Mechanism of Voriconazole-Induced Transient Visual Disturbance: Reversible Dysfunction of Retinal ON-Bipolar Cells in Monkeys

Kinoshita, Junzo; Iwata, Noriaki; Ohba, Mitsuhiro; Kimotsuki, Tomofumi; Yasuda, Mitsuya

doi:10.1167/iovs.11-7183

Cited by 18 publications

(13 citation statements)

References 21 publications

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“…Interestingly, voriconazole‐induced ERG in humans had resemble recordings of the attenuated b‐wave and its amplitude was approximately 13% lower than normal 5 . Similar ERG presentations were found in animal models and the direct blocking of TRPM1 currents by voriconazole had also been verified in mouse retinal slices in vitro 37,38 . Taken together, TRPM1 may be the potential target of voriconazole in causing VVH.…”

Section: Discussionsupporting

confidence: 57%

Genetic polymorphisms of transient receptor potential melastatin 1 correlate with voriconazole‐related visual adverse events

Jiang

Wang

et al. 2020

Mycoses

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Background: Causes of voriconazole-related visual adverse events (VVAE) remained controversial.Objectives: We aimed to explore the relationship between voriconazole serum concentrations and VVAE as well as the potential influence of transient receptor potential melastatin 1 (TRPM1) on VVAE.Patients/methods: This prospective observational cohort study was done in two stages. Patients who received voriconazole for invasive fungal diseases were consecutively enrolled. Correlations between voriconazole trough levels and VVAE were explored in 76 patients. Genotyping was further conducted for 17 tag SNPs of TRPM1 in a larger population of 137 patients. Genotype distributions were compared between patients with and without VVAE. Result:Of the 76 patients, a total of 229 steady-state voriconazole trough levels were evaluated, 69.9% of which were within the target range (1-5.5 mg/L). No correlations were found between voriconazole trough levels and VVAE. Of the total 137 patients, VVAE occurred in 37 (27.0%) patients, including visual hallucination (13.9%, 19/137) and visual disturbances (19.0%, 26/137). Significant difference in TRPM1 genotype distribution was only observed in patients with visual hallucination but not with visual disturbances. We found that rs890160 G/T genotype was underpresented (OR, 0.11; 95% CI, 0.01-0.84; P = .011) and rs1378847 C/C genotype was more frequently detected (OR, 8.89; 95% CI, 1.14-69.02; P = .013) in patients with visual hallucination when compared with those without.Conclusion: Transient receptor potential melastatin 1 was genetically associated with voriconazole-related visual hallucination. The correlation was failed to found between voriconazole trough levels and VVAE.

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Section: Discussionsupporting

confidence: 57%

Genetic polymorphisms of transient receptor potential melastatin 1 correlate with voriconazole‐related visual adverse events

Jiang

Wang

et al. 2020

Mycoses

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“…While photopsias are most commonly described, transient dyschromatopsia has also been reported, and typically involves the tritan axis . Animal studies have suggested that toxicity is due to selective and reversible inhibition of the retinal ON‐bipolar cells in rod and cone pathways of the retina . Moreover, Ziong et al identified that the blockage of TRPM1 channels is involved in the inhibition of ON bipolar cells occurring secondary to voriconazole .…”

