PHOTOREFRACTIVE INTRASTROMAL CXL (PiXL)

Figure A: Scheimpflug imaging data showing preoperative curvature data; Figure B: Custom CXL pattern applied in three-step overlaid patterns, a circular, and two single arcs. Exposure time and fluence (and consecutively, delivered energy) are all customisable. The CXL ‘action’ was targeted on the thinnest cornea;Figure C: Postoperative map depicts significant ‘cone’ reduction, and a postoperative cornea appearing a lot more ‘regular’ 

 Images: Courtesy of John Kanellopoulos MD

PiXL, or Photorefractive Intrastromal CXL, was introduced clinically by John Kanellopoulos, Athens, who has also contributed a significant amount of other pioneering work in the field of corneal crosslinking (CXL) such as the use of higher fluence; use of non-dextran containing riboflavin solution; introduction of the Athens protocol which uses a combination of CXL with topography guided excimer normalisation of ectatic corneas; prophylactic CXL in routine myopic and hyperopic LASIK, as well as in-situ CXL through femtosecond laser created corneal pockets.

These and other significant developments in the field have allowed the corneal surgeon an expanded armamentarium of options in effectively planning treatment of ectatic corneas, as well as providing a potentially novel treatment technique for correction of refractive errors. PiXL refers to a customised, variable fluence CXL treatment to productively utilise the potential refractive changes derived from CXL differentials that may be generated within the same cornea.

PRINCIPLE OF PiXL

Customisable, differential CXL application to specific corneal areas may induce predictable refractive changes. The Avedro team (Waltham, MA) pursued this principle in theory and groundbreaking device design. Spatially selective corneal stromal stiffening can modulate corneal curvature, resulting in the achievement of a planned refractive change.

This theory has also been recently supported by computer simulation patterns innovated by BJ Dupps et al at the Cleveland Clinic Foundation. “PiXL may radically enlarge the use of CXL not just in the field of stabilising ectatic disorders, but also to refractive surgery by reshaping the cornea by means of localised, differential tissue strengthening. It could be used for healthy corneas of patients with small refractive errors up to 3 dioptres for myopia, hyperopia and/or astigmatic corrections as well as for mildly keratoconic patients where CXL is desired to be combined with customised refractive correction of myopia and/or cylinder without causing tissue removal. We were fortunate to be trusted first with this fascinating technology and conduct the initial feasability clinical work,” says Dr Kanellopoulos.

TECHNIQUE

The differential UV delivery system offered by the novel KXL II device (Avedro Inc, Waltham, MA) makes it possible to deliver differential and variable UV-A illumination, and therefore modulate the CXL effect. Custom-application may make myopic, astigmatic as well as hyperopic refractive change possible.

A central circular pattern of UV-A application may be used for myopic correction, a bow tie pattern for astigmatic and a doughnut pattern for treatment of hyperopia. PiXL may be performed as epithelium-on (transepithelial) or epithelium-off. The epi-on may be advantageous in simplicity, minimal postoperative discomfort, rapid recovery and safety. Titration by retreatment may be done. The weaker biomechanical effect can be compensated for by using higher fluence UV-A and by achieving higher riboflavin penetration via techniques that weaken the epithelial cell junctions and increase riboflavin penetration.

RESULTS

Dr Kanellopoulos says: “Endothelial Cell Count (ECC) examination by confocal specular microscopy both preoperatively as well as one-month postoperatively is an integral part of our clinical protocol. Our data have not yet indicated any statistically significant difference in ECC. In-vivo biomechanical measurements show low specificity and sensitivity.

“We have used objective biaxial stress-strain measurements which are likely to be superior to corneal strip extensiometry utilised in past experiments, considering the non-uniform topographic distribution of corneal strength profile. Studies show substantial ex-vivo evidence that significant corneal strengthening takes place even when UV-A light is projected through the intact corneal epithelium, Bowman’s membrane and superficial stroma, to reach underlying riboflavin-soaked stroma in order to induce cross-linking. Predictability may be assessed by further studies, as currently we are conducting initial, proofing clinical evaluation.

“Currently we have applied the PiXL application in more than 40 cases, over the course of more than 18 months. We have presented pioneering studies that achieved myopic refractive change. Astigmatic changes have also been reported, as well hyperopic changes."

ADDRESSING KERATOCONUS WITH PiXL

Customised patterns of delivered energy may be applied by customising UV-A patterns, fluence and exposure times to allow customised changes in topography of mildly keratectatic patients. Dr Kanellopoulos says: “In the example shown in Figures A-C, a keratoconic patient was treated with a customisable version of PiXL. Custom CXL pattern was applied in three-step overlaid patterns, a circular, and two single arcs. CXL ‘action’ was targeted on the thinnest cornea. Comparison of preoperative to postoperative data indicate a significant ‘cone’ reduction, and a postoperative cornea appearing a lot more ‘regular’. This patient can now be managed with a spectacle refraction, as the postoperative astigmatism has been managed to significantly more regular, in comparison to the preoperative.”

“The future lies in establishing and refining a nomogram, the optimal optical zone(s) and of course data that may be attempted and evaluated in future studies. We note, however, that the ease and essentially null morbidity that this procedure offers may additionally offer the possibility to titrate the effect through two or more treatments through time,” he says.

* Dr Soosan Jacob is a Senior Consultant Ophthalmologist at Dr Agarwal’s Eye Hospital, Chennai, India and can be reached at dr_soosanj@hotmail.com