Ocular Symptoms of Myotonic Dystrophy

Key Points at a Glance

Key Points of This Disease

• Myotonic dystrophy (DM) is an autosomal dominant nucleotide repeat disorder, broadly classified into two types: DM1 (Steinert disease) and DM2.
• Cataract is the most common ocular manifestation in DM, occurring in over 90% of cases.
• DM-specific cataracts have two types: polychromatic granular opacities in the superficial cortex (Vogt type) and stellate fibrous opacities in the posterior cortex (Fleischer type).
• Various ocular symptoms such as ptosis, eye movement disorders, miosis, low intraocular pressure, and pigmentary retinopathy are observed.
• In DM1 patients, the complication rate of Fuchs endothelial corneal dystrophy has been reported to be up to 46%, which has attracted attention in recent years.
• Currently, no disease-modifying therapy exists, and management focuses on symptomatic treatment for each symptom.
• Due to high sensitivity to anesthesia, special anesthetic management considerations are necessary for ophthalmic procedures including cataract surgery.

1. Ocular symptoms of myotonic dystrophy

Myotonic dystrophy (DM) is a multisystem disorder characterized by skeletal muscle atrophy, muscle weakness, and myotonia. It is inherited in an autosomal dominant pattern and is caused by the expansion of nucleotide repeat sequences.

There are two main types of DM. DM1 (Steinert disease) is caused by a CTG repeat expansion in the DMPK gene on chromosome 19, while DM2 is caused by a CCTG repeat expansion in the CNPB gene on chromosome 3.

Epidemiology: The prevalence of DM in Europe was estimated at approximately 1 in 8,000 people. However, recent genetic studies suggest that the mutation frequency may be as high as 1 in 2,760, indicating that the actual prevalence may be higher.

Since DM is a multisystem disorder, ocular symptoms are managed as part of the overall disease. Cataracts are the most frequent ophthalmic complication, and they may be the initial symptom leading to an ophthalmology visit before systemic symptoms are detected.

Q What systemic symptoms are associated with myotonic dystrophy?

A

These include a wide range of symptoms such as skeletal muscle weakness, myotonia, ptosis, hatchet face, premature baldness, cardiac conduction defects, respiratory impairment, sleep disorders, endocrine abnormalities, and cognitive dysfunction. DM1 has an earlier onset and is more severe than DM2, with cardiac complications being the main cause of death.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

The most commonly reported symptom is decreased vision when cataracts have progressed. Other symptoms include the following.

• Ptosis: Myogenic ptosis due to weakness of the levator palpebrae superioris muscle. The patient feels difficulty opening the eyes.
• Diplopia: Caused by impaired eye movement due to weakness or myotonia of the extraocular muscles.
• Photophobia: In cases complicated by Fuchs endothelial corneal dystrophy, temporary corneal edema may occur after waking, making it difficult to see.
• Poor response to mydriatics: Due to a tendency toward miosis, dilation with standard mydriatics may be insufficient.

Clinical Findings

Lens Findings

Vogt type: Polychromatic granular opacities in the superficial cortex. Commonly found in the superficial cortex of the pupillary area and well observed by retroillumination. Differentiation from focal dots of age-related cataract is necessary.

Fleischer type: Fibrous opacities in the superficial posterior cortex. Can be observed by retroillumination as stellate opacities spreading along the Y-shaped suture. As it progresses, it becomes white fibrous opacities, causing severe visual impairment.

Ocular Adnexa and Anterior Segment

Ptosis: Myogenic and often bilateral. Eyebrow drooping due to frontalis muscle weakness may also occur.

Miosis: Incomplete pupillary dilation even after pharmacological mydriasis. This is thought to be caused by dysfunction of the pupillary dilator muscle.

Low intraocular pressure: The average intraocular pressure in DM patients is about 23% lower than in healthy individuals. Ciliary body detachment is considered one of the causes.

Fuchs endothelial corneal dystrophy (FECD): The frequency of FECD in DM1 patients is estimated to be up to 46%. It has been found that CTG repeat expansion in the DMPK gene can cause clinical symptoms of FECD through RNA-mediated toxicity. This is an important and recently recognized ophthalmic complication.

Pigmentary retinopathy: May present findings similar to pattern dystrophy with butterfly-shaped macular changes. It is not a consistent finding in either DM1 or DM2, and its appearance is variable.

Ocular motility disorders: Abnormal saccade velocity and external ophthalmoplegia myotonia are observed. Isolated ocular muscle palsy is relatively rare, but various patterns have been reported.

Q At what stage of DM does cataract appear?

A

Cataracts appear relatively early in both DM1 and DM2. In DM2, cataracts may be the first presenting symptom. The characteristic opacification patterns (Vogt type, Fleischer type) often lead to the discovery of the systemic disease.

