JAMA Ophthalmology Clinical Challenge: A Man Who Cannot Elevate His Right Eye or Abduct His Left Eye

Case report:

A 54-year-old man presented with a 3-day history of right ptosis and double vision. He was otherwise healthy and did not take any regular medications. Initially, he had horizontal diplopia on the first day that was worse at the end of the day, but this resolved when the right eyelid ptosis became complete. He denied any difficulty with his speech, swallowing, weakness, or sensory changes.

He presented to the emergency department, and the emergency department physician reported a normal neurological examination result apart from the right-sided ptosis and limited eye movements.

He was referred to ophthalmology and had a visual acuity of 20/20 OU. Both pupils were equal sizes and reactive to light. He was found to only have a complete limitation of elevation of his right eye and a limitation of abduction in his left eye.

He was orthophoric in primary position, and there were no eyelid twitches. Orbicularis oculi strength was reduced on both sides. A dilated fundus examination had normal results bilaterally. An initial neurological examination, including assessments of motor strength in the upper and lower extremities and reflexes and a sensory examination, had normal results.

Patient was diagnosed having Ocular myasthenia gravis confirmed by Ice pack test.

This patient had new-onset right ptosis with an inability to elevate his right eye and abduct his left eye, with otherwise normal neurologic examination results. This combination of examination findings cannot be localized in the central nervous system, because there is involvement of the levator muscle and superior rectus on the right (innervated by cranial nerve III) and the lateral rectus on the left (innervated by cranial nerve VI). This should raise concern for ocular myasthenia gravis, and a readily accessible test in the clinic is an ice pack test or rest test, which should result in an improvement in the ptosis, as was seen in this patient.

His palpebral fissure measured 1 mm before ice was applied and 6 mm 5 minutes after the application of ice. The ice test has been reported to have a sensitivity of 0.94% and specificity of 0.97% in ocular myasthenia and is based on the principle that cooler temperatures result in reduced acetylcholinesterase activity. It involves placing ice on the involved eyelid for at least 2 minutes and comparing the pretest to posttest measurements. The test is considered to have positive results when there is an increase in the size of the palpebral fissure compared with the pretest measurement.

This patient had no symptoms of giant cell arteritis, such as headache, scalp tenderness, or jaw claudication, and he was relatively young for this condition. Neuroimaging would not be the next best step, because his examination findings could not be localized. Computed tomography angiography or magnetic resonance angiography would be indicated in a third nerve palsy, but this patient did not have this. He had no orbital signs (eg, proptosis, conjunctival chemosis, eyelid retraction), and an orbital lesion would not explain the ptosis.

Ocular myasthenia gravis is an autoimmune disease of the neuromuscular junction confined to the ocular muscles. In ocular myasthenia gravis, autoantibodies develop against the acetylcholine receptors or other associated proteins at the neuromuscular junction, leading to muscle weakness and fatigability. Patients typically present with ptosis and diplopia that is worse with muscle use, with normal pupil reactions. While more than 85% of patients with the systemic variant have detectable autoantibodies in their serum, patients with the ocular variant have 45% to 60% sensitivity with the same test.

In seronegative ocular myasthenia gravis, single-fiber electromyography may be used to evaluate neuromuscular transmission. In this patient, serum acetylcholine receptor antibody tests had negative results, but single-fiber electromyography was highly suggestive of a postsynaptic neuromuscular junction disorder.

Initial therapy for ocular myasthenia gravis consists of acetylcholinesterase inhibitors, such as 30 to 150 mg of pyridostigmine 3 to 4 times daily. Many patients need additional immunosuppression for full clinical remission, including prednisone, azathioprine, and mycophenolate mofetil. Approximately two-thirds of patients with ocular myasthenia gravis will progress to systemic disease, and patients should be counseled on seeking medical attention if they have clinically significant sequelae, such as difficulty breathing.

Patient Outcome:

The patient's ptosis and diplopia mildly improved with 60 mg of pyridostigmine 3 times daily, and prednisone daily was started at 10 mg and titrated up to 40 mg, resulting in complete remission. At his 6-month follow-up, a slow taper of prednisone was initiated because he continued to have no ptosis and normal ocular motility.

Source: Jennifer Ling, Andrew Micieli, Jonathan A. Micieli; JAMA Ophthalmology Clinical Challenge

doi:10.1001/jamaophthalmol.2021.0028