Background

Band keratopathy, also known as corneal calcification, is a degenerative condition affecting the cornea, the transparent front of the eye. It is generally characterized by the deposition of calcium in the corneal tissue, forming a band-like opacity across the cornea. This condition can cause visual disturbances and discomfort for affected individuals.

Band keratopathy usually develops gradually over time and is often associated with underlying systemic or ocular conditions. The most common underlying causes include:

• Chronic Hypercalcemia: Elevated calcium levels in the bloodstream can lead to its deposition in the cornea. This can occur in individuals with hyperparathyroidism, renal failure, sarcoidosis, and vitamin D toxicity.
• Chronic Ocular Inflammation: Long-standing inflammation in the eye, such as uveitis, can trigger the development of band keratopathy. Inflammatory cells release enzymes that promote the deposition of calcium salts in the cornea.
• Intraocular Surgery or Trauma: Certain types of intraocular surgeries or trauma to the eye can disrupt the delicate balance of calcium metabolism in the cornea, resulting in calcification.
• Local Factors: Conditions that affect the ocular surface, such as dry eye syndrome, recurrent corneal erosions, and corneal dystrophies, can predispose individuals to develop band keratopathy.

The symptoms of band keratopathy may vary depending on the extent of corneal calcification and associated conditions. Common signs and symptoms include blurred or decreased vision, a gritty sensation in the eye, redness, and light sensitivity. Sometimes, band keratopathy may be asymptomatic and only detected during a routine eye examination.

Epidemiology

• The incidence rate was nearly 0.14%, which was conducted in a research study on the risk of the band Keratopathy in individuals with End stage renal disease.
• Bullous keratopathies have been observed to occur in approximately 1%-2% of patients going through cataract surgery globally, which translates to an estimated 2 to 4 million individuals globally. A research study revealed that keratopathy was present in 89% of the aniridic eyes.
• In cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, it has been observed that 43% to 89% of individuals develop the chronic ocular complications, with keratopathy being a significant component.
• According to research study conducted by the Bates et al., among 30 cases of keratitis after penetrating keratoplasty, they identified five cases of the infectious crystalline keratopathy.

Anatomy

Pathophysiology

The pathophysiology of band keratopathy involves the abnormal deposition of calcium salts in the cornea, leading to the formation of a band-like opacity. This deposition occurs due to an imbalance in the calcium metabolism within the corneal tissue.

The exact mechanisms underlying the development of band keratopathy are not fully understood, but several factors are believed to contribute to its pathogenesis:

• Metabolic Calcium Imbalance: The cornea typically maintains a delicate balance of calcium metabolism. Under normal conditions, the corneal epithelium actively pumps calcium out of the cornea, preventing its accumulation. In-band keratopathy, this balance is disrupted, leading to an enhance in the concentration of calcium in the cornea.
• Altered Corneal Physiology: Various ocular and systemic conditions can disrupt normal corneal physiology, impairing the cornea’s ability to regulate calcium. Chronic inflammation, as seen in uveitis or other ocular inflammatory diseases, can release inflammatory mediators and enzymes that promote the deposition of calcium salts in the cornea. Similarly, specific ocular surface abnormalities, such as dry eye syndrome or corneal dystrophies, can create an environment that favors calcium precipitation.
• Elevated Calcium Levels: Systemic factors, such as chronic hypercalcemia, contribute to the development of band keratopathy. Conditions like hyperparathyroidism, renal failure, sarcoidosis, and vitamin D toxicity can increase calcium levels in the bloodstream. Elevated calcium levels provide excess calcium that can be deposited in the cornea.
• Corneal Trauma or Surgery: Intraocular surgeries or traumatic injuries to the eye can disrupt normal corneal physiology and induce the formation of band keratopathy. The trauma or surgical intervention can cause damage to the epithelial layer or alter the balance of calcium metabolism, leading to calcium deposition.

The deposition of calcium salts in the cornea typically occurs in the Bowman’s layer, a thin layer between the corneal epithelium and stroma. Initially, the calcium deposits appear as fine granular opacities. Over time, these opacities may merge to form a band-like opacity across the cornea parallel to the limbus.

