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Retinal-detachment repair and vitreous-like-body reformation via a thermogelling polymer endotamponade

Nature Biomedical Engineering volume 3, pages 598–610 (2019)Cite this article

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Abstract

Internal-tamponade agents are crucial surgical adjuncts in vitreoretinal surgery. Clinically used endotamponade agents act through buoyancy forces, yet can result in prolonged post-operative positioning, temporary loss of vision, raised intra-ocular pressure, cataract formation or the need for additional removal surgery. Here, we describe a thermogelling polymer that provides an internal tamponade effect through surface tension and swelling counter-forces. We tested the long-term biocompatibility of the polymer endotamponade in rabbit vitrectomy models, and its surgical efficacy and biocompatibility in a non-human primate retinal-detachment model. We also show that, while the thermogel biodegrades during the three months following surgery, it promotes the reformation of a vitreous-like body that mimics the biophysical properties of the natural vitreous. The thermogelling endotamponade might serve as a long-term vitreous substitute.

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Fig. 1: Rheological characterization of EPC-3%, EPC-7% and EPC-12% gel.
Fig. 2: Live in vivo imaging of rabbits implanted with different hydrogels at day 7 post-operation.
Fig. 3: In vivo imaging and ex vivo retinal analysis of rabbits at 3 months post-implantation of EPC-3% and EPC-7% thermogels.
Fig. 4: Functional assessment of rabbit retina by ERG.
Fig. 5: An NHP surgical retinal-detachment model demonstrates EPC-7% thermogel to be an effective endotamponade.
Fig. 6: Proteome profile of EPC reformed vitreous-like body.

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Data availability

The authors declare that all data supporting the results in this study are available within the paper and its Supplementary Information. The MS proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org/) via the PRIDE partner repository, with the dataset identifier PXD009525.

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Acknowledgements

This study was supported by a Biomedical Engineering Programme (BEP) grant, A*STAR, Singapore (2014 POC/1521480032), the NUS Start-up grant NUHSRO/2016/100/SU/01 and IAF-PP (HMBS Domain) H17/01/a0/013 (OrBID): OculaR BIomaterials and Device. We would like to acknowledge the veterinary team at the Translational Pre-Clinical Model Platform (Singapore Eye Research Institute, Singapore) for providing support in NHP surgery preparation and animal follow-up.

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Authors and Affiliations

  1. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Zengping Liu, Graham E. Holder, Bhav Harshad Parikh, Veluchamy Amutha Barathi, Clement Woon Teck Tan, Caroline K. Chee, Gopal Lingam & Xinyi Su

  2. Singapore Eye Research Institute, Singapore, Singapore

    Zengping Liu, Veluchamy Amutha Barathi, Rajamani Lakshminarayanan, Caroline K. Chee, Gopal Lingam & Xinyi Su

  3. Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), Singapore, Singapore

    Sing Shy Liow, Zibiao Li, Mein Jin Tan & Xian Jun Loh

  4. Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Singapore, Singapore

    Siew Li Lai, Asfa Alli-Shaik, Jayantha Gunaratne, Walter Hunziker & Xinyi Su

  5. UCL Institute of Ophthalmology, London, UK

    Graham E. Holder

  6. Vision Research Foundation, Chennai, India

    Subramanian Krishnakumar

  7. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Jayantha Gunaratne

  8. Ophthalmology Academic Clinical Research Program, DUKE-NUS Medical School, Singapore, Singapore

    Veluchamy Amutha Barathi

  9. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Walter Hunziker

  10. Department of Ophthalmology, National University Hospital, Singapore, Singapore

    Clement Woon Teck Tan, Caroline K. Chee, Paul Zhao, Gopal Lingam & Xinyi Su

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Contributions

X.S., X.J.L., G.L. and Z. Liu designed experiments and prepared the manuscript. G.L., P.Z. and X.S. performed the in vivo animal surgeries. Z. Liu performed the in vivo assessment of animals post-surgery. V.A.B. provided assistance in large-animal surgeries. S.S.L., Z. Li and M.J.T. synthesized thermogels and performed rheological assessments. R.L. provided assistance in rheological assessments of the thermogels. S.L.L. and J.G. performed MS analysis and A.A.-S. performed the vitreous proteome analysis. G.E.H. analysed the ERG data and contributed to manuscript preparation. B.H.P. performed immunohistochemistry experiments. S.K. performed the H&E histology experiments. W.H. provided assistance in ex vivo analysis of retina and manuscript preparation. C.W.T.T., C.K.C. and P.Z. provided clinical inputs on clinical application of thermogel, and preparation of the manuscript. All authors reviewed and commented on the manuscript.

Corresponding authors

Correspondence to Gopal Lingam, Xian Jun Loh or Xinyi Su.

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Supplementary information

Supplementary Information

Supplementary figures, and video and table captions.

Reporting Summary

Supplementary Dataset

List of proteins identified by MS-based LFQ proteomics analysis.

Supplementary Video 1

Gel injection in the rabbit eye.

Supplementary Video 2a

Dissection of the EPC-filled eye, 3 months post-operation.

Supplementary Video 2b

Dissection of the native vitreous.

Supplementary Video 2c

Dissection of the operated control (BSS-filled eye), 3 months post-operation.

Supplementary Video 3a

SD-OCT volume scan of the retinotomy site of the non-human primate, 12 months post-operation.

Supplementary Video 3b

SD-OCT volume scan of the macula of the non-human primate, 2 months post-operation.

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Liu, Z., Liow, S.S., Lai, S.L. et al. Retinal-detachment repair and vitreous-like-body reformation via a thermogelling polymer endotamponade. Nat Biomed Eng 3, 598–610 (2019). https://doi.org/10.1038/s41551-019-0382-7

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