A clear cell renal cell carcinoma inhibiting the response to intravitreal antivascular endothelial growth factor therapy in wet age-related macular disease.
OBJECTIVE
Wet age-related macular degeneration (AMD) is an ocular disorder that can be successfully treated with intravitreal antivascular endothelial growth factor (VEGF) therapy. We report a case of incomplete response to intravitreal therapy associated with a clear cell renal cell carcinoma (ccRCC).


METHODS
A 72-year-old male with wet AMD responded poorly to intravitreal bevacizumab and ranibizumab injections. The removal of a ccRCC led to the spontaneous stabilization of the choroidal neovascular lesion. The renal carcinoma was examined for Von Hippel-Lindau (VHL) gene alterations. Immunohistochemical profiling of the hypoxia-inducible factor (HIF) pathway addressing the marker HIF-1α and its downstream targets VEGF, glucose transporter 1 and carbonic anhydrase IX was performed.


RESULTS
Genotyping of the ccRCC revealed the presence of a truncating VHL mutation (p.E134fs*25). Immunohistochemistry displayed HIF pathway target activation and VEGF expression in the ccRCC tumour cells. Following tumour removal, the neovascular lesion remained stable for 6 months without any further anti-VEGF therapy.


CONCLUSIONS
The somatic VHL mutation correlates with persistent high levels of HIF-1α pathway targets and VEGF expression in the ccRCC. We postulate that this increased VEGF in the tumour and subsequently in the plasma levels could have caused the incomplete response to intravitreal anti-VEGF therapy. Stabilization of the wet AMD following tumour removal indicates that the angiogenic secreting tumour (ccRCC) abrogates the response to VEGF inhibitor therapy. Thus, in cases of poor response to intravitreal anti-VEGF therapy, systemic evaluation including plasma levels of VEGF and/or systemic screening for VEGF-producing tumours should be considered.
Faculty of Medicine, University of Porto, Porto, Portugal ; Department of Ophthalmology, Hospital de São João, Porto, Portugal.
Manuel S
MS
Falcão
João
J
Vinagre
Paula
P
Soares
José Manuel
JM
Lopes
Elisete
E
Brandão
Angela M
AM
Carneiro
Bevacizumab; Pseudohypoxia; Ranibizumab; Renal cell carcinoma; Vascular endothelial growth factor; Von Hippel-Lindau; Wet age-related macular degeneration