Calcium deposits within the cornea disrupt average transparency, leading to visual disturbances. The extent and location of the calcium deposition determine the severity of symptoms experienced by affected individuals.

Etiology

Band keratopathy, or corneal calcification, can have various etiological factors. It is often associated with underlying systemic conditions or ocular disorders that contribute to the development of this condition. The primary etiologies of band keratopathy include:

• Hypercalcemia: Elevated calcium levels in the bloodstream, known as hypercalcemia, commonly cause band keratopathy. Hypercalcemia can result from different conditions, such as:
• Hyperparathyroidism: Overactive parathyroid glands can produce excessive parathyroid hormone (PTH), which regulates calcium levels. Increased PTH levels cause calcium levels in the blood, leading to corneal calcification.
• Renal Failure: Impaired kidney function affects the body’s ability to excrete excess calcium, leading to hypercalcemia and subsequent band keratopathy.
• Sarcoidosis: Sarcoidosis is a systemic inflammatory disease affecting multiple organs, including the lymph nodes, lungs, and eyes. In sarcoidosis, the abnormal immune response triggers the release of inflammatory cytokines, leading to hypercalcemia and corneal calcification.
• Vitamin D Toxicity: Excessive intake of vitamin D or its derivatives can cause increased calcium absorption in the intestines, leading to hypercalcemia and subsequent band keratopathy.
• Ocular Inflammation: Chronic inflammation within the eye, known as uveitis, is another significant cause of band keratopathy. Uveitis leads to the release of inflammatory mediators and enzymes that promote the deposition of calcium salts in the cornea. Conditions such as juvenile idiopathic arthritis, Behçet’s disease, and autoimmune uveitis are often associated with band keratopathy.
• Ocular Surface Disorders: Certain ocular surface disorders can contribute to the development of band keratopathy. These include:
• Dry Eye Syndrome: Insufficient tear production or poor tear quality in dry eye syndrome can disrupt normal corneal physiology, leading to calcification.
• Recurrent Corneal Erosions: Recurrent corneal erosions, which involve the repeated breakdown of the corneal epithelium, can trigger chronic inflammation and predispose the cornea to calcium deposition.
• Corneal Dystrophies: Inherited corneal dystrophies, such as lattice dystrophy or Schnyder corneal dystrophy, can result in abnormal calcium metabolism and subsequent band keratopathy.
• Intraocular Surgery or Trauma: Trauma to the eye or certain types of intraocular surgeries can disrupt the corneal tissue and lead to corneal calcification. These can include penetrating injuries, corneal transplants, or intraocular lens implantation.

Genetics

Prognostic Factors

The prognosis of band keratopathy depends on several factors, including the underlying cause, the extent of corneal calcification, and the presence of associated ocular or systemic conditions. Some prognostic factors that can influence the outcome of band keratopathy are as follows:

• Underlying Cause: The prognosis can be influenced by the specific underlying cause of band keratopathy. The prognosis may be more favorable if the underlying cause is treatable or controllable, such as correcting hypercalcemia or managing ocular inflammation. Treating the underlying cause can slow down or halt the progression of corneal calcification and improve visual outcomes.
• Severity and Extent of Corneal Calcification: The extent and density of calcium deposition within the cornea can impact visual acuity and prognosis. If the calcification is limited to a small area and not centrally located, visual impairment may be minimal, and treatment options may be more effective. However, extensive and centrally located calcification can significantly affect vision and may be more challenging to manage.
• Visual Impact: Significant visual impairment during diagnosis can influence the prognosis. If band keratopathy has caused significant visual disturbances, achieving complete vision restoration may be lower. However, early detection and intervention can lead to better visual outcomes.
• Associated Ocular and Systemic Conditions: Additional ocular or systemic conditions can influence the prognosis of band keratopathy. For example, suppose there is a concurrent severe ocular surface disease or underlying systemic disease with a poor prognosis. In that case, it can complicate the management of band keratopathy and impact the overall prognosis.
• Response to Treatment: The response to treatment can also serve as a prognostic factor. Some cases of band keratopathy may respond well to conservative measures, such as lubricating eye drops or topical medications to manage inflammation. However, if conservative measures fail, more invasive interventions like corneal debridement or transplantation may be required, and the success of these procedures can affect the prognosis.

