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Repercussões retinianas na doença de Alzheimer
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RESUMO: Introdução - A doença de Alzheimer é uma doença degenerativa prevalente com grande impacto social. Trata‐se da causa mais frequente de demência acima dos 65 anos e os sintomas visuais são relatados em estádios iniciais da doença, muito antes do diagnóstico estar claramente estabelecido. As alterações visuais descritas incluem dificuldades na leitura, em encontrar objetos, perceção de profundidade e do movimento, reconhecimento de cores e diminuição da sensibilidade ao contraste espacial. A disfunção visual da doença de Alzheimer foi atribuída durante muitos anos apenas às lesões no córtex visual primário e áreas corticais superiores. No entanto, evidências crescentes baseadas em estudos com modelos animais da doença de Alzheimer e em seres humanos demonstraram que a neurodegenerescência pré‐cortical pode
desempenhar um importante papel e as alterações visuais observadas nesta doença podem ser causadas por lesões que ocorrem a qualquer nível das vias óticas. As evidências anatomopatológicas demonstraram envolvimento das células ganglionares da retina, dos axónios do nervo ótico, da microcirculação da retina e da coroideia nos doentes com Alzheimer. Estes achados anatomopatológicos foram corroborados pela avaliação in vivo da retina e da coroideia, bem como da sua vascularização. A tomografia de coerência ótica tem
mostrado grande utilidade na avaliação destas alterações podendo tornar‐se uma ferramenta útil na deteção precoce e, possivelmente, no acompanhamento da progressão da doença. O objetivo principal deste estudo consistiu em identificar alterações estruturais das diferentes camadas da retina peripapilar e macular e da coroideia dos doentes com doença de Alzheimer através de Spectral Domain – Optical Coherence Tomography. Métodos - Estudo observacional transversal realizado no Centro Hospitalar de Lisboa Central, entre Outubro de 2014 e Abril de 2016, que incluiu 50 olhos de 50 doentes com doença de Alzheimer e 152 olhos de 152 indivíduos sem a referida doença. Todos os indivíduos foram submetidos a observação neurológica e oftalmológica completa. Os exames tomográficos foram obtidos utilizando o Spectralis Spectral Domain Optical Coherence Tomography, programas Retinal Nerve Fiber Layer Single Exam Report OU with FoDi™ para a análise peripapilar e Fast Macular Thickness para a análise retiniana com segmentação automática para obtenção dos valores da espessura de cada camada retiniana, assim como da retina total.
Foi também utilizado o software Enhanced Depth Imaging para a obtenção de imagens da coroideia. A sua medição foi realizada de forma manual em 13 localizações: na zona subfoveal e em intervalos de 500 μm até 1500 μm nasal, temporal, superior e inferior à fóvea. Foi ainda acrescentado um grupo de 50 olhos de 50 indivíduos com idade superior a 78 anos, sem Doença de Alzheimer para medição da espessura da coroideia. Para a análise dos dados foram utilizados modelos de regressão linear, adotando‐se o nível de significância α=0,05. Resultados - De salientar, a ausência de diferenças estatisticamente significativas entre os três grupos
estudados relativamente ao género, pressão intraocular, comprimento axial, equivalente esférico e terapêutica com beta‐bloqueantes/diuréticos. Nos exames tomográficos registámos diferenças estatisticamente significativas entre o grupo doença de Alzheimer e o grupo controlo. Relativamente à camada de fibras nervosas peripapilar, a média global e o quadrante temporal superior registaram os valores com as diferenças de maior significado estatístico. Na retina macular total e nas diferentes camadas retinianas, as principais diferenças foram observadas nos setores superiores da retina total, nos setores periféricos da camada de células ganglionares (superior, temporal e nasal) e nos setores superiores da camada plexiforme interna. Relativamente à coroideia, obtivemos diferenças estatisticamente significativas nas 13 localizações quando comparámos os dois grupos (doença de Alzheimer e o grupo controlo). Para testar a robustez destes resultados comparámos o grupo doença de Alzheimer com indivíduos muito idosos e ainda obtivemos diminuições de espessura no grupo com doença mais pronunciadas na região subfoveal e em 2 localizações temporais à fóvea (500 e 1000 μm). Conclusões - Na tomografia por coerência ótica, a espessura média da camada de fibras nervosas peripapilar encontra‐se diminuída de forma significativa nos doentes com Alzheimer, sendo sobretudo expressiva no quadrante temporal superior. Nos modelos de regressão multivariável, após correção de Bonferroni, também a espessura total da retina estava diminuída nos setores superiores. As camadas retinianas mais atingidas na doença de Alzheimer incluem a camada de células ganglionares e os seus setores periféricos superior, temporal e nasal localizados entre os 3 e os 6 mm centrados à fóvea e os sectores superiores pericentral e periférico da camada plexiforme interna. A espessura da coroideia encontra‐se estatisticamente reduzida na área macular dos doentes com Alzheimer. Confirmou‐se a relação inversa entre a espessura da coroideia e a idade e identificaram‐se três localizações da coroideia, subfoveal e temporais à fóvea, com espessura diminuída de forma muito pronunciada, mesmo quando comparadas com indivíduos cerca de 10 anos mais idosos.
