Managing Keratoconus: A Surgeon’s Approach to Corneal Cross-Linking

Introduction to Corneal Cross-Linking

Corneal cross-linking (CXL) is a revolutionary procedure designed to treat keratoconus and other corneal ectatic disorders. It involves the use of ultraviolet A (UVA) light and riboflavin (vitamin B2) to strengthen the collagen fibers in the cornea, thereby halting the progression of these conditions. Since its introduction, CXL has become a cornerstone in the management of keratoconus, providing an effective and minimally invasive option for patients at risk of progressive vision loss.

Indications for Corneal Cross-Linking

CXL is primarily indicated for patients with progressive keratoconus, which is characterized by the thinning and bulging of the cornea, leading to irregular astigmatism and visual impairment. The procedure is also used in the management of other ectatic conditions, including:

• Post-LASIK Ectasia: A rare but serious complication following laser-assisted in situ keratomileusis (LASIK) surgery, where the cornea begins to weaken and bulge after the procedure.
• Pellucid Marginal Degeneration (PMD): A degenerative corneal condition that causes thinning in a crescent shape at the inferior periphery of the cornea.
• Corneal Ulcers and Infections: CXL has been explored as an adjunctive therapy for infectious keratitis, particularly in resistant cases, due to its antimicrobial properties.

Preoperative Evaluation

Before proceeding with CXL, a thorough preoperative evaluation is essential. This includes:

1. Patient History: A detailed history should be obtained to confirm the diagnosis of keratoconus or other ectatic conditions. The progression of the disease should be documented, and any previous ocular surgeries or conditions should be noted.
2. Visual Acuity Assessment: Baseline visual acuity should be measured, including best-corrected visual acuity (BCVA) with spectacles or contact lenses.
3. Corneal Topography: This imaging technique maps the surface curvature of the cornea and is critical in assessing the degree of ectasia and monitoring disease progression.
4. Pachymetry: Corneal thickness measurement is crucial as it determines eligibility for the procedure. A minimum corneal thickness of 400 micrometers is generally required to proceed with CXL to avoid potential damage to the endothelial cells.
5. Slit-Lamp Examination: This allows for the evaluation of the anterior segment of the eye, checking for signs of scarring, thinning, or other abnormalities that might contraindicate the procedure.
6. Informed Consent: Patients should be fully informed about the nature of the procedure, potential risks, and expected outcomes. It is important to set realistic expectations, particularly regarding the halting of disease progression rather than a significant improvement in visual acuity.

Contraindications

While CXL is a valuable tool in the management of corneal ectasias, certain contraindications must be considered:

• Corneal Thickness Less Than 400 Micrometers: As mentioned, inadequate corneal thickness increases the risk of damage to the endothelium and other deeper ocular structures.
• Active Ocular Infections or Inflammation: Any active infection or inflammation must be treated and resolved before considering CXL to avoid exacerbating the condition.
• Severe Corneal Scarring: Significant scarring may limit the effectiveness of the procedure and could be an indication for alternative treatments.
• Autoimmune Disorders: Patients with autoimmune conditions affecting the eye may have a higher risk of complications, and CXL should be approached with caution.
• Pregnancy: Due to potential risks to the developing fetus and changes in corneal physiology during pregnancy, CXL is typically deferred until after delivery.

Surgical Techniques and Steps

There are two main types of CXL: epithelium-off (epi-off) and epithelium-on (epi-on), also known as transepithelial CXL. The choice between these techniques depends on various factors, including corneal thickness, the extent of ectasia, and surgeon preference.

1. Epithelium-Off (Epi-Off) Technique

This is the traditional and most widely used method.

Steps:

1. Topical Anesthesia: The procedure is performed under topical anesthesia to ensure patient comfort.
2. Epithelial Removal: The corneal epithelium is carefully removed to allow better penetration of riboflavin into the stroma.
3. Riboflavin Application: Riboflavin drops are applied to the cornea every 2-5 minutes for approximately 30 minutes. This step ensures adequate saturation of the corneal stroma with riboflavin.
4. UVA Irradiation: The cornea is exposed to UVA light (typically 365-370 nm) for about 30 minutes. During this time, riboflavin continues to be applied intermittently.
5. Postoperative Care: A bandage contact lens is placed on the eye, and patients are prescribed antibiotics and anti-inflammatory drops to prevent infection and reduce inflammation.

2. Epithelium-On (Epi-On) Technique

This technique preserves the corneal epithelium, potentially reducing discomfort and recovery time.

