Lasers in Medicine: The Changing Role of Therapeutic Laser-Induced Retinal Damage—From de rigeuer to Nevermore

Abstract

For over five decades, laser-induced retinal damage (LIRD) was thought to be the necessary cost of all therapeutic effects of laser treatment for the most important causes of irreversible visual loss, the chronic progressive retinopathies (CPRs). The development of modern retinal laser therapy with the discovery of “low-intensity/high-density subthreshold micropulse” laser (SDM) showed that the supposed need for LIRD represented a case of confusing association with causation. This revealed that LIRD was unnecessary and detrimental to clinical outcomes, and thus, contraindicated as the most severe complication of retinal laser treatment. SDM allowed for an understanding of the mechanism of retinal laser treatment as a physiologic reset effect, triggered by heat-shock protein (HSP) activation upregulating the unfolded protein response and restoring proteostasis by increasing protein repair by 35% in dysfunctional cells via a thermally sensitive conformational change in the K10 step of HSP activation kinetics. Because HSP activation kinetics are catalytic, even low levels (the “reset” threshold) of HSP activation result in a maximal treatment response. SDM and the study of HSP activation kinetics in the retina show that the therapeutic effects of retinal laser treatment can be fully realized without any degree of LIRD. Besides LIRD, all effects of retinal laser treatment are restorative and therapeutic, without any known adverse treatment effects. Without LIRD, the benefits of retinal laser treatment are infinitely renewable and direct treatment of the fovea is possible. Elimination of LIRD from retinal laser treatment has revolutionized the clinical potential of retinal laser treatment to broaden treatment indications to permit, for the first time, effective early and preventive treatment to reduce visual loss from the most frequent causes of irreversible visual loss worldwide, the CPRs.