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1.
Med Clin North Am ; 105(3): 455-472, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33926641

RESUMO

The retinal vasculature is the only neurovascular system directly visible to the human eye, easily evaluated by fundoscopy and many imaging modalities. This window allows physicians to diagnose and treat retinal pathologies and detect systemic diseases including diabetes, hypertension, hypercoagulable/hyperviscosity syndromes, and vasculitis. Diabetic retinopathy is the most common retinal vascular disease, followed by retinal vein and artery occlusion. Patients with these conditions require medical optimization to prevent further damage to the eyes and to the other organs. Both the internists and medical subspecialists play a crucial role in the prevention, detection, evaluation, and management of vision-threatening retinal vascular diseases.


Assuntos
Retinopatia Diabética , Doenças Vasculares , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/etiologia , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/terapia , Humanos , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/etiologia , Oclusão da Artéria Retiniana/fisiopatologia , Oclusão da Artéria Retiniana/terapia , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Doenças Retinianas/fisiopatologia , Doenças Retinianas/terapia , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/etiologia , Oclusão da Veia Retiniana/fisiopatologia , Oclusão da Veia Retiniana/terapia , Doenças Vasculares/complicações , Doenças Vasculares/fisiopatologia
2.
Biomed Environ Sci ; 33(9): 701-707, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-33106215

RESUMO

Objective: To evaluate the association between diabetic retinopathy (DR) and mean ocular perfusion pressure (MOPP) in patients with type 2 diabetes mellitus (T2DM). Methods: Patients from the Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT), a community-based prospective cohort study conducted in northeast China, were included in this study. The presence and severity of DR were determined by grading fundus photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy scale. Systolic and diastolic blood pressure (SBP and DBP) were recorded using an electronic sphygmomanometer. Intraocular pressure (IOP) was measured using an iCare rebound tonometer. MOPP was calculated using the formula MOPP = 2/3 [DBP + 1/3 (SBP - DBP)] - IOP. Results: In total, 1,857 patients who had gradable fundus photography and MOPP data were enrolled in this study. Male patients had a higher MOPP than female patients (52.25 ± 8.75 vs. 50.96 ± 8.74 mmHg, P = 0.002). Overall, both male and female patients with any type of DR, non-proliferative DR (NPDR), or non-sight-threatening DR (non-STDR) had significantly higher MOPP relative to patients without DR. Increased MOPP (per 1 mmHg) was in turn associated with the presence of any type of DR [odds ratio ( OR) = 1.03, 95% confidence interval ( CI) : 1.02-1.04], NPDR ( OR= 1.03 95% CI: 1.02-1.04), and non-STDR ( OR= 1.03, 95% CI: 1.01-1.04) after adjusting for confounders. Increased MOPP (per 1 mmHg) was also associated with an increased likelihood of macular edema ( OR= 1.02 , 95% CI: 1.01-1.04). Conclusions: The results suggest that increased MOPP was associated with DR and macular edema in northeastern Chinese patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/epidemiologia , Pressão Intraocular/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Estudos Prospectivos , Fatores de Risco
4.
PLoS One ; 15(9): e0238727, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941450

RESUMO

PURPOSE: Female mice have been found to be resistant to streptozotocin (STZ)-induced diabetes, and pre-clinical research related to diabetic complications commonly omits females. The purpose of this study was to develop a method to induce diabetes in female mice, and to determine if retinas of diabetic female mice develop molecular changes and histopathological abnormalities comparable to those which develop in male diabetic mice. METHODS: To induce diabetes, animals of both sexes received daily intraperitoneal (i.p.) injection of STZ for 5 consecutive days at 55 mg/kg BW (a dose that is known to induce diabetes in male mice) or for females, 75 mg/kg BW of STZ. Retinal abnormalities that have been implicated in the development of the retinopathy (superoxide generation and expression of inflammatory proteins, iNOS and ICAM-1) were evaluated at 2 months of diabetes, and retinal capillary degeneration was evaluated at 8 months of diabetes. RESULTS: Daily i.p. injection of STZ for 5 consecutive days at a concentration of 55 mg/kg BW was sufficient to induce diabetes in 100% of male mice, but only 33% of female mice. However, females did become hyperglycemic when the dose of STZ administered was increased to 75 mg/kg BW. The resulting STZ-induced hyperglycemia in female and male mice was sustained for at least 8 months. After induction of the diabetes, both sexes responded similarly with respect to the oxidative stress, expression of iNOS, and degeneration of retinal capillaries, but differed in the limited population evaluated with respect to expression of ICAM-1. CONCLUSIONS: The resistance of female mice to STZ-induced diabetes can be overcome by increasing the dose of STZ used. Female mice can, and should, be included in pre-clinical studies of diabetes and its complications.


