Band Shaped Keratopathy (Calcific band keratopathy, or band keratopathy) is a non-specific corneal condition characterised by chronic deposition of calcium salts (principally hydroxyapatite) within the basement membrane, Bowman’s layer and anterior stromal lamellae of the corneal epithelium (leaving remainder of the cornea clear). Initially, corneal degenerative changes begin near the limbus, either on nasal, temporal or both sides together in exposed palpebral fissure at 3 to 9 o’clock position. Calcific band is concentric with the limbus but is separated from it by a clear zone (representing a lucid interval) due to lack of Bowman’s layer at the periphery, or due to buffering action at the limbus. Keratopathy appears as a superficial greyish-white corneal opacity having frosted or ground glass appearance. The opacity is covered by clear epithelium with lacunae of uninvolved tissue. There are numerous holes where corneal nerves penetrate the Bowman’s layer. The disease progresses toward the corneal center and thickens as well in its anterior and posterior dimensions, resulting in more opaque, whitish surface with increased nodularity. Calcium deposits thicken and may cause breakdown of the overlying epithelium, resulting in the appearance of spontaneous and recurrent corneal epithelial erosions.
Band shaped keratopathy may occur as isolated condition or in association with a variety of disease entities. The corneal involvement is described as band shaped keratopathy because of the band-like distribution of the deposits across the interpalpebral zone. Unlike band shaped keratopathy, calcareous degeneration usually spares the basement and Bowman’s membrane and is characterised by clumps of calcium salts in the superficial and deep stroma.
Patients with keratopathy may remain relatively asymptomatic for a considerable length of time in early stages of the disease, as long as the central visual axis of the cornea remains clear. With progression of the disease, there is diminution of visual acuity and pain in the eyes due to disruption of the corneal epithelium.
Identification of corneal and conjunctival degenerations has improved with the use of confocal microscopy, immuno-histochemical staining and genetic testing.
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Patients with band shaped keratopathy are asymptomatic in the early stages of the disease.
Patients with band shaped keratopathy may complain of:
Numerous mechanisms, whether systemic or local to the eye, by which the balance of the calcium phosphate solubility product are tilted toward abnormal tissue calcification resulting nonspecific finding of band keratopathy. As such, there are many diseases associated with this condition. Though we tend to think first of conditions such as uveitis and systemic hypercalcaemia, in a recent series the most commonly associated causes of calcific band keratopathy were chronic corneal oedema, phthisis bulbi, and even idiopathic cases.
Systemic disease associations:
Hypercalcaemia (elevated serum calcium level) may be due to:
In some cases, reversal of serum hypercalcaemia through treatment of the underlying disease will lead to spontaneous resolution of band keratopathy within a few months.
Hyperuricaemia: Hyperuricaemia may lead to band keratopathy and is differentiated based on clinical history, the golden-brown colour on examination, and elevated uric acid levels.
Heredity: Primary hereditary band keratopathy.
Association with chronic ocular conditions:
Numerous chronic ocular conditions may similarly predispose to the development of calcific band keratopathy such as:
- Mercurial preservatives: Degenerative calcium deposition associated with chronic damage from mercurial preservatives in many ophthalmic preparations (e.g. phenyl-mercuric nitrate or thiomersal).
- Topical steroid-phosphate preparations.
- Intraocular use of silicone oil.
- Intraocular use of sodium hyaluronate and chondroitin sulphate: Intraocular use of sodium hyaluronate and chondroitin sulphate during routine cataract extraction.
The causes of band shaped keratopathy can be broadly divided into six categories:
Since its first description by Dixon in 1848, much remains elusive regarding the exact pathogenesis of Band keratopathy. It is not clear why the disease typically starts at the limbus with an intervening clear space.
The principal calcium salt deposited in band keratopathy, hydroxyapatite, is a complex crystal composed primarily of calcium and phosphate. The solubility of calcium phosphate in organic tissues in general is quite low and this product exists in a near supersaturated state in blood and interstitial tissue. Disruption of this equilibrium with resultant precipitation of calcium phosphate may readily occur with:
It is surmised that hypercalcaemia alone was likely not sufficient to produce disease. The suggested possible mechanisms may be:
Some have asserted that the limbal vasculature may provide a buffer against pH changes, possibly explaining the commonly noted clear interval of uninvolved tissue at the limbus.
Diagnosis of band shaped keratopathy depends upon clinical presentation.
Patients with band shaped keratopathy are asymptomatic in the early stages of the disease. Symptomatic patients should be enquired about the severity and duration of symptoms.
History of systemic disease:
History of ocular conditions:
A general medical workup is advisable in patients with systemic association of the disease.
Examination of eyes should be carried out under slit lamp (bio-microscopy) by an eye specialist.
There is deposition of calcium in epithelial basement membrane, Bowman’s layer and anterior stroma which is characteristically seen as sub-epithelial basophilic granular degeneration in band shaped distribution with haematoxylin and eosin stain (H&E stain). With disease progression, large calcium phosphate granules, with traces of sulphur and silicone, become confluent and hyaline deposits may be appreciable between layers of redundant, calcified Bowman’s membrane. Masses of eosinophilic amorphous connective tissue insinuate themselves between the fragments of calcified Bowman’s layer and the overlying epithelium, and there is patchy calcification of the anterior lamellae of the stroma. Calcium is also deposited in areas where there are signs of fibroblastic proliferation.
Special stains such as alizarin red or von-kossa stain may be used to confirm the findings.
