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

Abstract

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.

Treatment effect with 2 photorefractive intrastromal cross‐linking protocols in low‐grade myopia through 24‐month follow‐up

“…Epi‐on PiXL in high oxygen is a novel therapeutic procedure that reshapes the corneal stroma without the need for epithelial debridement or stromal removal (Lim et al 2017; Fredriksson et al 2019; El Hout et al 2019; Sachdev et al 2020). Epi‐on techniques are beneficial with potentially less postoperative ocular discomfort, faster recovery for the patient and lower risks for serious complications such as postoperative infections and corneal scarring (Meek & Hayes 2013; Stulting et al 2018).…”

“…A modified variant of CXL, photorefractive intrastromal collagen cross‐linking (PiXL) has been introduced to deliver customized energy patterns to re‐model and flatten the corneal curvature in a controlled manner (Kanellopoulos 2014; Nordstrom et al 2017). By illuminating the central part of the cornea, the flattening effect has been shown by us and others to reduce or eliminate low‐grade myopia in healthy eyes (Kanellopoulos 2014; Elling et al 2017; Lim et al 2017; Elling et al 2018; Fredriksson et al 2019; El Hout et al 2019; Sachdev et al 2020). The impression from our previous studies is that an initial postoperative central haze could slow the post‐treatment improvement in visual acuity after such treatments (Beckman Rehnman et al 2014; Nordstrom et al 2017).…”

“…However, if available, oxygen from the ambient air reacts with the excited photosensitizer to form reactive oxygen species such as singlet oxygen and superoxide radicals, inducing collagen cross‐linking bonds in a type 2 reaction (Muller et al 2020). Thus, CXL causes biomechanical stiffening and stromal stabilization (Raiskup & Spoerl 2013), but the treatment also alters the corneal shape with a flattening of the corneal curvature (Meek & Hayes 2013), an effect that could potentially be used as a refractive treatment for myopia (Elling et al 2017; Lim et al 2017; Elling et al 2018; Fredriksson et al 2019; El Hout et al 2019; Sachdev et al 2020).…”

“…CXL without epithelial debridement has been suggested as a way to facilitate the healing process and diminish the initial ocular discomfort (Stulting et al 2018). However, the treatment effect in such ‘epi‐on’ cross‐linking is confined under restricted oxygen supply (Richoz et al 2013; Fredriksson et al 2019; Hill et al 2019; Rubinfeld et al 2019). In this perspective, a strategy might be to increase the oxygen concentration during the epi‐on treatment to enhance the type 2 reaction and thereby the cross‐linking effect (Fredriksson et al 2019).…”

“…However, the treatment effect in such ‘epi‐on’ cross‐linking is confined under restricted oxygen supply (Richoz et al 2013; Fredriksson et al 2019; Hill et al 2019; Rubinfeld et al 2019). In this perspective, a strategy might be to increase the oxygen concentration during the epi‐on treatment to enhance the type 2 reaction and thereby the cross‐linking effect (Fredriksson et al 2019). A modified variant of CXL, photorefractive intrastromal collagen cross‐linking (PiXL) has been introduced to deliver customized energy patterns to re‐model and flatten the corneal curvature in a controlled manner (Kanellopoulos 2014; Nordstrom et al 2017).…”