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A novel, minimally invasive implant to assist in repeated intraocular drug delivery

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Abstract

The standard of care for posterior segment disorders such as wet age-related macular degeneration, diabetic macular oedema and retinal vascular occlusions is pharmacotherapy by intravitreal drug delivery. Since the therapeutic effect of these drugs lasts only around 4 to 8 weeks, repeated intravitreal injections are required. Pain is experienced by the patients during injection as the needle courses through the sclera and choroid. The current work describes the design and development of a novel anodized titanium alloy implant that allows for intravitreal injections through the implant so that the needle transverses only the conjunctiva, thus minimizing discomfort to the patient. Both ex-vivo testing of the implant in enucleated goat’s eye as well as in-vivo validation in rabbit eyes was carried out. The implant was placed through pars plana via a minor surgical procedure and was sutured to the sclera and covered with conjunctiva. Subsequent intravitreal injections were administered under topical anaesthesia with a 30-gauge needle through the implant thus delivering the drug into the vitreous cavity. Repeated intravitreal injections were administered every 2 weeks via the implant for 3 months in 4 rabbits. Apart from cataract in 1 rabbit, no complications were observed. There was no evidence of intra-ocular inflammation or infection at final follow-up. Histopathological analysis did not reveal any inflammation or necrosis around the area of implant. The implants were subsequently removed at 5 months and scleral wound was closed with a single suture. The sclera and overlying conjunctiva healed well and no intraocular complications were observed after removal.

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References

  • E.M. Del Amo, A. Urtti, Exp. Eye Res. 137, 111 (2015)

    Article  Google Scholar 

  • P.S. Apaolaza, M. Busch, E. Asin-Prieto, K. Peynshaert, R. Rathod, K. Remaut, N. Dünker, A. Göpferich, Exp. Eye Res. 198, 108151 (2020)

    Article  Google Scholar 

  • T. Baba, G. Miura, T. Tatsumi, M. Sakurai, S. Yamamoto, Jpn J. Ophthalmol. 65, 492 (2021)

    Article  Google Scholar 

  • I. Bekerman, P. Gottlieb, M. Vaiman, J. Ophthalmol. 2014, (2014)

  • B. Bilgin, Ş Bilak, Middle East. Afr. J. Ophthalmol. 26, 55 (2019)

    Article  Google Scholar 

  • A.V. Bux, F. Fortunato, A. Barone, V. Russo, N.Delle Noci, C. Iaculli, Eur. J. Ophthalmol. 11206721211024804 (2021)

  • P.A. Campochiaro, D.M. Marcus, C.C. Awh, C. Regillo, A.P. Adamis, V. Bantseev, Y. Chiang, J.S. Ehrlich, S. Erickson, W.D. Hanley, J. Horvath, K.F. Maass, N. Singh, F. Tang, G. Barteselli, Ophthalmology 126, 1141 (2019)

    Article  Google Scholar 

  • Food and Drug Administration, J. Int. Assoc. Physicians AIDS Care 1, 37 (1995)

    Google Scholar 

  • F. Gomi, R. Toyoda, A.H. Yoon, K. Imai, J. Clin. Med. 10, 3106 (2021)

    Article  Google Scholar 

  • M.S. Habib, Ther. Deliv 9, 547 (2018)

    Article  Google Scholar 

  • J.S. Heier, A.N. Antoszyk, P.R. Pavan, S.R. Leff, P.J. Rosenfeld, T.A. Ciulla, R.F. Dreyer, R.C. Gentile, J.P. Sy, G. Hantsbarger, N. Shams, Ophthalmology 113, 633 (2006)

    Article  Google Scholar 

  • N.M. Holekamp, P.A. Campochiaro, M.A. Chang, D. Miller, D. Pieramici, A.P. Adamis, C. Brittain, E. Evans, D. Kaufman, K.F. Maass, S. Patel, S. Ranade, N. Singh, G. Barteselli, C. Regillo, A. Investigators, Ophthalmology 129, 295 (2022)

