Treatment of Keratoconus Using Collagen Cross-Linking

Treatment of Keratoconus Using Collagen Cross-Linking By Means of Topical Riboflavin and UV Light.

The purpose of this study is to determine the effectiveness of collagen cross-linking in the cornea in halting the progression and possibly partially reversing the effects of keratoconus. Keratoconus is a progressive weakening in the cornea that causes irregular astigmatism and thinning of the cornea. The overall effect is reduction of vision, and in more advanced cases, scarring of the cornea that may lead to the need for corneal transplantation. Cross-linking has been shown increase the rigidity of the cornea. The patients would be treated once and then followed over 24 months. .

Study Overview

• Status: Unknown
• Conditions: Keratoconus
• Intervention / Treatment: Drug: Riboflavin-5-phosphate; Drug: Sham cross-linking

Detailed Description

The goal is for two groups of approximately 66 patients to be included in the study. One eye from the first group will undergo treatment, while the second group of age matched individuals will serve as a control. It will be a prospective, randomized, blinded study. Each patient will be randomized at the beginning of enrollment in the study and will receive a randomization number. The following parameters will be followed: 1. Best corrected spectacle acuity (BCSA) 2. The steepest keratometry measurement (KMax) as measured by computerized corneal topography 3. Apical corneal thickness 4. Corneal mechanical resistance. These measurements will be repeated at 1 month, 3 months, 6 months, 12, 18, and 24 months following treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Amherst, New York, United States, 14228
      • Recruiting
      • Fichte,Endl, & Elmer EyeCare
      • Contact: Linda Grant, C.O.M.T.; Phone Number: 716-564-2020; Email: linda.grant@fichte.com
      • Contact: Michael Endl, M.D.; Phone Number: 716-564-2020; Email: mpderme@aol.com
      • Principal Investigator: Michael Endl, M.D.
      • Sub-Investigator: Thomas R Elmer, M.D.
    • Buffalo, New York, United States, 14209
      • Recruiting
      • The Ira G. Ross Eye Institute
      • Contact: James J Reidy, M.D.; Phone Number: 716-881-7920; Email: jreidymd@mac.com
      • Principal Investigator: James J Reidy, M.D.
      • Sub-Investigator: Sandra L Everett, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 35 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• no prior history of ocular surgery
• treatment eye must have a maximum corneal power of between 47 D and 60 diopters
• corneal thickness must be greater than 400 µ
• absence of corneal scarring

• patients must meet the diagnostic criteria for keratoconus, which include one or more of the following features:

  • high myopia
  • corneal ectasia as viewed by slit-lamp exam or measured by pachometry
  • Vogt's striae
  • topographic findings of superior flattening and inferior steepening of the cornea
  • presence of Fleischer ring

Exclusion Criteria:

