Higher Irradiance in Keratoconus Ectasia - Full Text View

Purpose

The purpose of the study is to see if brighter lights will allow us to shorten the treatment time required to stabilize the eyes of patients with keratoconus or a bulging cornea. The investigators will be comparing the effects of two different higher brightnesses of ultra violet light on a riboflavin treated eye. One light will be twice as bright as the other and the exposure time of these brighter light will be reduced from the standard 30 minutes to 10 and 5 minutes. Riboflavin is vitamin B12 and the investigators are trying to determine if they can get an identical clinical effect when they use the brighter treatment lights for shorter times. The investigators will also monitor the clinical effect and the status of the cornea to see if additional risks are associated with the brighter light.

Condition	Intervention
Keratoconus Ectasia	Device: UVA Light with irradiance exposure of 9 mW/cm2 Drug: Riboflavin 0.1% ophthalmic solution Device: UVA Light with irradiance exposure of 18 mW/cm2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Study of the Safety and Effectiveness of Photochemically Induced Collagen Cross- Linking at Higher Irradiances in Patients With Keratoconus or Ectasia

Resource links provided by NLM:

MedlinePlus related topics: Corneal Disorders

Drug Information available for: Riboflavin

U.S. FDA Resources

Further study details as provided by Columbia University:

Primary Outcome Measures:

Change in Total Higher Order Aberrations of the Cornea [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
The change in corneal topography and optical properties from baseline will be evaluated at 3 and 6 months for all eyes.

Secondary Outcome Measures:

Change in Uncorrected Visual Acuity (UCVA) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
Change in Best Spectacle Corrected Visual Acuity (BSCVA) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
Change in Manifest Refraction [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]

Other Outcome Measures:

Change in depth of the effect with Optical Coherence Tomography (OCT) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
To assess the hypothesis the higher irradiance produces the same pattern of change, we will measure the depth of the effect with Optical Coherence Tomography. If the depth and pattern of the interaction is equivalent for both the low and high irradiances, then we will clearly demonstrate that the nature of the photochemical interaction is identical. If, on the other hand, the higher irradiance creates a different effect as noted on the OCT, then the hypothesis of equivalence must be questioned.

Estimated Enrollment:	6
Study Start Date:	August 2010
Estimated Study Completion Date:	February 2013
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 9 mw/cm2 group Three patients will be treated at 9 mw/cm2.	Device: UVA Light with irradiance exposure of 9 mW/cm2 The device's light emitting diode (LED) is used to deliver a metered dose of UV-A light to a targeted treatment area for illuminating the cornea during corneal collagen cross-linking. The aperture setting will be set at 10 mm, and the eye will be irradiated for 10 minutes for the high irradiance exposure of 9 mW/cm2. During the exposure, instillation of riboflavin will continue (1 drop every 3 minutes). Drug: Riboflavin 0.1% ophthalmic solution The speculum is removed and one (1) drop of Riboflavin 0.1% ophthalmic solution will be instilled topically in the eye every 3 minutes for 30 minutes. At the end of the 30 minute riboflavin pre-treatment period, the eye will be examined to assure the presence of a yellow flare in the anterior chamber, indicating riboflavin saturation of the corneal tissue. If the yellow flare is not detected, riboflavin will continue to be instilled until the presence of the yellow flare in the anterior chamber is confirmed. During UVA irradiation, instillation of riboflavin will be continued every 3 minutes. For a 30-minute pre-treatment and 30-minute irradiation, the total dose of riboflavin solution is approximately 32 drops, or 1.6 ml (1 drop = 0.05 ml; 1.6 mL = 1.6 mg riboflavin). Other Name: Riboflavin
18 mw/cm2 group Three patients will be treated at 9 mw/cm2. If the endothelial studies show no damage then the next three patients will be treated at 18 mw/cm2.	Drug: Riboflavin 0.1% ophthalmic solution The speculum is removed and one (1) drop of Riboflavin 0.1% ophthalmic solution will be instilled topically in the eye every 3 minutes for 30 minutes. At the end of the 30 minute riboflavin pre-treatment period, the eye will be examined to assure the presence of a yellow flare in the anterior chamber, indicating riboflavin saturation of the corneal tissue. If the yellow flare is not detected, riboflavin will continue to be instilled until the presence of the yellow flare in the anterior chamber is confirmed. During UVA irradiation, instillation of riboflavin will be continued every 3 minutes. For a 30-minute pre-treatment and 30-minute irradiation, the total dose of riboflavin solution is approximately 32 drops, or 1.6 ml (1 drop = 0.05 ml; 1.6 mL = 1.6 mg riboflavin). Other Name: Riboflavin Device: UVA Light with irradiance exposure of 18 mW/cm2 The device's light emitting diode (LED) is used to deliver a metered dose of UV-A light to a targeted treatment area for illuminating the cornea during corneal collagen cross-linking. The aperture setting will be set at 10 mm, and the eye will be irradiated for 5 minutes at 18 mW/cm2. During the exposure, instillation of riboflavin will continue (1 drop every 3 minutes).

Arms

Assigned Interventions

Experimental: 9 mw/cm2 group

Three patients will be treated at 9 mw/cm2.

Device: UVA Light with irradiance exposure of 9 mW/cm2

The device's light emitting diode (LED) is used to deliver a metered dose of UV-A light to a targeted treatment area for illuminating the cornea during corneal collagen cross-linking.

The aperture setting will be set at 10 mm, and the eye will be irradiated for 10 minutes for the high irradiance exposure of 9 mW/cm2. During the exposure, instillation of riboflavin will continue (1 drop every 3 minutes).

