Ocular Safety Profile of BRAF and MEK Inhibitors

Mettler, C.; Monnet, Dominique; Kramkimel, N.; Tréluyer, Jean‐Marc; Mouthon, Luc; Brézin, Antoine P.; Dupin, Nicolas; Valnet-Rabier, Marie-Blanche; Chouchana, Laurent; Terrier, B.

doi:10.1016/j.ophtha.2021.05.008

Cited by 21 publications

(14 citation statements)

References 31 publications

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“…Within the literature, studies report systemic adverse events such as fatigue, nausea, arthralgia, reduced ejection fraction, and pyrexia (3,6). However, the prevalence and severity of ocular adverse effects related to combined dabrafenib and trametinib therapy continue to be poorly documented and are largely limited to clinical trials (4,5,6).…”

Section: Discussionmentioning

confidence: 99%

“…With the increased use of combined BRAF and MEK inhibitors in the management of melanoma, multiple studies have reported various ocular adverse effects, including dry eyes, ocular and orbital in ammation, neuro-ophthalmic disorders, and serous retinopathy (1). Treatment-related VKH-like syndrome is rare presentation but considered a severe ocular adverse event associated with combined therapy (4,5).…”

Section: Introductionmentioning

confidence: 99%

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VKH-like syndrome in the setting of Dabrafenib and Trametinib therapy for BRAF mutant metastatic melanoma: A case report

Gunaratnam,

Sivagurunathan,

FRANZCO

2023

Preprint

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Background: To report a unique case of Vogt‒Koyanagi‒Harada (VKH)-like uveitis in a patient with BRAF mutant metastatic melanoma associated with concurrent use of BRAF and MEK inhibitors. Case presentation: A 49-year-old woman with stage IV metastatic cutaneous melanoma developed bilateral acute pan-uveitis with multifocal serous retinal detachments, four months after starting combined dabrafenib and trametinib therapy. Clinical assessment, together with fluorescein angiography, optical coherence tomography, and serology, to exclude other key differential diagnoses led to the diagnosis of VKH-like uveitis. Prompt systemic corticosteroids and modification of the dosing schedule of the suspected offending agents resulted in the resolution of intraocular inflammation and serous retinal detachments. Currently, systematic reviews reporting ocular adverse effects of combined dabrafenib and trametinib therapy are limited, although a retrospective study by Mettler et al. reported an odds ratio of 21.8 for VKH-like disease. Management of VKH in reported cases involves discontinuation of offending agents and initiation of intravenous corticosteroids for three days, followed by tapering oral corticosteroid treatment. Conclusion: Both ophthalmologists and oncologists should be aware of the potential association between VKH-like uveitis and BRAF and MEK inhibitors, as these medications are becoming more common in the management of metastatic malignancies. Early and prompt recognition of this condition and treatment can be sight saving without compromising treatment for metastatic malignancy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

VKH-like syndrome in the setting of Dabrafenib and Trametinib therapy for BRAF mutant metastatic melanoma: A case report

Gunaratnam,

Sivagurunathan,

FRANZCO

2023

Preprint

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“…Mevcut veriler yan etkinin doz ve süre bağımlı olabileceğine işaret etmektedir. [96] Ek olarak, BRAF/MEK inhibitörlerinin, uzun süreli ve eşzamanlı kullanımı olası bir sinerjistik veya aditif etki ile panüveit gibi ciddi bir tabloyu beraberinde getirebilmektedir. Tanı için, metastatik cilt kanseri tedavisi alan ve üveit bulguları saptanan olgular, halk arasında 'akıllı ilaç tedavisi' olarak bilinen BRAF/MEK inhibitörlerinin kullanımı açısından detaylıca sorgulanmalıdır.…”

Section: Melanom Için Hedefe Yönelik İlaç Tedavileriunclassified

Drugs Causing Uveitis: Pathogenesis, Diagnosis and Treatment

2023

Güncel Retina (Current Retina)

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Drug-induced uveitis, which may result from systemic, periocular, intraocular, and topical application of certain drugs, has been covered extensively in numerous publications over the last decade. The dose and duration of the drug and other drugs used simultaneously may be determinative in the development of the uveitis. Drug-induced uveitis, which is rare and can occur in a wide clinical spectrum from mild to severe, usually regresses rapidly with accurate diagnosis and discontinuation of the relevant drug. Therefore, it is important for clinicians to be aware of the drugs that cause uveitis.

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“…Die Uveitis lässt sich meist ohne Absetzen der tumorrelevanten Therapie mit der Gabe von Kortikosteroiden therapieren. Auch BRAF- und MEK-Inhibitoren können eine Uveitis induzieren 21 .…”

Section: Retinopathien Durch Exogen Zugeführte Substanzenunclassified

“…In diesen Signalweg kann an verschiedenen Stellen über BRAF-, MEK- und ERK-Inhibitoren blockierend eingegriffen werden. Bei der Therapie von metastasierenden kutanen Melanomen können kurz nach Therapiebeginn (Tage bis 4 Wochen) multifokale neurosensorische Abhebungen auftreten 16 , 21 . Diese werden auch als MEKAR (MEK inhibitor-associated retinopathy) bezeichnet.…”

Section: Retinopathien Durch Exogen Zugeführte Substanzenunclassified

Exogen bedingte Retinopathien

Kellner¹,

Kellner²,

Weinitz³

et al. 2022

Klin Monbl Augenheilkd

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ZusammenfassungExogen bedingte Retinopathien werden am häufigsten durch externe Stimulanzien, seltener durch unerwünschte Arzneimittelwirkungen systemisch oder intravitreal eingesetzter Medikamente und noch seltener durch Impfungen oder die Einwirkung von Lichtstrahlung verursacht. Die Kenntnis exogener Ursachen und ihre mögliche Symptomatik ist zur Prophylaxe oder zur Früherkennung schädigender Wirkungen und zur adäquaten Beratung der Patienten wichtig.

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Ocular Safety Profile of BRAF and MEK Inhibitors

Cited by 21 publications

References 31 publications

VKH-like syndrome in the setting of Dabrafenib and Trametinib therapy for BRAF mutant metastatic melanoma: A case report

VKH-like syndrome in the setting of Dabrafenib and Trametinib therapy for BRAF mutant metastatic melanoma: A case report

Drugs Causing Uveitis: Pathogenesis, Diagnosis and Treatment

Exogen bedingte Retinopathien

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