Progressive External Ophthalmoplegia (PEO)

Progressive external ophthalmoplegia (PEO) is a mitochondrial muscle condition where the muscles that move the eyes slowly become weak. Over years, people develop droopy eyelids (ptosis) and reduced eye movements. Many people tip their chin up or use the forehead muscles to see under a heavy lid. PEO can occur by itself or with other problems (called CPEO-plus), like exercise intolerance, hearing loss, neuropathy, or trouble with balance. Most people live a normal life span, but eye symptoms slowly worsen. The problem usually starts in early to mid-adulthood. PEO can be caused by mitochondrial DNA deletions or by changes in nuclear genes that maintain mitochondrial DNA (e.g., POLG, TWNK, RRM2B, SPG7). Diagnosis comes from exam, genetic testing, and sometimes muscle biopsy showing “ragged-red fibers.” MDPI+3PMC+3NCBI+3

Progressive external ophthalmoplegia (PEO) is a muscle disease that mainly affects the muscles that move the eyes and lift the eyelids. “Progressive” means it gets worse slowly over years. “External ophthalmoplegia” means the eye muscles on the outside of the eyes become weak and stiff. The most visible signs are droopy eyelids (ptosis) and limited eye movements. People may turn their head instead of moving the eyes, and they can have double vision. PEO is most often caused by mitochondrial problems. Mitochondria are tiny power stations inside cells. When their DNA is damaged, muscles do not get enough energy, so they tire and weaken. Many people with PEO have changes in mitochondrial DNA (mtDNA) or in nuclear genes that maintain mtDNA. Muscle biopsy often shows special features of mitochondrial disease, such as ragged-red fibers and COX-negative fibers. Medscape+3PMC+3New England Journal of Medicine+3

Other names

PEO is also called:

• Chronic progressive external ophthalmoplegia (CPEO)

• Mitochondrial PEO

• PEO-plus (when eye muscle weakness comes with other body problems)

• Kearns–Sayre syndrome (KSS) when PEO appears with retinopathy and other features starting before age 20 (a classic “syndromic” form). NCBI+1

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Types

1. Isolated (pure) PEO.
   Only eyelids and eye-moving muscles are clearly involved. People develop droopy eyelids and slow loss of eye movement. Other systems may be normal or only mildly affected. This form is common in adults. It is often linked to single large-scale deletions of mtDNA or to nuclear gene changes that cause multiple mtDNA deletions in muscle. NCBI+1

2. PEO-plus.
   Eye muscle weakness occurs plus problems in other parts of the body, such as mild limb weakness, hearing loss, numbness, ataxia (balance problems), or swallowing trouble. This pattern reflects wider mitochondrial energy failure. PMC

3. Kearns–Sayre syndrome (KSS).
   This is a syndromic subtype defined by onset before 20 years, PEO, and a special retinal problem (pigmentary retinopathy). People can also have heart block, high spinal fluid protein, and ataxia. It is usually due to a single large-scale mtDNA deletion. NCBI+1

4. Genetic subtype by causative gene.
   PEO can result from mtDNA deletions or from nuclear gene defects that damage mtDNA maintenance. The most frequent nuclear genes are POLG, TWNK (C10orf2/PEO1), POLG2, RRM2B, and SLC25A4 (ANT1), among others. NCBI+2ScienceDirect+2

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Causes

Most causes act by reducing the amount or quality of mitochondrial DNA in muscle, which lowers energy production and weakens muscles that must work all day, like eye muscles.

1. Single large-scale mtDNA deletion.
   A “chunk” of mtDNA is missing in many muscle cells. This is the best-known cause of PEO and KSS and often arises sporadically (new in the person). NCBI+1

2. Multiple mtDNA deletions in muscle.
   Here, many different deletions build up over time because the cell’s mtDNA maintenance machinery is faulty, often due to nuclear gene variants. ScienceDirect

3. POLG variants (polymerase-gamma).
   POLG encodes the enzyme that copies mtDNA. Faulty POLG leads to mtDNA deletions/depletion and is a frequent cause of autosomal dominant or recessive PEO. NCBI

4. POLG2 variants.
   POLG2 encodes the accessory subunit that stabilizes polymerase-gamma on mtDNA. Changes reduce copying fidelity, causing PEO with multiple mtDNA deletions. ScienceDirect

5. TWNK (C10orf2/PEO1) variants.
   TWNK encodes Twinkle, the mtDNA helicase. Faults in Twinkle slow mtDNA unwinding and copying, leading to dominant or recessive PEO. ScienceDirect

