Photorefractive Keratectomy
Conditions
Brief summary
This is a randomized, double-masked, placebo-controlled study to determine the safety of pAF in patients who undergo PRK.
Detailed description
Photorefractive Keratectomy (PRK) is a common elective surgery used to correct refractive errors. We propose that amniotic fluid drops may be beneficial in promoting ocular surface healing following PRK. Purified amniotic fluid (pAF) contains anti-inflammatory, anti-microbial and regenerative factors similar to solid amniotic membrane. Individual patients will be randomized to one of two post-operative drop regimens, control eyes that will receive placebo saline solution (NaCl 0.9%, Baxter Medical), and study eyes that will receive pAF four times daily for seven days. This is a randomized, double-masked, placebo-controlled study to determine * the safety of pAF in patients who undergo PRK * if pAF hastens re-epithelialization following PRK compared to placebo * if pAF reduces post-operative pain following PRK compared to placebo * if pAF affects visual outcome following PRK compared to placebo * if pAF affects ocular surface staining and corneal regularity following PRK compared to placebo
Interventions
BIOLOGICALAmniotic Fluid (AFED)
One drop (0.25 mL) of Amniotic Fluid Eye Drops (AFED) in each eye four times daily for seven days
OTHERSaline Solution
One drop (0.25 mL) of Saline Solution in each eye four times daily for seven days
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion: 1. Patients aged 21 years and older. 2. Patients undergoing PRK for visual correction in both eyes. 3. Willing and able to give consent for study participation and comply with study procedures, including follow-up visits. Exclusion: 1. Patients with any active eye disease, including keratoconus or any other ectactic disorders. 2. Patients with documented uncontrolled diabetes. 3. Patients with severe dry eye as measured by corneal staining. 4. Patients with calculated PRK treatment resulting in residual stromal bed \<300 um. 5. Patients who have had previous eye surgery or refractive laser procedures. 6. Patients with any active collagen vascular disease. 7. Patients who do not have potential of 20/20 or better best corrected vision in each eye.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Adverse Events Including Serious Adverse Events | Up to 12 months after the last study dose | Ocular adverse events using MedDRA and CTCAE and serious adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Uncorrected Visual Acuity | Post-operative months 1, 3, 6, and 12 | Ophthalmologic assessment to determine uncorrected visual acuity |
| Pain in Each Eye | Post-operative days 1 - 8 | Patient reported pain using a visual analog scale (VAS) with 0 as no pain and 10 as worst pain |
| Time to Complete Re-epithelization | Post-operative days 1 - 8 | Ophthalmologic assessment to determine re-epithelialization. Dimensions of the epithelial defects will be directly measured using slit lamp bio-microscopy. The baseline epithelial defect will be measured by surgeons on Day 1 at the time of surgery. A vertical and horizontal measure of defect in mm will be performed, and defect area calculated. A complete re-epithelization (absence of a defect) is defined when the measures equal zero. |
| Corneal Staining in Each Eye | Post-operative months 1, 3, 6, and 12 | Ocular surface staining to determine ocular dryness using an area density index with 16 index options. A0D0 equals no dry eye to A3D3 equals most severe dryness (A=area and D=density). |
| Corneal Surface Regularity | Post-operative months 1, 3, 6, and 12 | Surface Regularity Index (SRI) obtained via Zeiss Atlas 9000 Corneal Topography™. SRI is a measure of central and paracentral corneal irregularity. A lower SRI suggests more regularity of the anterior surface of the central cornea. Lower values are considered better. The minimum value is 0 and no maximum. And, a value less than 1.55 is considered normal. |
| Count of Participants Who Reported Oral Pain Medication Usage | Post-operative days 1 - 8 | Patient reported oral pain medication usage in the first seven days of post-surgical follow-up (yes/no), where yes corresponds to any use of oral pain medication. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Amniotic Fluid (AFED) Amniotic Fluid (AFED): One drop (0.25 mL) of Amniotic Fluid Eye Drops (AFED) in each eye four times daily for seven days | 28 |
| Saline Solution Saline Solution: One drop (0.25 mL) of Saline Solution in each eye four times daily for seven days | 32 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Amniotic Fluid (AFED) | Saline Solution | Total |
|---|---|---|---|
| Age, Continuous | 33.8 years | 32.7 years | 33.4 years |
| Current Smoker or exposed to secondhand smoke | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 29 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 26 Participants | 30 Participants | 56 Participants |
| Region of Enrollment United States | 28 participants | 32 participants | 60 participants |
| Sex: Female, Male Female | 13 Participants | 19 Participants | 32 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 32 |
| other Total, other adverse events | 2 / 28 | 1 / 32 |
| serious Total, serious adverse events | 0 / 28 | 0 / 32 |
Outcome results
Primary
Safety - Adverse Events Including Serious Adverse Events
Ocular adverse events using MedDRA and CTCAE and serious adverse events
Time frame: Up to 12 months after the last study dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amniotic Fluid (AFED) | Safety - Adverse Events Including Serious Adverse Events | 1 Participants |
| Saline Solution | Safety - Adverse Events Including Serious Adverse Events | 1 Participants |
p-value: 1Fisher Exact
Secondary
Corneal Staining in Each Eye
Ocular surface staining to determine ocular dryness using an area density index with 16 index options. A0D0 equals no dry eye to A3D3 equals most severe dryness (A=area and D=density).
