title: Retinal imaging by laser polarimetry and optical coherence tomography evidence of axonal degeneration in multiple sclerosis.
abstract: BACKGROUND
  Optical coherence tomography (OCT) and scanning laser polarimetry with variable corneal compensation (GDx) are similar yet provide information on different aspects of retinal nerve fiber layer (RNFL) structure (thickness values similar to histology for OCT vs birefringence of microtubules for GDx).
  
  
  OBJECTIVE
  To compare the ability of OCT and GDx to distinguish eyes of patients with multiple sclerosis (MS) from eyes of disease-free controls and thus identify RNFL abnormalities. We also sought to examine the capacity of these techniques to distinguish MS eyes from those without a history of optic neuritis and to correlate with visual function.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Academic tertiary care MS center.
  
  
  METHODS
  Eighty patients with MS (155 eyes) and 43 disease-free controls (85 eyes) underwent both OCT and GDx imaging using protocols that measure RNFL thickness.
  
  
  METHODS
  Areas under the curve (AUC), adjusted for within-patient, intereye correlations, were used to compare the abilities of OCT and GDx temporal-superior-nasal-inferior-temporal average RNFL thicknesses to discriminate between MS and control eyes and to distinguish MS eyes with a history of optic neuritis. Visual function was evaluated using low-contrast letter acuity and high-contrast visual acuity.
  
  
  RESULTS
  Average peripapillary RNFL thickness (360 degrees around the optic disc) was reduced in patients with MS compared with controls for both methods. Age-adjusted AUC did not differ between OCT (0.80; 95% confidence interval [CI], 0.72-0.88) and GDx (0.78; 95% CI, 0.68-0.86; P = .38). Optical coherence tomography-measured RNFL thickness was somewhat better at distinguishing MS eyes with a history of optic neuritis from those without (OCT: AUC, 0.73; 95% CI, 0.64-0.82; GDx: AUC, 0.66; 95% CI, 0.57-0.66; P = .17). Linear correlations of RNFL thickness for OCT vs GDx were significant yet moderate (r = 0.67, P < .001); RNFL thickness measures correlated moderately and significantly with low-contrast acuity (OCT: r = 0.54, P < .001; GDx: r = 0.55, P < .001) and correlated less with high-contrast visual acuity (OCT: r = 0.44, P < .001; GDx: r = 0.32, P < .001).
  
  
  CONCLUSIONS
  Scanning laser polarimetry with variable corneal compensation measurements of RNFL thickness corroborates OCT evidence of visual pathway axonal loss in MS and provides new insight into structural aspects of axonal loss that relate to RNFL birefringence (microtubule integrity). These results support validity for RNFL thickness as a marker for axonal degeneration and support use of these techniques in clinical trials that examine neuroprotective and other disease-modifying therapies.
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Maulik S
authors.initials: MS
authors.lastname: Zaveri
authors.forename: Amy
authors.initials: A
authors.lastname: Conger
authors.forename: Amber
authors.initials: A
authors.lastname: Salter
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Frohman
authors.forename: Steven L
authors.initials: SL
authors.lastname: Galetta
authors.forename: Clyde E
authors.initials: CE
authors.lastname: Markowitz
authors.forename: Dina A
authors.initials: DA
authors.lastname: Jacobs
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cutter
authors.forename: Gui-Shuang
authors.initials: GS
authors.lastname: Ying
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Maguire
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Balcer
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Frohman
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007834:Lasers / Q000592:standards; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods / Q000592:standards; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D009410:Nerve Degeneration / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D009412:Nerve Fibers / Q000473:pathology; D009898:Optic Disk / Q000473:pathology; D012160:Retina / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology; D041623:Tomography, Optical Coherence / Q000379:methods* / Q000592:standards; D014792:Visual Acuity / Q000502:physiology