A prospective evaluation of photorefractive intrastromal cross-linking for the treatment of low-grade myopia

Acta Ophthalmol. 2020 Mar;98(2):201-206. doi: 10.1111/aos.14190. Epub 2019 Jul 12.


Purpose: To evaluate photorefractive intrastromal cross-linking (PiXL) treatment for low-grade myopia, comparing three treatment protocols.

Methods: Healthy individuals, 25.6 ± 3.6 years of age, with low-grade myopia underwent epi-on PiXL with either: 4-mm zone treated in high oxygen environment (4 mm-HIGH; n = 15), 4-mm/room air (4-mm LOW; n = 6), or 6-mm/high oxygen (6-mm HIGH; n = 6). Efficacy was determined by change in uncorrected visual acuity (UCVA), manifest refractive spherical equivalent (MRSE) and corneal curvature (Kmean ) over a 12-month follow-up. Safety was determined by best spectacle corrected visual acuity (BSCVA), corneal endothelial cell loss and registration of side-effects.

Results: Twenty-seven subjects were included. Due to insufficient effect with the 4-mm LOW treatment and an unacceptable degree of initial light sensitivity/ocular irritation in the 6-mm HIGH group, the inclusions to these treatments were stopped after inclusion of 6 patients in each group. The 4-mm HIGH treatment showed a significantly larger improvement in UCVA (-0.45 ± 0.27 LogMAR) and MRSE (+0.99 ± 0.44 D) at 1, 6 and 12 months compared with the 4-mm LOW treatment (p < 0.05). At 12 months posttreatment, endothelial cell count and BSCVA were unaltered. More initial side-effects were noted with the 6-mm HIGH treatment, compared with the 4-mm HIGH treatment (p < 0.05).

Conclusion: Epi-on PiXL may become a safe and effective non-ablative treatment for low-grade myopia. The effect is augmented by high oxygen environment and remains stable for 12 months. The initial ocular irritation is acceptable with a 4-mm treatment zone. The present results justify further clinical studies on PiXL, including refinements of the technique and long-term results.

Keywords: PiXL; corneal collagen cross-linking; myopia; refractive cross-linking.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Collagen / metabolism
  • Corneal Endothelial Cell Loss / physiopathology
  • Corneal Stroma / drug effects*
  • Corneal Stroma / metabolism
  • Corneal Topography
  • Cross-Linking Reagents*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Myopia / drug therapy*
  • Myopia / metabolism
  • Myopia / physiopathology
  • Photosensitizing Agents / therapeutic use*
  • Prospective Studies
  • Riboflavin / therapeutic use
  • Treatment Outcome
  • Ultraviolet Rays
  • Visual Acuity / physiology
  • Young Adult


  • Cross-Linking Reagents
  • Photosensitizing Agents
  • Collagen
  • Riboflavin