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1.
BMC Med Genet ; 21(1): 25, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32028915

RESUMO

BACKGROUND: The aim of this study was to explore the association between diabetic retinopathy (DR) and the variants of uncoupling proteins (UCPs) genes in a Chinese population of type 2 diabetes, in total and in patients of different glycemic status separately. METHODS: This case-control study included a total of 3107 participants from two datasets, among which 662 were DR patients (21.31%). Eighteen tag single nucleotide polymorphisms (SNPs) of UCP1, UCP2, and UCP3 were selected as genetic markers. TaqMan probes, Sequenom MassARRAY MALDI-TOF mass spectrometry platform and Affymetrix Genome-Wide Human SNP Array were used for genotyping. Online SHEsis software was used for association analysis. Bonferroni correction was used for multiple comparisons correction. RESULTS: Three SNPs of UCP1: rs7688743 (A allele, OR = 1.192, p = 0.013), rs3811787 (T allele, OR = 0.863, p = 0.023), and rs10011540 (G allele, OR = 1.368, p = 0.004) showed association with DR after the adjustment of glucose, but only rs10011540 was marginally significantly associated with DR when Bonferroni correction was strictly applied (padj = 0.048). In patients with uncontrolled glucose, rs7688743 (A allele, p = 0.012, OR = 1.309), rs10011540 (G allele, p = 0.033, OR = 1.432), and rs3811787 (T allele, p = 0.022, OR = 0.811) were associated with DR, while in participants with well controlled glucose, the rs2734827 of UCP3 was associated with DR (A allele, p = 0.017, OR = 0.532). Rs3811787 of UCP1 showed a protective effect to sight threatening DR (T allele, p = 0.007, OR = 0.490), and the association existed after the adjustment for environmental factors and the correction. In patients with uncontrolled glucose, the rs3811787 of UCP1 (T allele, p = 0.017, OR = 0.467) and the rs591758 of UCP3 (C allele, p = 0.026, OR = 0.103) were associated with STDR. While in those with well controlled glucose, only the rs7688743 of UCP1 showed a protective effect (A allele, p = 0.024, OR = 0.049). None of the associations remain significant when Bonferroni correction was strictly applied (all p < 0.05). CONCLUSIONS: The rs10011540 and rs3811787 of the UCP1 gene was marginally significantly associated with DR in Chinese type 2 diabetes patients. There might be different mechanisms of DR development in patients with different glycemic status.


Assuntos
Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/genética , Predisposição Genética para Doença , Proteína Desacopladora 1/genética , Idoso , Alelos , Retinopatia Diabética/fisiopatologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Desacoplamento Mitocondrial/genética , Polimorfismo de Nucleotídeo Único/genética , Proteína Desacopladora 2/genética , Proteína Desacopladora 3/genética
2.
Am J Pathol ; 190(3): 630-641, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32093902

RESUMO

The investigation of erythropoietin (EPO) has expanded to include potential nonhematopoietic roles in neural and retinal diseases, including diabetic retinopathy. However, it remains unclear how EPO functions to support the neural retina. Transgenic mice with hypoactive EPO receptor (EPOR) signaling (hWtEPOR) were compared with littermate control mice (WT) to test the role of EPOR signaling under normal conditions and after vascular injury and regrowth into the retina. Although retinal function tested with OptoMotry and electroretinography was comparable to adult (8-week-old) littermate WT mice, hWtEPOR mice had thinner inner and outer plexiform layers and a greater number of amacrine cells. Injury and repair caused by the oxygen-induced retinopathy model reduced visual acuity thresholds, reduced electroretinography amplitudes, and thinned the outer plexiform and inner nuclear layers of both WT and hWtEPOR 8-week-old mice. In hWtEPOR compared with WT mice, scotopic a-wave amplitudes were reduced by injury, despite no change in outer nuclear layer thickness; and peripheral rod, but not cone number, was reduced. Scotopic b-waves were reduced in injured hWtEPOR mice compared with WT, and rod bipolar cell ectopic neurites were increased in both genotypes after injury, suggesting a potential reparative process to preserve connectivity and the b-wave. Normal EPOR signaling appeared important because ectopic neurites and b-waves were lower in the hWtEPOR than WT injured mice.


