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Chronic Progressive External Ophthalmoplegia


Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disorder stemming from several genetic mutations. The most characteristic feature of the disease is extraocular muscle weakness leading to ptosis and limited eye movements. Generalized weakness, cataracts, ataxia, depression, heart conduction abnormalities, and hearing loss are other notable manifestations of the disease. The diagnosis rests on a thorough clinical assessment followed by imaging and muscle biopsy studies. Molecular genetic testing for detection of mitochondrial DNA mutations is necessary for a confirmation of the diagnosis.


Chronic progressive external ophthalmoplegia (CPEO) is considered to be one of the diseases enclosed in the group of mitochondrial disorders in the adult population [1]. Various mutations in the mitochondrial DNA, either in a familial or sporadic pattern, present the underlying cause of the disease [2] [3]. CPEO is by some authors regarded as a part of the continuum of the mitochondrial myopathy disease spectrum, together with CPEO plus and Kearns-Sayre syndrome [4]. The clinical presentation develops as a result of progressive muscle weakness [1] [4]. Extraocular muscle weakness is the cardinal manifestation of chronic progressive external ophthalmoplegia, manifesting as bilateral ptosis and limited eye movements [5]. Cataracts can sometimes be observed [5]. In addition to ocular symptoms, mitochondrial DNA mutations affect other structures including the skeletal muscles, the retina, and the cerebellum [1]. Generalized fatigue and painful movements of the limbs is reported by the majority of patients, which may be severe enough to limit daily activities and significantly impair the quality of life [1]. These complaints are the probable reason why depression may be encountered, another important constituent of the clinical presentation of CPEO [1] [5]. Defects of the cerebellum and the vestibulocochlear system may lead to symptoms such as ataxia and hearing loss [1] [4] [5]. Heart conduction disorders are also reported in a significant number of cases and are the hallmarks of a more severe phenotype of the disease.

Limited Mobility
  • In practice, it is hard to separate difficulty with sporting activities due to limited mobility and stamina with that due to poor vision. References 1. Chinnery PF , Turnbull DM . Epidemiology and treatment of mitochondrial disorders .[doi.org]
Excessive Daytime Sleepiness
  • Thirty-five percent of patients fulfilled the criteria for restless legs syndrome, 30% excessive daytime sleepiness, and 70% significant periodic limb movements. PSG recordings revealed several indicators of a disrupted sleep architecture.[ncbi.nlm.nih.gov]
Left Ventricular Dysfunction
  • CONCLUSION: Although cardiac involvement in patients with CPEO is generally considered to be limited to the cardiac conduction system, left ventricular dysfunction may be present and should receive more attention in the management of patients with CPEO[ncbi.nlm.nih.gov]
  • The EMG of the ocular muscles suggested myopathy. A specimen of ocular muscle was obtained by biopsy and examined with the light microscope and-for the first time-under the electron microscope.[ncbi.nlm.nih.gov]
  • BACKGROUND: Mitochondrial myopathy is the commonest morphological diagnosis in the patients with the syndrome of chronic progressive external ophthalmoplegia. This syndrome consists of a group of clinically heterogeneous disorders.[ncbi.nlm.nih.gov]
  • We report a 14-year-old boy with CPEO and a mild proximal myopathy without these characteristic "ragged red" fibres.[ncbi.nlm.nih.gov]
  • We suggest that partial cytochrome oxidase deficiency is the underlying defect in mitochondrial myopathy associated with the oculocraniosomatic syndromes.[ncbi.nlm.nih.gov]
  • Measures of visual disability should be included in studies of natural history and treatment of mitochondrial ocular myopathies.[ncbi.nlm.nih.gov]
Average Intelligence
  • The patient was born of consanguineous parents, developed normally, and was of average intelligence.[ncbi.nlm.nih.gov]


To make the diagnosis of a mitochondrial myopathy, the physician must perform a thorough clinical assessment, starting with a proper patient history. The onset of symptoms, their progression, as well as severity must be covered, as they can provide vital clues toward the diagnosis of myopathic disorders. When generalized weakness accompanied by muscle pain, ocular deficits, impaired coordination, and hearing loss are present, a more detailed investigation should be sought. An electrocardiogram (ECG) is useful for detecting heart conduction abnormalities. Imaging studies such as magnetic resonance imaging (MRI) of the head and MR spectroscopy may show atrophy of the cerebrum and cerebellum, as well as a reduced size of the extraocular muscles [4] [6] [7]. Nevertheless, these changes, although suggestive of mitochondrial myopathy, are not specific to CPEO [4]. For this reason, muscle biopsy and subsequent histopathological examination need to be performed [3] [5] [8] [9]. The biopsy will usually depict the presence of ragged red fibers and cytochrome c oxidase (COX)-deficient fibers, which are highly specific for a mitochondrial disease [5]. Approximately 25% of patients will have normal biopsy results, thus molecular genetic studies are considered to be the main method of confirming chronic progressive external ophthalmoplegia [3] [5] [8] [9].

