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15 November 2023: Articles  Saudi Arabia

Severe Dry Eye Disease in Charcot-Marie-Tooth Disease: A Comprehensive Case Report

Challenging differential diagnosis, Rare coexistence of disease or pathology

Khalid A. Aldihan1ABDEF, Musa Johaiman AlRashedi1ABDEF, Halah Bin Helayel ORCID logo1ABDEF*, Mohammed AlMutlak1ABDEF, Sami T. Hameed1ABDEF

DOI: 10.12659/AJCR.941094

Am J Case Rep 2023; 24:e941094




BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a hereditary neurological disorder that primarily leads to peripheral neuropathy, characterized by progressive muscle weakness, atrophy, and loss of sensation in the extremities. It can also present with some ocular manifestations, such as glaucoma, nystagmus, and cranial nerve involvement. The purpose of this article was to report a case of severe dry eye disease (DED) possibly associated with Charcot-Marie-Tooth disease.

CASE REPORT: We report the clinical presentation, workup, and management of a woman diagnosed with CMT type 2EE based on genetic testing who suffered from severe DED sequelae. The patient had regularly followed up in the cornea service at our hospital due to DED for several years. A thorough workup to exclude causes associated with dry eye disease, including rheumatoid factor, erythrocyte sedimentation rate (ESR), anti-nuclear antibody (ANA), anti-Sjögren’s-syndrome-related antigen A (anti-SSA), and anti-Sjögren’s-syndrome-related antigen B (Anti-SSB), were performed, and all came out negative. She recently presented to the emergency room with redness, tearing, and a decline in visual acuity after minor ocular trauma 3 weeks before her presentation. The slit lamp examination showed central corneal perforation measuring 2×2 mm with a positive Seidel test. The case was managed first by multiple attempts to seal the defect with cyanoacrylate glue, and then a patch corneal graft was performed as the anterior chamber failed to deepen.

CONCLUSIONS: DED may be one of the many ocular manifestations associated with CMT. Hence, a thorough assessment and multidisciplinary approach, including supportive therapy, are warranted to prevent long-term ocular sequelae, including visual loss.

Keywords: Charcot-Marie-Tooth disease, Dry Eye Syndromes, Genetic Diseases, Inborn


Charcot-Marie-Tooth disease (CMT) is an inherited neuromuscular disorder characterized by neuropathies without metabolic disorders [1]. CMT can be inherited by several patterns, including autosomal dominant, autosomal recessive, and X-linked inheritance [1]. It is characterized by sensory neuropathy, muscular atrophy, and foot deformities [1].

The prevalence of CMT is 10.8–17.5 cases per 100,000 population [2,3]. CMT was first described in the mid-1800s. In 1968, it was subdivided into CMT 1 and CMT 2 according to the pathological features. Further subdivisions evolved with the advancement of genetic testing [4]. CMT 1 is a peripheral demyelination disorder resulting in numbness and weakness. Usually, pain and temperature sensations are preserved. CMT 2 is an axonal disorder, while CMT 3 and 4 are demyelinated disorders with infantile and childhood onset [5–7].

CMT has been associated with multiple ocular manifestations, including glaucoma, nystagmus, and optic nerve atrophy [8]. Cranial nerve involvement with CMT has been previously described, especially oculomotor and trigeminal nerve involvement [9]. A case-control study by Tavakoli et al showed a reduction in corneal sensitivity, corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length, and corneal nerve fiber tortuosity in patients with CMT [10]. However, they included only cases with CMT type 1A.

In this report, we describe a case of CMT associated with severe dry eye disease (DED) and corneal perforation after trivial trauma. To the best of our knowledge, DED has not previously been described as being associated with CMT.

Case Report

A 28-year-old woman with a known case of CMT first presented to our hospital a few years ago due to eye redness and visual acuity decline. Her medical history indicated peripheral neuropathy with muscular weakness since she was 3 years old. A slit lamp examination showed she had severe dry eye disease, positive fluorescein staining in the form of corneal epithelial defect, and central corneal scarring. The Schirmer test II result was less than 1 mm after 5 min. Therefore, she was diagnosed with severe DED. To identify the cause of DED, extensive laboratory workup was ordered, including rheumatoid factor, erythrocyte sedimentation rate (ESR), anti-nuclear antibody (ANA), and workup for Sjögren’s, including anti-Sjögren’s-syndrome-related antigen A (anti-SSA) and anti-Sjögren’s-syndrome-related antigen B (Anti-SSB). All laboratory tests came back negative. Genetic testing was done and revealed CMT type 2EE with a pathogenic homozygous mutation in MPV17, c.122G>A p.(Arg41Gln), resulting in length-dependent severe sensory motor axonal polyneuropathy. The patient was given lubricants in the form of drops, gel, and ointment.

