Simultaneous TransPRK and Corneal Collagen Cross-Linking

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Prospective Trial of Simultaneous Combined Transepithelial Photorefractive Keratectomy and Corneal Collagen Cross-linking for Keratoconus

Conditions
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Keratoconus

Intervention / Treatment
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* Procedure: Transepithelial Photorefractive Keratectomy (TransPRK)
* Procedure: Corneal Collagen Cross-Linking (CXL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with progressive stage II or III keratoconus CDVA < 0.00 logMAR or subjective problems with spectacle corrected visual quality (ghost images or light scatter symptoms) Exclusion Criteria: Active ocular surface disease Minimum corneal thickness <390µm (leaving 325µm residual stromal thickness after transPTK - in line with minimum thickness recommendations for the study CXL protocol) Vulnerable groups (patients whose capacity for giving informed consent to participate in the trial may be impaired)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Interventional case series with matched historical controls
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TransPRKCXL<br>Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL) | Procedure: Transepithelial Photorefractive Keratectomy (TransPRK)<br>* 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).<br>* Other names: Corneal surface excimer laser treatment;Procedure: Corneal Collagen Cross-Linking (CXL)<br>* 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)<br>* Other names: Rapid corneal collagen cross-linking;|
| Active Comparator: CXL only<br>Corneal collagen cross-linking (CXL) using the same protocol without transepithelial photorefractive keratectomy | Procedure: Corneal Collagen Cross-Linking (CXL)<br>* 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)<br>* Other names: Rapid corneal collagen cross-linking;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LogMAR Corrected Distance Visual Acuity (CDVA) | Change in spectacle corrected logarithm minimum angle of resolution (LogMAR) distance visual acuity recorded in a 4m testing lane in photopic lighting conditions between baseline measurement and final review at 24 months (note that negative change = better vision; 0.1 logMAR units = 1 line on the test chart) | Preoperative vs 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically Significant Visual Gain | Number of participants with gain of ≥2 lines (≥0.20 logMAR units) corrected distance visual acuity (CDVA) on a standard 5 letter per line EDTRS visual acuity testing chart | Preoperative vs 24 months postoperative | 
| Clinically Significant Visual Loss | Number of participants with loss of ≥2 lines (≥0.20 LogMAR units) corrected distance visual acuity (CDVA) | preoperative vs 24 months postoperative | 
| Change in Kmax - Maximum Local Anterior Corneal Surface Curvature on Tomography Map | Pentacam (www.oculus.de) measure: Maximum local curvature (Kmax). Reduction in dioptric value = corneal flattening | Preoperative vs 24 months postoperative | 
| Progression Rate | The number of participants with possible keratoconus disease progression after treatment defined by a ≥1.5D increase in Kmax, anterior and posterior K2 (maximum local corneal curvature, maximum anterior and posterior meridional corneal curvature) measured using a Pentacam HD corneal tomographer (www.oculus.de). | 6 months postoperative - 24 months postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Keratoconus, Corneal collagen cross-linking, Photorefractive keratectomy