Decreased Vital Capacity
  • Expiratory weakness was associated with a decreased vital capacity (ρ 0.502, p 0.015) and decreased peak expiratory flow (ρ 0.422, p 0.045).[ncbi.nlm.nih.gov]


  • Effective treatment does not exist, and corrective surgery of the ptosis as a palliative measure is a treatment option. PATIENTS AND METHODS: This was a retrospective study of 10 years' duration gathering patients with the diagnosis.[ncbi.nlm.nih.gov]
  • There is currently no defined treatment to ameliorate the muscle weakness of CPEO. Treatments used to treat other pathologies causing ophthalmoplegia has not been shown to be effective.[en.wikipedia.org]
  • Three of 7 patients without pacemaker treatment died, and 5 were successfully treated with pacemaker. The disturbances in AV-conduction are not thought to be a mere coincidence to the ocular disorder. Cardiomyopathy has been suggested.[ncbi.nlm.nih.gov]
  • Treatment is limited, but newer therapies are being investigated.[ncbi.nlm.nih.gov]
  • RESULTS: Fundus photos, retinal optical coherence tomography, and fluorescein angiography were significant for findings consistent with bilateral cystoid macular edema, which were found to have resolved after 18 months without treatment.[ncbi.nlm.nih.gov]


  • The prognosis and aetiology of the condition are discussed.[ncbi.nlm.nih.gov]
  • Therefore, we suggest that C10orf2 gene should be screened in CPEO individuals with multiple mtDNA deletions, which might help in prognosis of this disease and appropriate genetic counseling.[ncbi.nlm.nih.gov]
  • Prognosis Luckily, people with CPEO have a good prognosis and the disease should not effect other aspects of health. While the disease is progressive and symptoms tend to get worse over time, the severity of the disease differs with each patient.[healthguideinfo.com]
  • Ischemic Visual Loss 235 1335 Orbital Manifestations 236 1343 LargeVessel Vasculitis 237 135 Laboratory Investigations in GCA 238 1352 CReactive Protein 239 1355 Anemia 240 1361 Temporal Artery Biopsy 241 1363 Role of Ultrasound 243 137 Treatment and Prognosis[books.google.it]
  • KSS is slowly progressive and prognosis varies depending on severity and the number of systems or organs involved which widely varies from patient to patient.[umdf.org]


  • Significant pain, proptosis, or pupil involvement are not features of CPEO and should prompt evaluation for alternative etiologies. Mitochondrial DNA mutations are increasingly being recognized as the etiology for CPEO syndromes.[ncbi.nlm.nih.gov]
  • In both cases, hematological studies and neuroimaging ruled out alternative etiologies, whereas muscle biopsy showed findings of mitochondrial myopathy.[ncbi.nlm.nih.gov]
  • MeSH terms, Substance MeSH terms Adult Audiometry, Pure-Tone DNA, Mitochondrial/genetics Evoked Potentials, Auditory Female Gene Deletion Hearing Loss, Sensorineural/epidemiology* Hearing Loss, Sensorineural/etiology* Hearing Loss, Sensorineural/physiopathology[ncbi.nlm.nih.gov]
  • In both cases, hematological studies and neuroimaging ruled out alternative etiologies, whereas muscle biopsy showed findings of mitochondrial myopathy. No Reference information available - sign in for access.[ingentaconnect.com]
  • She was diagnosed with CPEO and cerebellar ataxia of unclear etiology. Imaging 1, Patient with CPEO and gaze-evoked nystagmus Contributor Daniel R. Gold, D.O. Publisher Spencer S.[collections.lib.utah.edu]


  • MeSH terms, Substance MeSH terms Adult Audiometry, Pure-Tone DNA, Mitochondrial/genetics Evoked Potentials, Auditory Female Gene Deletion Hearing Loss, Sensorineural/epidemiology* Hearing Loss, Sensorineural/etiology* Hearing Loss, Sensorineural/physiopathology[ncbi.nlm.nih.gov]
  • April 2014 Volume 55, Issue 13 Free ARVO Annual Meeting Abstract April 2014 A national epidemiological study of chronic progressive external ophthalmoplegia in the United Kingdom - molecular genetic features and neurological burden Author Affiliations[iovs.arvojournals.org]
  • EPIDEMIOLOGY Incidence CPEO typically have an onset in childhood or early adolescence but they can occur at any age.[entokey.com]
  • Diagnosis: Chronic Progressive External Ophthalmoplegia (CPEO) - Kearns Sayre Syndrome EPIDEMIOLOGY Rare cause of chronic ptosis ophthalmoplegia Usually present in 2nd decade of life SIGNS Ptosis with poor levator function Loss of Bell’s reflex (eyes[webeye.ophth.uiowa.edu]
  • The balance of oxidative demands of a given tissue and the proportion of deleted mtDNA it contains will ultimately determine whether the tissue is affected clinically. [12] Epidemiology Frequency Worldwide Worldwide, the prevalence of mitochondrial disease[emedicine.com]
Sex distribution
Age distribution