6. RRM2B variants.
   RRM2B helps supply DNA building blocks to mitochondria. Shortage of these blocks causes mtDNA depletion/multiple deletions and PEO. PMC+1

7. SLC25A4 (ANT1) variants.
   ANT1 transports ATP/ADP across the inner mitochondrial membrane; variants disrupt energy exchange and lead to PEO with mtDNA deletions. ScienceDirect

8. SPG7 variants.
   SPG7 encodes paraplegin, a mitochondrial protease; variants impair mtDNA maintenance and can present as PEO. PMC

9. DNA2 variants.
   DNA2 is a nuclease/helicase that helps mtDNA repair. Faults increase mtDNA errors and deletions, producing PEO. UMDF

10. RNASEH1 variants.
    RNASEH1 helps remove RNA primers during mtDNA replication. Variants cause replication stress and PEO. UMDF

11. TK2 variants.
    TK2 supplies nucleotides to mitochondria in muscle. Deficiency lowers mtDNA replication, sometimes causing an adult PEO picture. PMC

12. DGUOK variants.
    DGUOK also contributes to mitochondrial nucleotide pools. Adult forms may include PEO with mtDNA deletions. UMDF

13. MPV17 variants.
    MPV17 helps maintain mtDNA integrity. Adult cases can include myopathy with PEO due to mtDNA loss. UMDF

14. MGME1 variants.
    MGME1 processes mtDNA ends; variants lead to accumulated mtDNA errors and PEO. UMDF

15. OPA1 variants.
    OPA1 shapes mitochondrial networks; some families have optic atrophy with PEO because mitochondrial dynamics and DNA are disturbed. UMDF

16. AFG3L2 variants.
    This mitochondrial protease keeps respiratory chain proteins healthy; variants can cause neurologic disease with PEO. UMDF

17. C1QBP variants.
    This matrix protein binds mtDNA/ribosomes; variants can reduce mtDNA maintenance and lead to PEO. UMDF

18. TOP3A variants.
    A mitochondrial topoisomerase that untangles DNA; faults cause mtDNA instability and PEO. UMDF

19. GMPR (and other rare genes).
    Less common nuclear genes in mtDNA metabolism have been linked to PEO in cohort studies, showing the genetic diversity of this disorder group. UMDF

20. Primary mtDNA point mutations.
    Less often, a single base change in mtDNA (often in tRNA genes) impairs protein synthesis and leads to PEO-like disease. PMC

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Symptoms and signs

1. Droopy eyelids (ptosis).
   The eyelid muscle weakens, so lids sit low. People may lift their brows or tilt their head back to see. EyeWiki

2. Limited eye movements.
   Looking up, down, and sideways becomes slow and stiff. Head turns replace eye turns. EyeWiki

3. Double vision.
   When the eyes no longer move together, images split into two, especially when looking to the sides or up.

4. Slowly progressive course.
   Changes happen over years, not days or weeks. This slow pace helps distinguish PEO from nerve or junction diseases. EyeWiki

5. Face weakness.
   Some people notice a flat facial expression or trouble with tight eye closure due to facial muscle involvement. PMC

6. Exercise intolerance.
   Muscles tire quickly and may ache after mild effort because ATP production is limited.

7. Mild limb weakness.
   Hips and shoulders can be weak, especially after long standing or climbing stairs, reflecting a mitochondrial myopathy. PMC

8. Swallowing difficulty (dysphagia).
   Throat muscles can fatigue, causing coughing with liquids and slow eating in some patients. StatPearls

9. Hoarse or nasal voice.
   Weak palate or laryngeal muscles may change voice quality.

10. Hearing loss.
    Sensorineural hearing decline may develop because mitochondria also power inner-ear hair cells. NCBI

11. Balance problems (ataxia).
    The cerebellum and peripheral nerves may be involved, causing unsteady walking in PEO-plus/KSS. NCBI

12. Numbness or tingling.
    Peripheral neuropathy can occur in some genetic subtypes (for example with POLG or RRM2B changes). NCBI

13. Retinal problems.
    In KSS, the back of the eye shows a “salt-and-pepper” pattern (pigmentary retinopathy) and can reduce night vision. NCBI

14. Heart conduction block (KSS).
    The heart’s wiring can slow or pause, sometimes needing a pacemaker. This is why heart screening matters in syndromic cases. NCBI

15. Endocrine issues in KSS.
    Short stature, diabetes, or thyroid problems can occur because mitochondria support hormone-producing tissues. NCBI

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Diagnostic tests

A) Physical exam (bedside and observation)

1. Ptosis assessment.
   The clinician measures how far the eyelid covers the pupil and how much the lid lifts when looking up. Worsening over years suggests PEO rather than sudden nerve palsy. EyeWiki

2. Ocular motility testing in all directions.
   The doctor tracks how far and how fast the eyes move. In PEO, movements are limited in several directions and often symmetrical. EyeWiki

3. Head-turn compensation check.
   Because eyes move poorly, patients turn the head. This habitual pattern points to a chronic extraocular myopathy.

