Chronic progressive external ophthalmoplegia (CPEO): symptoms, treatments, and emerging therapies

Schedule an Appointment or call 732-615-9300.

This article is for educational purposes only and is not medical advice. If you think you may have CPEO or another neuromuscular or mitochondrial condition, seek evaluation by a qualified clinician (often neuro-ophthalmology, neurology, and genetics). Seek urgent care for sudden vision loss, severe eye pain, or new neurologic symptoms.

Chronic progressive external ophthalmoplegia, often shortened to CPEO, is a rare condition that slowly weakens the muscles that move the eyes and lift the eyelids. People often notice droopy lids (ptosis) first, then a gradual limitation in looking up, down, or side-to-side. The pace is typically slow, but the day-to-day impact can be significant, especially for reading, driving, and comfort.

If you are in Red Bank or elsewhere in Monmouth County and you are exploring practical ways to see more comfortably while you pursue specialist evaluation, an optometry team can sometimes help with functional tools like prism lenses, dry eye support, and carefully fitted ptosis crutches that attach to glasses.

What is CPEO?

CPEO is a chronic, slowly progressive weakness of the extraocular muscles, the small muscles that move the eyes. Many cases are linked to mitochondrial dysfunction. Mitochondria are structures in cells that help make energy. When they do not work properly, muscles with high energy demands, including eye muscles, may fatigue or weaken over time.

CPEO can occur on its own, or as part of broader mitochondrial syndromes (sometimes called “CPEO-plus”), where symptoms extend beyond the eyes. Onset is often in adulthood, and progression is typically gradual rather than sudden.

ICD-10 codes (commonly used)

These codes are commonly seen in clinical documentation for CPEO-related presentations. Coding varies by documentation, payer, and local rules. Always confirm coding guidance with your billing team and the clinician’s documentation.

• H49.4: Progressive external ophthalmoplegia

• H49.40: Progressive external ophthalmoplegia, unspecified eye

• G71.3: Mitochondrial myopathy, not elsewhere classified (often used when documenting the broader mitochondrial myopathy context)

• H02.42: Myogenic ptosis of eyelid (when coding ptosis due to muscle weakness, if applicable)

Symptoms and signs

Common eye and vision features include:

• Bilateral ptosis (droopy upper eyelids), often worsening with fatigue

• Limited eye movements (ophthalmoplegia), which can make scanning and tracking harder

• Strabismus or double vision (diplopia) in some people

• Compensatory head and face posture, such as a chin-up posture or frequent brow elevation to lift the lids

• Functional impacts, including eye strain, fatigue with reading, and reduced visual field when the lid blocks the pupil

Some people have additional symptoms outside the eyes (CPEO-plus). Examples can include limb weakness, exercise intolerance, hearing issues, or cardiac conduction problems. These systemic features warrant medical evaluation because they may change what screening is appropriate.

How CPEO is managed today

There is no universally proven disease-stopping therapy for CPEO today, so care is typically supportive and multidisciplinary. Management often focuses on improving function, reducing symptoms, and screening for associated systemic risks when indicated.

Ptosis management options

Depending on the person’s anatomy, symptoms, and ocular surface health, options may include:

• Observation, when lid droop is mild and vision is not significantly blocked

• Lubricating drops or ointment if incomplete blinking or exposure is a concern

• Surgery in selected cases, typically after careful evaluation of eyelid muscle function and corneal protection

• Nonsurgical options, including ptosis crutches

What are ptosis crutches? Ptosis crutches are a small bar or support attached to eyeglass frames that mechanically helps lift the upper eyelid to clear the visual axis. Because they physically interact with the eyelid, fit and comfort matter. Some people need adjustments to reduce irritation, support blinking as much as possible, and avoid worsening dry eye.

Local opticianry note (example): in a case example we often see, a person with stable but visually significant ptosis uses a custom, carefully adjusted ptosis crutch for reading and errands, while continuing medical workup with a neuro-ophthalmologist. The goal is functional support, not a cure.

If you would like to learn what a custom fitting can look like, see ptosis crutches and eyewear modifications and examples in the ptosis crutch gallery

Diplopia and strabismus options

• Prism glasses can sometimes reduce double vision in certain gaze positions.

• Strabismus surgery may be considered in selected cases, usually guided by specialists.

General care and referrals

Many patients benefit from coordinated care that may include:

• Referral to neuro-ophthalmology and/or neurology

• Genetic counseling and testing, when appropriate, to clarify cause and guide trial eligibility

• Screening for associated systemic risks when indicated, for example cardiac evaluation if symptoms or history suggest conduction issues

When to seek urgent care

Seek urgent evaluation for sudden vision loss, severe eye pain with redness, new neurologic deficits (new weakness, trouble speaking, new severe headache), fainting or palpitations, or a rapid change in symptoms.

Future and emerging treatments

Research in mitochondrial disorders is active. It is helpful to think of future therapies in categories.

Mitochondria-targeted therapeutics

These approaches aim to improve mitochondrial function more broadly, rather than targeting a single eye muscle. One medication in this area is elamipretide, marketed as Forzinity.

Important context: Forzinity (elamipretide) is FDA-approved via accelerated approval to improve muscle strength in people with Barth syndrome. Use in CPEO is investigational. Some clinicians have reported limited human experience through research, compassionate use, or expanded-access programs, but it is not an FDA-approved treatment for CPEO yet.

