Intravenous And Intrathecal Umbilical Cord Blood Stem Cells Fail To Improve Vision In LHON Patient With G11778A Mutation

Abstract

Purpose: : To describe our observations of an LHON patient with acute visual loss who went to China for intravenous and intrathecal umbilical cord stem cell therapy.

Methods: : A 42-year-old woman who presented to us on 08/26/2009 with complaints of sudden visual loss in both eyes since 08/01/2009 underwent a complete neuro-ophthalmic examination that included ETDRS visual acuity measurements, automated visual fields, pattern electroretinogram (PERG) and Stratus OCT. Venous blood was drawn for mitochondrial genetic analysis and phosphorylated neurofilament heavy chain (NfH) quantitation of axonal loss. She subsequently received intravenous and intrathecal umbilical cord stem cells in China on 11/2009. We examined her again on 02/24/2010 and 09/08/2010 after stem cell therapy.

Results: : Genetic analysis was positive for mtDNA G11778A homoplasmy. Also noted was an additional mutation in the ND4 gene, G11719A changing Gly to Glu at amino acid 320. There were no mutations in ND1 or ND6. Baseline ETDRS acuity was 55 letters OD and 71 OS. Humphrey visual field MD was -2.31 OD and -0.80 OS. Ophthalmoscopy revealed bilateral disc edema with peripapillary telangiectasias. OCT RNFL thickness was 130 µm OD and 134 µm OS. PERG amplitudes were reduced to 0.44 µV OD and 0.38 µV OS (normal = 1.0 µV). PNF-H (square root) level was 0.29 ng/ml. Approximately 3 months after Chinese stem cell therapy ETDRS visual acuity had dropped to 20 OD and 15 OS. Visual fields revealed dense central scotomas with MD = -19.86 OD and -21.98 OS. Optic disc edema had resolved with RNFL = 97 µm OD and 91 µm OS. The PERG amplitudes improved to 0.80 µV OD and 0.74 µV OS. The PNF-H (square root) level had increased to 0.54 ng/ml. Nine months after stem cell therapy visual acuity had dropped further to ETDRS 13 OD and 4 OS. Optic atrophy was prominent with RNFL = 67 µm OD and 69 µm OS. Pattern electroretinogram amplitudes of 0.73 µV OD and 0.62 µV OS continued to be almost double the baseline values obtained prior to Chinese umbilical stem cell therapy.

Conclusions: : Intravenous and intrathecal umbilical cord stem cell therapy performed in China failed to improve vision or prevent optic atrophy in a patient with acute LHON. The increase in the PERG amplitude changes were inverse to the progressive visual failure and RNFL loss. The paradoxical PERG amplitude changes in this single case are unexplained and require study with additional cases.

Keywords: mitochondria • neuro-ophthalmology: optic nerve