Clinical History

Clinical history

The clinical presentation of band keratopathy can vary depending on the age group, associated comorbidities or activities, and the acuity of presentation. Here’s a general overview:

Age Group: Band keratopathy can affect individuals of any age group, although it is commonly seen in older individuals. The condition can occur in children, adults, and older people.

Physical Examination

Physical examination

During a physical examination of band keratopathy, an eye care professional will assess the cornea and perform various tests to evaluate the extent of corneal calcification and its impact on visual function. Here are some components of the physical examination:

• Visual Acuity Testing: This involves measuring the clarity of vision using an eye chart. Visual acuity is assessed with and without any corrective lenses to determine the level of impairment caused by band keratopathy.
• Slit-Lamp Biomicroscopy: Slit-lamp biomicroscopy is a specialized examination technique that allows detailed examination of the anterior segment of the eye, including the cornea. The eye care professional will use a slit-lamp microscope with a magnifying lens and a narrow beam of light to visualize the cornea.
• Corneal Evaluation: The eye care professional will closely examine the cornea for the presence of calcification. They will observe the calcium deposits’ extent, density, and location. Corneal calcification often appears as a white or grayish band-like opacity parallel to the limbus, the border between the cornea and the sclera.
• Fluorescein Staining: Fluorescein staining involves applying a dye (fluorescein) to the eye’s surface to highlight any irregularities or damage to the cornea. It helps detect corneal erosions or epithelial defects that may be associated with band keratopathy.
• Measurement of Intraocular Pressure (IOP): The eye care professional may measure the intraocular pressure using a tonometer. Elevated intraocular pressure may indicate the presence of associated ocular conditions, such as uveitis, which can contribute to band keratopathy.
• Assessment of Visual Function: In addition to visual acuity testing, the eye care professional may perform additional tests to evaluate visual function. This may include an assessment of contrast sensitivity, color vision, and visual field testing to determine the impact of band keratopathy on overall vision.

It’s worth noting that the physical examination might vary depend on the individual case and the patient’s specific needs. Additional tests or evaluations may be performed to assess the underlying cause of band keratopathy or to rule out any associated ocular or systemic conditions.

Age group

Associated comorbidity

Associated Comorbidity or Activity:

The presence of associated comorbidities or activities can provide additional context to the clinical presentation of band keratopathy. Common conditions or activities associated with band keratopathy include:

Systemic Conditions: Band keratopathy is frequently associated with systemic conditions that cause hypercalcemia, such as hyperparathyroidism, renal failure, sarcoidosis, and vitamin D toxicity.

Ocular Inflammation: Chronic ocular inflammation, such as uveitis, can be associated with the development of band keratopathy.

Ocular Surface Disorders: Conditions affecting the ocular surface, such as dry eye syndrome, recurrent corneal erosions, and corneal dystrophies, can contribute to the development of band keratopathy.
Trauma or Surgery: Band keratopathy can occur following ocular trauma or certain intraocular surgeries.

Associated activity

Acuity of presentation

The acuity of Presentation:

The acuity of presentation refers to the severity or extent of symptoms experienced by the individual. It can vary from mild to severe. Some factors related to the acuity of presentation in band keratopathy include:

Visual Disturbances: Band keratopathy can cause various visual symptoms, such as blurred vision, diminished visual acuity, or distortion. The extent of corneal calcification and its impact on the visual axis determine the severity of visual disturbances.

Asymptomatic Presentation: In some cases, band keratopathy may be asymptomatic and only detected during a routine eye examination. Individuals may not experience any noticeable visual symptoms in these cases.

Gradual Onset: Band keratopathy usually develops gradually over time. As such, the onset of symptoms may be insidious, with individuals noticing a slow progression of visual disturbances.