Assuntos
Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/fisiopatologia , Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Modelos Animais de Doenças , Caracteres Sexuais , Animais , Capilares/efeitos dos fármacos , Capilares/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Retina/efeitos dos fármacos , Retina/patologia , Estreptozocina/farmacologia
5.
PLoS One ; 15(9): e0238958, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915904

RESUMO

PURPOSE: To investigate the correlation between quantifiable vessel density, computed in an automated fashion, from ultra-widefield fluorescein angiography (UWFFA) images from patients with proliferative diabetic retinopathy (PDR) with visual acuity and macular thickness. METHODS: We performed a secondary analysis of a prospective randomized controlled trial. We designed and trained an algorithm to automate retinal vessel detection from input UWFFA images. We then used our algorithm to study the correlation between baseline vessel density and best corrected visual acuity (BCVA) and CRT for patients in the RECOVERY study. Reliability of the algorithm was tested using the intraclass correlation (ICC). 42 patients from the Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy (RECOVERY) trial who had both baseline UWFFA images and optical coherence tomography (OCT) data were included in our study. These patients had PDR without significant center-involving diabetic macular edema (central retinal thickness [CRT] ≤320µm). RESULTS: Our algorithm analyzed UWFFA images with a reliability measure (ICC) of 0.98. A positive correlation (r = 0.4071, p = 0.0075) was found between vessel density and BCVA. No correlation was found between vessel density and CRT. CONCLUSIONS: Our algorithm is capable of reliably quantifying vessel density in an automated fashion from baseline UWFFA images. We found a positive correlation between computed vessel density and BCVA in PDR patients without center-involving macular edema, but not CRT. TRANSLATIONAL RELEVANCE: Our work is the first to offer an algorithm capable of quantifying vessel density in an automated fashion from UWFFA images, allowing us to work toward studying the relationship between retinal vascular changes and important clinical endpoints, including visual acuity, in ischemic eye diseases.


Assuntos
Retinopatia Diabética/diagnóstico , Angiofluoresceinografia , Vasos Retinianos/patologia , Adulto , Algoritmos , Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Feminino , Angiofluoresceinografia/estatística & dados numéricos , Humanos , Interpretação de Imagem Assistida por Computador , Macula Lutea/patologia , Edema Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica , Acuidade Visual
6.
PLoS One ; 15(7): e0236867, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735583

RESUMO

PURPOSE: To compare the anatomical and functional outcomes of severe diabetic macular edema (DME) with massive hard exudates managed by pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling or nonsurgical treatment. METHODS: We retrospectively reviewed 40 eyes with DME and massive hard exudates treated with either PPV with ILM peeling (vitrectomy group, 21 eyes) or nonsurgical treatment with anti-vascular endothelium growth factor (VEGF) and/or steroids (nonsurgical group, 19 eyes). Changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) and resolution of macular hard exudates were compared between the two groups. RESULTS: After treatment, CRT decreased steadily in the vitrectomy group but fluctuated in the nonsurgical group. Compared with eyes in the nonsurgical group, eyes in the vitrectomy group had better visual improvement (P < 0.05 at 6 and 12 months and the final visit) and greater decrease in CRT (P < 0.05 at 3 and 6 months and the final visit) after adjustment for baseline BCVA. Hard exudates resolved more rapidly in the vitrectomy group than in the nonsurgical group, with 94.1% versus 47.4% eyes showing significant absorption after 6 months of the treatment (P = 0.003). In the vitrectomy group, 62% eyes did not require any further injections for treating DME after the operation. CONCLUSIONS: PPV with ILM peeling resulted in rapid resolution of hard exudates with significant anatomical and functional improvement in DME with massive hard exudates.


Assuntos
Retinopatia Diabética , Membrana Epirretiniana/cirurgia , Edema Macular , Vitrectomia/métodos , Idoso , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/cirurgia , Retinopatia Diabética/terapia , Feminino , Humanos , Edema Macular/fisiopatologia , Edema Macular/cirurgia , Edema Macular/terapia , Masculino , Pessoa de Meia-Idade , Retina/fisiopatologia , Doenças Retinianas/cirurgia , Doenças Retinianas/terapia , Estudos Retrospectivos , Resultado do Tratamento
7.
Diab Vasc Dis Res ; 17(7): 1479164120945910, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32746630

