Ocular toxicity of experimental intravitreal itraconazole

Schulman, Joel A.; Peyman, Gholam A.; Dietlein, Johanna; Fiscella, Richard G.

doi:10.1007/bf00150975

Cited by 20 publications

(8 citation statements)

References 15 publications

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“…Thus, it is possible that the changes seen in our acute data would return to normal with time. Results from studies employing similar intravitreal concentrations of DMSO in other species are inconsistent [2,3,5,23]. Our findings are in agreement with an early ocular toxicity study by Silverman (1983) in rabbits, who revealed a transient, though general, scotopic ERG reduction 1 h following a single injection of C 3.5% DMSO.…”

Section: Discussionsupporting

confidence: 92%

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Dimethyl sulphoxide dose–response on rat retinal function

2009

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The aim of the study is to determine whether dimethyl sulphoxide (DMSO), a common laboratory solvent, impacts retinal function. Long Evans rats (n = 17) were intravitreally injected with five different doses of DMSO representative of those reported in the literature and spanning over 3 log units of vitreal concentration (0.01-8%). Retinal function was evaluated 1 h after injection using electroretinograms, and the waveform was decomposed into outer (photoreceptor), middle (ON-bipolar cell) and inner retinal (amacrine and ganglion cell) components. DMSO induces a dose-dependent decrease in retinal function for concentrations of 0.6% or more which is retinal layer specific. The photoreceptors of the outer retina returned normal responses at all doses (P > 0.05), whereas the mid-retinal bipolar cell response showed dose-dependent losses ranging from 21 +/- 1 to 82 +/- 1% (0.6-8% DMSO; P < 0.05). In a similar dose-dependent fashion, the inner retinal response was also affected by DMSO (0.6-8%: 23 +/- 12 to 98 +/- 3% loss, P < 0.05). A single dose of DMSO < or =0.1% (2.96 x 10(-5) microM) may be safely used to dilute compounds injected into the vitreous of a rat eye. Higher doses produce short-term (at least 24 h) retinal dysfunction.

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Section: Discussionsupporting

confidence: 92%

“…Coupled with the belief that DMSO has low ocular toxicity, it is not surprising that DMSO is one of the most frequently used carriers for in vivo administration, including intravitreal delivery [1][2][3][4][5][6][7][8] of inorganic compounds (reviewed in [9][10][11]). …”

Section: Introductionmentioning

confidence: 99%

Dimethyl sulphoxide dose–response on rat retinal function

2009

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“…In an experimental animal model, itraconazole (2.5 mg/ml) that had been administered subconjunctivally was found to persist for at least 24 h in normal and debrided corneas, in contrast to amphotericin B, miconazole, fluconazole, and ketoconazole, which did not persist beyond 4 to 8 h (193). However, intravitreal injection of itraconazole appears to cause focal areas of retinal necrosis when doses exceeding 10 g are used (344). There are no reports of itraconazole being administered subconjunctivally or intravitreally in a clinical setting.…”

Section: Azolesmentioning

confidence: 98%

Current Perspectives on Ophthalmic Mycoses

2003

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Fungi may infect the cornea, orbit and other ocular structures. Species of Fusarium, Aspergillus, Candida, dematiaceous fungi, and Scedosporium predominate. Diagnosis is aided by recognition of typical clinical features and by direct microscopic detection of fungi in scrapes, biopsy specimens, and other samples. Culture confirms the diagnosis. Histopathological, immunohistochemical, or DNA-based tests may also be needed. Pathogenesis involves agent (invasiveness, toxigenicity) and host factors. Specific antifungal therapy is instituted as soon as the diagnosis is made. Amphotericin B by various routes is the mainstay of treatment for life-threatening and severe ophthalmic mycoses. Topical natamycin is usually the first choice for filamentous fungal keratitis, and topical amphotericin B is the first choice for yeast keratitis. Increasingly, the triazoles itraconazole and fluconazole are being evaluated as therapeutic options in ophthalmic mycoses. Medical therapy alone does not usually suffice for invasive fungal orbital infections, scleritis, and keratitis due to Fusarium spp., Lasiodiplodia theobromae, and Pythium insidiosum. Surgical debridement is essential in orbital infections, while various surgical procedures may be required for other infections not responding to medical therapy. Corticosteroids are contraindicated in most ophthalmic mycoses; therefore, other methods are being sought to control inflammatory tissue damage. Fungal infections following ophthalmic surgical procedures, in patients with AIDS, and due to use of various ocular biomaterials are unique subsets of ophthalmic mycoses. Future research needs to focus on the development of rapid, species-specific diagnostic aids, broad-spectrum fungicidal compounds that are active by various routes, and therapeutic modalities which curtail the harmful effects of fungus- and host tissue-derived factors

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“…Intravitreal antifungals are often used in conjunction with systemic treatment, as ocular candidiasis is most often a manifestation of systemic disease. Several studies have investigated the safety and efficacy of intravitreal antifungals [56,[77][78][79][80][81][82].…”

Section: Intravitreal Antifungalsmentioning

confidence: 99%