br Acknowledgments This work was supported by
Acknowledgments This work was supported by Région Auvergne “Nouveau chercheur”. This study has been performed with the assistance of Christelle Damon-Soubeyrand for histology technical assistance using “Anipath” Platform (GReD) and Sandrine Plantade, Keredine Ouchen and Philippe Mazuel for animal facilities. Thanks to master students that worked on training project “Enolase” (Sabrina Boudon, Sylvain Lamoine, Gweltas Odye, Maxime Voisin).
Introduction Autoimmune retinopathy and optic neuropathy are poorly-understood diseases thought to be the result of an immune reaction to auto-antigens. Cancer-associated, or paraneoplastic, retinopathy is considered a subset of autoimmune retinopathy secondary to a tumor as the source of antigens. Among many potential antigens, alpha-enolase is a well-described 46 kD protein known to cause cancer-associated and autoimmune retinopathy. Oncocytomas are benign tumors rarely associated with paraneoplastic syndromes. Here, we present a case of profound vision loss secondary to autoimmune retinopathy and optic neuropathy associated with an alpha-enolase-positive renal oncocytoma, with remarkable improvement of vision after tumor resection.
Case report A 41-year-old man presented with 2 weeks of bilateral, painless vision loss in the absence of any systemic symptoms. On initial examination, visual acuity measured 20/125 OD and 20/1250 OS. Goldmann perimetry showed bilateral, cecocentral scotomas, with complete loss of the I2e isopter OU (Fig. 1A and B). Dilated fundus exam showed telangiectatic vessels on the optic nerves and in the maculae (Fig. 2A and B). Optical coherence tomography (OCT) showed thinning of the nerve fiber and ganglion cell layers, as well as outer plexiform layer irregularities bilaterally (Fig. 3A and B). An autoimmune retinopathy panel was obtained and demonstrated multiple anti-optic nerve and anti-retinal autoantibodies (40-kDa, 46-kDa [alpha-enolase], and 70-kDa), with binding of the patient's serum to bipolar Elacridar mg on human retinal tissue. Full-field electroretinography (ERG) demonstrated reduced photopic greater than scotopic signals (Table 1; Fig. 4). PET-CT demonstrated hypermetabolic activity only at the known right renal mass (Fig. 5A). Biopsy of the renal mass was consistent with a benign oncocytoma, confirmed by positive CD117 immunohistochemical staining. Additional immunohistochemical staining was negative for CK7, distinguishing the tumor from renal cell carcinoma, and positive for alpha-enolase (Fig. 5B). Extensive additional investigations, including serum and CSF paraneoplastic panels, as well as for rheumatologic (ANA, ANCA, SS-a/b antibodies, complement levels, ACE), infectious (tuberculosis, lyme, Bartonella, syphilis, HIV, hepatitis A and B) and demyelinating causes (multiple sclerosis, neuromyelitis optica), were negative. The patient was treated with a five-day course of intravenous methylprednisolone (1 g/day), followed by five rounds of plasmapheresis with minimal improvement. Surgical excision of the oncocytoma with partial nephrectomy was thus performed 3 months after diagnosis. Histologic inspection of the tumor confirmed a benign oncocytoma throughout the sample. The patient experienced gradual, progressive improvement in vision following tumor resection. By 9 months post-operatively, visual acuity had improved to 20/40 OU, with recovery of the I2e isopter OU (Fig. 1C and D), improved waveforms with reduced latencies on ERG (Table 1, Fig. 4), and consolidation of the outer plexiform layer irregularities on OCT (Fig. 3C and D).
Discussion Enolase associated autoimmune retinopathy has been well described. Multiple reports have shown the association of both alpha-enolase and gamma-enolase antibodies in serum to autoimmune retinopathy., Serum anti-enolase antibodies can be found in other inflammatory conditions and their presence does not prove causality in the context of autoimmune retinopathy., However, in this case, an extensive workup for autoimmune retinopathy was negative except for the large renal oncocytoma, which was positive for alpha-enolase throughout the biopsy sample on immunohistochemistry. Hence, we postulate in this case that the large burden of alpha-enolase expressed by the tumor was the inciting antigen for the autoimmune retinopathy and optic neuropathy.