RESUMO

BACKGROUND: The effect of interarm blood pressure difference on the development of diabetic retinopathy, proteinuria and chronic kidney disease remains unknown. We investigated to determine the impact of interarm blood pressure difference on the prevalence of diabetic retinopathy, proteinuria and chronic kidney disease in patients with type 2 diabetes. METHODS: The study included 563 patients with diabetes, who were evaluated with a simultaneous bilateral blood pressure measurement. The cutoff values for interarm blood pressure difference were 5, 10 and 15 mmHg. Logistic regression analysis was used to explore the relation between interarm blood pressure difference and diabetic retinopathy, proteinuria and chronic kidney disease. RESULTS: Diabetic patients with systolic interarm blood pressure difference ⩾5, ⩾10 and ⩾15 mmHg showed an increased risk of diabetic retinopathy [adjusted odds ratio = 1.48 (95% confidence interval = 1.01-2.18), odds ratio = 1.80 (95% confidence interval = 0.99-3.22), odds ratio = 2.29 (95% confidence interval = 1.00-5.23)] after adjustment. There were significant associations between interarm blood pressure difference ⩾5 and ⩾10 mmHg and proteinuria [odds ratio = 1.68 (95% confidence interval = 1.15-2.44), 1.89 (95% confidence interval = 1.05-3.37)]. CONCLUSION: The association between interarm blood pressure difference and the presence of diabetic retinopathy emerged even for systolic interarm blood pressure difference ⩾5 mmHg without interaction of systolic blood pressure. Systolic interarm blood pressure difference should be considered a surrogate marker for vascular complication in patients with type 2 diabetes.


Assuntos
Pressão Sanguínea , Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/fisiopatologia , Extremidade Superior/irrigação sanguínea , Idoso , Índice Tornozelo-Braço , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/fisiopatologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Proteinúria/diagnóstico , Proteinúria/epidemiologia , Proteinúria/fisiopatologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Seul/epidemiologia
8.
Brasília; CONITEC; ago. 2020.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1145409

RESUMO

INTRODUÇÃO: O EMD é a principal causa de perda visual observada na retinopatia diabética (RD), a qual é uma das principais complicações relacionadas à diabetes mellitus (DM). Caracteriza-se pelo espessamento do tecido da mácula, como resultado do extravasamento de líquido dos capilares sanguíneos ou a presença de exsudatos duros no centro da mácula. As principais terapias para o tratamento do EMD disponíveis no SUS são terapias a laser (fotocoagulação e pan-fotocoagulação), cirurgia vitrectomia e, conforme a recente incorporação, o antiangiogênico aflibercepte. PERGUNTA: O uso de ranibizumabe é eficaz e seguro como opção de anti-VEGF para o tratamento do edema macular diabético quando comparado aos tratamentos atualmente disponíveis no SUS (fotocoagulação a laser e aflibercepte)? EVIDÊNCIAS CIENTÍFICAS: Foram incluídos 12 estudos pelo demandante, sendo 3 revisões sistemáticas e 9 ensaios clínicos que avaliaram ranibizumabe. Foram também incluídas 2 metanálises que o demandante havia excluído de sua análise original. Todos os estudos primários compararam o ranibizumabe com o tratamento com o laser e apresentaram resultados significativos de superioridade de eficácia do ranibizumabe na melhora da acuidade visual em pacientes com EMD. As revisões sistemáticas que avaliaram o ranibizumabe com outros anti-VEGF mostraram que estes têm eficácia semelhantes, com alguns estudos sugerindo superioridade do aflibercepte como tratamento. Segundo resultados atualizados da metanálise de Virgilli e colaboradores, aflibercepte e ranibizumabe foram mais efetivos do que laser, melhorando a visão em 2 ou mais linhas depois de um ano de tratamento (alta qualidade). O risco relativo (RR) versus laser foi de 3,66 (IC95% 2,79 a 4,79) para aflibercepte e RR 2,76 (IC95% CI 2,12 a 3,59) para ranibizumabe. Pessoas com EMD em tratamento com ranibizumabe foram menos propensas a ganhar 3 ou mais linhas de acuidade visual em um ano comparado com aflibercepte - RR 0,75 (IC95% 0,60 a 0,94). Aflibercepte e ranibizumabe não diferiram com relação a eventos adversos graves sistêmicos. Outra metanálise em rede de Zhang e colaboradores mostrou que ranibizumabe teve melhores resultados que o aflibercepte na melhora do BCVA em 6 meses com odds ratio (OR) 7,01 (IC95% 2,56 a 11,39), mas o aflibercepte apresentou melhor eficácia aos 12 meses de tratamento com OR 8,19 (IC95% 5,07 a 11,96). Esses resultados demonstram que tanto o ranibizumabe quando o aflibercepte tem eficácia semelhante para o EMD. AVALIAÇÃO ECONÔMICA: A avaliação apresentada pelo demandante foi uma análise de custominimização utilizando como comparador o aflibercepte. Ranibizumabe é uma alternativa poupadora de recursos quando comparada ao aflibercepte para o tratamento de pacientes adultos com edema macular diabético (EMD). O custo total estimado com ranibizumabe para três anos de tratamento foi de R$ 18.171,48 e para o aflibercepte de R$ 21.629,11 proporcionando uma economia de aproximadamente 16% com o tratamento com ranibizumabe. A análise apresentada avaliou os custos de tratamento por paciente relacionados a aquisição, administração e acompanhamento e monitorização do tratamento. Porém não considerou gastos relacionados à segurança. Custos com complicações e eventos adversos podem impactar no resultado econômico do tratamento. Como não foram considerados esses custos, faltou avaliar esse parâmetro na análise de sensibilidade disponibilizada. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: A análise de impacto orçamentária (AIO) apresentada incluiu a população estimada com RD com presença de EMD aplicando taxas de prevalência de 11,7% de acordo com estudo realizado no Brasil. O cenário proposto com ranibizumabe projetado para tratamento anual chega a R$ 79.266.917,64 no ano 1 e estima-se R$ 181.283.719,49 no ano 5 em relação ao aflibercepte que teve o valor estimado em R$ 69.312.302,72 para o primeiro ano de incorporação e de R$ 154.658.419,96 para o quinto ano. A AIO demonstrou que a incorporação de ranibizumabe como uma alternativa de tratamento para EMD além do aflibercepte pode promover uma economia de recursos de até R$ 104,1 milhões ao longo de cinco anos considerando uma difusão de mercado de 50%. Em todos os cenários avaliados pela análise de sensibilidade observou-se a geração de economia devido a incorporação de ranibizumabe para EMD no SUS. O modelo possui algumas limitações na análise, como incerteza no tamanho da cota de mercado do ranibizumabe (considerada em 50%), incerteza de que ocorrerá indicação terapêutica apenas para pacientes com espessamento de retina maior que 400 micrometros , incerteza da origem dos valores da taxa de difusão apresentadas o que pode comprometer os resultados. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: As buscas encontraram dois medicamentos novos no horizonte para tratamento do EMD, Brolucizumabe (inibidor de VEGF-A) e Faricizumabe (inibidor VEGF-A e inibidor de ligante de angiopoietina-2) em estudo clínico de fase 3 em andamento. Ainda foram encontrados biossimilares do aflibercepte e ranibizumabe. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Pelo exposto, a Conitec, em sua 86ª reunião ordinária, nos dias 04 e 05 de março de 2020, recomendou-se que o tema fosse levado em consulta pública com recomendação preliminar favorável a incorporação no SUS do Ranibizumabe para o tratamento de pacientes adultos com edema macular diabético (EMD). CONSULTA PÚBLICA: O relatório de recomendação inicial da Conitec foi disponibilizado para contribuições por meio da consulta pública nº 16/2020 entre os dias 30/03/2020 e 20/04/2020. Foram recebidas 978 contribuições, sendo 156 contribuições de cunho técnico-científico e 822 contribuições de experiência pessoal ou opinião. Destas 95,5% e 92,3% concordavam com a recomendação preliminar da Conitec, respectivamente. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da Conitec presentes na 89ª reunião ordinária, no dia 05/08/2020, deliberaram, por unanimidade, recomendar a incorporação do ranibizumabe para o tratamento do edema macular diabético, conforme protocolo do Ministério da Saúde e assistência oftalmológica no SUS. DECISÃO: Incorporar o ranibizumabe para tratamento de Edema Macular Diabético (EMD), no âmbito do Sistema Único de Saúde - SUS, conforme protocolo do Ministério da Saúde e a assistência oftalmológica no SUS, conforme Portaria n° 39, publicada no Diário Oficial da União n° 181, seção 1, página 235, em 21 de setembro de 2020.


