Stem Cell Ophthalmology Treatment Study (SCOTS): Bone Marrow-Derived Stem Cells in the Treatment of Age-Related Macular Degeneration

Jeffrey N Weiss, Steven Levy, Jeffrey N Weiss, Steven Levy

Abstract

Background: Dry age-related macular degeneration (AMD) is one of the leading causes of vision loss in older patients. The macula accumulates drusen with loss of retinal pigment epithelial cells and photoreceptors. Abnormal subretinal neovascularization is absent. There is no effective drug therapy for dry AMD and a large proportion of patients progress to legal blindness from macular atrophy. The Stem Cell Ophthalmology Treatment Study (SCOTS) was conducted to assess the effect of bone marrow-derived stem cells (BMSCs) on dry AMD and other retinal and optic nerve diseases. Methods: Thirty-two eyes were treated with BMSC per the protocols in SCOTS. Provision of BMSCs in Arm 1 was via retrobulbar (RB), sub-tenons (ST) and intravenous (IV); Arm 2 via intravitreal, RB, ST and IV; Arm 3 via subretinal and IV. Patient age averaged 78 years old and ranged from 69 to 90. Visual acuity preoperatively ranged from counting fingers to 20/50-2 with an average preoperative LogMAR of 1.125. Results: Following treatment, 20 of 32 (63%) of eyes experienced improvement in visual acuity averaging 27.6% on LogMAR and ranging from 2.5% to 44.6%. The mean improvement in LogMAR was 0.963 with a standard deviation (SD) of 0.42. The visual acuity remained stable in 34% of treated eyes. One eye continued to worsen as a consequence of disease progression. The results showed high statistical significance with p ≤ 0.001. The procedures were conducted safely, and no complications were observed. Conclusion: Treatment of dry AMD with BMSC using the protocols developed in the SCOTS clinical trial has shown statistically significant clinical benefit improving visual acuity and potentially delaying visual loss in the disease.

Keywords: AMD; age-related macular degeneration; bone marrow stem cells; degeneration; macula; retina; stem cells.

Conflict of interest statement

The authors indicated no potential conflicts of interest.

