Diabetic Macular Edema
Conditions
Keywords
DME, micropulse laser
Brief summary
Diabetic retinopathy is one of the most common complications of diabetes and diabetic macular edema (DME) is one of the most common causes of vision loss in diabetes. The purpose of this study is to determine if early intervention with micropulse laser treatment in eyes with good visual acuity (20/32 or better) will improve or stabilize vision loss due to the complications of diabetic macular edema.
Detailed description
This is a randomized, controlled clinical trial comparing subthreshold micropulse laser versus sham laser treatment for eyes with diabetic macular edema with good visual acuity of 20/32 or better. Subjects will be randomized to receive either subthreshold micropulse laser treatment or no treatment (sham). Randomization will occur as a ratio of 2:1 and will take place during the clinic visit. Subjects selected for the study will undergo a complete ophthalmic examination, including measurements of best corrected visual acuity, low luminance visual acuity, contrast sensitivity (using ETDRS testing with a masked coordinator), intraocular pressure, slit lamp exam including documentation of lens status, and dilated funduscopic exam with standard dilating agents used at the UC Davis Eye Center. Subjects will then undergo baseline imaging including Spectral Domain Ocular Coherence Tomography (SD-OCT), fundus autofluorescence (FAF) and microperimetry testing. Both the use of OCT, FAF, and microperimetry testing are within the standard of care for the management of DME. The duration of an individual subject's participation in the study will be two years which will include at least 10 total visits at various time points including on the day of enrollment, followed by 1, 3, 6, 9, and 12, 15, 18, 21, 24 months after the day of enrollment. The subjects in the treatment arm will be treated on the day of randomization by SML photocoagulation using the Iridex IQ577 laser unit with TxCell scanning laser delivery system. Subjects in the sham treatment arm will undergo the same set up procedures as those receiving the laser treatment, however, no actual laser treatment will occur. Subjects will then return to the clinic for repeat ophthalmic exam, OCT imaging, and microperimetry at 1 month, 3 month, 6 month, 9 month, 12 month, 15 month, 18 month, 21 month and 24 month time points, which is similar in frequency as standard of care. Patients in the treatment arm are eligible for repeat SML laser at any subsequent visit if there is any decline in vision (1 or more ETDRS lines) or worsening in edema (\>10% increase), at the discretion of the treating physician. If vision declines to 20/40 or worse at any study visit, patients in the treatment arm will undergo repeat treatment with SML laser, while those in the sham arm will undergo repeat sham laser.
Interventions
Participant's study eye will be dilated prior to being comfortably seated at the slit lamp for treatment. Application of micropulse laser on retinal surface will occur using TxCell Scanning Delivery System in a 7 x 7 grid to surround the fovea.
DEVICESham Treatment
Participant's study eye will be dilated prior to being comfortably seated at the slit lamp for treatment. No actual laser treatment will occur.
Sponsors
IRIDEX Corporation
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Subjects will be masked to their treatment assignment. The research coordinator that performs the measurement of best corrected visual acuity will be masked to the treatment assignment. The reading center analyst responsible for reviewing and analyzing OCT and microperimetry reports will be masked to treatment assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>=18 years 2. Type 1 or type 2 diabetes mellitus 3. Clinical evidence of center-involved DME confirmed on OCT, and defined by OCT Central Subfield (CSF) thickness at the time of randomization by the following: 1. Zeiss Cirrus: 275μ in women, and 290μ in men 2. Heidelberg Spectralis: 290μ in women, and 305μ in men 4. Best corrected visual acuity of 20/32 or better on ETDRS testing
Exclusion criteria
1. Macular edema from causes other than DME 2. An ocular condition is present such that in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (i.e/foveal atrophy, pigment abnormalities, dense hard exudates) 3. An ocular condition is present other than DME which may contribute to macular edema (i.e/vein occlusion, ERM, uveitis, RP, etc…). 4. Cataract that in the opinion of the investigator may alter visual acuity throughout the course of the study 5. History of prior laser or other surgical, intravitreal, or peribulbar treatment for DME in the study eye within the prior 6 months. 6. More than 4 prior intraocular injections for treatment of DME at any time 7. More than 1 prior focal/grid macular photocoagulation session for treatment of DME at any time 8. History of topical steroid or NSAID treatment within 30 days prior to randomization 9. History of PRP within 4 months prior to randomization or anticipated need for PRP in the 6 months following randomization. 