Assuntos
Retinopatia Diabética/fisiopatologia , Eritropoetina/metabolismo , Receptores da Eritropoetina/metabolismo , Doenças Retinianas/fisiopatologia , Transdução de Sinais , Lesões do Sistema Vascular/fisiopatologia , Animais , Eletrorretinografia , Eritropoetina/genética , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Receptores da Eritropoetina/genética , Retina/fisiopatologia
3.
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
4.
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
5.
Eur J Ophthalmol ; 30(1): 34-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30539668

RESUMO

PURPOSE: To compare the outcome of the sequence in the two treatments (intravitreal ranibizumab and panretinal photocoagulation) in high-risk proliferative diabetic retinopathy. METHODS: This retrospective study included 35 patients with newly diagnosed high-risk proliferative diabetic retinopathy in 43 eyes; 18 (22 eyes) received intravitreal ranibizumab before panretinal photocoagulation (intravitreal ranibizumab+ group), while the other 17 (21 eyes) received panretinal photocoagulation before intravitreal ranibizumab (panretinal photocoagulation+ group). Each subject received three intravitreal ranibizumabs that were interleaved with three panretinal photocoagulations. The first treatment (either intravitreal ranibizumab or panretinal photocoagulation) was done 1 week before the second one. The interval between intravitreal ranibizumabs was 4 weeks, panretinal photocoagulation was 2 weeks. The power and pulse duration were determined based upon the status of each retinal spot before each panretinal photocoagulation. The retinal non-perfusion region was measured with fundus fluorescein angiography before and 1 month after the final treatment. The central macular thickness was measured with optical coherence tomography within 1 week before the first treatment, before each panretinal photocoagulation, and 1 month after the final intravitreal ranibizumab. RESULTS: The panretinal photocoagulation energy required for effective treatment was lower in intravitreal ranibizumab+ group in the first and second sessions and in total energy (p < 0.05). Central macular thickness reduction before the second panretinal photocoagulation session was significant in the intravitreal ranibizumab+ group (p < 0.05). CONCLUSION: The sequence used in intravitreal ranibizumab+ group showed clear advantages over that in panretinal photocoagulation+ group in the treatment of proliferative diabetic retinopathy, not only in the use of lower energy for panretinal photocoagulation but also in the more rapid regression of neovascularization and less need of additional treatment.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/terapia , Fotocoagulação a Laser , Ranibizumab/uso terapêutico , Adulto , Protocolos Clínicos , Terapia Combinada , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/cirurgia , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Retina/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual
6.
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
7.
Adv Exp Med Biol ; 1185: 335-339, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884634

RESUMO

Diabetic retinopathy (DR) is a multifaceted disease, combining the deleterious effects of hyperglycemia and the propensity for accumulation of reactive oxygen species. Studies indicate that auto-oxidation of glucose, reduced antioxidant activity, and metabolic aberrations contribute to the pathogenesis of DR. These abnormalities stem from a fundamental imbalance between ROSs and antioxidant scavengers. To correct this imbalance and downstream effects, we propose that superoxide dismutase 3 (SOD3) is a viable therapeutic target for DR.


Assuntos
Retinopatia Diabética/fisiopatologia , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Antioxidantes/metabolismo , Diabetes Mellitus , Humanos , Espécies Reativas de Oxigênio/metabolismo
8.
Adv Exp Med Biol ; 1185: 575-579, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884673

RESUMO

The retina and RPE together constitute the most metabolically active ecosystem in the body, harboring high levels of flavins. Although diabetic patients have been reported to suffer from riboflavin deficiency and use of flavins as nutritional interventions to combat diabetic insult on other tissues have been investigated, such attempts have never been tested for the retina to avoid diabetic retinopathy. Furthermore, the role of flavins in pathophysiology of the retina and RPE has mostly been overlooked. Herein, we review the impact of flavins on various clinical manifestations of diabetic retinopathy and discuss possible ways to address them.


