Astigmatism, Myopia
Conditions
Keywords
PRK, myopia, astigmatism
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of the ALLEGRETTO WAVE EYE-Q excimer laser system for the reduction of myopia with or without astigmatism in subjects undergoing photorefractive keratectomy (PRK) treatment.
Detailed description
This was a prospective, multi-center, single group study. Subjects underwent bilateral PRK in which the second eye was treated no sooner than 1 week and no later than 30 days after the first eye's PRK treatment. Subjects were followed for 2 years after surgery. The protocol underwent 4 amendments. The key differences between the protocol versions were clarifications of the planned analyses and adverse event reporting procedures. There were no changes in the inclusion and exclusion criteria or non-adverse event related study assessments between the protocol versions 1-5. Refractive stability of manifest refraction spherical equivalent (MRSE) and manifest refractive cylinder was defined as established when: * At least 95% of the treated eyes had a change ≤ 1.0 diopter between manifest refractions performed at any 2 manifest refractions at least 3 months apart * The mean rate of change, as determined by a paired analysis, was ≤ 0.5 diopter per year (0.04 D/month) over the same time period * The mean rate of change decreased monotonically over time, with a projected asymptote of zero or a rate of change attributable to normal aging * The 95% confidence interval for the mean rate of change included zero or a rate of change attributable to normal aging. Refractive stability was assessed for pairs of visits within an interval and was defined to occur at the latter time point of the first interval at which stability was achieved. In the final amendment to the protocol, 3 secondary objectives were made co-primary in response to Agency comments. All endpoints and analyses were modified to match.
Interventions
PROCEDUREPhotorefractive keratectomy (PRK)
In this corneal surgical procedure, the outer corneal epithelial layer will be removed, after which the corneal stroma will be reshaped by excimer laser ablation to reduce or eliminate refractive errors.
DEVICEALLEGRETTO WAVE EYE-Q excimer laser system
The ALLEGRETTO WAVE EYE-Q excimer laser system is used for corneal stroma reshaping during PRK surgery
Sponsors
Alcon Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects desiring refractive correction of myopia up to -6.00 Diopter (D) sphere with or without astigmatism 0 to -3.00 D and up to -6.00 D manifest refraction spherical equivalent (MRSE) at the spectacle plane measured by manifest refraction; * Minimum best spectacle corrected visual acuity (BSCVA) in the treated eye of 20/25; * Uncorrected visual acuity (UCVA) 20/40 or worse in the treated eye; * Less than 0.75 D spherical equivalent (SE) difference between cycloplegic and manifest refractions; * Stable refraction (within ± 0.5 D), as determined by MRSE for a minimum of 12 months prior to surgery; * Demonstrated stable refraction for contact lens wearers, as specified in protocol; * Signed informed consent document; * Willing and able to comply with schedule for follow-up visits; * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* Females who are pregnant, lactating, or planning a pregnancy during the time course of the study, or have another condition associated with the fluctuation of hormones that could lead to refractive changes; * Participation in other clinical trials during this study; * Acute or chronic disease or illness that would increase the operative risk or confound the outcomes of the study; * Dry eye syndrome as determined by the short questionnaire for dry eye syndrome; * Systemic medications that may confound the outcome of the study or increase the risk to the subject by affecting wound healing or tissue repair, including, but not limited to steroids, antimetabolites, immune response modifying drugs, etc.; * Nystagmus or any other condition that would prevent a steady gaze during the PRK treatment or other diagnostic tests; * Ocular condition that may predispose the subject to future complications; * Previous intraocular or corneal surgery; * Subjects who desire to have monovision; * A known sensitivity to medications used for study procedures, including PRK; * Presence or history of any condition or finding that makes the subject unsuitable as a candidate for PRK or study participation or may confound the outcome of the study, in the opinion of the Investigator; * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Eyes With a BSCVA Worse Than 20/40 (for Eyes With BSCVA of 20/20 or Better Preoperatively) at Refractive Stability | Month 6 (post second eye surgery) | Visual acuity with correction was assessed monocularly using the ETDRS chart at 4 meters under photopic conditions . |