Section: Casementioning

confidence: 99%

When medicine transforms art

Belga

MacDonald

Kabbani

et al. 2019

Transplant Infectious Dis

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A 40-year-old female from Canada with a history of type 1 diabetes mellitus, diabetic retinopathy, and solitary pancreas transplant, presented with increase in her pancreatic enzymes 1-year post-transplant. Her induction immunosuppression consisted of anti-thymocyte globulin and maintenance immunosuppression at the time of her presentation was cyclosporine, mycophenolate mofetil and low-dose prednisone. Other medical history was significant for failed islet cell transplant in 2003 and prolonged neutropenia that later resolved with discontinuation of tacrolimus. Incidentally, a 1.1 cm right lower lobe cavity (Figure 1) was identified during her workup. A pancreas biopsy confirmed acute cellular rejection for which she was started on methylprednisolone. Upon interview with the patient, she reported extensive travel history that included parts of Central and South America, Africa, and Arizona in the United States. Her exposure history was also significant for frequent gardening and camping. Bronchoalveolar lavage from the right lower lobe revealed galactomannan index of 0.63. Serum galactomannan, serum cryptococcal antigen, Histoplasma, Blastomyces and Cococidioides serologies were all negative. Given the augmentation of immunosuppression, voriconazole was empirically started for possible invasive pulmonary aspergillosis pending final culture results. Shortly thereafter, she developed visual disturbances characterized by altered color perception with a purple predominance. Of note, voriconazole trough level was within therapeutic range at 2.0 mg/L. Potential drug-to-drug interactions were appropriately reviewed and cyclosporine dosing was reduced accordingly, with its level remaining within the target range. As the patient was a painter and continued painting throughout her hospitalization, significant changes in the colors of her paintings (Figures 2 and 3) were noted. The patient indicated she tried to reproduce the exact colors she perceived in her artwork. This resulted in a change of the color tones to purple. However, 2 weeks into voriconazole therapy, the respiratory specimen cultures grew Coccidioides immitis/posadasii (Figure 4) and thus voriconazole was switched to fluconazole with rapid resolution of her visual changes. The overall clinical picture was consistent with asymptomatic cavitation of a solitary coccidioidal pulmonary nodule. The patient remains clinically well on fluconazole 6 months post-pancreas graft rejection. Voriconazole has been reported to cause visual disturbances in approximately 30% of patients. 1 While photopsias are most Abstract A 40-year-old female with a history of type 1 diabetes mellitus and solitary pancreas transplant, presented with pancreatic graft rejection 1-year post-transplant. Incidentally, a 1.1 cm right lower lobe cavity was identified during her workup. Given the augmentation of immunosuppression, voriconazole was empirically started for possible invasive pulmonary aspergillosis. As the patient was a painter, this resulted in a significant change in the colors of h...

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“…Voriconazole is a triazole antifungal factor that inhibits fungal ergosterol biosynthesis. It is structurally related to fluconazole with the major difference being the substitution of a fluoropyrimidine group in place of a triazole moiety . It is a triazole antifungal agent with a broad spectrum of biological activities.…”

Section: Introductionmentioning

confidence: 99%

“…It is structurally related to fluconazole with the major difference being the substitution of a fluoropyrimidine group in place of a triazole moiety. [1,2] It is a triazole antifungal agent with a broad spectrum of biological activities. Voriconazole is accessible and used as a powder for oral suspension and as a solution for intravenous infusion.…”

Section: Introductionmentioning

confidence: 99%

Inhibition profiles of Voriconazole against acetylcholinesterase, α‐glycosidase, and human carbonic anhydrase I and II isoenzymes

Topal

2019

J Biochem & Molecular Tox

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In this work, the inhibitory activity of Voriconazole was measured against some metabolic enzymes, including human carbonic anhydrase (hCA) I and II isoenzymes, acetylcholinesterase (AChE), and α‐glycosidase; the results were compared with standard compounds including acetazolamide, tacrine, and acarbose. Half maximal inhibition concentration (IC50) values were obtained from the enzyme activity (%)‐[Voriconazole] graphs, whereas Ki values were calculated from the Lineweaver‐Burk graphs. According to the results, the IC50 value of Voriconazole was 40.77 nM for α‐glycosidase, while the mean inhibition constant (Ki) value was 17.47 ± 1.51 nM for α‐glycosidase. The results make an important contribution to drug design and have pharmacological applications. In addition, the Voriconazole compound demonstrated excellent inhibitory effects against AChE and hCA isoforms I and II. Voriconazole had Ki values of 29.13 ± 3.57 nM against hCA I, 15.92 ± 1.90 nM against hCA II, and 10.50 ± 2.46 nM against AChE.

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Mechanism of Voriconazole-Induced Transient Visual Disturbance: Reversible Dysfunction of Retinal ON-Bipolar Cells in Monkeys

Cited by 18 publications

References 21 publications

Genetic polymorphisms of transient receptor potential melastatin 1 correlate with voriconazole‐related visual adverse events

Genetic polymorphisms of transient receptor potential melastatin 1 correlate with voriconazole‐related visual adverse events

When medicine transforms art

Inhibition profiles of Voriconazole against acetylcholinesterase, α‐glycosidase, and human carbonic anhydrase I and II isoenzymes

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