Treatment of Keratoconus Using Collagen Cross-Linking - Full Text View

Sponsored by:	University at Buffalo School of Medicine
Information provided by:	University at Buffalo School of Medicine
ClinicalTrials.gov Identifier:	NCT00841386

Purpose

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. .

Condition	Intervention	Phase
Keratoconus	Drug: Riboflavin-5-phosphate Drug: Sham cross-linking	Phase II Phase III

Drug Information available for: Riboflavin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Double Blind (Subject, Caregiver, Outcomes Assessor), Parallel Assignment, Placebo Control, Randomized, Safety/Efficacy Study, Treatment
Official Title:	Treatment of Keratoconus Using Collagen Cross-Linking By Means of Topical Riboflavin and UV Light.

Further study details as provided by University at Buffalo School of Medicine:

Primary Outcome Measures:

Best corrected visual acuity [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
Spherical equivalent power of the cornea (Best spectacle refraction) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
KMax: the maximum corneal curvature [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
Average corneal power of the cornea in the central 4 mm. [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Corneal resistance factor. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Maximal posterior surface elevation of the cornea. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Apical corneal thickness. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
Endothelial count. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	150
Study Start Date:	September 2008
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Cross-linking treatment: Experimental 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.
Sham treatment group: Sham Comparator 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.

Arms

Assigned Interventions

Cross-linking treatment: Experimental

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.

Sham treatment group: Sham Comparator

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.

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.

Eligibility

Ages Eligible for Study:	16 Years to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00841386

Contacts

Contact: James J. Reidy, M.D.	716-881-7920	jreidymd@mac.com
Contact: Jeanne Stutz	716-881-7920	jstutz@buffalo.edu

Locations

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

Sponsors and Collaborators

University at Buffalo School of Medicine

Investigators

Principal Investigator:

James J Reidy, M.D.

SUNY at Buffalo School of Medicine & Biomedical Sciences

More Information

Additional Information:

National Keratoconus Foundation This link exits the ClinicalTrials.gov site

Publications of Results:

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. 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.

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. Review.

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.

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.

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.

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.

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.

Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol. 2006 Aug;17(4):356-60. Review.

Responsible Party:	Department of Ophthalmology, SUNY at Buffalo ( James J. Reidy, M.D. )
Study ID Numbers:	101365
Study First Received:	February 10, 2009
Last Updated:	February 10, 2009
ClinicalTrials.gov Identifier:	NCT00841386 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University at Buffalo School of Medicine:

Collagen cross-linking
Cornea
Ectasia
Keratoconus
Riboflavin

Study placed in the following topic categories:

Corneal Diseases
Vitamin B Complex
Dilatation, Pathologic
Eye Diseases
Flavin Mononucleotide
Lidocaine
Anesthetics
Trace Elements

Keratoconus
Photosensitizing Agents
Radiation-Sensitizing Agents
Riboflavin
Vitamins
Micronutrients
Dextrans

Additional relevant MeSH terms:

Corneal Diseases
Vitamin B Complex
Eye Diseases
Growth Substances
Flavin Mononucleotide
Physiological Effects of Drugs
Keratoconus
Pharmacologic Actions

Photosensitizing Agents
Riboflavin
Radiation-Sensitizing Agents
Therapeutic Uses
Vitamins
Micronutrients
Dermatologic Agents

ClinicalTrials.gov processed this record on March 13, 2009