LAST YEAR, one of our corneal specialists decided to perform LASIK on his 29-year-old brother as a gift. Their initial discussion was full of excitement, as the brother always wanted to see clearly without glasses or contact lenses. During the initial pre-op exam, however, that excitement quickly waned, as corneal topography revealed forme fruste keratoconus.

It was determined corneal collagen cross-linking (CXL) would be beneficial. The reasons: (1) The procedure is designed to halt the corneal ectasia that stems from an abnormal posterior and anterior corneal steepening by strengthening the cornea through rigidity, enzymatic degradation resistance and collagen fiber thickness. (2) The brother was younger than age 40. Corneal ectasia progression is uncommon among those older than 40, so the younger the patient is when diagnosed and CXL is performed, the better off he or she will be.

Here, I provide an overview of the FDA-approved CXL procedures and co-management.

ICD 10
Corneal ectasia, bilateral H18.713
Keratoconus, unspecified H18.60
Peripheral corneal degeneration, unspecified eye H18.469


Although there are two forms of CXL (epithelium on and epithelium off), the FDA has only approved the epithelium off procedure, also known as “epi-off,” which is available via Avedro, a Massachusetts-based pharmaceutical and medical device company.

Specifically, a central area of the cornea is removed via epithelial debridement to expose it. (Patients are given topical anesthesia during this manual process.)

Next, drops of riboflavin solution are instilled every two minutes for 30 minutes. (Different versions of riboflavin are used, some off-label compounded concentrations and Avedro’s FDA-approved solutions.)

Corneal pachymetry is then done to measure the patient’s corneal thickness intraoperatively. If the corneal thickness is 400 µm or higher, UV exposure is started. If the corneal thickness is less than 400 µm, additional riboflavin drops are instilled to achieve greater corneal absorption, which increases corneal thickness.

The final step in CXL is UV exposure, or irradiation, to the cornea. This is accomplished using a device that produces a wavelength of light of 365nm at 3mW/cm2 for 30 minutes. The UV light causes the riboflavin to fluoresce, which creates increased structural bonds between collagen molecules and, thus, strengthens the cornea to cease ectasia progression.


Although O.D.s are not yet permitted to perform CXL, we do have a role in co-management. Specifically, we must have these patients return for follow-up on day 1, day 5, day 14 and day 30.

On day 1, prescribe topical antibiotics (the fluoroquinolone family) q.i.d. to decrease the risk of infection, non-preserved artificial tears to help with healing and patient comfort, a topical steroid to prevent corneal scarring and treat inflammation (tapered through a few weeks) and a topical NSAID q.d. for inflammation and pain.

On day 5, remove the bandage contact lens, which has been placed to accelerate epithelial defect healing, and start monitoring the patient for signs of adverse events, such as endothelial damage. Use the rest of the appointments to monitor healing.

CXL patients can resume wearing glasses after the procedure and contact lenses upon the full healing of the epithelium and discontinuation of steroids. A caveat: Refract the patient once he or she has healed, so you can see whether refractive prescription changes are needed.

Note the inferior steepening on topography.


In the case mentioned above, the corneal specialist’s brother underwent a CXL procedure, and his cornea has maintained its integrity with no increased ectasia, progression of his astigmatism or increased corneal thinning or steepening for more than a year now.

While the brother was disappointed about not getting LASIK, his forme fruste keratoconus makes it possible for him to undergo PRK in the future — something he is looking forward to investigating. OM