Steps:

1. Topical Anesthesia: Similar to the epi-off technique, topical anesthesia is administered.
2. Riboflavin Application: Riboflavin drops are applied over the intact epithelium. Special formulations or enhancers may be used to improve riboflavin penetration.
3. UVA Irradiation: UVA light is applied as in the epi-off technique.
4. Postoperative Care: Similar postoperative care is provided, with the addition of lubricating drops to aid epithelial healing.

Postoperative Care

Postoperative management is critical for ensuring optimal outcomes and minimizing complications. Key aspects include:

• Bandage Contact Lens: This is typically worn for several days to protect the cornea and reduce discomfort. It is removed once the epithelium has healed, usually within 3-7 days.
• Medications: Patients are prescribed topical antibiotics to prevent infection and corticosteroids to control inflammation. The duration of corticosteroid use may vary depending on the individual case.
• Pain Management: Mild to moderate discomfort is common in the first few days postoperatively. Oral analgesics may be prescribed if necessary.
• Follow-Up Visits: Regular follow-up appointments are essential to monitor healing, detect any complications early, and assess the effectiveness of the procedure.

Possible Complications

While CXL is generally safe, complications can occur. These include:

• Corneal Haze: Temporary haze is common and usually resolves over several weeks to months. Persistent haze, however, may require further intervention.
• Infection: Though rare, postoperative infections can occur, emphasizing the importance of strict adherence to postoperative care instructions.
• Endothelial Damage: This is a risk particularly in cases where the cornea is too thin or the UVA dosage is too high.
• Delayed Epithelial Healing: Prolonged healing of the epithelium can occur, particularly in the epi-off technique.
• Sterile Infiltrates: These may appear as white spots in the cornea and are generally treated with topical corticosteroids.

Different Techniques and Innovations

Several modifications and innovations in CXL techniques have emerged to enhance the procedure’s effectiveness and safety:

• Accelerated CXL: This approach reduces the treatment time by increasing the intensity of the UVA light. While the procedure time is shorter, studies are ongoing to determine if the outcomes are equivalent to the standard protocol.
• Customized CXL: This technique tailors the UVA irradiation pattern to the individual corneal topography, potentially providing a more targeted treatment.
• Pulsed-Light CXL: Pulsed application of UVA light may allow for better oxygenation of the corneal tissue during the procedure, potentially improving outcomes.

Prognosis and Outcome

The primary goal of CXL is to halt the progression of keratoconus and other ectatic disorders. In most cases, the procedure successfully stabilizes the cornea, preventing further deterioration in vision. Some patients may also experience a modest improvement in visual acuity, particularly in terms of reduced irregular astigmatism.

Long-term studies have demonstrated the durability of CXL, with many patients remaining stable for up to 10 years post-procedure. However, it is important to note that CXL does not reverse existing corneal deformation, and patients with advanced keratoconus may still require additional interventions, such as corneal transplantation.

Alternative Options

For patients who are not candidates for CXL or who have advanced disease, alternative treatments include:

• Intrastromal Corneal Ring Segments (ICRS): These are small plastic inserts placed within the cornea to flatten its shape and reduce irregular astigmatism.
• Corneal Transplantation: In cases of severe keratoconus with significant scarring or thinning, penetrating keratoplasty (full-thickness transplant) or deep anterior lamellar keratoplasty (DALK) may be necessary.
• Phakic Intraocular Lenses (IOLs): These lenses are implanted inside the eye to correct high degrees of refractive error associated with keratoconus.

Average Cost of Corneal Cross-Linking

The cost of CXL varies depending on geographic location, the type of technique used, and whether the procedure is covered by insurance. On average, the cost ranges from $2,500 to $4,000 per eye in the United States. Patients should be informed about the cost and potential for additional expenses related to postoperative care and follow-up.

Recent Advances

Recent research in CXL has focused on improving the procedure's safety and effectiveness. Innovations include:

• Photoactivated Chromophore for Keratitis (PACK-CXL): This is an adaptation of CXL for treating infectious keratitis. PACK-CXL enhances the antimicrobial effects of UVA and riboflavin, offering a potential alternative to antibiotics, especially in resistant cases.
• Combined Procedures: CXL is increasingly being combined with other procedures, such as ICRS implantation or refractive surgery, to address both ectasia and refractive errors simultaneously.

Conclusion

Corneal cross-linking has revolutionized the management of keratoconus and other ectatic disorders. By halting the progression of these conditions, CXL offers hope to patients at risk of significant vision loss. With ongoing advancements in techniques and technology, CXL continues to evolve, promising even better outcomes for patients in the future.