Assuntos
Humanos , Edema Macular/tratamento farmacológico , Retinopatia Diabética/fisiopatologia , Ranibizumab/uso terapêutico , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
10.
Invest Ophthalmol Vis Sci ; 61(5): 8, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32392316

RESUMO

Purpose: The purpose of this study was to compare perfusion parameters of the parafovea with scans outside the parafovea to find an area most susceptible to changes secondary to diabetic retinopathy (DR). Methods: Patients with different DR severity levels as well as controls were included in this cross-sectional clinical trial. Seven standardized 3 × 3 mm areas were recorded with Swept Source Optical Coherence Tomography Angiography: one centered on the fovea, three were temporal to the fovea, and three nasally to the optic disc. The capillary perfusion density (PD) of the superficial capillary complex (SCC) and deep capillary complex (DCC) as well as the fractal dimension (FD) were generated. Statistical analyses were done with R software. Results: One hundred ninety-two eyes (33 controls, 51 no-DR, 41 mild DR, 37 moderate/severe DR, and 30 proliferative DR), of which 105 patients with diabetes and 25 healthy controls were included (59 ± 15 years; 62 women). Mean PD of the DCC was significantly less in patients without DR (parafovea = 0.48 ± 0.03; temporal = 0.48 ± 0.02; and nasal = 0.48 ± 0.03) compared to controls (parafovea = 0.49 ± 0.02; temporal = 0.50 ± 0.02; and nasal = 0.50 ± 0.03). With increasing DR severity, PD and FD of the SCC and DCC further decreased. Conclusions: Capillary perfusion of the retina is affected early by diabetes. PD of the DCC was significantly reduced in patients with diabetes who did not have any clinical signs of DR. The capillary network outside the parafovea was more susceptible to capillary perfusion deficits compared to the capillaries close to the fovea. Trial Registration: clinicaltrial.gov, NCT03765112, https://clinicaltrials.gov/ct2/show/NCT03765112?term=NCT03765112&rank=1.


