Better Outcomes for CXL Treated Patients

Recommendations focus on optimising CXL efficacy and performing safe post-CXL visual rehabilitation. Cheryl Guttman Krader reports from the 39th Congress of the ESCRS in Amsterdam

Optimising outcomes for patients undergoing corneal cross-linking (CXL) for progressive keratoconus or postLASIK ectasia involves strategies implemented during and after the CXL procedure, said Theo G Seiler Jr, MD.

“Customisation of the ultraviolet A (UVA) light irradiation pattern and increasing the availability of oxygen during CXL can improve the efficacy of the CXL. Additional wavefront-guided photorefractive keratectomy (WFG PRK) targeting reduction of selected higher-order aberrations (HOAs) is a powerful treatment option when contact lens-intolerant patients seek functional vision improvement,” Dr Seiler said.

Discussing how to improve the results of the CXL procedure, Dr Seiler focused on increasing oxygen availability to the corneal tissue to increase aerobic reaction throughout the intended stromal depth.

“Oxygen is definitely the bottleneck for achieving sufficient CXL. In 2013, Richoz [et al.] showed by measuring Young’s modulus that CXL is insufficient if the procedure is performed without oxygen. Performing the procedure by providing a 100% oxygen environment can optimise the results,” he said.

In a laboratory study published in 2021,i Dr Seiler and colleagues measured oxygen concentrations at corneal depths of 100, 200, and 300 μm during CXL performed under normoxic (21% oxygen) or hyperoxic (100% oxygen) conditions and using UVA irradiances of 3, 9, 18, or 30 mW/cm2. The results showed that when the procedure was done in the normoxic environment and according to the standard Dresden protocol using an irradiance level of 3 mW/cm2, there was sufficient oxygen available to achieve CXL at all measured depths. However, when the irradiance level was raised to just 9 mW/ cm2, sufficient oxygen for achieving CXL was available only down to 200 μm depth and only in the anterior 100 μm for higher irradiances.

“Our study results are congruent with previously reported OCT data evaluating the depth of the CXL corneal stromal demarcation line using different levels of UVA irradiance,” Dr Seiler said.

Oxygen measurements taken when CXL was performed in the 100% oxygen environment showed a surplus of oxygen was present at all measured depths using the 9 mW/cm2 UVA irradiance level. With CXL performed at 18 and 30 mW/cm2 of irradiance, there was not enough oxygen available to achieve sufficient CXL posterior than 100 μm, indicating an optimal irradiance between 9 and 18 mW/cm2 when using supplemental oxygen.

CLINICAL TRANSLATION Dr Seiler said findings from a clinical study submitted for publication indicate performing CXL in a 100% oxygen environment generally results in a threefold greater reduction in keratometric flattening compared to CXL done under normoxic conditions. The change achieved in most patients ranged from 3.0 to 5.0 D, he said.

In a case presentation, Dr Seiler showed that the use of supplemental oxygen during CXL could result in even greater corneal flattening and an extraordinarily deep demarcation line in some eyes. The patient he described benefited with a 6 to 8 D change in keratometry and had a demarcation line at 380 μm. However, Dr Seiler also noted some eyes achieved only a minor change of just 1 or 2 D.

He added that supplementing oxygen might also improve outcomes of transepithelial CXL.

“We know we do not get deep penetration of oxygen when performing epithelial-on CXL, since the corneal epithelium is the main consumer of oxygen in the cornea and acts as a diffusion barrier. Results of a study by Mazzotta et al.ii showed significant flattening of the steep keratometry and a demarcation line deeper than 300 μm performing transepithelial CXL with supplemental oxygen.”

VISUAL REHABILITATION Visual function is what matters to patients, and when considering an excimer laser procedure for visual rehabilitation in a contact lens-intolerant patient who requires CXL or has undergone CXL, the physician needs to take into account the effect of the ablation on the biomechanical stability of an already weak cornea. Therefore, the goal is to minimise the depth of tissue removal. A WFG PRK procedure targeting the reduction of only selected HOAs represents one approach.

“We do not need to totally correct the lower order aberrations (LOAs) and improve uncorrected visual acuity. Reducing HOAs can improve best spectacle-corrected visual acuity (BSCVA), and we can tell the patient to wear a soft contact lens or spectacles for further visual rehabilitation,” Dr Seiler said.

Performing the ablation with a smaller optical zone diameter or to use a myopic target refraction are also ways to reduce and achieve a tolerable amount of tissue removed in the ectatic region of the cornea. However, the viability of this approach needs to be investigated and simulated in the preoperative examination. Informed consent must always make patients aware of the potential complications, Dr Seiler said.

Underscoring the latter point, he presented a case involving a patient who underwent topography guided PRK with simultaneous CXL with satisfying topographic results. However, because of stromal scarring presence, the patient’s postoperative BSCVA was only 20/100.

“I performed DALK in this patient, and I definitely would have faced a legal issue if I had not provided good information preoperatively about the possible risks of the laser treatment,” Dr Seiler emphasised.

i Am J Ophthalmol. 2021; 223: 368–376. ii J Cataract Refract Surg. 2020; 46(12): 1582–1587.

Theo G Seiler Jr, MD is senior physician in the Department of Ophthalmology at the University of Düsseldorf, Germany, and at the Institute für Refraktive und Ophthalmo-Chirurgie (IROC), Zurich, Switzerland. theo@seiler.tv