Gene-based approaches

Because mitochondrial disease can be caused by nuclear DNA genes or mitochondrial DNA (mtDNA) variants, research includes multiple strategies:

• AAV gene therapy for some nuclear-encoded mitochondrial disorders, where a healthy copy of a gene is delivered to cells. This is an active area of preclinical research, with important delivery and safety challenges. PMC

• Mitochondrial genome editing and base editing, aiming to shift or correct mtDNA variants. These tools are early-stage and still face major hurdles, including safe delivery to the right tissues and avoiding off-target effects. PMC

Metabolic or substrate therapies

Some mitochondrial disorders involve pathways where metabolic or substrate strategies may help, depending on the gene involved. For example, nucleoside-based approaches have been studied in certain mtDNA maintenance disorders. Applicability depends on the underlying genetic cause, and these therapies are not one-size-fits-all.

A realistic outlook

Progress is accelerating, but timelines and eligibility depend on genetics, trial criteria, and long-term safety data. If you have a confirmed diagnosis, ask your specialist whether clinical trials or registries are appropriate for you.

Bottom line

CPEO is usually slow but impactful. Current care focuses on function, comfort, and coordinated evaluation. For many people, practical supports such as prism lenses, dry eye protection, and well-fitted ptosis crutches can make daily life easier while specialist care and genetic testing clarify the bigger picture.

If you are near Red Bank, NJ and would like help with glasses-based support options, <a href=”https://crystaleyecarenj.com/about-us/red-bank-eye-doctor/”>book an exam</a> or call us at 732-615-9300. Call now — see what you have been missing.

If you are collecting patient feedback for your care team, consider adding a short “reviews and testimonials” section to your clinic website or intake packet to help future patients understand what to expect.

FAQ

Q: Is CPEO the same as typical age-related droopy eyelids?
A: Not always. Age-related ptosis is common and often relates to the eyelid tendon. CPEO is a neuromuscular condition where eye muscles weaken over time, and evaluation often involves neuro-ophthalmology and sometimes genetics.

Q: Do ptosis crutches treat the underlying cause?
A: No. Ptosis crutches are a mechanical support attached to glasses. They can help clear the pupil and improve function, but they do not change the underlying mitochondrial process.

Q: Can CPEO affect more than the eyes?
A: Yes. Some people have “CPEO-plus” with symptoms outside the eyes. If you have exercise intolerance, hearing changes, fainting, or palpitations, bring it to your clinician’s attention.

Q: Is Forzinity (elamipretide) approved for CPEO?
A: No. Forzinity is FDA-approved for Barth syndrome. Use in CPEO is investigational, but promising.

Q: Who should I see for evaluation?
A: Often a neuro-ophthalmologist, neurologist, and a genetics team. An optometrist can help address functional vision needs and coordinate referrals.

Schedule an Appointment or call 732-615-9300.

References

U.S. Food and Drug Administration. (2025). FORZINITY (elamipretide) prescribing information (U.S.) [PDF]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf

United Mitochondrial Disease Foundation. (n.d.). CPEO. https://umdf.org/cpeo/

United Mitochondrial Disease Foundation. (n.d.). FORZINITY (elamipretide). https://umdf.org/forzinity-elamipretide/

PubMed. (2024). Expanded-Access Use of Elamipretide Improves Quality of Life in Patients With Rare Mitochondrial Disorders Characterized by Ophthalmic Symptoms: A Case Series. https://pubmed.ncbi.nlm.nih.gov/39619320/

National Library of Medicine. (2023). ICD-10-CM code H49.4: Progressive external ophthalmoplegia (VSAC). https://vsac.nlm.nih.gov/context/cs/codesystem/ICD10CM/version/2023/code/H49.4/info

National Library of Medicine. (2023). ICD-10-CM code H49.40: Progressive external ophthalmoplegia, unspecified eye (VSAC). https://vsac.nlm.nih.gov/context/cs/codesystem/ICD10CM/version/2023/code/H49.40/info

National Library of Medicine. (2023). ICD-10-CM code H02.42: Myogenic ptosis of eyelid (VSAC). https://vsac.nlm.nih.gov/context/cs/codesystem/ICD10CM/version/2023/code/H02.42/info

National Library of Medicine. (2023). ICD-10-CM code G71.3: Mitochondrial myopathy, not elsewhere classified (VSAC). https://vsac.nlm.nih.gov/context/cs/codesystem/ICD10CM/version/2023/code/G71.3/info

Sun, M. G., et al. (2018). 3D printing for low-cost, rapid prototyping of eyelid crutches for ptosis. https://pmc.ncbi.nlm.nih.gov/articles/PMC6119648/

Wadhwani, M., et al. (2024). Crutch glass assembly. https://pmc.ncbi.nlm.nih.gov/articles/PMC11573018/

Hanaford, A. R., et al. (2022). AAV-vector based gene therapy for mitochondrial disease. https://pmc.ncbi.nlm.nih.gov/articles/PMC9169410/

Lim, K., et al. (2024). Mitochondrial genome editing: strategies, challenges, and applications. https://pmc.ncbi.nlm.nih.gov/articles/PMC10828433/