Serum vascular endothelial growth factor changes and safety after topical anti‐human VEGF antibody bevacizumab in healthy dogs

Abstract

ObjectiveTo evaluate ocular and general safety of topical anti‐human VEGF bevacizumab and the effect on serum vascular endothelial growth factor (VEGF) values in healthy dogs.ProceduresNine university‐owned beagles received 0.05 mL of 0.25% bevacizumab eyedrops (Avastin®, Roche) in one eye and 0.05 mL of 0.9% saline solution in the other eye as a control, administered at 12 hours intervals over a period of 28 days. Continuous monitoring for vital parameters and ocular examinations were conducted. Complete blood counts including hematology and coagulation parameters were performed before trial start as well as 24 hours, 7 days, and 28 days after trial start. Measurements of serum VEGF values were obtained using an ELISA‐based approach at days 0, 7, and 28. The experiment was designed as a masked placebo‐controlled study.ResultsNo clinical signs of ocular toxicity or systemic incompatibility were noted in any dog at any time point of the study. No signs of pain were present in any dog at any time point. All blood count values remained in normal clinical ranges without relevant variation. There was no significant change in mean serum VEGF values between day 0 and day 7 and between day 0 and day 28.ConclusionsThe results indicate that topical bevacizumab treatment is safe in healthy dogs. However, further studies are needed to assess safety and efficacy in diseased dogs with naturally occurring corneal neovascularization.

Topical bevacizumab for the treatment of corneal vascularization in dogs: A case series

“…In healthy dogs, administration of topical 0.25% bevacizumab for 28 days was shown to have no effect on systemic VEGF levels. 44 Although the uptake of bevacizumab into the bloodstream may be different in an inflamed cornea and conjunctiva, we do not believe that bevacizumab given for a short time and at a low dose of 0.25% would reach a therapeutic concentration high enough to cause systemic side effects. 48 Since the dogs died several months after the last bevacizumab administration, showed no abnormalities in the physical examinations during bevacizumab treatment, and the dose was very low, a causative relation is considered unlikely.…”

“…Both dogs had no signs of cardiovascular or pulmonary dysfunction prior or during the study. In healthy dogs, administration of topical 0.25% bevacizumab for 28 days was shown to have no effect on systemic VEGF levels 44 . Although the uptake of bevacizumab into the bloodstream may be different in an inflamed cornea and conjunctiva, we do not believe that bevacizumab given for a short time and at a low dose of 0.25% would reach a therapeutic concentration high enough to cause systemic side effects 48 .…”

“…In our study, we investigated the dosage of 2.5 mg/ml for the duration of 28 days. Due to the lack of knowledge of bevacizumab's safety profile in dogs, we opted for a low dose for a short period of time 44 9,10,25,45 .…”

“…Due to the lack of knowledge of bevacizumab's safety profile in dogs, we opted for a low dose for a short period of time. 44 Various treatment regimes and drug doses of topical bevacizumab have been investigated. 9 , 10 , 25 , 45 Higher doses up to 25 mg/ml four times a day for 2 weeks, 45 10 mg/ml either two or four times a day for 3 weeks, 9 , 10 or 5 mg/ml one to ten times a day for up to 12 months 25 are reported to be effective for the treatment of corneal vascularization in humans.…”

Adjunctive bevacizumab therapy in an equine corneal stromal invasive squamous cell carcinoma with a 53-months follow-up

“…Topical bevacizumab 0.25% q12h in one eye over 28 days was a safe treatment in healthy beagles 17 and adverse effects appeared unlikely in diseased dogs 10 . In the present case, only subconjunctival 18 or intrastromal applications were considered effective since the corneal epithelium was intact.…”