Randomized clinical trial evaluating the effect of photobiomodulation compared with sham on central subfield thickness (CST) in eyes with central-involved DME and good vision.

This study is being conducted to assess the effects of photobiomodulation on CST compared with sham in eyes with central-involved DME and good vision. Photobiomodulation is irradiation by light in the 630-900 nanometer region of the spectrum.

Furthermore, this pilot study is being conducted to determine whether the conduct of a pivotal trial has merit based on an anatomic outcome and provide information on outcome measures needed to design a pivotal trial.

Inclusion Criteria:

• Age ≥ 18 years

• Diagnosis of diabetes mellitus (type 1 or type 2). Any one of the following will be considered to be sufficient evidence that diabetes is present:

  1. Current regular use of insulin for the treatment of diabetes.
  2. Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes.
  3. Documented diabetes by American Diabetes Association and/or the World Health Organization criteria.
  4. Able and willing to provide informed consent.

Atleast one eye meeting the following criteria:

1. Best corrected E-ETDRS visual acuity letter score ≥ 79 (i.e., 20/25 or better)
2. Ophthalmoscopic evidence of central-involved DME, confirmed by CST on spectral domain OCT: Zeiss Cirrus: ≥290µm in women, and ≥305µm in men, Heidelberg Spectralis: ≥305µm in women, and ≥320µm in men
3. Media clarity, pupillary dilation, and study participant

Exclusion Criteria:

• History of chronic renal failure requiring dialysis or kidney transplant.
• A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status that might preclude completion of follow-up).
• Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months.
• Participation in an investigational trial that involved treatment within 30 days of randomization with any drug/device that has not received regulatory approval for the indication being studied. Note: study participants cannot participant in another investigational trial that involves treatment with an investigational drug or device while participating in the study.
• Systolic blood pressure above 180 or diastolic blood pressure above 110. If blood pressure is brought below 180 systolic and 110 diastolic by anti-hypertensive treatment, individual can become eligible.
• Systemic anti-vascular endothelial growth factor (anti-VEGF) or pro-VEGF treatment within 4 months prior to randomization. These drugs should not be used during the study.
• For women of child-bearing potential: pregnant or intending to become pregnant within the next 8 months. Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed.
• Individual is expecting to move out of the area during the 8 months of the study.

A participant will be excluded if the study eye meets any of the following criteria:

• Macular edema is considered to be due to a cause other than DME. An eye should not be considered eligible if: (1) the macular edema is considered to be related to ocular surgery such as cataract extraction or (2) clinical exam and/or investigator assessment of OCT suggests that vitreoretinal interface abnormalities (e.g., a taut posterior hyaloid or epiretinal membrane) are contributing to the macular edema.
• An ocular condition is present such that, in the opinion of the investigator, any visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition).
• An ocular condition is present (other than DME) that, in the opinion of the investigator, might affect visual acuity during the course of the study or require intraocular treatment (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.)
• Cataract is present that, in the opinion of the investigator, may alter visual acuity during the course of the study.
• History of major ocular surgery (including cataract, scleral buckle, any intraocular surgery, etc.) within prior 4 months or major ocular surgery anticipated during the study period.
• Any history of prior laser or other surgical, intravitreal, or peribulbar treatment for DME or DR (such as panretinal photocoagulation, focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, or anti-VEGF) within the prior 12 months. If treatment was given more than 12 months prior, no more than 4 prior intraocular injections. Enrollment will be limited to a maximum of 15 percent of the planned sample size with any history of anti-VEGF treatment and a maximum of 15% with any history of PRP.
• Anticipated need to treat DME or DR during the study period
• History of topical steroid or non-steroidal anti-inflammatory drug treatment within 30 days prior to randomization.
• History of YAG capsulotomy performed within 2 months prior to randomization
• Any history of vitrectomy.
• Aphakia
• Uncontrolled glaucoma

Optical coherence tomography technicians and visual acuity testers, including refractionists, will be masked to treatment group at outcome visits. Study participants will be masked to their treatment group assignment. Every effort will be made to keep investigators masked. Study coordinators who will be involved with training and compliance assessment will not be masked to treatment group