Band Keratopathy

Background

Band keratopathy is characterized by the appearance of an opaque white band of variable density across the central cornea, formed by the precipitation of calcium salts on the corneal surface (directly under the epithelium).^[1] This form of corneal degeneration can result from a variety of causes, either systemic or local, with visual acuity decreasing in proportion to the intensity of the deposition (see the image below). (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 generally restores vision and comfort for most patients with band keratopathy, although failure to manage the source of the condition often leads to recurrence. (See Prognosis, Treatment, and Medication.)

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Etiology

Corneal deposition of calcium salt

Serum and normal body fluids (eg, tears, aqueous humor) contain calcium and phosphate in concentrations that approach their solubility product. Evaporation of tears tends to concentrate solutes and to increase the tonicity of tears; this is especially true in the intrapalpebral area, where the greatest exposure of the corneal surface to ambient air occurs. Elevated serum calcium or serum phosphate can tip the balance in favor of precipitation.

In addition, elevation of the surface pH out of the physiologic range changes the solubility product and favors precipitation. This type of tissue pH change can be seen in chronically inflamed eyes and may explain why patients of all ages with uveitis are at risk for the development of band keratopathy.^{[2, 3, 4]}

Endothelial function may also play a role in calcium deposition. Compromise of endothelial function and corneal edema are sometimes seen in patients who have silicone oil inside the eye, when the oil comes into contact with the posterior cornea. The exact reasons for this association remain uncertain.^{[5, 6]}

Band keratopathy was one of the main long-term complications (8% of patients) in a study of 50 ophthalmologic patients treated with silicone oil in whom the oil remained inside the eye for an unusually long period of time (median, 30 months).^[7]

Systemic risk factors

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

• Hyperparathyroidism
• Excessive vitamin D intake
• Renal failure^[8]
• Hypophosphatasia
• Milk-alkali syndrome
• Paget disease
• Sarcoidosis

Discoid lupus erythematosus and tuberous sclerosis are other systemic conditions associated with band keratopathy.

Local ocular risk factors

Local ocular conditions associated with band keratopathy include the following:

• Chronic uveitis
• Juvenile idiopathic arthritis with uveitis
• Phthisis bulbi
• End-stage glaucoma^[9]
• 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]
• Pilocarpine-containing, mercury-based preservatives
• Viscoelastic agents - Rare, early formulations; may be related to phosphate buffers
• Silicone oil
• Topical medications containing phosphate buffers - Especially in the setting of chemical eye burns^[11]
• Intraocular use of tissue plasminogen activator^[12]

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  Calcium deposition associated with the use of dexamethasone phosphate. The calcium plaques appear as elevated white lesions at the edge of a persisten....

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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.

   

  

   

Chemical fume ̶ related risk factors include the following:

• Mercury vapor
• Calcium bichromate vapor

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Prognosis

Patients with band keratopathy may experience a decrease in vision as the deposition progresses across the visual axis. A foreign body sensation and irritation associated with an irregular surface are common symptoms. The ocular discomfort may worsen to the point of becoming disabling, especially as smaller segments of the plaque loosen and become partially mobile. The plaque itself often is visible and of cosmetic concern to the patient and family members.

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 will be associated with a high incidence 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
• Redness (occasionally)
• Photophobia

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, plaquelike deposition that occurs in a band across the cornea. The very periphery of the cornea may be spared because of 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 may be very fine or thick and plaquelike. When it is thick, it may partially flake off, particularly in the plaque periphery, causing epithelial defects and painful symptoms.

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Approach Considerations

Laboratory Studies

Patients who present with band keratopathy should have a serum calcium and phosphate level drawn unless the deposition has been documented previously and the underlying cause is known.

Renal function tests, such as blood urea nitrogen (BUN) and creatinine, should be performed as well. Renal failure and the need for dialysis can be associated with an elevation in serum phosphate and calcific band keratopathy.^{[14, 15]}

If sarcoid is suspected, angiotensin-converting enzyme (ACE) testing, chest radiography, or chest spiral CT scanning should be obtained. In otherwise idiopathic cases, parathyroid hormone levels should be checked.

Histologic Findings

Band keratopathy is characterized by calcium deposition involving the Bowman layer and the superficial stroma of the cornea. 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.

Calcium is deposited intracellularly when hypercalcemia is the cause; extracellular deposits are characteristic of local ocular disease.

