title: Correlation between human tear cytokine levels and cellular corneal changes in patients with bacterial keratitis by in vivo confocal microscopy.
abstract: OBJECTIVE
  We investigated bilateral tear cytokine levels in patients with unilateral bacterial keratitis (BK) as associated with in vivo confocal microscopic (IVCM) alterations in corneal nerves and dendritiform immune cells (DCs).
  
  
  METHODS
  A total of 54 (13 BK, 13 contralateral, 28 healthy controls) tear samples was collected prospectively and analyzed by multiplex microbeads assay. The IVCM of the central cornea was performed on the same day, and assessed for corneal nerve and DC alterations.
  
  
  RESULTS
  Interleukin-1β, IL-6, and IL-8 were significantly elevated only in affected eyes (66.6 ± 26.8, 7174 ± 2430, and 810 ± 315 ρg/mL, respectively; P = 0.04, P < 0.001, and P < 0.001, respectively), compared to healthy controls (13.0 ± 4.0, 171.8 ± 32.1, and 56.5 ± 33.8 ρg/mL). Levels of chemokine ligand 2 (CCL-2), IL-10, and IL-17a were elevated only in contralateral eyes (813 ± 478, 86.7 ± 38.3, and 3350 ± 881 ρg/mL, respectively; P = 0.02, P = 0.01, and P = 0.04, respectively), compared to controls (73.7 ± 25.3, 17.5 ± 4.9, and 1350 ± 337 ρg/mL). Triggering receptor expressed on myeloid cells (TREM)-1 was significantly elevated in affected (551 ± 231 ρg/mL, P = 0.02) and contralateral unaffected (545 ± 298 ρg/mL, P = 0.03) eyes compared to controls (31.3 ± 12.4 ρg/mL). The density of DCs was significantly increased in affected (226.9 ± 37.3 cells/mm(2), P < 0.001) and unaffected (122.3 ± 23.7 cells/mm(2), P < 0.001) eyes compared to controls (22.7 ± 5.9 cells/mm(2)). Sub-basal nerve density significantly decreased in affected (3337 ± 1615 μm/mm(2), P < 0.001) and contralateral (13,230 ± 1635 μm/mm(2), P < 0.001) eyes compared to controls (21,200 ± 545 μm/mm(2)). Levels of IL-1β, IL-6, and IL-8 were significantly correlated with DC density (R = 0.40, R = 0.55, and R = 0.31, all P < 0.02) and nerve density (R = -0.30, R = -0.53, and R = -0.39, all P < 0.01).
  
  
  CONCLUSIONS
  Proinflammatory tear cytokines are elevated bilaterally in patients with unilateral BK, and are correlated strongly with alterations in DCs and nerve density as detected by IVCM.
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Bernardo M
authors.initials: BM
authors.lastname: Calvacanti
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cruzat
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Yureeda
authors.initials: Y
authors.lastname: Qazi
authors.affiliation: Department of Surgery, Brigham Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Shizu
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Department of Surgery, Brigham Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Akinori
authors.initials: A
authors.lastname: Osuka
authors.affiliation: Department of Surgery, Brigham Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: James
authors.initials: J
authors.lastname: Lederer
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Pedram
authors.initials: P
authors.lastname: Hamrah
mesh_terms: D000208:Acute Disease; D000328:Adult; D003315:Cornea / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism*; D015818:Eye Infections, Bacterial / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007634:Keratitis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods*; D011446:Prospective Studies; D013666:Tears / Q000737:chemistry*
chemical_list: D016207:Cytokines
keywords: corneal infection; cytokines; dendritic cells; infectious keratitis; tears