title: Relationship between orbital optic nerve axon counts and retinal nerve fiber layer thickness measured by spectral domain optical coherence tomography.
abstract: OBJECTIVE
  We determined the relationship between total optic nerve axon counts and peripapillary retinal nerve fiber layer thickness (RNFLT) measured in vivo by spectral domain optical coherence tomography (SDOCT).
  
  
  METHODS
  A total of 22 rhesus macaques had three or more baseline measurements in both eyes of peripapillary RNFLT made by SDOCT. Laser photocoagulation then was applied to the trabecular meshwork of one eye to induce chronic unilateral IOP elevation. SDOCT measurements of RNFLT continued approximately every two weeks until the predefined study endpoint was reached in each animal. At endpoint, animals were sacrificed and the optic nerve was sampled approximately 2 mm behind the globe to obtain thin sections for histologic processing and automated axon counting across 100% of the optic nerve cross-sectional area.
  
  
  RESULTS
  At the final imaging session, the average loss of RNFLT was 20 ± 21%, ranging from essentially no loss to nearly 65% loss. Total optic nerve axon count in control eyes ranged from 812,478 to 1,280,474. The absolute number of optic nerve axons was related linearly to RNFLT (axon count = 12,336 × RNFLT((μm)) - 257,050, R(2) = 0.65, P < 0.0001), with a Pearson correlation coefficient of 0.81. There also was a strong linear relationship between relative optic nerve axon loss (glaucomatous-to-control eye) and relative RNFLT at the final imaging session, with a slope close to unity but a significantly negative intercept (relative axon loss((%)) = 1.05 × relative RNFLT loss((%)) - 14.4%, R(2) = 0.75, P < 0.0001). The negative intercept was robust to variations of fitted model because relative axon loss was -14% on average for all experimental glaucoma (EG) eyes within 6% (measurement noise) of zero relative loss.
  
  
  CONCLUSIONS
  There is a strong linear relationship between total optic nerve axon count and RNFLT measured in vivo by SDOCT. However, substantial loss of optic nerve axons (∼10%-15%) exists before any loss of RNFLT manifests and this discrepancy persists systematically throughout a wide range of damage.
authors.affiliation: Discoveries in Sight Research Laboratories, Devers Eye Institute, and Legacy Research Institute, Legacy Health, Portland, Oregon 97232, USA.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Cull
authors.forename: Juan
authors.initials: J
authors.lastname: Reynaud
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: George A
authors.initials: GA
authors.lastname: Cioffi
authors.forename: Claude F
authors.initials: CF
authors.lastname: Burgoyne
authors.forename: Brad
authors.initials: B
authors.lastname: Fortune
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D005901:Glaucoma / Q000150:complications / Q000473:pathology*; D008253:Macaca mulatta; D008297:Male; D009412:Nerve Fibers / Q000473:pathology*; D009900:Optic Nerve / Q000473:pathology*; D009901:Optic Nerve Diseases / Q000209:etiology / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence / Q000379:methods*; D014129:Trabecular Meshwork / Q000473:pathology