July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
High serum HGF and anti-69-kDa autoantibodies as potential etiology for bilateral diffuse uveal melanocytic proliferation masquerading as neovascular AMD
Author Affiliations & Notes
  • John Niffenegger
    Retina Associates of Sarasota, Sarasota, Florida, United States
  • Arysol Soltero
    Retina Associates of Sarasota, Sarasota, Florida, United States
  • James Niffenegger
    School of Engineering and Applied Sciences, Harvard College, Cambridge, Massachusetts, United States
  • Sufang Yang
    Casey Eye Institute, Oregon Health & Science Institute, Portland, Oregon, United States
  • Grazyna Adamus
    Casey Eye Institute, Oregon Health & Science Institute, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   John Niffenegger, None; Arysol Soltero, None; James Niffenegger, None; Sufang Yang, None; Grazyna Adamus, None
  • Footnotes
    Support  grant P30 EY010572 from the NIH and unrestricted funding from Research to Prevent Blindness (New York, NY).
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4493. doi:
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    • Get Citation

      John Niffenegger, Arysol Soltero, James Niffenegger, Sufang Yang, Grazyna Adamus; High serum HGF and anti-69-kDa autoantibodies as potential etiology for bilateral diffuse uveal melanocytic proliferation masquerading as neovascular AMD. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4493.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) is a rare paraneoplastic condition with increasing incidence that may masquerade as neovascular age-related macular degeneration (n-AMD), resulting in delayed diagnosis and treatment. Hepatocyte growth factor (HGF) stimulation of melanocytes up-regulates its receptor mesenchymal-epithelial transition factor (c-MET). The goal of this case study was to test the hypothesis that high serum HGF and anti-69-kDa retinal autoantibodies contribute to pathology of BDUMP.

Methods : We examined specimens collected from a 73 year-old male patient with BDUMP simulating n-AMD in stage 4 and papillary renal cell carcinoma with tumor MET gene mutation Y1230C for serum anti-retinal autoantibodies by western blotting, and HGF and c-Met by ELISA. After informed consent, the electronic medical records and multimodal imaging were reviewed and documented. Visual complaints consisted of rapid bilateral vision loss, photophobia and scotomas. Cancer therapy with nivolumab and axtinib were noted.

Results : The HGF levels pre-plasmapheresis, from plasmapheresis fluid and final post-plasmapheresis were: 1990 pg/ml, 681 pg/ml and 452 pg/ml (respectively). C-MET levels at all three time-points were not detectible. Pre and post-plasmapheresis serum demonstrated anti-retinal autoantibodies against 69-kDa protein of the same molecular size as the alpha subunit of HGF. Plasmapheresis resulted in improved inflammation, resolution of exudative detachments and eventual improvement in vision after cataract surgery and continued survival 1 year after the diagnosis of BDUMP.

Conclusions : BDUMP was associated with high levels of HGF as well as anti-retinal autoantibodies against 69-kDa protein. Therapy with an epidermal growth factor tyrosine kinase inhibitor may contribute to the high HGF levels, which may affect the immune response. These results suggest a new etiology for high levels of HGF combined with likely immune response to the alpha subunit of HGF (69-kDa) in the pathogenesis of BDUMP.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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