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Symptoms ⬇

Slowly progressive, symmetric ophthalmoplegia and droopy eyelids. Almost never have diplopia. Usually bilateral; there is no diurnal variation; there may be a family history.

Signs ⬆ ⬇

Critical

Ptosis, limitation of ocular motility (sometimes complete limitation), normal pupils, and orthophoric.

Other

Weak orbicularis oculi muscles, weakness of limb and facial muscles, and exposure keratopathy.

Differential Diagnosis ⬆ ⬇

The following syndromes must be ruled out when CPEO is diagnosed:

  • Kearns–Sayre syndrome: Onset of CPEO before age 20 years associated with retinal pigmentary degeneration (classically exhibiting a salt-and-pepper appearance) and heart block that usually occurs years after the ocular signs and may cause sudden death. Other signs may include hearing loss, mental retardation, cerebellar signs, short stature, delayed puberty, nephropathy, vestibular abnormalities, increased cerebrospinal fluid protein, and characteristic “ragged red fiber” findings on muscle biopsy. Although some are inherited maternally, the vast majority are due to spontaneous mitochondrial deletions.
  • Progressive supranuclear palsy (Steele–Richardson–Olszewski syndrome): Rare progressive neurodegenerative disorder affecting the brainstem that causes early gait instability and ophthalmoplegia. Often downgaze affected first followed by other gaze limitations; vertical more than horizontal. Other eye movement problems include abnormalities in the saccadic and pursuit subsystems of horizontal gaze. Often the eyelids are held wide open resulting in a “staring” type of facial expression. Neck and axial rigidity is an important sign.
  • Abetalipoproteinemia (Bassen–Kornzweig syndrome): Retinal pigmentary degeneration similar to retinitis pigmentosa, diarrhea, ataxia, and other neurologic signs. Acanthocytosis of red blood cells is seen on peripheral blood smear and LP demonstrates increased cerebrospinal fluid protein. See 11.28, RETINITIS PIGMENTOSA AND INHERITED CHORIORETINAL DYSTROPHIES.
  • Refsum disease: Retinitis pigmentosa and increased blood phytanic acid level. May have polyneuropathy, ataxia, hearing loss, anosmia, and others. See 11.28, RETINITIS PIGMENTOSA AND INHERITED CHORIORETINAL DYSTROPHIES.
  • Oculopharyngeal dystrophy: Difficulty swallowing, sometimes leading to aspiration of food; may have autosomal dominant inheritance.
  • Mitochondrial myopathy and encephalopathy, lactic acidosis, and stroke-like episodes: Occurs in children and young adults. May have headache, transient hemianopsia, hemiparesis, nausea, and vomiting. Elevated serum and cerebrospinal fluid lactate levels and may have abnormalities on MRI.

Work Up ⬆ ⬇

Workup
  1. Careful history: Determine the rate of onset (gradual versus sudden, as in cranial nerve disease).
  2. Family history.
  3. Carefully examine the pupils and ocular motility.
  4. Test orbicularis oculi strength.
  5. Fundus examination: Look for diffuse pigmentary changes.
  6. Check swallowing function.
  7. Ice test, rest test, or edrophonium chloride test to check for myasthenia gravis.
  8. Prompt referral to a cardiologist for full cardiac workup (including yearly electrocardiograms) if Kearns–Sayre syndrome is suspected.
  9. If neurologic signs and symptoms develop, consult a neurologist for workup (including possible LP).
  10. Lipoprotein electrophoresis and peripheral blood smear if abetalipoproteinemia suspected.
  11. Serum phytanic acid level if Refsum disease suspected.
  12. Consider genetic testing.
NOTE:

Some patients with CPEO are supersensitive to edrophonium chloride which may precipitate heart block and arrhythmias.

Treatment ⬆ ⬇

There is no cure for CPEO, but associated abnormalities are managed as follows:

  1. Treat exposure keratopathy with lubricants at night and artificial tears during the day. See 4.5, EXPOSURE KERATOPATHY.
  2. Single vision reading glasses or base-down prisms within reading glasses may help reading when downward gaze is restricted.
  3. In Kearns–Sayre syndrome, a pacemaker may be required.
  4. In oculopharyngeal dystrophy, dysphagia and aspirations may require cricopharyngeal surgery.
  5. In severe ptosis, consider ptosis crutches or surgical repair, but watch for worsening exposure keratopathy.
  6. Genetic counseling as needed.

Follow Up ⬆

Depends on ocular and systemic findings.