Comparison of ophthalmic loteprednol etabonate and prednisolone acetate effects on adrenocortical response to ACTH in dogs

Vet Ophthalmol. 2022 Nov;25(6):468-475. doi: 10.1111/vop.13017. Epub 2022 Aug 1.


Objective: This study served to compare the degree of adrenocortical suppression following a 2-week administration of loteprednol etabonate (LE) and prednisolone acetate (PA) ophthalmic drops.

Procedures: In this prospective double-masked triple-crossover study, 21 clinically healthy dogs were randomized to receive loteprednol etabonate ophthalmic suspension 0.5%, prednisolone acetate ophthalmic suspension 1%, or artificial tears (AT). Each group (LE, PA, and AT) received one drop in each eye every 12 h for 2 weeks, followed by a 3-week washout period between treatment blocks. ACTH stimulation tests were performed before and after each treatment block. Serum cortisol samples were drawn before and 60 min after administration of 1 μg/kg cosyntropin IV. Repeated-measurement ANOVA followed by a Tukey's multiple comparisons test (or a Friedman test followed by a Dunn's multiple comparisons test) were used to compare pre- and post-treatment cortisol values between each group. A p-value of ≤.05 was considered significant.

Results: A total of 18 dogs completed the study. Prestimulation cortisol values were lower in the PA group compared to the LE (p = .0106), but not AT (p = .0589) groups, and post-stimulation cortisol values were lower in the PA group than either LE (p = .0005) or AT (p = .0002) groups. There was no significant difference detected in pre- or post-stimulation cortisol values after the treatment periods between LE and AT.

Conclusions: Based on the reduced suppression of cortisol values, LE caused significantly less hypothalamic-pituitary-adrenal axis suppression than PA. A topical steroid with minimal adrenocortical suppression, such as LE, may be favorable in patients where systemic glucocorticoid effects should be avoided.

Keywords: adrenocortical suppression; canine hypothalamic-pituitary-adrenal axis; loteprednol etabonate; prednisolone acetate.

Publication types

  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Adrenocorticotropic Hormone / pharmacology
  • Androstadienes / adverse effects
  • Animals
  • Cross-Over Studies
  • Dogs
  • Hydrocortisone*
  • Hypothalamo-Hypophyseal System*
  • Loteprednol Etabonate
  • Ophthalmic Solutions / adverse effects
  • Pituitary-Adrenal System
  • Prospective Studies


  • Loteprednol Etabonate
  • prednisolone acetate
  • Hydrocortisone
  • Androstadienes
  • Ophthalmic Solutions
  • Adrenocorticotropic Hormone