Application of subthreshold laser therapy in retinal diseases: a review

Abstract

Introduction: Laser photocoagulation has been a valuable tool in the ophthalmologist’s armamentarium for decades. Conventional laser photocoagulation relies on visible retinal burns as a treatment endpoint, which is thought to result in photocoagulative necrosis of retinal tissue. Recent studies have suggested that using subthreshold (ST) laser, which does not cause detectable damage to the retina may also have therapeutic effects in a variety of retinal diseases. Areas covered: We review the proposed biological mechanisms mediating the therapeutic effects of subthreshold laser on the retina, followed by the evidence for ST laser efficacy in retinal diseases such as diabetic macular edema, central serous chorioretinopathy, age-related macular degeneration, and retinal vein occlusion. Expert Commentary: Multiple clinical studies demonstrate that subthreshold laser does not cause structural damage to the retina based on multimodal imaging. Evidence suggests that there is a therapeutic effect on decreasing diabetic macular edema and subretinal fluid in chronic central serous retinopathy; however, the effect may be relatively modest and is not as efficacious as first line treatments for these diseases. Given the repeatability and lack of damage to the retina by this treatment, subthreshold laser deserves further study to determine its place in the retina specialist’s armamentarium.

Subthreshold Micropulse Laser Modulates Retinal Neuroinflammatory Biomarkers in Diabetic Macular Edema

“…Studies performed in vitro and on animals showed a series of retinal glial cell-derived cytokines and extracellular matrix-mediated responses [ 15 ]. Experiments on rabbits and mice proved that heat shock protein (HSP) expression after subthreshold laser irradiation did not significantly differ from other more damaging energy settings [ 16 ].…”

Nondamaging retinal laser therapy in recurrent diabetic macular edema after anti- VEGF injections

“…It is reported that by using the landmark pattern feature, the surgeon can choose to leave visible markers for reference and documentation of the treatment region [16]. In that study, the presence of markers or atrophic lesions after NRT therapy-was not observed with fundus autofluorescence during the follow-up (Figure 1C-1D and 2C-2D).…”

“…Thirdly, the EpM has the Landmark Pattern feature, which enables us to treat lesions subvisible, while leaving visible markers for reference and documentation of the treatment region. And EpM can be repeated as often as necessary [16].…”

Comparison of Subthreshold 577 and 810 nm Micropulse Laser Effects on Heat-Shock Protein Activation Kinetics: Implications for Treatment Efficacy and Safety

“…2,[17][18][19]22,23,27 Implementation of the principles of modern retinal laser therapy allows effective treatment for conventional retinal laser indications, including diabetic macular edema, proliferative diabetic retinopathy, central serous chorioretinopathy, and retinal vein occlusions with improved safety allowing transfoveal treatment and early treatment, and thus improved visual results. 21,[23][24][25][26][27][28][29][30][31][32][33][34][35][36] Moreover, modern retinal laser therapy allows effective therapeutic and preventive treatment of other important sight-threatening disorders, all neurodegenerations, precluded to conventional photocoagulation. The improved understanding of the mechanisms and neuroprotective effects of laser action introduced by SDM predicted these new laser applications.…”

“…2,[17][18][19][20][21][22] Other applications reported include pseudophakic and uveitic cystoid macular edema, retinal vasculitis, macular telangiectasia, dome-shaped maculae, macular macroaneurysms, and macular edema associated with epiretinal membranes. [33][34][35][36] Our current understanding of the therapeutic mechanism of SDM is that it acts as a physiologic "reset" stimulus, improving, and thus normalizing, RPE and hence retinal function by activating RPE heat-shock proteins (HSPs). [8][9][10][11][12][13][14][15]17,18,27,37 This effect is agnostic to the cause of retinal dysfunction, accounting for the wide range of clinical applications afforded to modern retinal laser therapy.…”