Unlike conventional photocoagulation, non-damaging retinal laser therapy (NRT) limits laser-induced heating to stay
below the retinal damage threshold and therefore requires careful dosimetry. Without the adverse effects associated with
photocoagulation, NRT can be applied to critical areas of the retina and repeatedly to manage chronic disorders. Although
the clinical benefits of NRT have been demonstrated, the mechanism of therapeutic effect and width of the therapeutic
window below damage threshold are not well understood. Here, we measure activation of heat shock response via laser-induced
hyperthermia as one indication of cellular response. A 577 nm laser is used with the Endpoint Management (EpM)
user interface, a titration algorithm, to set experimental pulse energies relative to a barely visible titration lesion. Live/dead
staining and histology show that the retinal damage threshold in rabbits is at 40% of titration energy on EpM scale. Heat
shock protein 70 (HSP70) expression in the retinal pigment epithelium (RPE) was detected by whole-mount
immunohistochemistry after different levels of laser treatment. We show HSP70 expression in the RPE beginning at 25%
of titration energy indicating that there is a window for NRT between 25% and 40% with activation of the heat shock
protein expression in response to hyperthermia. HSP70 expression is also seen at the perimeter of damaging lesions, as
expected based on a computational model of laser heating. Expression area for each pulse energy setting varied between
laser spots due to pigmentation changes, indicating the relatively narrow window of non-damaging activation and
highlighting the importance of proper titration.
Jenny Wang, Philip Huie, Roopa Dalal, Seungjun Lee, Gavin Tan, Daeyoung Lee, Daniel Lavinksy M.D., and Daniel Palanker, "Heat shock protein expression as guidance for the therapeutic window of retinal laser therapy," Proc. SPIE 9693, Ophthalmic Technologies XXVI, 969319 (Presented at SPIE BiOS: February 14, 2016; Published: 4 March 2016); https://doi.org/10.1117/12.2213171.
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