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Laser-induced nanobubbles safely ablate vitreous opacities in vivo

Nature Nanotechnology volume 17, pages 552–559 (2022)Cite this article

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Abstract

In myopia, diabetes and ageing, fibrous vitreous liquefaction and degeneration is associated with the formation of opacities inside the vitreous body that cast shadows on the retina, appearing as ‘floaters’ to the patient. Vitreous opacities degrade contrast sensitivity function and can cause notable impairment in vision-related quality of life. Here we introduce ‘nanobubble ablation’ for safe destruction of vitreous opacities. Following intravitreal injection, hyaluronic acid-coated gold nanoparticles and indocyanine green, which is widely used as a dye in vitreoretinal surgery, spontaneously accumulate on collagenous vitreous opacities in the eyes of rabbits. Applying nanosecond laser pulses generates vapour nanobubbles that mechanically destroy the opacities in rabbit eyes and in patient specimens. Nanobubble ablation might offer a safe and efficient treatment to millions of patients suffering from debilitating vitreous opacities and paves the way for a highly safe use of pulsed lasers in the posterior segment of the eye.

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Fig. 1: Vitreous liquefaction and concept of nanobubble-mediated ablation of vitreous opacities.
Fig. 2: Laser-induced ablation of vitreous opacities from gold nanoparticles.
Fig. 3: In vitro and ex vivo investigation of ICG for nanobubble-mediated ablation of vitreous opacities.
Fig. 4: In vivo investigation of ICG for nanobubble-mediated ablation of vitreous opacities.
Fig. 5: Retinal safety of nanobubble-mediated ablation of vitreous opacities.

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Data availability

Source data are provided with this paper. All data supporting the findings of this study are available within the paper and its Supplementary Information. Any further related information can be provided by the corresponding authors on reasonable request.

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Acknowledgements

This research was supported by the Research Foundation Flanders (FWO, 12X3222N, F.S.).

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Author notes

  1. These authors contributed equally: Félix Sauvage, Van Phuc Nguyen.

Authors and Affiliations

  1. Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium

    Félix Sauvage, Aranit Harizaj, Viktor Van Havere, Karen Peynshaert, Juan C. Fraire, Katrien Remaut, Kevin Braeckmans & Stefaan C. De Smedt

  2. Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA

    Van Phuc Nguyen, Yanxiu Li & Yannis M. Paulus

  3. NTT-Hitech Institutes, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam

    Van Phuc Nguyen

  4. VMR Institute for Vitreous Macula Retina, Huntington Beach, CA, USA

    J. Sebag

  5. Doheny Eye Institute/UCLA, Los Angeles, CA, USA

    J. Sebag

  6. Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium

    Dimitri Roels

  7. Joint Laboratory of Advanced Biomedical Materials, International Innovation Center for Forest Chemicals and Materials, College of Chemical Engineering, Nanjing Forestry University, Nanjing, China

    Ranhua Xiong & Stefaan C. De Smedt

  8. Department of Ophthalmology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium

    Marie-José Tassignon

  9. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA

    Yannis M. Paulus

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Contributions

F.S., K.B. and S.C.D.S. conceived the concept of nanobubble ablation of vitreous opacities. F.S., V.V.H., R.X. and A.H. performed and analysed the in vitro/ex vivo experiments. R.X. and K.B. designed the optical set-up. J.S. contributed to the writing of the manuscript and performed vitrectomies. J.C.F. synthesized and characterized the AuNPs. V.P.N. and Y.L. performed the experiments in rabbits. F.S., V.P.N. and Y.L. performed the analysis of the experiments in rabbits (OCT, PAM, histology and ERG). F.S., S.C.D.S., V.P.N. and Y.M.P. designed the in vivo experiments. K.R., D.R., M.-J.T., K.P., K.B., J.S., Y.M.P., A.H. and S.C.D.S. advised and provided guidance on experiments and data analysis. All authors discussed the experimental results and jointly wrote the manuscript.

Corresponding authors

Correspondence to Yannis M. Paulus, Kevin Braeckmans or Stefaan C. De Smedt.

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The authors declare no competing interests.

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Nature Nanotechnology thanks Lingam Gopal, James McLaughlan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–6.

Reporting Summary

Supplementary Video 1

ICG (0.5 mg ml−1) mixed with exogenous collagen opacities (0.02 mg ml−1) locally generate VNBs leading to their mechanical destruction.

Supplementary Video 2

ICG (0.5 mg ml−1) mixed with opacities obtained in patients during vitrectomy locally generate VNBs leading to their mechanical destruction.

Source data

Source Data Fig. 3

Number of pulses needed for the destruction of collagen fibres as a function of the fluence and type of photosensitizer.

Source Data Fig. 5

Source data of electroretinograms (b-wave amplitude and implicit time).

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Sauvage, F., Nguyen, V.P., Li, Y. et al. Laser-induced nanobubbles safely ablate vitreous opacities in vivo. Nat. Nanotechnol. 17, 552–559 (2022). https://doi.org/10.1038/s41565-022-01086-4

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