title: An open-label, investigator-masked, crossover study of the ocular drying effects of two antihistamines, topical epinastine and systemic loratadine, in adult volunteers with seasonal allergic conjunctivitis.
abstract: BACKGROUND
  Systemic antihistamines such as loratadine are efficacious in the treatment of many allergic conditions. However, their use has been associated with drying effects, particularly of the ocular surface.
  
  
  OBJECTIVE
  The purpose of this study was to compare the ocular drying effects of topical treatment with epinastine hydrochloride ophthalmic solution 0.05 % twice daily and systemic treatment with loratadine 10 mg once daily in patients with seasonal allergic conjunctivitis through the use of several standard clinical tests for dry eye.
  
  
  METHODS
  This was a single-center, 4-visit, open-label, investigator-masked crossover study in healthy adult volunteers with a history of seasonal allergic conjunctivitis. Participants received 4 days of treatment with topical epinastine administered as 1 drop per eye twice daily and 4 days of treatment with systemic loratadine once daily, with a 10-day washout between treatments. Fluorophotometry was conducted at the baseline visit, at the crossover visit, and after 4 days of each treatment to assess tear volume, tear flow, and tear turnover rate. Decreases from baseline in tear volume, tear flow, or tear turnover rate were considered indicative of a drying effect. Keratitis, global (corneal and conjunctival) fluorescein staining (scale from 0-20 points), and tear film break-up time (TFBUT) were assessed after fluorophotometry at each visit. An increase in keratitis (as measured by global fluorescein staining) and conjunctival lissamine green staining, and a decrease in TFBUT were considered further evidence of a drying effect.
  
  
  RESULTS
  Eighteen subjects were enrolled in and completed the study (78% female; 94% white; age range, 18-55 years). After 4 days of twice-daily use, topical epinastine was associated with no significant changes in tear volume, tear flow, or global fluorescein staining. After 4 days of once-daily use, systemic loratadine was associated with a 33.7% reduction in tear volume (mean reduction, 4.5 microL; range, -7.53 to 22.36 microL; P < 0.05), a 35.0% reduction in tear flow (mean reduction, 0.93 microL/min; range, -2.57 to 2.73 microL/min; P < 0.05), and a 21.7% increase in global fluorescein staining (mean increase, 0.74 point; range, -2.5 to 6.5 points; P < 0.05). No significant change in TFBUT was observed with either treatment.
  
  
  CONCLUSIONS
  These healthy adult volunteers with a history of seasonal allergic conjunctivitis had no clinical signs of ocular drying after 4 days of twice-daily treatment with topical epinastine. After 4 days of once-daily dosing, systemic loratadine was associated with clinical signs of ocular dryness, including decreased tear volume and tear flow. Use of loratadine was also associated with an increase in global fluorescein staining, indicating an increase in ocular surface damage.
authors.affiliation: ORA Clinical Research and Development, North Andover, Massachusetts 01845, USA. gousler@oraclinical.com
authors.forename: George W
authors.initials: GW
authors.lastname: Ousler
authors.forename: D Andrew
authors.initials: DA
authors.lastname: Workman
authors.forename: Gail L
authors.initials: GL
authors.lastname: Torkildsen
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D003233:Conjunctivitis, Allergic / Q000188:drug therapy; D018592:Cross-Over Studies; D003984:Dibenzazepines / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D015590:Fluorophotometry; D006634:Histamine H1 Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D017336:Loratadine / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011446:Prospective Studies; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy; D016037:Single-Blind Method; D014985:Xerophthalmia / Q000139:chemically induced*
chemical_list: D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D009883:Ophthalmic Solutions; D017336:Loratadine; C053090:epinastine