4. Fatigability and sustained upgaze.
   Holding the gaze up can increase lid droop from muscle fatigue. In PEO the change is slow and consistent over time, not fluctuating hour-to-hour as in myasthenia.

5. Orbicularis and facial strength.
   Weak eye closure and mild facial weakness may be present, supporting a myopathic process. PMC

B) Manual/bedside discriminatory tests

6. Ice-pack test (to rule out myasthenia gravis).
   Cooling the eyelid briefly can improve ptosis in myasthenia but not in PEO. This simple trick helps separate a nerve-junction problem from a muscle energy problem.

7. Edrophonium or pyridostigmine response (historical/clinical trial).
   A clear, fast improvement suggests myasthenia, not PEO. Lack of response supports a myopathic diagnosis (these tests are used cautiously today).

8. Cover–uncover and alternate cover tests.
   These identify ocular misalignment causing double vision and help document the fixed pattern typical in long-standing PEO.

9. Sustained horizontal gaze.
   Holding side gaze can show endurance limits of the lateral rectus muscles, again pointing to a chronic myopathy.

10. Simple functional scores (ptosis/ophthalmoplegia scales).
    Clinicians sometimes use practical scales to follow disease slowly over time, supporting the “progressive” nature.

C) Laboratory and pathological tests

11. Serum lactate and pyruvate.
    They can be normal, but mild elevation may suggest mitochondrial energy strain in some patients. Results guide deeper testing. PMC

12. Creatine kinase (CK).
    CK is often normal or mildly raised; this helps separate PEO from inflammatory myopathies, which usually show higher CK.

13. Muscle biopsy with special stains.
    Ragged-red fibers on modified Gomori trichrome and COX-negative fibers are classic mitochondrial signs in PEO. Electron microscopy can show abnormal mitochondria. PMC+2ScienceDirect+2

14. Respiratory chain enzyme assay (muscle).
    Biochemical testing can show reduced activity of complexes I, III, or IV, supporting mitochondrial dysfunction when biopsy is abnormal.

15. mtDNA deletion testing (muscle/blood).
    Long-range PCR, next-generation sequencing, and MLPA can detect single large-scale deletions or multiple deletions. Muscle is often more informative than blood in adults. PMC

16. Nuclear gene panel for PEO.
    Targeted or exome sequencing for POLG, TWNK, POLG2, RRM2B, SLC25A4, SPG7, DNA2, RNASEH1 and others identifies causes and inheritance. ScienceDirect+1

D) Electrodiagnostic and cardiac tests

17. Needle EMG (electromyography).
    EMG often looks “myopathic” (short, small motor units). This supports a primary muscle problem rather than a nerve or junction disorder.

18. Repetitive nerve stimulation / single-fiber EMG (to rule out myasthenia).
    These tests are typically normal in PEO. Abnormal decrement or jitter would suggest myasthenia gravis instead.

19. ECG and Holter monitoring (especially if KSS features).
    Screening looks for heart block or arrhythmia. Early detection can prevent dangerous events and may lead to pacemaker therapy. NCBI

E) Imaging tests

20. Orbital and brain MRI; ocular imaging (OCT).
    MRI can show thin/atrophic extraocular muscles in PEO and sometimes brain changes in mitochondrial disease. Optical coherence tomography can document retinal findings. These images support diagnosis and help rule out other causes. EyeWiki

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Non-pharmacological treatments (therapies & others)

Important: These help symptoms and function. They do not cure the disease.

