Acute Exudative Paraneoplastic Polymorphous Vitelliform Maculopathy During Vemurafenib and Pembrolizumab Treatment for Metastatic Melanoma

Abstract

Purpose To describe a case of a patient with BRAF mutation-positive cutaneous melanoma who developed acute exudative polymorphous vitelliform maculopathy (AEPVM) during vemurafenib and pembrolizumab treatment for metastatic melanoma. Methods Retrospective case report documented with wide-field fundus imaging, spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence imaging. Results A 55-year-old woman bilateral ductal breast carcinoma and BRAF mutation positive metastatic cutaneous melanoma complained of bilateral blurred vision within five days of starting vemurafenib (BRAF inhibitor). She had been on pembrolizumab (program death receptor antibody) and intermittently on dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) and had a normal ophthalmologic exam. On presentation three weeks after the introduction of vemurafenib her visual acuity (VA) had declined to 20/40, both eyes. Her exam showed diffuse elevation of the fovea with multifocal yellow-white, crescent-shaped subretinal deposits within the macula of both eyes and bilateral neurosensory retinal detachments by SD-OCT. Discontinuation of vemurafenib and introduction of difluprednate and dorzolamide led to a gradual resolution (over four months) of the neurosensory detachments with recovery of vision. Conclusion This case report suggests AEPVM may be directly associated with the use of BRAF inhibitors as treatment for metastatic cutaneous melanoma, or indirectly by triggering autoimmune-paraneoplastic processes. Future identification of similar associations is required to unequivocally link vemurafenib and/or pembrolizumab to AEPVM in metastatic melanoma.

<p>A Case Of Ipilimumab-Induced Unusual Serous Retinal Detachment In Bilateral Eyes</p>

“…To our knowledge, there were two reports that showed similar OCT findings to those in our case during the course of chemotherapy with immune checkpoint inhibitor for malignant melanoma 9. Recently, Sandhu et al reported a case of paraneoplastic polymorphous vitelliform maculopathy during vemurafenib and pembrolizumab treatment and OCT findings were similar to those in our case 10…”

Bilateral multiple serous retinal detachments after treatment with nivolumab: a case report

“…Therefore, paraneoplastic AEPVM is thought to be a variant of melanoma-associated retinopathy. There is a recent report describing paraneoplastic AEPVM as closely resembling the course of our case in their patient treated with a combination of vemurafenib (a BRAF inhibitor) and pembrolizumab, which has the same mechanism of action as nivolumab, administered as an anti-PD-1 antibody agent for metastatic melanoma [8]. Discontinuation of vemurafenib and introduction of difluprednate and dorzolamide led to a gradual resolution of AEPVM.…”

“…Another possible diagnosis is the paraneoplastic acute exudative polymorphous vitelliform maculopathy (AEPVM) seen in patients with metastatic melanoma [8,9]. AEPVM is a rare disorder associated with multifocal areas of serous detachment and subretinal accumulation of hyperautofluorescent yellowish material in the posterior pole [10].…”

Paraneoplastic acute exudative polymorphous vitelliform maculopathy improved with intravitreal methotrexate

“…There can be consideration given to the fact that the patient was formerly on pembrolizumab as well which has been seen to cause inflammatory changes in the eye, 8 and has also been a medication used during another documented case of AEPVM. 9 The authors of this case describe a patient developing AEPVM days after starting vemurafenib, which was subsequently stopped due to ocular symptoms, all the while on pembrolizumab among other forms of therapy. These authors also considered whether pembrolizumab could be a cause of the condition, however the patient had been on this therapy for some time and the condition improved over four months while still on the medication, which should seemingly argue against it being causative.…”