Band Keratopathy

Background

Band keratopathy is characterized by the appearance of an opaque white band of variable density across the central cornea, caused by the precipitation of calcium salts, primarily hydroxyapatite, on the underside of the corneal epithelium.^[1] This corneal degeneration can result from a variety of causes, either systemic or local, with visual acuity decreasing in proportion to the density of the deposition. (See Etiology.)

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Band keratopathy. Note the bandlike whitish-grey lesion across the central corneal surface, most prominent on the exposure surfaces, sparing the super....

Superficial debridement often restores vision and comfort for most patients with band keratopathy; however, inadequate treatment of the inciting condition can lead to recurrence. (See Prognosis, Treatment, and Medication.)

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Etiology

Corneal deposition of calcium salt

The concentration of cations (including calcium and phosphate) in tears approaches their solubility products. Evaporation of tears can concentrate these solutes to a degree that they precipitate, particularly in the interpalpebral zone of exposure in the eye. Additionally, chronically inflamed eyes (ie, uveitis) raise the tear pH, further favoring participation of solutes.^{[2, 3, 4, 5]}  

The use of silicone oil, often employed after treatment of an open globe injury, has been implicated in the incidence of band keratopathy. Interestingly, the retention time of the silicone oil (>6 months) is directly proportional to the risk for band keratopathy. The exact etiology of this interaction remains to be fully elucidated; however, hypotheses point to changes in pH and localized toxic reactions caused by the silicone oil.^[6]

Systemic risk factors

The following conditions are associated with hypercalcemia, a risk factor for band keratopathy:

• Hyperparathyroidism
• Excessive vitamin D intake
• Renal failure^[7]
• Hypophosphatasia
• Milk-alkali syndrome
• Paget disease
• Sarcoidosis

Local ocular risk factors

Local ocular conditions associated with band keratopathy include the following ^{[8, 9]} :

• Chronic uveitis
• Juvenile idiopathic arthritis with uveitis
• Keratitis sicca
• Exposure keratopathy
• Phthisis bulbi
• End-stage glaucoma
• Anterior mosaic dystrophy
• Neurotrophic keratitis
• Chronic herpes simplex stromal keratitis
• Herpes zoster keratitis

Chemically associated risk factors

Drug-associated calcium deposition can result from the following:

• Steroid phosphate preparations (see the images below)^[10]
• Long-term use of glaucoma medications
• Pilocarpine-containing, mercury-based preservatives
• Viscoelastic agents - Rare, early formulations; may be related to phosphate buffers
• Silicone oil^{[11, 12, 6]}
• Topical medications containing phosphate buffers - Especially in the setting of chemical eye burns ^[13]
• Intraocular use of tissue plasminogen activator^[14]
• Certain noxious vapors (Mercury and calcium bichromate)

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The image shown is of a patient who developed a calcium plaque following a corneal transplant and the use of a topical steroid phosphate preparation.

It is important to note, however, that a large percentage of cases of band keratopathy are idiopathic. Recent studies have demonstrated that upwards of 35% of cases have no identifiable systemic or local cause. 

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Prognosis

Patients with band keratopathy experience a decrease in vision as the deposition progresses across the visual axis. Commonly, the irregular surface epithelium causes a foreign body sensation. The ocular discomfort may worsen to the point of disability, especially as smaller segments of the plaque loosen and partially mobilize. The plaque itself often is visible and of cosmetic concern to the patient and family.

Superficial debridement or lamellar keratectomy can restore vision and comfort in most patients with band keratopathy, with a very low incidence of adverse outcomes following this procedure. Unless underlying conditions have been addressed, removing the calcium deposits in band keratopathy is associated with a higher rate of recurrence.

