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Young woman presents with bilateral photophobia and corneal opacities
Both corneas had round and oval-shaped anterior stromal opacities arranged in a circle paracentrally.
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A 24-year-old woman presented to New England Eye Center upon referral from her outside ophthalmologist complaining of several years of light sensitivity, burning pain and blurred vision in both eyes.
The patient’s ocular symptoms first began in childhood with a foreign body sensation in both eyes. By her early teenage years, the foreign body sensation worsened and was associated with a sharp, shooting pain and light sensitivity. These symptoms had acutely worsened 3 months before presentation. The patient had multiple changes in her refractive error over the last few years and felt her vision was constantly hazy. The patient had no other ocular history besides her present symptoms. She denied any pertinent medical history and only took an oral contraceptive pill. She denied a family history of ocular disease although her paternal family history was unknown. She had no known drug allergies.
Examination
On examination, the patient’s best corrected visual acuity was 20/30+3 in the right eye and 20/30+1 in the left eye with +3.50 D and +2.75 D of cylinder, respectively. Pupils were equal and reactive to light without evidence of an afferent pupillary defect. Confrontational visual fields and extraocular movements were full in both eyes. IOPs were normal bilaterally. Bilateral lids and adnexa were normal. Anterior exam revealed trace follicles on the palpebral conjunctiva in both eyes. The patient’s corneas in both eyes were notable for round and oval anterior stromal opacities arranged in a circle paracentrally (Figure 1), with the intervening cornea exhibiting a grainy appearance, densest centrally. There were few scattered, smaller, deep endothelial opacities peripherally extending to the limbus. There was no overlying epithelial staining. The anterior chamber was quiet without cell or flare. Dilated fundus exam was unremarkable.
Source: Alison J. Lauter, MD, and Michael B. Raizman, MD
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Corneal stromal opacities
Our patient was found to have bilateral round and oval-shaped corneal stromal opacities with intervening corneal haze associated with debilitating photophobia, foreign body sensation and blurred vision. The differential diagnosis of bilateral corneal stromal opacities that have been present for several years includes many of the corneal stromal dystrophies such as macular corneal dystrophy, granular corneal dystrophy (type 1 and 2), Schnyder corneal dystrophy, fleck corneal dystrophy and congenital stromal dystrophy. Additionally, the differential should include systemic diseases and medications that cause corneal deposits such as amiodarone use, Fabry disease, cystinosis and plasma cell dyscrasias. An infectious cause was felt to be unlikely due to the chronicity of the opacities.
The clinical appearance and history were felt to be characteristic of a hereditary corneal dystrophy, and therefore no further workup was performed. Granular, Schnyder, fleck and congenital corneal dystrophies are all autosomal dominantly inherited, and the lack of family history of a corneal disease made these entities unlikely. The round and oval-shaped stromal opacities demonstrated in this patient resembled those typically seen in granular dystrophy, but the intervening haze was atypical. Intervening corneal haze with stromal and endothelial opacities that extend to the limbus are more characteristic of macular corneal dystrophy (MCD). A preliminary diagnosis of MCD was made.
Discussion
Corneal dystrophies are rare inherited diseases of the cornea that are typically bilateral and slowly progressive. Of the three classic stromal dystrophies, macular, granular and lattice, MCD is the least common. The disease was first documented by German ophthalmologist Oskar Fehr in 1904 and was originally named “Fehr spotted dystrophy.” While rare in the United States, MCD has a higher prevalence in Iceland, Saudi Arabia and southern India.
The disease exhibits an autosomal recessive inheritance pattern and is due to mutations in the CHST6 gene on chromosome 16q22. Mutations in this gene prevent normal sulfation of corneal keratan, resulting in deposition of glycosaminoglycans (GAGs) in all layers of the cornea except the epithelium. The presence of GAGs in the corneal depositions can be confirmed using Alcian blue and colloidal iron stains.
Three distinct variants of MCD have been identified based upon the distribution and reactivity within the serum and cornea of keratan sulfate. In MCD type I, keratan sulfate is absent in both the serum and cornea. In MCD type II, keratan sulfate is present but in decreased levels in both the serum and cornea. In MCD type IA, keratan sulfate is absent in the serum but present in the cornea; stromal keratocytes exhibit immunoreactivity to keratan sulfate antibodies.
Patients are born with clear corneas, and the first MCD lesions are often evident within the first decade of life. Typically, GAG deposition begins in the central anterior stroma and progresses downward and peripherally. Clinically, the deposits appear as grayish-white focal opacities with irregular borders and a characteristic haze of the intervening cornea. The presence of corneal guttae may indicate involvement of the endothelium and Descemet’s membrane. While epithelial erosions can occur, they are much less common in MCD than the other stromal dystrophies. As the disease progresses, common early symptoms include photophobia and pain. Visual acuity becomes affected often by the third decade of life.
Management of MCD involves close observation and management of the patient’s symptoms. Photophobia can be reduced with the use of tinted contact lenses. Phototherapeutic keratectomy can be used for symptomatic anterior lesions; however, it is at best a temporizing measure as MCD inevitably progresses to full-thickness corneal involvement. By the time a patient’s activities of daily living are significantly limited by the disease, penetrating keratoplasty is indicated to improve visual acuity. As MCD is the result of an enzymatic defect, recurrence is common and therefore long-term follow-up is indicated. Recurrence has been reported to occur 20 months to 30 years after PK, often requiring repeat PK. In the last several years, deep anterior lamellar keratoplasty has been proposed as a treatment option for MCD if the endothelium is not yet involved due to a decreased risk for rejection and endothelial cell loss compared with PK. This may be a reasonable option to improve visual function and delay the need for PK.
Clinical course continued
The patient was monitored closely for several years until her disease became more visually significant. Three years later, the photophobia and decreased vision resulted in difficulty completing daily tasks such as driving and work. Her BCVA was 20/50+2 in the right eye and 20/30– in the left eye at this time with +3.50 D of cylinder in both eyes on manifest refraction. The stromal opacities now extended limbus to limbus and full thickness in the corneal stroma to Descemet’s membrane (Figure 2). Because the patient’s symptoms were subjectively worse in the left eye, the decision was made to proceed with PK in the left eye first. She underwent an 8.5- to 8.25-mm PK in the left eye. The corneal button revealed subepithelial and stromal deposits, stromal edema and endothelial degeneration (Figure 3) that stained positively with Alcian blue, confirming the diagnosis of MCD (Figure 4). At her 1 month postoperative visit, she had complete resolution of symptoms and no evidence of recurrence. Surgical intervention for the right eye will be considered in the coming months.
- References:
- Aggarwal S, et al. Surv Ophthalmol. 2018;doi:10.1016/j.survophthal.2018.03.004.
- Cheng J, et al. Ophthalmology. 2013;doi:10.1016/j.ophtha.2012.07.037.
- Marcon AS, et al. Cornea. 2003;22(1):19-21.
- Reddy JC, et al. Cornea. 2015;doi:10.1097/ICO.0000000000000327.
- Sogutlu Sari E, et al. Am J Ophthalmol. 2013;doi:10.1016/j.ajo.2013.03.007.
- For more information:
- Alison J. Lauter, MD, and Michael B. Raizman, MD, can be reached at New England Eye Center, Tufts University School of Medicine. 800 Washington Street, Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Aubrey R. Tirpack, MD, and Astrid C. Werner, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.