Laboratory diagnosis may include tests to diagnose any systemic association of band shaped keratopathy such as:
Imaging studies may help in a search for lytic lesions affecting the bones.
Calcific band keratopathy should be differentiated from:
Calcific band keratopathy versus calcareous degeneration of the cornea:
Calcareous degeneration of the cornea usually affects the deep layers as well as the anterior layers. Calcareous degeneration occurs in severely diseased eyes with exposed stroma and vascular compromise or in eyes undergoing multiple operations. It has also been reported in a failed corneal graft. Calcareous degeneration of the cornea as seen in seriously injured eyes, phthisis bulbi, and necrotic neoplasms is often accompanied by bone formation elsewhere in the globe. However, primary calcareous degeneration may occur in the absence of systemic disease or calcium metabolic disturbances. The sub epithelial deposition is bilateral, and occasional bouts of irritation may occur.
Management should be carried out under medical supervision.
Therapeutic goals for the management of band keratopathy are:
Ocular therapy is indicated only if the patient is symptomatic.
Distinguishing local and systemic causes of band shaped keratopathy appropriately outlines treatment options and prognosis for the patient. Removal of the inciting agent in iatrogenic cases or correction of the systemic metabolic disturbance may correct the pathology. Correction of the systemic metabolic disturbance may delay recurrence of the disease after treatment. More so, detection of band keratopathy may occasionally uncover a systemic disease which may be life-threatening.
Superficial debridement or lamellar keratectomy in band keratopathy is usually effective in restoring normal vision. Adverse outcomes such as corneal scarring and vision loss may result from the procedure, but the incidence of such complications is low.
Although medical therapy is ineffective in treating band keratopathy, underlying systemic conditions associated with elevated levels of calcium and phosphate should be treated to prevent recurrence.
The goal of surgery is to remove opaque plaques of calcium, without inducing visually significant stromal scarring.
Prior to surgical management of band keratopathy, it is important to consider:
Candidates for surgical treatment of band keratopathy are:
Contraindications to surgery:
Superficial debridement: The primary goal of superficial debridement is to clear the visual axis. Superficial debridement of band keratopathy can be performed in a sterile manner in outpatient setting preferably under magnification. Though, any local anaesthesia (e.g. proparacaine) may be used, but cocaine as local anaesthetic facilitates the separation of corneal epithelium from Bowman’s layer. This allows ethylenediaminetetra acetic acid (EDTA) to work more effectively.
Corneal epithelium is removed with a blunt spatula from the limbus toward the center (out-to-in or centripetal direction). For difficult areas of calcium, a diamond-burr tip on a Fisch drill may be used.
Following the procedure, irrigate the eye thoroughly to remove EDTA solution from the conjunctival surface and fornices. Pressure patch is applied after cyclopentolate and topical steroid-antibiotic drops or ointment.
Neodymium- doped Yttrium Aluminium Garnet laser (Nd: YAG laser): Calcific band keratopathy can be treated using an Nd: YAG laser. This technique offers advantages of ease of performance, rapid resolution of the patient symptoms, and a smooth corneal surface. It has fallen out of favour with the advent of Argon fluoride excimer laser.
Excimer laser phototherapeutic keratectomy: Excimer laser phototherapeutic keratectomy may be used to polish the irregular corneal surface to make it smooth, after the plaque has been removed. Excimer laser should not be used to remove calcium in band keratopathy. Attempt to remove band keratopathy with the excimer laser alone may result in significant irregular corneal astigmatism, since the cornea may be ablated preferentially. Excimer laser does not differentiate between normal corneal tissue and calcified lesions. Further, the excimer laser ablates normal tissues at faster rates than calcified or scarred lesions.
Lamellar keratectomy: Lamellar keratectomy may be required for more advanced cases. A lamellar keratectomy involving removal of epithelium, Bowman’s layer, and a portion of the anterior stroma, may be performed in cases in which the corneal surface is thickened irregularly and the area of pathology is fairly extensive. It is accomplished with a blade or rotating diamond burr. Any bleeding from associated corneal neovascularisation or interstitial keratitis requires pressure patching or topical vasoconstrictors.
Anterior segment – optical coherence tomography (AS-OCT) or Rotating Scheimpflug imaging technique (measures anterior and posterior corneal surfaces) can help measure the extent of the pathology as well as the expected residual stromal bed.
Bandage contact lens: Bandage contact lens may be used following superficial debridement or lamellar keratectomy. The bandage contact lenses produce significant relief in pain, protect blink disruption of re-epithelialisation, and provide a scaffold for epithelial migration from the limbus.
Amniotic membrane graft: In recalcitrant cases, amniotic membrane graft may be applied to cover and promote healing, particularly when delayed epithelialisation is anticipated, such as in patients with chronic ocular surface inflammation or advanced age.
Amniotic membrane graft can be used as an adjunct therapy after the calcific deposits are surgically or chemically removed. The amniotic membrane graft should include a thick amniotic membrane with basement membrane to promote wound healing and replace the lost basement membrane and stromal matrix. The amniotic membrane should be placed in a ‘’ basement membrane down” orientation so that the basement membrane is in direct contact with the underlying stroma. Amniotic membrane graft is secured with sutures or biocompatible fibrin glue. Graft cannot be used as a sole therapy for band keratopathy.
Patients with band keratopathy may experience diminution of 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.
Unless underlying conditions have been addressed, removing the calcium deposits in band keratopathy will be associated with a high incidence of recurrence. In general, however, superficial debridement or lamellar keratectomy restores vision and comfort for most of the patients with band keratopathy, with the incidence of adverse outcomes following this procedure being very low.