Assuntos
Retinopatia Diabética/diagnóstico por imagem , Angiofluoresceinografia , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica , Capilares/diagnóstico por imagem , Estudos Transversais , Retinopatia Diabética/fisiopatologia , Feminino , Fóvea Central/irrigação sanguínea , Fóvea Central/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Retina/fisiopatologia , Vasos Retinianos/diagnóstico por imagem
11.
Am J Ophthalmol ; 217: 268-277, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32360332

RESUMO

PURPOSE: To assess the association between optical coherence tomography angiography (OCTA)-quantified avascular areas (AAs) and diabetic retinopathy (DR) severity, progression, and treatment requirement in the following year. DESIGN: Prospective cohort study. METHODS: We recruited patients with diabetes from a tertiary academic retina practice and obtained 3-mm × 3-mm macular OCTA scans with the AngioVue system and standard 7-field color photographs at baseline and at a 1-year follow-up visit. A masked grader determined the severity of DR from the color photographs using the Early Treatment of Diabetic Retinopathy scale. A custom algorithm detected extrafoveal AA (EAA) excluding the central 1-mm circle in projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). RESULTS: Of 138 patients, 92 (41 men, ranging in age from 26-84 years [mean 59.4 years]) completed 1 year of follow-up. At baseline, EAAs for SVC, ICP, and DCP were all significantly correlated with retinopathy severity (P < .0001). DCP EAA was significantly associated with worse visual acuity (r = -0.24, P = .02), but SVC and ICP EAA were not. At 1 year, 11 eyes progressed in severity by at least 1 step. Multivariate logistic regression analysis demonstrated the progression was significantly associated with baseline SVC EAA (odds ratio = 8.73, P = .04). During the follow-up period, 33 eyes underwent treatment. Multivariate analysis showed that treatment requirement was significantly associated with baseline DCP EAA (odds ratio = 3.39, P = .002). No baseline metric was associated with vision loss at 1 year. CONCLUSIONS: EAAs detected by OCTA in diabetic eyes are significantly associated with baseline DR severity, disease progression, and treatment requirement over 1 year.


Assuntos
Retinopatia Diabética/diagnóstico , Gerenciamento Clínico , Angiofluoresceinografia/métodos , Macula Lutea/patologia , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/terapia , Progressão da Doença , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
12.
Invest Ophthalmol Vis Sci ; 61(3): 50, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32232345

RESUMO

Purpose: To investigate the microvascular changes in macular retina and choriocapillaris (CC) in diabetic eyes without retinopathy using swept-source optical coherence tomography angiography (SS-OCTA). Methods: A commercial SS-OCTA system was used to collect 6 × 6-mm macular scans from patients. Three depth-resolved retinal slabs and a CC slab were segmented by a validated semiautomated algorithm. Retinal vessel area density, vessel skeleton density, and nonperfusion area were calculated on segmented retinal slabs. Foveal avascular zone was automatically measured based on en face image of the whole retinal layer. For CC quantification, the percentage of flow deficits (FD%) and the flow deficit (FD) sizes were measured. Results: Sixteen eyes from 16 diabetic patients without clinically detectable retinopathy and 16 eyes from 16 age-matched nondiabetic controls were included. There was no significant difference between the two groups in all retinal vessel quantitative parameters (all P > 0.05). However, the mean FD% and mean FD sizes were significantly increased in CC in the central 1.0-mm disk (P = 0.011 and P = 0.017, respectively), the central 1.5-mm rim (P = 0.003 and P = 0.009, respectively), the central 2.5-mm rim (P = 0.018 and P = 0.020, respectively), and the entire 5.0-mm disk (P = 0.009 and P = 0.008, respectively) in diabetic eyes compared with controls. Conclusions: CC perfusion in the macula is decreased in diabetic patients without retinopathy as compared to age-matched normal controls. Decreased CC perfusion in the macula may be an early indicator of otherwise clinically undetectable diabetic vasculopathy.