ABSTRACT: Introduction - Alzheimer’s disease is a prevalent, long‐term progressive degenerative disorder with great social impact. Visual symptoms are frequent and are an early clinical manifestation; a number of psychophysiologic changes occur in visual function, including visual field defects, abnormal contrast sensitivity, abnormalities in colour vision, depth perception deficits, and motion detection abnormalities. These visual changes were initially believed to be solely due to neurodegeneration in the posterior visual pathway. However, evidence from pathology studies in both animal models of Alzheimer’s disease and humans has demonstrated that neurodegeneration also takes place in the anterior visual pathway, with involvement of the retinal ganglion cells, dendrites, somata and axons in the optic nerve. These studies additionally showed patients with Alzheimer’s disease have changes in retinal and choroidal microvasculature. Pathology findings have been corroborated by in vivo assessment of the retina and optic nerve head, as well as the retinal and choroidal vasculature. Optical coherence tomography has shown great utility in the assessment of these changes, and it may become a useful tool for early detection and monitoring disease progression in Alzheimer’s disease. The main objective of this study was to identify structural alterations of the different layers of the peripapillary and macular retina and of the choroid of patients with Alzheimer’s disease using Spectral Domain – Optical Coherence Tomography. Methods - Cross‐sectional observational study included 50 eyes of 50 patients with AD and 152 eyes of 152 normal subjects. All subjects underwent observation ophthalmologic and neurological / neuropsychological observation. Optical Coherence Tomography scans were obtained using the Spectralis Spectral Domain‐Optical Coherence Tomography (Heidelberg Engineering, Heidelberg, Germany®) and programs RNFL Single Exam Report OU with FoDi ™", Fast Macular Thickness for retinal analysis with automatic segmentation to obtain the values the thickness of each retinal layer. The Enhanced Depth Imaging Optical Coherence Tomography was chosen to measure the choroidal thickness at 13 locations: in the subfoveal region and at intervals of 500 to 1500 μm nasal, temporal, superior and inferior to the fovea. A group of 50 eyes of 50 individuals aged over 78 years without Alzheimer's Disease was also added to measure the choroidal thickness. For the analysis of the data, linear regression models were used, adopting the level of significance α = 0.05. Results We verify absence of statistically significant differences between the study groups with respect to gender, visual acuity, intraocular pressure, axial length, spherical equivalent and treatment with beta‐blocker / diuretic therapy. In tomographic studies we have noted significant differences between Alzheimer's disease group and the control group. Regarding the peripapillary retinal nerve fiber layer, the overall mean and the upper temporal quadrant had the most statistically significant differences. In the total macular retina and in the different retinal layers, the main differences were observed in the upper sectors of the total retina, in the peripheral sectors of the ganglion cell layer (superior, temporal and nasal) and in the upper sectors of the internal plexiform layer. Concerning choroid, we obtained statistically significant differences in the 13 locations when we compared the two groups (Alzheimer's disease and the control group). In order to test the robustness of these results, we compared the Alzheimer's disease group with very elderly individuals and we also obtained decreases in thickness in the group with more pronounced differences in the subfoveal region and in 2 locations temporal to the fovea (500 and 1000 μm). Conclusions - The Optical Coherence Tomography shows a significant peripapillary retinal nerve fiber layer thickness reduction in patients with Alzheimer disease, particularly in the upper temporal quadrant. Retinal layers most affected in Alzheimer's disease include the ganglion cels layer/inner plexiform layer complex and the most affected macular sectors are the superior 1 ‐ 6 mm and the temporal from 1 to 3 mm counting from the center of the fovea. The choroid has a reduced thickness in the macular area in patients with AD. This thickness reduction is not related to age, and seems to be characteristic of Alzheimer's disease but not pathognomonic. In the multivariable regression models, after Bonferroni correction, the total retinal thickness was also decreased in the upper sectors. The most affected retinal layers in Alzheimer's disease include the ganglion cell layer and its upper, temporal and nasal peripheral sectors located between 3 and 6 mm centered on the fovea and the pericentral and peripheral upper sectors of the inner plexiform layer. The choroidal thickness is statistically reduced in the macular area of patients with Alzheimer. The negative relationship between choroidal thickness and age was confirmed and three choroidal locations, subfoveal and 500 and 1000 μm temporal to the fovea, were identified as the most reduced, even when compared to individuals 10 years older.
