Band Shaped Keratopathy : Introduction, Symptoms, Causes, Diagnosis, Management and Prevention - www.genericdrugscan.com

Band Shaped Keratopathy : Information

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, Bowmans 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 oclock 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 Bowmans 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 Bowmans 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 Bowmans 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:

• Ocular (eye) irritation.
• Foreign body sensation.
• Diminution of vision.
• Lacrimation or watering of eyes.
• Pain.
• Epithelial defects.
• Photophobia (increased sensitivity to light).
• Visible plaque in the eye.
• Redness (less common).]

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:

• Hyperparathyroidism.
• Over treatment for hypoparathyroidism.
• Vitamin D intoxication.
• Sarcoidosis.
• Multiple myeloma.
• Paget s disease.
• Milk-alkali syndrome.
• End stage renal disease: In end-stage renal disease, elevation of either serum calcium, phosphate, or both may disrupt the equilibrium towards precipitation.
• Hypophosphatasia: Hypophosphatasia, an inborn error of metabolism involving decreased alkaline phosphatase activity and resultant hypercalcaemia (less common).
• Tumoral calcinosis: Tumoral calcinosis, a rare syndrome characterised by periarticular calcium deposition, has also been reported as a systemic association (less common).

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:

• Uveitis (chronic iritis in particular, affiliated with Juvenile idiopathic arthritis). In general, the severity of band keratopathy relates directly to the duration of ocular inflammation, though the specific details of the cause and effect relationship between uveitis and corneal mineralisation remains poorly understood.
• Chronic ocular inflammation.
• Absolute glaucoma.
• Chronic corneal oedema.
• Phthisis bulbi.
• Interstitial keratitis.
• Ocular toxicity: Whereas band keratopathy typically develops over months to years, several of these iatrogenic aetiologies demonstrate rapid onset of the corneal changes. Ocular toxicity may be due to:

- 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:

• Chronic inflammation: Chronic keratitis, chronic uveitis of any cause and ocular trauma, along with its accompanying chronic Inflammation, are the most common ocular causes of band shaped keratopathy.
• Mercurial preservatives: Degenerative calcium deposition associated with chronic damage from mercurial preservatives in many ophthalmic preparations viz. long-term use of phenyl-mercuric nitrate preserved miotic therapy,or thiomersal containing artificial tears used for severe dry eye.
• Hypercalcaemia: Hypercalcaemia secondary to milk alkali syndrome, vitamin D toxicity, sarcoidosis, hyperparathyroidism, lytic lesions affecting the bones, and other systemic diseases.
• Raised serum phosphorus levels: Chronic renal failure, uraemia, or other conditions, that may cause a rise in serum phosphorus levels.
• Heredity: Primary hereditary band keratopathy.
• Silicone oil instillation in an aphakic eye.

Pathogenesis:

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:

• An increase in pH
• Increase in local concentration of either ion
• Abrupt loss of solvent (e.g. evaporative loss of aqueous tear layer) or
• Appearance of calcium phosphate crystal nucleus in near supersaturated tissue.

It is surmised that hypercalcaemia alone was likely not sufficient to produce disease. The suggested possible mechanisms may be:

• Abnormalities in the transport and mobilisation of calcium in interstitial fluid: Abnormalities in the transport and mobilisation of calcium in interstitial fluid likely drive deposition.
• Dysfunction of the sodium bicarbonate co-transporter (NBCe1): Dysfunction of the sodium bicarbonate co-transporter (NBCe1) in corneal tissues, sufficiently impairs efflux of bicarbonate from the stroma into the aqueous, thereby raising local pH and predisposing to band keratopathy.
• Localisation of disease to the interpalpebral fissure: Localisation of disease to the interpalpebral fissure, while unrelated to ultraviolet light exposure, may stem from the local effects of evaporative tear film loss.
• Loss of carbon dioxide: Loss of carbon dioxide through diffusion at any exposed mucosal surface would raise local pH and thereby promote deposition. Local pH may explain further the propensity for the crystals to deposit in Bowman s layer and anterior stromal layers, as deeper corneal lamellae have a lower pH due to lactic acid accumulation from anaerobic glycolysis. It is still not clear whether epithelial basement membrane is structurally more conducive to the sudden precipitation of crystalline calcium phosphate.

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.

