Corneal Collagen Cross-Linking (CXL) Performed With Epi-ON Versus Epi-OFF in Eyes With Keratoconus and Other Corneal Ectatic Disorders

Study Overview
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Brief Summary
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This is a prospective, randomized, single investigative site study to compare the safety and effectiveness of Epi-OFF CXL treatment (performed using Ricrolin+ and VEGA UV-A system) compared to Epi-ON CXL (performed using Ricrolin+ and VEGA UV-A system) in eyes with keratoconus and other corneal ectatic disorders.Subjects will be randomized to receive the CXL treatment with either the Epi-On or Epi-Off technique.

Official Title
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Comparison of Corneal Collagen Cross-Linking Performed With Epi-ON Versus Epi-OFF Techniques in Eyes With Keratoconus and Other Corneal Ectatic Disorders

Conditions
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Keratoconus, Ectasia

Intervention / Treatment
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* Drug: Ricrolin+
* Device: VEGA UV-A system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be at least 12 years of age or older, male or female, of any race. Having a diagnosis of keratoconus or other corneal ectatic disorder. Presence of central or inferior steepening on the topography map. Axial topography consistent with keratoconus or other corneal ectatic disorder. For eyes diagnosed with keratoconus, presence of one or more slit lamp findings associated with keratoconus, such as: Scissoring of the retinoscopic reflex Fleischer ring Vogt striae Corneal thinning e .Corneal scarring BSCVA 20/20 or worse. Subject is willing to have CXL performed by the Epi-OFF or Epi-ON techniques. Provide written informed consent and a signed HIPPA form. Pediatric subjects less than 14 years of age must sign an assent and a parent or legal guardian must sign an informed consent. Willingness and ability to follow all instructions and comply with schedule for follow-up visits. If female and capable of becoming pregnant, must not be lactating or pregnant and must agree to use a medically acceptable form of birth control for at least one week prior to the treatment visit and to continue o one month following treatment. Exclusion Criteria: One of the randomized CXL techniques (Epi-OFF or Epi-ON) is contraindicated or, in the investigator's clinical judgment, is not able to be performed in the study eye. Study eye keratoconus severity is classified as being normal or atypical normal based on the OPD-Scan III keratoconus classification indices. A history of previous corneal transplant in the study eye. A history of prior CXL in the study eye. Corneal pachymetry < 375 microns at the thinnest point as measured by ultrasound pachymetry in the study eye before epithelium removal. [NOTE: Eyes with corneal pachymetry between <375 microns and 325 microns may be enrolled in the compassionate use group.] Presence of Intacs or corneal rings or segments in the study eye. 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 unrelated to keratoconus. Eyes which are aphakic. Eyes which are pseudophakic and do not have a UV blocking lens implanted. A known contraindication, sensitivity, or allergy to the test article or its components or to study medications. Nystagmus or any other condition that would prevent a steady gaze during the cross-linking treatment or other diagnostic tests. If female, pregnant, nursing or planning a pregnancy, or having a positive urine pregnancy test prior to the randomization of, or treatment of, either eye during the course of the study. A condition that, in the investigator's opinion, would interfere with or prolong epithelial healing, including a history of chemical injury or delayed epithelial healing in the study eye. Presence or history or 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.

Ages Eligible for Study
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Minimum Age: 12 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Epi-OFF CXL<br>The Epi-ON treatment will be performed without removal of the corneal epithelium. Ricrolin+will be used as the riboflavin formulation for the pre-treatment and irradiation steps of the Epi-ON treatments. The VEGA UV-A light will be used during the irradiation steps of the Epi-ON treatment. | Drug: Ricrolin+<br>* 1 to 2 drops of Ricrolin+ will be instilled topically in the eye every 2 minutes for 30 minutes. At the end of the Ricrolin+ pre-treatment period, the eye will be examined at the slit lamp to detect the presence of a yellow flare in the anterior chamber, indicating adequate riboflavin saturation of the corneal tissue. If the yellow flare is not detected, Ricrolin+ will continue to be instilled 1 drop every 2 minutes for an additional 5 to 10 minutes; and the anterior chamber will be rechecked for yellow flare. This process will be repeated as necessary. During the irradiation period, 1 to 2 drops of Ricrolin+ to cover the cornea (in the same manner as during the riboflavin pre-treatment) before the start of irradiation and every 5 minutes during irradiation until irradiation is complete.<br>Device: VEGA UV-A system<br>* The VEGA light will be administered for 30 minutes. The VEGA light will stop automatically every 5 minutes for Ricrolin+ administration.<br>|
| Active Comparator: Epi-ON CXL<br>The Epi-OFF treatment will be performed with removal of the corneal epithelium before the first dose of riboflavin is administered. Ricrolin+ will be used as the riboflavin formulation for the pre-treatment and irradiation steps of the Epi-OFF treatments. The VEGA UV-A light will be used during the irradiation steps of the Epi-OFF treatment. | Drug: Ricrolin+<br>* 1 to 2 drops of Ricrolin+ will be instilled topically in the eye every 2 minutes for 30 minutes. At the end of the Ricrolin+ pre-treatment period, the eye will be examined at the slit lamp to detect the presence of a yellow flare in the anterior chamber, indicating adequate riboflavin saturation of the corneal tissue. If the yellow flare is not detected, Ricrolin+ will continue to be instilled 1 drop every 2 minutes for an additional 5 to 10 minutes; and the anterior chamber will be rechecked for yellow flare. This process will be repeated as necessary. During the irradiation period, 1 to 2 drops of Ricrolin+ to cover the cornea (in the same manner as during the riboflavin pre-treatment) before the start of irradiation and every 5 minutes during irradiation until irradiation is complete.<br>Device: VEGA UV-A system<br>* The VEGA light will be administered for 30 minutes. The VEGA light will stop automatically every 5 minutes for Ricrolin+ administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in corneal curvature | Percentage of eyes that had a greater than 2D increase in Kmax measured by the OPD-Scan III | Baseline, 6 Months, and 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in manifest refraction spherical equivalent | Change in refraction | Baseline, 6 Months, and 12 Months | 
| Change in best-corrected visual acuity (BSCVA) | Percentage of eyes that had a loss of 2 or more lines in BSCVA | Baseline, 6 Months, and 12 Months | 
| Change in uncorrected-visual acuity (UCVA) |  | Baseline, 6 Months, and 12 Months | 
| Change in thinnest pachymetry | measured by ultrasound | Baseline, 6 Months, and 12 Months |