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Dry eye exam reveals corneal deposits
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A 66-year-old Caucasian woman presented to the clinic with a chief complaint of dry eyes and interest in contact lenses for correction of her vision. She noticed that her dry eyes and vision in both eyes appeared to be worsening over the past few years and that she had insufficient relief of her dry eyes and mild light sensitivity with artificial tears.
The patient recalled a childhood history of painful “cuts” in her eyes, especially in the morning, that decreased as she became older and a history of an unknown laser procedure of both her corneas 5 years prior outside of the U.S. She denied any other relevant personal or family ocular history.
Best-corrected visual acuities with spectacles were 20/40 OD with +5.50 D -2.00 D x 120 and 20/50 OS with +6.50 D -0.50 D x 095, not improving with pinhole. Preliminary testing was normal. Anterior segment biomicroscopy revealed a reduced tear meniscus height and an almost instantaneous tear film break-up time in each eye.
Close examination of her cornea revealed bilateral diffuse gray-white reticular opacities in Bowman’s layer in each eye and grade 2 inferior corneal fluorescein staining of each eye. A central anterior stromal haze was also noted in both eyes. No LASIK flaps were present, and the anterior chambers were deep and quiet in both eyes. Her palpebral conjunctiva, lids, lashes and hazel irises were clear and intact in both eyes.
Further examination of her cornea with anterior segment OCT (Cirrus OCT, Carl Zeiss Meditec) showed hyper-reflective deposits just below the epithelium in both eyes. The patient’s corneal topographies revealed oblate corneas with a small degree of irregular astigmatism. Intraocular pressures were 14 mm Hg OD and OS by Goldmann tonometry, and fundus examination was unremarkable for both eyes. Central pachymetry measured 461 µm OD and 459 µm OS.
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Based on patient history and the location and appearance of the deposits, the patient was diagnosed with Reis-Bücklers corneal dystrophy. Also known as granular corneal dystrophy type 3, this is a dystrophy of Bowman’s layer that is inherited in an autosomal dominant fashion. It is associated with a mutation of the transforming growth factor beta 1 (TGFB1) gene on chromosome 5q31 encoding for keratoepithelin. Mutated TGFB1 produces rod-shaped deposits of hyaline-like material that disrupt and replace Bowman’s membrane. Despite the patient’s denial of ocular problems among ancestors, the diagnosis was crystallized by the clinical findings.
On slit lamp examination, the reticular opacities give the corneal surface a rough map-like surface or ground-glass appearance bilaterally, as seen in our patient. On anterior segment OCT, the deposits will appear as hyperfluorescent areas within and above Bowman’s layer.
Because this dystrophy disrupts the integrity of the epithelial basement membrane, these patients are subject to recurrent corneal erosions during the first and second decade of life with associated sensitivity to light. These changes are consistent with the patient’s history. Later stages of the disease can present with stromal haze and irregular astigmatism as seen with our patient, and vision loss can be progressive due to increasing corneal opacification. Additionally, the corneal irregularities can result in poor tear film and mucin distribution associated with dry eye.
A definitive diagnosis of Reis-Bücklers corneal dystrophy is best confirmed through genetic testing or electron microscopy histopathology studies if the patient is interested or if the clinical picture is not diagnostic. Unfortunately, our patient declined genetic testing and electron microscopy histopathology studies.
Potential diagnoses
While the clinical presentation here points to Reis-Bücklers corneal dystrophy, there are other conditions that warrant consideration.
Thiel-Behnke corneal dystrophy presents similarly to Reis-Bücklers with subepithelial opacities in the central cornea. However, these opacities are usually less defined, grouped in honeycomb-like structures and are symptomatically less severe. The definitive diagnosis is made by identifying “curly fibers” in Bowman’s layer on electron microscopy.
Granular corneal dystrophy (type 1) presents with discrete, white breadcrumb-like deposits of hyaline material in the anterior stroma.
Lattice corneal dystrophy presents with amyloid filamentary deposits in the anterior stroma in a fine branching and interlaced pattern.
Avellino corneal dystrophy (also called granular corneal dystrophy type 2 or combined granular-lattice corneal dystrophy) presents with both a combination of granular hyaline and lattice amyloid deposits in the anterior stroma. Granular deposits usually appear first. This corneal dystrophy is especially important to distinguish before any refractive surgery. Several case reports have shown that LASIK and LASEK may exacerbate granular-lattice corneal dystrophy (Kim et al., Lee). This exacerbation occurred in patients with both pre-existing corneal disease and unremarkable corneal findings. It is hypothesized that damage to the epithelial cells triggers TGFB1 as part of the normal wound repair cascade, which leads to synthesis of mutated keratoepithelin, especially at the flap-stroma interface.
Macular corneal dystrophy presents with an accumulation of numerous small, circular indiscrete glycosaminoglycan deposits that appear as gray-white spots in the anterior stroma of the central cornea and in the posterior stroma of the peripheral cornea. Early stages will present with corneal thinning, while late stages of the disease result in corneal thickening due to edema. Late stages will also involve the entire stroma and extend to the limbus. Macular corneal dystrophy is one of the few autosomal recessive corneal dystrophies.
Meesmann epithelial dystrophy presents with irregular thickening of the basement membrane and numerous intraepithelial cysts extending from the center outward without reaching the limbus. This condition is non-progressive and caused by a mutation in the genes involved in corneal epithelial metabolism.