Clinical history:

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:

• Any systemic disease causing hyperglycaemia.
• Vitamin D intake: Patients should be questioned concerning excessive vitamin D ingestion. Although corneal calcification may be reversible with discontinuation of the vitamin, nephrocalcinosis may still develop.
• Joint pains.

History of ocular conditions:

• Ocular symptoms like Irritation, foreign body sensation, watering or diminution of vision.
• Any history suggestive of chronic uveitis or inflammation of eyes.
• Use of topical eye preparations containing steroid phosphate or mercurial preservatives.
• Silicone eye injection.
• Long standing glaucoma.

Clinical examination:

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.

• Band shaped keratopathy: Initially, corneal degenerative changes are seen concentric with the limbus, either on nasal, temporal or both sides together in exposed palpebral fissure at 3 to 9 o clock position. Calcific band is separated from the limbus by a clear zone (representing a lucid interval). Keratopathy appears as a superficial greyish-white corneal opacity resembling frosted or ground glass, with white flecks and clear spots interspersed within the band, giving it a Swiss cheese appearance. The opacity is covered by clear epithelium with lacunae of uninvolved tissue. Later, the disease progresses toward the corneal center and thickens resulting in more opaque, whitish surface with increased nodularity. Thickened calcium deposits may cause breakdown of the overlying epithelium, resulting in the appearance of spontaneous and recurrent corneal epithelial erosions or epithelial defects.
• Signs of chronic inflammation or uveitis.
• Signs of long standing glaucoma.
• Silicone oil in anterior chamber.

Histopathology:

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:

Laboratory diagnosis may include tests to diagnose any systemic association of band shaped keratopathy such as:

• Serum calcium and phosphate levels.
• Serum parathormone level.
• Renal function tests viz. blood urea nitrogen and creatinine levels.
• Angiotensin converting enzyme levels, x-ray or spiral computerised tomography (CT) scan of chest may be done in suspected cases of sarcoid.

Imaging studies:

Imaging studies may help in a search for lytic lesions affecting the bones.

Calcific band keratopathy should be differentiated from:

• Primary and secondary calcareous degeneration of cornea.
• Spheroidal degeneration or droplet keratopathy which shows band like deposition of hyaline.
• Salzmann nodular degeneration.
• Blood staining of cornea.
• Advanced anterior basement membrane dystrophy of cornea.
• Calciphylaxis: Calciphylaxis is a condition of induced ocular and systemic hypersensitivity reaction, characterised by calcium deposition in response to specific antigens or agents. For example, it takes place in children with uveitis or in patients given calciferol.
• Topical ciprofloxacin solution particle deposition.
• Limbal stem cell deficiency.

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:

• To re-establish normal corneal and limbal topography,
• To improve visual function if there is potential for it, and
• To provide symptomatic relief from recurrent erosions and ulcers.

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.

General measures:

• Diet: Diet may be controlled to prevent excessive absorption and serum elevation of calcium associated with vitamin D intake and milk-alkali syndrome as a measure for band keratopathy.
• Topical artificial tears: Topical artificial tears may be used as ocular surface lubricants in patients with mild symptoms of discomfort.

Medical therapy:

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.

Surgical therapy:

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:

• Visual acuity and future visual potential of the affected eye.
• Health and visual function of the contra-lateral eye.
• Age, level of cooperation, and family support of patient.
• Assurance to the patient about the surgery.
• Although final visual acuity is difficult to predict, patient can expect improved visual function.
• Patient should be prepared for realistic postoperative goals.
• The probability of recurrent corneal disease always exists. Degeneration may recur even bilaterally following corneal transplantation.

Candidates for surgical treatment of band keratopathy are:

• Patients with central or paracentral corneal involvement affecting visual function.
• Band keratopathy causing recurrent epithelial erosions with pain.

Contraindications to surgery:

• Active infectious process such as keratitis: Active infectious process such as keratitis, should be treated first.
• Gross lid abnormalities and mal-positions: Any gross lid abnormalities and malpositions (e.g. ectropion, entropion, or severe seborrhoeic blepharitis) should be treated beforehand, since it alleviates wound healing complications in the postoperative period.
• Herpes disease: It is advisable to proceed cautiously in patients with known herpetic disease. The surgical trauma and postoperative steroids may reactivate an immunologic response. Perioperative treatment with antivirals acyclovir or valcyclovir is recommended to lessen the risk of disease recurrence.

Surgical procedures:

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.

Prognosis:

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.