Open Access
Letters to the Editor  |   August 2020
International Retinal Laser Society Guidelines For Subthreshold Laser Treatment
Author Affiliations
  • Jan E. E. Keunen
    University of Radboud, Nijmegen, The Netherlands
  • Maurizio Battaglia-Parodi
    University Vita-Salute Scientific Institute San Raffaele, Milan, Italy
  • Stela Vujosevic
    Eye Clinic University Hospital San Giuseppe, IRCCS Multimedica, Milan, Italy
  • Jeffrey K. Luttrull
    Ventura County Retina Vitreous Medical Group, Ventura, California, USA. e-mail:
Translational Vision Science & Technology August 2020, Vol.9, 15. doi:
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      Jan E. E. Keunen, Maurizio Battaglia-Parodi, Stela Vujosevic, Jeffrey K. Luttrull; International Retinal Laser Society Guidelines For Subthreshold Laser Treatment. Trans. Vis. Sci. Tech. 2020;9(9):15.

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      © ARVO (1962-2015); The Authors (2016-present)

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The recent advent of new laser approaches has revolutionized the laser treatment techniques for retinal diseases. In particular, the goal of modern subthreshold laser (STL) treatment is now retinal preservation and normalization, rather than destruction.18 Despite the proven effectiveness of STL, lack of standardization has limited its clinical application and usefulness.28 The International Retinal Laser Society (LIGHT) would like to provide simple evidence-based treatment guidelines to optimize STL application for all users.9 
The Target
The target of treatment is the retinal pigment epithelium (RPE). The therapeutic effects of retinal laser are the result of RPE cell hyperthermia caused by laser absorption in RPE melanosomes.16 
Low-Intensity Treatment
All therapeutic effects of STL arise from RPE cells affected, but not killed, by laser exposure, through thermal activation and enhanced function of intra-RPE heat-shock proteins (HSPs).36,10 As an enzymatic threshold phenomenon, the response at the cellular level is switch-like; “on/off,” all-or-nothing, rather than graduated.10 Treatment intensities exceeding the HSP activation threshold increase the risk of retinal damage but do not improve therapeutic effects. Designed to respond to acute existential threats, HSP activation is catalytic; initiating reparative cascades within the cell, locally, and systemically to normalize function.36,11 The therapeutic range (TR) is the zone wherein treatment is therapeutically effective and safe, sublethal to the retina. The breadth of the TR, and thus likelihood of clinical treatment safety, varies markedly depending on laser mode and parameters.4,5 The TR is broadened and safety maximized by use of longer wavelengths, longer pulse durations, and low-frequency pulse trains4,5,10 (Table). 
Example Treatment Parameters for Various Laser Modes and Settings and Effects on Therapeutic (Clinical Safety) Ranges
Example Treatment Parameters for Various Laser Modes and Settings and Effects on Therapeutic (Clinical Safety) Ranges
High-density Treatment
Normalization of RPE function at the cellular level requires amplification to achieve and maximize therapeutic clinical effects. This is accomplished by confluent treatment of broad areas of dysfunctional retina to recruit and normalize the RPE en masse. The most common error with modern retinal laser therapy is undertreatment; characterized by too few spot applications, of insufficient density, over too small areas 26 
Titration of laser treatment intensity is an idea rooted in the photocoagulation era, which used immediately visible physical, rather than invisible physiologic, endpoints. Titration is discouraged by LIGHT because it increases the likelihood of unintended retinal damage.4,5 Instead, LIGHT recommends use of published “fixed” laser parameters (identical settings in all eyes) shown to be reliably safe and effective (Table). 
Bearing in mind the action of STL is mediated through the RPE, an extensive RPE area must be treated to maximize clinical outcomes.4 Thus traditional targeted focal and local treatment is discouraged. For most applications, we consider panmacular treatment the optimal approach.6 In panmacular treatment, the entire retina between the vascular arcades is “painted” with confluent laser spots, several times over in a single treatment session, to ensure complete coverage and avoid undertreatment. The number of laser spots required depends on the spot size. For example, panmacular treatment with a 125-μm spot may require 2000 shots, whereas a 500-μm spot requires only 400 to 450. STL can be used like a drug to treat the entire retina, repeated as necessary, and used in conjunction with surgery or drugs to maximize management options and treatment outcomes. 
Dorin G . Subthreshold and micropulse diode laser photocoagulation. Semin Ophthalmol. 2003; 18: 147–153. [CrossRef] [PubMed]
Battaglia Parodi M, Iacono P. Re: van Dijk et al.: Half-dose photodynamic therapy versus high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy: the PLACE trial (Ophthalmology. 2018;125:1547–1555). Ophthalmology. 2019; 126: e29–e30. [CrossRef] [PubMed]
Luttrull JK . Comment on: van Rijssen TJ, van Dijk EHC, Scholz P, et al. Focal and Diffuse Chronic Central Serous Chorioretinopathy Treated With Half-Dose Photodynamic Therapy or Subthreshold Micropulse Laser: PLACE Trial Report No. 3. Am J Ophthalmol. 2020 Jan 27. pii: S0002-9394(19)30574-4, doi:10.1016/j.ajo.2019.10.037.
Luttrull JK, Dorin G. Subthreshold diode micropulse photocoagulation as invisible retinal phototherapy for diabetic macular edema. A review. Current Diabetes Reviews. 2012; 8: 274–284. [CrossRef] [PubMed]
Luttrull JK, Sramek C, Palanker D, Spink CJ, Musch DC. Long-term safety, high-resolution imaging, and tissue temperature modeling of subvisible diode micropulse photocoagulation for retinovascular macular edema. Retina. 32: 375–386. [CrossRef] [PubMed]
Luttrull JK, Margolis BWL. Functionally guided retinal protective therapy as prophylaxis for age-related and inherited retinal degenerations. A Pilot Study. Invest Ophthalmol Vis Sci. 2016; 7: 265–275. [CrossRef]
Battaglia Parodi M, Spasse S, Iacono P, et al. Subthreshold grid laser treatment of macular edema secondary to branch retinal vein occlusion with micropulse infrared (810 nanometer) diode laser. Ophthalmology. 2006; 113: 2237–2242. [CrossRef] [PubMed]
Vujosevic S, Martini F, Longhin E, et al. Subthreshold micropulse yellow laser versus subthreshold micropulse infrared laser in center-involving diabetic macular edema: Morphologic and functional safety. Retina. 2015; 35: 1594–1603. [CrossRef] [PubMed]
LIGHT: The International Retinal Laser Society 5th annual meeting, September 4, 2019, Paris, France.
Chang DB, Luttrull JK. Comparison of subthreshold 577 nm and 810 nm micropulse laser effects on heat-shock protein activation kinetics: Implications for treatment efficacy and safety. Trans Vis Sci Tech. 2020; 9.5: 23. [CrossRef]
De Cillà S, Vezzola D, Farruggio S, et al. The subthreshold micropulse laser treatment of the retina restores the oxidant/antioxidant balance and counteracts programmed forms of cell death in the mice eyes. Acta Ophthalmol. 2019; 97: e559–e567. [CrossRef] [PubMed]
Example Treatment Parameters for Various Laser Modes and Settings and Effects on Therapeutic (Clinical Safety) Ranges
Example Treatment Parameters for Various Laser Modes and Settings and Effects on Therapeutic (Clinical Safety) Ranges

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