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To Make a Smart Decision, You Need to Understand Epithelium-On versus Off

Why Was the Epithelium Scraped Off for Epithelium-Off CXL in the 1990s? 

Technology was not available to get Vitamin B2 (Riboflavin) into the cornea without removing the epithelium 

Note no green riboflavin in the cornea (arrow)

Dr. Rubinfeld and his teams patented systems to get green riboflavin (arrow) into the cornea without epithelium removal

Epithelium-Off Crosslinking

In Epithelium-Offcrosslinking, the protective front surface (epithelium) of your cornea is surgically taken off to get Vitamin B2 into the cornea- a more invasive procedure with slower recovery, more pain, and more risks.

Scraping off the corneal epithelium to get vitamin B2 into the cornea

Scrub brush surgically removing  the epithelium in Epi-Off CXL

Epithelium-On Crosslinking

1 day after Epithelium-On CXL.
The epithelium is clear and intact.

4 days after Epithelium-Off CXL. Green stain shows where the epithelium is missing.

Re:Vision no longer performs the older Epithelium-Off type of crosslinking. 

Dr. Rubinfeld and his teams invented effective ways to get riboflavin into the cornea without scraping off the epithelium.


Epstein; Cornea 2023, Hersh; Ophthalmology, 2017

How the Eye Works

Light enters the Cornea and Pupil of the eye. If you can’t see clearly through the pupil because of cornea damage like infections or scars your vision suffers.

Side View
Front View

Published complications after Epithelium-Off crosslinking include:

Delayed Healing of Epithelium after Surgical Removal for Epi-Off CXL

Cagil, N., et al., Mechanical epithelial removal followed by corneal collagen crosslinking in progressive keratoconus: short-term complications. J Cataract Refract Surg, 2015. 41(8): p, 730-7.

When the Epithelium is not surgically removed and left “On” in Epithelium On CXL, it doesn’t need to heal and grow back. 

Staph Infection Days after Epi-Off CXL 

Shetty, R., et al., Profile of microbial keratitis after corneal collagen cross-linking. Biomed Res Int, 2014. 2014: p. 340509.

When the Epithelium is not surgically removed and left “On” in Epithelium On CXL, it doesn’t need to heal and grow back. 

Infection of Cornea and Melting after Epi-Off CXL

Shetty, R., et al., Profile of microbial keratitis after corneal collagen cross-linking. Biomed Res Int, 2014. 2014: p. 340509.

Long Term Corneal Haze after Epi-Off CXL

Ameba Corneal Infection After Epi-Off CXL

Rama, P., et al., Acanthamoeba keratitis with perforation after corneal crosslinking and bandage contact lens use. J Cataract Refract Surg, 2009. 35(4): p. 788-91.

The cornea developed a hole in it requiring emergency surgery.

According to the Inventors of Epithelium-Off CXL:

  • Corneal Scarring up to 2.8%
  • Corneal Infiltrates up to 7.6%
  • Failure of Treatment, Continued Worsening 7.6%
  • Corneal Haze up to 90%

Medical Literature on Our Less Invasive Epithelium-On CXL:

NO (Zero) Serious Adverse Events in Thousands of Eyes Since 2012 

  • NO serious adverse events from treatment in 2,228 subjects in this FDA Phase 2 trial; Cornea, 2022.
  • NONE in another study of 592 eyes; JCRS, 2018.
  • NONE in other similar clinical  trials involving many thousands   of people
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