Comparative Evaluation of Several Methods and Conditions for the in Vivo Measurement of Corneal Thickness in Rabbits and Rats

Abstract

Un ion Ca rbide Cor por a t ion , Dan bu ry, Con n ect icu t , USA S u san M . Ch ristop h er E li Lilly a n d Com p a n y, Gr een ® eld, In dian a , USA J ean S . Ch u n P P G In du st r ies, In c., Allison Pa r k, Pen n sylva n ia, USA In vivo corn eal th ick n ess (CT ) m easurem en ts can be u sed to pred ict corn eal inju rin g potent ial in low -volu m e ocu lar in stillation an d low-con centration vaporexposu re stu dies. In t his stud y, CT w as m easured u sin g several techn iqu es an d con d ition s to assess th e m ost accurate an d h u m an e m eth od s for use in pred ictin g corneal in ju ry. In itially, CT w as m easured in th e u nan esth etized cornea of u nsedated rabbits u sing an op tical or u ltrason ic pach ym eter; accurate m easurem ents could n ot be obtain ed becau se of rabbit excitability. S u bsequen tly, ch anges in corneal th ickn ess w ere evaluated in rabbits followin g treatm ent w ith com bin ation s of t he sedative ketam in e, th e topical an esth etic propa racain e, an d / or th e m ild irritan t d ichlorom eth an e (DCM; 0.1 m L ) usin g an u ltrason ic pach ym eter. M ean CT w as u p to 17% lower in eyes of sedated rabbits receivin g proparacain e th an in eyes w ith ou t proparacain e. For eyes tested w ith DCM an d proparacain e, CT in creases correlated w ell w ith observed eye irritation (r = 0.73). Corn eal in ju ry and iritis w ere m ore severe in an im als w ith ou t topical an esth esia. An u ltrason ic pach ym eter w as u sed to m easure CT in rabbits previou sly con d ition ed to rem ain calm in cat ba gs, and in rats restrain ed w ith paper tow els; n o sedative or topical an esth etic w as u sed . After instillation of DCM , CT in creased in rabbits correspon din g to th e severity of irritat ion (r = 0.79). U n treated eyes sh ow ed con sisten t valu es th rou gh ou t th e d ay. CT w as also m easured in con trol (untreated ) rat s and a grou p of rats h avin g bis[2-(dim eth ylam in o)ethyl]eth er, an irritan t, applied to t he eye. Ch an ges w ere m easured in both irritan t-treated an d con trol eyes. CT valu es in u n treated rat eyes varied by u p to 21%, bu t th e corneal th ickn ess of th e irritan t-treated eyes dou bled. Th e ® n d in gs d em on strated th at a relatively good correlation betw een corneal th ickn ess an d ocular irritation can be obtain ed u sin g an u ltrason ic pach ym eter on gen tly restrain ed an im als. Th e d ata con ® rm th at m easurem en t of corneal t hick ness is a u sefu l an d sen sitive qu an titative m eth od for assessm en t of eye irritation .Ke y w o rd s cor nea , cor n eal t h ickn ess, r a t , r a bbit, pa ch ym et er, ret am in e, pr op a ra cain e, dichlorom et h a n e Received 14 N ovem ber 1997; a ccept ed 15 Ma y 1998. Addr ess cor respon den ce t o Dr. Brya n Ba llan t yn e, Applied Toxicology Gr ou p, Un ion Car bide Cor por a t ion , Sect ion K-3, 39 Old Ridgebur y Roa d, Da n bu r y, CT 06817-0001, USA.