| Percentage of Eyes Achieving Uncorrected Visual Acuity (UCVA) of 20/40 or Better at Refractive Stability in Eyes With Best Spectacle-corrected Visual Acuity (BSCVA) of 20/20 or Better Preoperatively | Month 6 (post second eye surgery) | Visual acuity, with and without correction, was assessed monocularly using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at 4 meters under photopic conditions . The with-correction assessment was made with the manifest refraction at 4 meters. |
| Percentage of Eyes Achieving Manifest Refraction Spherical Equivalent (MRSE) Within ± 1.0 D of Zero at Refractive Stability | Month 6 (post second eye surgery) | Manifest refraction spherical equivalent (MRSE) is calculated as follows: sphere + 1/2 cylinder. The sphere and cylinder values are from the manifest refraction assessment. The manifest refraction assessment was conducted monocularly with the ETDRS chart at 4 meters under photopic conditions using a phoropter. |
| Percentage of Eyes Achieving MRSE Within ± 0.5 D of Zero at Refractive Stability | Month 6 (post second eye surgery) | Manifest refraction spherical equivalent (MRSE) is calculated as follows: sphere + 1/2 cylinder. The sphere and cylinder values are from the manifest refraction assessment. The manifest refraction assessment was conducted monocularly with the ETDRS chart at 4 meters under photopic conditions using a phoropter. |
| Percentage of Eyes Achieving Manifest Refractive Cylinder Within ± 1.0 D of Zero at Refractive Stability | Month 6 (post second eye surgery) | Manifest refraction was performed monocularly under photopic lighting conditions using an ETDRS chart at 4 meters. The subject was manually refracted to his/her best correction using a phoropter. |
| Percentage of Eyes Achieving Manifest Refractive Cylinder Within ± 0.5 D of Zero at Refractive Stability | Month 6 (post second eye surgery) | Manifest refraction was performed monocularly under photopic lighting conditions using an ETDRS chart at 4 meters. The subject was manually refracted to his/her best correction using a phoropter. |
| Percentage of Eyes That Have a Change of ≤ 1.0 D in MRSE and Manifest Refractive Cylinder Between Consecutive Scheduled Visits | Up to Month 24 (post second eye surgery) | MRSE is calculated as sphere + 1/2 cylinder. The sphere and cylinder values are from the manifest refraction assessment. The manifest refraction assessment was conducted monocularly with the ETDRS chart at 4 meters under photopic conditions using a phoropter. |
| Cumulative Incidence of Ocular Serious Adverse Events by Eye | Up to Month 24 (post second eye surgery) | Participants were followed for the duration of the study, an expected average of 24 months. |
| Percentage of Eyes With BSCVA Decrease of ≥ 2 Lines From Baseline at Refractive Stability | Month 6 (post second eye surgery) | Visual acuity with correction was assessed monocularly using the ETDRS chart at 4 meters under photopic conditions . A decrease in 2 lines or more is considered clinically relevant (i.e. worse). |
| Percentage of Eyes With > 2.0 D of Induced Manifest Refractive Cylinder Magnitude, as Compared to Baseline, at Refractive Stability | Month 6 (post second eye surgery) | Manifest refraction was performed monocularly under photopic lighting conditions using an ETDRS chart at 4 meters. The subject was manually refracted to his/her best correction using a phoropter. The cylinder value is from the manifest refraction assessment. The induced manifest refractive cylinder is the change in magnitude of cylinder compared to baseline. |
Participant flow
Recruitment details
Participants were recruited from 8 investigative sites located in the United States.
Pre-assignment details
Of the 176 participants enrolled, 15 did not meet inclusion and exclusion criteria and were exited prior to treatment as screen failures.