1. Structured aerobic exercise program
   Description (≈150 words): Regular, supervised aerobic activity (like brisk walking, cycling, or pool walking) 3–5 days per week at moderate intensity helps many people with mitochondrial muscle disease. Sessions usually last 20–40 minutes and are increased slowly. A physical therapist or exercise physiologist can tailor the plan to your fitness and symptoms. Warm-up and cool-down periods reduce strain. People monitor effort by how they feel (talk test) and by heart rate if advised. If fatigue is severe, short intervals with rest breaks are used. Exercise days are alternated with easy days to avoid over-fatigue.
   Purpose: Improve stamina, reduce fatigue, and help quality of life.
   Mechanism: Training can increase mitochondrial number and efficiency in working muscle and may shift the balance toward healthier mitochondria. Frontiers+3PMC+3PMC+3

2. Gentle resistance (strength) training
   Description: Low-to-moderate resistance (bands, light weights) and functional moves (sit-to-stand, step-ups) 2–3 times weekly help maintain muscle strength without overstraining eye muscles. Sessions stay short (15–30 minutes) and stop if pain or unusual fatigue develops.
   Purpose: Preserve limb strength for daily tasks and reduce injury risk.
   Mechanism: Resistance work stimulates muscle protein building and can improve neuromuscular efficiency without worsening mitochondrial stress when dosed appropriately. PMC+1

3. Energy-conservation & pacing strategy
   Description: Plan the day, cluster tasks, sit for grooming/cooking, and schedule rest breaks. Use “priority, plan, pace” to lower fatigue spikes.
   Purpose: Do more with less energy; avoid crashes.
   Mechanism: Reduces total metabolic demand on weakened muscle.

4. Protective eyelid care (lubricants day/night)
   Description: Regular use of preservative-free artificial tears by day and a lubricating gel/ointment at night helps if lids don’t close fully. Use as often as needed, especially before windy or screen-heavy activities.
   Purpose: Prevent dry eye and corneal damage (exposure keratopathy).
   Mechanism: OTC ophthalmic demulcents (e.g., carboxymethylcellulose) coat and protect the ocular surface; they are recognized as safe/effective under the FDA OTC ophthalmic monograph. eCFR+2FDA Access Data+2

5. Punctal occlusion (temporary plugs by an eye doctor)
   Description: Tiny plugs are placed in the tear drains to keep tears on the eyes longer. It’s an in-office procedure with quick recovery; plugs can fall out and sometimes irritate.
   Purpose: Raise tear volume to protect the cornea if blinking or lid closure is reduced.
   Mechanism: Mechanical blockage of tear outflow increases tear film residence time. Evidence shows mixed but often helpful results in moderate–severe dry eye. PMC+2AJMC+2

6. Eyelid taping at night (if incomplete closure)
   Description: A gentle hypoallergenic tape closes the lids during sleep; taught by a clinician.
   Purpose: Prevent exposure keratitis and morning irritation.
   Mechanism: Mechanical closure protects cornea from drying.

7. Moisture-chamber glasses / wraparound eyewear
   Description: Sealed or high-coverage frames reduce wind and evaporation when outdoors or on screens/air-conditioning.
   Purpose: Keep corneas moist; improve comfort.
   Mechanism: Creates a humid micro-environment around the eyes.

8. Spectacle-mounted ptosis crutch
   Description: A small bar attached to glasses lifts the upper lid. It requires fitting and periodic adjustment. Some people feel pressure or note less blink.
   Purpose: Improve the visual field without surgery when lids are very low.
   Mechanism: Mechanical support holds the lid up to clear the pupil. Entokey+1

9. Posture & head-position training
   Description: Safe ergonomic tips and core/neck exercises help counter chin-up posture people adopt to see under heavy lids.
   Purpose: Reduce neck strain and headaches; improve balance.
   Mechanism: Strengthens postural muscles to offset compensations.

10. Blue-light and glare management
    Description: Anti-glare coatings, hats, and filters reduce light sensitivity that comes with a dry ocular surface.
    Purpose: Comfort and sustained reading/screen work.
    Mechanism: Reduces photic stress on irritated corneas.

11. Speech/swallow screening if CPEO-plus
    Description: Some people have mild swallowing or voice issues; early referral prevents complications.
    Purpose: Prevent aspiration and weight loss.
    Mechanism: Targeted therapy strengthens safe swallow patterns. UMDF

12. Hearing checks if symptoms suggest
    Description: Audiology screening and hearing support if needed.
    Purpose: Maintain communication and safety.
    Mechanism: Early amplification improves function. NCBI

13. Fall-prevention & balance therapy
    Description: Balance exercises and home safety review (lighting, rugs) cut fall risk.
    Purpose: Safety and independence.
    Mechanism: Trains vestibular and proprioceptive systems.

14. Fatigue management education
    Description: Sleep hygiene, hydration, and small, frequent meals.
    Purpose: Improve daytime energy.
    Mechanism: Supports steady energy supply to muscles.