Time frame: Post-operative months 1, 3, 6, and 12
Population: Subjects were analyzed for every follow-up that was collected. Some subject missed one or more follow-ups.
| Arm | Measure | Group | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|---|
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 3 | A0D0 | 45 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 1 | A1D3 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 1 | A2D2 | 2 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 1 | A1D1 | 18 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 1 | A1D2 | 1 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 1 | A2D1 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 1 | A0D0 | 33 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 3 | A1D1 | 6 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 3 | A1D2 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 3 | A1D3 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 3 | A2D2 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 3 | A2D1 | 1 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 6 | A0D0 | 46 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 6 | A1D1 | 8 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 6 | A1D2 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 6 | A1D3 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 6 | A2D2 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 6 | A2D1 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 12 | A0D0 | 47 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 12 | A1D1 | 3 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 12 | A1D2 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 12 | A1D3 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 12 | A2D2 | 0 eyes |
| Amniotic Fluid (AFED) | Corneal Staining in Each Eye | Month 12 | A2D1 | 0 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 12 | A2D2 | 0 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 6 | A0D0 | 52 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 1 | A1D3 | 1 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 12 | A0D0 | 43 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 1 | A2D2 | 1 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 1 | A0D0 | 42 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 6 | A1D1 | 7 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 1 | A1D1 | 15 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 12 | A1D3 | 0 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 1 | A1D2 | 3 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 6 | A1D2 | 0 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 1 | A2D1 | 0 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 12 | A1D1 | 9 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 3 | A0D0 | 46 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 6 | A1D3 | 0 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 3 | A1D1 | 8 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 12 | A2D1 | 0 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 3 | A1D2 | 2 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 6 | A2D2 | 1 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 3 | A1D3 | 0 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 12 | A1D2 | 0 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 3 | A2D2 | 2 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 6 | A2D1 | 0 eyes |
| Saline Solution | Corneal Staining in Each Eye | Month 3 | A2D1 | 0 eyes |
p-value: 0.663Wilcoxon (Mann-Whitney)
p-value: 0.416Wilcoxon (Mann-Whitney)
p-value: 0.89Wilcoxon (Mann-Whitney)
p-value: 0.192Wilcoxon (Mann-Whitney)
Secondary
Corneal Surface Regularity
Surface Regularity Index (SRI) obtained via Zeiss Atlas 9000 Corneal Topography™. SRI is a measure of central and paracentral corneal irregularity. A lower SRI suggests more regularity of the anterior surface of the central cornea. Lower values are considered better. The minimum value is 0 and no maximum. And, a value less than 1.55 is considered normal.