The patient presented to the Emergency Department due to a decline in visual acuity, redness, and tearing. She reported having trauma by a fingernail to her left eye 3 weeks before the presentation. The examination showed that the left eye had central corneal perforation measuring 2×2 mm, a positive Seidel test, and a collapsed anterior chamber (AC) (Figure 1). The patient underwent multiple attempts at corneal gluing with cyanoacrylate. Unfortunately, the AC in the left eye was persistently shallow. Hence, we decided to reform the AC in the operating theater, remove cyanoacrylate glue, and use a mini-Descemet’s automated endothelial keratoplasty (DSAEK) tissue, amniotic membrane, and fibrin glue to seal the corneal perforation (Figure 2). Postoperatively, she was prescribed 1% prednisolone acetate 4 times daily on a tapering regimen, topical moxifloxacin 4 times daily, and frequent lubrication with non-preserved artificial tears. In addition, 20% autologous serum eye drops were prescribed 4 times daily for their lubricating benefits. The patient’s condition was stable 1 year postoperatively with no further ocular complications.


Several ocular manifestations of CMT have been described in the literature, including impaired ocular motility, retinitis pigmentosa, pupillary abnormalities, and optic neuropathy [8,11–14]. Our patient presented with severe DED complicated with corneal perforation secondary to minimal trauma. The Schirmer test result was low, indicating a decrease in lacrimal gland para-sympathetic stimulation, which could be explained by trigeminal nerve involvement. In the Tavakoli et al study, 12 patients diagnosed with CMT and 12 healthy control subjects were enrolled to compare corneal sensation using a non-contact corneal aesthesiometer [10]. The study showed a significant decrease in corneal sensitivity in the CMT group compared to the control group and a significant reduction in corneal fibers density and length in CMA, as demonstrated by corneal confocal microscopy. Disruption of corneal sensation can affect normal blinking and tear film reflexes, leading to DED [15].

Dry eye disease management requires a stepwise approach and consideration of other associated conditions, including systemic disorders, ocular surface inflammation, and meibomian gland dysfunction [16]. Artificial tears are the first-line treatment for any grade of dry eye disease. Artificial tears increase tear film stability, while topical cyclosporine A increases the production of tears by releasing parasympathetic neurotransmitters [17,18]. Scleral lenses can be used in severe cases.

Surgical management of DED is usually reserved for complicated cases such as persistent corneal epithelial defect or perforation. These procedures include tissue adhesives, conjunctival flaps, amniotic membrane transplant, Tenon’s patch graft, tarsorrhaphy, and keratoplasty [16,19]. Salivary gland transplantation to substitute for lacrimal glands has been described to manage reduced tear production [20]. However, long-term complications such as excessive lacrimation and corneal edema have been reported with this procedure [20]. Injection of botulinum A toxin to induce temporary paralysis of the orbicularis oculi muscle to decrease the pumping function during blinking is an option in severe cases of DED [21].

In our case, the patient’s condition was stabilized using the mini-DSAEK technique described by Vasquez-Perez et al, autologous serum eye drops, and frequent lubrication [22,23].


Severe dry eye disease can be encountered in CMT patients. To the best of our knowledge, this case report is the first to show an association between CMT and DED. However, this observation might be an incidental finding. Although infrequent in the ophthalmic setting, proper diagnosis of DED associated with CMT cases is crucial. This involves excluding common causes of DED through history, clinical examination, and extensive workup. Dryness in CMT can be encountered, and a multidisciplinary approach is very important, including communication with a rheumatologist to exclude autoimmune causes of dryness. Genetic confirmation of the diagnosis of CMT is essential. Supportive treatment should be considered in such cases to prevent devastating complications.


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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923