Trans-epithelial Versus Epithelium-off Corneal

Cross-linking for the Treatment of Progressive

Keratoconus: A Randomized Controlled Trial

NIENKE SOETERS, ROBERT P.L. WISSE, DANIEL A. GODEFROOIJ

AMERICAN JOURNAL OF OPHTHALMOLOGY, MAY 2015

PURPOSE

To compare the clinical effects and safety of trans-epithelial corneal cross-

linking (CXL) to epithelium-off (epi-off) CXL in progressive keratoconus.

DESIGN: Randomized clinical trial (noninferiority).

METHODS: Patients received either trans-epithelial CXL with Ricrolin TE (n [ 35) or epi-off CXL with isotonic riboflavin (n [ 26)

in 1 academic treatment center, using a simple unrestricted

randomization procedure. The main outcome measure was

clinical stabilization of keratoconus after 1 year, defined as a

maximal keratometry (Kmax) increase <1 diopter (D).

SURGICAL TECHNIQUE:

In the trans-epithelial CXL group

Local anesthetic eye drops (oxybuprocaine 0.4% and tetracaine 1%)

were applied 3 times during 5 minutes, and Ricrolin TE solution (consisting

of riboflavin 0.1% eye drops with Dextran T500 15 mg and EDTA; SOOFT

Italia) were instilled every 2 minutes for 15 minutes. Next, an eyelid

speculum was placed and a silicone ring was positioned between the eyelids; the ring was filled with Ricrolin TE and used to retain a Ricrolin

‘‘pool’’ on the cornea. After 15 minutes, the silicone ring was removed,

the cornea was rinsed with balanced salt solution, and pachymetry was

performed. UVA irradiation was performed during 30 minutes, while

Ricrolin TE solution was reapplied to the cornea every 5 minutes.

Epi-off CXL technique

was performed following the Dresden protocol, adjusted with the

avoidance of the eyelid speculum during riboflavin instillation. Epithelial

removal (9-mm) was performed using a blunt knife. After pachymetry

measurements, isotonic riboflavin 0.1% solution with 20% Dextran (Medio

Cross) was applied every 3 minutes for 30 minutes, with no eye lid

speculum in place

RESULTS

Average Kmax was stable at all visits in the transepithelial group, while after epi-off CXL a significant flattening of 1.2–1.5 D was demonstrated from the 3-month follow-up onwards. The trend over time in Kmax flattening was significantly different between the groups.

There was significant different trend in corrected distance visual acuity (CDVA), with a more favorable outcome in thetransepithelial group.

In the transepithelial group no complications were observed while in epi-off group, 4 eyes (15%) developed complications owing to healing problems (sterile infiltrate, herpes keratitis, central haze, and stromal scar).

DISCUSSION

This trial showed that transepithelial cross-linking with EDTA riboflavin* was

less effective to halt keratoconus progression after 1 year compared to

epithelium-off cross-linking.

indicators for a CXL effect

General indicators (with stabilization being the main purpose) are a

1. visible demarcation line,

2. a flattened keratometry, and

3. reduced pachymetry.

No demarcation line was found in the transepithelial CXL group and the

average central keratometry, maximal keratometry, and pachymetry were

unchanged after treatment.

The average Kmax flattening after 1 year in the epi-off group in this study

was more pronounced (-1.5 D).

CONCLUSION

This study showed that although transepithelial CXL was a safe procedure

without epithelial healing problems, 23% of cases showed a continued

keratoconus progression after 1 year