Voriconazole in Fungal Keratitis Caused by <i>Scedosporium apiospermum</i>

Prats, Hernández Carmen; Tello, Francisca Llinares; José, Amparo Burgos San; Otaolaurruchi, Juan Selva; Baines, Juan Pablo Ordovás

doi:10.1345/aph.1d128

Cited by 60 publications

(17 citation statements)

References 18 publications

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“…28 There is little information in the literature regarding the value of adding oral antifungal medications, despite the fact that it is a common practice among ophthalmologists. Two case reports 29,30 of successful treatment with combined topical, oral, and/or intravenous voriconazole and 1 small randomized clinical trial 31 found a possible improvement in time to ulcer healing among patients treated with oral voriconazole compared with oral itraconazole in Aspergillus species. However, a larger placebo-controlled trial 32 randomizing patients with severe culture-positive fungal ulcers to receive oral ketoconazole vs placebo plus topical natamycin, 5%, did not find a benefit in the group receiving the oral antifungal.…”

Section: Discussionmentioning

confidence: 99%

Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II)

et al. 2016

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for the Mycotic Ulcer Treatment Trial II Group OBJECTIVE To compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. DESIGN, SETTING, AND PARTICIPANTSThe Mycotic Ulcer Treatment Trial II (MUTT II), a multicenter, double-masked, placebo-controlled, randomized clinical trial, was conducted in India and Nepal, with 2133 individuals screened for inclusion. Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 (logMAR 1.3) or worse were randomized to receive oral voriconazole vs oral placebo; all participants received topical antifungal eyedrops. The study was conducted from May 24, 2010, to November 23, 2015. All trial end points were analyzed on an intent-to-treat basis.INTERVENTIONS Study participants were randomized to receive oral voriconazole vs oral placebo; a voriconazole loading dose of 400 mg was administered twice daily for 24 hours, followed by a maintenance dose of 200 mg twice daily for 20 days, with dosing altered to weight based during the trial. All participants received topical voriconazole, 1%, and natamycin, 5%. MAIN OUTCOMES AND MEASURESThe primary outcome of the trial was rate of corneal perforation or the need for therapeutic penetrating keratoplasty (TPK) within 3 months. Secondary outcomes included microbiologic cure at 6 days, rate of re-epithelialization, best-corrected visual acuity and infiltrate and/or scar size at 3 weeks and 3 months, and complication rates associated with voriconazole use.RESULTS A total of 2133 patients in India and Nepal with smear-positive ulcers were screened; of the 787 who were eligible, 240 (30.5%) were enrolled. Of the 119 patients (49.6%) in the oral voriconazole treatment group, 65 were male (54.6%), and the median age was 54 years (interquartile range, 42-62 years). Overall, no difference in the rate of corneal perforation or the need for TPK was determined for oral voriconazole vs placebo (hazard ratio, 0.82; 95% CI, 0.57-1.18; P = .29). In prespecified subgroup analyses comparing treatment effects among organism subgroups, there was some suggestion that Fusarium species might have a decreased rate of perforation or TPK in the oral voriconazole-treated arm; however, this was not a statistically significant finding after Holms-Šidák correction for multiple comparisons (effect coefficient, 0.49; 95% CI, 0.26-0.92; P = .03). Patients receiving oral voriconazole experienced a total of 58 adverse events (48.7%) compared with 28 adverse events (23.1%) in the placebo group (P < .001 after Holms-Šidák correction for multiple comparisons). CONCLUSIONS AND RELEVANCEThere appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. All patients in this study were enrolled in India and Nepal; therefore, it is possible that organisms in this region may exhibit characteristics different from those in other regions of the world. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00996736

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Section: Discussionmentioning

confidence: 99%

Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II)

et al. 2016

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“…79 Of note, in many case reports of successful treatment with topical voriconazole, oral and/or intravenous voriconazole was used in conjunction with the topical medication. 80,81 …”

Section: Fungal Keratitismentioning

confidence: 99%

Update on the Management of Infectious Keratitis

2017

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Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is critical, and while culture remains the prevailing diagnostic tool, newer techniques such as in vivo confocal microscopy are helpful for diagnosing fungal keratitis and Acanthameoba. Next generation sequencing holds the potential for early and accurate diagnosis even for organisms that are difficult to culture by conventional methods. Topical antibiotics remain the best treatment for bacterial keratitis, and a recent review found all commonly prescribed topical antibiotics to be equally effective. However outcomes remain poor secondary to corneal melting, scarring and perforation. Adjuvant therapies aimed at reducing the immune response responsible for much of the morbidity associated with keratitis include topical corticosteroids. The large, randomized controlled Steroids for Corneal Ulcers trial found that while steroids provided no significant improvement overall, they did appear beneficial for ulcers that were central, deep or large, non-Nocardia or classically invasive P. aeruginosa, patients with low baseline vision, and when started early after the initiation of antibiotics. Fungal ulcers often have worse clinical outcomes than bacterial ulcers, with no new treatments since the 1960’s when topical natamycin was introduced. The randomized controlled Mycotic Ulcer Treatment Trial showed a benefit of topical natamycin over topical voriconazole for fungal keratitis, particularly among those caused by Fusarium. The second Mycotic Ulcer Treatment Trial showed that oral voriconazole did not improve outcomes overall although there may have been some effect among Fusarium ulcers. Given an increase in non-serious adverse events the authors concluded that they could not recommend oral voriconazole at this time. Viral keratitis differs from bacterial and fungal cases in that is often recurrent and is common in developed countries. The first Herpetic Eye Disease Study (HEDS) showed a significant benefit of topical corticosteroids and oral acyclovir for stromal keratitis. HEDS II showed that oral acyclovir decreased the recurrence of any type of HSV keratitis by approximately half. Future strategies to reduce the morbidity associated with infectious keratitis are likely to be multidimensional with adjuvant therapies aimed at modifying the immune response to infection holding the greatest potential to improve clinical outcomes.

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“…Voriconazole has been used to treat posttraumatic fungal keratitis caused by S apiospermum. 11 There was no such predisposing factor in our case.…”

Section: Discussionmentioning

confidence: 46%

Management of tunnel fungal infection with voriconazole

Jhanji

Sharma

Mannan

et al. 2007

Journal of Cataract and Refractive Surgery

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A 59-year-old woman presented 1 month after cataract surgery in the right eye with a stromal infiltrate at the site of the cataract surgery wound. The visual acuity was perception of light with accurate projection. Corneal scraping of the infiltrate revealed septate hyphae. There was no response to 6 weeks of therapy with topical fortified antibiotic agents and topical antifungal therapy in the form of natamycin 5%, amphotericin B 0.15%, and intracameral amphotericin B. The patient was started on oral voriconazole 200 mg twice daily and topical voriconazole 1% every hour, and resolution of the ulcer was noted within 3 days. At the 4-month follow-up, a visual acuity of 20/60 was achieved, with the formation of a vascularized corneal opacity superiorly. This case illustrates that topical and oral voriconazole may be used in the treatment of recalcitrant cases of fungal tunnel infections not responding to conventional antifungal therapy.

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Voriconazole in Fungal Keratitis Caused by Scedosporium apiospermum

Abstract: Voriconazole shows promise as an effective alternative to conventional antifungals in the treatment of ScA keratitis. It is available both as oral and intravenous preparations, which is a great advantage in these lengthy infections.

Cited by 60 publications

References 18 publications

Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II)

Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II)

Update on the Management of Infectious Keratitis

Management of tunnel fungal infection with voriconazole

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