title: Efficacy and safety of three ophthalmic inserts for topical anaesthesia of the cornea. An exploratory comparative dose-ranging, double-blind, randomized trial in healthy volunteers.
abstract: BACKGROUND
  Cataract surgery requires prolonged anaesthesia, concomitant with permanent hydration and lubrication of the cornea, in order to provide a clear view of the operation area.
  
  
  OBJECTIVE
  The primary objective of the study was to assess several formulae of a soluble ophthalmic insert: TOPICSERT [bupivacaine (Bupi) + hyaluronic acid (HA) or sodium hyaluronate] in terms of complete and long-lasting anaesthesia of the cornea. The hydration properties of HA were not assessed in this study.
  
  
  METHODS
  In a prospective double-blind, cross-over, randomized study, with latin-square allocation of treatments, 16 healthy volunteers received a single dose of each formula (A, 1 mg Bupi and 0.1 mg HA; B, 0.5 mg Bupi and 0.1 mg HA; C, 1 mg Bupi and 0 mg HA, and D acting as a placebo) via the ocular route with 1 week of wash-out between each period. Corneal anaesthesia was measured using a Cochet-Bonnet esthesiometer.
  
  
  RESULTS
  There was a statistically significant difference between treatments with regard to the main criterion (complete anaesthesia lasting at least 20 min) when general association statistics were used (Mantel-Haenzel test, P < 0.0001): 68.75% (n = 11) of subjects receiving treatment A, 37.5% (n = 6) receiving treatment B, and 87.5% (n = 14) on treatment C reached complete and satisfactory anaesthesia, while this was not achieved in any of the subjects receiving placebo. Ninety-five percent confidence intervals of the difference between treatments were as follows: treatment A vs. B (-0.03, 0.66), treatment A vs. C (-0.47, 0.10), treatment B vs. C (-0.84, - 0.16). Only the difference between B and C was statistically significant (adjusted probability by the method of Bonferroni, P < 0.001). When complete anaesthesia was reached, mean (+/-SD) duration of anaesthesia was as follows: 20.7 (+/-6.5), 15.3 (+/-11.4) and 24.7 (+/-7.6) min for treatments A, B, C, respectively.
  
  
  CONCLUSIONS
  Bupivacaine 1 mg seems to be the efficient and safe dose. The value of hyaluronic acid as a corneal hydration agent and used in association with bupivacaine will be the subject of further studies.
authors.affiliation: Unité de Recherches Thérapeutiques, Hôpital Lariboisière, 2 Rue A. Paré 75010 Paris, France. isabelle.mahe@lrb.ap-hop-paris.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mahé
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mouly
authors.forename: Irène
authors.initials: I
authors.lastname: Jarrin
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Otéro
authors.forename: Catherine
authors.initials: C
authors.lastname: Tavera
authors.forename: Guy
authors.initials: G
authors.lastname: Simoneau
authors.forename: Yves
authors.initials: Y
authors.lastname: Tillet
authors.forename: Robert
authors.initials: R
authors.lastname: Conti
authors.forename: Saïd
authors.initials: S
authors.lastname: El Meski
authors.forename: Alain
authors.initials: A
authors.lastname: Gaudric
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bergmann
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000772:Anesthesia, Local / Q000379:methods; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000009:adverse effects; D002045:Bupivacaine / Q000008:administration & dosage* / Q000009:adverse effects; D002387:Cataract Extraction; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004343:Drug Implants; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D011446:Prospective Studies
chemical_list: D000276:Adjuvants, Immunologic; D000779:Anesthetics, Local; D004338:Drug Combinations; D004343:Drug Implants; D006820:Hyaluronic Acid; D002045:Bupivacaine