Safety and Effectiveness of Corneal Crosslinking (CXL): Keratoconus and Post-Refractive Ectasia

Study Overview
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Brief Summary
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This prospective, randomized study is being conducted to evaluate the safety and effectiveness of corneal cross-linking (CXL) in patients with keratoconus or post-refractive ectasia (post-LASIK or PRK) utilizing two techniques: the standard Epi-Off technique or an Epi-On technique that utilizes iontophoresis (I-CXL) to deliver the riboflavin to the cornea without need for removal of the corneal epithelium. Patients will be randomized to receive CXL treatment with either the Epi-On or Epi-Off technique.

Official Title
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Safety and Effectiveness of Corneal Crosslinking (CXL): Keratoconus and Post-Refractive Ectasia

Conditions
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Keratoconus, Ectasia

Intervention / Treatment
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* Drug: Ricrolin+
* Drug: Epi-Off


Participation Criteria
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Eligibility Criteria
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Inclusion: 10 years of age or older Understand and have signed written IRB-approved informed consent Willingness and ability to comply with schedule for follow-up visits Having a diagnosis of keratoconus or post-refractive corneal ectasia (post-LASIK or PRK) Presence of central or inferior steepening on the Pentacam map Axial topography consistent with keratoconus or post-refractive corneal ectasia (post-LASIK or PRK) Presence of one or more slit lamp findings associated with keratoconus, such as: Scissoring of the retinoscopic reflex Fleischer ring Vogt striae Corneal thinning Corneal scarring BSCVA 20/20 or worse (<58 letters on ETDRS chart). Contact lens wearers only: Removal of contact lenses for the required period of time prior to the first refraction: Contact Lens Type Minimum Discontinuation Time Soft 3 Days Soft Extended Wear 1 Week Soft Toric 2 Weeks Rigid gas permeable 2 Weeks Hybrid lenses (SynergEyes; Rose K; Clear Kone) 2 Weeks Scleral Lenses 2 Weeks Exclusion Criteria: All subjects meeting any of the following criteria will be excluded from the study: A history of previous corneal surgery in the eye to be treated (including previous CXL treatment) a. Eyes with episodes of hydrops or scarring from hydrops may be included as long as there is no active inflammation Corneal pachymetry < 400 microns at the thinnest point measured by Pentacam Previous ocular condition (other than refractive error) in the eye(s) to be treated that may predispose the eye for future complications or prevent the possibility of improved vision, for example: History of corneal disease (e.g., herpes simplex, herpes zoster keratitis, recurrent erosion syndrome, corneal melt, or corneal dystrophy, etc.) Clinically significant corneal scarring in the treatment zone A history of chemical injury or delayed epithelial healing in the eye(s) to be treated Pregnancy (including plan to become pregnant) or lactation during the procedure A known sensitivity to study medications Nystagmus or any other condition that would prevent a steady gaze during the cross-linking treatment or other diagnostic tests A condition that, in the investigator's opinion, would interfere with or prolong epithelial healing Presence or history of any other condition or finding that, in the investigator's opinion, makes the patient unsuitable as a candidate for cross-linking or study participation or may confound the outcome of the study Inability to cooperate with diagnostic tests or inability to understand the informed consent. Concurrent use of systemic (including inhaled) medications that may impair healing, including but not limited to: antimetabolites, isotretinoin (Accutane®) within 6 months of treatment, and amiodarone hydrochloride (Cordarone®) within 12 months of treatment.

Ages Eligible for Study
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Minimum Age: 10 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Epi-Off CXL<br>Using topical anesthesia (proparacaine), the surgeon will create a complete corneal abrasion to facilitate riboflavin diffusion into the cornea. The epithelium will be removed by gently brushing the cornea with a scalpel. A corneal abrasion diameter of  9mm is recommended, which may be adjusted as needed at the discretion of the investigator to accommodate individual eye geometry. Ultrasound corneal pachymetry should be performed before dis-epithelialization and after dis- epithelialization. Local anesthetics will be administered as needed to maintain patient comfort during the CXL procedure. | Drug: Epi-Off<br>* Using topical anesthesia (proparacaine), the surgeon will create a complete corneal abrasion to facilitate riboflavin diffusion into the cornea. The epithelium will be removed by gently brushing the cornea with a scalpel. A corneal abrasion diameter of  9mm is recommended, which may be adjusted as needed at the discretion of the investigator to accommodate individual eye geometry. Ultrasound corneal pachymetry should be performed before dis-epithelialization and after dis- epithelialization. Local anesthetics will be administered as needed to maintain patient comfort during the CXL procedure.<br>|
| Experimental: Epi-On CXL<br>The IONTOPHOR CXL iontophoresis applicator and the associated blepharostat will be placed onto the cornea to be treated. The applicator will be secured to the cornea and filled with Ricrolin+ which as been aspirated from the bottle using a syringe with a needle. The generator will be switched on and set to 1 mA for 5 minutes. The generator will then be disconnected and the applicator will be removed from the cornea. | Drug: Ricrolin+<br>* The IONTOPHOR CXL iontophoresis applicator and the associated blepharostat will be placed onto the cornea to be treated. The applicator will be secured to the cornea and filled with Ricrolin+ which as been aspirated from the bottle using a syringe with a needle. The generator will be switched on and set to 1 mA for 5 minutes. The generator will then be disconnected and the applicator will be removed from the cornea.<br>* Other names: Epi-on (iontophoresis);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Kmax | Kmax = maximum simulated keratometry value | baseline and 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in steepest K | steepest K is the higher diopter number which represents the steepest meridian of the cornea | baseline and 2 years | 
| Change in astigmatism | Astigmatism is an imperfection in the curvature of the cornea, causing a refractive error diagnosed by standard eye exam with refraction test. | baseline and 2 years | 
| Change in keratometry | Keratometry is the measurement of the corneal radius of curvature | baseline and 2 years | 
| Change in pachymetry | Pachymetry is a common test for glaucoma and measures the thickness of the cornea | baseline and 2 years | 
| Changes in curvature | Shape of cornea | baseline and 2 years | 
| Change in sphere | Change in refraction | baseline and 2 years | 
| Change in cylinder | Cylinder is the amount of astigmatism that is present | 2 years | 
| Change in BCVA | Best-corrected visual acuity (BCVA) | baseline and 2 years |