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

Bovine herpesvirus-1 (BoHV-1) infection contributes to keratoconjunctivitis, respiratory disease, and reproductive losses in cattle. The objective of this study was to determine the most appropriate ophthalmic antiviral agent for BoHV-1 inhibition using in-vitro culture and novel ex-vivo bovine corneal modeling. Half-maximal inhibitory concentrations of BoHV-1 were determined for cidofovir, ganciclovir, idoxuridine, and trifluridine via in-vitro plaque reduction assays. In-vitro cytotoxicity was compared amongst these compounds via luciferase assays. Trifluridine and cidofovir were the most potent BoHV-1 inhibitors in vitro, while trifluridine and idoxuridine were the most cytotoxic agents. Therefore, cidofovir was the most potent non-cytotoxic agent and was employed in the ex-vivo corneal assay. Corneoscleral rings (n = 36) from fresh cadaver bovine globes were harvested and equally divided into an uninfected, untreated control group; a BoHV-1-infected, untreated group; and a BoHV-1-infected, cidofovir-treated group. Virus isolation for BoHV-1 titers was performed from corneal tissue and liquid media. Histologic measurements of corneal thickness, epithelial cell density, and tissue organization were compared between groups. Substantial BoHV-1 replication was observed in infected, untreated corneas, but BoHV-1 titer was significantly reduced in cidofovir-treated (1.69 ± 0.08 × 103 PFU/mL) versus untreated (8.25 ± 0.25 × 105 PFU/mL, p < 0.0001) tissues by day 2 of culture. No significant differences in histologic criteria were observed between groups. In conclusion, cidofovir warrants further investigation as treatment for BoHV-1 keratoconjunctivitis, with future studies needed to assess in-vivo tolerability and efficacy.

Effect of multiple head positions on intraocular pressure in healthy, anesthetized horses during hoisting.

OBJECTIVE: To evaluate changes in intraocular pressure (IOP) with variable head position in healthy, anesthetized horses in hoisted inversion and to assess the influence of various cofactors (age, sex, body weight, body condition score, and neck length) on IOP changes during hoisting. ANIMALS STUDIED: Seventeen healthy adult horses without significant ocular abnormalities. PROCEDURES: Subjects were administered intravenous xylazine/butorphanol premedication and ketamine/midazolam induction with xylazine/ketamine boluses for anesthetic maintenance. While hoisted, IOP was measured in triplicate for each eye via rebound tonometry (TonoVet) at neutral head position (ie, eyes level with the withers), at multiple 5 cm increments above and below neutral (-20 cm through +20 cm) using foam pads for head support, and with eyes above heart level via manual support. RESULTS: In hoisted positions, IOP ranged from 18 to 51 mmHg. Intraocular pressure significantly decreased with head position elevated ≥+15 cm from neutral and significantly increased when lowered ≤-5 cm from neutral. Neck length significantly influenced IOP (P = .0328) with linear regression indicating a median (range) increase of 0.244 (0.034-0.425) mmHg in IOP for every 1 cm increase in neck length. Age, sex, breed, body weight, body condition score, and eye (OD vs OS) did not significantly influence IOP. Intraocular pressure only varied significantly between eyes at +10 cm above neutral (OS > OD, 1.7 ± 0.6 mm Hg, P = .0044). CONCLUSIONS: Intraocular pressure in healthy, anesthetized horses varies with head position during hoisting; increased neck length may be associated with larger changes in IOP during hoisting.