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Giorgio Dorin; Threshold and Subthreshold Retinal Laser Therapy. But which Threshold?. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4142.
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To define subthreshold laser therapy within the range of cellular and molecular changes inducible with laser exposures and its therapeutic window for effective treatments without retinal burns, once believed essential prerequisite for a useful therapy.
Analysis of concomitant photothermal interactions occurring with laser photocoagulation, the current effective, but also destructive standard of care for diabetic retinopathy. Postulation of new hypotheses on the mechanism of action to understand the outcomes of several randomized clinical trials comparing the treatment of Diabetic Macular Edema (DME) with non-destructive subthreshold micropulse versus destructive modified ETDRS focal/grid threshold laser photocoagulation, which disprove the deeply rooted notion that a useful treatment must destroy RPE cells that produce angiogenic factors, oxygen-avid rods and cones, and close microaneurysms.
In ophthalmic parlance threshold photocoagulation is a treatment with minimum power to reach the threshold of visible tissue reaction. Similar transactional biological activities are elicited indirectly with threshold photocoagulation and directly with sub-visible-threshold treatments. Similar therapeutic pathways induce similar clinical benefits, affected however by the different tissue damage and inflammation. Destructive laser burns are superfluous and major cause of complications. Sublethal photothermal rises obtained with micropulse laser suffice to alter and rebalance the retinal gene expression profile as an endogenous pharmacotherapy, which, avoiding iatrogenic damage and risks, can ultimately lead to superior clinical benefits. The therapeutic window, spanning from its lowest level, just above the threshold of cellular biological activation, to its higher level, below the threshold of visible tissue reaction, is quite wide.
Subthreshold micropulse is a non-destructive therapy, which, in the treatment of DME, has been shown to retain neural retina physiological functions on mf-ERG and to improve retinal sensitivity on microperimetry. The avoidance of burns and enlarging scars discernable at any time postoperatively allows high density applications, shown to lead to new levels of functional and anatomical benefits, enhanced by the possibility of re-treatments pro re nata, alone or in combination with pharmacological therapies.
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