Treatment of Cytomegalovirus Retinitis With Dihydroxy Propoxymethyl Guanine

Palestine, Alan G.; Stevens, Garth; Lane, H. Clifford; Masur, Henry; Fujikawa, Leslie S.; Nussenblatt, Robert B.; Rook, Alain H.; Manischewitz, Jody; Baird, Barbara; Megill, Margaret; Quinnan, Gerald V.; Gelmann, Edward P.; Fauci, Anthony S.

doi:10.1016/0002-9394(86)90470-8

Cited by 132 publications

(24 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several pharmacological treatments, including vidarabine, acyclovir, alpha-interferon and interleukin-2 had been tried without success (30). Since 1989, with the release of ganciclovir for intravenous use in the US, the natural history of the disease has changed.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant

Muccioli

Belfort

2000

Braz J Med Biol Res

View full text Add to dashboard Cite

The objective of this prospective study was to evaluate the efficacy and complications of the use of an intraocular sustained-release ganciclovir implant for the treatment of active cytomegalovirus (CMV) retinitis in AIDS patients. Thirty-nine eyes of 26 patients were submitted to ocular surgery. All patients underwent complete ocular examination before and after surgery. The surgical procedure was always done under local anesthesia using the same technique. The mean time for the surgical procedure was 20 min (range, 15 to 30 min). The average follow-up period was 3.7 months. Of all patient, only 4 presented recurrence of retinitis after 8, 8, 9 and 2 months, respectively. Three of them received a successful second implant. All 39 eyes of the 26 patients presented healing of retinitis as shown by clinical improvement evaluated by indirect binocular ophthalmoscopy and retinography. Retinitis healed within a period of 4 to 6 weeks in all patients, with clinical regression signs from the third week on. Six (15.4%) eyes developed retinal detachment. None of the patients developed CMV retinitis in the contralateral eye. The intraocular implant proved to be effective in controlling the progression of retinitis for a period of up to 8 months even in patients for whom systemic therapy with either ganciclovir or foscarnet or both had failed. The intraocular sustained-release ganciclovir implant proved to be a safe new procedure for the treatment of CMV retinitis, avoiding the systemic side effects caused by the intravenous medications and improving the quality of life of the patients.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Indications include patients who are unable to receive intravenous therapy and as a supplement in patients whose retinal disease is not completely controlled using maximum tolerated systemic medication. Perhaps the best use of local therapy is in association with oral forms (30).…”

Section: Introductionmentioning

confidence: 99%

Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant

Muccioli

Belfort

2000

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…In the 3-day pretreatment paradigm, compound 2242 was superior to ganciclovir (P < 0.04), but there was no clear difference between the two with regard to their effects on an established infection. The pharmacokinetics of compound 2242 in 10 rabbits injected intravitreally with 30 M showed an intravitreal half-life of 8 h. This compound, which may be orally active in its pro form, has a very high therapeutic index in the eye and is more efficient than ganciclovir in this animal model of herpes retinitis.Administration of ganciclovir or foscarnet is a useful treatment for patients with cytomegalovirus (CMV) retinitis (8,16,18,28). However, both drugs can cause serious systemic toxicity, and during therapy with either drug, clinically resistant retinitis may develop in a significant proportion of these patients (9).…”

mentioning

confidence: 99%

“…Administration of ganciclovir or foscarnet is a useful treatment for patients with cytomegalovirus (CMV) retinitis (8,16,18,28). However, both drugs can cause serious systemic toxicity, and during therapy with either drug, clinically resistant retinitis may develop in a significant proportion of these patients (9).…”

mentioning

confidence: 99%

Evaluation of retinal toxicity and efficacy of the anticytomegalovirus compound 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine

Besen

Paz

Tatebayashi

et al. 1995

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Compound 2242, also known as 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine, is the first known antivirally active nucleoside analog with the side chain substituted at the N-7 position of the purine ring system. Our purpose was to evaluate its retinal toxicity and assess the efficacy of its highest nontoxic concentration in a rabbit model of herpes simplex retinitis. Concentrations of the drug from 0.5 to 2,000 M were injected intravitreally in twelve New Zealand White rabbits. Fundoscopic, histologic, and electrophysiologic data revealed no evidence of toxicity even at the highest dose of the compound. Dutch pigmented rabbits (n ‫؍‬ 34) had their left eyes injected with herpes simplex virus type 1 3 days after, concurrently, or 3 days before intravitreal injection of either 2,000 M compound 2242 or 480 M ganciclovir (final concentration in the eye). Both compound 2242 and ganciclovir were equally effective compared with saline when administered simultaneously with the virus (P < 0.0001). In the 3-day pretreatment paradigm, compound 2242 was superior to ganciclovir (P < 0.04), but there was no clear difference between the two with regard to their effects on an established infection. The pharmacokinetics of compound 2242 in 10 rabbits injected intravitreally with 30 M showed an intravitreal half-life of 8 h. This compound, which may be orally active in its pro form, has a very high therapeutic index in the eye and is more efficient than ganciclovir in this animal model of herpes retinitis.Administration of ganciclovir or foscarnet is a useful treatment for patients with cytomegalovirus (CMV) retinitis (8,16,18,28). However, both drugs can cause serious systemic toxicity, and during therapy with either drug, clinically resistant retinitis may develop in a significant proportion of these patients (9). For some patients, a change from one drug to the other does not ameliorate the retinitis, and combination therapy must also be used (22). Local intraocular antiviral therapy has been widely used for patients unable to tolerate systemic therapy (2,4,5,14,17,32). Unfortunately, both ganciclovir and foscarnet have short intravitreal half-lives and durations of action, making weekly injections necessary, with all the risks associated with frequent procedures (11,30). A recently developed intravitreal ganciclovir implant is capable of releasing ganciclovir for up to 8 months, but surgery with potential complications is required, and experience with the use of the device is quite limited (1,24,29). Although the systemic role of CMV is not yet clear, another concern with local therapy is that it does not treat possible clinically inapparent infection with CMV. In addition, strains of the virus resistant to both drugs have been isolated (7, 21). A continuing need for an orally administered drug for the management of CMV retinitis exists, and a safe intravitreal compound that would allow for the control of retinitis with infrequent injections is required.Since the discovery of the selective antiherpes action of acyclovir, a...

show abstract

“…Foscarnet and ganciclovir are the drugs which have been approved for the treatment of the disease [3][4][5], Although both o f them prevent the further replication of viral DNA, their intravenous administration evokes general toxicity and myelosuppression.…”

mentioning

confidence: 99%

Intravitreal Application of Ganciclovir in Rabbits: ERG and Electron-Microscopic Findings

et al. 1996

View full text Add to dashboard Cite

The retinal toxic effect after intravitreal use of ganciclovir has been the subject of our experimental investigation on 20 New Zealand rabbits. Different doses of ganciclovir ranging from 200 to 600 µg/0.1 ml were injected intravitreously, and ERG changes were recorded at different time points after drug administration. Finally the animals were killed and the retinal lesions were studied by electron microscopy. According to our experiments, ganciclovir doses of 300-600 µg/0.1 ml have a clearly toxic effect on the retina as shown by ERG changes. One month after the injection, the electroretinogram is either extinguished or clearly affected. Noteworthy is the fact that in a dose of 200 µg/0.1 ml, the ERG b-wave shows a 20% reduction of its normal amplitude 4 months after ganciclovir delivery. Electron microscopy of the retina revealed in the inner segment of the receptor cells the existence of dilatation and vesiculation of the endoplasmic reticulum in the surrounding nuclear cytoplasm and swelling of the mitochondria with fragmentation of the cristae in several of them. In the outer segment of the photoreceptor cells, degeneration and destruction of the lamellae accompagnied by disintegration of the adjacent protoplasm in parts of certain rods and cones appeared. Finally large vacuoles of irregular shape in the synapses and degenerative mitochondria and empty vacuoles in the optic nerve fibers were shown.

show abstract

Treatment of Cytomegalovirus Retinitis With Dihydroxy Propoxymethyl Guanine

Cited by 132 publications

References 2 publications

Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant

Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant

Evaluation of retinal toxicity and efficacy of the anticytomegalovirus compound 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine

Intravitreal Application of Ganciclovir in Rabbits: ERG and Electron-Microscopic Findings

Contact Info

Product

Resources

About