A Patient's Guide to Corneal Crosslinking (CXL) for Keratoconus

If you or a loved one has been diagnosed with Keratoconus, you're likely searching for effective treatment options. Corneal Crosslinking (CXL) is often described as a game-changer because it's the only procedure proven to stop the progression of this condition. This guide will walk you through what CXL is, how it works, the different methods available, and the exciting new FDA-approved options.

What is Keratoconus?

Keratoconus is an eye condition where the cornea, the clear, dome-shaped front surface of your eye, gradually thins and bulges outward into a cone shape. This change in shape causes blurry and distorted vision. The reason this happens is that the natural collagen fibers inside your cornea, which should act like supporting beams, are weak.

How Corneal Crosslinking Works

Think of your cornea's collagen fibers as ropes holding up a tent. In Keratoconus, these ropes are loose. The goal of CXL is to tie new knots between these ropes, making the structure much stronger and stiffer so it can resist the pressure that causes the bulging.

The CXL procedure combines two key elements:

• Riboflavin Drops (Vitamin B2): This special liquid is applied to your eye. It acts as a photosensitizer, a substance that reacts strongly to light.
• Ultraviolet A (UVA) Light: Once the riboflavin has saturated the cornea, a controlled beam of UVA light is applied.

When the Riboflavin and the UVA light meet, they trigger a chemical reaction that creates millions of new, strong bonds (crosslinks) between the collagen fibers. This reaction can increase the mechanical strength of the cornea by over 300%, effectively halting the progression of the cone shape.

Below is a diagram illustrating the key difference between the two main procedures:

The Two Main Methods: Epi-Off vs. Epi-On

CXL is generally performed using one of two techniques, named based on how the cornea's outermost layer (the epithelium) is treated. Each method has distinct advantages and recovery periods.

1. Epithelium-Off (Epi-Off) Crosslinking

The Epi-Off technique is the traditional, first-generation CXL procedure and remains a gold standard for many doctors, especially for aggressive cases. It is often referred to by the FDA-approved brand name iLink (using Photrexa solutions and the KXL system).

• The Process: The surgeon first gently removes the thin outer layer of the cornea (the epithelium). This removal is necessary because the epithelium acts as a barrier, preventing the riboflavin from soaking deep into the underlying corneal tissue (the stroma).
• The Benefits: Removing the barrier ensures maximum penetration of the riboflavin, leading to the strongest, deepest crosslinking effect. This is the most established method with the longest follow-up data.
• The Recovery: Because the epithelium is removed, the procedure is essentially creating a large scrape (like an abrasion) on the eye. This results in:
  • Significant Discomfort/Pain: Usually lasts for the first 3 to 5 days until the epithelium heals.
  • Slower Healing: A protective bandage contact lens must be worn until the surface heals. Full visual recovery can take 3 to 6 months.
  • Risk: There is a slightly higher risk of infection or temporary corneal haze during the healing period.

2. Epithelium-On (Epi-On) Crosslinking

The Epi-On (or trans-epithelial) technique leaves the epithelium intact. It is designed to maximize patient comfort and speed up recovery.

• The Process: The epithelium is left in place. New, specially formulated riboflavin drops (like Epioxa) are used, often combined with technologies to enhance penetration and oxygen delivery (as oxygen is critical to the crosslinking reaction).
• The Benefits:
  • Minimal Discomfort: Since the eye's natural protective layer is not removed, there is significantly less pain after the procedure.
  • Faster Recovery: Patients usually return to normal activities much sooner, often within a few days.
  • Lower Risk: The risk of infection or wound-related complications is greatly reduced.
• The Challenge: Historically, the intact epithelium limited the depth and strength of the crosslinking compared to Epi-Off. However, recent FDA-approved technologies are designed specifically to overcome this challenge.

The Latest FDA Approvals: A New Era of Epi-On CXL

For many years, the only FDA-approved CXL procedure in the United States was the Epi-Off technique (iLink with Photrexa). However, this changed recently, marking a significant step forward in patient care.

Initial FDA Approval (2016)

The first FDA approval was granted to Glaukos (formerly Avedro) for the Epi-Off procedure, utilizing the KXL System and the proprietary Photrexa and Photrexa Viscous riboflavin solutions. This remains a highly effective and widely covered treatment option for progressive Keratoconus.

Newest FDA Approval (The Incision-Free Option)

The most recent and groundbreaking FDA approval is for the Epioxa (riboflavin 5'-phosphate ophthalmic solution) drug combination, also by Glaukos, for use in Epithelium-On corneal crosslinking.

• What this Means: Epioxa is the first and only FDA-approved topical drug solution for CXL that does not require the surgical removal of the corneal epithelium.
• The Protocol: The Epi-On procedure using Epioxa involves sequentially administering two riboflavin formulations (Epioxa HD and Epioxa) and then applying the UVA light while delivering supplemental oxygen via a specialized system (such as the O2n System and Boost Goggles).
• For Patients: This is a major advancement, offering a less painful, incision-free alternative with a quicker return to daily life, while still achieving clinically meaningful results in halting disease progression.

What Should You Discuss with Your Doctor?

Corneal crosslinking is a highly personalized treatment. The choice between the Epi-Off and the newer Epi-On procedure depends entirely on your specific condition, including:

• The thickness of your cornea.
• How advanced your Keratoconus is.
• Your tolerance for pain and required recovery time.

The most important step is to have a thorough discussion with your ophthalmologist or cornea specialist. They will evaluate your eye's unique characteristics and recommend the specific FDA-approved protocol (Epi-Off or Epi-On) that offers you the best chance for long-term corneal stabilization.