15. Psychological support / peer groups
    Description: Counseling and patient communities (e.g., UMDF) help with coping and problem-solving.
    Purpose: Reduce stress, improve adherence.
    Mechanism: Social and behavioral strategies improve self-management. UMDF

16. Workplace/school accommodations
    Description: Task breaks, larger screens, adjustable chairs, and flexible schedules.
    Purpose: Maintain productivity with less fatigue.
    Mechanism: Environmental fit reduces effort per task.

17. Sun and wind protection
    Description: Hats, humidifiers, avoiding direct fans.
    Purpose: Reduce ocular surface stress.
    Mechanism: Less evaporation = less dryness.

18. Home blinking reminders
    Description: Set reminders during screen time to blink fully and use tears.
    Purpose: Keep corneas lubricated.
    Mechanism: Restores normal tear spread.

19. Driving/vision safety review
    Description: Low-light driving or highway merging can be unsafe with limited eye movement; clinicians can advise on restrictions and alternatives.
    Purpose: Public and personal safety.
    Mechanism: Matches visual demands to functional limits.

20. Pre-op eye surface optimization (before ptosis surgery)
    Description: Intensify lubricants, treat blepharitis, and assess Bell’s phenomenon.
    Purpose: Lower corneal risk after surgery.
    Mechanism: A healthier surface tolerates surgery better. AAO+1

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Drug treatments

Key disclaimer: No drug treats the underlying mitochondrial defect in PEO. Many medicines below are symptom-directed or off-label in PEO; FDA labels confirm indications/safety for their approved uses, not PEO. Always use under clinician guidance. PMC

1. Oxymetazoline 0.1% ophthalmic (UPNEEQ®)
   Class: Topical α-adrenergic agonist.
   Dose/Time: 1 drop in the affected eye(s) once daily.
   Purpose: Temporarily raises the upper lid opening (MRD-1) in acquired blepharoptosis; may help PEO-related ptosis symptomatically.
   Mechanism: Stimulates Müller’s muscle to elevate the lid.
   Side effects: Eye irritation, headache; caution in cardiovascular disease.
   Evidence/Regulatory: FDA-approved for acquired blepharoptosis in adults (not disease-modifying for PEO). FDA Access Data+2FDA Access Data+2

2. Preservative-free artificial tears (OTC demulcents)
   Class: Ophthalmic demulcents/emollients.
   Dose/Time: As needed; gels/ointments at night.
   Purpose: Protect cornea when blink/closure is reduced.
   Mechanism: Lubrication shields the surface and stabilizes tear film.
   Safety: Generally recognized as safe/effective per OTC monograph. eCFR+1

3. Cyclosporine ophthalmic 0.05% (RESTASIS®)
   Class: Topical calcineurin inhibitor.
   Dose/Time: 1 drop twice daily.
   Purpose: Increase natural tear production in inflammatory dry eye; useful if exposure causes ocular surface inflammation.
   Mechanism: Reduces T-cell–mediated inflammation in lacrimal glands/ocular surface.
   Side effects: Burning, redness.
   Evidence/Regulatory: FDA-approved for increasing tear production in dry eye disease. FDA Access Data+1

4. Lifitegrast 5% (XIIDRA®)
   Class: LFA-1 antagonist (anti-inflammatory for dry eye).
   Dose/Time: 1 drop twice daily.
   Purpose: Reduce signs and symptoms of dry eye that worsen exposure risk.
   Mechanism: Blocks LFA-1/ICAM-1, lowering ocular surface inflammation.
   Side effects: Dysgeusia, irritation.
   Regulatory: FDA-approved for dry eye disease. FDA Access Data+1

5. Erythromycin ophthalmic ointment (night protection)
   Class: Macrolide antibiotic ointment.
   Dose/Time: Small ribbon at bedtime if exposure risks corneal abrasion or if blepharitis present.
   Purpose: Surface protection and infection prevention.
   Mechanism: Lubrication plus antibacterial effect.
   Safety: Generally well tolerated.
   Regulatory: FDA-approved ophthalmic ointment formulations. DailyMed

6. Lubricating hypertonic saline (5%) for morning edema
   Class: Hypertonic agent.
   Dose/Time: As directed.
   Purpose: Draws fluid from cornea if swelling occurs with exposure.
   Mechanism: Osmotic effect improves clarity.
   Regulatory: Covered under OTC ophthalmic monograph. eCFR

7. Topical anti-inflammatory pulses (short courses, Rx)
   Class: Mild topical steroids or NSAIDs (clinician-directed).
   Purpose: Calm severe surface inflammation before/after procedures.
   Mechanism: Reduces cytokine-driven irritation; used judiciously to avoid side effects.
   Note: Physician-supervised only; consider IOP monitoring. AAO

