Clinical trial NCT01325298: UVA-Riboflavin Crosslinking Treatment of Corneal Ectasia
Official title: UVA-Riboflavin Crosslinking Treatment of Corneal Ectasia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Keratoconus
Ectasia
Corneal Ectasia
Keywords: Keratoconus
Ectasia
cross linking
collagen cross linking
corneal crosslinking
corneal diseases
eye diseases
Lead sponsor: Mercy Center for Corrective Eye Surgery
Sponsor class: OTHER
First posted: 2011-03-29
Enrollment: 250
Sex: ALL
Minimum age (years): 14
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in corneal curvature
timeFrame: 6 months
Secondary outcomes:
measure: corrected distance acuity
timeFrame: 6 months
measure: corneal endothelial cell count
timeFrame: 6 months
measure: pachymetry
timeFrame: 6 months
Other outcomes:
Locations:
city: McHenry
country: United States
facility: Mercy Center for Corrective Eye Surgery
state: Illinois
Study officials:
affiliation: Mercy Center for Corrective Eye Surgery
name: Robert L Epstein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Caporossi A, Mazzotta C, Baiocchi S, Caporossi T. Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. Am J Ophthalmol. 2010 Apr;149(4):585-93. doi: 10.1016/j.ajo.2009.10.021. Epub 2010 Feb 6.
citation: Goldich Y, Marcovich AL, Barkana Y, Avni I, Zadok D. Safety of corneal collagen cross-linking with UV-A and riboflavin in progressive keratoconus. Cornea. 2010 Apr;29(4):409-11. doi: 10.1097/ICO.0b013e3181bd9f8c.
citation: Wittig-Silva C, Whiting M, Lamoureux E, Lindsay RG, Sullivan LJ, Snibson GR. A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results. J Refract Surg. 2008 Sep;24(7):S720-5. doi: 10.3928/1081597X-20080901-15.
citation: 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.
citation: 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. doi: 10.1177/112067210601600405.
citation: 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. doi: 10.1016/j.jcrs.2006.01.091.