A Randomized Trial of Photobiomodulation Therapy for Center-Involved Diabetic Macular Edema with Good Visual Acuity (Protocol AE)

Published:October 07, 2021DOI:


      • Précis: Photobiomodulation, as used in this study, did not improve central subfield thickness in eyes with center-involved diabetic macular edema and good vision



      To determine if treatment with a photobiomodulation (PBM) device results in greater improvement in central subfield thickness as compared with placebo in eyes with center-involved diabetic macular edema (CI-DME) and good vision


      Phase 2 randomized clinical trial


      Participants had CI-DME and visual acuity (VA) 20/25 or better in the study eye and were recruited from 23 clinical sites in the US.


      One eye of each participant was randomly assigned 1:1 to a 670-nm light-emitting PBM eye patch or an identical device emitting broad-spectrum white light at low power. Treatment was applied for 90 seconds twice daily for 4 months.

      Main Outcome Measure

      Change in central subfield thickness (CST) on spectral-domain optical coherence tomography (OCT) at 4 months.


      From April 2019 to February 2020, 135 adults were randomly assigned to either PBM (N = 69) or placebo (N = 66); median age was 62, 37% were female and 82% were white. Median device compliance was 92% with PBM and 95% with placebo. OCT CST increased from baseline to 4 months by a mean (SD) of 13 (53) μm in PBM eyes and 15 (57) μm in placebo eyes (mean difference (95% CI) = -2 (-20 to 16) μm; p = .84). CI-DME, based on DRCR Retina Network sex and machine-based thresholds, was present in 61 (90%) of PBM eyes and 57 (86%) of placebo eyes at 4 months (adjusted odds ratio (95% CI) = 1.30 (0.44 to 3.83); p = .63). Visual acuity decreased by a mean (SD) of -0.2 (5.5) letters and -0.6 (4.6) letters in the PBM and placebo groups, respectively (difference (95% CI) = 0.4 (-1.3 to 2.0) letters; p = .64). There were eight adverse events possibly related to the PBM device, and two adverse events possibly related to the placebo device. None were serious.


      PBM as given in this study, while safe and well tolerated, was not found to be effective for the treatment of CI-DME in eyes with good vision.
      To read this article in full you will need to make a payment


      Subscribe to Ophthalmology Retina
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. International Diabetes Federation. Diabetes facts and figures: IDF Diabetes Atlas Ninth edition 2019. Accessed 23 June 2021.

      2. National Eye Institute. Facts about diabetic eye disease. 2015;

        • Diabetic Retinopathy Clinical Research Network
        Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema.
        Ophthalmology. 2010; 117 (e1035): 1064-1077
        • Nguyen Q.D.
        • Brown D.M.
        • Marcus D.M.
        • et al.
        Ranibizumab for diabetic macular edema: Results from 2 phase III randomized trials: RISE and RIDE.
        Ophthalmology. 2012; 119: 789-801
        • Korobelnik J.F.
        • Do D.V.
        • Schmidt-Erfurth U.
        • et al.
        Intravitreal aflibercept for diabetic macular edema.
        Ophthalmology. 2014; 121: 2247-2254
        • Mitchell P.
        • Bandello F.
        • Schmidt-Erfurth U.
        • et al.
        The RESTORE study ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema.
        Ophthalmology. 2011; 118: 615-625
        • Wells J.A.
        • Glassman A.R.
        • et al.
        • Diabetic Retinopathy Clinical Research Network
        Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema.
        N Engl J Med. 2015; 372: 1193-1203
        • Eells J.T.
        • Gopalakrishnan S.
        • Valter K.
        Near-Infrared Photobiomodulation in Retinal Injury and Disease.
        Adv Exp Med Biol. 2016; 854: 437-441
        • Tang J.
        • Herda A.A.
        • Kern T.S.
        Photobiomodulation in the treatment of patients with non-center-involving diabetic macular oedema.
        Br J Ophthalmol. 2014; 98: 1013-1015
        • Tang J.
        • Du Y.
        • Lee C.A.
        • Talahalli R.
        • Eells J.T.
        • Kern T.S.
        Low-intensity far-red light inhibits early lesions that contribute to diabetic retinopathy: in vivo and in vitro.
        Invest Ophthalmol Vis Sci. 2013; 54: 3681-3690
        • Cheng Y.
        • Du Y.
        • Liu H.
        • Tang J.
        • Veenstra A.
        • Kern T.S.
        Photobiomodulation Inhibits Long-term Structural and Functional Lesions of Diabetic Retinopathy.
        Diabetes. 2018; 67: 291-298
        • Baker C.W.
        • Glassman A.R.
        • Beaulieu W.T.
        • et al.
        Effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular edema involving the center of the macula and good visual acuity: a randomized clinical trial.
        JAMA. 2019; 321: 1880-1894