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).
3–6,10 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.
3–6,11 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 trains
4,5,10 (
Table).