Keratoconus, Post-Refractive Ectasia
Conditions
Keywords
Keratoconus, Ectasia, cross linking, collagen cross linking
Brief summary
The purpose of this study is to evaluate the effectiveness of using riboflavin and UV light to treat progressive keratoconus or post-refractive corneal ectasia.
Detailed description
The primary objective of this study is to evaluate two riboflavin-dosing regimens for corneal collagen cross-linking to slow the progressive changes in corneal curvature in eyes with progressive keratoconus or post-refractive ectasia.
Interventions
DRUGRiboflavin
Riboflavin 0.1% eye drops are applied before and during irradiation of the cornea.
DEVICEUVX light
UVX 365 nm wavelength light source is applied with continued application of riboflavin.
Sponsors
Price Vision Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 10 years of age or older 2. 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 36 months or less before randomization: 1. An increase of ≥ 1.00 D in the steepest keratometry value (or sim K) 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 4. Documented decrease in visual acuity associated with irregular astigmatism and topographic features of ectasia. 3. Subjects with keratoconus diagnosis only: a. Axial topography consistent with keratoconus b. Presence of central or inferior steepening on the Pentacam map. c. Presence of one or more slit lamp findings associated with keratoconus, such as: i. Fleischer ring ii. Vogt striae iii. Corneal thinning iv. Corneal scarring 4. Contact Lens Wearers Only: Removal of contact lenses for the required period of time prior to the screening refraction: Contact Lens Type Minimum Discontinuation Time Soft 3 Days Soft Extended Wear 1 Week Soft Toric 2 Weeks Rigid gas permeable 2 Weeks 5. Signed written informed consent
Exclusion criteria
* 1\. Any keratoconus patient over 21 years of age without evidence of progression of his corneal deformity. 2\. Patients with excessively thin corneas. 3. Previous ocular condition in the eyes to be treated that may predispose the eye for future complications, for example: a. History of corneal disease (e.g., herpes simplex, herpes zoster keratitis, recurrent erosion syndrome, corneal melt, corneal dystrophy, etc.) b. Clinically significant corneal scarring in the proposed treatment zone 4. A history of chemical injury or delayed epithelial healing in the eye(s) to be treated. 5\. A known sensitivity to treatment medications. 6. Patients with a current condition that, in the treating physician's opinion, would interfere with or prolong epithelial healing. 7\. Pregnancy (including plan to become pregnant) or lactation during the course of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Maximum Keratometry From Baseline to 6 Months After Treatment | 6 months | Change in maximum keratometry (Kmax) between baseline and 6 months after treatment, measured by corneal tomography. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pachymetry | 6 months | Minimum corneal thickness measured by corneal tomography |
| Corrected Distance Visual Acuity (CDVA) | 6 months | Corrected distance visual acuity (CDVA) reported in logarithm of the minimum angle of resolution (logMAR). Lower numbers represent better vision; 0.0 corresponds to 20/20 vision. Each increase of 0.1 on the logMAR scale corresponds to one less line read on the eye chart. |
| Uncorrected Distance Visual Acuity (UDVA) | 6 months | Uncorrected distance visual acuity reported in logarithm of the minimum angle of resolution units. Lower numbers represent better vision; 0.0 corresponds to 20/20 vision without any type of correction such as glasses. Each increase of 0.1 on the logMAR scale corresponds to one less line read on the eye chart. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Riboflavin 0.1% Eyedrops Every 5 Minutes The eye will be irradiated for 30 minutes with UVX light, during which time instillation of riboflavin will continue (1 drop every 5 minutes for this arm).
Riboflavin: Riboflavin 0.1% eye drops are applied before and during irradiation of the cornea.
UVX light: UVX 365 nm wavelength light source is applied with continued application of riboflavin. | 253 |
| Riboflavin 0.1% Eyedrops Every 2 Minutes The eye will be irradiated for 30 minutes with UVX light, during which time instillation of riboflavin will continue (1 drop every 2 minutes for this arm).
Riboflavin: Riboflavin 0.1% eye drops are applied before and during irradiation of the cornea.
