Ocular Manifestations of Myotonic Dystrophy
Myotonic dystrophy (DM) is a multi-system disease characterized by myopathy, myotonia, and other multi-organ manifestations. It is a nucleotide repeat disease with autosomal dominant inheritance. There are two major forms of DM: Myotonic dystrophy 1 (DM1), historically termed Steinert’s disease, and myotonic dystrophy 2 (DM2).
The prevalence of DM has previously been estimated in European populations at around 1 in 8000. However, more recent genetic studies have suggested that the true prevalence may be much higher, with mutational frequency identified in as many as 1 in 2,760.
The systemic clinical features of DM1 are numerous and include skeletal muscle weakness, muscle pain, myotonia, cardiac abnormalities, impaired respiratory function, sleep disturbance, endocrine abnormalities, and cognitive impairment. In DM2, muscle weakness, pain, and myotonia are common, while other systemic features tend to be less frequent and milder in severity.
Muscle weakness and myotonia resulting from DM can cause associated oculomotor abnormalities, including ophthalmoplegia, extraocular muscle myotonia, and blepharoptosis or brow ptosis. Isolated ophthalmoplegia is a relatively uncommon symptom of DM but a variety of patterns have been reported in DM patients. Abnormalities in saccadic velocity have also been noted in DM, likely due to extraocular muscle myotonia which is more pronounced after prolonged fixation. Myogenic blepharoptosis and brow ptosis from weakness of the levator palpebrae superioris and frontalis muscles, respectively, are common in DM.
Miosis (constricted pupils), usually evident as impaired pupillary dilation following administration of pharmacologic dilating agents, has been observed in DM patients. Although the pathophysiology has not been fully elucidated, it has been theorized to be due to underlying dilator smooth muscle dysfunction.
Low intraocular pressure has frequently been observed in DM patients. In one study, DM patients had a mean IOP about 23% lower than control eyes, a difference which could not be accounted for by corneal abnormalities. In one study, ciliary body detachment was observed in all DM1 patients studied, suggesting a possible etiology for hypotony in this population.
The association between DM1 and Fuchs’ endothelial corneal dystrophy (FECD) was described relatively recently after several members of a cohort of DM patients were noted to also have corneal abnormalities consistent with FECD. FECD is most closely associated with CTG trinucleotide repeat expansion in the TCF4 gene of chromosome 18. However, this trinucleotide expansion is not common in DM patients. Further studies have instead found that DMPK trinucleotide expansion, which is the causative mutation in DM1, can also cause FECD clinical disease, likely through RNA-mediated toxicity. The frequency of FECD in DM1 patients has been estimated to be as high as 46%, making this an important and newly recognized ocular manifestation.
Cataracts are the most frequent ocular manifestation of DM, common in both DM1 and DM2. Early-onset posterior subcapsular cataract, usually described as a ''Christmas-tree cataract,” is classically associated with DM. This manifestation can be the first presenting symptom for DM2 patients in particular and is common in DM1 patients as well.
Pigmentary retinal changes in DM patients usually resemble a pattern dystrophy with butterfly-like macular changes. These can have a variable appearance and are not a consistent finding in either DM1 or DM2.
In most cases, DM is diagnosed clinically in the setting of intellectual disability, muscle pain, or muscle weakness. Genetic testing for CTG repeats in DMPK is confirmatory for DM1 as is CCTG expansion in CNPB for DM2. Genetic testing has largely replaced EMG and muscle biopsy in the initial diagnosis of DM, although these modalities may also be helpful in certain atypical cases. Electrocardiography is critical to assess for cardiac conduction defects in all DM patients.
Due to its multisystem manifestations, DM should be managed in a multi-disciplinary manner in collaboration with cardiac, pulmonary, neurologic, and endocrine sub-specialists. Currently, no disease-modifying therapy for DM exists, so management is focused on symptoms.
Ophthalmic management of DM consists largely of treatment of ocular sequelae. Cataracts that are visually significant, for example, should be treated with surgical cataract extraction. Similarly, symptomatically significant oculomotor abnormalities, such as blepharoptosis or brow ptosis, can be treated with surgical repair. Strabismus surgery rarely is indicated.
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