3. Causes and Risk Factors

DM1 is caused by an expansion of the CTG repeat in the DMPK gene, and DM2 by an expansion of the CCTG repeat in the CNBP gene. Both are autosomal dominant disorders with familial occurrence.

The pathogenesis of lens opacification is not fully understood, but the following factors are considered.

• RNA toxicity: RNA produced from abnormally expanded repeats accumulates in the nucleus, impairing the function of RNA-binding proteins.
• Splicing abnormality: Dysfunction of RNA-binding proteins (such as MBNL1) leads to abnormal splicing of lens proteins.
• Ion channel abnormality: Primary defects in sodium and chloride channels of the muscle cell membrane are involved.

Regarding the association with FECD, it has been shown that the CTG repeat expansion in DMPK, the causative mutation of DM1, can cause clinical symptoms of FECD, likely through RNA-mediated toxicity. Although FECD is also associated with CTG repeat expansion in the TCF4 gene, it is thought to occur through a different mechanism in DM patients.

Prevention and Daily Care

• If you have been diagnosed with myotonic dystrophy, please undergo regular eye examinations. Ocular symptoms such as cataracts and ptosis often progress gradually, and early detection is important.
• If you notice decreased vision, see an ophthalmologist promptly. Depending on the severity of the cataract, surgery may be necessary.
• When undergoing ophthalmic procedures or surgery, be sure to inform the attending physician of a DM diagnosis. Special considerations are needed for anesthesia management.

4. Diagnosis and Examination Methods

The diagnosis of DM is primarily made through neurological evaluation, but ophthalmic findings often provide the initial clue.

Systemic Diagnosis

• Genetic testing: Measurement of CTG repeats in the DMPK gene (DM1) or CCTG repeats in the CNPB gene (DM2) provides a definitive diagnosis. Normal CTG repeat count is 5–35, but in DM1 it greatly exceeds this.
• Electromyography (EMG): Shows myotonic discharges and short-duration motor unit action potentials. With the widespread use of genetic testing, it is now considered an adjunctive diagnostic tool.
• Electrocardiogram: Extremely important for evaluating cardiac conduction disorders; should be performed in all DM patients.

Ophthalmic Examination

Examination	Purpose	Findings
Slit-lamp microscopy	Assessment of cataracts	Determination of Vogt type and Fleischer type
Transillumination method	Confirmation of opacity pattern	Stellate opacity along Y-suture, etc.
Corneal endothelial cell examination	Assessment of FECD complication	Decreased endothelial cell count
Tonometry	Confirmation of low intraocular pressure	Reported to be 23% lower than in healthy individuals

The opacity pattern of cataracts is characteristic. Under mydriasis, polychromatic granular opacities (Vogt type) and posterior cortical stellate opacities (Fleischer type) are observed. Parathyroid cataract shows similar findings and requires differentiation, but can be distinguished by the combination of systemic findings.

5. Standard Treatment

Currently, there is no disease-modifying therapy for DM. Management focuses on symptomatic treatment for each symptom.

Treatment of Cataracts

Cataracts that affect visual function are treated with cataract surgery (phacoemulsification). Progression is relatively slow, but if Fleischer-type opacities progress, visual function declines and surgery becomes necessary.

Anesthesia precautions: DM patients show very high sensitivity to the respiratory depressant effects of sedatives, hypnotics, and opioids. Avoid succinylcholine as it may cause unpredictable reactions. Neuromuscular blocking agent antagonists (neostigmine) may also worsen myotonia. Surgery should ideally be performed under local anesthesia (topical anesthesia or peribulbar anesthesia). The efficacy and safety of peribulbar anesthesia with ropivacaine for cataract surgery have been reported.

Treatment of Ptosis and Ocular Motility Disorders

Surgical repair is indicated when ptosis or brow ptosis affects visual function. Strabismus surgery is rarely indicated.

Points to note in treatment

• General anesthesia and sedation in DM patients carry special risks. Preoperative collaboration with neurology and anesthesiology is essential.
• Succinylcholine administration may induce myotonic crisis and is contraindicated.
• Benzodiazepines and long-acting opioids are also recommended to be avoided.
• Reversal agents for anesthesia such as honphytaline (neostigmine, etc.) may also induce or worsen myotonia, so caution is needed.
• In intraocular pressure management after cataract surgery, the pre-existing tendency toward low intraocular pressure should be considered.

Q Can cataract surgery be performed safely in DM patients?

A

Cataract surgery can be safely performed in DM patients using local anesthesia. However, collaboration with anesthesiologists and internists familiar with DM is important. If general anesthesia is required, volatile anesthetics such as desflurane or sevoflurane, ultra-short-acting opioids (remifentanil), and non-depolarizing neuromuscular blocking agents (vecuronium, rocuronium) are recommended.

