What is C3R (Corneal Collagen Cross-linking with Riboflavin) surgery for the cornea?

Corneal Collagen Cross-linking with Riboflavin (C3R) Surgery for Cornea

C3R surgery is a minimally invasive procedure that strengthens the cornea by creating new chemical bonds between collagen fibers using ultraviolet-A light and riboflavin (vitamin B2) as a photosensitizer, primarily used to halt progression of keratoconus and post-refractive surgery corneal ectasia. 1

Mechanism of Action

C3R works through a photochemical reaction:

• Riboflavin (vitamin B2) acts as a photosensitizing agent
• When activated by UVA light (365-370 nm wavelength), it creates reactive oxygen species
• These oxygen species induce formation of new chemical bonds (cross-links) between collagen fibers in the corneal stroma
• The result is increased biomechanical rigidity and stability of the cornea 1, 2

FDA-Approved Indications

• Progressive keratoconus in patients aged 14-65 years
• Corneal ectasia following keratorefractive surgery (such as LASIK) 1

Technique Options

Conventional Dresden Protocol (FDA-approved)

1. Removal of corneal epithelial layer
2. Application of topical 0.1% riboflavin solution every 2-3 minutes for 30 minutes
3. UVA irradiation (3 mW/cm²) for 30 minutes with continued riboflavin application
4. Total procedure time: approximately 60 minutes 1

Alternative Protocols (Under Investigation)

• Accelerated CXL: Uses higher UVA intensity to shorten treatment time
• Transepithelial ("epithelium-on"): Preserves epithelium using agents to increase permeability
• Iontophoresis: Uses small electric current to improve riboflavin penetration without epithelial removal 1, 3

Clinical Outcomes

Effectiveness

• Primary outcome: Halts progression of corneal ectasia in 90+% of cases
• Secondary benefits:
  • Corneal flattening of 1.0-2.5 diopters
  • Improved visual acuity (both uncorrected and corrected)
  • Reduced maximum keratometry values
  • Some reduction in astigmatism 1

Evidence Base

• Phase III FDA approval study showed a 1.6 ± 4.2 D decrease in maximum keratometry at 1 year in treated eyes versus continued progression in control group 1
• Long-term studies confirm that standard Dresden protocol effectively stops keratoconus progression
• European studies have reported significant reductions in corneal transplantation rates since introduction of CXL 1

Safety Profile

Contraindications

• Corneal stromal thickness below 400 μm (risk of endothelial damage)
• Advanced corneal scarring
• History of herpetic keratitis
• Severe corneal infections
• Autoimmune disorders 1

Potential Complications

• Transient corneal haze
• Epithelial healing issues
• Temporary decrease in visual acuity
• Potential endothelial cell density decrease, especially in thin corneas (below 400 μm) 4
• Corneal infections (rare)

Clinical Pearls and Pitfalls

When to Consider C3R

• Early intervention is crucial - treat at first signs of progression rather than waiting until significant visual deterioration
• Consider in pediatric patients with keratoconus, who often have more aggressive disease progression 1

Common Pitfalls to Avoid

1. Delayed treatment: Waiting until corneal thinning progresses too far may result in the patient becoming ineligible for the procedure
2. Inadequate riboflavin saturation: Proper stromal saturation is critical for both treatment effectiveness and endothelial protection
3. Improper patient selection: Patients with very thin corneas require special consideration due to potential endothelial damage 4

Post-procedure Management

• Soft bandage contact lens application
• Antibiotic and anti-inflammatory eye drops
• Preservative-free artificial tears
• Follow-up at 1 week to evaluate epithelial healing, then regular intervals to monitor treatment effect 5

C3R represents a significant advancement in keratoconus management, potentially delaying or eliminating the need for corneal transplantation in many patients while improving visual outcomes and quality of life.