Assuntos
Retinopatia Diabética/fisiopatologia , Flavinas/fisiologia , Epitélio Pigmentado da Retina/patologia , Diabetes Mellitus , Humanos
9.
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
10.
Invest Ophthalmol Vis Sci ; 60(14): 4865-4871, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31747687

RESUMO

Purpose: To evaluate the perfusion status of the retina and choriocapillaris in the area of laser scars on swept-source optical coherence tomography angiography (OCTA) images of eyes previously treated with panretinal photocoagulation (PRP). Methods: Cross-sectional exploratory analysis of swept-source OCTA images, which were retrospectively reviewed for laser scars. The appearance of the capillary networks in the area of previous laser were evaluated following a three-step grading system (normal/sparse/missing capillary network). The superficial and deep capillary plexus of the retina and the choriocapillaris were graded separately. Results: A total of 3140 laser scars in 54 eyes of 31 patients (13 female, mean age 57 ± 12 years) were included in this analysis. In the retina, 6.8% of the superficial and deep capillary network in the area evaluated appeared normal, 58% and 56% sparse, and 35% and 37% missing. Capillary dropout in the retina was not restricted to the area of prior laser treatment. The choriocapillaris decorrelation signal was either sparse (61%) or completely missing (38%) within the laser scar area. The perfusion of the choriocapillaris appeared normal in the area adjacent to laser scars. Conclusions: Capillary non-perfusion in the choriocapillaris was found within the laser scar area. Laser treatment seems to cause sustained non-perfusion of choriocapillaris in the area treated.


Assuntos
Corioide/irrigação sanguínea , Cicatriz/fisiopatologia , Retinopatia Diabética/fisiopatologia , Fotocoagulação a Laser , Vasos Retinianos/fisiologia , Idoso , Capilares/fisiologia , Cicatriz/diagnóstico , Estudos Transversais , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/cirurgia , Feminino , Angiofluoresceinografia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/fisiologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
11.
Ophthalmic Surg Lasers Imaging Retina ; 50(11): e300-e310, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755982

RESUMO

BACKGROUND AND OBJECTIVE: Diabetic macular edema (DME) is a leading cause of vision loss worldwide. The object of this study is to compare global differences of baseline characteristics of patients undergoing initiation of anti-vascular endothelial growth factor (VEGF) therapy for DME. PATIENTS AND METHODS: This multicenter, cross-sectional study included diabetic patients with foveal-involving retinal edema secondary to DME as documented by fundus exam and optical coherence tomography who were undergoing initiation of intravitreal anti-VEGF drugs. Variables were collected to find possible risk factors and to create an epidemiological profile of DME patients undergoing initiation of anti-VEGF agents. RESULTS: Nine hundred two patients were selected. Mean age was 62.4 (±11) years, 49.7% were Caucasians, 57.6% were male, and 96% had type two diabetes with an average disease duration of 181.7 months ± 113 months. Of the patients included, 74.7% suffered from hypertension, 26.6% from cardiovascular disease, 12.1% from cerebrovascular disease, 12.8% from peripheral vascular disease, and 12.8% from renal insufficiency. Best-corrected visual acuity (BCVA) was 65 (±20) Early Treatment Diabetic Retinopathy Study letters, central subfield thickness was 364 (±162) µm, cube volume 11.1 ± 3.1 mm3, cube average thickness 328.8 µm ± 61 µm, and 63.9% had nonproliferative diabetic retinopathy. Comparison between U.S. versus international patients, and patients with BCVA 70 letters or less versus more than 70 letters were performed, significant differences were acknowledged, and risk factors were recognized. CONCLUSION: There were key differences in the epidemiologic profile between patients presenting with DME in the U.S. and internationally. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e300-e310.].


Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética , Edema Macular , Ranibizumab/uso terapêutico , Idoso , Estudos Transversais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Edema Macular/patologia , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Retina/patologia , Fatores de Risco , Acuidade Visual/fisiologia
12.
Invest Ophthalmol Vis Sci ; 60(14): 4711-4716, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31725170

RESUMO

Purpose: Neuroretinopathy is increasingly being recognized as an independent cause of vision loss in diabetes. Visual field loss, as detected by frequency doubling technology (FDT)-based visual perimetry, is a sign of neuroretinopathy and occurs in early stages of diabetic retinopathy (DR). Here, we hypothesized that FDT visual field testing could identify patients with diabetic neuroretinopathy in the absence of clinically detectable microvascular DR. Methods: All National Health and Nutrition Examination Survey (NHANES) 2005-2008 participants receiving fundus photography and visual field screening by FDT were included in this study. Participants with self-reported glaucoma, use of glaucoma medications, or determination of glaucoma based on disk features were excluded. Visual fields were screened using FDT protocol in which participants underwent a 19-subfield suprathreshold test. Results: Patients with diabetes but no DR were more likely to have ≥1 subfield defects at 5%, 2%, and 1% probability levels than patients without diabetes (41.3% vs. 28.6%; 27.4% vs. 17.5%; 15.9% vs. 9.4%; all P < 0.0008). Multivariable regression showed that each additional glycated hemoglobin % (HbA1c) was associated with 19% greater odds of having ≥1 visual subfield defects in those with diabetes without DR (odds ratio: 1.19, 95% confidence interval: 1.07-1.33; P = 0.0020). Conclusions: Patients with diabetes have visual field defects in the absence of clinically detectable DR, suggesting neuroretinopathy precedes classical microvascular disease. These defects become more frequent with the onset of visible retinopathy and worsen as the retinopathy becomes more severe. Longitudinal studies are required to understand the pathogenesis of diabetic neuroretinopathy in relation to classic DR.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Retinopatia Diabética/diagnóstico , Transtornos da Visão/diagnóstico , Campos Visuais/fisiologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/fisiopatologia , Feminino , Hemoglobina A Glicada/metabolismo , Inquéritos Epidemiológicos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fotografação , Transtornos da Visão/fisiopatologia , Testes de Campo Visual
13.
Medicine (Baltimore) ; 98(46): e17792, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725621

RESUMO

OBJECTIVE: The primary aim of this study is to examine the hemodynamics of retrobulbar and intrarenal in the changes of early stage of type 2 diabetes mellitus (T2DM) patients from 2000 to 2015 and to assess incidence associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR). METHOD: Our study contained 60 subjects newly diagnosed of T2DM were divided into 2 groups base on the mean resistive index (RI) (≤0.7 and >0.7) of hemodynamic and to compare between-group differences of the early changes in hemodynamics of retrobulbar and intrarenal and also to conclude the incidences of diabetic kidney disease (DKD) and diabetic retinopathy (DR)subsequently with a long follow-up duration(2000-2015). First, to compare the mean RI of central retinal artery (CRA) between 2 groups. Second, to compare the mean RI of intrarenal hemodynamics in the bilateral interlobular renal arteries, renal function parameters (blood urea nitrogen (BUN), creatinine (Cr), blood glucose parameters (glycosylated hemoglobinA1c (HbA1c), fasting plasma glucose (FBG), and 2-hour postprandial blood glucose (2hPBG)), glomerular filtration rate (GFR), albumin excretion rate (AER), and urine albumin-to-creatinine ratio (UACR) between 2 groups. RESULTS: First part of our follow-up studies was to compare hemodynamic RI index of retrobulbar in years of 2000 and 2015, both renal function and blood glucose parameters were fund significantly enhanced in subject group RIs ≤0.7. Incidence of DKD and DR was notably lower in group RIs ≤0.7 than group RIs > 0.7, difference was statistically significant (P < .05). Incidence of HbA1c ≤7% was higher in group RIs ≤0.7 than group RIs >0.7, but difference was not statistically significant (P > .05). Incidence of proliferative diabetic retinopathy (PDR) was notably lower in group RIs ≤0.7 than group RIs >0.7, but the difference was not statistically significant (P > .05). Second part of our follow-up studies was to compare hemodynamic RI index of interlobular renal in years of 2000 and 2015, both renal function and blood glucose parameters were fund significantly enhanced in subject group RIs ≤0.7. Compared data of various incidences from first part of study were coherent with second part. (Incidence of DKD and DR was notably lower in group RIs ≤0.7 than group RIs >0.7, difference was statistically significant (P < .05). Incidence of HbA1c ≤7% was higher in group RIs ≤0.7 than group RIs >0.7, but difference was not statistically significant (P > .05). Incidence of PDR was notably lower in group RIs ≤0.7 than group RIs >0.7, but the difference was not statistically significant (P > .05). CONCLUSIONS: RIs of retrobulbar and interlobular renal which would serve as a good predictors for the hemodynamics changes in retrobulbar and intrarenal would assess incidence of DKD and DR during the preclinical stage in long-term range excluding renal function and HbA1c in T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/fisiopatologia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/fisiopatologia , Idoso , Glicemia , Feminino , Seguimentos , Hemoglobina A Glicada , Hemodinâmica/fisiologia , Humanos , Rim/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Artéria Renal/fisiopatologia , Artéria Retiniana/fisiopatologia
14.
Curr Med Sci ; 39(5): 754-758, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612393

