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

NCT03080077 | Unknown Phase 3

• 1 other identifier: GCO 16-0627
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Keratoconus; Ectasia

Outcome Measures

Primary Outcomes (1)

• Change in Kmax

  Kmax = maximum simulated keratometry value

  baseline and 2 years

Secondary Outcomes (8)

• Change in steepest K

  baseline and 2 years

• Change in astigmatism

  baseline and 2 years

• Change in keratometry

  baseline and 2 years

• Change in pachymetry

  baseline and 2 years

• Changes in curvature

  baseline and 2 years

Study Arms (2)

Epi-Off CXL

ACTIVE COMPARATOR

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

Epi-On CXL

EXPERIMENTAL

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+

Interventions

Ricrolin+ DRUG

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.

Also known as: Epi-on (iontophoresis)

Epi-On CXL

Epi-Off DRUG

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.

Epi-Off CXL

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (2)

• 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.

  PMID: 25263041 BACKGROUND

• 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.

  PMID: 23187160 BACKGROUND

MeSH Terms

Conditions

Keratoconus; Dilatation, Pathologic

Interventions

Iontophoresis; Corneal Cross-Linking

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Electrophoresis; Electrochemical Techniques; Investigative Techniques; Photochemotherapy; Combined Modality Therapy; Phototherapy

Study Officials

• Penny A Asbell, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Ophthalmology, Director of Cornea and Refractive Services, Director of the Cornea Fellowship Program

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 15, 2017
• Study Start: June 1, 2016
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: June 7, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)