8. Antibacterial lid hygiene (if blepharitis)
   Class: Hypochlorous acid sprays or antibiotic ointments.
   Purpose: Reduce lid margin inflammation that worsens dry eye.
   Mechanism: Antimicrobial/anti-biofilm effects improve meibomian function. AAO

9. Allergy eye drops (if allergic surface disease coexists)
   Class: Antihistamine/mast-cell stabilizers.
   Purpose: Limit itch/rub that increases exposure risk.
   Mechanism: Blocks histamine/mast-cell pathways; symptomatic relief.
   Regulatory: Many OTC per monograph. eCFR

10. Lubricating gels/ointments (nighttime)
    Class: Ophthalmic emollients.
    Purpose: Overnight surface protection with lagophthalmos.
    Mechanism: Thicker barrier; slower evaporation.
    Regulatory: OTC monograph. eCFR

11. Analgesics for headache/neck strain (as needed)
    Class: Acetaminophen preferred at standard doses; avoid chronic high doses.
    Purpose: Manage secondary pain from posture compensation.
    Mechanism: Central analgesia.
    Note: In mitochondrial disease, some groups advise caution with high-dose acetaminophen—use standard doses and clinician guidance. UMDF

12. Avoid/replace potentially mitochondrial-toxic meds
    Class: Medication review rather than a “drug to take.”
    Purpose: Reduce risk of worsening mitochondrial symptoms.
    Mechanism: Stop or avoid agents linked to mitochondrial toxicity when safer alternatives exist (e.g., valproic acid is contraindicated in patients with POLG mutations; some antibiotics warrant caution).
    Regulatory/Evidence: Consensus guidance from mitochondrial experts. PMC+2UMDF+2

13. Short-term oxymetazoline “trial” for function testing
    Purpose: In some clinics, response to oxymetazoline can help decide if ptosis surgery might be helpful by showing potential functional gain.
    Mechanism: Temporary Müller’s muscle contraction elevates lid. FDA Access Data

14. Prescription moisture-chamber solutions
    Class: Not a drug; special devices prescribed by clinicians to reduce evaporation.
    Purpose/Mechanism: Physical barrier retains tears. (Device-based adjunct.) AAO

15. Topical cyclosporine or lifitegrast before/after surgery
    Purpose: Optimize surface to reduce postoperative exposure.
    Mechanism: Anti-inflammatory ocular surface prep. FDA Access Data+1

16. Hypertonic saline ointment (5%) nightly
    Purpose: For recurrent corneal swelling or erosions.
    Mechanism: Osmotic; forms a barrier film overnight. eCFR

17. Antibiotic prophylaxis only when indicated
    Purpose: If abrasions or exposure ulcers occur.
    Mechanism: Prevents infection while surface heals (e.g., erythromycin). DailyMed

18. Prescription antihypertensives review
    Purpose: If using oxymetazoline drops, clinicians review systemic blood pressure meds due to α-agonist effects.
    Mechanism: Safety measure. FDA Access Data

19. Topical lubricants with lipid component
    Purpose: Stabilize tear film if meibomian gland dysfunction coexists.
    Mechanism: Restores tear lipid layer; reduces evaporation. AAO

20. Short courses of topical antibiotics for blepharitis flares
    Purpose: Calm lid margin overgrowth.
    Mechanism: Lowers bacterial load; improves meibum quality. AAO

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Dietary molecular supplements

(Reminder: quality varies; discuss with your clinician. These do not cure PEO.)

1. Coenzyme Q10 (ubiquinone/ubiquinol)
   Description (≈150 words): CoQ10 is a key mitochondrial electron-transport carrier. Some people with mitochondrial myopathy report more stamina or less fatigue with daily CoQ10. Ubiquinol is the reduced form and can be better absorbed in some individuals. Doses often range 100–300 mg/day divided with food; higher doses are sometimes tried under medical supervision. If you take blood thinners or certain heart drugs, your doctor will check for interactions.
   Function/Mechanism: Supports electron transport and may improve cellular ATP output; antioxidant effects may reduce oxidative stress.
   Evidence: Mixed; small studies and reviews in mitochondrial disease suggest benefit for some. UMDF

2. Riboflavin (Vitamin B2)
   Description: Cofactor for complex I/II enzymes; sometimes helps exercise tolerance. Typical dose 100–400 mg/day with food.
   Function/Mechanism: Supports flavoproteins in mitochondrial oxidation.
   Evidence: Small open-label reports; used in consensus guidance. UMDF

