posterior: R = -0.31, P = .016; midperiphery: R = -0.35, P = .007; and far periphery: R = -0.31, P = .015). CONCLUSIONS: Peripheral FD on ultrawide-field FA is reduced in DR eyes compared with normal eyes and is correlated with severity of retinal nonperfusion. FD can be calculated automatically without the need for correction of peripheral distortion, and therefore it may prove to be a useful surrogate biomarker when precise quantification of nonperfusion is not feasible.


Assuntos
Retinopatia Diabética/fisiopatologia , Fractais , Isquemia/fisiopatologia , Edema Macular/fisiopatologia , Vasos Retinianos/patologia , Adulto , Inibidores da Angiogênese/uso terapêutico , Terapia Combinada , Estudos Transversais , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/terapia , Feminino , Angiofluoresceinografia/métodos , Humanos , Injeções Intravítreas , Isquemia/diagnóstico , Fotocoagulação a Laser , Edema Macular/diagnóstico , Edema Macular/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
15.
Am J Ophthalmol ; 209: 88-98, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31473216

RESUMO

PURPOSE: To compare the severity of macular vascular changes in children with sickle cell disease (SCD) vs age- and race-matched controls. DESIGN: Cross-sectional study. METHODS: Children (<18 years old) with HbSS and HbS variant (HbSC and HbS thalassemia) genotypes, and their age- and race-matched controls, were recruited between January 2017 and December 2018. All subjects underwent optical coherence tomography angiography (OCTA) scans centered on the fovea and temporal macula. Retinal thickness, superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density (VD), and foveal avascular zone (FAZ) size were measured and compared between HbSS and HbS variant vs controls. RESULTS: Thirty-four HbSS, 34 HbS variant (Goldberg staging 0-3 for SCD eyes), and 24 control eyes (total 48 children, aged 5-17 years) were included. Total VD (3-mm ETDRS circle) was lower in HbS variant eyes than in controls for both the SCP (42.9% vs 47.7%, P = .02) and DCP (47.4% vs 52.6%, P = .01). In HbSS eyes, VD was lower in the DCP (47.7%, P = .008) but not in the SCP (45.5%, P = .5), compared to controls. A higher proportion of HbSS (n = 18, 55%) than HbS variant eyes (n = 9, 26%) had pathologic areas of retinal thinning associated with SCP and DCP flow loss (P = .03). However, retinal thickness measurements and FAZ size did not differ between either HbSS or HbS variant group vs controls. CONCLUSIONS: Children with SCD have similar retinal thickness but less dense vasculature on OCTA compared to age and race-matched controls, suggesting that microvascular insult may precede structural thinning.


Assuntos
Anemia Falciforme/diagnóstico , Retina/patologia , Doenças Retinianas/diagnóstico , Vasos Retinianos/patologia , Adolescente , Anemia Falciforme/fisiopatologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Angiofluoresceinografia/métodos , Hemoglobina Falciforme/metabolismo , Humanos , Masculino , Tamanho do Órgão , Estudos Prospectivos , Doenças Retinianas/fisiopatologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologia
16.
Am J Ophthalmol ; 209: 206-212, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31526797

RESUMO

PURPOSE: To compare retinal vessel density in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) to age-matched healthy eyes by using projection-resolved optical coherence tomography angiography (PR-OCTA). DESIGN: Prospective cross-sectional study. METHODS: Study participants underwent macular 3- × 3-mm OCTA scans with spectral domain OCTA. Reflectance-compensated retinal vessel densities were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Quantitative analysis using normalized deviation compared the retinal vessel density in GA regions, 500-µm GA rim regions, and non-GA regions to similar macular locations in control eyes. RESULTS: Ten eyes with GA and 10 control eyes were studied. Eyes with GA had significantly lower vessel density in the SVC (54.8 ± 2.4% vs. 60.8 ± 3.1%; P < 0.001), ICP (34.0 ± 1.5% vs. 37.3 ± 1.7%; P = 0.003) and DCP (24.4 ± 2.3% vs. 28.0 ± 2.3%; P < 0.001) than control eyes. Retinal vessel density within the GA region decreased significantly in SVC, ICP, and DCP. Retinal vessel density in the GA rim region decreased in SVC and ICP but not in DCP. The non-GA region did not significantly deviate from normal controls. Eyes with GA had significantly reduced photoreceptor layer thickness; but similar nerve fiber layer, ganglion cell complex, inner nuclear layer, and outer plexiform layer thickness. CONCLUSIONS: Eyes with GA have reduced retinal vessel density in SVC, ICP, and DCP compared to those in controls. Loss is greatest within regions of GA. Vessel density may be more sensitive than retinal layer thickness measurement in the detection of inner retinal change in eyes with GA.