6. Pathophysiology and Detailed Pathogenesis

The basic pathophysiology of DM is RNA-mediated toxicity caused by RNA produced from abnormally expanded nucleotide repeats.

Molecular mechanism of DM1: CUG repeat RNA (r(CUG)n) produced by CTG repeat expansion in the 3’ untranslated region of the DMPK gene forms nuclear RNA foci. These RNA foci sequester and inactivate RNA-binding proteins such as MBNL1 (Muscleblind-like 1). This leads to abnormal pre-mRNA splicing of numerous genes regulated by MBNL1 (e.g., ClC-1 chloride channel, insulin receptor). Abnormal ClC-1 splicing is the direct cause of skeletal muscle myotonia.

Association with ocular symptoms:

• Cataract: Splicing dysregulation of lens proteins is thought to cause characteristic polychromatic granular opacities (Vogt type).
• Fuchs endothelial corneal dystrophy: CTG repeat expansion in the DMPK gene causes corneal endothelial cell dysfunction through RNA toxicity. This pathway differs from TCF4 gene expansion (the main cause of isolated FECD).
• Ocular hypotony: Aqueous humor production may decrease due to myogenic dysfunction of the ciliary body. Some studies have found ciliary body detachment in all DM1 patients, suggesting it is the cause of ocular hypotony.
• Miosis: It is thought to be caused by smooth muscle dysfunction of the iris dilator muscle.

Differences from DM2: In DM2, RNA foci containing a CCTG repeat expansion are formed. Cataracts are seen in both DM1 and DM2, but systemic complications such as cardiac conduction defects and cognitive decline are less frequent and less severe in DM2 than in DM1.

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7. Latest Research and Future Perspectives (Research-stage Reports)

For patients: Please read this

The following content is currently at the research stage or under clinical trial and is not standard treatment available at general hospitals. It is reference information for experts regarding future medical developments.

Antisense nucleic acid therapy

Antisense oligonucleotides (ASOs) targeting CUG repeat RNA are being studied. Animal models have shown improvement in myotonia and correction of splicing abnormalities. Future research is expected for application to ocular symptoms.

Gene editing using CRISPR/Cas9

Approaches to directly edit the CTG repeat expansion region are being explored. This is at the research stage at the cellular and animal model level.

Research on the association with Fuchs endothelial corneal dystrophy

The molecular common ground between DM1 and FECD is becoming clearer. Screening for FECD in DMPK mutation carriers and exploration of common therapeutic targets are progressing.

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8. References

1. Moshirfar M, Webster CR, Seitz TS, Ronquillo YC, Hoopes PC. Ocular Features and Clinical Approach to Cataract and Corneal Refractive Surgery in Patients with Myotonic Dystrophy. Clin Ophthalmol. 2022;16:2837-2842. PMID: 36046572. DOI: 10.2147/OPTH.S372633

2. Winkler NS, Milone M, Martinez-Thompson JM, Raja H, Aleff RA, Patel SV, Fautsch MP, Wieben ED, Baratz KH. Fuchs’ Endothelial Corneal Dystrophy in Patients With Myotonic Dystrophy, Type 1. Invest Ophthalmol Vis Sci. 2018;59(7):3053-3057. PMID: 30025114. DOI: 10.1167/iovs.17-23160

3. Mootha VV, Hansen B, Rong Z, Mammen PP, Zhou Z, Xing C, Gong X. Fuchs’ Endothelial Corneal Dystrophy and RNA Foci in Patients With Myotonic Dystrophy. Invest Ophthalmol Vis Sci. 2017;58(11):4579-4585. PMID: 28886202. DOI: 10.1167/iovs.17-22350

4. Pagoulatos D, Kapsala Z, Makri OE, Georgakopoulos CD. Christmas tree cataract and myotonic dystrophy type 1. Eye (Lond). 2018;32(11):1794-1795. PMID: 29988074. DOI: 10.1038/s41433-018-0161-9

5. Kubo K, Oie Y, Koto R, Nishida N, Kai C, Maeno S, Kubota T, Nakamori M, Takahashi MP, Tsujikawa M, Nishida K. Analysis of Corneal Phenotypes in Japanese Patients With Myotonic Dystrophy Type 1. Cornea. 2025;44(4):427-433. PMID: 39167633. DOI: 10.1097/ICO.0000000000003679

6. Kimizuka Y, Kiyosawa M, Tamai M, Takase S. Retinal changes in myotonic dystrophy. Clinical and follow-up evaluation. Retina. 1993;13(2):129-135. PMID: 8337494.

7. Wong VA, Beckingsale PS, Oley CA, Sullivan TJ. Management of myogenic ptosis. Ophthalmology. 2002;109(5):1023-1031. PMID: 11986113. DOI: 10.1016/s0161-6420(02)01009-6