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

• ClinicalTrials.gov Identifier: NCT03080077
• Recruitment Status: Unknown
• First Posted: March 15, 2017
• Last Update Posted: June 7, 2018
• Sponsor: Icahn School of Medicine at Mount Sinai
• Information provided by (Responsible Party): Penny Asbell, Icahn School of Medicine at Mount Sinai

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Keratoconus; Ectasia	Drug: Ricrolin+; Drug: Epi-Off	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Safety and Effectiveness of Corneal Crosslinking (CXL): Keratoconus and Post-Refractive Ectasia
• Study Start Date: June 2016
• Estimated Primary Completion Date: June 2019
• Estimated Study Completion Date: June 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Epi-Off CXL; 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; 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.
Experimental: Epi-On CXL; 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+; 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.; Other Name: Epi-on (iontophoresis)

Outcome Measures

Primary Outcome Measures :

1. Change in Kmax [ Time Frame: baseline and 2 years ]
   Kmax = maximum simulated keratometry value

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 10 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion:

1. 10 years of age or older
2. Understand and have signed written IRB-approved informed consent
3. Willingness and ability to comply with schedule for follow-up visits
4. Having a diagnosis of keratoconus or post-refractive corneal ectasia (post-LASIK or PRK)
5. Presence of central or inferior steepening on the Pentacam map
6. Axial topography consistent with keratoconus or post-refractive corneal ectasia (post-LASIK or PRK)

7. Presence of one or more slit lamp findings associated with keratoconus, such as:

   1. Scissoring of the retinoscopic reflex
   2. Fleischer ring
   3. Vogt striae
   4. Corneal thinning
   5. Corneal scarring
8. BSCVA 20/20 or worse (<58 letters on ETDRS chart).
9. 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:

1. 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

2. Corneal pachymetry < 400 microns at the thinnest point measured by Pentacam

3. 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:

   1. History of corneal disease (e.g., herpes simplex, herpes zoster keratitis, recurrent erosion syndrome, corneal melt, or corneal dystrophy, etc.)
   2. Clinically significant corneal scarring in the treatment zone
4. A history of chemical injury or delayed epithelial healing in the eye(s) to be treated
5. Pregnancy (including plan to become pregnant) or lactation during the procedure
6. A known sensitivity to study medications
7. Nystagmus or any other condition that would prevent a steady gaze during the cross-linking treatment or other diagnostic tests
8. A condition that, in the investigator's opinion, would interfere with or prolong epithelial healing
9. 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
10. Inability to cooperate with diagnostic tests or inability to understand the informed consent.
11. 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.

Contacts and Locations

Locations

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

Sponsors and Collaborators

Icahn School of Medicine at Mount Sinai

Investigators

• Principal Investigator: Penny A Asbell, MD; Icahn School of Medicine at Mount Sinai

More Information

Publications:

Lombardo M, Serrao S, Rosati M, Ducoli P, Lombardo G. Biomechanical changes in the human cornea after transepithelial corneal crosslinking using iontophoresis. J Cataract Refract Surg. 2014 Oct;40(10):1706-15. doi: 10.1016/j.jcrs.2014.04.024.

Koller T, Schumacher S, Fankhauser F 2nd, Seiler T. Riboflavin/ultraviolet a crosslinking of the paracentral cornea. Cornea. 2013 Feb;32(2):165-8. doi: 10.1097/ICO.0b013e318269059b.

• Responsible Party: Penny Asbell, Professor of Ophthalmology, Director of Cornea and Refractive Services, Director of the Cornea Fellowship Program, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT03080077
• Other Study ID Numbers: GCO 16-0627
• First Posted: March 15, 2017
• Last Update Posted: June 7, 2018
• Last Verified: June 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Keratoconus; Dilatation, Pathologic; Corneal Diseases; Eye Diseases; Pathological Conditions, Anatomical