Treatment of age related macular degeneration using nanosecond laser therapy: Safety profile studies in humans and mice

Abstract

Purpose : Clinical trials for the treatment of age related macular degeneration (AMD) with subthreshold nanosecond laser therapies are currently underway. The aim of this study was to investigate the safety profile of this treatment in humans and mice.

Methods : Retinal sensitivity was assessed with microperimetry in patients (n=7) with AMD following treatment with nanosecond pulsed laser at subthreshold, energy doses (0.15-0.45mJ). A range of retinal and vascular responses were assessed in adult C57BL6J mice (n=20) treated with sub- (0.065 mJ) and supra-threshold (0.5 mJ) energy doses at 7 days and 3 months after treatment. In vivo fundus imaging and optical coherence tomography (OCT) were performed. Structural (confocal and electron microscopy) and gene changes (quantitative PCR for angiogenic genes) were also assessed.

Results : In patients, microperimetry analysis 6 months to 7 years after treatment showed laser therapy had no effect on retinal sensitivity under the treated areas (p=0.21). In mice, subthreshold treatment reduced RPE pigmentation on fundus imaging but quantitative OCT analysis showed no focal loss in retinal layer thickness directly under the laser sites. At 7 days post-laser, electron microscopy revealed that the RPE and Bruch’s membrane remained intact throughout the laser treated-regions with subtle changes in melanosome composition of the RPE. Confocal microscopy showed there were no changes consistent with choroidal neovascularization following treatment. Suprathreshold laser treatment induced a fundus lesion and loss of retinal neurons but did not induce changes in angiogenic genes associated with neovascularisation in retina or RPE samples. Instead pigment epithelium derived factor, a potent anti-angiogenic factor was upregulated.

Conclusions : In patients, local retinal sensitivity was not affected short or long term by subthreshold, pulsed nanosecond laser treatment. In mice, subthreshold laser treatment did not damage retinal structure or Bruch’s membrane, or induce neovascularization. These findings highlight there are minimal side effects of this nanosecond laser when used in a subthreshold manner.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.