Photorefractive Intrastromal Cross-Linking
Corneal collagen cross-linking (CXL) was FDA-approved for the treatment of keratoconus in April of 2016and has since become routine for stabilizing corneal ectasia. Post-CXL improvement in visual acuity as a result of corneal stiffening has been reported in the literature.   To achieve more pronounced refractive changes, higher fluence of UV light was used in the CXL procedure, thus creating photorefractive intrastromal cross-linking (PiXL). PiXL is a refractive procedure. Achievability of predictable refractive changes and tolerability of this procedure have been confirmed.
Objectives & Candidates
PiXL is appropriate for patients with low myopia or hyperopia as a second line to conventional refractive surgeries (i.e. LASIK, PRK, intraocular lens implant), and for patients who require correction of residual refractive error or refractive regression after conventional refractive surgeries. PiXL is recommended for patients with corneal topography inappropriate for conventional refractive surgeries, i.e. forme fruste keratoconus, because corneal tissue ablation is unnecessary. PiXL has also been applied to presbyopia.
PiXL is a high-fluence CXL administered in a customizable pattern and intensity in order to steepen or flatten the cornea through corneal strengthening. The specific application of UV-A for each patient takes into account the refractive error and corneal topography. The major components of the therapy are riboflavin injection and UV-A irradiation, and the procedure is followed by a course of topical antibiotics and corticosteroids. Details of the procedure and patient positioning are depicted in the figures below (Figures 1 and 2).
Figure 1: PiXL Procedure.
Figure 2: PiXL Patient Positioning. 
Types of PiXL
Epithelium-On or Transepithelial: No debridement of corneal epithelium
- Improved post-procedure comfort
- Lower risk of corneal infection
- Less stable result in hyperopic patients
Epithelium-Off: Debridement of corneal epithelium
- More stable result in hyperopic patients
- Higher risk of the following:
- Corneal infection
- Sub-epithelial haze
- Sterile corneal infiltrates
- Corneal scarring
- Endothelial damage
- Herpetic activation
PiXL offers the potential for immediate improvement in visual acuity without pain or discomfort. The adverse effect profile includes moderate to severe dry eyes. No significant changes in endothelial cell counts or corneal clarity have been reported. PiXL has shown sustained visual acuity results up to 12 months of follow-up. In one study of myopic patients an average of 2.3D of visual acuity improvement occurred in the first post-procedural (epithelium-on) week, which regressed to 1.44D at 1 month and subsequently remained stable at the 6 month follow-up. This is consistent with results from other studies, which cite a reduction of myopic refractive error with epithelium-on approach by -1.00 to -1.35D3 and 0.72+/-0.43D. A study of PiXL in hyperopia has achieved a +0.85D hyperopic correction with an epithelium-on method.
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- Lim, W. K., Soh, Z. D., Choi, H. K. Y., & Theng, J. T. S. (2017). Epithelium-on photorefractive intrastromal cross-linking (PiXL) for reduction of low myopia. Clinical Ophthalmology (Auckland, N.Z.), 11, 1205–1211. http://doi.org/10.2147/OPTH.S137712
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