    Article  Google Scholar 

  • M. Hu, G. Huang, F. Karasina, V.G. Wong, Invest. Ophthalmol. Vis. Sci. 49, 5627 (2008)

    Google Scholar 

  • X. Huang, Y. Chau, Exp. Eye Res. 186, 107711 (2019)

    Article  Google Scholar 

  • Y.F.K. Islam, C.R. Blake, S.K. Gibran, Eye 35, 1850 (2021)

    Article  Google Scholar 

  • G.J. Jaffe, D. Martin, D. Callanan, P.A. Pearson, B. Levy, T. Comstock, Ophthalmology 113, 1020 (2006)

    Article  Google Scholar 

  • A.M. Khanani, D. Callanan, R. Dreyer, S. Chen, J.G. Howard, J.J. Hopkins, C. Lin, M. Lorenz-candlin, S. Makadia, S. Patel, T. Tam, S. Gune, Ophthalmol. Retin 5, 775 (2020)

    Article  Google Scholar 

  • R. Lee, T.Y. Wong, C. Sabanayagam, Eye Vis. 2, 1 (2015)

    Article  Google Scholar 

  • M.G. Maguire, D.F. Martin, G.-S. Ying, G.J. Jaffe, E. Daniel, J.E. Grunwald, C.A. Toth, F.L. Ferris, S.L. Fine, Physiol. Behav. 176, 139 (2017)

    Article  Google Scholar 

  • A. Martel, S. Nahon-Esteve, K. Martini, F. Almairac, S. Baillif, Graefe’s Arch. Clin. Exp. Ophthalmol. 258, 1395 (2020)

    Article  Google Scholar 

  • D.F. Martin, M.G. Maguire, S.L. Fine, G. Ying, G.J. Jaffe, J.E. Grunwald, C. Toth, M. Redford, F.L. Ferris, Ophthalmology 119, 1388 (2013)

    Article  Google Scholar 

  • E. Moisseiev, A. Loewenstein, Harefuah 158, 121 (2019)

    Google Scholar 

  • E. Moisseiev, M. Waisbourd, E. Ben-Artsi, E. Levinger, A. Barak, T. Daniels, K. Csaky, A. Loewenstein, I.S. Barequet, Graefe’s Arch. Clin. Exp. Ophthalmol. 252, 331 (2014)

    Article  Google Scholar 

  • B.P. Nicholson, R.P. Singh, J.E. Sears, C.Y. Lowder, P.K. Kaiser, Am. J. Ophthalmol. 154, 969 (2012)

    Article  Google Scholar 

  • A. Nieto, H. Hou, M.J. Sailor, W.R. Freeman, L. Cheng, Exp. Eye Res. 116, 161 (2013)

    Article  Google Scholar 

  • S.F.E. Nilsson, J. Ver Hoeve, S. Wu, P.L. Kaufman, A. Alm, Adler’s Physiology of the Eye, 11th ed. (2011)

  • A. Oishi, M. Mandai, A. Nishida, M. Hata, T. Matsuki, Y. Kurimoto, Eur. J. Ophthalmol. 21, 777 (2011)

    Article  Google Scholar 

  • M. Pancholy, P.P. Storey, H.J. Levin, A. Obeid, S.N. Patel, B. Kuley, J. Hsu, M.J. Spirn, M. Fineman, M.A. Klufas, O. Gupta, A.C. Ho, S.J. Garg, Curr. Eye Res. 46, 1370 (2021)

    Article  Google Scholar 

  • V.T. Papastavrou, H. Zambarakji, I. Dooley, H. Eleftheriadis, T.L. Jackson, Retin. Cases Br. Reports 11, 44 (2017)

    Article  Google Scholar 

  • A. Reiner, M.E.C. Fitzgerald, N. Del Mar, C. Li, Prog. Retin. Eye Res. 64, 96 (2018)

    Article  Google Scholar 

  • K.A. Rezaei, J.C. Wen, MedEdPORTAL 12, 10502 (2016)