3. L-Carnitine
   Description: Transports fatty acids into mitochondria. Doses 500–1,500 mg/day in divided doses are commonly used. May cause GI upset or fishy odor.
   Function/Mechanism: Supports fatty-acid oxidation to make ATP.
   Evidence: Widely used in mitochondrial care though randomized data are limited. UMDF

4. Alpha-lipoic acid
   Description: Antioxidant cofactor for mitochondrial enzymes; typical 300–600 mg/day.
   Function/Mechanism: Recycles antioxidants and may reduce oxidative stress in muscle. UMDF

5. Creatine monohydrate
   Description: Energy buffer for muscle; 3–5 g/day may support short-burst tasks.
   Function/Mechanism: Replenishes phosphocreatine for quick ATP recycling. UMDF

6. B-complex vitamins
   Description: B1, B6, B12 support nerve and muscle energy metabolism.
   Function/Mechanism: Coenzymes for carbohydrate, amino acid, and mitochondrial reactions. UMDF

7. Vitamin D
   Description: Check and correct deficiency for muscle/bone health.
   Function/Mechanism: Supports muscle function, immunity, bone integrity. UMDF

8. Magnesium
   Description: Co-factor in ATP reactions; helps cramps in some people.
   Function/Mechanism: Stabilizes ATP and NMJ function. UMDF

9. Omega-3 fatty acids (EPA/DHA)
   Description: Anti-inflammatory support; 1–2 g/day combined EPA/DHA after discussing bleeding risk.
   Function/Mechanism: May reduce systemic inflammation that worsens fatigue. UMDF

10. N-acetylcysteine (NAC)
    Description: Antioxidant precursor to glutathione; typical 600–1,200 mg/day as advised.
    Function/Mechanism: Replenishes intracellular antioxidant defenses. UMDF

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Immunity-booster / regenerative / stem-cell–type

(Straight talk: none are proven disease-modifiers for PEO; these notes explain concepts used or explored in mitochondrial medicine.)

1. Antioxidant “cocktails”
   About 100 words + dosing: Combinations (e.g., CoQ10 100–300 mg/day + riboflavin 100–400 mg/day + L-carnitine 500–1,500 mg/day) are sometimes used for symptom relief.
   Function/Mechanism: Reduce oxidative stress and support energy pathways. UMDF

2. Mitochondria-targeted therapy research (e.g., exercise-induced biogenesis)
   Dose/Timing: Structured, progressive aerobic/resistance plan under guidance.
   Function/Mechanism: Stimulates mitochondrial biogenesis and can improve oxidative capacity. MDPI

3. Vitamins as immunomodulatory support (D, B12)
   Dose: Correct deficiencies to normal ranges.
   Mechanism: Supports neuromuscular and immune function; not disease-specific. UMDF

4. Topical cyclosporine for ocular surface “immune calm”
   Dose: 1 drop BID.
   Mechanism: Local immunomodulation increases natural tear production; protects cornea. FDA Access Data

5. Investigational agents (e.g., redox modulators)
   Mechanism: Aim to tweak mitochondrial redox balance; not approved for PEO.
   Note: Only within clinical trials. MDPI

6. Cell-based/“stem cell” ideas
   Mechanism: Currently experimental and not a standard for PEO; no FDA-approved cell therapy for PEO. Discuss only in research settings. PMC

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Surgeries

1. Frontalis suspension (sling) for severe ptosis with poor levator function
   Procedure: A sling (silicone rod or fascia) connects the lid to the brow so the forehead muscle can lift the eyelid.
   Why: When the levator muscle is too weak, this method lets the brow elevate the lid to clear the pupil and improve vision. Careful selection is crucial if Bell’s reflex is poor to protect the cornea. PMC+2Lippincott+2

2. Levator advancement/resection for moderate ptosis with residual function
   Procedure: Tightening and advancing the levator aponeurosis via an anterior approach.
   Why: If some levator function remains, this can raise the lid more naturally. PubMed

3. Combined or staged ptosis procedures
   Procedure: Surgeons may combine techniques or stage one side at a time.
   Why: Tailors lift and reduces exposure keratopathy risk in PEO. oftalmoloji.org

4. Temporary external lid support (crutch) as a “bridge”
   Procedure: Non-surgical crutch on glasses.
   Why: For those not yet ready for surgery or with high exposure risk. Entokey

5. Adjunct ocular surface procedures
   Procedure: In significant exposure, clinicians may use punctual occlusion or optimize meibomian function before/after ptosis surgery.
   Why: Protect the cornea while improving lid position. PMC