References

    1. Harris J.R., Fisher R., Jorgensen M., Kaushal S., Scott E.W. CD 133 progenitor cells from the bone marrow contribute to retinal pigment epithelial repair. Stem Cells. 2009;27:457–466. doi: 10.1634/stemcells.2008-0836.
    1. Gong L., Wu Q., Song B., Lu B., Zhang Y. Differentiation of rat mesenchymal stem cells transplanted into the subretinal space of sodium iodate-injected rats. Clin. Exp. Ophthalmol. 2008;36:666–671. doi: 10.1111/j.1442-9071.2008.01857.x.
    1. Jiang Y., Zhang Y., Zhang L., Wang M., Zhang X., Li X. Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells on Laser-Induced Retinal Injury in Mice. Int. J. Mol. Sci. 2014;15:9372–9385. doi: 10.3390/ijms15069372.
    1. Becker S., Jayaram H., Limb G.A. Recent Advances towards the Clinical Application of Stem Cells for Retinal Regeneration. Cells. 2012;1:851–873. doi: 10.3390/cells1040851.
    1. Pesaresi M., Bonilla-Pons S.A., Simonte G., Sanges D., Di Vicino U., Cosma M.P. Endogenous Mobilization of Bone-Marrow Cells Into the Murine Retina Induces Fusion-Mediated Reprograming of Müller Glia Cells. EBioMedicine. 2018;30:38–51. doi: 10.1016/j.ebiom.2018.02.023.
    1. Weiss J.N., Levy S., Malkin A. Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: A preliminary report. Neural Regen Res. 2015;10:982–988.
    1. Weiss J.N., Levy S., Benes S.C. Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: A case report of improvement in relapsing auto-immune optic neuropathy. Neural Regen Res. 2015;10:1507–1515.
    1. Weiss J.N., Benes S.C., Levy S. Stem Cell Ophthalmology Treatment Study (SCOTS): Improvement in serpiginous choroidopathy following autologous bone marrow derived stem cell treatment. Neural Regen Res. 2016;11:1512. doi: 10.4103/1673-5374.191229.
    1. Weiss J.N., Levy S., Benes S.C. Stem Cell Ophthalmology Treatment Study: Bone marrow derived stem cells in the treatment of non-arteritic ischemic optic neuropathy (NAION) Stem Cell Investig. 2017;4:94. doi: 10.21037/sci.2017.11.05.
    1. Weiss J.N., Levy S. Stem Cell Ophthalmology Treatment Study (SCOTS): Autologous bone-marrow derived stem cells in the treatment of hereditary macular degeneration. EC Ophthalmol. 2019;10:526–532.
    1. Schmier J.K., Covert D.W., Lau E.C. Patterns and costs associated with progression of age-related macular degeneration. Am. J. Ophthalmol. 2012;154:675–681. doi: 10.1016/j.ajo.2012.04.017.
    1. Wong W.L., Su X., Li X., Cheung C.M.G., Klein R., Cheng Wong T.Y. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis. Lancet Glob. Health. 2014;2:106–116. doi: 10.1016/S2214-109X(13)70145-1.
    1. Buschini E., Fea A.M., Lavia C.A., Nassisi M., Pignata G., Zola M., Grignolo F.M. Recent developments in the management of dry age-related macular degeneration. Clin. Ophthalmol. 2015;9:563–574. doi: 10.2147/OPTH.S59724.
    1. Cheung L.K., Eaton A. Age-related macular degeneration. Pharmacotherapy. 2013;33:838–855. doi: 10.1002/phar.1264.
    1. Chew E.Y., Clemons T.E., Agrón E., Sperduto R.D., SanGiovanni J.P., Davis M.D., Ferris F.L. Age-Related Eye Disease Study Research: Ten-year follow-up of age-related macular degeneration in the age-related eye disease study: AREDS report no. 36. JAMA Ophthalmol. 2014;132:272–277. doi: 10.1001/jamaophthalmol.2013.6636.
    1. Suter M., Remé C., Grimm C., Wenzel A., Jäättela M., Esser P., Kociok N., Leist M., Richter C. Age-related macular degeneration. The lipofusion component N-retinyl-N-retinylidene ethanolamine detaches proapoptotic proteins from mitochondria and induces apoptosis ibn mammalian retinal pigment epithelial cells. J. Biol. Chem. 2000;275:39625–39630. doi: 10.1074/jbc.M007049200.
    1. Baudouin C., Peyman G.A., Fredj-Reygrobellet D., Gordon W.C., Lapalus P., Gastaud P., Bazan N.G. Immunohistological study of subretinal membranes in age-related macular degeneration. Jpn. J. Ophthalmol. 1992;36:443–451.
    1. Danis R.P., Lavine J.A., Domalpally A. Geographic atrophy in patients with advanced dry age-related macular degeneration: Current challenges and future prospects. Clin. Ophthalmol. 2015;9:2159–2174. doi: 10.2147/OPTH.S92359.
    1. Maller J., George S., Purcell S., Fagerness J., Altshuler D., Daly M.J., Seddon J.M. Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration. Nat. Genet. 2006;38:1055–1059. doi: 10.1038/ng1873.
    1. Weiss J.N., Benes S.C., Levy S. Stem Cell Ophthalmology Treatment Study (SCOTS): Bone marrow derived stem cells in the treatment of Lebers Hereditary Optic Neuropathy. Neural Regen. Res. 2016;11:1685.
    1. Weiss J.N., Levy S. Stem Cell Ophthalmology Treatment Study: Bone marrow derived stem cells in the treatment of retinitis pigmentosa. Stem Cell Investig. 2018;5:18. doi: 10.21037/sci.2018.04.02.
    1. Schwartz S.D., Regillo C.D., Lam B.L., Eliott D., Rosenfeld P.J., Gregori N.Z., Hubschman J.-P., Davis J.L., Heilwell G., Spirn M., 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 ½ studies. Lancet. 2015;385:509–516. doi: 10.1016/S0140-6736(14)61376-3.
    1. Forest D.L., Johnson L.V., Clegg D.O. Cellular models and therapies for age-related macular degeneration. Dis. Model Mech. 2015;8:421–427. doi: 10.1242/dmm.017236.
    1. Song W.K., Park K.M., Kim H.J., Lee J.H., Choi J., Chong S.Y., Shim S.H., Del Priore L.V., Lanza R. Treatment of Macular Degeneration Using Embryonic Stem Cell-Derived Retinal Pigment Epithelium: Preliminary Results in Asian Patients. Stem Cell Rep. 2015;4:860–872. doi: 10.1016/j.stemcr.2015.04.005.

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