Participants by arm
| Arm | Count |
|---|---|
| PRK ALLEGRETTO Photorefractive keratectomy (PRK) surgery using the ALLEGRETTO WAVE EYE-Q excimer laser system for myopic wavefront-optimized ablation | 161 |
| Total | 161 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Screen failure (prior to treatment) | 15 |
| Overall Study | Unable to make future visits | 2 |
Baseline characteristics
| Characteristic | PRK ALLEGRETTO |
|---|---|
| Age, Continuous | 31.5 years STANDARD_DEVIATION 7.4 |
| Region of Enrollment United States | 161 participants |
| Sex: Female, Male Female | 72 Participants |
| Sex: Female, Male Male | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 176 | 123 / 161 |
| serious Total, serious adverse events | 0 / 176 | 6 / 161 |
Outcome results
Primary
Cumulative Incidence of Ocular Serious Adverse Events by Eye
Participants were followed for the duration of the study, an expected average of 24 months.
Time frame: Up to Month 24 (post second eye surgery)
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRK ALLEGRETTO | Cumulative Incidence of Ocular Serious Adverse Events by Eye | Corneal infiltrates | 2 eyes |
| PRK ALLEGRETTO | Cumulative Incidence of Ocular Serious Adverse Events by Eye | Corneal oedema | 1 eyes |
Primary
Percentage of Eyes Achieving Manifest Refraction Spherical Equivalent (MRSE) Within ± 1.0 D of Zero at Refractive Stability
Manifest refraction spherical equivalent (MRSE) is calculated as follows: sphere + 1/2 cylinder. The sphere and cylinder values are from the manifest refraction assessment. The manifest refraction assessment was conducted monocularly with the ETDRS chart at 4 meters under photopic conditions using a phoropter.
Time frame: Month 6 (post second eye surgery)
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRK ALLEGRETTO | Percentage of Eyes Achieving Manifest Refraction Spherical Equivalent (MRSE) Within ± 1.0 D of Zero at Refractive Stability | 99.7 percentage of eyes |
Primary
Percentage of Eyes Achieving Manifest Refractive Cylinder Within ± 0.5 D of Zero at Refractive Stability
Manifest refraction was performed monocularly under photopic lighting conditions using an ETDRS chart at 4 meters. The subject was manually refracted to his/her best correction using a phoropter.
Time frame: Month 6 (post second eye surgery)
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRK ALLEGRETTO | Percentage of Eyes Achieving Manifest Refractive Cylinder Within ± 0.5 D of Zero at Refractive Stability | 92.7 percentage of eyes |
Primary
Percentage of Eyes Achieving Manifest Refractive Cylinder Within ± 1.0 D of Zero at Refractive Stability
Manifest refraction was performed monocularly under photopic lighting conditions using an ETDRS chart at 4 meters. The subject was manually refracted to his/her best correction using a phoropter.
Time frame: Month 6 (post second eye surgery)
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRK ALLEGRETTO | Percentage of Eyes Achieving Manifest Refractive Cylinder Within ± 1.0 D of Zero at Refractive Stability | 99.0 percentage of eyes |
Primary
Percentage of Eyes Achieving MRSE Within ± 0.5 D of Zero at Refractive Stability
Manifest refraction spherical equivalent (MRSE) is calculated as follows: sphere + 1/2 cylinder. The sphere and cylinder values are from the manifest refraction assessment. The manifest refraction assessment was conducted monocularly with the ETDRS chart at 4 meters under photopic conditions using a phoropter.
Time frame: Month 6 (post second eye surgery)
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRK ALLEGRETTO | Percentage of Eyes Achieving MRSE Within ± 0.5 D of Zero at Refractive Stability | 93.3 percentage of eyes |
Primary
Percentage of Eyes Achieving Uncorrected Visual Acuity (UCVA) of 20/40 or Better at Refractive Stability in Eyes With Best Spectacle-corrected Visual Acuity (BSCVA) of 20/20 or Better Preoperatively
Visual acuity, with and without correction, was assessed monocularly using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at 4 meters under photopic conditions . The with-correction assessment was made with the manifest refraction at 4 meters.
