It’s All About Biomechanics!

Understanding corneal biomechanics and customised cross-linking protocols is crucial to allow more patients to be eligible for corneal refractive surgery and avoid over- and undertreatment, according to Ingemar Gustafsson MD, PhD. As clinical studies demonstrate, corneal biomechanical decompensation and weakness can lead to the formation of ectatic diseases, and this can also happen after corneal refractive surgery as tissue is ablated, leading to a lower biomechanical strength.

Reviewing biomechanical characteristics, ex vivo and in vivo experiments showed a weak central area of the ectatic cornea but a quite normal-looking outside, with few differences in a healthy cornea.^1,2 As Dr Gustafsson remarked, if there is a focal problem, it should be addressed focally, and that is the purpose of customised cross-linking—dedicating more irradiance to the central part before gradually decreasing it.

“This has an important biomechanical impact because you have a strong flattening over the cone and an increased curvature outside,” he said. “So, you have a regularisation of the eye—which is good for visual acuity—but also increased survival of keratocytes and nerve regeneration that can be interesting in refractive surgery.”

The ophthalmology literature demonstrated the superiority of customised cross-linking over the standard one in visual outcomes, benefits for the epithelium, and clarity of the cornea in patients with keratoconus.^3,4 It can also be considered an additive treatment (Xtra) to refractive surgery because it enhances corneal biomechanics.

Looking at the refractive surgical techniques (PRK, LASIK, and KLEx), there is minimal risk of ectasia, but Dr Gustafsson said this depends on the inclusion criteria considered by the surgeon as well as the factors beyond the known risk factors. A recent longitudinal investigation demonstrated that after 20 years of follow-up, 1.2% patients had keratoconus, and another 2.2% developed it between year 20 and 28.⁵

“In these cases, we need biomechanical assessment because the disease was already present in the eye, but we cannot see it yet and corneal tomography results [show as] normal,” he remarked.

Additionally, key ectasia risk factors to evaluate are ethnic and geographic differences, age, and hormones, which are difficult to include in an algorithm and are another reason why, according to Dr Gustafsson, the field needs new ways to assess corneal biomechanics objectively.

He further explained Xtra protocols are generally safe, given some reservations with PRK Xtra, which has some risks of haze and reduction in visual acuity, most likely due to the epi-off nature of the protocol. This is not the case in LASIK Xtra and KLEx Xtra, which use epi-on protocols, sometimes with an adapted fluence strategy.

Dr Gustafsson recently published a randomised trial showing that 75% of patients treated with isoosmolar riboflavin and 15% of those treated with hypoosmolar riboflavin had a significant reduction in corneal thickness below the commonly used safety limit of 400 μm.⁶ “What I suggest is to check the intrastromal thickness, add sterile water when appropriate, or convert to sub400 protocol to reduce the risk of over-cross-linking if an epi-off strategy is used,” he said.

Moreover, additive cross-linking protocols to refractive surgery have been shown to be beneficial in high myopia compared to corneal laser refractive surgery alone. This could be due to a stronger and regularised stroma, which consequently leads to a regularised epithelium—essential for the quality of vision.

Assessing corneal biomechanics and customised cross-linking use would be beneficial in the future, as Dr Gustafsson stressed.

“We know we have myopic times ahead, and there will be a significant increase also in high myopia,” he said. “And the refractive surgery industry is growing. So, these are relevant topics to understand and address in the future.”

Dr Gustafsson spoke at the 2024 ESCRS Congress in Barcelona.

Ingemar Gustafsson MD, PhD is senior consultant at the cornea service at Skåne University Hospital and researcher at Lund University, both of Sweden. ingemar.gustafsson@med.lu.se

1. Scarcelli G, et al. “Biomechanical characterization of keratoconus corneas ex vivo with Brillouin microscopy,” Invest Ophthalmol Vis Sci, 2014 June 17; 55(7): 4490–4495.

2. Scarcelli G, et al. “In vivo biomechanical mapping of normal and keratoconus corneas,” JAMA Ophthalmol, 2015 April; 133(4): 480–482.

3. Cassagne M, et al. “Customized Topography-Guided Corneal Collagen Cross-linking for Keratoconus,” J Refract Surg, 2017 May 1; 35(5): 290–297.

4. Nordström M, et al. “Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results,” Br J Ophthalmol, 2017 Jul; 101(7): 920–925.

5. Chan E, et al. Ophthalmology, 2023 April; 130(4): 445–448.

6. Gustafsson I, et al. “Early findings in a randomised controlled trial on crosslinking protocols using isoosmolar and hypoosmolar riboflavin for the treatment of progressive keratoconus,” Acta Ophthalmologica, 2025; 103(1): 23–32. Published online early 2024 July 5.