2′-nor-cGMP, a new cyclic derivative of 2′NDG, inhibits HSV-1 replication<i>in vitro</i>and in the mouse keratitis model

Yj, Gordon; Capone, Antonio; Sheppard, John D.; Gordon, Alun; Romanowski, Eric G.; Araullo-Cruz, T

doi:10.3109/02713688709020099

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…Ganciclovir is a nucleoside analogue that gets selectively phosphorylated by virus-encoded thymidine kinase, and is subsequently phosphorylated by cellular enzymes. Ganciclovir triphosphate inhibits HSV DNA polymerase and arrests HSV replication [28][29][30]. Following topical application, the drug has been shown to penetrate the corneal stroma and can reach the aqueous humor at therapeutic levels [31].…”

Section: Corneal Transplantation In Patients With Herpetic Keratitismentioning

confidence: 99%

Pharmacologic strategies in the prevention and treatment of corneal transplant rejection

Tabbara

2007

Int Ophthalmol

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Corneal transplantation remains one of the most successful organ transplantation procedures in humans. The unique structure of the cornea, with its absence of blood vessels and corneal lymphatic, allows the survival of corneal allograft. Recent advances in sutures, storage media, microsurgical instrumentation, and new pharmacological strategies have greatly improved the success of corneal transplantation and the prevention of corneal allograft rejection. Our strategies in the management and prevention of corneal graft rejection can modify and improve the survival of corneal allografts. Preoperative evaluation, understanding the risk factors, and management of ocular surface disorders may greatly improve the survival of the corneal transplant. Early recognition of corneal allograft rejection and aggressive treatment may improve the survival of the corneal graft. Furthermore, patients who undergo corneal transplantation should be maintained under close ophthalmic surveillance and patients should be informed to report immediately whenever symptoms of corneal graft rejection occur. The mainstay of therapy is topical corticosteroids. In severe cases, periocular, intravenous, and oral corticosteroids therapy can be rendered. New therapeutic modalities such as cyclosporine, tacrolimus, daclizumab, mycophenolate mofetil, leflunomide, rapamycin, and others may prove to be of help in the prevention and treatment of corneal graft rejection. Early recognition of corneal graft rejection and prompt treatment are mandatory for the successful survival of the corneal allograft.

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Section: Corneal Transplantation In Patients With Herpetic Keratitismentioning

confidence: 99%

Pharmacologic strategies in the prevention and treatment of corneal transplant rejection

Tabbara

2007

Int Ophthalmol

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“…This finding suggests that topical ganciclovir may be slightly less toxic than trifluridine, especially during more extended therapy 103. Gordon et al looked at the antiherpetic effects of ganciclovir, the cyclic ganciclovir derivative 2′-nor-cGMP, and trifluridine in BALB/c mice inoculated with HSV-1 109. The two forms of ganciclovir were found to be significantly more effective than trifluridine in reducing ocular HSV titers and improving epithelial keratitis in the mice ( P =0.0001).…”

Section: Tolerability and Adverse Effectsmentioning

confidence: 99%

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

Chou¹,

Hong²

2014

TCRM

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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.

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“…In the treatment of patients with this disease entity, the discovery of this viral aetiology has lead to the possibility of including anti-viral medications to the treatment regime in addition to topical anti-inflammatory and topical anti-glaucoma medications Ganciclovir is a potent inhibitor of herpes viruses, including CMV. It is a nucleoside analogue that suppresses the replication of herpes viruses [ 5 , 6 ] and functions as a virustatic agent. Ganciclovir has been used systemically, in the form of intravitreal injections and implants for CMV infections of the eye [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of topical ganciclovir in the management of cytomegalovirus (CMV)-related anterior uveitis

Wong

Agrawal

Wong

et al. 2016

J Ophthal Inflamm Infect

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BackgroundThe aim of this study was to evaluate the efficacy and safety of topical ganciclovir 0.15 % gel in the management of patients with cytomegalovirus (CMV) anterior uveitis.ResultsThis was a retrospective cohort study of the disease course of 31 patients (33 eyes) with aqueous polymerase chain reaction (PCR) positive for CMV. Data from a total of 160 episodes of anterior uveitis flare for 20 years, dating from December 1992 to December 2012, was collected. All patients were treated with concomitant topical anti-inflammatory medication. The disease course of each eye was analysed before and after the use of topical ganciclovir 0.15 %. The mean age at initial presentation of anterior uveitis was 57.5 ± 12.6 years. Twenty-eight (90.3 %) patients were Chinese. Patients on topical ganciclovir gel had a statistically significant fewer episodes of uveitis flare per person year (median −0.88 episodes/person years, p = 0.029). The time-to-quiescence was not significantly affected by topical ganciclovir use (median −1.25 days, p = 0.610). In the survival analysis using the Cox regression model, the use of topical ganciclovir was associated with a lower risk of recurrence, but this was not statistically significant (hazard ratio = 0.857, 95 % CI 0.543–1.36, p = 0.511). The overall median time-to-recurrence was 290 days (95 % CI 113 to 274 days) and 164 days (125 to 404 days) (p = 0.492), with and without topical ganciclovir, respectively.ConclusionsTopical ganciclovir may be beneficial in reducing the frequency of recurrence in patients with CMV anterior uveitis, but it was not statistically associated with prolonging the time-to-recurrence. The time-to-quiescence was also not significantly affected by topical ganciclovir. Prospective studies with a larger number of patients would be required to verify our findings.

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2′-nor-cGMP, a new cyclic derivative of 2′NDG, inhibits HSV-1 replicationin vitroand in the mouse keratitis model

Cited by 5 publications

References 20 publications

Pharmacologic strategies in the prevention and treatment of corneal transplant rejection

Pharmacologic strategies in the prevention and treatment of corneal transplant rejection

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

Efficacy and safety of topical ganciclovir in the management of cytomegalovirus (CMV)-related anterior uveitis

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