Abstract
Cell therapies are currently in clinical development for the treatment of a number of retinal disorders. Such therapies must be delivered to the subretinal space, which has traditionally been accomplished through conventional pars plana vitrectomy with the creation of a retinotomy and subsequent transfer of cells. Delivering cells in this fashion is thought to incur a risk of retinal detachment and the development of proliferative vitreoretinopathy. Indeed, preclinical studies of palucorcel (human umbilical tissue derived cells developed by Janssen Research & Development for the treatment of geographic atrophy secondary to age related macular degeneration) delivered using this tranvitreal approach suggested that the presence of these cells in the vitreous had the potential to stimulate ERM formation and retinal detachments due to PVR. Accordingly, Janssen began to explore alternative routes to the subretinal space. After considering a number of potential techniques, they developed a novel approach using the suprachoroidal space as a conduit to the posterior pole. This approach involves the creation of a sclerotomy, introduction of a specialized cannula into the suprachoroidal space, advancement of the cannula under direct visualization to the desired delivery site, advancement of an internal needle through the choroid into the subretinal space, and delivery of cells. The system has completed small-scale preclinical validation studies and is now being tested in conjunction with clinical trials of palucorcel for the treatment of geographic atrophy secondary to ARMD. There is optimism surrounding these trials as well as the device’s specific design to access the subretinal space.
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References
Stein JD, et al. Adverse events after pars plana vitrectomy among medicare beneficiaries. Arch Ophthalmol. 2009;127(12):1656–63.
Sadaka A, Giuliari GP. Proliferative vitreoretinopathy: current and emerging treatments. Clin Ophthalmol. 2012;6:1325–33.
Wang LC, et al. Assessment of retinal pigment epithelial cells in epiretinal membrane formation. J Chin Med Assoc. 2015;78(6):370–3.
Vedantham V, Ramasamy K. Pigmented epiretinal membranes caused by RPE migration: OCT-based observational case reports. Indian J Ophthalmol. 2007;55(2):148–9.
Schwartz SD, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet. 2015;385(9967):509–16.
Song WK, et al. Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients. Stem Cell Reports. 2015;4(5):860–72.
Lutton BV, et al. Approaches to avoid immune responses induced by repeated subcutaneous injections of allogeneic umbilical cord tissue-derived cells. Transplantation. 2010;90(5):494–501.
Cho PS, et al. Immunogenicity of umbilical cord tissue derived cells. Blood. 2008;111(1):430–8.
Spencer R, et al. Case study of epiretinal membrane in a subject with retinitis pigmentosa who received palucorcel (CNTO 2476) via transvitreal subretinal delivery. Submitted, 2016.
Ho, A.C., T.S. Chang, and M. Samuel. A novel cell-based therapy administered subretinally to eyes with geographic atrophy secondary to age-related macular degeneration. Submitted, 2016.
Olsen TW, et al. Cannulation of the suprachoroidal space: a novel drug delivery methodology to the posterior segment. Am J Ophthalmol. 2006;142(5):777–87.
Krohn J, Bertelsen T. Corrosion casts of the suprachoroidal space and uveoscleral drainage routes in the pig eye. Acta Ophthalmol Scand. 1997;75(1):28–31.
Krohn J, Bertelsen T. Corrosion casts of the suprachoroidal space and uveoscleral drainage routes in the human eye. Acta Ophthalmol Scand. 1997;75(1):32–5.
Krohn J, Bertelsen T. Light microscopy of uveoscleral drainage routes after gelatine injections into the suprachoroidal space. Acta Ophthalmol Scand. 1998;76(5):521–7.
Bailey AK, Sarkisian Jr SR, Vold SD. Ab interno approach to the suprachoroidal space. J Cataract Refract Surg. 2014;40(8):1291–4.
Patrianakos TD. Anatomic and physiologic rationale to be applied in accessing the suprachoroidal space for management of glaucoma. J Cataract Refract Surg. 2014;40(8):1285–90.
Gigon A, Shaarawy T. The suprachoroidal route in glaucoma surgery. J Curr Glaucoma Pract. 2016;10(1):13–20.
Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008;146(4):496–500.
Yiu G, et al. Characterization of the choroid-scleral junction and suprachoroidal layer in healthy individuals on enhanced-depth imaging optical coherence tomography. JAMA Ophthalmol. 2014;132(2):174–81.
Michalewska Z, et al. Suprachoroidal layer and suprachoroidal space delineating the outer margin of the choroid in swept-source optical coherence tomography. Retina. 2015;35(2):244–9.
Spaide RF, Ryan Jr EH. Loculation of fluid in the posterior choroid in eyes with central serous chorioretinopathy. Am J Ophthalmol. 2015;160(6):1211–6.
Kim JH, et al. Imaging suprachoroidal layer in exudative age-related macular degeneration. Curr Eye Res. 2016;41(5):715–20.
Peyman GA, Lad EM, Moshfeghi DM. Intravitreal injection of therapeutic agents. Retina. 2009;29(7):875–912.
Olsen TW, et al. Pharmacokinetics of pars plana intravitreal injections versus microcannula suprachoroidal injections of bevacizumab in a porcine model. Invest Ophthalmol Vis Sci. 2011;52(7):4749–56.
Patel SR, et al. Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye. Invest Ophthalmol Vis Sci. 2012;53(8):4433–41.
Gilger BC, et al. Treatment of acute posterior uveitis in a porcine model by injection of triamcinolone acetonide into the suprachoroidal space using microneedles. Invest Ophthalmol Vis Sci. 2013;54(4):2483–92.
Pearce W, Hsu J, Yeh S. Advances in drug delivery to the posterior segment. Curr Opin Ophthalmol. 2015;26(3):233–9.
Mittl RN, Tiwari R. Suprachoroidal injection of sodium hyaluronate as an ‘internal’ buckling procedure. Ophthalmic Res. 1987;19(5):255–60.
El Rayes EN, Elborgy E. Suprachoroidal buckling: technique and indications. J Ophthalmic Vis Res. 2013;8(4):393–9.
El Rayes EN, Oshima Y. Suprachoroidal buckling for retinal detachment. Retina. 2013;33(5):1073–5.
El Rayes EN. Suprachoroidal buckling. Dev Ophthalmol. 2014;54:135–46.
Saunders AL, et al. Development of a surgical procedure for implantation of a prototype suprachoroidal retinal prosthesis. Clin Exp Ophthalmol. 2014;42(7):665–74.
Villalobos J, et al. Cortical activation following chronic passive implantation of a wide-field suprachoroidal retinal prosthesis. J Neural Eng. 2014;11(4):046017.
Ayton LN, et al. First-in-human trial of a novel suprachoroidal retinal prosthesis. PLoS One. 2014;9(12):e115239.
Conflict of Interest
James Baldassarre is an employee of Janssen R&D.
Michael Keane is an employee of Janssen R&D.
Jeffrey S. Heier, MD, has received research support from and served as a scientific consultant to Janssen R&D, Acucela, Astellas, and Genentech/Roche.
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Baldassarre, J.S., Joseph, A., Keane, M., Heier, J.S. (2017). Subretinal Delivery of Cells via the Suprachoroidal Space: Janssen Trial. In: Schwartz, S., Nagiel, A., Lanza, R. (eds) Cellular Therapies for Retinal Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-49479-1_8
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DOI: https://doi.org/10.1007/978-3-319-49479-1_8
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