title: Objective characterization of the relative afferent pupillary defect in MS.
abstract: OBJECTIVE
  To develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent pupillary defects (RAPD) in patients with MS.
  
  
  METHODS
  Binocular infrared pupillometry was performed in 40 control subjects and 32 MS patients with RAPDs, using two precisely defined sequences of alternating light flashes (right-left and left-right). We analyzed three distinct pupillary metrics in response to light stimulation. These included percent diameter change (DC), constriction curve area (CCA), which measures change in diameter over time, and the phase-plane curve area (PCA) which measures change in diameter with change in velocity. Direct and consensual response ratios (for each eye) were computed and analyzed for each metric in response to both the first flash (i.e. first phase) and second flash (i.e. second phase) of the 'swinging flashlight' test.
  
  
  RESULTS
  Second flash pupillary response metric asymmetry ratios yielded the highest discriminatory power for RAPD detection. Receiver operating characteristic areas under the curve for each of the pupillary metric response asymmetry ratios were as follows: diameter change: 0.97; constriction curve area: 0.96; phase-plane curve area: 0.95 (p<0.0001 for all comparisons compared to normal subjects). The sum of these three squared ratios (SSR) yielded a combined metric with the greatest discriminatory power (receiver operator characteristic area under the curve=0.99).
  
  
  CONCLUSIONS
  Second flash (i.e. the second phase of the swinging light test) pupillary metric response asymmetry ratios are highly sensitive and specific for the confirmation and characterization of an RAPD in patients with MS. This objective neurophysiologic method may be useful for studying the relationship between a stereotyped reflex, and nervous system architecture, with potential ramifications for detecting and monitoring neuroprotective and restorative effects of novel agents in MS treatment trials.
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Blazek
authors.forename: Scott L
authors.initials: SL
authors.lastname: Davis
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Greenberg
authors.forename: Amy
authors.initials: A
authors.lastname: Conger
authors.forename: Darrel
authors.initials: D
authors.lastname: Conger
authors.forename: Steven
authors.initials: S
authors.lastname: Vernino
authors.forename: Shin
authors.initials: S
authors.lastname: Beh
authors.forename: Olaf
authors.initials: O
authors.lastname: Stuve
authors.forename: Shiv
authors.initials: S
authors.lastname: Saidha
authors.forename: John N
authors.initials: JN
authors.lastname: Ratchford
authors.forename: Ari
authors.initials: A
authors.lastname: Green
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Balcer
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Frohman
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Frohman
mesh_terms: D000328:Adult; D000344:Afferent Pathways / Q000503:physiopathology; D000886:Anthropometry / Q000379:methods*; D016022:Case-Control Studies; D005260:Female; D005544:Forecasting; D006801:Humans; D008027:Light; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications*; D009902:Optic Neuritis / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D010775:Photic Stimulation; D011681:Pupil Disorders / Q000175:diagnosis* / Q000209:etiology; D012025:Reflex, Pupillary / Q000502:physiology / Q000528:radiation effects; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity