title: Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer's disease.
abstract: OBJECTIVE
  To determine alterations in the retina of patients with Alzheimer's disease (AD) by the newly developed technique of fluorescence lifetime imaging ophthalmoscopy (FLIO) in a pilot study.
  
  
  METHODS
  FLIO set-up uses a scanning laser ophthalmoscope (HRA2, Heidelberg Engineering, Germany), which was modified by the use of an excitation pulse laser BLD440 (Becker&Hickl, Berlin, Germany) and detection of fluorescence lifetime by time-correlated single photon counting (TCSPC; Becker&Hickl) in two spectral channels (channel 1: 490-560 nm, channel 2: 560-700 nm). Least square fit of three exponential functions was used for fluorescence decay analysis. That resulted in three fluorescent components with lifetimes τi , amplitudes αi and relative contributions Qi . 16 patients with AD (mean age 77.2 ± 7.0 years) were investigated. After regular ophthalmic investigation, FLIO examination and OCT examination were performed. Alzheimer-specific clinical data were collected (MMSE, cerebrospinal fluid (CSF) concentration of amyloid-β (1-42), total-tau and phosphorylated tau181 (p-tau181) protein).
  
  
  RESULTS
  The FLIO parameters of the second fluorescent component α2 and Q2 (channel 2) correlated significantly with MMSE score (Q2 , R = -0.757, p = 0.007; α2 , R = -0.618, p = 0.043) as well as p-tau181-protein concentration in CSF (Q2 , R = 0.919, p = 0.009; α2 , R = 0.881, p = 0.020) in patients with AD. OCT measurements of retinal nerve fibre layer thickness, optic disc excavation and macular thickness neither correlated with Alzheimer-specific CSF data nor MMSE score.
  
  
  CONCLUSIONS
  Unlike conventional techniques, such as OCT, the new technique of FLIO revealed changes in the retina of patients with AD in relation to Alzheimer-specific markers in this pilot study.
authors.affiliation: Department of Ophthalmology, University Hospital Jena, Jena, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Jentsch
authors.affiliation: Department of Ophthalmology, University Hospital Jena, Jena, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Schweitzer
authors.affiliation: Department of Ophthalmology, University Hospital Jena, Jena, Germany.
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Schmidtke
authors.affiliation: Department of Ophthalmology, University Hospital Jena, Jena, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Peters
authors.affiliation: Department of Ophthalmology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Dawczynski
authors.affiliation: Department of Psychiatry, University Hospital Jena, Jena, Germany.
authors.forename: Karl-Jürgen
authors.initials: KJ
authors.lastname: Bär
authors.affiliation: Department of Ophthalmology, University Hospital Jena, Jena, Germany.|Center for Medical Optics and Photonics, University of Jena, Jena, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hammer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D009412:Nerve Fibers; D009887:Ophthalmoscopy; D061848:Optical Imaging; D012164:Retinal Diseases / Q000175:diagnosis* / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000166:cytology; D012720:Severity of Illness Index; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; C054369:MAPT protein, human; D016875:tau Proteins
keywords: Alzheimer's disease; amyloid-β; fluorescence lifetime imaging ophthalmoscopy; fundus autofluorescence; nerve fibre layer; tau-protein