A novel suprachoroidal microinvasive glaucoma implant: in vivo biocompatibility and biointegration

BMC Biomedical Engineering - 2020
Ian Grierson1, Don S. Minckler2, Marian K. Rippy3, Andrew J. Marshall4, Nathalie Collignon5, Jessica Bianco6, Bruno Detry7, Murray Johnstone8
1Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
2University of California, Irvine, School of Medicine, Irvine, CA, USA
3Rippy Pathology Solutions, Inc., Woodbury, MN, USA
4Healionics Corporation, Seattle, Washington, USA
5Department of Ophthalmology, Centre Hospitalier Universitaire of Liège, Liège, Belgium
6NAMSA Clinical and Consulting, Chasse sur Rhone, France
7iSTAR Medical SA, Avenue Sabin 6, 1300, Wavre, Belgium
8Department of Ophthalmology, University of Washington Seattle, Washington USA

Tóm tắt

Abstract Background A major challenge for any glaucoma implant is their ability to provide long-term intraocular pressure lowering efficacy. The formation of a low-permeability fibrous capsule around the device often leads to obstructed drainage channels, which may impair the drainage function of devices. These foreign body-related limitations point to the need to develop biologically inert biomaterials to improve performance in reaching long-term intraocular pressure reduction. The aim of this study was to evaluate in vivo (in rabbits) the ocular biocompatibility and tissue integration of a novel suprachoroidal microinvasive glaucoma implant, MINIject™ (iSTAR Medical, Wavre, Belgium). Results In two rabbit studies, no biocompatibility issue was induced by the suprachoroidal, ab-externo implantation of the MINIject™ device. Clinical evaluation throughout the 6 post-operative months between the sham and test groups were similar, suggesting most reactions were related to the ab-externo surgical technique used for rabbits, rather than the implant material itself. Histological analysis of ocular tissues at post-operative months 1, 3 and 6 revealed that the implant was well-tolerated and induced only minimal fibroplasia and thus minimal encapsulation around the implant. The microporous structure of the device became rapidly colonized by cells, mostly by macrophages through cell migration, which do not, by their nature, impede the flow of aqueous humor through the device. Time-course analysis showed that once established, pore colonization was stable over time. No fibrosis nor dense connective tissue development were observed within any implant at any time point. The presence of pore colonization may be the process by which encapsulation around the implant is minimized, thus preserving the permeability of the surrounding tissues. No degradation nor structural changes of the implant occurred during the course of both studies. Conclusions The novel MINIject™ microinvasive glaucoma implant was well-tolerated in ocular tissues of rabbits, with observance of biointegration, and no biocompatibility issues. Minimal fibrous encapsulation and stable cellular pore colonization provided evidence of preserved drainage properties over time, suggesting that the implant may produce a long-term ability to enhance aqueous outflow.

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Tài liệu tham khảo

Chen PP. Blindness in patients with treated open-angle glaucoma. Ophthalmology. 2003;110(4):726–33.

Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081–90.

Mansouri K, Medeiros FA, Weinreb RN. Global rates of glaucoma surgery. Graefes Arch Clin Exp Ophthalmol. 2013;251(11):2609–15.

Chen DZ, Sng CCA. Safety and efficacy of microinvasive glaucoma surgery. J Ophthalmol. 2017;2017:3182935.

Manasses DT, Au L. The new era of Glaucoma micro-stent surgery. Ophthalmol Ther. 2016;5(2):135–46.

Conlon R, Saheb H, Ahmed II. Glaucoma treatment trends: a review. Can J Ophthalmol. 2017;52(1):114–24.

Myers JS, Masood I, Hornbeak DM, Belda JI, Auffarth G, Jünemann A, et al. Prospective evaluation of two iStent® trabecular stents, one iStent supra® suprachoroidal stent, and postoperative prostaglandin in refractory glaucoma: 4-year outcomes. Adv Ther. 2018;35(3):395–407.

