title: Longitudinal alterations in the dynamic autoregulation of optic nerve head blood flow revealed in experimental glaucoma.
abstract: OBJECTIVE
  To use a novel dynamic autoregulation analysis (dAR) to test the hypothesis that the optic nerve head (ONH) blood flow (BF) autoregulation is disrupted during early stages of experimental glaucoma (EG) in nonhuman primates.
  
  
  METHODS
  Retinal nerve fiber layer thickness (RNFLT, assessed by optical coherence tomography) and ONH BF (assessed by laser speckle imaging technique) were measured biweekly before and after unilateral laser treatment to the trabecular meshwork. Each nonhuman primate was followed until reaching either an early stage of damage (RNFLT loss < 20%, n = 6) or moderate to advanced stages of damage (RNFLT loss > 20%, n = 9). At each test, dAR was assessed by characterizing ONH BF changes during the first minute of rapid manometrical intraocular pressure (IOP) elevation from 10 to 40 mm Hg. The dAR analysis extracted the following parameters: baseline BF, average BF 10 seconds before IOP elevation; BFΔmax, maximum BF change from baseline BF; Tr, time from baseline BF to the BFΔmax; Kr, average descending BF rate.
  
  
  RESULTS
  Mean postlaser IOP was 20.2 ± 5.9 and 12.3 ± 2.6 mm Hg in EG and control eyes, respectively (P < 0.0001). Compared with prelaser values, baseline BF was higher in early EG, but lower in moderate to advanced EG (P = 0.01). Tr was increased and Kr was reduced in both stages (P < 0.01). BFΔmax was smaller in the early EG (P = 0.05) and remained low in the moderate to advanced EG (P = 0.15). No changes in the parameters were observed in control eyes.
  
  
  CONCLUSIONS
  Chronic IOP elevation causes ONH autoregulation dysfunction in the early stage of EG, characterized by a disrupted BF response and delayed Tr, revealed by dAR analysis.
authors.affiliation: Devers Eye Institute, Legacy Research Institute, Portland, Oregon, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Devers Eye Institute, Legacy Research Institute, Portland, Oregon, United States.
authors.forename: Grant
authors.initials: G
authors.lastname: Cull
authors.affiliation: Devers Eye Institute, Legacy Research Institute, Portland, Oregon, United States.
authors.forename: Claude F
authors.initials: CF
authors.lastname: Burgoyne
authors.affiliation: Devers Eye Institute, Legacy Research Institute, Portland, Oregon, United States.
authors.forename: Simon
authors.initials: S
authors.lastname: Thompson
authors.affiliation: Devers Eye Institute, Legacy Research Institute, Portland, Oregon, United States.
authors.forename: Brad
authors.initials: B
authors.lastname: Fortune
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D005901:Glaucoma / Q000473:pathology / Q000503:physiopathology*; D006706:Homeostasis / Q000502:physiology*; D007429:Intraocular Pressure; D008253:Macaca mulatta; D008297:Male; D009898:Optic Disk / Q000098:blood supply* / Q000503:physiopathology; D012039:Regional Blood Flow / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000473:pathology; D012171:Retinal Vessels / Q000503:physiopathology*; D041623:Tomography, Optical Coherence
keywords: autoregulation; experimental glaucoma; optic nerve head