Adapted Fluence Settings for Corneal Collagen Cross-linking in Mild to Moderate Progressive Keratoconus

Adapted Fluence Settings for Corneal Collagen Cross-linking in Progressive Mild to Moderate Keratoconus Aged 18 to 30

the purpose of this study is to compare the efficacy and safety of a new method of corneal cross-linking that uses UV-A irradiation intensity of 9mW/cm2 for 7 minutes to well-known Accelerated corneal cross-linking (9 mW/cm2 UV-A irradiation for 10 minutes)

Study Overview

• Status: Unknown
• Conditions: Keratoconus
• Intervention / Treatment: Radiation: adjusted corneal collagen cross-linking; Drug: riboflavin 0.1% combined with dextran 20 %; Procedure: epithelial debridement; Radiation: accelerated corneal collagen cross-linking

Detailed Description

This study is a Prospective interventional clinical trial comparing two groups of mild to moderate progressive keratoconic patients; Control group will be treated with routine accelerated protocol of corneal cross-linking, while exposure time will be decreased in the experimental group.

we considered two groups of patients in our study:

• Group 1 (experimental): Exposure to 7 minutes at 9 mW/cm2 = 3.78 J/cm2
• Group 2 (controls): Exposure to 10 minutes at 9 mW/cm2 = 5.4 J/cm2

All demographic data of patients, their uncorrected distance visual acuity (UCDVA), corrected distance visual acuity (BCDVA), sphere and cylinder refraction, keratometry readings (k1 and k2) and other topographic parameters of the patients before the procedure and at every follow up visit will be recorded.

Corneal hysteresis and resistance factor will be checked by Ocular response analyzer before surgery and will be rechecked at 6 month follow up.

Intraoperative pain will also be recorded based on the visual analog scale (VAS + FACES pain scale) immediately after the completion of surgery.

Confocal microscopy will be used to evaluate changes in corneal stromal collagen fibers and keratocytes following cross-linking at 3 and 6 and 12 month post op period.

All procedures will be done by a single surgeon. We will use topical anesthesia by tetracaine followed by mechanical epithelial debridement at a radius of 9 millimeters. Then riboflavin 0.1% combined with dextran 20 % will be instilled every 3 minutes for 25 minutes. A short irrigation of the surface with BSS (to avoid a layer of riboflavin on the cornea during irradiation) will be performed. Corneal thickness will be determined by ultrasound pachymetry. If needed, hypoosmolar solution will be used to swell the cornea over 400 µm. If 400 µm cannot be reached, then irradiation will not be performed. Then we will irradiate the eye by the UV A light source 5cm away from the eye with a light intensity of 9 mW/cm2 for 10 minutes in control group and 7 minutes in experimental group and riboflavin will be instilled after 5 minutes for further in both groups, followed by a short irrigation of the surface with BSS (to avoid a layer of riboflavin on the cornea during irradiation).

After the procedure we will apply a bandage contact lens for 5- 7 days and will prescribe topical betamethasone every 6 hours for 2 weeks, tapered to TDS, BID and HS weekly for a total duration 5 weeks. A topical antibiotic drop (Oftaquix every 6 hours) will be used for the first week.

Patients will be followed up at day 1, day 6, 1 month, 3 months and 6 months and 12 months after surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1336616351
    • Farabi Eye Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Mild to moderate progressive KCN (Grade I and II) based on Amsler-krumeich classification; progression is defined as the old fashioned way in the lack of a consensus for more modern methods that is increase of > 1D of Kmax readings within 12 months
• Age> 18 y, and <35 years
• Kmax lower than 58 D
• Signing informed consent form

Exclusion Criteria:

• Any other ocular disease
• Corneal scar
• History of hydrops
• Any other ocular surgery including previous CCL, corneal inlay or keratorefractive surgery
• Inability to complete follow up schedule

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental; Radiation: adjusted corneal collagen cross-linking (9mW/cm2 UV-A irradiation for 7 minutes after 30 mitunes of riboflavin instillation) riboflavin 0.1%: after mechanical epithelial removal riboflavin drop will be instilled every 5 minutes for 30 minutes and then instillation will be continued during irradiation epithelial debridement: corneal epithelium will be removed by a cottons swab	Radiation: adjusted corneal collagen cross-linking; UV-A irradiation for 7 minutes; Drug: riboflavin 0.1% combined with dextran 20 %; after mechanical epithelial removal riboflavin drop will be instilled every 5 minutes for 30 minutes and then instillation will be continued during irradiation; Procedure: epithelial debridement; corneal epithelium will be removed by a cottons swab; Other Names: epithelium removal
Active Comparator: control; radiation: accelerated corneal collagen cross-linking (9mW/cm2 UV-A irradiation for 10 minutes after 30 minutes of riboflavin instillation) riboflavin 0.1%: after mechanical epithelial removal riboflavin drop will be instilled every 5 minutes for 30 minutes and then instillation will be continued during irradiation epithelial debridement: corneal epithelium will be removed by a cottons swab	Drug: riboflavin 0.1% combined with dextran 20 %; after mechanical epithelial removal riboflavin drop will be instilled every 5 minutes for 30 minutes and then instillation will be continued during irradiation; Procedure: epithelial debridement; corneal epithelium will be removed by a cottons swab; Other Names: epithelium removal; Radiation: accelerated corneal collagen cross-linking; UV-A irradiation for 10 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
keratometric values on pentacam measured by Javal keratometer	one year
best corrected visual acuity	one year
uncorrected distant visual acuity	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
clinical refraction	one year
endothelial cell count	one year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
corneal thickness		one year
corneal hysteresis		one year
corneal resistance factor		one year
intraoperative discomfort and pain	Visual Analog scale	up to 1 hour

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Investigators: Principal Investigator: Fateme Alipour, MD, Eye research center, Farabi eye hospital, Tehran university of medical science

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): February 1, 2016

Study Registration Dates

• First Submitted: August 6, 2014
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (Estimate): July 23, 2015

Study Record Updates

• Last Update Posted (Estimate): July 23, 2015
• Last Update Submitted That Met QC Criteria: July 22, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: keratoconus , corneal collagen cross-linking
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Anticoagulants; Vitamin B Complex; Plasma Substitutes; Blood Substitutes; Riboflavin; Dextrans
• Other Study ID Numbers: ERC/S/9341