Katz LJ, Erb C, Carceller Guillamet A, Fea AM, Voskanyan L, Giamporcaro JE, et al. Long-term titrated IOP control with one, two, or three trabecular micro-bypass stents in open-angle glaucoma subjects on topical hypotensive medication: 42-month outcomes. Clin Ophthalmol. 2018;12:255–62.

Le C, Kazaryan S, Hubbell M, Zurakowski D, Ayyala RS. Surgical outcomes of phacoemulsification followed by iStent implantation versus Goniotomy with the Kahook dual blade in patients with mild primary open-angle Glaucoma with a minimum of 12-month follow-up. J Glaucoma. 2019;28(5):411–4.

Salinas L, Chaudhary A, Berdahl JP, Lazcano-Gomez GS, Williamson BK, Dorairaj SK, et al. Goniotomy using the Kahook dual blade in severe and refractory glaucoma: 6-month outcomes. J Glaucoma. 2018;27(10):849–55.

Ondrejka S, Korber N. 360 degrees ab-interno Schlemm's canal viscodilation in primary open-angle glaucoma. Clin Ophthalmol. 2019;13:1235–46.

Sarkisian SR, Mathews B, Ding K, Patel A, Nicek Z. 360 degrees ab-interno trabeculotomy in refractory primary open-angle glaucoma. Clin Ophthalmol. 2019;13:161–8.

Gallardo MJ, Supnet RA, Ahmed IIK. Viscodilation of Schlemm's canal for the reduction of IOP via an ab-interno approach. Clin Ophthalmol. 2018;12:2149–55.

Kammer JA, Mundy KM. Suprachoroidal devices in glaucoma surgery. Middle East Afr J Ophthalmol. 2015;22(1):45–52.

Denis P, Hirneiß C, Reddy KP, Kamarthy A, Calvo E, Hussain Z, et al. A first-in-human study of the efficacy and safety of MINIject in patients with medically uncontrolled open-angle glaucoma (STAR-I). Ophthalmol Glaucoma. 2019;2(5):290–7.

Fea A, Cannizzo PM, Consolandi G, Lavia CA, Pignata G, Grignolo FM. Managing drawbacks in unconventional successful Glaucoma surgery: a case report of stent exposure. Case Rep Ophthalmol Med. 2015;2015:847439.

Pérez-Torregrosa VT, Olate-Pérez Á, Cerdà-Ibáñez M, Gargallo-Benedicto A, Osorio-Alayo V, Barreiro-Rego A, et al. Combined phacoemulsification and XEN45 surgery from a temporal approach and 2 incisions. Arch Soc Esp Oftalmol. 2016;91(9):415–21.

Hollo G, Naghizadeh F. High magnification in vivo evaluation of the mechanism of failure of an ex-PRESS shunt implanted under the sclera flap. Eur J Ophthalmol. 2014;24(4):617–9.

Lee JW, Park WY, Kim EA, Yun IH. Tissue response to implanted Ahmed glaucoma valve with adjunctive amniotic membrane in rabbit eyes. Ophthalmic Res. 2014;51(3):129–39.

Schmidt W, Kastner C, Sternberg K, Allemann R, Lobler M, Guthoff R, et al. New concepts for glaucoma implants--controlled aqueous humor drainage, encapsulation prevention and local drug delivery. Curr Pharm Biotechnol. 2013;14(1):98–111.

Tung I, Marcus I, Thiamthat W, Freedman SF. Second glaucoma drainage devices in refractory pediatric glaucoma: failure by fibrovascular ingrowth. Am J Ophthalmol. 2014;158(1):113–7.

Valimaki J, Uusitalo H. Immunohistochemical analysis of extracellular matrix bleb capsules of functioning and non-functioning glaucoma drainage implants. Acta Ophthalmol. 2014;92(6):524–8.

Giovingo M. Complications of glaucoma drainage device surgery: a review. Semin Ophthalmol. 2014;29(5–6):397–402.

