Gold nanoparticles for the treatment of eye floaters by light-induced vapor nanobubbles

Abstract

Purpose : Vitreous opacities are collagen aggregates that form in the vitreous body due to myopia and/or age-related structural changes (i.e. fibrous liquefaction) which cast shadows on the retina, impacting vision. Current therapies are based on laser treatment with an yttrium garnet laser (YAG) or vitrectomy The efficacy of YAG laser vitreolysis is unproven and vitrectomy remains invasive with associated side effects).
We propose a nanotechnology-based treatment of floaters using the plasmon properties of gold nanoparticles (AuNPs). AuNPs bind to vitreous opacities, and when exposed to pulsed-laser light (typically a nanosecond laser), heat up and generate vapour nanobubbles (VNBs) due to the evaporation of the surrounding water. These VNBs then burst, providing sufficient mechanical energy to fragment and destroy the opacities.

Methods : In Vitro: Type I collagen fibers were prepared as artificial floaters and human vitreous opacities were obtained from patients after vitrectomy. Samples were mixed with Hyaluronic (HA) coated AuNPs (10 nm) and irradiated with a pulsed laser (<7ns; 561 nm) at different fluences. Dark field imaging was performed to assess effects.
In Vivo: Type I collagen fibers were injected intravitreally in rabbits so that they were located close to the retina (<500 µm). 5 days later, HA-AuNPs were injected. Three days after the injection of AuNPs, fibers were irradiated with a nanosecond laser (<7ns; 530 nm). Photoacoustic imaging was performed to assess binding of gold on the injected fibers, and optical coherence tomography was performed to assess destruction of the fibers.

Results : HA-AuNPs can diffuse in the vitreous and bind to collagen fibers and vitreous opacities.
Type I collagen fibers and vitreous opacities could be completely destroyed in vitro and ex vivo at a fluence of 4.5 J/cm². In vivo, collagen fibers could be destroyed after 7 scans at a fluence of 1.9 J/cm². Preliminary retinal toxicity assesment (TUNEL and H&E staining) did not reveal significant changes compared to untreated rabbits.

Conclusions : This approach can effectively and rapidly destroy vitreous opacities ex vivo and collagen fibers in vivo, using lower energy levels than YAG therapy and paves the way for the vitreolysis with pulsed-lasers and nanotechnologies

This is a 2021 ARVO Annual Meeting abstract.