Chronic Progressive External Ophthalmoplegia (CPEO)

CPEO, or Chronic Progressive External Ophthalmoplegia, is a rare mitochondrial disease that causes weakness of muscles that control eye movement. This leads to problems with eyelid position and eye movement, often making it difficult to see. The name literally describes what happens – muscle weakness around the eyes that gets gradually worse over time.

What is CPEO?

CPEO describes a group of patients who experience progressive weakness in the muscles that control eye movement. The condition typically results in restricted eye mobility and ptosis (drooping eyelids), which can significantly impact a person's field of vision.

It’s usually caused by changes in mitochondrial DNA (the DNA inside the tiny energy-producing parts of cells) but may sometimes involve nuclear DNA.

This form of mitochondrial disease can begin at any age, but it most commonly presents in young adulthood.

What are the symptoms of CPEO?

The primary symptoms of CPEO include a gradual loss of the ability to move the eyes normally and drooping of one or both eyelids. As the muscle weakness is progressive, people may find it increasingly difficult to see straight ahead and may compensate by tilting their head or lifting their eyelids with their fingers.

For some people, symptoms remain limited to the eyes. For others, CPEO can form part of a broader mitochondrial condition, sometimes referred to as ‘CPEO-plus’. Possible additional symptoms include:

• Weakness in other muscles
• Difficulty swallowing (dysphagia)
• Heart problems
• Hearing loss
• Limb weakness
• Ataxia or unsteady movement
• Exercise intolerance and fatigue
• Balance difficulties
• Sensory neuropathy, including altered or reduced sensation in the hands and feet
• Mood changes such as depression

It’s important to note that symptoms and severity vary widely between individuals, so someone with CPEO may not experience all the symptoms listed above.

What causes Chronic Progressive External Ophthalmoplegia?

Many different genetic abnormalities can cause CPEO. Some patients have changes affecting mitochondrial DNA, while others have changes in nuclear DNA. Determining the genetic cause is an important part of care, as it can provide information about inheritance, the risk to other family members and the likelihood of developing additional symptoms, some of which may be treatable or manageable.

When CPEO affects other body systems, it may be described as CPEO-plus or, in more extensive cases of mitochondrial disease, may form part of Kearns-Sayre syndrome (KSS).

Is CPEO hereditary?

CPEO is often sporadic, meaning it occurs by chance. However, it can sometimes be inherited, including through maternal inheritance, or follow other genetic patterns depending on the gene involved. A specialist mitochondrial or genetics team can help explain what this means for individuals and families in the UK.

How do you get a diagnosis of CPEO?

Diagnosing CPEO requires ruling out other causes of eyelid or eye movement problems. Diagnosis typically involves several steps:

1. Clinical exam: An eye specialist (ophthalmologist), ideally one with experience of mitochondrial diseases, evaluates eyelid position and eye movement patterns.
2. Genetic testing: Blood tests to look for mitochondrial DNA deletions or nuclear gene mutations.
3. Muscle biopsy: In some cases, a small muscle sample is examined for ‘ragged-red fibres’ and abnormal mitochondria – both classic features of mitochondrial CPEO.
4. Specialised metabolic tests: Blood or urine tests, including mitochondrial biomarkers such as FGF-21 or GDF-15, may be used.

What treatments are available for CPEO?

Like all forms of mitochondrial disease, there is no cure yet for CPEO. Treatment focuses on managing symptoms, maintaining independence and improving quality of life, usually through NHS specialist care.

Ongoing management of CPEO often involves a multidisciplinary NHS team and should include input from an ophthalmologist familiar with the condition.

Symptom-focused care

Management is tailored to the individual and may include:

• Ptosis surgery or eyelid supports such as specialist glasses (sometimes called a ptosis crutch) to improve vision where drooping eyelids interfere with daily activities.
• Strabismus surgery may be considered in some people to help improve eye alignment and reduce double vision. The aim is usually to improve comfort and head posture rather than restore full eye movement, and results can vary over time as muscle weakness progresses.
• Physical and occupational therapy to support muscle strength, mobility and fatigue management.
• Hearing assessments and hearing aids if hearing loss is present.
• Monitoring and management of other affected systems, such as the heart or swallowing difficulties, where relevant.

Ideally, care is co-ordinated by a multidisciplinary team with experience of mitochondrial disease.

Supplements and lifestyle

Some clinicians may recommend specific nutritional supplements, such as coenzyme Q10. Responses vary between individuals, and evidence for benefit in CPEO remains limited. Any supplements should be discussed with a specialist team, as they’re not appropriate or effective for everyone.

Lifestyle approaches, including energy conservation, pacing and managing fatigue, can also be an important part of living with CPEO.

Does Chronic Progressive External Ophthalmoplegia shorten life expectancy?

Many people with isolated CPEO have normal life expectancy, but involvement of other organ systems may affect overall health.

What research is underway into CPEO?

Because CPEO is uncommon and often overlaps with broader mitochondrial conditions, there’s limited research focused solely on CPEO. However, UK and international research into mitochondrial disease more broadly may also benefit people living with CPEO.

Current research efforts are focusing on:

• Improving our understanding of the genetic causes of mitochondrial dysfunction.
• Exploring biomarkers that may help with earlier or more accurate diagnosis of mitochondrial diseases.
• Studies that look at the natural history of mitochondrial conditions to better inform prognosis and care.

At present, there are no widely available disease-modifying treatments specifically for CPEO. Most clinical research efforts remain focused on broader mitochondrial disease groups, which may include people with CPEO as part of larger studies.

What support is available for CPEO patients?

The NHS Highly Specialised Services for Mitochondrial Disorders provide expert care, including diagnosis, management of symptoms and ongoing monitoring. They also provide access to genetic counselling through NHS services to help families understand inheritance patterns and inform any future family planning.

The Lily Foundation exist to offer emotional support and practical advice to all patients and family members affected by a diagnosis of CPEO, from in-person support weekends and information days to online meet-ups and private Facebook groups.

If you or someone you love is dealing with a diagnosis of a mitochondrial disease such as CPEO, please take a look at our mitochondrial disease Q & A page which should help answer some of the questions you have. Please don’t hesitate to get in touch should you have further questions or would like to talk to someone about mitochondrial disease.