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Laser-induced nanobubbles safely ablate vitreous opacities in vivo


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.


  1. Chiti, F. & Dobson, C. M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75, 333–366 (2006).

    Article  CAS  Google Scholar 

  2. Sebag, J. Vitreous and vision degrading myodesopsia. Prog. Retin. Eye Res. (2020).

  3. Asakura, A. Histochemistry of hyaluronic acid of the bovine vitreous body by electronmicroscopy. Nippon Ganka Gakkai Zasshi 89, 179–191 (1985).

    CAS  Google Scholar 

  4. Sebag, J. & Balazs, E. A. Morphology and ultrastructure of human vitreous fibers. Invest. Ophthalmol. Vis. Sci. 30, 1867–1871 (1989).

    CAS  Google Scholar 

  5. Sebag, J. Floaters and the quality of life. Am. J. Ophthalmol. 152, 3–4.e1 (2011).

    Article  Google Scholar 

  6. Webb, B. F., Webb, J. R., Schroeder, M. C. & North, C. S. Prevalence of vitreous floaters in a community sample of smartphone users. Int. J. Ophthalmol. 6, 402–405 (2013).

    Google Scholar 

  7. Zou, H., Liu, H., Xu, X. & Zhang, X. The impact of persistent visually disabling vitreous floaters on health status utility values. Qual. Life Res. 22, 1507–1514 (2013).

    Article  Google Scholar 

  8. Wagle, A. M., Lim, W.-Y., Yap, T.-P., Neelam, K. & Au Eong, K.-G. Utility values associated with vitreous floaters. Am. J. Ophthalmol. 152, 60–65.e1 (2011).

    Article  Google Scholar 

  9. Kim, Y.-K. et al. Psychological distress in patients with symptomatic vitreous floaters. J. Ophthalm. (2017).

  10. Milston, R., Madigan, M. C. & Sebag, J. Vitreous floaters: etiology, diagnostics, and management. Surv. Ophthalmol. 61, 211–227 (2016).

    Article  Google Scholar 

  11. Sebag, J., Yee, K. M. P., Wa, C. A., Huang, L. C. & Sadun, A. A. Vitrectomy for floaters: prospective efficacy analyses and retrospective safety profile. Retina 34, 1062–1068 (2014).

    Article  Google Scholar 

  12. Macherner, R. The development of pars plana vitrectomy: a personal account. Graefes Arch. Clin. Exp. Ophthalmol. 233, 453–468 (1995).

    Article  Google Scholar 

  13. Holekamp, N. M., Shui, Y.-B. & Beebe, D. C. Vitrectomy surgery increases oxygen exposure to the lens: a possible mechanism for nuclear cataract formation. Am. J. Ophthalmol. 139, 302–310 (2005).

    Article  Google Scholar 

  14. Kunimoto, D. Y. & Kaiser, R. S. Incidence of endophthalmitis after 20- and 25-gauge vitrectomy. Ophthalmology 114, 2133–2137 (2007).

    Article  Google Scholar 

  15. Tsai, W. F., Chen, Y. C. & Su, C. Y. Treatment of vitreous floaters with neodymium YAG laser. Br. J. Ophthalmol. 77, 485–488 (1993).

    Article  CAS  Google Scholar 

  16. Procedure guide: vitreous opacities. Ellex Medical Pty (2022).

  17. Rockwell, B. A., Thomas, R. J. & Vogel, A. Ultrashort laser pulse retinal damage mechanisms and their impact on thresholds. Med. Laser Appl. 25, 84–92 (2010).

    Article  Google Scholar 

  18. Delaney, Y. M., Oyinloye, A. & Benjamin, L. Nd:YAG vitreolysis and pars plana vitrectomy: surgical treatment for vitreous floaters. Eye 16, 21–26 (2002).

    Article  CAS  Google Scholar 

  19. Koo, E. H., Haddock, L. J., Bhardwaj, N. & Fortun, J. A. Cataracts induced by neodymium–yttrium-aluminium-garnet laser lysis of vitreous floaters. Br. J. Ophthalmol. 101, 709–711 (2017).

    Article  Google Scholar 

  20. Xiong, R., Xu, R. X., Huang, C., Smedt, S. D. & Braeckmans, K. Stimuli-responsive nanobubbles for biomedical applications. Chem. Soc. Rev. (2021).

  21. Xiong, R. et al. Comparison of gold nanoparticle mediated photoporation: vapor nanobubbles outperform direct heating for delivering macromolecules in live cells. ACS Nano 8, 6288–6296 (2014).

    Article  CAS  Google Scholar 

  22. Liu, J. et al. Repeated photoporation with graphene quantum dots enables homogeneous labeling of live cells with extrinsic markers for fluorescence microscopy. Light Sci. Appl. 7, 47 (2018).

    Article  Google Scholar 

  23. Harizaj, A. et al. Photoporation with biodegradable polydopamine nanosensitizers enables safe and efficient delivery of mRNA in human T cells. Adv. Funct. Mater. 31, 2102472 (2021).

    Article  CAS  Google Scholar 

  24. Barras, A. et al. Carbon quantum dots as a dual platform for the inhibition and light-based destruction of collagen fibers: implications for the treatment of eye floaters. Nanoscale Horiz. (2021).

