Safety and Effectiveness of Collagen Cross Linking in Progressive Mild and Moderate Keratoconus

Progressive Keratoconus Clinical Trial

Official title:

The Safety and Effectiveness of Collagen Cross Linking With Riboflavin and Ultraviolet-A Light in Progressive Mild and Moderate Grades of Keratoconus.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00815256
• Other study ID #: 1970/07
• Status: Recruiting
• Phase: Phase 3
• First received: December 26, 2008
• Last updated: December 26, 2008
• Start date: August 2008

Study information

• Verified date: November 2008
• Source: Federal University of São Paulo
• Contact: Patricia Z Serapicos, MD
• Phone: 55(11)82738907
• Email: patricia.serapicos[@]yahoo.com.br
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effectiveness of collagen cross linking (CXL) in reducing progression of mild and moderate progressive keratoconus.

Description:

Keratoconus is a corneal degeneration characterized by bilateral conical protusion and corneal thinning. The course of the disease varies from slight irregular astigmatism to severe visual impairment due to increasing protrusion and subepithelial scarring. There is no treatment available that can stop keratoconus progression. Thus, because of its progressive nature, keratoconus is the most frequent reason for keratoplasty worldwide in the past 3 decades.

The collagen crosslinking (CXL) technique using riboflavin and ultraviolet - A (UVA) light was recently developed to counteract the progressive corneal thinning, and thus the progression of keratoconus. With crosslinking, additional covalent binding between collagen molecules can be achieved, which stabilizes the collagen scaffold and enhances corneal resistance.

Prospective longitudinal randomized case-control study including progressive keratoconus cases is addressed to evaluate the effectiveness of collagen cross linking (CXL) in reducing progression of mild and moderate progressive keratoconus. Progression is based on increase in the cone apex keratometry of - 0,75 D, alteration of - 0,75 D in the spherical equivalent or increase of the anterior chamber depth on Pentacan, in a period of at least six months. All patients must be between 15 and 40 year old and are randomized and allocated in the treated or the control groups. Complete exam before and after exam included best corrected visual acuity, refraction, IOP, fundoscopy, imaging exams such as corneal computerized topographic, pentacan, orbscan, ultrasound pachymetry, esthesiometry, endothelial cell count, HRT II system confocal microscopy, optic coherence tomography (VISANTE), ORA , optic coherence tomography (Stratus OCT) and dynamic contour tonometry . All the exams are repeated 1, 3, 6 and 12 months after the procedure. The cross linking is performed as follows: after topical anesthesia, the epithelial tissue is removed in a 8.0mm diameter area of the central cornea, the 0,1% riboflavin solution is applied every 2 min, for 30 min followed by cornea irradiation with UVA light with a wavelength of 370 nm and an irradiance of 3 mW/cm2. During the irradiation, drops of the riboflavin solution is continuously applied onto the cornea every 5 min.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 40 Years

Eligibility

Inclusion Criteria:

• Keratoconus patients, with progression of the disease, based on an increase in the cone apex keratometry of - 0,75 D, alteration of - 0,75 D in the spherical equivalent or increase of the anterior chamber depth on pentacan, in a period of at least six months.

Exclusion Criteria:

• pregnancy, corneal thickness less than 400 µm, history of corneal surgery, herpes ocular infection, other corneal disease or scarring, chemical injuries and riboflavin allergy

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cornea Degeneration
• Keratoconus
• Progressive Keratoconus

Intervention

Procedure:
• Collagen Cross Linking with Riboflavin and UVA light
The patients randomized and allocated to this group are submitted to the treatment with riboflavin and ultraviolet -A light, if they do not match any of the exclusion criterion. The treatment is done as follows:after topical anesthesia, the epithelial tissue was removed in a 8.0mm diameter area of the central cornea, the 0,1% riboflavin solution were applied every 2 min, for 30 min followed by cornea irradiation with UVA light with a wavelength of 370 nm and an irradiance of 3 mW/cm2. During the irradiation, drops of the riboflavin solution were continuously applied onto the cornea every 5 min. After the procedure, a therapeutic contact lens and antibiotic eye ointment are applied onto the cornea for a week. We see the patient in the next day.

Locations

Country	Name	City	State
Brazil	Department of Ophthalmology, Federal University of São Paulo	São Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
Federal University of São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stop progression of keratoconus in cornea imaging exams		1, 3, 6 and 12 months	Yes
Secondary	Increase in the collagen fibrils density in the confocal microscopy; sensitivity in the esthesiometry; Keratometry (stabilizes or reduces) in the topography; anterior chamber depth on pentacan; etc		1, 3, 6 and 12 months	Yes