Sustained-Release Ganciclovir Therapy for Treatment of Cytomegalovirus Retinitis

Sanborn, George E.; Anand, Rajiv; Torti, Robert E.; Nightingale, Steven; Cal, Stanley X.; Yates, Bradley P.; Ashton, Paul; Smith, Thomas J.

doi:10.1001/archopht.1992.01080140044023

Cited by 217 publications

(79 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…26 Some intravitreal implants have been effective and safe for intraocular use. To date, two ocular drug delivery systems, Vitrasert 27 and Retisert, 28 which are intravitreal sustainedrelease implants of ganciclovir and fluocinolone acetonide, respectively, have been marketed. Although these devices release the drugs at relatively constant rates, they must be implanted surgically and later removed from the vitreous, which may cause complications and/or patient discomfort.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device in Monkey Eyes

Nagai

Yamada

Kawasaki³

et al. 2018

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Citation: Nagai N, Yamada S, Kawasaki J, et al. Pharmacokinetic and safety evaluation of a transscleral sustained unoprostone release device in monkey eyes. Invest Ophthalmol Vis Sci. 2018;59:644-652. https://doi.org/ 10.1167/iovs.17-22429 PURPOSE. We evaluate the ocular tissue distribution and retinal toxicity of unoprostone (UNO) during 12 months, after transscleral sustained-UNO administration using a drug delivery device in monkey eyes. METHODS.The device consisted of a reservoir, controlled-release cover, and a drug formulation of photopolymerized polyethylene glycol dimethacrylate. Six mg UNO was loaded into the device (length, 17 mm; width, 4.4 mm; height, 1 mm). The concentrations of M1, a primary metabolite of UNO, in the retina, choroid, vitreous, lens, aqueous humor, iris, ciliary body, and plasma were determined by liquid chromatography-tandem mass spectrometry at 3, 6, and 12 months after implantation. Retinal toxicity was evaluated by electroretinography (ERG), optical coherence tomography (OCT), and IOP at preimplantation, and at 6, 9, and 12 months after implantation. Focal ERGs were performed at 9 and 12 months after implantation.RESULTS. M1 was detected in the choroid and retina with maximum peaks of 243.2 and 8.41 ng/g at 6 months, respectively. M1 in the ciliary body and iris was detected with maximum peaks of 7.66 and 10.4 ng/g at 6 and 12 months, respectively. Less than 1 ng/mL or ng/g of M1 was detected in the aqueous humor, vitreous, and lens. No changes were observed in retinal function as assessed by ERG, IOP, or macula thickness and retinal histology by OCT examinations during the 12-month period. No differences in focal ERG amplitudes, especially in the macula, were observed.CONCLUSIONS. The device provided intraocular sustained delivery of UNO for 12 months without producing severe retinal toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device in Monkey Eyes

Nagai

Yamada

Kawasaki³

et al. 2018

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…This study included patients previously using intravenous ganciclovir and thus possibly presenting viral resistance, in contrast to other literature studies (38). Antiviral sensitivity was not determined.…”

Section: Discussionmentioning

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

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

“…Several studies have been carried out in an attempt to develop non-biodegradable intraocular implants containing ganciclovir for the treatment of cytomegalovirus retinitis Martin et al, 1994Sanborn et al, 1992Charles, Steiner, 1996). These studies were performed on animals and humans and, in 1996, led to the development of Vitrasert ® (Bausch & Lomb, USA) and its approval by the Food and Drug Administration (FDA) (Bourges et al, 2006).…”

Section: Non-biodegradable Implants In the Treatment Of Cytomegalovirmentioning

confidence: 99%

Implants as drug delivery devices for the treatment of eye diseases

Silva

Fialho

Siqueira³

et al. 2010

Braz. J. Pharm. Sci.

View full text Add to dashboard Cite

The treatment of diseases affecting the posterior segment of the eye is limited by the difficulty in transporting effective doses of drugs to the vitreous, retina, and choroid. Topically applied drugs are poorly absorbed due to the low permeability of the external ocular tissues and tearing. The blood-retina barrier limits drug diffusion from the systemic blood to the posterior segment, thus high doses of drug are needed to maintain therapeutic levels. In addition, systemic side effects are common. Intraocular injections could be an alternative, but the fast flowing blood supply in this region, associated with rapid clearance rates, causes drug concentration to quickly fall below therapeutic levels. To obtain therapeutic levels over longer time periods, polymeric sustained-drug release systems implanted within the vitreous are being studied for the treatment of vitreoretinal disorders. These systems are prepared using different kinds of biodegradable or non-biodegradable polymers. This review aims to demonstrate the main characteristics of these drug delivery implants and their potential for clinical application.Uniterms: Implants/biodegradation. Drugs/delivery systems. Drugs/prolonged delivery systems. Pharmaceutical technology.O tratamento de doenças do segmento posterior do olho é limitado pela dificuldade no transporte de doses efetivas de fármacos para o vítreo, retina e coróide. Os fármacos aplicados topicamente são pouco absorvidos por causa da baixa permeabilidade dos tecidos oculares externos e ao lacrimejamento. Embora a administração sistêmica seja capaz de transportar fármacos para o segmento posterior do olho, as barreiras hemato-aquosa e hematorretiniana dificultam a absorção e, normalmente, são necessárias doses elevadas, as quais estão geralmente associadas a potenciais efeitos adversos. Injeções intravitreais são capazes de transportar fármacos para o segmento posterior do olho, mas é uma técnica invasiva, pouco tolerada pelos pacientes e apresenta riscos de infecções oculares e danos aos tecidos. Visando a obtenção de níveis terapêuticos adequados de fármacos no segmento posterior do bulbo do olho por longos períodos, sistemas de liberação poliméricos implantados diretamente no vítreo estão sendo investigados para o tratamento de várias doenças vítreo-retinianas. Esses implantes podem ser preparados a partir de diferentes polímeros biocompatíveis, biodegradáveis ou não-biodegradáveis. Nesta revisão, as principais características destes implantes transportadores de fármacos são descritas, expondo suas potencialidades de aplicação clínica.Unitermos: Implantes oculares/biodegradação. Fármacos/sistemas de liberação. Fármacos/ Fármacos/ ação prolongada. Tecnologia farmacêutica.

show abstract

Sustained-Release Ganciclovir Therapy for Treatment of Cytomegalovirus Retinitis

Cited by 217 publications

References 26 publications

Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device in Monkey Eyes

Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device in Monkey Eyes

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

Implants as drug delivery devices for the treatment of eye diseases

Contact Info

Product

Resources

About