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History and Physical Examination

History

Patients with band keratopathy complain of the following:

• Decreased vision
• Foreign body sensation
• Ocular irritation
• Photophobia
• Redness (occasionally)

Physical examination

Visual acuity will be decreased in proportion to the density of calcium salt deposition in the central cornea. Slit lamp examination often reveals a grayish white, plaque-like deposition that occurs in a band across the cornea. The far periphery of the cornea may be spared due to the buffering effect of limbal blood vessels. Holes in the plaque may be apparent; these represent spaces where the corneal nerves are traversing the Bowman membrane to the epithelial surface. (See the image below.)

View Image

Band keratopathy. Note the bandlike whitish-grey lesion across the central corneal surface, most prominent on the exposure surfaces, sparing the super....

The calcium deposition typically begins in the periphery and progresses centrally but, occasionally, may begin centrally. The calcium deposits range from being very fine or thick and plaque-like. When dense, areas of the lesion can flake off, often in the plaque periphery, causing epithelial defects and painful symptoms.

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Approach Considerations

Laboratory Studies

In patients without a previous history of band keratopathy, serium calcium and phosphate levels should be ordered. 

Renal function tests, such as blood urea nitrogen (BUN) and creatinine, should be performed. Renal failure and the need for dialysis can be associated with an elevation in serum phosphate and calcific band keratopathy.^{[16, 17]}

If sarcoid is suspected, angiotensin-converting enzyme (ACE) testing and chest imaging (often starting with chest x-ray, followed by chest CT if results are equivocal) may be indicated. In otherwise idiopathic cases, parathyroid hormone levels should be checked.

Histologic Findings

Band keratopathy is characterized by calcium deposition involving the Bowman layer and corneal stroma. The earliest changes include basophilic staining of the Bowman layer. Amorphous, eosinophilic connective tissue and a fibrous pannus often are present between the calcium deposition and the overlying epithelium in more advanced cases. (See the image below.)

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Total calcification of the cornea. Deep and superficial layers of the cornea are involved with this process.

When hypercalcemia is the cause, calcium is deposited intracellularly. In cases of local ocular disease, calcium is deposited extracellularly. 

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Approach Considerations

Superficial debridement with ethylenediamine-tetraacetic acid (EDTA) chelation is indicated to improve vision or reduce pain caused by band keratopathy. The risks of the procedure include corneal scarring or haze, nonhealing epithelial defect, infection, and vision loss. Underlying conditions associated with elevated levels of calcium or phosphate should be treated to prevent deposition from recurring.

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EDTA Chelation

Procedure

Superficial debridement with EDTA chelation can be performed in a minor operating room under topical anesthesia with proparacaine or tetracaine drops. Use of an operating microscope is recommended.

After adequate anesthesia is achieved, a lid speculum is inserted. The overlying epithelium can be debrided manually with a spatula, surgical blade, corneal knife, or Weck-Cel sponges. Alternatively, an alcohol solution diluted to a 20% concentration can be used to assist with superficial debridement of the epithelium by placing it in a circular pledget, circular optical zone marker, or LASIK well for 30 to 120 seconds. After time is elapsed, the alcohol can be absorbed using a Weck-Cel sponge. Any remaining alcohol should then be irrigated from the ocular surface.

Next, apply EDTA to the corneal surface using cellulose sponges or sterile cotton tip applicators. Alternatively, round surgical eye sponges (ie, Mentor® light shield) can be soaked in EDTA and applied to the cornea for 60 seconds or longer.

Disodium ethylenediamine-tetraacetic acid (EDTA) 1.5% to 3.75% can be prepared by some compounding pharmacies.

Dipotassium (K2-EDTA) can be prepared using sterile water and a K2-EDTA BD Vacutainer blood collection tube (Becton, Dickinson and Company, Franklin Lakes, NJ). The optimum concentration for K2-EDTA chelation has not been established and there are several methods described for K2-EDTA preparation. One method involves injecting 0.3 mL of sterile water into a 10-ml K2-EDTA tube and then using a cotton tip applicator to scrape the EDTA off the interior surface of the tube.^{[18, 19]}

Calcium deposits are then removed by firmly scraping the corneal surface with a spatula, surgical blade, corneal knife. Often, it is necessary to apply solution, followed by scraping several times to remove the plaque. The primary goal is to clear the visual axis. Thin calcium deposits may be removed in as little as 5 minutes. Thick plaques can take as long as 30-45 minutes to remove.