  25. Hua, D. et al. Bubble forming films for spatial selective cell killing. Adv. Mater. (2021).

  26. Ueno, N., Sebag, J., Hirokawa, H. & Chakrabarti, B. Effects of visible-light irradiation on vitreous structure in the presence of a photosensitizer. Exp. Eye Res. 44, 863–870 (1987).

    Article  CAS  Google Scholar 

  27. Filas, B. A., Zhang, Q., Okamoto, R. J., Shui, Y.-B. & Beebe, D. C. Enzymatic degradation identifies components responsible for the structural properties of the vitreous body. Invest. Ophthalmol. Vis. Sci. 55, 55–63 (2014).

    Article  CAS  Google Scholar 

  28. Sauvage, F. et al. Photoablation of human vitreous opacities by light-induced vapor nanobubbles. ACS Nano 13, 8401–8416 (2019).

    Article  CAS  Google Scholar 

  29. Ziefuss, A. R., Reich, S., Reichenberger, S., Levantino, M. & Plech, A. In situ structural kinetics of picosecond laser-induced heating and fragmentation of colloidal gold spheres. Phys. Chem. Chem. Phys. 22, 4993–5001 (2020).

    Article  CAS  Google Scholar 

  30. Pan, Y. et al. Size-dependent cytotoxicity of gold nanoparticles. Small 3, 1941–1949 (2007).

    Article  CAS  Google Scholar 

  31. Desmettre, T., Devoisselle, J. M. & Mordon, S. Fluorescence properties and metabolic features of indocyanine green (ICG) as related to angiography. Surv. Ophthalmol. 45, 15–27 (2000).

    Article  CAS  Google Scholar 

  32. Burk, S. E., Da Mata, A. P., Snyder, M. E., Rosa, R. H. & Foster, R. E. Indocyanine green-assisted peeling of the retinal internal limiting membrane. Ophthalmology 107, 2010–2014 (2000).

    Article  CAS  Google Scholar 

  33. Seitz, B. & Langenbucher, A. Lasers in ophthalmology. Lancet 356, S26 (2000).

    Article  Google Scholar 

  34. Masse, F., Ouellette, M., Lamoureux, G. & Boisselier, E. Gold nanoparticles in ophthalmology. Med. Res. Rev. 39, 302–327 (2019).

    Article  Google Scholar 

  35. Pereira, D. V. et al. Effects of gold nanoparticles on endotoxin-induced uveitis in rats. Invest. Ophthalmol. Vis. Sci. 53, 8036–8041 (2012).

    Article  CAS  Google Scholar 

  36. Chen, F., Si, P., Zerda, Adela, V. Jokerst, J. & Myung, D. Gold nanoparticles to enhance ophthalmic imaging. Biomater. Sci. 9, 367–390 (2021).

    Article  CAS  Google Scholar 

  37. Hayashi, A., Naseri, A., Pennesi, M. E. & de Juan, E. Subretinal delivery of immunoglobulin G with gold nanoparticles in the rabbit eye. Jpn. J. Ophthalmol. 53, 249–256 (2009).

    Article  CAS  Google Scholar 

  38. Rodrigues, E. B., Meyer, C. H., Mennel, S. & Farah, M. E. Mechanisms of intravitreal toxicity of indocyanine green dye: implications for chromovitrectomy. Retina 27, 958–970 (2007).

    Article  Google Scholar 

  39. Kwok, A. K. H., Lai, T. Y. Y., Yew, D. T. W. & Li, W. W. Y. Internal limiting membrane staining with various concentrations of indocyanine green dye under air in macular surgeries. Am. J. Ophthalmol. 136, 223–230 (2003).

    Article  Google Scholar 

  40. Wels, M., Roels, D., Raemdonck, K., De Smedt, S. C. & Sauvage, F. Challenges and strategies for the delivery of biologics to the cornea. J. Control. Release 333, 560–578 (2021).

    Article  CAS  Google Scholar 

  41. Del Amo, E. M. et al. Pharmacokinetic aspects of retinal drug delivery. Prog. Retin. Eye Res. 57, 134–185 (2017).

    Article  Google Scholar 

  42. Käsdorf, B. T., Arends, F. & Lieleg, O. Diffusion regulation in the vitreous humor. Biophys. J. 109, 2171–2181 (2015).

    Article  Google Scholar 

  43. Lapotko, D. Optical excitation and detection of vapor bubbles around plasmonic nanoparticles. Opt. Express 17, 2538–2556 (2009).

    Article  CAS  Google Scholar 

  44. Xiong, R. et al. Laser-assisted photoporation: fundamentals, technological advances and applications. Adv. Phys. X 1, 596–620 (2016).

    CAS  Google Scholar 

  45. Lukianova-Hleb, E. et al. Plasmonic nanobubbles as transient vapor nanobubbles generated around plasmonic nanoparticles. ACS Nano 4, 2109–2123 (2010).

    Article  CAS  Google Scholar 

  46. Lukianova-Hleb, E. Y. et al. Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria. Proc. Natl Acad. Sci. USA 111, 900–905 (2014).

    Article  CAS  Google Scholar 

  47. Palanker, D. Femtosecond lasers for ophthalmic surgery enabled by chirped-pulse amplification. N. Engl. J. Med. 379, 2267–2269 (2018).

    Article  Google Scholar 

  48. American National Standard for Safe Use of Lasers ANSI Z136.1-2014 (Laser Institute of America, 2015);

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

Author information

Authors and Affiliations



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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Peer review information

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).

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