• history of prior ocular surgery (history of contact lens use is not an exclusion criterion)
• average corneal power > 60 D
• presence of corneal scarring
• corneal thickness 400 µ or less
• history of herpes simplex virus keratitis
• history of uveitis
• pre-existing glaucoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cross-linking treatment; Topical anesthesia (lidocaine jelly 2%) will be used. The central 9 mm of corneal epithelium will be removed cautiously with an Amoils brush. Riboflavin 0.1% solution will be applied (10 mg riboflavin-5-phosphate in 10 ml dextran T-500 20% solution, supplied in a sterile, single dose container) to the cornea every 2-3 minutes for 15 minutes and then every 5 minutes thereafter. The UV source will be from the CBM VEGA X-linker (CSO, Florence, Italy). A wavelength of 370 nm will be used to direct 5.4 J/cm2 to the area of cornea debrided for 30 minutes. The distance from the UV source to the cornea will be 1.5 to 5.4 cm.	Drug: Riboflavin-5-phosphate; Riboflavin 0.1% (10 mg riboflavin-5-phosphate in 10 ml dextran T-500 20% solution, supplied in a sterile, single dose container) will be applied to the cornea every 2-3 minutes for 15 minutes prior to starting UV irradiation. The UV irradiation will be given in six 5 minute intervals. Additional riboflavin will be administered following each 5 minute UV treatment.; Other Names: Ricrolin (SOOFT Italia Inc.)
SHAM_COMPARATOR: Sham treatment group; Topical anesthesia (lidocaine jelly 2%) will be used. Differing from the treatment group, no epithelium will be debrided, but instead, this step will be skipped and a 2% methylcellulose solution combined with 1% fluorescein dye will be applied to the cornea every 5 minutes for 30 minutes. The patient will be placed under the UV device, but instead of the UV light, the LED aiming beam will be applied for 30 minutes.	Drug: Sham cross-linking; Topical anesthesia (lidocaine jelly 2%) will be used. Differing from the treatment group, no epithelium will be debrided, but instead, this step will be skipped and 2% methylcellulose solution with 1% sodium fluorescein will be applied to the cornea every 5 minutes for 15 minutes, and then every 5 minutes during the sham UV treatment. The patient will be placed under the UV device, and the aiming beam applied.; Other Names: Goniosol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Best corrected visual acuity	24 months
Spherical equivalent power of the cornea (Best spectacle refraction)	24 months
KMax: the maximum corneal curvature	24 months
Average corneal power of the cornea in the central 4 mm.	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Corneal resistance factor.	24 months
Maximal posterior surface elevation of the cornea.	24 months
Apical corneal thickness.	24 months
Endothelial count.	24 months

Collaborators and Investigators

• Sponsor: University at Buffalo
• Investigators: Principal Investigator: James J Reidy, M.D., SUNY at Buffalo School of Medicine & Biomedical Sciences

Publications and helpful links

General Publications

• Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7. doi: 10.1016/s0002-9394(02)02220-1.
• Natarajan R, Padmanabhan P, Guruswami S. Hydration behavior of porcine cornea crosslinked with riboflavin and ultraviolet A. J Cataract Refract Surg. 2007 Sep;33(9):1503. doi: 10.1016/j.jcrs.2007.04.047. No abstract available.
• Mazzotta C, Balestrazzi A, Traversi C, Baiocchi S, Caporossi T, Tommasi C, Caporossi A. Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomograph II in vivo confocal microscopy in humans. Cornea. 2007 May;26(4):390-7. doi: 10.1097/ICO.0b013e318030df5a.
• Spoerl E, Mrochen M, Sliney D, Trokel S, Seiler T. Safety of UVA-riboflavin cross-linking of the cornea. Cornea. 2007 May;26(4):385-9. doi: 10.1097/ICO.0b013e3180334f78.
• 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.
• Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol. 2006 Aug;17(4):356-60. doi: 10.1097/01.icu.0000233954.86723.25.
• 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.
• Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE. Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg. 2006 Feb;32(2):279-83. doi: 10.1016/j.jcrs.2005.12.092.
• Mencucci R, Mazzotta C, Rossi F, Ponchietti C, Pini R, Baiocchi S, Caporossi A, Menchini U. Riboflavin and ultraviolet A collagen crosslinking: in vivo thermographic analysis of the corneal surface. J Cataract Refract Surg. 2007 Jun;33(6):1005-8. doi: 10.1016/j.jcrs.2007.03.021.

Helpful Links

• National Keratoconus Foundation

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ANTICIPATED): December 1, 2011
• Study Completion (ANTICIPATED): December 1, 2011

Study Registration Dates

• First Submitted: February 10, 2009
• First Submitted That Met QC Criteria: February 10, 2009
• First Posted (ESTIMATE): February 11, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): February 11, 2009
• Last Update Submitted That Met QC Criteria: February 10, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Keywords: Cornea; Keratoconus; Riboflavin; Ectasia; Collagen cross-linking
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Vitamin B Complex; Riboflavin; Flavin Mononucleotide
• Other Study ID Numbers: 101365