Assuntos
Atrofia Geográfica/diagnóstico , Degeneração Macular/complicações , Vasos Retinianos/patologia , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Estudos Transversais , Feminino , Angiofluoresceinografia/métodos , Fundo de Olho , Atrofia Geográfica/etiologia , Atrofia Geográfica/fisiopatologia , Humanos , Pressão Intraocular , Masculino , Estudos Prospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologia
17.
Ophthalmic Surg Lasers Imaging Retina ; 50(12): 771-778, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31877222

RESUMO

BACKGROUND AND OBJECTIVE: To explore the effect of peripheral ischemia identified on ultra-widefield fluorescein angiography (UWFA) as a biomarker of response to a switch in therapy from bevacizumab to aflibercept in persistent diabetic macular edema (DME). PATIENTS AND METHODS: Prospective clinical trial of 38 eyes from 38 patients previously treated with bevacizumab and persistent DME. Patients subsequently received aflibercept per protocol and were followed up for 48 weeks. UWFA was obtained for all patients at baseline and 48 weeks. Images were graded and used to calculate an overall ischemic index (II) and macular ischemic index (MII). II was compared with visual and central macular thickness (CMT) outcomes. Paired and independent samples t-tests and Fisher's exact tests were used to assess change and associations. RESULTS: Patients with an II greater than or equal to 50% at baseline had a poorer baseline visual acuity (VA) (60.1 ± 10.2 vs. 70.7 ± 9.0 letters; P = .005) and a worse MII (6.9 ± 25 vs. 56 ± 52%; P < .001). These patients gained significantly more vision at 48 weeks (8.3 ± 9.3 vs. 2.6 ± 5.9 letters; P = .03). At 48 weeks, there was no significant difference in VA of patients with an II greater or less than 50% (68.4 ± 6.0 vs. 73.3 ± 9.6 letters; P = .16). CONCLUSIONS: Patients with persistent DME treated with bevacizumab and worse II had poorer baseline VA, potentially due to worse macular ischemia. These patients had greater visual gain with similar final visual outcomes of those without marked peripheral ischemia subsequent to switching to aflibercept. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:771-778.].


Assuntos
Inibidores da Angiogênese/uso terapêutico , Biomarcadores , Retinopatia Diabética/tratamento farmacológico , Isquemia/diagnóstico , Edema Macular/tratamento farmacológico , Doenças Retinianas/diagnóstico , Vasos Retinianos/patologia , Idoso , Bevacizumab/uso terapêutico , Retinopatia Diabética/fisiopatologia , Substituição de Medicamentos , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia
18.
PLoS One ; 14(12): e0226629, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31887149

RESUMO

PURPOSE: To quantify vessel tortuosity and fractal dimension of the superficial capillary plexus (SCP) of the macula in different stages of diabetic retinopathy (DR), and following panretinal photocoagulation (PRP) using optical coherence tomography angiography (OCTA). METHODS: 75 eyes of 75 subjects were divided into five groups; healthy controls, diabetes with no clinical DR, non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and patients who received PRP for PDR (PDR+PRP).For vessel tortuosity, SCP slabs from 3x3 mm macular OCTA scans were processed using imageJ (NIH, USA), where large perifoveal vessels were traced and their length was measured with tortuosity calculated as the ratio between the actual length and the straight Euclidean length. For fractal dimension, SCP slabs were processed and imported to Fractalyse (ThéMA, France), where box-counting analyses produced fractal dimension values. RESULTS: We found a significant difference in vessel tortuosity and fractal dimension between the five groups (one-way ANOVA, p < 0.001both). NPDR and PDR had significantly more tortuous vessels and lower fractal dimension compared to healthy controls (Tukey HSD: p = 0.02, 0.015,0.015 and <0.001, respectively). Fractal dimension was also significantly lower in NPDR and PDR compared to eyes with no clinical DR (p <0.001 both), and in PDR compared to NPDR (p = 0.014). Following PRP, vessel tortuosity was significantly lower and fractal dimension was higher in PDR+PRP compared to PDR (p = 0.001 and 0.031, respectively). CONCLUSIONS: We used macular OCTA scans to demonstrate significantly higher perifoveal large vessel tortuosity, and lower fractal dimension in NPDR and PDR compared to healthy controls. Vessel tortuosity shows more dramatic normalization than fractal dimension and could be explored as a sensitive marker for successful PRP.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Retinopatia Diabética/diagnóstico por imagem , Fotocoagulação a Laser/métodos , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Estudos de Casos e Controles , Retinopatia Diabética/patologia , Feminino , Fractais , Humanos , Masculino , Pessoa de Meia-Idade , Vasos Retinianos/patologia , Estudos Retrospectivos , Resultado do Tratamento
19.
PLoS One ; 14(12): e0226728, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31869361