Time frame: Month 6 (post second eye surgery)
Population: Intent to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRK ALLEGRETTO | Percentage of Eyes Achieving Uncorrected Visual Acuity (UCVA) of 20/40 or Better at Refractive Stability in Eyes With Best Spectacle-corrected Visual Acuity (BSCVA) of 20/20 or Better Preoperatively | 100 percentage of eyes |
Primary
Percentage of Eyes That Have a Change of ≤ 1.0 D in MRSE and Manifest Refractive Cylinder Between Consecutive Scheduled Visits
MRSE is calculated as sphere + 1/2 cylinder. The sphere and cylinder values are from the manifest refraction assessment. The manifest refraction assessment was conducted monocularly with the ETDRS chart at 4 meters under photopic conditions using a phoropter.
Time frame: Up to Month 24 (post second eye surgery)
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRK ALLEGRETTO | Percentage of Eyes That Have a Change of ≤ 1.0 D in MRSE and Manifest Refractive Cylinder Between Consecutive Scheduled Visits | Week 1 to Month 1 | 90.9 percentage of eyes |
| PRK ALLEGRETTO | Percentage of Eyes That Have a Change of ≤ 1.0 D in MRSE and Manifest Refractive Cylinder Between Consecutive Scheduled Visits | Month 1 to Month 3 | 95.6 percentage of eyes |
| PRK ALLEGRETTO | Percentage of Eyes That Have a Change of ≤ 1.0 D in MRSE and Manifest Refractive Cylinder Between Consecutive Scheduled Visits | Month 3 to Month 6 | 99.7 percentage of eyes |
| PRK ALLEGRETTO | Percentage of Eyes That Have a Change of ≤ 1.0 D in MRSE and Manifest Refractive Cylinder Between Consecutive Scheduled Visits | Month 6 to Month 9 | 100 percentage of eyes |
| PRK ALLEGRETTO | Percentage of Eyes That Have a Change of ≤ 1.0 D in MRSE and Manifest Refractive Cylinder Between Consecutive Scheduled Visits | Month 9 to Month 12 | 99.7 percentage of eyes |
| PRK ALLEGRETTO | Percentage of Eyes That Have a Change of ≤ 1.0 D in MRSE and Manifest Refractive Cylinder Between Consecutive Scheduled Visits | Month 12 to Month 24 | 100 percentage of eyes |
Primary
Percentage of Eyes With > 2.0 D of Induced Manifest Refractive Cylinder Magnitude, as Compared to Baseline, at Refractive Stability
Manifest refraction was performed monocularly under photopic lighting conditions using an ETDRS chart at 4 meters. The subject was manually refracted to his/her best correction using a phoropter. The cylinder value is from the manifest refraction assessment. The induced manifest refractive cylinder is the change in magnitude of cylinder compared to baseline.
Time frame: Month 6 (post second eye surgery)
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRK ALLEGRETTO | Percentage of Eyes With > 2.0 D of Induced Manifest Refractive Cylinder Magnitude, as Compared to Baseline, at Refractive Stability | 0.0 percentage of eyes |
Primary
Percentage of Eyes With a BSCVA Worse Than 20/40 (for Eyes With BSCVA of 20/20 or Better Preoperatively) at Refractive Stability
Visual acuity with correction was assessed monocularly using the ETDRS chart at 4 meters under photopic conditions .
Time frame: Month 6 (post second eye surgery)
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRK ALLEGRETTO | Percentage of Eyes With a BSCVA Worse Than 20/40 (for Eyes With BSCVA of 20/20 or Better Preoperatively) at Refractive Stability | 0.0 percentage of eyes |
Primary
Percentage of Eyes With BSCVA Decrease of ≥ 2 Lines From Baseline at Refractive Stability
Visual acuity with correction was assessed monocularly using the ETDRS chart at 4 meters under photopic conditions . A decrease in 2 lines or more is considered clinically relevant (i.e. worse).
Time frame: Month 6 (post second eye surgery)
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRK ALLEGRETTO | Percentage of Eyes With BSCVA Decrease of ≥ 2 Lines From Baseline at Refractive Stability | 0.0 percentage of eyes |