Epithelial basement membrane dystrophy (Cogan’s microcystic dystrophy or map-dot-fingerprint dystrophy) presents with a variable appearance. Extra sheets of basement membrane extend into the epithelium, creating amorphous clear zones in the epithelium with distinct borders within a gray/hazy area known as “map” lesions. “Dot” lesions appear as small gray-white opacities, and “fingerprint” lesions consist of parallel or concentric circles best seen on retro-illumination.
Diffuse lamellar keratitis (“sands of Sahara”) is a LASIK complication that occurs 1 to 7 days after the procedure. Inflammatory cells can usually be seen 1 to 2 days post-op at the peripheral LASIK flap interface in stage 1. Stage 2 occurs when the cells migrate across the pupillary axis, and in stage 3, the cells will begin to clump together. Stage 3 can lead to a decrease in vision, so flap irrigation to remove the cells is warranted. A key differentiating factor between diffuse lamellar keratitis and a true corneal dystrophy is its timing of onset after surgery.
Managing Reis-Bücklers
Because Reis-Bücklers results in recurrent corneal erosions (RCEs), treatment is aimed at treating and preventing future occurrences of the RCEs. Copious lubrication during the day with nonpreserved artificial tears can keep the cornea well-hydrated and help with re-epithelization. A nighttime ointment is commonly added to decrease the frictional force between the lids and anterior cornea in the morning.
Bandage soft contact lenses (BSCLs) may be used in recurrent corneal erosions recalcitrant to topical treatments. BSCLs not only help provide improved comfort when corneal erosions occur by covering the sensitive corneal nerve endings, but also serve as a barrier between the defect and external shearing forces. Careful observation and an antibiotic is needed for extended wear of the bandage soft contact lenses with an epithelial defect.
Eventually, irregular astigmatism can occur in Reis-Bücklers corneal dystrophy due to the uneven distribution of deposits along the Bowman’s layer. When this occurs, there may be a need for specialty contact lens correction. Recently, scleral gas permeable lenses have gained popularity in treating ocular surface disease. Scleral lenses are also an option for Reis-Bücklers patients as they not only provide visual rehabilitation, but also create a long-lasting moist environment that can nurture the ocular surface throughout the day due to the retention of a lubricating reservoir of artificial tears behind the lens. Furthermore, like a bandage soft contact lens, the scleral lens can act to protect the vulnerable cornea from the friction of the eyelids during blinking and external forces.
Surgical treatment options for Reis-Bücklers include phototherapeutic keratectomy (PTK), deep lamellar keratoplasty (DALK) or penetrating keratoplasty (PK). PTK is a minimally invasive procedure where the epithelium is removed and then an excimer laser removes the affected superficial layers of the cornea by photoablation. Sometimes a masking agent, such as hydroxypropyl methylcellulose 0.7% to 2% can be used to help isolate the irregular surface protrusions while protecting the layers underneath.
What laser procedure did the patient most likely have? PTK is most likely the unknown surgical procedure the patient underwent due to her history of Reis-Bücklers corneal dystrophy, remaining refractive error, topography and lack of a corneal flap or other corneal incisions. Due to attendant risks, more invasive surgical options such as PK and DALK are reserved only when noninvasive or minimally invasive therapies have failed. Woreta and colleagues and Kim and colleagues have shown that recurrence of Reis-Bücklers basement membrane deposits may occur in up to 50% of the cases after 1 to 2 years in PTK, PKP or DALK. Some studies have shown that the use of topical mitomycin C with PTK may be helpful in delaying or preventing the recurrence of the disease. However, further studies on the efficacy and safety profile of mitomycin C are needed (Kim et al., Lee et al., Woreta et al.).
Patient outcome
Our patient achieved maximum relief of her symptoms and signs with scleral gas permeable lenses. After 3 weeks of scleral lens wear and adequate adherence to a nonpreserved artificial tear regimen, the patient had significantly improved dry eye signs and no symptoms. Over 5 months since her initial visit, the patient’s density of corneal deposits has remained stable without recurrent corneal erosions. In addition, her vision improved to and has remained 20/20 OU. Scleral lenses were both a practical therapeutic and vision rehabilitative option for success with this patient.
- References:
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- Melki SA, Fava MA. Diffuse lamellar keratitis. In: Melki SA, Fava MA, eds. Cornea and Refractive Atlas of Clinical Wisdom. Thorofare, NJ: SLACK Incorporated; 2011:207–210.
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- For more information:
- Chandra Mickles, OD, MSc, FAAO, FSLS, is an associate professor at Nova Southeastern University College of Optometry. She is the coordinator of the university’s Dry Eye Care Center and teaches and publishes in the areas of contact lenses and ocular surface disease. She can be reached at: cmickles@nova.edu.
- Carol Yu, OD, is a graduate of University of California Berkeley College of Optometry and a current primary care and cornea and contact lens resident at Nova Southeastern University College of Optometry. She can be reached at: cyu@nova.edu.
- Edited by Leo P. Semes, OD, FAAO, a Primary Care Optometry News Editorial Board member. He can be reached at: leopsemes@gmail.com.
Disclosures: Mickles is a consultant for Johnson & Johnson Vision and Alcon. She also has received research funding from Alcon. Semes and Yu report no relevant financial disclosures.