Combination of cross-linking, intracorneal ring implantation shows synergistic effects in study

Used in conjunction, the two techniques may work together to improve corneal biomechanics and topography.

The combination of collagen cross-linking and implanting an intracorneal ring has a synergistic effect on keratoconus, leading to enhanced visual results and stability, according to a study.

Collagen cross-linking is performed in corneas with proven progressive keratoconus, quantified as a 1 D increase in 6 months, David Touboul, MD, said at the meeting of the French Society of Ophthalmology in Paris. Only patients younger than 35 years with a maximum keratometry of less than 58 D and corneal thickness more than 400 µm are eligible for the treatment. Collagen cross-linking has been shown effective in halting progression of the disease.

Intracorneal ring implantation is also a recognized treatment for keratoconus, improving quality of vision in mild to severe cases. For safe implantation of an intracorneal ring, pachymetry at the site of insertion must be more than 450 µm with a maximum keratometry of less than 60 D.

“In patients with good central optical clearance, progressive keratoconus, central corneal thickness higher than 400 µm and intolerance to contact lenses, we actually recommend the association of [intracorneal ring] and [collagen cross-linking] to postpone or avoid keratoplasty,” Dr. Touboul said.

The two techniques together might act synergistically, improving corneal biomechanics and leading to better corneal topography, he noted.

“We don’t know for sure whether [intracorneal rings] halt the progression of the disease, but [collagen cross-linking] certainly does. On the other hand, [intracorneal rings] have been shown to reduce corneal abnormalities by flattening the ectasia in 80% of the cases, and cross-linking can contribute to this effect,” he said.

Collagen cross-linking and intracorneal rings have complementary effects on the biomechanics of the ectatic cornea. Collagen cross-linking produces modifications of the anterior cornea, while the posterior fibers are unaffected. Intracorneal rings, on the other hand, provide traction and flattening effects on deeper layers.

The double procedure in 34 eyes

The effects of simultaneous treatment with collagen cross-linking and intracorneal rings, either Intacs (Addition Technology) or Ferrara (Ferrara Ophthalmics), were demonstrated in a preliminary study of 34 eyes with keratoconus, mostly stage 2 or 3. The two treatments were performed simultaneously in all eyes. The mean follow-up was 5 months.

Intracorneal ring implantation was performed first, using the IntraLase FS femtosecond laser system (Abbott Medical Optics).

“Performing [intracorneal ring] implantation after [collagen cross-linking] would make the patient uncomfortable with the suction unit,” Dr. Touboul said. “The eye would be cut and tunnelized after disepithelialization, increasing pain and the risk of infection. The optical focalization properties would also be changed.”

Three months postop intracorneal ring segments insertion comparing Ferrara rings above and Intacs down below, with Visante OCT. Cross-linking was performed within the same procedure. In both cases, corneal topography and functional results were significantly improved. Image: Touboul D

The choice between Intacs and Ferrara rings was made on the basis of keratometry, corneal thickness, topographic pattern, degree of astigmatism and the need to drive at night.

“Intacs are very good in case of typical paracentral keratoconus and to regularize horizontal astigmatism. Most of the time, one segment only is enough. Ferrara rings perform better in more advanced keratometric stages, with greater astigmatism and significant thinning asymmetry. If the patient’s main activity is night driving, Ferrara rings are never proposed,” he said.

After intracorneal ring insertion, the pupil was constricted with pilocarpine to protect the inner structures of the eye from the potential damage of excessive UVA exposure. Collagen cross-linking was carried out in a standard fashion.

Postoperatively, patients immediately received dexamethasone and tobramycin drops. A soft contact lens bandage was left in place for 3 days, and lubricating drops in addition to steroid drops were used three times per day for 1 month. Patients were advised not to use rigid contact lenses in the first month and to wear UV protection for the first week.

“We could see interesting topographical changes. All eyes gained two to three BCVA lines. Myopia decreased by about 4.5 D. The [maximum keratometry] was about 4 D less compared to preop, and pachymetry was stable. No significant change in corneal biomechanical properties was measured by the [Ocular Response Analyzer]. Disease progression was halted in all cases,” Dr. Touboul said.

One case of superficial abscess was reported at 1 month, and extrusion occurred in one case at 1 year.

Assessing important points

According to Dr. Touboul, the answer to two questions will be crucial in the future.

“First, we need randomized studies to compare the results of the two separate vs. combined procedures. We are going to start investigating this in a few months. Second, we should perform in vivo evaluation of biomechanical changes — with any kind of elastography technique — to establish whether the two techniques are better performed simultaneously or sequentially,” he said.

In theory, implanting intracorneal rings first facilitates obtaining the desired corneal shape changes before locking them in with collagen cross-linking. It may be beneficial to wait a few months to perform collagen cross-linking after intracorneal ring implantation, because the intracorneal ring effect progresses up to 6 months postop, he said.

On the other hand, if collagen cross-linking increases Young’s modulus with tissue tightening, the impact of intracorneal rings on the corneal shape could be amplified by simultaneous implantation, he noted. – by Michela Cimberle

• David Touboul, MD, can be reached at CHU de Bordeaux, site Pellegrin, centre Xavier François Michelet, place Amélie Raba-Léon Bordeaux, 33000 Bordeaux, France; e-mail: toubould@gmail.com.

The combination of collagen cross-linking and intracorneal ring segments has an additive effect on keratoconus. This combination can be performed sequentially, with the rings first or cross-linking first, or simultaneously. Implanting ring segments first appears to be more logical, because their effect progresses up to 6 months postop. After these changes, cross-linking can be planned.

For several years we have been using intracorneal ring segments to halt keratoconus progression, but recently, since cross-linking has been introduced, we were able to prove that a combination of the two procedures has synergistic beneficial effects. This report encourages surgeons to perform the two treatments simultaneously rather than implanting the ring segments first and then, after a few months, tightening the cornea with cross-linking.

There is a need for randomized studies with a longer follow-up to compare different time intervals between the two procedures, to assess the safety and efficacy of simultaneous vs. sequential treatments and to evaluate the advantages and disadvantages of performing intracorneal ring segment implantation followed by collagen cross-linking or vice versa.

– Aylin Kilic Uzbek, MD
Kudret Eye Hospital, Ankara, Turkey