Subthreshold Nano-Second Laser Treatment and Age-Related Macular Degeneration

Abstract

The presence of drusen is an important hallmark of age-related macular degeneration (AMD). Laser-induced regression of drusen, first observed over four decades ago, has led to much interest in the potential role of lasers in slowing the progression of the disease. In this article, we summarise the key insights from pre-clinical studies into the possible mechanisms of action of various laser interventions that result in beneficial changes in the retinal pigment epithelium/Bruch's membrane/choriocapillaris interface. Key learnings from clinical trials of laser treatment in AMD are also summarised, concentrating on the evolution of laser technology towards short pulse, non-thermal delivery such as the nanosecond laser. The evolution in our understanding of AMD, through advances in multimodal imaging and functional testing, as well as ongoing investigation of key pathological mechanisms, have all helped to set the scene for further well-conducted randomised trials to further explore potential utility of the nanosecond and other subthreshold short pulse lasers in AMD.

Keywords: age-related macular degeneration; drusen; laser.

Figure 1

Human retinas treated with continuous wave (CW) or nanosecond laser irradiation. Cross sections of human retinas are shown immunolabelled for the neuronal marker calretinin (green), and the nuclear maker bisenzimide (blue). Sections corresponding to an area well away are shown in Figure 2. RT^® (2RT) or CW treatment (CW). Significant disruption of photoreceptors is evident in the region treated with the continuous wave laser. Abbreviations: ONL—outer nuclear layer; INL—inner nuclear layer; GCL—ganglion cell layer. Figure adapted from Jobling et al. (2005).

Figure 2

Nanosecond laser thins Bruch’s membrane in a mouse model with features of early AMD. (A,B) Electron micrographs of the Bruch’s membrane (BM) of a non-laser treated 12-month-old ApoEnull mouse and an ApoEnull mouse that had received nanosecond laser treatment 3 months prior to fixation. Abbreviations: BM-Bruch’s membrane; RPE-retinal pigmental epithelium. (C) Graph showing percentage change in Bruch’s membrane thickness in control, lasered, and unlasered fellow eyes of ApoENull mice that had received laser treatment 3 months prior. Application of the nanosecond laser induced significant thinning of Bruch’s membrane compared to control or fellow unlasered eyes (one-way ANOVA, Tukey’s post-hoc test; ** p < 0.01). Figure adapted from Jobling et al. (2005).