Drug: Riboflavin 0.1% ophthalmic solution

The speculum is removed and one (1) drop of Riboflavin 0.1% ophthalmic solution will be instilled topically in the eye every 3 minutes for 30 minutes. At the end of the 30 minute riboflavin pre-treatment period, the eye will be examined to assure the presence of a yellow flare in the anterior chamber, indicating riboflavin saturation of the corneal tissue. If the yellow flare is not detected, riboflavin will continue to be instilled until the presence of the yellow flare in the anterior chamber is confirmed.

During UVA irradiation, instillation of riboflavin will be continued every 3 minutes. For a 30-minute pre-treatment and 30-minute irradiation, the total dose of riboflavin solution is approximately 32 drops, or 1.6 ml (1 drop = 0.05 ml; 1.6 mL = 1.6 mg riboflavin).

Other Name: Riboflavin

18 mw/cm2 group

Three patients will be treated at 9 mw/cm2. If the endothelial studies show no damage then the next three patients will be treated at 18 mw/cm2.

Drug: Riboflavin 0.1% ophthalmic solution

The speculum is removed and one (1) drop of Riboflavin 0.1% ophthalmic solution will be instilled topically in the eye every 3 minutes for 30 minutes. At the end of the 30 minute riboflavin pre-treatment period, the eye will be examined to assure the presence of a yellow flare in the anterior chamber, indicating riboflavin saturation of the corneal tissue. If the yellow flare is not detected, riboflavin will continue to be instilled until the presence of the yellow flare in the anterior chamber is confirmed.

During UVA irradiation, instillation of riboflavin will be continued every 3 minutes. For a 30-minute pre-treatment and 30-minute irradiation, the total dose of riboflavin solution is approximately 32 drops, or 1.6 ml (1 drop = 0.05 ml; 1.6 mL = 1.6 mg riboflavin).

Other Name: Riboflavin

Device: UVA Light with irradiance exposure of 18 mW/cm2

The device's light emitting diode (LED) is used to deliver a metered dose of UV-A light to a targeted treatment area for illuminating the cornea during corneal collagen cross-linking.

The aperture setting will be set at 10 mm, and the eye will be irradiated for 5 minutes at 18 mW/cm2. During the exposure, instillation of riboflavin will continue (1 drop every 3 minutes).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects who have one or both eyes that meet two of the following criteria will be considered candidates for this study:

18 years of age or older
Having a diagnosis of progressive keratoconus defined as one or more of the following changes over a period of 24 months or less before randomization:
1. An increase of ≥ 1.00 D in the steepest keratometry value (or simK)
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
Presence of central or inferior steepening on the Pentacam map.
Axial topography consistent with keratoconus
Steepest manual keratometry (Kmax) value ≥ 47.00 D
Best spectacle corrected visual acuity (BSCVA) worse than 20/20
Signed written informed consent
Willingness and ability to comply with schedule for follow-up visits
Contact lens removal prior to treatment

Inclusion criteria for ectasia

History of having undergone a keratorefractive procedure and:
1. Steepening by topography, either Pentacam or Humphrey
2. Thinning of cornea
3. Shift in the position of thinnest portion of cornea
4. Change in refraction with increasing myopia
5. Development of myopic astigmatism
6. Development of irregular astigmatism
7. Loss of BSCVA
At least two of the above criteria must be present.

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from this study:

Eyes classified as either normal, atypical normal, or keratoconus suspect on the severity grading scheme.
A history of previous corneal surgery or the insertion of Intacs in the eye(s) to be treated.
Corneal pachymetry ≤ 350 microns at the thinnest point measured by Pentacam in the eye to be treated
A history of chemical injury or delayed epithelial healing in the eye to be treated.
Pregnancy (including plan to become pregnant) or lactation during the course of the study
A known sensitivity to study medications
Patients with nystagmus or any other condition that would prevent a steady gaze during the Collagen Cross-Linking (CCL) treatment or other diagnostic tests.
Patients with a current condition that, in the investigator's opinion, would interfere with or prolong epithelial healing.
Taking Vitamin C (ascorbic acid) supplements within 1 week of the cross-linking treatment.
Patients who are unable to remain supine and tolerate a lid speculum for an extended period of time.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01789333

Contacts

Contact: MaEdylin Bautista

212-305-5922

mmb2225@columbia.edu

Locations

United States, New York
Edward Harkness Eye Institute-Columbia University Medical Center	Recruiting
New York, New York, United States, 10032
Contact: MaEdylin Bautista 212-305-5922 mmb2225@columbia.edu
Principal Investigator: Stephen Trokel, MD

Sponsors and Collaborators

Stephen Trokel

Investigators

Principal Investigator:

Stephen Trokel, MD

Columbia University

More Information

No publications provided

Responsible Party:	Stephen Trokel, Professor of Clinical Ophthalmology, Columbia University
ClinicalTrials.gov Identifier:	NCT01789333 History of Changes
Other Study ID Numbers:	AAAF4157
Study First Received:	November 20, 2012
Last Updated:	February 8, 2013
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by Columbia University:

Keratoconus
Ectasia
UVA light

riboflavin
post-LASIK
irregular astigmatism

Additional relevant MeSH terms:

Riboflavin
Dilatation, Pathologic
Keratoconus
Pathological Conditions, Anatomical
Corneal Diseases
Eye Diseases
Photosensitizing Agents
Radiation-Sensitizing Agents

Physiological Effects of Drugs
Pharmacologic Actions
Dermatologic Agents
Therapeutic Uses
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on May 21, 2013