Subepithelial mucinous corneal dystrophy (SMCD) is an autosomal dominant corneal dystrophy characterized by bilateral deposition of mucin beneath the corneal epithelium. It was first reported by Feder et al. in 1993 1, and the main components of the deposits are the glycosaminoglycans chondroitin-4-sulfate and dermatan sulfate 1.
To date, this disease has only been confirmed in a single family spanning three generations 1,2. In the third edition of the International Classification of Corneal Dystrophies (IC3D), SMCD is classified as Category 4, where the causative gene locus and responsible gene have not been identified 2. Patients with SMCD show no evidence of systemic mucopolysaccharidosis 1.
SMCD is extremely rare among corneal dystrophies, reported in only a single family worldwide. Diagnosis has been confirmed in multiple members of the same family across three generations, but no other families have been reported. The causative gene locus remains unidentified, and the full picture of the disease has not yet been elucidated.
It follows an autosomal dominant inheritance pattern1,2. The genetic locus has not been identified, and it is classified as IC3D Category 4 (causative gene unidentified)2,3. Chondroitin-4-sulfate and dermatan sulfate accumulate just anterior to Bowman’s layer1. It is not associated with systemic mucopolysaccharidosis1.
Risk is increased if there is a family history. No other risk factors have been identified.
Clinical Diagnosis
Slit-lamp microscopy: Confirms bilateral subepithelial diffuse opacities. The pattern of denser opacity centrally and thinner peripherally is characteristic.
Family history taking: Confirms correlation with a family history consistent with autosomal dominant inheritance.
Pathology and Special Tests
Histochemical staining: Eosinophilic, PAS-positive, Alcian blue-positive, hyaluronidase-sensitive material is observed in a band-like pattern just anterior to Bowman’s layer 1,2. Trichrome staining is also used as a diagnostic aid 5.
Immunohistochemical staining: Positive staining with monoclonal antibodies specific for chondroitin-4-sulfate/dermatan sulfate 1,2.
Electron microscopy: Deposition of fibrous material is observed beneath the epithelium 1,2.
| Differential Disease | Differences from SMCD |
|---|---|
| Epithelial Basement Membrane Dystrophy | Map-like, dot-like, and fingerprint-like lesions. Erosion onset after age 40. |
| Meesmann Corneal Dystrophy | Infantile-onset dew-drop-like intraepithelial cysts. Visual impairment is rare. |
| Gelatinous Drop-like Corneal Dystrophy | Mulberry-like appearance. Congo red positive. Prone to recurrence after PKP. |
Other differential diagnoses include Lisch corneal dystrophy (X-linked dominant, feathery/whorl pattern, no erosion) and Reis-Bücklers corneal dystrophy (TGFB1 gene mutation, fishnet/corona-shaped opacities). In atypical Reis-Bücklers dystrophy, morphological differentiation from SMCD may be difficult, and TGFB1 genetic testing or immunohistochemical staining can be useful.
EBMD presents characteristic “map-like”, “dot-like”, and “fingerprint-like” lesions due to corneal epithelial basement membrane dysplasia. Erosion typically occurs after the age of 40. In SMCD, glycosaminoglycans deposit beneath the epithelium, and erosion begins within the first 10 years of life. The immunohistochemical staining pattern of deposits also differs.
The first-line treatment for recurrent corneal erosion in general is preservative-free artificial tears and lubricating eye ointment at bedtime 4. The goal is to relieve eye pain and promote healing. Topical antibiotics, cycloplegics, and pressure patching may be used in combination. Therapeutic soft contact lenses are also useful for preventing further erosion, providing immediate pain relief and corneal protection 4. Recurrent erosion in SMCD differs from other epithelial dystrophies in that it spontaneously resolves after adolescence 1,2.
Surgical intervention is considered when visual acuity is significantly reduced due to corneal opacity.
Superficial Keratectomy (SK): Removes subepithelial deposits. It is indicated because the lesion is confined to the superficial layer 1.
Penetrating Keratoplasty (PKP): Performed when corneal opacity is severe. In the original report by Feder et al., one case of PKP combined with posterior chamber intraocular lens implantation showed improvement of 2 or more lines in both eyes 1. No disease recurrence has been confirmed postoperatively 1.
Phototherapeutic Keratectomy (PTK): Although there are no clear reports of PTK for SMCD, it may theoretically be indicated because the lesion is superficial 2. However, note that histopathological staining for definitive diagnosis cannot be performed after PTK.
Visual improvement has been reported with superficial keratectomy (SK) or penetrating keratoplasty (PKP). In one case that underwent PKP combined with posterior chamber intraocular lens implantation, improvement of 2 or more lines was observed in both eyes. No disease recurrence has been reported to date. However, the number of cases is extremely limited, and further observation is needed for long-term prognosis.
Dermatan sulfate and chondroitin-4-sulfate are deposited beneath the corneal epithelium 1,2. The deposits are densest in the central region and become thinner toward the periphery 1. They extend locally and irregularly into the anterior stroma 1. They are observed as a homogeneous eosinophilic layer distinct from the epithelial basement membrane 1,2.
Subepithelial deposits interfere with normal epithelial function and cause poor epithelial adhesion 1. This leads to recurrent corneal erosion in childhood 1. Recurrent corneal erosion generally involves poor adhesion between the corneal epithelium and basement membrane, with a decrease in hemidesmosomes and disruption of the basement membrane 4.
Loss of optical transparency and disruption of the normal refractive curvature of the cornea lead to progressive visual impairment over decades 1. In the original report by Feder et al., the most pronounced visual impairment was observed in the oldest patients examined (71 and 82 years old at initial presentation) 1.