Marshall AJ, Ratner BD. Quantitative characterization of sphere-templated porous biomaterials. AICHE J. 2005;51(4):1221–32.

Madden LR, Mortisen DJ, Sussman EM, Dupras SK, Fugate JA, Cuy JL, et al. Proangiogenic scaffolds as functional templates for cardiac tissue engineering. Proc Natl Acad Sci U S A. 2010;107(34):15211–6.

Pourjavan S, Collignon NJM, De Groot V, Eiferman RA, Marshall AJ, Roy CJ. STARfloTM: a suprachoroidal drainage implant made from STAR® biomaterial. In: Samples JR, Ahmed IIK, editors. Surgical innovations in Glaucoma. New York: Springer New York; 2014. p. 235–51.

Sussman EM, Halpin MC, Muster J, Moon RT, Ratner BD. Porous implants modulate healing and induce shifts in local macrophage polarization in the foreign body reaction. Ann Biomed Eng. 2014;42(7):1508–16.

Osathanon T, Linnes ML, Rajachar RM, Ratner BD, Somerman MJ, Giachelli CM. Microporous nanofibrous fibrin-based scaffolds for bone tissue engineering. Biomaterials. 2008;29(30):4091–9.

Bryers JD, Giachelli CM, Ratner BD. Engineering biomaterials to integrate and heal: the biocompatibility paradigm shifts. Biotechnol Bioeng. 2012;109(8):1898–911.

Marée R, Stévens B, Rollus L, Rocks N, Lopez XM, Salmon I, et al. A rich internet application for remote visualization and collaborative annotation of digital slides in histology and cytology. Diagn Pathol. 2013;8:S26 Copyright © 2013 Marée et al; licensee BioMed Central Ltd.

Hoeh H, Ahmed II, Grisanti S, Grabner G, Nguyen QH, Rau M, et al. Early postoperative safety and surgical outcomes after implantation of a suprachoroidal micro-stent for the treatment of open-angle glaucoma concomitant with cataract surgery. J Cataract Refract Surg. 2013;39(3):431–7.

Hoeh H, Vold SD, Ahmed IK, Anton A, Rau M, Singh K, et al. Initial clinical experience with the CyPass micro-stent: safety and surgical outcomes of a novel supraciliary microstent. J Glaucoma. 2016;25(1):106–12.

Garcia-Feijoo J, Rau M, Grisanti S, Hoh H, Erb C, Guguchkova P, et al. Supraciliary micro-stent implantation for open-angle glaucoma failing topical therapy: 1-year results of a multicenter study. Am J Ophthalmol. 2015;159(6):1075–81.e1.

Bouhenni RA, Dunmire J, Sewell A, Edward DP. Animal models of glaucoma. J Biomed Biotechnol. 2012;2012:692609.

De Feo F, Jacobson S, Nyska A, Pagani P, Traverso CE. Histological biocompatibility of a stainless steel miniature glaucoma drainage device in humans: a case report. Toxicol Pathol. 2009;37(4):512–6.

Doyle JW, Sherwood MB, Khaw PT, McGrory S, Smith MF. Intraoperative 5-fluorouracil for filtration surgery in the rabbit. Invest Ophthalmol Vis Sci. 1993;34(12):3313–9.

Schultz G, Khaw PT, Oxford K, MaCauley S, Van Setten G, Chegini N. Growth factors and ocular wound healing. Eye (Lond). 1994;8(Pt 2):184–7.

Norton JN, Kohnen T, Hackett RB, Patel A, Koch DD. Ocular biocompatibility testing of intraocular lenses: a 1 year study in pseudophakic rabbit eyes. J Cataract Refract Surg. 1999;25(11):1467–79.

Acosta AC, Espana EM, Orozco M, Yamamoto H, Pinchuk L, Dubovy S, et al. A novel glaucoma implant: a comparative SIBS vs. PDMS study in normal rabbit eyes. Investig Ophthalmol Visual Sci. 2006;47(13):3545.

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