title: Effects of corneal nerve density on the response to treatment in dry eye disease.
abstract: OBJECTIVE
  To evaluate whether levels of corneal subbasal nerve fiber length (SNFL) in dry eye disease (DED) could prognosticate the level of improvement in signs and symptoms after treatment.
  
  
  METHODS
  Phase IV, double-masked, randomized clinical trial.
  
  
  METHODS
  Sixty patients with meibomian gland dysfunction-associated DED and 27 age-matched controls.
  
  
  METHODS
  Patients with DED were randomized to receive topical artificial tears, loteprednol etabonate 0.5%, or loteprednol etabonate 0.5%/tobramycin 0.3% twice daily for 4 weeks. At baseline, in vivo confocal microscopy of central cornea was performed in both eyes. Patients with DED were divided into 2 subgroups: those with low baseline SNFL and those with near-normal baseline SNFL for this purpose (the cutoff point: the mean SNFL in controls minus 2 standard deviations). Clinical signs and symptoms at baseline and after 4 weeks of treatment were compared between the subgroups with low and near-normal SNFL for all therapeutic groups.
  
  
  METHODS
  Symptom questionnaires, corneal fluorescein staining (CFS), conjunctival staining with lissamine green, tear break-up time, Schirmer's test, and SNFL.
  
  
  RESULTS
  In patients with DED, baseline SNFL (17.06±5.78 mm/mm(2)) was significantly lower than in controls (23.68±3.42 mm/mm(2), P = 0.001). In the artificial tear and loteprednol groups, although no significant improvement in any sign or symptom was noted in patients with low baseline SNFL (<16.84 mm/mm(2)), subjects with near-normal baseline SNFL (≥16.84 mm/mm(2)) showed significant improvement in both symptoms and CFS score (all P < 0.05). In the loteprednol/tobramycin group, no significant change was evident for any sign or symptom in either subgroup of low or near-normal baseline SNFL.
  
  
  CONCLUSIONS
  Significant improvements in CFS and patient symptomatology after DED treatment were evident only in the subgroup with near-normal corneal SNFL. Consideration of SNFL may assist in explaining the variability of patients' response to DED therapy.
authors.affiliation: Cornea & Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Kheirkhah
authors.affiliation: Cornea & Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Dohlman
authors.affiliation: Cornea & Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Francisco
authors.initials: F
authors.lastname: Amparo
authors.affiliation: Cornea & Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Arnoldner
authors.affiliation: Cornea & Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Arsia
authors.initials: A
authors.lastname: Jamali
authors.affiliation: Cornea & Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Pedram
authors.initials: P
authors.lastname: Hamrah
authors.affiliation: Cornea & Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. Electronic address: Reza_Dana@meei.harvard.edu.
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage*; D018926:Anti-Allergic Agents / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D003315:Cornea / Q000294:innervation*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000188:drug therapy*; D005141:Eyelid Diseases / Q000175:diagnosis / Q000188:drug therapy; D005260:Female; D006801:Humans; D000069559:Loteprednol Etabonate; D065346:Lubricant Eye Drops / Q000008:administration & dosage; D008297:Male; D008537:Meibomian Glands / Q000187:drug effects / Q000473:pathology; D018613:Microscopy, Confocal; D008875:Middle Aged; D009882:Ophthalmic Nerve / Q000473:pathology*; D009883:Ophthalmic Solutions; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D014031:Tobramycin / Q000008:administration & dosage*
chemical_list: D000730:Androstadienes; D018926:Anti-Allergic Agents; D000900:Anti-Bacterial Agents; D065346:Lubricant Eye Drops; D009883:Ophthalmic Solutions; D014031:Tobramycin; D000069559:Loteprednol Etabonate