RESUMO

The aim of this research was to study the clinical features and microvascular complications risk factors of early-onset type 2 diabetes mellitus (T2DM). We analyzed the clinical data from 1421 T2DM inpatients at Wuhan Union Hospital. Subjects were divided into early-onset T2DM group (diagnostic age <40 years) and late-onset T2DM group (diagnostic age >40 years). All subjects underwent a standardized assessment of microvascular complications. Data were compared with independent-samples t test or Chi-square test. Multiple logistic regression was used to determine the risk factors of microvascular complications. Patients with early-onset T2DM were more inclined to have a lower systolic blood pressure (SBP), a longer duration of diabetes and higher levels of body mass index (BMI), uric acid (UA), fasting plasma glucose (FPG), total cholesterol (TC)- triglyceride (TG) and glycosylated hemoglobin (HbA1c) than those with late-onset T2DM (P<0.05). The prevalence of diabetic retinopathy (DR) was significantly higher and that of diabetic peripheral neuropathy (DPN) was significantly lower in early-onset group than in late-onset group (P<0.05). For DN, UA was an independent risk factor in early-onset T2DM. SBP and TG were independent risk factors in late-onset T2DM. For DR, duration of diabetes and SBP were independent risk factors in early-onset T2DM. Duration of diabetes, SBP and HbA1c were independent risk factors in late-onset T2DM. This study demonstrated that the clinical characteristics of early-onset T2DM were metabolic disorders, including glucose metabolism, lipid metabolism and amino acid metabolism. Early-onset T2DM was more likely to be associated with DR. The potential pathogenesis of early and late-onset T2DM might be different. The management of metabolic risk factors especially HbA1c, SBP, TG and UA is advised to be performed in the early stage of diabetes.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Retinopatia Diabética/fisiopatologia , Ácido Úrico/sangue , Adulto , Idade de Início , Idoso , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/complicações , Retinopatia Diabética/sangue , Retinopatia Diabética/complicações , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Rim/irrigação sanguínea , Rim/metabolismo , Rim/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Retina/metabolismo , Retina/patologia , Fatores de Risco , Triglicerídeos/sangue
15.
Invest Ophthalmol Vis Sci ; 60(13): 4310-4318, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622467

RESUMO

Purpose: To evaluate whether retinal capillary nonperfusion is found predominantly adjacent to arteries or veins in eyes with diabetic retinopathy (DR). Methods: Sixty-three eyes from 44 patients with proliferative DR (PDR) or non-PDR (NPDR) were included. Images (12 × 12-mm) foveal-centered optical coherence tomography (OCT) angiography (OCTA) images were taken using the Zeiss Plex Elite 9000. In 37 eyes, widefield montages with five fixation points were also obtained. A semiautomatic algorithm that detects nonperfusion in full-retina OCT slabs was developed, and the percentages of capillary nonperfusion within the total image area were calculated. Retinal arteries and veins were manually traced. Based on the shortest distance, nonperfusion pixels were labeled as either arterial-side or venous-side. Arterial-adjacent and venous-adjacent nonperfusion and the A/V ratio (arterial-adjacent nonperfusion divided by venous-adjacent nonperfusion) were quantified. Results: Twenty-two eyes with moderate NPDR, 16 eyes with severe NPDR, and 25 eyes with PDR were scanned. Total nonperfusion area in PDR (median: 8.93%) was greater than in moderate NPDR (3.49%, P < 0.01). Arterial-adjacent nonperfusion was greater than venous-adjacent nonperfusion for all stages of DR (P < 0.001). The median A/V ratios were 1.93 in moderate NPDR, 1.84 in severe NPDR, and 1.78 in PDR. The A/V ratio was negatively correlated with the total nonperfusion area (r = -0.600, P < 0.0001). The results from the widefield montages showed similar patterns. Conclusions: OCTA images with arteries and veins traced allowed us to estimate the nonperfusion distribution. In DR, smaller nonperfusion tends to be arterial-adjacent, while larger nonperfusion tends toward veins.