Differential Diagnoses

Differential Diagnosis

Certain conditions could be included in the differential diagnosis:

• Salzmann’s Nodular Degeneration: Salzmann’s nodular degeneration is characterized by elevated, grayish-white nodules on the cornea. These nodules can resemble the appearance of band keratopathy. However, in Salzmann’s nodular degeneration, the calcium deposits are located in the superficial cornea rather than the Bowman’s layer, as in-band keratopathy.
• Stromal Scarring: Corneal scarring from previous trauma, infection, or corneal ulceration can result in opacities resembling band keratopathy. However, the opacity’s distribution and appearance differ from band keratopathy, and a history of trauma or infection may be present.
• Corneal Dystrophies: Certain corneal dystrophies, such as lattice or Schnyder corneal dystrophy, can cause opacities in the cornea. These opacities can have a band-like appearance similar to band keratopathy. A detailed examination and consideration of the patient’s medical and family history can help differentiate corneal dystrophies from band keratopathy.
• Limbal Girdle of Vogt: Limbal girdle of Vogt is a condition, as it is characterized by the deposition of lipid material around the corneal limbus, resulting in a grayish-white band-like opacity. It can mimic the appearance of band keratopathy but is differentiated by its location and composition.
• Corneal Trauma: Previous corneal trauma, such as a chemical burn or foreign body injury, can lead to corneal opacities that may resemble band keratopathy. The history of trauma and the location of the opacity can help distinguish it from band keratopathy.
• Band-shaped Keratitis: Band-shaped keratitis is a specific type of inflammation that can cause a band-like opacity in the cornea. It is often associated with certain autoimmune conditions, like rheumatoid arthritis or systemic lupus erythematosus. A complete evaluation of the patient’s history and additional clinical findings can aid the differential diagnosis.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The treatment of band keratopathy aims to manage the underlying cause, improve visual function, and alleviate symptoms associated with corneal calcification. The management of band keratopathy can involve various approaches, including modification of the environment, administration of pharmaceutical agents, and intervention with procedures. The specific management phase can vary depending on the severity and extent of the condition. Here’s an overview:

Modification of Environment:

• Lubrication: Using artificial tears or lubricating eye drops can help alleviate dryness and improve corneal surface quality in cases where dry eye syndrome contributes to band keratopathy. Regular application of lubricants can reduce discomfort and promote healing.
• UV Protection: Ultraviolet (UV) radiation can exacerbate corneal inflammation and calcification. Wearing sunglasses with UV protection or using protective eyewear in bright sunlight can help minimize UV exposure and prevent further damage to the cornea.

Administration of Pharmaceutical Agents:

• Chelating Agents: In some cases, chelating agents such as ethylenediaminetetraacetic acid (EDTA) may help dissolve the cornea’s calcium deposits. These agents bind to the calcium ions and promote their removal from the corneal tissue. Topical or subconjunctival administration of chelating agents can be considered, although the efficacy may vary.
• Topical Medications: Anti-inflammatory medications, such as corticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs), may be prescribed to manage associated ocular inflammation and reduce discomfort.

Intervention with Procedures:

• Corneal Debridement: Superficial corneal debridement involves the removal of the superficial layer of the cornea, including the calcium deposits. This procedure aims to improve visual function by smoothening the corneal surface. Corneal debridement may be performed using various techniques, such as scraping or laser ablation.
• Corneal Transplantation: In cases where band keratopathy causes significant visual impairment or if other treatment options have failed, corneal transplantation may be considered. This surgical procedure involves replacing the diseased cornea with a healthy donor cornea. Different types of corneal transplantation may be selected based on the patient’s specific needs, such as penetrating keratoplasty or lamellar keratoplasty.

The phase of Management:

The phase of management can vary depend on the severity and progression of band keratopathy:

• Conservative Management: In mild cases with minimal visual impairment, conservative measures such as lubrication, protective eyewear, and topical medications may be sufficient to manage symptoms and slow the condition’s progression.
• Interventional Management: When band keratopathy is more advanced and causes significant visual impairment, more invasive interventions like corneal debridement or transplantation may be required to restore visual function.

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Future Trends

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References

Risk of Band Keratopathy in Patients with End-Stage Renal Disease – PMC (nih.gov)

[Bullous keratopathy: etiopathogenesis and treatment] – PubMed (nih.gov)

Keratopathy – StatPearls – NCBI Bookshelf (nih.gov)