title: The Eye as a Window to the Brain: Neuroretinal Thickness Is Associated With Microstructural White Matter Injury in HIV-Infected Children.
abstract: Despite combination antiretroviral therapy (cART), perinatal HIV-infection can cause decreased gray and white matter volume, microstructural white matter injury, and retinal structural abnormalities. As neuroretinal tissue is directly connected to the brain, these deficits may have a shared pathogenesis. We aimed to assess associations between neuroretinal thickness and cerebral injury in cART-treated perinatally HIV-infected children and healthy controls.
  
  
  
  This cross-sectional observational study included 29 cART-treated perinatally HIV-infected children and 35 matched healthy controls. All participants underwent 3.0 Tesla magnetic resonance imaging (MRI), determining gray and white matter volumes from T1-weighted sequences, and white matter diffusivity using diffusion tensor imaging (DTI). Regional individual and total neuroretinal layer thickness was quantified using spectral-domain optical coherence tomography. We explored associations between retinal and cerebral parameters using multivariable linear regression analysis.
  
  
  
  In HIV-infected children, lower foveal and pericentral neuroretinal thickness was associated with damaged white matter microstructure, in terms of lower fractional anisotropy and higher mean and radial diffusivity. In healthy controls only, neuroretinal thickness was associated with gray and white matter volume.
  
  
  
  Decreased neuroretinal thickness is associated with microstructural white matter injury, but not with lower cerebral volume in HIV-infected children. This suggests that HIV-induced retinal thinning and microstructural white matter injury may share a common pathogenesis, and longitudinal assessment of neuroretinal alterations in parallel with MRI and neuroinflammatory markers may further our insight into the pathogenesis of HIV-induced cerebral injury in children.
authors.affiliation: Department of Hematology Immunology and Infectious Diseases, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Blokhuis
authors.affiliation: Department of Ophthalmology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Nazli
authors.initials: N
authors.lastname: Demirkaya
authors.affiliation: Department of Hematology Immunology and Infectious Diseases, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Sophie
authors.initials: S
authors.lastname: Cohen
authors.affiliation: Department of Global Health, Academic Medical Center, University of Amsterdam, and Amsterdam Institute for Global Health and Development, The Netherlands 4Department of Internal Medicine, Division of Infectious Diseases, Center for Infection and Immunity.
authors.forename: Ferdinand W N M
authors.initials: FW
authors.lastname: Wit
authors.affiliation: Department of Hematology Immunology and Infectious Diseases, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Henriëtte J
authors.initials: HJ
authors.lastname: Scherpbier
authors.affiliation: Department of Global Health, Academic Medical Center, University of Amsterdam, and Amsterdam Institute for Global Health and Development, The Netherlands 4Department of Internal Medicine, Division of Infectious Diseases, Center for Infection and Immunity.
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.affiliation: Department of Ophthalmology and Visual Sciences, Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States 7Department of Biomedical Engineering and Department of Electrical and Computer Engineering, University of I.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Abramoff
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Matthan W A
authors.initials: MW
authors.lastname: Caan
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Charles B L M
authors.initials: CB
authors.lastname: Majoie
authors.affiliation: Department of Ophthalmology, Academic Medical Center, University of Amsterdam, The Netherlands 9Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, The Netherlands 10Department of Ophthalmology, VU Universit.
authors.forename: Frank D
authors.initials: FD
authors.lastname: Verbraak
authors.affiliation: Department of Hematology Immunology and Infectious Diseases, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Dasja
authors.initials: D
authors.lastname: Pajkrt
mesh_terms: D000293:Adolescent; D001927:Brain Diseases / Q000473:pathology* / Q000821:virology; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D012160:Retina / Q000473:pathology* / Q000821:virology*; D012164:Retinal Diseases / Q000473:pathology* / Q000821:virology; D041623:Tomography, Optical Coherence; D066127:White Matter / Q000473:pathology* / Q000821:virology