After debridement, the eye should be thoroughly irrigated to remove EDTA solution from the ocular surface and fornices.

Once the deposits have been removed, an assessment of the smoothness of the underlying stroma can be made. If the surface is very irregular, phototherapeutic keratectomy with an excimer laser can be performed to smooth the surface. Ideally, this procedure is performed in the same setting.

Note that the excimer laser should not be used to remove calcium. Attempting to remove band keratopathy with the excimer laser alone will result in significant irregular astigmatism, since the cornea, not calcium, will be ablated preferentially. The role of the excimer is solely to polish the surface after the plaque has been removed.^[20]

Irrigate the eye thoroughly following the procedure to remove EDTA solution from the conjunctival surface and fornices.

Place a bandage contact lens over the cornea. Alternatively, pressure patching or frequent antibiotic ointment can be used.

More advanced cases, particularly those that invade the Bowman membrane, may require a more extensive lamellar keratectomy technique including subtenon’s, peribulbar, or retrobulbar anesthesia and operating-room control of the surgical field. These procedures can be accomplished with a Beaver Blade followed by Weck-cel sponge polishing. More extensive polishing of exposed Bowman membrane with a rotating diamond burr may minimize irregular astigmatism after extensive keratectomy.

Extensive keratectomy inevitably creates limbal bleeding, particularly in cases associated with superficial corneal neovascularization or interstitial keratitis. Controlling bleeding with pressure or topical vasoconstrictors alone is important, because cautery application can damage limbal stem cells.

A therapeutic bandage soft contact lens (CTL) is important in recovery following debridement or lamellar keratectomy. The CTL provides significant pain relief and protection from blink disruption of re-epithelialization.

Amniotic membrane can be applied to the ocular surface to enhance healing, particularly when delayed epithelialization is anticipated, such as in patients with neurotrophic disease, chronic ocular surface inflammation, Sjögren’s disease, or advanced age.

Postoperative care

Postoperative care includes the insertion of a bandage contact lens that is left in place until the epithelium heals.

An antibiotic drop should be prescribed while the bandage contact lens is in place. Use of a topical steroid drop (eg, prednisolone acetate, not prednisolone phosphate) is helpful for comfort and treatment of the inflammation and corneal edema that often are present in the early post-procedure period. These medications can be stopped when the epithelium is healed and the bandage contact lens is removed (usually within the first 1-2 weeks).

Complications

The main complications related to the removal of calcium deposits on the corneal surface include the following:

• Pain
• Recurrence of the calcium band
• Need for additional procedures
• Corneal scarring
• Corneal edema
• Infection
• Decreased vision or vision loss
• Persistent or aggravated irregular astigmatism

Occasionally, a mild subepithelial haze can be seen weeks after EDTA chelation. This may be self-limiting. A mild topical steroid (eg, fluorometholone 0.1%) may help to resolve this haze. If there is significant damage to the Bowman membrane, the haze may be permanent.

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Medication Summary

As previously mentioned, 1.5% to 3.75% neutral disodium EDTA can be applied to the corneal surface for EDTA chelation in band keratopathy.

Historically disodium EDTA chelation was used; however, it no longer is commercially available and can only be obtained from some compounding pharmacies.

Dipotassium (K2-EDTA) can be prepared using sterile water and a K2-EDTA BD Vacutainer blood collection tube (Becton, Dickinson and Company, Franklin Lakes, NJ). The optimum concentration for K2-EDTA chelation has not been established and there are several methods described for K2-EDTA preparation.^{[18, 19]}

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