title: Ganglion cell loss in relation to visual disability in multiple sclerosis.
abstract: OBJECTIVE
  We used high-resolution spectral-domain optical coherence tomography (SD-OCT) with retinal segmentation to determine how ganglion cell loss relates to history of acute optic neuritis (ON), retinal nerve fiber layer (RNFL) thinning, visual function, and vision-related quality of life (QOL) in multiple sclerosis (MS).
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  A convenience sample of patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes). Among MS eyes, 87 had a history of ON before enrollment.
  
  
  METHODS
  The SD-OCT images were captured using Macular Cube (200×200 or 512×128) and ONH Cube 200×200 protocols. Retinal layer segmentation was performed using algorithms established for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus control eyes and MS ON versus non-ON eyes. The relation between changes in macular thickness and visual disability was also examined.
  
  
  METHODS
  The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement composite score.
  
  
  RESULTS
  Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (P<0.001 and P = 0.001) and in MS ON versus non-ON eyes (P<0.001 for both measures). Peripapillary RNFL, macular RNFL, GCL+IPL, and the combination of macular RNFL+GCL+IPL were significantly correlated with VA (P≤0.001), 2.5% LCLA (P<0.001), and 1.25% LCLA (P≤0.001). Among OCT measurements, reductions in GCL+IPL (P<0.001), macular RNFL (P = 0.006), and the combination (macular RNFL+GCL+IPL; P<0.001) were most strongly associated with lower (worse) NEI-VFQ-25 and 10-Item Supplement QOL scores; GCL+IPL thinning was significant even accounting for macular RNFL thickness (P = 0.03 for GCL+IPL, P = 0.39 for macular RNFL).
  
  
  CONCLUSIONS
  We demonstrated that GCL+IPL thinning is most significantly correlated with both visual function and vision-specific QOL in MS, and may serve as a useful structural marker of disease. Our findings parallel those of magnetic resonance imaging studies that show gray matter disease is a marker of neurologic disability in MS.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Walter
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Galetta
authors.forename: Reiko E
authors.initials: RE
authors.lastname: Sakai
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Feller
authors.forename: Sam B
authors.initials: SB
authors.lastname: Henderson
authors.forename: James A
authors.initials: JA
authors.lastname: Wilson
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Maguire
authors.forename: Steven L
authors.initials: SL
authors.lastname: Galetta
authors.forename: Elliot
authors.initials: E
authors.lastname: Frohman
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: Joel S
authors.initials: JS
authors.lastname: Schuman
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Balcer
mesh_terms: D000328:Adult; D000465:Algorithms; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009412:Nerve Fibers / Q000473:pathology*; D009902:Optic Neuritis / Q000503:physiopathology*; D011788:Quality of Life; D012165:Retinal Ganglion Cells / Q000473:pathology*; D018434:Sickness Impact Profile; D011795:Surveys and Questionnaires; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000503:physiopathology; D014792:Visual Acuity / Q000502:physiology*