Ocular Manifestations of Myotonic Dystrophy

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Ocular Manifestations of Myotonic Dystrophy
Classification and external resources
OMIM 160900
DiseasesDB 8739


Disease Entity

Definition

Myotonic Dystrophy is a multi-system disease, which can initially present with symptoms of ptosis, ophthalmoplegia, extraocular myotonia, and decreased visual acuity. Myotonic Dystrophy is a tri-nucleotide repeat, autosomal dominant disease characterized by an inability to relax (myotonia) and muscle wasting (muscular dystrophy). In addition to the myotonia and muscular dystrophy, Myotonic Dystrophy 1 is a debilitating multi-system disease having affects on the eye, pulmonary, cardiac, endocrine, and central nervous system. Respiratory failure is the leading cause of death in theses patients, responsible for 30% of mortalities. Cardiac conduction abnormalities are the second leading cause of death at approximately 20% of mortalities.

Two main types of myotonic dystrophy exist:

  • Myotonic Dystrophy 1 (DM1)
    • Greater severity of symptoms
    • Most common adult form of muscular dystrophy
    • Affecting nearly 1 in 8,000 people worldwide
    • Chromosome 19
    • CTG trinucleotide repeat
  • Myotonic Dystrophy 2 (DM2)
    • Also known as Proximal Myotonic Myopathy
    • Chromosome 3
    • CCTG Repeat

Risk Factors

Early onset presentation of a bilateral iridescent cataract, especially at age less than 40 and without pre-existing diabetes, in a patient with a positive family history of myotonic dystrophy should undergo genetic testing to confirm the presence of the disease.

General Pathophysiology

Inherited, Autosomal Dominant

In myotonic dystrophy 1 (DM1) the CTG repeats on Chromosome 19 affect the 3’ untranslated region of the myotonic dystrophy protein kinase gene (DMPK), causing a decreased expression of the protein. Decreased DMPK expression in extraocular muscles, ciliary body, and cellular layers of the retina can account for the symptoms seen in myotonic Dystrophy. Interestingly, very little to no DMPK expression is seen in lens epithelium. The tri-nucleotide repeat expansion decreases the expression of the downstream six5 gene, which has been hypothesized to be the cause of the distinct cataract in mytonic dystrophy.

The cataract first begins with iridescently colored fine opacities on the outer layer of the lens (cortical and subcapsular). As the cataract matures, these fine opacities increase and cortical spoking develop making it difficult to distinguish it from a cortical cataract. An increased level of Gamma-Glutamyl Transpeptidase in these patients may be responsible for low levels of lenticular glutathione and thus leading to the cataract formation. A distinctive cataract presents in 100% of patients with either Myotonic Dystrophy, which can aid in the diagnosis of this complex disease.

Diagnosis

History

Family history. Sustained muscle contraction (myotonia) exacerbated by excitement, extreme temperatures and fatigue.

Signs & Symptoms

Due to its wide range of symptoms, diagnosis of this disease is sometimes difficult and may be prolonged. However, ocular manifestations of the disease may be one of the first presenting symptoms and thus cause a patient to seek care.

General appearance may show muscle wasting and frontal balding. A ‘Hatchet Face’ appearance due to temporalis and masseter muscle wasting. During a hand shake, the patient may have difficulty with release due to exaggerated myotonia.

Ocular Exam

  • Va - May be reduced
    • Due to combination of cataract and retinal degeneration
    • Visually significant ptosis
  • EOM - Ophthalmoplegia and extraocular myotonia
    • The finding of ophthalmoplegia consists of limited adduction, labeled as “pseudo-internuclear ophthalmoplegia .” Multiple cases of bilateral adduction restriction have been reported, as well as those with divergent strabismus and convergence paralysis. The abducting eye does not present with nystagmus.
    • Extraocular mytonia is manifested as slowed and disconjugate saccades. More specifically, the abnormalities consist of a reduction in saccade peak velocity and increased saccade duration primarily if the eye is fixed on an object for a longer period of time (long interstimulus interval) , thus highlighting the phenomenon of myotonia.
  • Pupils - Miosis, slowly responsive to light.
  • Pressure - Low pressure
    • Possibly due to ciliary body detachment

SLE:

  • L/L: Blepharoptosis. Brow ptosis.
  • Lens: Cataract with fine dust like opacities on the outer layers of the lens that are highly colored and iridescent, producing a “Christmas Tree” appearance.