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Approach Considerations

Superficial debridement or lamellar keratectomy in band keratopathy is usually effective in restoring normal vision. Various adverse outcomes can result from the procedure, including corneal scarring and vision loss, but the incidence of such complications is very low. Although medical therapy is ineffective in treating band keratopathy, underlying conditions associated with elevated levels of calcium or phosphate should be treated to prevent deposition from recurring.

Diet

Excessive vitamin D intake has been associated with band keratopathy, as has milk-alkali syndrome. Excessive absorption and serum elevation of calcium is the consequence of these 2 diet-related problems.

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Superficial Debridement and Lamellar Keratectomy

Superficial debridement can be performed in a minor operating room under topical anesthesia. Proparacaine or tetracaine drops can be used for this purpose. Use of an operating microscope is recommended.

Procedure

Place a lid speculum to hold open the eyelids, and debride the epithelium overlying the calcium with an ophthalmic surgical blade or spatula.

Apply 0.05 mol, 1.5% neutral disodium ethylenediaminetetra-acetic acid (EDTA) to the corneal surface, if available. Weck-cel sponges soaked in this solution can be used for this purpose. Alternatively, the solution can be placed in a water bath over the cornea to limit ocular exposure.

Calcium deposits are then removed with firm scraping of the corneal surface with a blunt spatula or a No. 64 or No. 69 Beaver Blade. (A Paton spatula works well.) 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 come off in 5 minutes, while thick plaques may take 30-45 minutes to dissolve.

Once the deposits have been scraped, 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 to polish the surface after the plaque has been removed.^[16]

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 with retrobulbar anesthesia and operating-room control of the surgical field. These procedures are best 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. Facilitation of calcium removal with the application of EDTA has been recommended in the past but has fallen from popularity owing to a lack of controlled trials, the absence of extensive case series, and difficulties in obtaining the EDTA from compounding pharmacies.

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

A therapeutic bandage soft contact lens (CTL) is instrumental in recovery following debridement or lamellar keratectomy. The CTL provides significant pain relief, protection from blink disruption of re-epithelialization, and a scaffold for epithelial migration from the limbus.

A sutureless amniotic membrane can be applied to enhance healing, particularly when delayed epithelialization is anticipated, such as in patients with neurotrophic disease, chronic ocular surface inflammation, or advanced age.

Postoperative care

Postoperative care includes the insertion of a bandage contact lens that is left in place until the epithelium heals. Topical nonsteroidal agents are useful for pain control immediately following the procedure and for the first few days afterwards.

An antibiotic drop should be prescribed with the bandage contact lens 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 are often present in the early postprocedure period. These medications can be stopped when the epithelium is healed and the bandage contact lens is removed (usually within the first 1-2 wk).

Complications

The main complications related to the removal of calcium deposits on the corneal surface include the following (it is also possible that additional procedures will be needed):

• Pain
• Recurrence of the calcium band
• 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 resolve on its own. 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

The goals of pharmacotherapy are to reduce plasma calcium levels, to prevent complications, and to reduce morbidity. As previously mentioned, 0.05 mol, 1.5% neutral disodium EDTA can be applied to the corneal surface to aid in superficial debridement for band keratopathy. Weck-cel sponges soaked in this solution can be used for this purpose, or the solution can be placed in a water bath over the cornea to limit ocular exposure. After debridement, the eye should be thoroughly irrigated to remove EDTA solution from the conjunctival surface and fornices.

Lee et al (2018) described another source of EDTA for use in the treatment of band keratopathy. Dipotassium-EDTA (K2-EDTA) is often used in blood draw tubes; EDTA can be obtained by rinsing these tubes with balanced salt solution and collecting the fluid. Calcific band keratopathy has been successfully treated using this solution.^[17]

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Edetate calcium disodium

• Dosing, Interactions, etc.

Clinical Context:  This compound chelates with many divalent and trivalent metals. Because of its affinity for calcium, it lowers serum calcium levels during intravenous (IV) infusion. Slow infusion causes mobilization of extracirculatory calcium stores. Edetate calcium disodium also chelates with other polyvalent metals, therefore increasing urinary excretion of magnesium, zinc, and other trace elements. Although it does not chelate with potassium, it may reduce the serum potassium level. Do not use this medication for lead toxicity.

Edentate calcium disodium is indicated for the emergency treatment of hypercalcemia but is rarely used, since newer drugs are now available to treat this indication. It must be specially compounded and buffered for topical formulation. This medication is not indicated for the treatment of band keratopathy or recovery after superficial or lamellar keratectomy.

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Class Summary

Some agents in this drug category can lower serum calcium levels.

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