UVX light: UVX 365 nm wavelength light source is applied with continued application of riboflavin. | 257 |
| Total | 510 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 26 | 25 |
Baseline characteristics
| Characteristic | Riboflavin 0.1% Eyedrops Every 2 Minutes | Total | Riboflavin 0.1% Eyedrops Every 5 Minutes |
|---|---|---|---|
| Age, Continuous | 32 years STANDARD_DEVIATION 13 | 32 years STANDARD_DEVIATION 13 | 32 years STANDARD_DEVIATION 12 |
| Keratoconus/ectasia classification Ectasia after refractive surgery | 54 Participants | 104 Participants | 50 Participants |
| Keratoconus/ectasia classification Keratoconus mild (flat K <51D and astigmatism <8D) | 139 Participants | 279 Participants | 140 Participants |
| Keratoconus/ectasia classification Keratoconus moderate | 43 Participants | 86 Participants | 43 Participants |
| Keratoconus/ectasia classification Keratoconus severe (flat K >56D by tomography) | 21 Participants | 41 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 23 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 52 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 220 Participants | 435 Participants | 215 Participants |
| Region of Enrollment United States | 257 participants | 510 participants | 253 participants |
| Sex: Female, Male Female | 61 Participants | 123 Participants | 62 Participants |
| Sex: Female, Male Male | 196 Participants | 387 Participants | 191 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 253 | 0 / 257 |
| other Total, other adverse events | 12 / 253 | 13 / 257 |
| serious Total, serious adverse events | 0 / 253 | 0 / 257 |
Outcome results
Primary
Change in Maximum Keratometry From Baseline to 6 Months After Treatment
Change in maximum keratometry (Kmax) between baseline and 6 months after treatment, measured by corneal tomography.
Time frame: 6 months
Population: Per protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riboflavin 0.1% Eyedrops Every 5 Minutes | Change in Maximum Keratometry From Baseline to 6 Months After Treatment | 0.76 diopters | Standard Deviation 2.4 |
| Riboflavin 0.1% Eyedrops Every 2 Minutes | Change in Maximum Keratometry From Baseline to 6 Months After Treatment | 0.97 diopters | Standard Deviation 3.2 |
Secondary
Corrected Distance Visual Acuity (CDVA)
Corrected distance visual acuity (CDVA) reported in logarithm of the minimum angle of resolution (logMAR). Lower numbers represent better vision; 0.0 corresponds to 20/20 vision. Each increase of 0.1 on the logMAR scale corresponds to one less line read on the eye chart.
Time frame: 6 months
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riboflavin 0.1% Eyedrops Every 5 Minutes | Corrected Distance Visual Acuity (CDVA) | 0.32 logMAR | Standard Deviation 0.29 |
| Riboflavin 0.1% Eyedrops Every 2 Minutes | Corrected Distance Visual Acuity (CDVA) | 0.31 logMAR | Standard Deviation 0.28 |
Secondary
Pachymetry
Minimum corneal thickness measured by corneal tomography
Time frame: 6 months
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riboflavin 0.1% Eyedrops Every 5 Minutes | Pachymetry | 438 microns | Standard Deviation 51 |
| Riboflavin 0.1% Eyedrops Every 2 Minutes | Pachymetry | 434 microns | Standard Deviation 20 |
Secondary
Uncorrected Distance Visual Acuity (UDVA)
Uncorrected distance visual acuity reported in logarithm of the minimum angle of resolution units. Lower numbers represent better vision; 0.0 corresponds to 20/20 vision without any type of correction such as glasses. Each increase of 0.1 on the logMAR scale corresponds to one less line read on the eye chart.
Time frame: 6 months
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riboflavin 0.1% Eyedrops Every 5 Minutes | Uncorrected Distance Visual Acuity (UDVA) | 0.95 logMAR | Standard Deviation 0.53 |
| Riboflavin 0.1% Eyedrops Every 2 Minutes | Uncorrected Distance Visual Acuity (UDVA) | 0.91 logMAR | Standard Deviation 0.55 |