Effect of intravitreal dexamethasone on vitreous vancomycin concentrations in patients with suspected postoperative bacterial endophthalmitis

Gan, Ivan M; Ugahary, Luana C; Dissel, Jaap T. van; Meurs, Jan C. van

doi:10.1007/s00417-005-1182-1

Cited by 66 publications

(34 citation statements)

References 9 publications

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“…Liquefaction and convection has been stated to be major pharmacokinetic differences between the rabbit and elderly patients (Laude et al, 2010). However, no significant difference in the intravitreal concentrations in patients with and without vitrectomy was observed in Gan's study (Gan et al, 2005) and the apparent CL ivt value of vancomycin was not higher in vitrectomized patients (Ferencz et al, 1999) compared to non-vitrectomized patients (Haider et al, 2001) (Fig. 3, Table 2).…”

Section: Rabbit As An Animal Model In Intravitreal Pharmacokineticsmentioning

confidence: 89%

Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data

Amo

Urtti

2015

Experimental Eye Research

191

136

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Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics.

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Section: Rabbit As An Animal Model In Intravitreal Pharmacokineticsmentioning

confidence: 89%

Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data

Amo

Urtti

2015

Experimental Eye Research

191

136

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“…We also reviewed studies examining the effect of IVT dexamethasone on vitreous vancomycin concentration in acute endophthalmitis. 17, 20, 31–32 …”

Section: Methodsmentioning

confidence: 99%

“…To complicate matters further, in a prospective randomized clinical trial of suspected post-operative bacterial endophthalmitis, there was no statistically significant difference between the mean vitreous vancomycin concentrations in the presence or absence of dexamethasone. 31 Even though a 0.2 mg (instead of the usual 1.0 mg) dose was used, the vitreous concentration of vancomycin remained above the MIC for most organisms for well over a week. 31 …”

Section: The Effect Of Ivt Corticosteroids On Vitreous Antibiotic Conmentioning

confidence: 99%

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Evidence for and Against Intravitreous Corticosteroids in Addition to Intravitreous Antibiotics for Acute Endophthalmitis

Bui

Carvounis

2014

International Ophthalmology Clinics

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The use of adjunctive intravitreous corticosteroids in endophthalmitis is controversial. Preclinical models showed that early administration of corticosteroids may be important although they reported mixed results in terms of their effects on antibiotic pharmacokinetics, control of infection and prevention of retinal damage. Most published retrospective clinical studies showed no beneficial effects associated with their use. However, a single well-conducted retrospective study showed a deleterious effect. Randomized controlled trials also showed a lack of beneficial effects. At the present time, the best available evidences do not support the routine use of adjunctive intravitreous corticosteroids for treatment of acute endophthalmitis.

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“…[10, 11] It is a water-soluble synthetic glucocorticoid, three times more potent than triamcinolone. [12] The drug–copolymer complex is inserted into the eye through the pars plana with a 22 gauge injector. [13] After the first two months, the DEX implant concentration declines, until the fourth month, and then maintains a lower concentration until month 6.…”

Section: Introductionmentioning

confidence: 99%

New Drugs and New Posterior Delivery Methods in CME

Dias

Nunes

Goldhardt

2017

Curr Ophthalmol Rep

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Purpose To discuss the characteristics, indications and adverse events (AEs) of sustained-release corticosteroid devices for the treatment of cystoid macular edema (CME). Recent findings Ozurdex® is approved for the treatment of diabetic macular edema (DME), retinal vein occlusion related-CME and noninfectious posterior uveitis (NIPU). It releases dexamethasone over a maximum period of 6 months making repeated intravitreal injections necessary for recurrent CME. Iluvien® releases fluocinolone for up to 36 months and is effective for the treatment of chronic DME. Retisert® (Bausch & Lomb, Rochester, NY) also releases fluocinolone, and is approved for chronic NIPU. Both Iluvien® and Retisert® are non-biodegradable devices and are highly associated with cataract and glaucoma. Summary Long-acting intraocular corticosteroid formulations offer a more predictable drug-release profile and reduced dosing frequency in comparison to conventional formulations of the same compounds but the risk-benefit ratio must be taken into consideration previous to the implantation of those devices.

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Effect of intravitreal dexamethasone on vitreous vancomycin concentrations in patients with suspected postoperative bacterial endophthalmitis

Abstract: Intravitreal dexamethasone does not lead to decreased vancomycin concentrations, when given simultaneously in the treatment of patients with suspected bacterial endophthalmitis.

Cited by 66 publications

References 9 publications

Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data

Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data

Evidence for and Against Intravitreous Corticosteroids in Addition to Intravitreous Antibiotics for Acute Endophthalmitis

New Drugs and New Posterior Delivery Methods in CME

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