UVA-Riboflavin Crosslinking Treatment of Corneal Ectasia

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate two different ultraviolet (UV) dosing regimens for corneal collagen cross linking to slow the progressive changes in corneal curvature in eyes with progressive keratoconus or post-refractive surgery ectasia.

Official Title
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UVA-Riboflavin Crosslinking Treatment of Corneal Ectasia

Conditions
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Keratoconus, Ectasia, Corneal Ectasia

Intervention / Treatment
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* Device: UV-X Light
* Drug: Riboflavin
* Device: UV-X Light
* Drug: Riboflavin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: i. Age 14 years or older for keratoconus subjects since disease often begins at puberty, and 18 years or older for post-refractive surgery keratectasia and post-transplant patients ii. Signed, dated, written informed consent iii. Having documented ectasia on topography or tomography after previous refractive surgery OR progressive keratoconus defined as one or more of the following changes over a period of 24 months or less before randomization: An increase of at least 1.0 diopter in the steepest keratometry value (or sim K), or an increase of at least 1.0 diopter in regular astigmatism evaluated by subjective manifest refraction, or a myopic shift (decrease in the spherical equivalent) of at least 0.5 diopters on subjective refraction, or documented decrease in visual acuity associated with irregular astigmatism and topographic features of ectasia iv. Have minimal preoperative corneal thickness of 375 microns or more, as measured in the office with epithelium not yet removed v. For subjects with non-post refractive surgery keratoconus diagnosis only: 14 years or older to 55 years of age, axial topography consistent with keratoconus such as presence of abnormal central or paracentral steepening on the corneal topography map, or presence of one or more slit lamp findings associated with keratoconus, such as Fleischer ring Vogt striae Corneal thinning Corneal scarring vi. For contact lens wearers only: Removal of contact lenses for the required period of time prior to final screening refraction: Contact lens minimum discontinuation time two weeks for soft, extended wear, soft toric, and rigid gas permeable lenses vii. For patients with post-refractive surgery keratectasia: History of excimer laser refractive surgery with increasing refractive astigmatism and corneal topographic or keratometric astigmatism of 0.5 or more, or a history of decreasing best spectacle corrected visual acuity associated with the presence of topography suggestive of keratoconus or pellucid marginal degeneration or abnormal higher order aberrations (especially coma) on the aberration mapping of the eye. viii. For patients with corneal transplants: History of corneal transplant for keratoconus with documented increasing refractive astigmatism and corresponding topographic irregularity occurring at least one year after corneal transplantation, not attributable to transplant suture removal and occurring during the most recent two years. Exclusion Criteria: i. Patients with excessively thin corneas. (Intraoperative minimal corneal thickness in the swollen state with the epithelium removed must exceed 400 microns) ii. Keratometric readings greater than 62D iii. No evidence of keratoconus/keratectasia progression over the prior three years iv. Age less than 55 years but under 14 years for keratoconus patients 18 years for post-refractive surgery keratectasia and post-transplant patients v. Previous ocular condition in the eye(s) to be treated that might, in the investigator's opinion, predispose to complications (such as history herpes simplex keratitis, corneal melt, perforated corneal ulcer, descemetocele, prior corneal damage from chemical injury, herpes zoster keratitis, nystagmus, corneal scarring that significantly impairs vision, pre-existing glaucoma, glaucoma suspect, Goldmann applanation pressure exceeding 23 mm Hg, cataract, history of uveitis, active ocular disease that might lead to infection, corneal endothelial cell count below 1800 cells per square millimeter) vi. Patients with a systemic condition that, in the investigator's opinion, might predispose to complications (such as Down syndrome, autoimmune disease, pregnancy or nursing at the time of initial treatment, history of alcohol abuse, being immunocompromised, allergy to riboflavin or other study medications) vii. Patients who are unwilling or unable to comply with the study regimen and doctor's advice viii. Patients unwilling to discontinue wear of rigid contact lenses in the eye to be operated on for at least one month before baseline examination, and for the first six months post-operatively ix. Patient unwilling to discontinue contact lenses prior to baseline exam: one week for soft lenses, two weeks for rigid or soft toric lenses x. Pregnancy at the time of proposed crosslinking xi. Known hypersensitivity to riboflavin xii. Central corneal endothelial cell count below 1400 cells per square millimeter. xiii. Presence of significant central corneal stromal scar xiv. History of delayed wound healing xv. Immunocompromised patient xvi. History of connective tissue disease (such as systemic lupus erythematosus, rheumatoid arthritis) xvii. History of glaucoma, a Goldmann applanation pressure measured in keratoconus evaluation of above 24, or glaucoma suspect, xviii. Significant existing cataract xix. Macular degeneration or confluent drusen of Bruchs membrane xx. Evidence of past or present herpes simplex of the cornea

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 20 Minute UV-X Light Treatment Duration<br>20 Minute UV-X Light Treatment Duration Note: UV-X is the trademark of Peschke GmbH | Device: UV-X Light<br>* UV-X 365 nm wavelength light source is applied to the cornea with continued application of riboflavin 0.1%<br>Drug: Riboflavin<br>* Riboflavin 0.1% is applied to the cornea every 2 minutes for 14 minutes prior to and also during UV-X Light treatment.<br>|
| Active Comparator: 30 Minute UV-X Light Treatment Duration<br>30 Minute UV-X Light Treatment Duration | Device: UV-X Light<br>* UV-X 365 nm wavelength light source is applied to the cornea with continued application of riboflavin 0.1%<br>Drug: Riboflavin<br>* Riboflavin 0.1% is applied to the cornea every 2 minutes for 14 minutes prior to and also during UV-X Light treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in corneal curvature | Measured by maximum keratometry (Kmax) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| corrected distance acuity | best spectacle corrected distance acuity | 6 months | 
| corneal endothelial cell count |  | 6 months | 
| pachymetry | Minimal corneal thickness | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Keratoconus, Ectasia, cross linking, collagen cross linking, corneal crosslinking, corneal diseases, eye diseases