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Original Investigation |

Uveitis in Patients With Late-Stage Cutaneous Melanoma Treated With Vemurafenib

Mikael Guedj, MD1,2; Astrid Quéant, MD1,2; Elisa Funck-Brentano, MD3; Nora Kramkimel, MD2,4; Judith Lellouch, MD1; Dominique Monnet, MD, PhD1,2; Christine Longvert, MD, PhD3; Amelie Gantzer, MD3; Antoine P. Brézin, MD, PhD1,2
[+] Author Affiliations
1Department of Ophthalmology, Cochin-Hôtel-Dieu Hospital, Paris, France
2Faculté de Médecine, Université Paris Descartes, Paris, France
3Department of Dermatology, Ambroise Paré Hospital, Boulogne-Billancourt, France
4Department of Dermatology, Cochin Hospital, Paris, France
JAMA Ophthalmol. 2014;132(12):1421-1425. doi:10.1001/jamaophthalmol.2014.3024.
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Importance  This case series highlights the risk of uveitis in patients treated with vemurafenib for unresectable or metastatic cutaneous melanoma.

Objective  To assess the occurrence and severity of uveitis as an adverse effect of vemurafenib therapy.

Design, Setting, and Patients  In this observational small case series, data were collected successively from May 1, 2012, through February 31, 2013, from patients with clinical signs of ocular inflammation treated with vemurafenib at the Department of Ophthalmology, Cochin-Hôtel-Dieu Hospital.

Main Outcomes and Measures  Patients’ demographics, vemurafenib dosages, and the intervals between the onset of treatment and the first ocular symptoms were recorded. The characteristics of ocular inflammatory manifestations were analyzed. The effect of the discontinuation of vemurafenib therapy on ocular manifestations was assessed, as well as the effect of rechallenging when vemurafenib was reintroduced.

Results  Seven patients (mean [SD] age, 74.7 [4.0] years) had uveitis. The vemurafenib dose was 960 mg twice per day in 6 patients and a half dose in 1 patient. The mean (SD) time until the appearance of ocular signs was 5.6 (2.3) months (range, 19 days to 7 months), and inflammation ranged from mild or low-grade anterior uveitis to severe explosive panuveitis complicated by retinal detachment. Signs of ocular inflammation were always bilateral. Optical coherence tomography revealed a macular edema in only 1 of the 7 patients. Clinical improvement occurred when vemurafenib therapy was stopped in 5 of 7 patients. The rechallenge at treatment reintroduction was positive in 2 of 7 patients.

Conclusions and Relevance  This small case series highlights that uveitis can be a noteworthy adverse effect of vemurafenib therapy in patients with metastatic cutaneous melanoma. However, these cases of uveitis were usually restricted to the anterior segment and manageable with local corticosteroid therapy, which justified the continuation of vemurafenib therapy because the benefits regarding the patients’ survival were greater than the risk to their vision.

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Figure 1.
Clinical Presentation of Uveitis in Patient 5

A, Nongranulomatous anterior uveitis 3 weeks after vemurafenib treatment onset. In the left eye, pigment deposits are seen on the anterior capsule at the site of synechiae, which were subsequently broken. B, Vitritis (anterior chamber cells [4+]) in the left eye; optic disc edema is seen through the dense vitreous haze.

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Figure 2.
Clinical Presentation of Uveitis in Patient 6

Nongranulomatous anterior uveitis in the left eye 7 months after onset of vemurafenib treatment. The intense inflammation resulted in posterior synechiae, some of which remained despite the mydriatic and corticosteroid local treatment.

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