In vitro efficacy of ganciclovir against feline herpesvirus type 1 and assessment of ocular tolerability in healthy cats

Abstract

Objectives Feline herpesvirus-1 (FHV-1) is a prevalent cause of ocular disease in cats and limited topical options for treatment currently exist. The first objective of this study was to confirm the efficacy of ganciclovir against FHV-1 in vitro. The second objective was to assess the safety and ocular tolerability of topically applied ganciclovir eye gel (GEG) in healthy cats. Methods FHV-1 was used to infect tissue culture wells covered in maximally confluent Crandall–Rees feline kidney cells prior to the addition of three molarities of ganciclovir (8.9 µM, 17.8 µM and 89 µM) before being incubated for 48 h. Ganciclovir efficacy in vitro was then assessed using standard plaque reduction assay. Commercially available GEG (0.15%) was applied q8h to one randomly chosen eye of four healthy cats for 7 days. Commercially available lubricating eye gel (LEG) was applied to the opposite eye q8h. Complete blood counts (CBC), blood chemistry panels (CHEM) and urinalysis (UA) were performed on all cats before and after the study period. Ocular lesions were assessed daily using a standardized scheme. Results Ganciclovir led to a significant reduction in FHV-1 plaque number, area and diameter at all tested molarities in vitro. The highest molarity assessed (89 µM) caused a 100% reduction in viral plaque number. There was no significant difference in lesion scores between eyes receiving GEG and LEG. Animals remained healthy throughout the study period with CBC, CHEM and UA showing no clinically significant alterations. Conclusions and relevance Based on the in vitro results, ganciclovir appears to be effective against FHV-1 in vitro. When applied q8h as a commercial 0.15% gel to a small group of cats with normal eyes, this medication was well tolerated. Taken together, these data suggest this medication warrants further investigation in cats with ocular disease caused by FHV-1.

Evaluation of compounded cidofovir, famciclovir, and ganciclovir for the treatment of feline herpesvirus ocular surface disease in shelter‐housed cats

“…Ganciclovir has previously demonstrated good efficacy against FHV-1 in experimental in vitro studies. 31,34 A recent abstract on the use of 0.15% ganciclovir ointment in cats experimentally infected with FHV-1 reported a significant improvement in ocular clinical signs for cats treated with ganciclovir compared with placebo treatment, and no significant difference in viral shedding compared with placebo treatment. 35 For this study, cats received topical ophthalmic 0.15% ganciclovir ointment three times daily for 14 days and were monitored for a total of 30 days following viral challenge.…”

“…33 Ganciclovir, another antiviral medication applied topically to the eye, was shown to have high efficacy against FHV-1 in vitro, and has been evaluated for ocular tolerance and side effects in cats, with no significant side effects noted following administration every 8 h over 7 days. 31,34 Ganciclovir (administered every 8 h) has preliminarily been evaluated in experimentally FHV-1 infected cats for the treatment of ocular disease and led to a significant improvement in clinical signs. 35 The objective of this masked placebo-controlled study was to simultaneously evaluate efficacy of three commonly utilized compounded antiviral drugs for the treatment of FHV-1 ocular disease in naturally-infected shelter-housed cats.…”

“…In cats experimentally infected with FHV‐1, cidofovir has been shown to decrease ocular viral shedding and improve ocular clinical signs (administered every 12 h) 33 . Ganciclovir, another antiviral medication applied topically to the eye, was shown to have high efficacy against FHV‐1 in vitro, and has been evaluated for ocular tolerance and side effects in cats, with no significant side effects noted following administration every 8 h over 7 days 31,34 . Ganciclovir (administered every 8 h) has preliminarily been evaluated in experimentally FHV‐1 infected cats for the treatment of ocular disease and led to a significant improvement in clinical signs 35 …”

Assessment of Cidofovir for Treatment of Ocular Bovine Herpesvirus-1 Infection in Cattle Using an Ex-Vivo Model

“…This drug belongs to a family of nucleoside analogue agents that inhibit viral replication by truncating nucleotide strands during viral DNA production. They are the primary means of treating herpes simplex keratitis in human patients [ 37 ] and have been studied extensively in vitro and in vivo for use against other herpesviruses causing ophthalmic disease in domestic animal species, particularly cats [ 10 , 11 , 12 , 14 , 15 , 18 , 19 , 38 , 39 , 40 , 41 ]. Cidofovir inhibition of BoHV-1 has been studied previously, with Gilliam and Field calculating an in-vitro IC 50Number of 10 μg/mL (35.8 μM) [ 23 ], which is very similar to our independently calculated value described here (39.7 μM).…”

Comparative Efficacy of Topical Ophthalmic Ganciclovir and Oral Famciclovir in Cats with Experimental Ocular Feline Herpesvirus-1 Epithelial Infection

“…18 , 19 A recent study determined that ganciclovir 0.15% aqueous ophthalmic gel was well-tolerated and nontoxic when applied to a small group of laboratory cats without ocular disease 3 times daily for 1 week, but the efficacy of ganciclovir has not been evaluated in cats with ocular FHV-1 infections. 20 …”