Assuntos
Retinopatia Diabética/fisiopatologia , Isquemia/fisiopatologia , Artéria Retiniana/fisiopatologia , Veia Retiniana/fisiopatologia , Idoso , Capilares/fisiopatologia , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico por imagem , Feminino , Angiofluoresceinografia , Humanos , Isquemia/diagnóstico por imagem , Edema Macular/diagnóstico por imagem , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Retiniana/diagnóstico por imagem , Veia Retiniana/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
16.
Turk J Ophthalmol ; 49(4): 194-200, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31486606

RESUMO

Objectives: To evaluate the relationship between cyst characteristics and macular and peripheral ischemia in diabetic macular edema (DME). Materials and Methods: We retrospectively reviewed eyes with DME and included those with clinically significant macular edema as defined by ETDRS (Early Treatment Diabetic Retinopathy Study) and cystoid spaces in optical coherence tomography scans in this study. Central subfield thickness (CSFT), horizontal and vertical diameters of the largest cyst, cyst area, and the remaining retinal thickness outside the cyst were determined. The presence and number of hyperreflective foci in the cyst wall and the internal reflectivity of the cyst were analyzed. Outer retinal damage was graded. Fluorescein angiography was used to determine the areas of macular and peripheral ischemia, which were graded as mild or severe. Correlations between macular and peripheral ischemia and cyst-related measurements and structural changes in the retina were evaluated. Results: This retrospective study included 250 eyes of 186 patients with DME. Mean CSFT was significantly greater in eyes with macular ischemia (510.4±144.7 µm) compared to eyes without macular ischemia (452.1±114.6 µm) (p=0.001). Horizontal and vertical diameter of the largest cyst increased with the presence and severity of macular ischemia (p=0.045 and p=0.016, respectively). Remaining retinal thickness increased with the presence and severity of peripheral ischemia (p=0.009). There was a statistically significant relationship between the number of the hyperreflective foci in the cyst wall and internal reflectivity of the cyst (p=0.007). Patients with greater CSFT had a 1.04-times higher odds of having macular ischemia and 0.25-times higher odds of having outer retinal damage. Conclusion: The likelihood of macular ischemia increases with larger cyst diameter, CSFT, and extent of outer retinal damage. Thickness of the noncystic area is increased in the presence of peripheral ischemia.


Assuntos
Cistos/patologia , Retinopatia Diabética/patologia , Edema Macular/patologia , Retina/patologia , Adulto , Idoso , Análise de Variância , Estudos Transversais , Retinopatia Diabética/fisiopatologia , Feminino , Angiofluoresceinografia , Humanos , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Retina/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual
17.
Invest Ophthalmol Vis Sci ; 60(12): 3762-3767, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31499531