Time frame: Post-operative months 1, 3, 6, and 12
Population: Some patients missed one or more follow-up windows. We analyzed all available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amniotic Fluid (AFED) | Corneal Surface Regularity | Month 6 | 1.07 Surface regularity index | Standard Deviation 0.376 |
| Amniotic Fluid (AFED) | Corneal Surface Regularity | Month 1 | 1.34 Surface regularity index | Standard Deviation 0.567 |
| Amniotic Fluid (AFED) | Corneal Surface Regularity | Month 12 | 1.03 Surface regularity index | Standard Deviation 0.459 |
| Amniotic Fluid (AFED) | Corneal Surface Regularity | Month 3 | 1.11 Surface regularity index | Standard Deviation 0.616 |
| Saline Solution | Corneal Surface Regularity | Month 12 | 1.05 Surface regularity index | Standard Deviation 0.661 |
| Saline Solution | Corneal Surface Regularity | Month 1 | 1.58 Surface regularity index | Standard Deviation 0.748 |
| Saline Solution | Corneal Surface Regularity | Month 6 | 0.97 Surface regularity index | Standard Deviation 0.389 |
| Saline Solution | Corneal Surface Regularity | Month 3 | 1.07 Surface regularity index | Standard Deviation 0.407 |
p-value: 0.528Mixed Models Analysis
p-value: 0.21Mixed Models Analysis
p-value: 0.057Mixed Models Analysis
p-value: 0.853Mixed Models Analysis
Secondary
Count of Participants Who Reported Oral Pain Medication Usage
Patient reported oral pain medication usage in the first seven days of post-surgical follow-up (yes/no), where yes corresponds to any use of oral pain medication.
Time frame: Post-operative days 1 - 8
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amniotic Fluid (AFED) | Count of Participants Who Reported Oral Pain Medication Usage | 26 Participants |
| Saline Solution | Count of Participants Who Reported Oral Pain Medication Usage | 31 Participants |
p-value: 0.594Fisher Exact
Secondary
Pain in Each Eye
Patient reported pain using a visual analog scale (VAS) with 0 as no pain and 10 as worst pain
Time frame: Post-operative days 1 - 8
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amniotic Fluid (AFED) | Pain in Each Eye | 4 score on a scale |
| Saline Solution | Pain in Each Eye | 5 score on a scale |
p-value: 0.614t-test, 2 sided
Secondary
Time to Complete Re-epithelization
Ophthalmologic assessment to determine re-epithelialization. Dimensions of the epithelial defects will be directly measured using slit lamp bio-microscopy. The baseline epithelial defect will be measured by surgeons on Day 1 at the time of surgery. A vertical and horizontal measure of defect in mm will be performed, and defect area calculated. A complete re-epithelization (absence of a defect) is defined when the measures equal zero.
Time frame: Post-operative days 1 - 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amniotic Fluid (AFED) | Time to Complete Re-epithelization | 5 days | Standard Deviation 0.6 |
| Saline Solution | Time to Complete Re-epithelization | 5 days | Standard Deviation 0.5 |
p-value: 0.869Mixed Models Analysis
Secondary
Uncorrected Visual Acuity
Ophthalmologic assessment to determine uncorrected visual acuity
Time frame: Post-operative months 1, 3, 6, and 12
Population: Some patients missed one or more follow-up windows. We analyzed all available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amniotic Fluid (AFED) | Uncorrected Visual Acuity | Month 6 | -0.07 LogMAR | Standard Deviation 0.085 |
| Amniotic Fluid (AFED) | Uncorrected Visual Acuity | Month 12 | -0.09 LogMAR | Standard Deviation 0.058 |
| Amniotic Fluid (AFED) | Uncorrected Visual Acuity | Month 3 | -0.06 LogMAR | Standard Deviation 0.097 |
| Amniotic Fluid (AFED) | Uncorrected Visual Acuity | Month 1 | -0.03 LogMAR | Standard Deviation 0.103 |
| Saline Solution | Uncorrected Visual Acuity | Month 3 | -0.05 LogMAR | Standard Deviation 0.103 |
| Saline Solution | Uncorrected Visual Acuity | Month 6 | -0.06 LogMAR | Standard Deviation 0.091 |
| Saline Solution | Uncorrected Visual Acuity | Month 12 | -0.06 LogMAR | Standard Deviation 0.107 |
| Saline Solution | Uncorrected Visual Acuity | Month 1 | 0.04 LogMAR | Standard Deviation 0.123 |
p-value: 0.007Mixed Models Analysis
p-value: 0.953Mixed Models Analysis
p-value: 0.841Mixed Models Analysis
p-value: 0.137Mixed Models Analysis