Ganciclovir ophthalmic gel 0.15% for the treatment of acute herpetic keratitis: background, effectiveness, tolerability, safety, and future applications

Abstract

Eye disease due to herpes simplex virus (HSV) is a leading cause of ocular morbidity and the number one infectious cause of unilateral corneal blindness in the developed parts of the globe. Recurrent keratitis can result in progressive corneal scarring, thinning, and vascularization. Antiviral agents employed against HSV have primarily been nucleoside analogs. Early generation drugs included idoxuridine, iododesoxycytidine, vidarabine, and trifluridine. While effective, they tended to have low bioavailability and measurable local cellular toxicity due to their nonselective mode of action. Acyclovir 0.3% ointment is a more selective agent, and had become a first-line topical drug for acute HSV keratitis in Europe and other places outside of the US. Ganciclovir 0.15% gel is the most recently approved topical treatment for herpes keratitis. Compared to acyclovir 0.3% ointment, ganciclovir 0.15% gel has been shown to be better tolerated and no less effective in several Phase II and III trials. Additionally, topical ganciclovir does not cause adverse systemic side effects and is therapeutic at lower concentrations. Based on safety, efficacy, and tolerability, ganciclovir 0.15% gel should now be considered a front-line topical drug in the treatment of dendritic herpes simplex epithelial keratitis. Topics of future investigation regarding other potential uses for ganciclovir gel may include the prophylaxis of recurrent HSV epithelial keratitis, treatment of other forms of ocular disease caused by herpesviruses and adenovirus, and ganciclovir gel as an adjunct to antitumor therapy.

Update on the Management of Infectious Keratitis

“…In addition to treating HSV and VZV keratitis, topical ganciclovir is also effective in treating keratitis caused by CMV. 96 Ganciclovir has been shown to be just as effective as acyclovir, while causing less ocular toxicity. It may also be less likely to promote drug resistance.…”

“…It may also be less likely to promote drug resistance. 96,97 Northwestern University is currently conducting a large randomized controlled trial investigating ganciclovir for the treatment of VZV keratitis (NCT02382588).…”

Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis

“…In the following decade a purine analogue, vidarabine (adenine arabinoside, ARA-A), entered ophthalmic practice (Whitley 1980). Idoxuridine and vidarabine were then progressively superseded by other nucleoside analogues: trifluridine (trifluorothymidine, TFT) (Carmine 1982), acyclovir (acycloguanosine, ACV) (Richards 1983; Wagstaff 1994), brivudine (bromovinyldeoxyuridine, BVDU) (De Clerq 2005), and ganciclovir (dihydroxypropoxymethylguanine, DHPG) (Chou 2014; Croxtall 2011; Tabbara 2010). Cidofovir (hydroxyphosphonylmethoxypropylcytosine, HPMPC) is an acyclic nucleotide analogue.…”

Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents

“…The topical antiviral agents used against HSV have primarily been nucleoside analogues. They interrupt viral DNA synthesis by the irreversible binding of viral DNA polymerase within infected cells …”

“…Acyclovir is another purine nucleoside analogue, but with selective inhibitory activity against HSV DNA polymerase. It is able to inhibit viral DNA synthesis without concomitantly interrupting uninfected host cells . In Europe, ACV is available as a 3% ointment, and it has become the first‐line topical treatment for HSV epithelial keratitis in Europe and elsewhere outside of the USA.…”