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Preventions

1. Keep the eye surface wet: use preservative-free tears by day and gel at night. eCFR

2. Avoid fans, direct AC, and dusty/windy exposures; use wraparound glasses.

3. Blink fully and often during screen time; set reminders.

4. Humidify rooms; stay hydrated.

5. Treat eyelid margin disease (blepharitis) early with hygiene. AAO

6. Wear hats/sunglasses outdoors to reduce evaporation and glare.

7. Use oxymetazoline 0.1% only as directed; tell your doctor if you have heart or blood pressure issues. FDA Access Data

8. Review medicines with your doctor; avoid valproic acid in POLG disease and be cautious with other potentially mitotoxic drugs. PMC

9. Maintain a gentle exercise routine rather than prolonged inactivity. PMC

10. Before surgery, optimize the ocular surface and confirm corneal protective reflexes. AAO

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When to see doctors (red flags)

• Eyelids droop so much you cannot see forward or you lose your driver’s license vision standard.

• Pain, light sensitivity, or sudden worsening of vision—possible corneal exposure or abrasion.

• New double vision, severe headaches, or neurologic symptoms—needs evaluation.

• Signs of dry eye injury: burning, gritty sensation, or morning pain.

• Considering surgery or trying oxymetazoline 0.1%—you need a formal eye and medical review first. FDA Access Data+1

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What to eat” and “what to avoid”

What to eat

• Balanced meals with lean proteins, whole grains, fruits/vegetables to support energy.

• Omega-3–rich foods (fish, flax, walnuts) for anti-inflammatory support.

• Magnesium- and B-vitamin–rich foods (greens, legumes, whole grains) for muscle/nerve function.

• Small, frequent meals to smooth energy supply. UMDF

What to avoid or limit

• Dehydration; drink water regularly.

• Excess alcohol (can worsen neuropathy and sleep).

• Crash diets or fasting that trigger fatigue.

• Unsupervised high-dose supplements; review with your clinician, especially if on anticoagulants or other meds. UMDF

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Frequently Asked Questions

1. Is PEO life-threatening?
   PEO mainly affects the eye muscles and lids. Many people have a normal life span, though symptoms progress slowly. Some have extra problems (CPEO-plus). NCBI

2. Can PEO be cured?
   No cure exists yet. Treatment protects the eyes and supports function. PMC

3. Will exercise make me worse?
   Supervised, gentle aerobic and resistance training is generally helpful and considered safe when tailored. PMC+1

4. Are there drops to lift my eyelids?
   Oxymetazoline 0.1% can temporarily raise the lid opening in acquired ptosis and may help some people with PEO-related ptosis; it does not treat the disease itself. FDA Access Data

5. When do I need surgery?
   If lids block the pupil or daily life is limited despite non-surgical care, surgeons consider levator advancement (if some function remains) or frontalis sling (if levator is very weak). Corneal safety is key. PubMed+1

6. Why are lubricants so important?
   Reduced blink/closure dries the cornea. Preservative-free tears and gels prevent injury and pain. eCFR

7. What is a ptosis crutch?
   A small bar on glasses that props the lid up. It helps vision without surgery but needs fitting and can reduce blinking. Entokey

8. Are there medicines I should avoid?
   In mitochondrial disease, valproic acid is contraindicated in POLG-related disease and often avoided; other drugs (e.g., certain antibiotics) may warrant caution. Always ask your clinician. PMC

9. Do supplements help?
   Some patients feel better with CoQ10, riboflavin, L-carnitine, and others, but evidence is limited. Discuss doses and interactions first. UMDF

10. Will I go blind?
    PEO affects muscles, not the retina; vision loss usually comes from corneal exposure when lids don’t close. Good lubrication and protection prevent this. AAO

11. Is PEO genetic?
    Yes. It can be due to mitochondrial DNA deletions or nuclear genes that keep mitochondrial DNA healthy. Genetic counseling can help families. NCBI+1

12. What is CPEO-plus?
    PEO with added problems (e.g., limb weakness, ataxia, hearing loss). Care is still supportive but broader. UMDF

13. Can dry eye treatments be combined?
    Yes—lubricants, cyclosporine or lifitegrast, and punctal plugs are often layered to protect the cornea. FDA Access Data+2FDA Access Data+2

14. Are there clinical trials?
    Trials in mitochondrial disease focus on exercise, supportive measures, and investigational redox or metabolic therapies—not specific cures for PEO yet. Ask your specialist. MDPI

15. What is the long-term outlook?
    Symptoms slowly progress, mainly affecting eye movement and lid position. With protection, lubrication, and selective surgery, most people maintain function. PMC

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: October 13, 2025.

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