10. Any history of vitrectomy. 11. History of major ocular surgery (cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization 12. History of YAG capsulotomy performed within 2 months prior to randomization. 13. Aphakia 14. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Vision Loss to 20/40 or Worse | 6 months | BCVA measured using ETDRS testing. The study endpoint was reached if the study patient experienced vision loss of ≥10 letters (≥2 lines) at any visit or 5-9 letters (1-2 lines) at 2 consecutive visits ≤28 days apart, based on the criteria for initiating anti-VEGF therapy as defined in the DRCR Protocol V study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Acuity at 6 Month | 6 months | Visual acuity measured using ETDRS |
| Low Luminance Visual Acuity at 6 Months | 6 months | Low Luminance Visual acuity measured with a 2.0-log unit neutral density filter |
| Contrast Sensitivity at 6 Months | 6 months | Contrast sensitivity is measured using a single, large letter size (20/60 optotype) with contrast varying across groups of letters. The contrast sensitivity chart (CS) uses letters whose contrast varies from high to low. The scale is 0.0 (minimum) to 2.0 (maximum). A higher score equates to a better outcome. The score is based on the contrast of the last group in which 2 or 3 letters were correctly read. A score of 2.0 indicates normal CS of 100%. Scores \< than 2.0 signify poorer CS; scores \< than 1.5 is consistent with visual impairment; a score \< than 1.0 represents visual disability. |
| Central Subfield Thickness (CST) at 6 Months | 6 months | Using Heidelberg Spectralis device to measure central subfield thickness (CST) |
| Microperimetry Average Threshold at 6 Month | 6 months | Performed using the Macular Integrity Assessment (MAIA) Instrument |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Micropulse Laser Treatment Subjects assigned to the micropulse laser arm of the trial will undergo the following procedures:
1. Confirmation of the subject's identity and eye to be treated
2. Subject's eye will be dilated
3. Subject will be positioned at the slit lamp for treatment
4. Application of subthreshold micropulse laser using the Iridex IQ577 laser unit. (intermittent pulsed energy) in a 7 X 7 grid pattern surrounding the fovea.
Micropulse Laser Treatment: Participant's study eye will be dilated prior to being comfortably seated at the slit lamp for treatment. Application of micropulse laser on retinal surface will occur using TxCell Scanning Delivery System in a 7 x 7 grid to surround the fovea. | 16 |
| Micropulse Laser Treatment Subjects assigned to the micropulse laser arm of the trial will undergo the following procedures:
1. Confirmation of the subject's identity and eye to be treated
2. Subject's eye will be dilated
3. Subject will be positioned at the slit lamp for treatment
4. Application of subthreshold micropulse laser using the Iridex IQ577 laser unit. (intermittent pulsed energy) in a 7 X 7 grid pattern surrounding the fovea.
Micropulse Laser Treatment: Participant's study eye will be dilated prior to being comfortably seated at the slit lamp for treatment. Application of micropulse laser on retinal surface will occur using TxCell Scanning Delivery System in a 7 x 7 grid to surround the fovea. | 16 |
| Sham Treatment Subjects assigned to the sham arm of the trial will undergo the following procedures:
1. Confirmation of the subject's identity and eye to be treated
2. Subject's eye will be dilated
3. Subject will be positioned at the slit lamp for treatment
4. No Actual laser treatment will occur
Sham Treatment: Participant's study eye will be dilated prior to being comfortably seated at the slit lamp for treatment. No actual laser treatment will occur. | 11 |
| Sham Treatment Subjects assigned to the sham arm of the trial will undergo the following procedures:
1. Confirmation of the subject's identity and eye to be treated
2. Subject's eye will be dilated
3. Subject will be positioned at the slit lamp for treatment
4. No Actual laser treatment will occur
Sham Treatment: Participant's study eye will be dilated prior to being comfortably seated at the slit lamp for treatment. No actual laser treatment will occur. | 11 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 |
| Overall Study | Change to insurance | 2 | 1 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Other | 2 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Micropulse Laser Treatment | Sham Treatment |
|---|---|---|---|
| Age, Continuous | 56.2 Years STANDARD_DEVIATION 9.3 | 57.1 Years STANDARD_DEVIATION 8.4 | 54.9 Years STANDARD_DEVIATION 10.9 |
| Best Corrected Visual Acuity (BCVA) | 82.1 ETDRS Letters Read STANDARD_DEVIATION 4.5 | 81.8 ETDRS Letters Read STANDARD_DEVIATION 5 | 82.5 ETDRS Letters Read STANDARD_DEVIATION 4 |
