Accelerated Crosslinking Effective for Keratoconus

Laird Harrison

January 12, 2017

Accelerated transepithelial corneal crosslinking safely and effectively treats progressive keratoconus, researchers say.

Using increased illumination intensity, the technique achieves crosslinking in a few minutes rather than the hour required for the conventional procedure, write Wei Aixinjueluo, MD, and colleagues from the Department of Ophthalmology at the University of Tokyo in Japan.

"We observed faster recovery, and a reduced rate of complications and operative and postoperative discomfort related to epithelial removal," they write in an article published online January 5 in the British Journal of Ophthalmology.

Keratoconus causes progressive thinning and distortion of the cornea that can result in myopia, astigmatism, and even blindness. Corneal collagen crosslinking halts the progress of keratoconus by strengthening chemical bonds in the cornea. Successful crosslinking can avert the need for a corneal transplant.

The US Food and Drug Administration approved a riboflavin ophthalmic solution (Photrexa, Avedro) for use in the procedure in April 2016, as reported by Medscape Medical News. The procedure gained earlier approval in Europe and Asia.

In the conventional procedure, commonly called the Dresden protocol, surgeons remove the epithelium, apply photosensitizing riboflavin drops for 30 minutes, then expose the cornea to ultraviolet A (370 nm at an irradiance of 3 mW/cm2 radiation at 1-cm distance for 30 minutes with a total energy of 5.4 J/cm.

This approach has been shown to increase corneal stiffness by up to 328.8% and to flatten and regularize the cornea in many patients. This in turn can reduce myopia and astigmatism.

But removing the epithelium can cause infections, corneal haze, corneal edema, sterile infiltrates, and intense pain. To avoid this, researchers have increased the transepithelial penetration of riboflavin solutions by adding enhancers such as benzalkonium chloride, tetracaine, surfactants, ethylenediaminetetraacetic acid (EDTA) and trometamol.

The modified procedure offers particular benefits to patients who are sensitive to the possible effects of epithelial debridement and patients with central corneal thickness of less than 400 μm, Dr Aixinjueluo and colleagues report.

In addition, recently introduced devices can accelerate the operation time by increasing the intensity of illumination.

To examine the safety and effectiveness of this approach, the researchers tested it on 30 eyes of 19 patients, 16 male and 3 female, with a mean age of 24.9 years.

All the patients were older than 14 years of age, and all had evidence of progressing keratoconus and corneal thickness measuring at least 380 μm at the thinnest point.

After administering 4% lidocaine as a topical anesthetic, the researchers applied 0.25% riboflavin with benzalkonium chloride, EDTA, trometamol, hydroxypropyl-methylcellulose (ParaCel, Avedro) for 4 minutes, and 0.25% riboflavin solution (VibeX Xtra, Avedro) for 6 minutes. They applied an additional drop every 90 seconds during the soak time.

They then treated corneas at 370-nm wavelength at an irradiance of 30 mW/cm2 for 3 minutes, delivering a dose of 5.4 J/cm2 without corneal epithelial debridement. They also applied a drop of 0.25% riboflavin solution (VibeX Xtra) every 90 seconds during the irradiation.

After the irradiation, they instilled optical antibiotic ointment (0.3% ofloxacin) and applied an eye bandage for 1 day. Patients used a topical antibiotic and corticosteroid (1.5% levofloxacin, 0.1% fluorometholone) for a week.

The results are promising, the researchers report. Log10 minimum angular resolution (logMAR) best corrected visual acuity (BCVA) scores improved, reaching 0.96 ± 0.57 at 1 week and 0.91 ± 0.52 at 12 months (P = .001).

Maximum keratometry (Kmax) also improved, reaching 61.43 ± 9.95 D at week 1 and 58.11 ± 9.40 D at 12 months (P < .0001).

There was no significant change in average keratometry (AveK) until month 3, when it reached 52.17 ± 7.76 D. The improvement continued to month 12, when it reached 51.38 ± 7.32 D (P = .003).

In four eyes of two patients younger than 18 years, the Kmax, AveK, and BCVA showed no deterioration at 12 months.

Endothelial cell density showed no significant change through month 12, when it was measured at 2857.4 ± 246.2; P = .922).

Central corneal thickness showed no significant change at month 12. Thinnest corneal thickness did not change until the sixth month, when it reached 398.7 ± 55.2 μm (P = .002). At month 12 it was 398.6 μm (P = .002).

Patients reported no postoperative corneal haze, corneal edema, sterile infiltrates, or infection. Their intraocular pressure and fundus showed no significant changes. Pain lasted no more than 1 week.

The outcomes were similar to those of other studies of corneal crosslinking for keratoconus, the authors wrote.

They acknowledged some limitations to their study, including a small sample size, a short follow-up time, and the lack of a control group.

It was not possible to assemble a control group, they explained, because the surgeons customarily explain the pros and cons of the accelerated and standard procedures, and patients generally opt for the accelerated procedure.

The authors have disclosed no relevant financial relationships.

Br J Ophthalmol. Published online January 5, 2017. Abstract

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