Corneal Crosslinking in Patients With Keratoconus and Post-Refractive Ectasia

Evaluation of Two Riboflavin Dosing Regimens for Corneal Collagen Cross-Linking in Eyes With Progressive Keratoconus or Ectasia

The purpose of this study is to evaluate the effectiveness of using riboflavin and UV light to treat progressive keratoconus or post-refractive corneal ectasia.

Study Overview

• Status: Completed
• Conditions: Keratoconus; Post-Refractive Ectasia
• Intervention / Treatment: Drug: Riboflavin; Device: UVX light

Detailed Description

The primary objective of this study is to evaluate two riboflavin-dosing regimens for corneal collagen cross-linking to slow the progressive changes in corneal curvature in eyes with progressive keratoconus or post-refractive ectasia.

• Study Type: Interventional
• Enrollment (Actual): 510
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Price Vision Group

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 10 years of age or older

2. Having documented ectasia on topography or tomography after previous refractive surgery OR progressive keratoconus defined as one or more of the following changes over a period of 36 months or less before randomization:

   1. An increase of ≥ 1.00 D in the steepest keratometry value (or sim K)
   2. An increase of ≥ 1.00 D in regular astigmatism evaluated by subjective manifest refraction
   3. A myopic shift (decrease in the spherical equivalent) of ≥ 0.50 D on subjective manifest refraction
   4. Documented decrease in visual acuity associated with irregular astigmatism and topographic features of ectasia.

3. Subjects with keratoconus diagnosis only:

   a. Axial topography consistent with keratoconus b. Presence of central or inferior steepening on the Pentacam map. c. Presence of one or more slit lamp findings associated with keratoconus, such as: i. Fleischer ring ii. Vogt striae iii. Corneal thinning iv. Corneal scarring

4. Contact Lens Wearers Only: Removal of contact lenses for the required period of time prior to the screening refraction:

   Contact Lens Type Minimum Discontinuation Time Soft 3 Days Soft Extended Wear 1 Week Soft Toric 2 Weeks Rigid gas permeable 2 Weeks

5. Signed written informed consent

Exclusion Criteria:

• 1. Any keratoconus patient over 21 years of age without evidence of progression of his corneal deformity.

  2. Patients with excessively thin corneas. 3. Previous ocular condition in the eyes to be treated that may predispose the eye for future complications, for example:

  a. History of corneal disease (e.g., herpes simplex, herpes zoster keratitis, recurrent erosion syndrome, corneal melt, corneal dystrophy, etc.) b. Clinically significant corneal scarring in the proposed treatment zone 4. A history of chemical injury or delayed epithelial healing in the eye(s) to be treated.

  5. A known sensitivity to treatment medications. 6. Patients with a current condition that, in the treating physician's opinion, would interfere with or prolong epithelial healing.

  7. Pregnancy (including plan to become pregnant) or lactation during the course of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Riboflavin 0.1% eyedrops every 5 minutes; The eye will be irradiated for 30 minutes with UVX light, during which time instillation of riboflavin will continue (1 drop every 5 minutes for this arm).	Drug: Riboflavin; Riboflavin 0.1% eye drops are applied before and during irradiation of the cornea.; Device: UVX light; UVX 365 nm wavelength light source is applied with continued application of riboflavin.
Active Comparator: Riboflavin 0.1% eyedrops every 2 minutes; The eye will be irradiated for 30 minutes with UVX light, during which time instillation of riboflavin will continue (1 drop every 2 minutes for this arm).	Drug: Riboflavin; Riboflavin 0.1% eye drops are applied before and during irradiation of the cornea.; Device: UVX light; UVX 365 nm wavelength light source is applied with continued application of riboflavin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Maximum Keratometry From Baseline to 6 Months After Treatment	Change in maximum keratometry (Kmax) between baseline and 6 months after treatment, measured by corneal tomography.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pachymetry	Minimum corneal thickness measured by corneal tomography	6 months
Corrected Distance Visual Acuity (CDVA)	Corrected distance visual acuity (CDVA) reported in logarithm of the minimum angle of resolution (logMAR). Lower numbers represent better vision; 0.0 corresponds to 20/20 vision. Each increase of 0.1 on the logMAR scale corresponds to one less line read on the eye chart.	6 months
Uncorrected Distance Visual Acuity (UDVA)	Uncorrected distance visual acuity reported in logarithm of the minimum angle of resolution units. Lower numbers represent better vision; 0.0 corresponds to 20/20 vision without any type of correction such as glasses. Each increase of 0.1 on the logMAR scale corresponds to one less line read on the eye chart.	6 months

Collaborators and Investigators

• Sponsor: Price Vision Group
• Investigators: Principal Investigator: Francis W Price, MD, Price Vision Group

Publications and helpful links

General Publications

• Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg. 2008 May;34(5):796-801. doi: 10.1016/j.jcrs.2007.12.039.
• Wittig-Silva C, Whiting M, Lamoureux E, Lindsay RG, Sullivan LJ, Snibson GR. A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results. J Refract Surg. 2008 Sep;24(7):S720-5. doi: 10.3928/1081597X-20080901-15.
• Caporossi A, Baiocchi S, Mazzotta C, Traversi C, Caporossi T. Parasurgical therapy for keratoconus by riboflavin-ultraviolet type A rays induced cross-linking of corneal collagen: preliminary refractive results in an Italian study. J Cataract Refract Surg. 2006 May;32(5):837-45. doi: 10.1016/j.jcrs.2006.01.091.
• Mazzotta C, Traversi C, Baiocchi S, Sergio P, Caporossi T, Caporossi A. Conservative treatment of keratoconus by riboflavin-uva-induced cross-linking of corneal collagen: qualitative investigation. Eur J Ophthalmol. 2006 Jul-Aug;16(4):530-5. doi: 10.1177/112067210601600405.
• Price MO, Fairchild K, Feng MT, Price FW Jr. Prospective Randomized Trial of Corneal Cross-linking Riboflavin Dosing Frequencies for Treatment of Keratoconus and Corneal Ectasia. Ophthalmology. 2018 Apr;125(4):505-511. doi: 10.1016/j.ophtha.2017.10.034. Epub 2017 Dec 2.

Helpful Links

• Price Vision Group Website

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): May 30, 2017
• Study Completion (Actual): August 30, 2017

Study Registration Dates

• First Submitted: June 11, 2010
• First Submitted That Met QC Criteria: June 11, 2010
• First Posted (Estimate): June 14, 2010

Study Record Updates

• Last Update Posted (Actual): June 6, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Keratoconus; cross linking; collagen cross linking; Ectasia
• Additional Relevant MeSH Terms: Eye Diseases; Pathological Conditions, Anatomical; Corneal Diseases; Keratoconus; Dilatation, Pathologic; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Vitamin B Complex; Riboflavin
• Other Study ID Numbers: 2010-0243 (M D Anderson Cancer Center)