Corneal Cross-Linking Comparing Variables

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the Safety and Efficacy of Corneal Cross Linking in a Continuous Beam versus Pulsed Treatments across epithelium on and epithelium off surfaces.

Official Title
-----------------
Study of Safety and Efficacy of Photochemically Induced Collagen Cross-Linking at an Irradiance of 18 mW/cm2 as Constant or Pulsed Treatment in Eyes With Unstable Corneas Due to Keratoconus, Ectasia, or Post-Incisional Refractive Surgery

Conditions
-----------------
Unstable Corneas

Intervention / Treatment
-----------------
* Drug: Epithelium-On Riboflavin
* Drug: Epithelium-Off Riboflavin
* Device: UV Light - Continuous Beam
* Device: UV Pulsed Beam


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Keratoconus: 12 years of age or older Having a clinical diagnosis of progressive keratoconus consistent with: An increase of ≥ 1.00 D in the steepest keratometry value An increase of ≥ 1.00 D in astigmatism manifest refraction A myopic shift (decrease in the spherical equivalent) of ≥ 0.50 D on subjective manifest refraction Presence of central or inferior steepening on the topography map. Axial topography consistent with keratoconus Steepest keratometry (Kmax) value ≥ 47.00 D Signed written informed consent Willingness and ability to comply with schedule for follow-up visits Contact lens removal prior to evaluation and treatment Inclusion Criteria Post-Surgical Ectasia: History of having undergone a keratorefractive procedure and: Steepening by topography Thinning of cornea Shift in the position of thinnest portion of cornea Change in refraction with increasing myopia Development of myopic astigmatism Development of irregular astigmatism Loss of Best Spectacle Corrected Visual Acuity At least two of the above criteria must be present. Inclusion Criteria Intacts: Should the patient have undergone prior Intacs or other intra-corneal ring segment surgery for keratoconus or post-surgical ectasia at least 6 months prior, and is also experiencing at least two of the above ectasia symptoms, they can be included in the study. These patients would have the choice of ring explant before Cross-Linking. Cross-Linking may still be performed if the patient wishes to retain the rings. Should a patient's situation due to factors such as significantly high myopia or astigmatism should warrant simultaneous placement of Intacs and cross-linking in the investigators opinion, then this option can be offered to the patient. Such interventions would be tracked as a different arm of the study. Inclusion Criteria RK/AK Fluctuation: History of having undergone radial keratotomy (RK) and or astigmatic keratotomy (AK) surgery. Expressing complaints about difficulties due to vision changing during the same day. A difference in their Manifest Refraction (MRx) of greater than 0.75 D measured on the same day, at least 6 hours apart. Intacs surgery will not be considered in patients with RK/AK. Exclusion Criteria: Eyes classified as either normal, atypical normal, Corneal pachymetry ≤ 350 microns at the thinnest point measured by Orbscan, Pentacam, or ultrasound in the eye to be treated A history of chemical injury or delayed epithelial healing in the eye to be treated. A known sensitivity to study medications Patients with significant nystagmus or any other condition that would prevent a steady gaze during the treatment Inability to cooperate with diagnostic tests. Patients with a current condition that, in the investigator's opinion, would interfere with or prolong epithelial healing. Taking Vitamin C (ascorbic acid) supplements within 1 week of the cross-linking treatment. Patients who are unable to remain comfortable and stable, and tolerate a lid speculum for the appointed period of time for the procedure.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Epi-On Continuous<br>Continuous beam of UV light treating cornea with surface epithelium present | Drug: Epithelium-On Riboflavin<br>* Riboflavin 0.1% Phosphate Sodium solution with Benzalkonium Chloride Preservative<br>* Other names: Vitamin B2;Device: UV Light - Continuous Beam<br>* 5 minutes of constant UV exposure to saturated cornea<br>* Other names: Peschke Vario CCL-365 UV system;|
| Active Comparator: Epi-Off Continuous<br>Continuous beam of UV light treating cornea without surface epithelium present | Drug: Epithelium-Off Riboflavin<br>* Riboflavin 0.1% Phosphate Sodium solution<br>* Other names: Vitamin B2;Device: UV Light - Continuous Beam<br>* 5 minutes of constant UV exposure to saturated cornea<br>* Other names: Peschke Vario CCL-365 UV system;|
| Active Comparator: Epi-On Pulsed<br>Pulsed beam of UV light treating cornea with surface epithelium present | Drug: Epithelium-On Riboflavin<br>* Riboflavin 0.1% Phosphate Sodium solution with Benzalkonium Chloride Preservative<br>* Other names: Vitamin B2;Device: UV Pulsed Beam<br>* 5 minutes of UV exposure to saturated cornea, alternating 1 minute of treatment with 1 minute rest for a total time of 10 minutes<br>* Other names: Peschke Vario CCL-365 UV system;|
| Active Comparator: Epi-Off Pulsed<br>Pulsed beam of UV light treating cornea without surface epithelium present | Drug: Epithelium-Off Riboflavin<br>* Riboflavin 0.1% Phosphate Sodium solution<br>* Other names: Vitamin B2;Device: UV Pulsed Beam<br>* 5 minutes of UV exposure to saturated cornea, alternating 1 minute of treatment with 1 minute rest for a total time of 10 minutes<br>* Other names: Peschke Vario CCL-365 UV system;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity | Uncorrected visual acuity | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cornea, keratoconus, ectasia, irradiance, riboflavin, crosslinking