title: Discordant Dry Eye Disease (An American Ophthalmological Society Thesis).
abstract: OBJECTIVE
  To improve understanding of dry eye disease and highlight a subgroup of patients who have a component of central sensitization and neuropathic pain contributing to their condition.
  
  
  METHODS
  Prospective, cross-sectional, IRB-approved study comparing isolated dry eye disease (n=48) to fibromyalgia (positive control; n=23) and healthy (negative control; n=26) individuals with ocular surface examination, corneal confocal microscopy, quantitative sensory testing, and self-reported ocular symptoms and systemic associations. A subset of patients also underwent skin biopsy and/or brain neuroimaging. Dry eye patients were split into concordant (ie, those with dry eyes on examination) and discordant (ie, those with dry eye symptoms but normal examination) subgroups for further analysis. We hypothesized that on the systemic measures included, concordant patients would resemble healthy controls, whereas discordant patients would show evidence of centralized mechanisms similar to fibromyalgia.
  
  
  RESULTS
  Schirmer test and Ocular Surface Disease Index (OSDI) scores indicated significant decreases in tear production (Schirmer: healthy, 18.5±8.2 mm; dry, 11.2±5.4 mm; fibromyalgia, 14.4±7.5;P<.001) and increases in self-reported dry eye symptoms (OSDI: healthy, 1.9±3.0; dry, 20.3±17.7; fibromyalgia, 20.3±17.1;P<.001) in the dry eye and fibromyalgia patients, compared to controls. The discordant subgroup had decreased corneal nerve density and decreased visual quality-of-life scores, similar to patients with fibromyalgia. Concordant patients were more similar to healthy controls on these measures.
  
  
  CONCLUSIONS
  Individuals with discordant dry eye may have a central pathophysiologic mechanism leading to their eye pain symptoms, which could be an important factor to consider in treatment of chronic idiopathic dry eye.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan Medical School (Dr Shtein, Mr Pallazola, Ms Hussain, Dr Sugar), and the Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan Medical School (Dr Harper, Dr Harte, Dr Williams, Dr Clauw).
authors.forename: Roni M
authors.initials: RM
authors.lastname: Shtein
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan Medical School (Dr Shtein, Mr Pallazola, Ms Hussain, Dr Sugar), and the Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan Medical School (Dr Harper, Dr Harte, Dr Williams, Dr Clauw).
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Harper
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan Medical School (Dr Shtein, Mr Pallazola, Ms Hussain, Dr Sugar), and the Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan Medical School (Dr Harper, Dr Harte, Dr Williams, Dr Clauw).
authors.forename: Vincent
authors.initials: V
authors.lastname: Pallazola
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan Medical School (Dr Shtein, Mr Pallazola, Ms Hussain, Dr Sugar), and the Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan Medical School (Dr Harper, Dr Harte, Dr Williams, Dr Clauw).
authors.forename: Steven E
authors.initials: SE
authors.lastname: Harte
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan Medical School (Dr Shtein, Mr Pallazola, Ms Hussain, Dr Sugar), and the Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan Medical School (Dr Harper, Dr Harte, Dr Williams, Dr Clauw).
authors.forename: Munira
authors.initials: M
authors.lastname: Hussain
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan Medical School (Dr Shtein, Mr Pallazola, Ms Hussain, Dr Sugar), and the Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan Medical School (Dr Harper, Dr Harte, Dr Williams, Dr Clauw).
authors.forename: Alan
authors.initials: A
authors.lastname: Sugar
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan Medical School (Dr Shtein, Mr Pallazola, Ms Hussain, Dr Sugar), and the Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan Medical School (Dr Harper, Dr Harte, Dr Williams, Dr Clauw).
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan Medical School (Dr Shtein, Mr Pallazola, Ms Hussain, Dr Sugar), and the Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan Medical School (Dr Harper, Dr Harte, Dr Williams, Dr Clauw).
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Clauw
mesh_terms: D000328:Adult; D000368:Aged; D003315:Cornea / Q000294:innervation / Q000378:metabolism / Q000473:pathology*; D003430:Cross-Sectional Studies; D015352:Dry Eye Syndromes / Q000150:complications* / Q000175:diagnosis; D058447:Eye Pain / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009885:Ophthalmology; D011446:Prospective Studies; D011788:Quality of Life; D012955:Societies, Medical; D013666:Tears / Q000378:metabolism; D014481:United States; D055815:Young Adult