ABSTRACT: Introduction - Alzheimer’s disease is a prevalent, long‐term progressive degenerative disorder with great social impact. Visual symptoms are frequent and are an early clinical manifestation; a number of psychophysiologic changes occur in visual function, including visual field defects, abnormal contrast sensitivity, abnormalities in colour vision, depth perception deficits, and motion detection abnormalities. These visual changes were initially believed to be solely due to neurodegeneration in the posterior visual pathway. However, evidence from pathology studies in both animal models of Alzheimer’s disease and humans has demonstrated that neurodegeneration also takes place in the anterior visual pathway, with involvement of the retinal ganglion cells, dendrites, somata and axons in the optic nerve. These studies additionally showed patients with Alzheimer’s disease have changes in retinal and choroidal microvasculature. Pathology findings have been corroborated by in vivo assessment of the retina and optic nerve head, as well as the retinal and choroidal vasculature. Optical coherence tomography has shown great utility in the assessment of these changes, and it may become a useful tool for early detection and monitoring disease progression in Alzheimer’s disease. The main objective of this study was to identify structural alterations of the different layers of the peripapillary and macular retina and of the choroid of patients with Alzheimer’s disease using Spectral Domain – Optical Coherence Tomography. Methods - Cross‐sectional observational study included 50 eyes of 50 patients with AD and 152 eyes of 152 normal subjects. All subjects underwent observation ophthalmologic and neurological / neuropsychological observation. Optical Coherence Tomography scans were obtained using the Spectralis Spectral Domain‐Optical Coherence Tomography (Heidelberg Engineering, Heidelberg, Germany®) and programs RNFL Single Exam Report OU with FoDi ™", Fast Macular Thickness for retinal analysis with automatic segmentation to obtain the values the thickness of each retinal layer. The Enhanced Depth Imaging Optical Coherence Tomography was chosen to measure the choroidal thickness at 13 locations: in the subfoveal region and at intervals of 500 to 1500 μm nasal, temporal, superior and inferior to the fovea. A group of 50 eyes of 50 individuals aged over 78 years without Alzheimer's Disease was also added to measure the choroidal thickness. For the analysis of the data, linear regression models were used, adopting the level of significance α = 0.05. Results We verify absence of statistically significant differences between the study groups with respect to gender, visual acuity, intraocular pressure, axial length, spherical equivalent and treatment with beta‐blocker / diuretic therapy. In tomographic studies we have noted significant differences between Alzheimer's disease group and the control group. Regarding the peripapillary retinal nerve fiber layer, the overall mean and the upper temporal quadrant had the most statistically significant differences. In the total macular retina and in the different retinal layers, the main differences were observed in the upper sectors of the total retina, in the peripheral sectors of the ganglion cell layer (superior, temporal and nasal) and in the upper sectors of the internal plexiform layer. Concerning choroid, we obtained statistically significant differences in the 13 locations when we compared the two groups (Alzheimer's disease and the control group). In order to test the robustness of these results, we compared the Alzheimer's disease group with very elderly individuals and we also obtained decreases in thickness in the group with more pronounced differences in the subfoveal region and in 2 locations temporal to the fovea (500 and 1000 μm). Conclusions - The Optical Coherence Tomography shows a significant peripapillary retinal nerve fiber layer thickness reduction in patients with Alzheimer disease, particularly in the upper temporal quadrant. Retinal layers most affected in Alzheimer's disease include the ganglion cels layer/inner plexiform layer complex and the most affected macular sectors are the superior 1 ‐ 6 mm and the temporal from 1 to 3 mm counting from the center of the fovea. The choroid has a reduced thickness in the macular area in patients with AD. This thickness reduction is not related to age, and seems to be characteristic of Alzheimer's disease but not pathognomonic. In the multivariable regression models, after Bonferroni correction, the total retinal thickness was also decreased in the upper sectors. The most affected retinal layers in Alzheimer's disease include the ganglion cell layer and its upper, temporal and nasal peripheral sectors located between 3 and 6 mm centered on the fovea and the pericentral and peripheral upper sectors of the inner plexiform layer. The choroidal thickness is statistically reduced in the macular area of patients with Alzheimer. The negative relationship between choroidal thickness and age was confirmed and three choroidal locations, subfoveal and 500 and 1000 μm temporal to the fovea, were identified as the most reduced, even when compared to individuals 10 years older.
Descrição
Palavras-chave
Doença de Alzheimer Tomografia por coerência ótica Retina Coroideia Alzheimer’s disease Optical coherence tomography Choroid