Assuntos
Corioide/irrigação sanguínea , Diabetes Mellitus/fisiopatologia , Vasos Retinianos/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Capilares/fisiopatologia , Diabetes Mellitus/diagnóstico por imagem , Retinopatia Diabética/fisiopatologia , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica , Adulto Jovem
13.
Invest Ophthalmol Vis Sci ; 61(4): 38, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32340033

RESUMO

Purpose: To test the hypothesis that hyperglycemia perturbs neurovascular\ coupling and compromises retinal vascular response during transition from dark to light in healthy subjects using optical coherence tomography angiography (OCTA). Methods: Ten eyes of 10 healthy subjects were tested, first during fasting and then after receiving a 75-g oral glucose solution. In both sessions, OCTA imaging was done in the dark-adapted state and at 50 seconds, 2 minutes, 5 minutes, and 15 minutes of ambient light. Parafoveal vessel density (VD) and adjusted flow index (AFI) were calculated for the superficial capillary plexus (SCP), middle capillary plexus (MCP), and deep capillary plexus (DCP), and vessel length density was calculated for the SCP. These measurements were compared among conditions after adjusting for age, refractive error, and OCTA scan quality. Results: Hyperglycemia leads to a complete reversal of dark/light adaptation trends in VD and AFI in all layers of the inner retina. In the dark, there is significantly decreased VD in the DCP in hyperglycemia. With a transition to light in hyperglycemia, we observed decreased VD in the SCP, increased vessel density in the MCP and DCP, and decreased AFI in all three layers. Conclusions: Our results show that hyperglycemia significantly disrupts neurovascular coupling in healthy eyes, with potential metabolic deficits affecting photoreceptor oxygen demands during dark adaptation and the inner retina during light exposure. In pathological states, such as diabetic retinopathy, where the vasculature is already attenuated, retinal neurons may be exquisitely vulnerable to intermittent hyperglycemic challenge, which should be the focus of future studies.


Assuntos
Adaptação Ocular/fisiologia , Adaptação à Escuridão/fisiologia , Glucose/efeitos adversos , Hiperglicemia/complicações , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto , Estudos de Coortes , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/fisiopatologia , Feminino , Glucose/administração & dosagem , Voluntários Saudáveis , Humanos , Modelos Lineares , Masculino , Acoplamento Neurovascular , Variações Dependentes do Observador , Estudos Prospectivos , Vasos Retinianos/patologia , Medição de Risco
14.
Invest Ophthalmol Vis Sci ; 61(4): 29, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32324858

RESUMO

Purpose: Previous studies on the association between choroidal thickness (CT) and severity of diabetic retinopathy (DR) gave conflicting results. The aim of this study was to evaluate the CT changes in diabetic patients and associated factors in a large sample of Chinese patients with diabetes. Methods: Type 2 diabetes mellitus patients without history of ocular treatment were recruited from the community health system in Guangzhou, China. The swept source OCT instrument was used to obtain high-definition retina and choroid images. The diabetic retinopathy (DR) status was graded based on the guidelines of the United Kingdom National Diabetic Eye Screening Programme. Univariate and multivariate linear regression analyses was used to explore the association of CT with DR severity, diabetic macular edema (DME), hemoglobin A1c, and vision function. Results: A total of 1347 patients were included in the final analysis. After adjusting for other factors, the patients with stage R3 DR had significantly thinner CT (ß = -29.1 µm, 95% CI -53.8 to -4.4, P = 0.021) in comparison in those with R0. After adjusting for other factors, the CTs were thicker than those in R0 patients with difference of 15.6 µm (95% CI 4.3-26.9, P = 0.007) for outer nasal sector, 15.7 µm (95% CI 3.8-25.5, P = 0.008) for outer inferior, and 12.2 µm (95% CI 0.4-24.0, P = 0.042) for inner inferior sector. The presence of DME and hemoglobin A1c levels did not significantly affect average CT. Higher average CT was significantly associated with better best corrected visual acuity, with a -0.02 LogMAR unit per 100 µm increase in average CT (95% CI -0.03 to -0.01, P < 0.001). Conclusions: CT increased in the early stage of DR, and further decreased with DR progression. DME was not significantly associated with CT. These findings provide more clues to suggest that choroid alterations play a role in the pathogenesis of DR.


Assuntos
Corioide/patologia , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico por imagem , Retina/patologia , Acuidade Visual , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China , Corioide/diagnóstico por imagem , Estudos Transversais , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/fisiopatologia , Progressão da Doença , Feminino , Angiofluoresceinografia/métodos , Hospitais Universitários , Humanos , Edema Macular/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Retina/diagnóstico por imagem , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais
15.
Sci Rep ; 10(1): 7177, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32346043

RESUMO

The ability to monitor progression of retinal vascular diseases like diabetic retinopathy in small animal models is often complicated by their failure to develop the end-stage complications which characterize the human phenotypes in disease. Interestingly, as micro-vascular dysfunction typically precedes the onset of retinal vascular and even some neurodegenerative diseases, the ability to visualize and quantify hemodynamic changes (e.g. decreased flow or occlusion) in retinal vessels may serve as a useful diagnostic indicator of disease progression and as a therapeutic outcome measure in response to treatment. Nevertheless, the ability to precisely and accurately quantify retinal hemodynamics remains an unmet challenge in ophthalmic research. Herein we demonstrate the ability to modify a commercial fundus camera into a low-cost laser speckle contrast imaging (LSCI) system for contrast-free and non-invasive quantification of relative changes to retinal hemodynamics over a wide field-of-view in a rodent model.