  • A complete cure is usually not possible but disease outcomes and life expectancy can be improved with supportive treatment and appropriate diets. α1-Antitrypsin deficiency (AAT deficiency) Mode of inheritance : autosomal codominant Pathophysiology α1-[amboss.com]
  • PATHOPHYSIOLOGY • The mitochondria is responsible for production of ATP by oxidative phosphorylation, the detoxification of reactive oxygen species, regulation of cell apoptosis, and other functions such iron metabolism, fatty acid oxidation, and amino[entokey.com]
  • Pathophysiology Mitochondrial DNA (mtDNA) encodes for essential components of the respiratory chain.[emedicine.com]
  • Article navigation 1 1 Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy Search for other[doi.org]
  • This comprehensive magnetic resonance study of patients with molecularly confirmed CPEO has revealed a number of important findings that are directly relevant to our understanding of the underlying pathophysiology in this mitochondrial ocular disorder[journals.plos.org]


  • A thorough ophthalmic history and examination before ptosis surgery may prevent the corneal complications resulting from surgical intervention.[ncbi.nlm.nih.gov]
  • Research is ongoing to develop a way to prevent the transmission of mitochondrial DNA mutations to future children.[mda.org.au]
  • Prevention There is no way to prevent ophthalmoplegia. Resources Organizations American Academy of Neurology. 1080 Montreal Ave., St. Paul, MN 55116. (612) 695-1940. .[medical-dictionary.thefreedictionary.com]
  • If the diagnosis ends up being ophthalmoplegia, fast treatment could mean slowing the progression of the condition and preventing more serious complications such as blurred or double vision.[belmarrahealth.com]
  • Ophthalmoplegia in these cases precedes the development of cardiac conduction deficits, and appropriate interdisciplinary work-up may be paramount in preventing lethal progression of the disease.[healio.com]



  1. Smits BW, Fermont J, Delnooz CC, Kalkman JS, Bleijenberg G, van Engelen BG. Disease impact in chronic progressive external ophthalmoplegia: more than meets the eye. Neuromuscul Disord. 2011;21(4):272-278.
  2. Auré K. Ogier de Baulny H, Laforêt P, Jardel C, Eymard B, Lombès A. Chronic progressive ophthalmoplegia with large-scale mtDNA rearrangement: can we predict progression? Brain. 2007;130(Pt 6):1516-1524.
  3. Wabbels B, Ali N, Kunz WS, Roggenkämper P, Kornblum C. Chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome : interdisciplinary diagnosis and therapy [Article in German] Ophthalmologe. 2008;105(6):550-556.
  4. Heidenreich JO, Klopstock T, Schirmer T, Saemann P, Mueller-Felber W, Auer DP. Chronic progressive external ophthalmoplegia: MR spectroscopy and MR diffusion studies in the brain. AJR Am J Roentgenol. 2006;187(3):820-824.
  5. Chen T, Pu C, Shi Q, et al. Chronic progressive external ophthalmoplegia with inflammatory myopathy. Int J Clin Exp Pathol. 2014;7(12):8887-8892.
  6. Wray SH, Provenzale JM, Johns DR, et al. MR of the brain in mitochondrial myopathy. Am J Neuroradiol 1995;16:1167-1173.
  7. Carlow TJ, Depper MH, Orrison WW. MR of extraocular muscles in chronic progressive external ophthalmoplegia. Am J Neuroradiol 1998;19:95-99.
  8. Kornblum C, Kunz WS, Klockgether T, Roggenkämper P, Schröder R. Diagnostic value of mitochondrial DNA analysis in chronic progressive external ophthalmoplegia (CPEO) [Article in German] Klin Monbl Augenheilkd. 2004;221(12):1057-1061.
  9. Sundaram C, Meena AK, Uppin MS, et al. Contribution of muscle biopsy and genetics to the diagnosis of chronic progressive external opthalmoplegia of mitochondrial origin. J Clin Neurosci. 2011;18(4):535-538.

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Last updated: 2018-06-21 16:57