RESUMO

Purpose: Diabetic retinopathy is characterized by disturbances in retinal blood flow mediated by capillary occlusion, intraretinal microvascular abnormalities (IRMAs), neovascularizations, and omega loops and reduplications. It is likely that the study of oxygen saturation in these abnormalities can provide knowledge about their role in the development of diabetic retinopathy. Methods: The oxygen saturation in IRMA vessels and venous loops and reduplications were studied in 40 diabetic patients with severe nonproliferative or proliferative diabetic retinopathy. The saturation values in the studied vascular abnormalities were compared to those of the larger retinal arterioles and venules. Results: There was a similar oxygen saturation (mean ± SD) in IRMAs observed to connect arterioles with venules (78.6% ± 11.8%, n = 22) and IRMAs connecting venules with venules (79.2% ± 9.0%, n = 12; P > 0.999). The saturation in IRMAs was significantly lower (P < 0.0002) than in arterioles (97.4% ± 5.2%, n = 40) and significantly higher (P < 0.0001) than the saturation in omega loops and reduplications (54.2% ± 19.3%, n = 6), which in turn showed no significant difference from the saturation in the venules (61.8% ± 6.8%, n = 40, P = 0.4). Conclusions: The findings suggest that the oxygen saturation in vascular abnormalities in diabetic retinopathy depends on the extent of arteriovenous (A-V) shunting, with venous saturation due to no A-V shunting in venous loops and reduplications, and intermediate oxygen saturation due to moderate shunting in IRMAs. This may precede the development of neovascularizations with arterial oxygen saturation due to high A-V shunting.


Assuntos
Malformações Arteriovenosas/fisiopatologia , Retinopatia Diabética/fisiopatologia , Oxigênio/sangue , Vasos Retinianos/anormalidades , Adulto , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Oximetria , Consumo de Oxigênio/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Artéria Retiniana/anormalidades , Artéria Retiniana/fisiologia , Veia Retiniana/anormalidades , Veia Retiniana/fisiologia , Vasos Retinianos/fisiopatologia , Acuidade Visual/fisiologia
18.
Expert Opin Investig Drugs ; 28(10): 861-869, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31513439

RESUMO

Introduction: The Tie-2/Angiopoietin pathway is a therapeutic target for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Activation of Tie-2 receptor via Ang-1 maintains vascular stability to limit exudation. Ang-2, a competitive antagonist to Ang-1, and VE-PTP, an endothelial-specific phosphatase, interfere with the Tie-2-Ang-1 axis, resulting in vascular leakage. Areas covered: Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials for nAMD and DME. Nesvacumab is an Ang-2 inhibitor; when coformulated with aflibercept, it failed to show benefit over aflibercept monotherapy in achieving visual gains in phase 2 studies of nAMD and DME. ARP-1536 is an intravitreally administered VE-PTP inhibitor undergoing preclinical studies. AKB-9778 is a subcutaneously administered VE-PTP inhibitor that, when combined with monthly ranibizumab, reduced DME more effectively than ranibizumab monotherapy in a phase 2 study. AKB-9778 monotherapy did not reduce diabetic retinopathy severity score compared to placebo. AXT107, currently in the preclinical phase, promotes conversion of Ang-2 into a Tie-2 agonist and blocks signaling through VEGFR2 and other receptor tyrosine-kinases. Expert opinion: Tie-2/Angiopoietin pathway modulators show promise to reduce treatment burden and improve visual outcomes in nAMD and DME, with potential to treat cases refractory to current treatment modalities.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Degeneração Macular/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Angiopoietina-1/antagonistas & inibidores , Angiopoietina-2/antagonistas & inibidores , Animais , Retinopatia Diabética/fisiopatologia , Humanos , Degeneração Macular/fisiopatologia , Edema Macular/tratamento farmacológico , Edema Macular/fisiopatologia , Receptor TIE-2/efeitos dos fármacos , Receptor TIE-2/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
BMC Ophthalmol ; 19(1): 200, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519158

RESUMO

BACKGROUND: To compare the reoperation rate in patients with vitreous hemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR) with or without preoperative intravitreal bevacizumab (IVB). METHODS: In this retrospective study, 280 patients (362 eyes) with diabetic VH were divided into a group that received preoperative IVB and a group that did not receive preoperative IVB. According to B-scan or color Doppler ultrasonography, the eyes were grouped as a VH group and a tractional retinal detachment (TRD) group. The reoperation rate, visual and anatomical outcomes of treatment were evaluated after 6 months. RESULTS: There were 17.4% of eyes in the VH group that did not receive preoperative IVB later required additional vitrectomy, while only 7.7% of the eyes in the VH group that received preoperative IVB required additional vitrectomy (P = 0.025). There were 45.5% of eyes in the TRD group that did not receive preoperative IVB had no reoperation, while only 21.4% of the eyes in the TRD group that received preoperative IVB had no reoperation (P = 0.004). The patients with one operation achieved better vision than those required reoperations in the VH group (P = 0.038) and TRD group (P = 0.019). CONCLUSIONS: Preoperative IVB significantly reduced the re-vitrectomy rate in patients with VH without TRD, but there was an increase in the reoperation rate in patients with VH combined with TRD.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Retinopatia Diabética/terapia , Vitrectomia , Hemorragia Vítrea/terapia , Idoso , Terapia Combinada , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/cirurgia , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Reoperação , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Ultrassonografia Doppler em Cores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Hemorragia Vítrea/tratamento farmacológico , Hemorragia Vítrea/fisiopatologia , Hemorragia Vítrea/cirurgia
20.
J. optom. (Internet) ; 12(3): 174-179, jul.-sept. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-185367

