The CV2/CRMP5 (Collapsin response-mediator protein-5) antibody is linked to paraneoplastic neurologic syndromes, typically presenting with limbic encephalitis, chorea, ataxia, and peripheral neuropathy. Although rare, ophthalmological presentations include optic neuritis, retinitis, vitritis, and uveitis. Such ocular presentations have rarely been reported to be associated with immune checkpoint inhibitors (ICIs). We report a rare case of CV/CRMP5 antibody-associated encephalopathy, optic neuropathy, and retinal vasculitis related to the ICI, pembrolizumab.

A 72-year-old man with Merkel cell carcinoma on pembrolizumab presented with two weeks of mental status changes, hallucinations, weakness, and appetite loss. Diagnosed with autoimmune encephalitis, he was treated with high-dose IV methylprednisolone, improving his mental status. He later developed bilateral vision loss and was diagnosed with paraneoplastic autoimmune retinopathy, subsequently being treated with monthly IVIG for 6 months. After treatment cessation, severe photophobia persisted, prompting neuro-ophthalmologic referral. Neuro-ophthalmology exam showcased severe bilateral visual acuity decline with a significantly constricted visual field, disc edema/hyperemia, pan uveitis, and retinal pigment epithelium loss. Retinal vasculitis was noted on Fluorescein angiogram, peripapillary photoreceptor loss on OCT retina, and electroretinography demonstrating generalized photoreceptor dysfunction. Lumbar puncture revealed elevated protein and lymphocytosis. Further investigation revealed mild gliosis with scattered perivascular lymphocytes infiltration on right dural biopsy and a positive CRMP-5 antibody. This led to treatment with oral steroids and rituximab, with improvement of optic neuropathy and retinal vasculitis.

This case highlights a unique presentation of CRMP5 sequelae, including encephalopathy, retinitis, optic neuropathy, and vasculitis. His mental status changes and ocular symptoms began after starting pembrolizumab. The introduction of this ICI likely triggered the formation of CRMP5 antibodies, resulting in a myriad of neurologic and ocular inflammatory signs and symptoms. In such cases, discontinuing the ICI and considering alternative immunotherapies is advisable. Early and aggressive immunotherapy remains strongly recommended for better prognosis.