Assuntos
Retinopatia Diabética , Fluxometria por Laser-Doppler , Microcirculação , Vasos Retinianos , Animais , Velocidade do Fluxo Sanguíneo , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/fisiopatologia , Feminino , Masculino , Camundongos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/fisiopatologia
16.
Am J Pathol ; 190(7): 1505-1512, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32275905

RESUMO

Diabetic retinopathy (DR) is a common complication of diabetes and a leading cause of blindness among the working-age population. Diabetic patients often experience functional deficits in dark adaptation, contrast sensitivity, and color perception before any microvascular pathologies on the fundus become detectable. Previous studies showed that the regeneration of 11-cis-retinal and visual pigment is impaired in a type 1 diabetes animal model, which negatively affects visual function at the early stage of DR. Here, Akita mice, type 1 diabetic model, were treated with the visual pigment chromophore, 9-cis-retinal. This treatment rescued a- and b-wave amplitudes of scotopic electroretinography responses, compared with vehicle-treated Akita mice. In addition, the administration of 9-cis-retinal alleviated oxidative stress significantly as shown by reduced 3-nitrotyrosine levels in the retina of Akita mice. Furthermore, the 9-cis-retinal treatment decreased retinal apoptosis as shown by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and DNA fragment enzyme-linked immunosorbent assay. Overall, these findings showed that 9-cis-retinal administration restored visual pigment formation and decreased oxidative stress and retinal degeneration, which resulted in improved visual function in diabetic mice, suggesting that chromophore deficiency plays a causative role in visual defects in early DR.


Assuntos
Retinopatia Diabética/fisiopatologia , Diterpenos/farmacologia , Retina/efeitos dos fármacos , Retinaldeído/farmacologia , Animais , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Estresse Oxidativo/efeitos dos fármacos , Retina/fisiopatologia
17.
Am J Ophthalmol ; 215: 25-36, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32224103

RESUMO

PURPOSE: This study was performed to investigate the association between changes in retinal layer thickness and perfusion status in the extramacular areas of eyes with diabetic retinopathy. DESIGN: Retrospective cross-sectional study. METHODS: The medical records of 70 eyes from 55 patients with diabetes were reviewed. The status of retinal perfusion in extramacular areas was evaluated using swept-source optical coherence tomography angiography. Retinal layer thickness was measured in nonperfused areas (NPA) larger than 2 optic disc areas, areas of sparse capillaries (SC), and perfused areas (PA-DR) in eyes with diabetic retinopathy. Retinal layer thickness was also measured in perfused areas in eyes without diabetic retinopathy (PA-NDR), and the thicknesses were then compared. In addition, swept-source optical coherence tomography angiography images and retinal thickness maps were compared to investigate the distribution of retinal thickness changes and spatial relationships to areas of retinal perfusion. RESULTS: The inner retinal thickness in NPA was significantly thinner than the inner retinal thicknesses in SC, PA-DR, and PA-NDR (all P < .001), and the inner retinal thickness in PA-NDR and SC was significantly thinner than that in PA-DR (P = .006 and .031, respectively). In a distribution analysis of the extramacular areas, NPA spatially overlapped with areas of severe retinal thinning in all locations. Local thickening with smooth shapes and gentle borders overlapped with areas of capillary abnormalities. Neovascularization was present at sites of local thickening with irregular shapes and unnatural clear borders. CONCLUSIONS: Changes in retinal layer thickness were associated with perfusion status, suggesting that retinal thickness maps can reflect perfusion status.


Assuntos
Retinopatia Diabética/fisiopatologia , Retina/patologia , Vasos Retinianos/fisiopatologia , Adulto , Idoso , Estudos Transversais , Retinopatia Diabética/diagnóstico por imagem , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Fluxo Sanguíneo Regional/fisiologia , Retina/diagnóstico por imagem , Células Ganglionares da Retina/patologia , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica
18.
Lancet Diabetes Endocrinol ; 8(4): 337-347, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32113513

RESUMO

Although the prevalence of all stages of diabetic retinopathy has been declining since 1980 in populations with improved diabetes control, the crude prevalence of visual impairment and blindness caused by diabetic retinopathy worldwide increased between 1990 and 2015, largely because of the increasing prevalence of type 2 diabetes, particularly in low-income and middle-income countries. Screening for diabetic retinopathy is essential to detect referable cases that need timely full ophthalmic examination and treatment to avoid permanent visual loss. In the past few years, personalised screening intervals that take into account several risk factors have been proposed, with good cost-effectiveness ratios. However, resources for nationwide screening programmes are scarce in many countries. New technologies, such as scanning confocal ophthalmology with ultrawide field imaging and handheld mobile devices, teleophthalmology for remote grading, and artificial intelligence for automated detection and classification of diabetic retinopathy, are changing screening strategies and improving cost-effectiveness. Additionally, emerging evidence suggests that retinal imaging could be useful for identifying individuals at risk of cardiovascular disease or cognitive impairment, which could expand the role of diabetic retinopathy screening beyond the prevention of sight-threatening disease.


