title: Topical drug formulations for prolonged corneal anesthesia.
abstract: OBJECTIVE
  Ocular local anesthetics currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect of the site 1 sodium channel blocker tetrodotoxin (TTX) on the duration of corneal anesthesia, applied with either proparacaine (PPC) or the chemical permeation enhancer octyl-trimethyl ammonium bromide (OTAB). The effect of test solutions on corneal healing was also studied.
  
  
  METHODS
  Solutions of TTX, PPC, and OTAB, singly or in combination, were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia was calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo after corneal debridement.
  
  
  RESULTS
  Combination of TTX and PPC resulted in corneal anesthesia that was 8 to 10 times longer in duration than that from either drug administered alone, whereas OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed after coadministration of TTX and PPC.
  
  
  CONCLUSIONS
  Coadministration of TTX and PPC significantly prolonged corneal anesthesia, but in view of delayed corneal reepithelialization, caution is suggested in the use of the drug combination.
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Wang
authors.forename: Sahadev A
authors.initials: SA
authors.lastname: Shankarappa
authors.forename: Rong
authors.initials: R
authors.lastname: Tong
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Ciolino
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Tsui
authors.forename: Homer H
authors.initials: HH
authors.lastname: Chiang
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: D000772:Anesthesia, Local / Q000379:methods*; D019162:Anesthetics, Combined; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D003315:Cornea / Q000187:drug effects* / Q000502:physiology; D060527:Corneal Keratocytes / Q000187:drug effects; D019573:Epithelium, Corneal / Q000187:drug effects; D006801:Humans; D008297:Male; D011430:Propoxycaine / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
chemical_list: D019162:Anesthetics, Combined; D000779:Anesthetics, Local; D000644:Quaternary Ammonium Compounds; D026941:Sodium Channel Blockers; C042006:octyltrimethylammonium; D013779:Tetrodotoxin; C005717:proxymetacaine; D011430:Propoxycaine