To report a case series of 4 patients and review pertinent literature about neuromuscular immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICPis), particularly with ocular weakness involvement and develop a diagnostic algorithm to approach these patients.

The increasing use of ICPis for cancer therapy has led to a recognition of a wide spectrum of irAEs, including neuromuscular disorders. While neuromuscular junction (NMJ) disorders are often considered with ocular symptoms, myositis, metastases to extraocular muscles, and demyelinating neuropathies should also be in the differential. Testing for these alternatives is imperative for management.

All four patients received ICPis and developed ocular symptoms. Three out of the four patients also had dyspnea, dysphagia or proximal weakness. Patient 1’s work-up showed elevated acetylcholine receptor (AChR) antibodies and elevated CK levels. At autopsy, biopsy of the superior rectus muscle showed myositis.  Thus, neuromuscular weakness was secondary to irMyositis and possible NMJ disorder. Patient 2’s work-up showed negative AChR antibody testing, elevated CK level, myopathic motor units on EMG, and triceps muscle biopsy showed myositis; thus, neuromuscular weakness was secondary to irMyositis. Patient 3’s work-up showed mildly elevated CK level, positive AChR antibodies, and EMG evidence of a demyelinating neuropathy. Deltoid muscle biopsy showed myositis; thus neuromuscular weakness was secondary to irMyositis, irDemyelinating neuropathy and possible irNMJ disorder. Patient 4 presented with diplopia only with normal CK level and negative AChR antibody testing. MRI Orbit revealed evidence of a metastasis to the left superior oblique muscle.

Ocular symptoms following ICPi therapy does not always represent a neuromuscular junction disorder. It is important to include myositis, demyelinating neuropathies, and orbital metastases to the differential because the natural history and management are variable.