RESUMO

Purpose: The purpose of this study was to determine the relationship between HbA1c values and retinal sensitivity at central 10° using the MP-1 microperimeter. Methods: A prospective study was carried out on 32 healthy subjects (control group) and 60 diabetic patients. The diabetic patients were divided into 2 groups. Group 1 comprised of 30 patients without diabetic retinopathy (DR) and group 2 had 30 patients with mild non-proliferative DR. A full-threshold microperimetry of the central 10° of retina (the macula) was performed on all subjects, utilizing 32 points with the MP-1. The relationship between light sensitivity and HbA1c value was calculated using linear regression analysis. Results: Total mean sensitivity at 10° for group 1 without DR, group 2 with mild NPDR and control group were 18.67±0.83, 17.98±1.42 and 19.45±0.34 (dB), respectively. There was a significant difference in total mean retinal sensitivity at 10° between the 3 groups (F(2,89)=18.14, p=0.001). A simple linear regression was calculated to predict HbA1c based on retinal sensitivity. A significant regression equation was found (F(1,90)=107.61, p=0.0001, with an R2 of 0.545). The linear regression analysis revealed that there was a 0.64dB decline in mean retinal sensitivity within the central 10° diameter with an increase of 1mmHg of HbA1c. Conclusion: Retinal sensitivity at the central 10° of the macula is affected by changes in HbA1c values


Objetivo: El objetivo de este estudio fue determinar la relación entre los valores de HbA1c y la sensibilidad de la retina en los 10 grados centrales de la misma utilizando el microperímetro MP-1. Métodos: Se realizó un estudio prospectivo en 32 sujetos sanos (grupo control) y 60 pacientes diabéticos. Los pacientes diabéticos se dividieron en dos grupos: el grupo 1 se compuso de 30 pacientes sin retinopatía diabética (RD), y el grupo 2 incluyó a 30 pacientes con RD no proliferativa leve. Se realizó una microperimetría umbral total de los 10° centrales de la retina (la mácula) a todos los sujetos, utilizando 32 puntos con el MP-1. Se calculó la relación entre la sensibilidad retiniana y el valor de HbA1c utilizando un análisis de regresión lineal. Resultados: La sensibilidad media total a los 10° para el grupo 1 sin RD, el grupo 2 con NPDR leve y el grupo control fue de 18,67 ± 0,83, 17,98 ± 1,42 y 19,45 ± 0,34 (dB), respectivamente. Se observó una diferencia significativa en cuanto a sensibilidad media total de la retina a 10° entre los tres grupos (F(2,89) = 18,14, p = 0,001). Se realizó un análisis de regresión lineal simple para predecir HbA1c en base a la sensibilidad de la retina. Se encontró una ecuación de regresión significativa (F(1,9) = 107,61, p = 0,0001, con R2 de 0,545). El análisis de regresión lineal reveló que existe un descenso de 0,64dB de la sensibilidad media de la retina dentro del diámetro de 10° centrales con un incremento de 1 mmHg de HbA1c. Conclusión: La sensibilidad de la retina en los 10 grados centrales de la mácula se ve afectada por los cambios de los valores de HbA1c


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/fisiopatologia , Hemoglobina A Glicada/fisiologia , Retina/fisiopatologia , Campos Visuais/fisiologia , Análise de Variância , Estudos de Casos e Controles , Estudos Prospectivos , Análise de Regressão , Testes de Campo Visual
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