DFE:

  • Cataract
  • Maculopathy
  • Peripheral pigmentary retinopathy

Diagnostic procedures

Diagnostic procedures include:

  • Genetic Testing (Blood)
  • EKG
    • An increase in the PR interval and a widened QRS may be the first asymptomatic signs
    • May eventually progress to Supraventricular Tachycardia (SVT), Ventricular Fibrillation, and asystole.
  • Electromyography (EMG) demonstrating typical myotonic discharges

Laboratory test

DM1 (CTG repeat) and DM2 (CCTG) blood tests are available. The decision to be tested can be facilitated by a genetic counselor.

Differential diagnosis

Chronic Progressive External Ophthalmoplegia (CPEO), Internuclear ophthalmoplegia (INO), or Other causes of myogenic ptosis

Management

Medical therapy

Treatment of symptoms as indicated. Due to pulmonary, cardiac, endocrine, and central nervous system involvement, these patient should be referred to specialty care for evaluation and treatment. Surgery as indicated.

Ocular Surgery

The cataract can be removed to help restore vision, but care must be taken in selecting an anesthetic agent in order to reduce the risk of intraoperative and postoperative complications . Some patients with Myotonic Dystrophy may have delayed recovery after an operation with use of certain anesthetic agents. However, traditionally cataract surgery utilizes local anesthesia, which causes no such problems of delayed recovery.

Significant ptosis may cause visual impairment however, caution must be taken in performing ptosis surgery if levator function is significantly reduced and/or severe frontalis and orbicularis muscle weakness is present, as this can limit the effectiveness of frontalis sling and increase the risk for exposure keratopathy. Brow ptosis is common due to frontalis weakness. Brow ptosis repair.

Complications

Post-operative ocular complications include recurrent post capsular opacification (PCO) and anterior capsulorhexis contracture, perhaps due to a greater than average fibroblastic, proliferative metaplasia of residual lens epithelial cells into myofibraoblasts. Other complications include posterior vitreous membrane. Case reports of patients undergoing multiple YAG laser capsulotomies to treat recurrent PCO have been reported.

Additional Resources

References

  1. Myopathies without EOM Weakness: Facioscapulohumeral + Myotonic Dystrophy. Washington University at St. Louis. 2014 June. Web. http://neuromuscular.wustl.edu/musdist/pe-eom.html.
  2. Pelargonio G, Dello Russo A, Sanna T, De Martino G, Bellocci F. Myotonic Dystrophy and the Heart. Heart. 2002 Dec; 88(6): 665–670.
  3. Cohen, A, Weinberg D. Evaluation and Management of Blepharoptosis. New York: Springer; 2011. 79 p.
  4. Sorge A, Devoelaere T, Sotodeh M, et. all. Exposure keratopathy following silicone frontalis suspension in adult neuro- and myogenic ptosis. Acta Ophthalmol. 2012; 90: 188-192.
  5. Versino M, Rossi B, Beltrami G, et. all. Ocular Motor Mytonic Phenomenon in Mytonic Dystrophy. J Neurol Neurosurg Psychiatry 2002; 72:236-240.
  6. Azuara-Blanco A, Katz LJ, Arkfeld DF, Walsh TJ. Myotonic dystrophy mimicking bilateral internuclear ophthalmoplegia. Neuro-ophthalmology 1997; 17:11-14.
  7. Burian HM, Burns CA. Ocular changes in myotonic dystrophy. Am J Ophthalmol 1967; 63: 22-34.
  8. Verhagen WIM, Ter Bruggen JP, Huygen PLM. Oculomotor, auditory, and vestibular responses in myotonic dystrophy. Arch Neruol 1992; 49:954-960.
  9. Rosa N, Lanza M, Borrelli M, et. all. Low Intraocular Pressure Resulting from Ciliary Body Detachment in Patients with Myotonic Dystrophy. Ophthalmology. 2011 Feb;118(2):260-4.
  10. Sarks J, Liu H, Killingsworth M, et. all. Retinal Changes in Myotonic Dystrophy: A Clinicomorphological Study. Australian and New Zealand Journal of Ophthalmology, 13: 19–36. doi: 10.1111/j.1442-9071.1985.tb00395.x
  11. Rhodes J. Cataract in Myotonic Dystrophy. International Myotonic Dystrophy Organization, Inc. Web. http://myotonicdystrophy.com/wp/wp-content/uploads/2012/09/Cataract-Brochure-Myotonic-Dystrophy.pdf
  12. Vassilopoulos D, Alevizos B, Spengos M. Cataract and gamma-glutamyl cycle in myotonic dystrophy. Ophthalmologica. 174 (3); 167-9.