Assuntos
Retinopatia Diabética/diagnóstico , Seleção Visual/organização & administração , Análise Custo-Benefício , Retinopatia Diabética/fisiopatologia , Progressão da Doença , Diagnóstico Precoce , Humanos , Oftalmologia , Encaminhamento e Consulta , Medição de Risco
19.
PLoS One ; 15(3): e0229665, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32134944

RESUMO

BACKGROUND: Clinical trials have shown beneficial effects of blood pressure (BP) control in reducing the risk of diabetic retinopathy (DR). However, association between BP control and DR in population-based studies is not clear. We aimed to examine the association of hypertension and BP control with DR. METHODS: We analysed data from a population-based cross-sectional study of Chinese, Malay and Indians adults with diabetes and hypertension (2004-2011, n = 2189, aged 40-80 years) in Singapore. DR severity was assessed from retinal photographs and graded for any- and vision-threatening DR (VTDR) using the modified Airlie House classification. Hypertension status was classified into (1) good control: on treatment (SBP < 130 and DBP < 80 mm Hg), (2) moderate control: on treatment, with BP levels other than group 1 and 3, (3) poor control: on treatment (SBP ≥140 and DBP ≥ 90 mm Hg), (4) untreated hypertension, any BP level. SBP, DBP and pulse pressure (PP) were analyzed as categories and as continuous variables. The association between BP and DR was assessed using multivariable logistic regression models. RESULTS: The prevalence of any-DR and VTDR in the study population was 33.8% and 9.0% respectively. Both poorly controlled and untreated hypertension were significantly associated with any-DR with odds ratio (OR) (95% confidence interval [CI]) of 1.97 (1.39-2.83), and 2.01 [1.34-3.05]. Among BP components, SBP and PP were associated with both any-DR and VTDR with OR (95% CI) of 1.45 (1.28-1.65) and 1.61 (1.41-1.84) for any-DR, and 1.44 (1.19-1.76) and 1.67 (1.37-2.06) for VTDR. CONCLUSION: In a population-based sample of Asian adults with diabetes and hypertension, treated but poorly controlled as well as untreated hypertension were significantly associated with any-DR. Among the BP components, higher SBP and PP levels were associated with both any-DR and VTDR. Further longitudinal studies are necessary to confirm our findings.


Assuntos
Glicemia/fisiologia , Retinopatia Diabética/etiologia , Hipertensão/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/métodos , Estudos Transversais , Diabetes Mellitus/fisiopatologia , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade
20.
Am J Ophthalmol ; 215: 14-24, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32209341

RESUMO

PURPOSE: To investigate baseline characteristics of patients undergoing additional antivascular endothelial growth factor (VEGF) injections for residual or recurrent diabetic macular edema (DME) in the first year after 0.19-mg fluocinolone acetonide (FAc) implant. DESIGN: Prospective cohort study. METHODS: Ninety-four eyes of 66 patients received an FAc implant. Eyes with persistent or recurrent DME were managed with pro re nata anti-VEGF agents. Demographic data and medical history were collected at baseline. Best-corrected visual acuity and central macular thickness were measured every 2 months. The 3 outcomes explored were 1) the risk factors for administration of additional anti-VEGF agents, 2) the interval from FAc to first anti-VEGF injection; and 3) the number of anti-VEGF doses required to maintain regression of DME. RESULTS: Eighteen eyes (19.1%) of 13 patients received 1.3 ± 0.6 anti-VEGF injections. These eyes had significantly thicker central macular thickness at baseline and over the entire follow-up period (P < .001); best-corrected visual acuity was similar at every time point to eyes that were not receiving extra DME treatments. Eyes without preexistent panretinal photocoagulation (PRP) had a higher risk to undergo supplemental treatments (hazard ratio 1.5 [95% confidence interval 1.1-2.5, P = .03). The interval between FAc implant and the first anti-VEGF had a significant linear positive relationship with the number of dexamethasone implants before FAc implant (P = .002, R2 = 0.47). No association was found between baseline factors and the number of injections given. CONCLUSION: Anti-VEGF agents are efficient treatment to maintain visual acuity in residual/recurrent DME after FAc. Patients with higher baseline central macular thickness and with no previous central macular thickness are more likely to require additional treatments to control DME.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/diagnóstico , Fluocinolona Acetonida/administração & dosagem , Glucocorticoides/administração & dosagem , Edema Macular/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/fisiopatologia , Implantes de Medicamento , Feminino , Humanos , Edema Macular/tratamento farmacológico , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Fatores de Risco , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia
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