| Central Subfield Thickness (CST) | 340.0 microns STANDARD_DEVIATION 52.4 | 329.7 microns STANDARD_DEVIATION 23.9 | 354.9 microns STANDARD_DEVIATION 76.6 |
| Contrast Sensitivity (CS) | 1.59 unit less STANDARD_DEVIATION 0.16 | 1.58 unit less STANDARD_DEVIATION 0.16 | 1.61 unit less STANDARD_DEVIATION 0.17 |
| Low Luminance Visual Acuity (LLVA) | 39.5 EDTDRS Letters Read STANDARD_DEVIATION 7.5 | 38.8 EDTDRS Letters Read STANDARD_DEVIATION 7.5 | 40.6 EDTDRS Letters Read STANDARD_DEVIATION 7.61 |
| Microperimetry Average Threshold | 24.6 decibels (dB) STANDARD_DEVIATION 2 | 24.8 decibels (dB) STANDARD_DEVIATION 1.9 | 24.5 decibels (dB) STANDARD_DEVIATION 2.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Eyes | 0 Eyes | 0 Eyes |
| Race (NIH/OMB) Asian | 0 Eyes | 0 Eyes | 0 Eyes |
| Race (NIH/OMB) Black or African American | 12 Eyes | 8 Eyes | 4 Eyes |
| Race (NIH/OMB) More than one race | 0 Eyes | 0 Eyes | 0 Eyes |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Eyes | 0 Eyes | 1 Eyes |
| Race (NIH/OMB) Unknown or Not Reported | 0 Eyes | 0 Eyes | 0 Eyes |
| Race (NIH/OMB) White | 14 Eyes | 8 Eyes | 6 Eyes |
| Sex: Female, Male Female | 10 Eyes | 6 Eyes | 4 Eyes |
| Sex: Female, Male Male | 17 Eyes | 10 Eyes | 7 Eyes |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 11 |
| other Total, other adverse events | 5 / 16 | 2 / 11 |
| serious Total, serious adverse events | 0 / 16 | 0 / 11 |
Outcome results
Primary
Percentage of Subjects With Vision Loss to 20/40 or Worse
BCVA measured using ETDRS testing. The study endpoint was reached if the study patient experienced vision loss of ≥10 letters (≥2 lines) at any visit or 5-9 letters (1-2 lines) at 2 consecutive visits ≤28 days apart, based on the criteria for initiating anti-VEGF therapy as defined in the DRCR Protocol V study.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Micropulse Laser Treatment | Percentage of Subjects With Vision Loss to 20/40 or Worse | 5 Eyes |
| Sham Treatment | Percentage of Subjects With Vision Loss to 20/40 or Worse | 3 Eyes |
Comparison: The target sample size for the study was 30 eyes, based on power calculations to achieve 80% power assuming 40% of sham-treated eyes will reach the vision loss threshold within 2 years, while SML treatment will reduce that value to 15%, using a 2:1 ratio for randomization (2 treatment : 1 sham).p-value: 0.76Kruskal-Wallis
Secondary
Central Subfield Thickness (CST) at 6 Months
Using Heidelberg Spectralis device to measure central subfield thickness (CST)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropulse Laser Treatment | Central Subfield Thickness (CST) at 6 Months | 357.8 microns | Standard Deviation 90.4 |
| Sham Treatment | Central Subfield Thickness (CST) at 6 Months | 356.9 microns | Standard Deviation 50 |
p-value: 0.96t-test, 2 sided
Secondary
Contrast Sensitivity at 6 Months
Contrast sensitivity is measured using a single, large letter size (20/60 optotype) with contrast varying across groups of letters. The contrast sensitivity chart (CS) uses letters whose contrast varies from high to low. The scale is 0.0 (minimum) to 2.0 (maximum). A higher score equates to a better outcome. The score is based on the contrast of the last group in which 2 or 3 letters were correctly read. A score of 2.0 indicates normal CS of 100%. Scores \< than 2.0 signify poorer CS; scores \< than 1.5 is consistent with visual impairment; a score \< than 1.0 represents visual disability.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropulse Laser Treatment | Contrast Sensitivity at 6 Months | 1.54 unit less | Standard Deviation 0.21 |
| Sham Treatment | Contrast Sensitivity at 6 Months | 1.61 unit less | Standard Deviation 0.23 |
p-value: 0.68t-test, 2 sided
Secondary
Low Luminance Visual Acuity at 6 Months
Low Luminance Visual acuity measured with a 2.0-log unit neutral density filter
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropulse Laser Treatment | Low Luminance Visual Acuity at 6 Months | 30.7 Letters Read | Standard Deviation 13.5 |
| Sham Treatment | Low Luminance Visual Acuity at 6 Months | 40.1 Letters Read | Standard Deviation 5.4 |
p-value: 0.12t-test, 2 sided
Secondary
Microperimetry Average Threshold at 6 Month
Performed using the Macular Integrity Assessment (MAIA) Instrument
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropulse Laser Treatment | Microperimetry Average Threshold at 6 Month | 22.5 dB | Standard Deviation 3.9 |
| Sham Treatment | Microperimetry Average Threshold at 6 Month | 24.4 dB | Standard Deviation 3.9 |
p-value: 0.5t-test, 2 sided
Secondary
Visual Acuity at 6 Month
Visual acuity measured using ETDRS
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Micropulse Laser Treatment | Visual Acuity at 6 Month | 79.4 Letters Read | Standard Deviation 8 |
| Sham Treatment | Visual Acuity at 6 Month | 83.9 Letters Read | Standard Deviation 6.3 |
p-value: 0.16t-test, 2 sided