    Article  Google Scholar 

  • M.M. Sachdeva, A. Moshiri, H.A. Leder, A.W. Scott, J. Ophthalmic Inflamm. Infect. (2016)

  • H. Selvan, A. Pujari, A. Kishan, A.K. Behera, T. Sidhu, V. Gupta, T. Dada, R. Sihota, Curr. Eye Res. 46, 78 (2021)

    Article  Google Scholar 

  • S. Sen, C. Mishra, N.B. Kannan, K. Ramasamy, G. Rameshkumar, P. Lalitha, Semin Ophthalmol. 36, 413 (2021)

    Article  Google Scholar 

  • A. Sudhalkar, P. Chauhan, A. Sudhalkar, R.H. Trivedi, Ophthalmology 119, 198 (2012)

    Article  Google Scholar 

  • C. Wang, H. Hou, K. Nan, M.J. Sailor, W.R. Freeman, L. Cheng, Exp. Eye Res. 129, 74 (2014)

    Article  Google Scholar 

  • W.L. Wong, X. Su, X. Li, C.M.G. Cheung, R. Klein, C.Y. Cheng, T.Y. Wong, Lancet Glob. Heal. 2, e106 (2014)

    Article  Google Scholar 

  • L. Xu, T. Lu, L. Tuomi, N. Jumbe, J. Lu, S. Eppler, P. Kuebler, L.A. Damico-Beyer, A. Joshi, Investig Ophthalmol. Vis. Sci. 54, 1616 (2013)

    Article  Google Scholar 

  • N.A. Yannuzzi, N.Z. Gregori, P.J. Rosenfeld, N. Relhan, N.A. Patel, N. Si, D. Miller, S.R. Dubovy, W.E. Smiddy, S.G. Schwartz, Ophthalmic Surgery, Lasers Imaging Retin. 49, 313 (2018)

  • J. Zeroni, J. Slager, R. Hegenrother, T. Kloke, S. Varner, Invest. Ophthalmol. Vis. Sci. 48, 5805 (2007)

    Google Scholar 

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Acknowledgements

The author acknowledge the efforts and support of Mr. Mateen Amin, Focus Ophthalmics LLC, USA for design modifications and manufacturing of the prototypes and Mr. Tapas Kumar Roy, PhD student in pharmacology who assisted in the procedures and performed fundus imaging. The authors would also like to acknowledge Ms. Lata Kaushik for performing the initial ELISA experiments and in drafting the design as per the instructions of the manufacturer.

Funding

The authors would like to acknowledge the funding agencies, IRD, IIT Delhi and AIIMS for partial financial support to the project via multi-institutional project:MI01884 (IITD) /A-05 (AIIMS).

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Authors and Affiliations

  1. Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, 110029, New Delhi, India

    Rohan Chawla

  2. Center for Biomedical Engineering, Indian Institute of Technology Delhi, 110016, New Delhi, India

    Jayanta Bhattacharyya, Anjali Phour & Dinesh Kalyanasundaram

  3. Department of Biomedical Engineering, All India Institute of Medical Sciences, 110029, New Delhi, India

    Jayanta Bhattacharyya & Dinesh Kalyanasundaram

  4. Department of Ocular Pharmacology, Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, 110029, New Delhi, India

    Laxmi Moksha & Thirumurthy Velpandian

  5. Department of Ocular Pathology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, 110029, New Delhi, India

    Seema Kashyap

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  1. Rohan Chawla
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  2. Jayanta Bhattacharyya
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  3. Laxmi Moksha
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  7. Dinesh Kalyanasundaram
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Correspondence to Dinesh Kalyanasundaram.

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Chawla, R., Bhattacharyya, J., Moksha, L. et al. A novel, minimally invasive implant to assist in repeated intraocular drug delivery. Biomed Microdevices 24, 17 (2022). https://doi.org/10.1007/s10544-022-00618-y

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  • DOI: https://doi.org/10.1007/s10544-022-00618-y

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