JCHR

Title

A Pilot Study Evaluating Photobiomodulation Therapy for Diabetic Macular Edema (DME)

Précis

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. 

Objectives

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 far-red (FR) to near-infrared (NIR) region of the spectrum (630-900 nm).

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. 

Study Design

Randomized, multi-center, sham-controlled clinical trial.

There are two phases of the study; the primary outcome will be evaluated at the end of phase 1 (4 months).  At the 4-month visit, participants will switch to the alternative treatment.  The switch serves two purposes:

1. to provide participants originally assigned to sham the opportunity to receive the active treatment and
2. to explore the post-switch effects within treatment group.  No statistical comparisons will be performed in Phase 2 to compare treatment groups. 

 Note: This is not a crossover design.

Number of Sites

Approximately 40

Endpoint

Primary Efficacy Outcome:

• Mean change in CST from baseline at 4 months

Key Secondary Efficacy Outcomes:

Treatment Group Comparisons

• Mean change in retinal volume from baseline at 4 months
• Percentage of eyes with CST below OCT machine- and gender-specific threshold for DME at 4 months
• Percentage of eyes receiving alternative treatment for DME by 4 months
• Percentage of eyes with a =5 letter loss in visual acuity
• Patient compliance
• Exploratory assessment of treatment effect after the device is stopped or started (see section 7.10 for more details)

Population

Key Inclusion Criteria

• Age >18 years
• Type 1 or type 2 diabetes
• At least one eye with each of the following:

o  Best corrected E-ETDRS visual acuity letter score = 79 (i.e., 20/25 or better)

o    Ophthalmoscopic evidence of central-involved DME in study eye confirmed by CST on spectral domain OCT:

§Zeiss Cirrus: =290 µm in women, and =305 µm in men

§Heidelberg Spectralis: =305µm in women, and =320 µm in men

Key Exclusion Criteria      

• No history of prior laser, surgical, intravitreous, or peribulbar treatment for DME or DR in the study eye within the prior 12 months

o   If more than 12 months ago, no more than 4 prior intraocular injections

o   Enrollment will be limited to a maximum of 15% of the planned sample size with any history of anti-VEGF treatment and a maximum of 15% with any history of PRP.

Sample Size

134

Treatment Groups

Random assignment (1:1) to photobiomodulation (PBM) or sham

Participant Duration

The trial will last up to 8 months for each participant (primary outcome at 4 months)

Protocol Overview

1.     Informed consent will be obtained.

2.   Study eligibility will be assessed.

3.   Prior to randomization, the participant’s willingness to proceed into the randomized trial will be confirmed.

4.   Eligible eyes (one per participant) will be randomly assigned to photobiomodulation or sham.  If a participant has two eligible eyes, the eye with the greatest CST will be selected as the study eye and the non-study eye will be followed to evaluate any potential contralateral effect.

5.  Training for at-home use will be performed with the randomized device on the day of randomization. 

6.   A follow-up phone call is performed at 1 week.

7.   Participants will return for a follow-up visit every month for the first 4 months and then every 2 months through 8 months.  The primary outcome assessment will be at 4 months.

8.  Following the primary outcome assessment, the participant will switch to the alternative treatment for the next 4 months. A summary of treatment procedures is included below.