RESUMO

BACKGROUND: Optical coherence tomography is commonly used to measure the retinal nerve fibre layer thickness in both normal and diseased eyes; however, variation among normal eyes is common and may limit the usefulness of the results. The aim of this study was to explore the interocular asymmetries in retinal nerve fibre layer thickness in a group of normal eyes and to investigate the influence of blood vessel diameter on local retinal nerve fibre layer thickness. METHODS: In this prospective study, retinal nerve fibre layer thickness and blood vessel diameter across 100 healthy participants were measured using two optical coherence tomography instruments. Individuals were categorised into two groups based on the presence or absence of interocular retinal nerve fibre layer thickness asymmetry beyond the 75th percentile of all participants. RESULTS: The superonasal sectoral retinal nerve fibre layer thickness was significantly greater in the left eye compared to the right, across all three sectors. Mean blood vessel diameter showed a corresponding difference in thickness at one of the superonasal sectors. Linear regression showed a positive and moderate correlation between blood vessel diameter and focal retinal nerve fibre layer thickness. This trend persisted across both arteries and veins, but veins showed larger variability between left and right eye in participants with marked superonasal retinal nerve fibre layer asymmetry. CONCLUSION: Retinal nerve fibre layer thickness and blood vessel diameter vary significantly between eyes even in healthy individuals. These asymmetries in a normal population should be taken into consideration when interpreting the retinal nerve fibre layer thickness measurements from optical coherence tomography to assist in distinguishing normal variations from disease.


Assuntos
Retina/diagnóstico por imagem , Doenças Retinianas/diagnóstico por imagem , Células Ganglionares da Retina/patologia , Vasos Retinianos/diagnóstico por imagem , Adulto , Idoso , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Retina/patologia , Doenças Retinianas/patologia , Células Ganglionares da Retina/citologia , Vasos Retinianos/anatomia & histologia , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Adulto Jovem
20.
Ophthalmic Surg Lasers Imaging Retina ; 50(11): 702-708, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755969

RESUMO

BACKGROUND AND OBJECTIVE: To evaluate the retinal and vasculature changes in infants with congenital Zika syndrome (CZS) using fluorescein angiography (FA). PATIENTS AND METHODS: This consecutive case series included six infants with CZS. FA and color fundus imaging were performed under general anesthesia in both eyes of all infants using a contact widefield digital imaging system. All color fundus images were obtained using a 130° field of view lens, and the FA images were captured using either a 130° or 80° field of view lens. The immunoglobulin M antibody capture enzyme-linked immunosorbent assay was positive for Zika virus in the cerebrospinal fluid samples of all infants. Other congenital infections were ruled out. RESULTS: The mean ± standard deviation age of the infants at the time of examination was 1.4 years ± 0.1 years (range: 1.3 years to 1.5 years). Contact fundus photographs showed macular abnormalities in seven eyes (58%) and retinal vasculature changes in two eyes (17%). FA detected macular abnormalities in all 12 eyes (100%) and retinal vasculature changes in five eyes (42%). The main retinal vasculature changes were peripheral avascularity in five eyes (42%) and microvasculature abnormalities in three eyes (25%). CONCLUSION: FA may be an important tool for detecting subtle macular and retinal vasculature changes in CZS. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:702-708.].


Assuntos
Macula Lutea/irrigação sanguínea , Vasos Retinianos/patologia , Infecção por Zika virus/patologia , Feminino , Angiofluoresceinografia , Humanos , Lactente , Masculino
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