Simultaneous TransPRK and Corneal Collagen Cross-Linking
Condition: Keratoconus
MeSH terms: Keratoconus
Study type: Interventional

Summary: 
      Young patients with keratoconus face two problems: disease progression and corneal shape
      irregularity leading to poor vision even in spectacles.

      Corneal collagen cross-linking (CXL) is a new treatment designed to halt disease progression
      in keratoconus. The aim is to stiffen the cornea thereby preventing further shape
      deterioration.

      Topography or wavefront guided transepithelial photorefractive keratectomy (transPRK) uses
      the excimer laser (the laser used to correct sight in 'laser eye surgery') to reduce corneal
      shape irregularity in early stage keratoconus, reducing dependence on contact lenses.

      In transPRK, the corneal skin layer is removed in a well controlled, no touch procedure,
      preparing the cornea for CXL. Performing both treatments simultaneously (combining both
      procedures in one operation) may offer several advantages over performing CXL first then
      waiting for corneal shape to stabilise before performing transPRK. In particular, visual
      rehabilitation may be faster. This study aims to evaluate visual recovery after simultaneous
      CXL and transPRK in progressive early stage keratoconus. Visual recovery in these patients
      will be compared with results for a similar group of patients with early stage keratoconus
      who have already been treated with CXL alone.
    

Detailed description: 
      Features which distinguish this trial from previous trials of combined photorefractive
      keratectomy (PRK) and corneal collagen cross-linking (CXL) are: a rapid, pulsed light, CXL
      protocol; and a treatment programming algorithm for PRK designed to target higher order
      aberrations only with no compensatory additional laser corneal tissue removal.

      Excimer laser treatment will be performed with the Schwind Amaris 750S laser
      (www.eye-tech-solutions.com). Unique features of this system utilised here include:

        -  Pre-programmed transepithelial ablation - laser removal of the minimum area of corneal
           epithelium required for PRK promoting more rapid recovery than conventional methods (20%
           alcohol application and manual epithelial removal). An 8mm diameter ablation zone will
           be applied throughout.

        -  Enhanced algorithms for minimal laser tissue removal - in this trial, the investigators
           are targeting higher order aberrations only (coma in particular) with the aim of
           improving spectacle corrected visual acuity without regard to the predicted
           spherocylindrical outcome. Unlike other current excimer laser platforms, Schwind Amaris
           treatment programming software allows treatment for irregular astigmatism without
           additional compensatory laser tissue removal to correct the spherocylindrical change
           induced by treatment of higher order aberrations. Higher order aberrations can also be
           treated selectively. The investigators will use an algorithm step that targets only
           aberrations (up to 6th order Zernike polynomials) with a value greater than 2 standard
           deviations from the population mean in normative data. These treatment planning steps
           allow the laser to create a large diameter treatment with minimal treatment depth.

      Laser epithelial removal alone (transPTK at depth 55µm) removes a maximum 65µm of tissue in
      the corneal periphery. For patients with 390µm at the thinnest point, transPTK will therefore
      leave above 325µm residual stromal thickness prior to CXL. This is in line with
      recommendations for minimum stromal thickness after epithelial removal in the CXL protocol
      used here. Limited stromal reshaping is achieved in this simple embodiment of transPRK for
      keratoconus by taking advantage of the masking effect of the corneal epithelium, which tends
      to be thinnest over the cone apex. Where the thinnest point is greater than 390µm, further
      reductions in corneal shape irregularity can be produced by adding either wavefront or
      topography guided additional stromal ablation using custom programming on the Schwind Amaris
      laser. Ocular wavefront (aberrometry) guided smoothing will be used for patients with a 5.5mm
      or larger pupil at scanning and a consistent scan sequence (3 scans within 0.5 dioptre (D)
      spherical equivalent refraction). Corneal wavefront (topography) guided smoothing will be
      used for patients with ocular wavefront scans which do not meet these criteria. In all cases,
      a minimum corneal stromal thickness prior to CXL of 325µm will be preserved.

      Immediately after PRK, corneal collagen cross-linking will be performed using the following
      protocol

      Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation
      (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation
      to remove excess riboflavin prior to UV light exposure.

      UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4
      minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light
      source)

      Mitomycin C will not be used. A bandage contact lens will be applied at the end of treatment
      and a standard post photorefractive keratectomy topical and systemic drug treatment regimen
      will be used in every case with initial clinical review 1 week after surgery.
    

Intervention name(s): Transepithelial Photorefractive Keratectomy (TransPRK); Corneal Collagen Cross-Linking (CXL)
Intervention type(s): Procedure; Procedure
Intervention description(s): Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).; Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)
Other intervention name(s): Corneal surface excimer laser treatment; Rapid corneal collagen cross-linking
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Interventional case series with matched historical controls
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Keratoconus; Corneal collagen cross-linking; Photorefractive keratectomy