Chronic Progressive External Ophthalmoplegia (CPEO) is a rare progressive disorder that affects ocular motility and the function of the levator palpebrae muscle and is characterized by bilateral ptosis and decreasing motility of the eyes in all directions of gaze,  ciliary and iris muscles are not involved, and pigmentary retinopathy may be associated.

CPEO is the most frequent manifestation of mitochondrial myopathies, it may occur in the absence of any other clinical sign, but it is usually associated with skeletal muscle weakness.

The onset is usually before 30 years of age, and in some cases the disease occurs early in childhood. Both sexes are equally involved, and familial occurrence is frequent.

Ptosis, which as a rule is bilateral, is often the first symptom, followed by slowly progressive limitation of ocular motility. In the extreme case, both eyes may become frozen. Because of the symmetric nature of this disorder, patients often do not complain of diplopia. They may be unaware of their decreased motility until it becomes severe. In many cases, downward gaze is preserved to a greater extent than up-gaze or horizontal movement. The course of CPEO is characterized by constant progression without periods of remission or exacerbation. Patients also may complain of dryness of the eyes due to exposure keratopathy. In addition to involvement of the extraocular and levator muscles, the orbicularis and other facial muscles may become affected, especially those used in mastication. Atrophy of the extraocular muscles, especially a decrease of muscle thickness, can be demonstrated on CT scans.

Systemic findings of CPEO include short stature, peripheral neuropathy, ataxia, spasticity, somatic muscle weakness, vestibular dysfunction, and deafness. The cardiac conduction disturbances have an onset typically 10 years after ptosis appears and may result in sudden death. Endocrine dysfunction may include hypoparathyroidism, diabetes mellitus, hypogonadism, or growth hormone deficiency.

The possibility of muscle disease should be considered whenever ophthalmoplegia does not correspond to the pattern of a cranial nerve palsy and when there is acquired ptosis. Most diagnoses are made through a process of exclusion and imaging studies. Diagnoses of mitochondrial disorders often are supported by histopathological and biochemical evidence of mitochondrial dysfunction.

In CPEO, magnetic resonance imaging (MRI) of the brain often shows hyperintensity in the thalamus and globus pallidus on T2-weighted images.

Electrocardiograms should be obtained for all patients suspected of mitochondrial cytopathies, to detect any life-threatening cardiac conduction abnormalities.

DD : Parkinson's disease, progressive supranuclear palsy, Myathenia gravis, cavernous sinus syndrome and thyroid eye disease.

In supranuclear lesions, only voluntary eye movements are lost, while involuntary eye movements ( Oculocephalic reflex, vestibulocular reflex and Bell's phenomenon ) are intact. On the other hand in nuclear or infranuclear lesions both voluntary and involuntary eye movements are lost, however Oculocephalic reflex, vestibulocular reflex and Bell's phenomenon may be intact early in CPEO but they are usually lost later with progression of the disease.

Therapy

Complaints that arise from ptosis often are handled by ptosis crutches or a careful surgical approach, in which the lid is raised minimally by addressing the visual obstruction rather than the cosmetic appearance. Overly aggressive attempts to treat the ptosis may result in exposure keratopathy and corneal ulceration because of weak orbicularis oculi muscles and a poor Bell's reflex. Symptomatic ocular deviations may be treated successfully with strabismus surgery.