title: Acute progressive paravascular placoid neuroretinopathy with negative-type electroretinography in paraneoplastic retinopathy.
abstract: Paraneoplastic retinopathy can be the first manifestation of systemic malignancy. A subset of paraneoplastic retinopathy is characterized by negative-type electroretinography (ERG) without fundus abnormality. Here we describe the multimodal imaging and clinico-pathological correlation of a unique case of acute progressive paravascular placoid neuroretinopathy with suspected retinal depolarizing bipolar cell dysfunction preceding the diagnosis of metastatic small cell carcinoma of the prostate.
  
  
  
  ERG was performed according to the International Society for Clinical Electrophysiology of Vision standards. Imaging modalities included near-infrared reflectance, blue-light autofluorescence, fluorescein and indocyanine green angiographies, spectral domain optical coherence tomography, ultra-widefield colour and green-light autofluorescence imaging, microperimetry and adaptive optics imaging. Patient serum was screened for anti-retinal antibodies using western blotting. Immunostaining and histological analyses were performed on sections from human retinal tissues and a patient prostate biopsy.
  
  
  
  Serial multimodal retinal imaging, microperimetry and adaptive optics photography demonstrated a paravascular distribution of placoid lesions characterized by hyper-reflectivity within the outer nuclear layer resembling type 2 acute macular neuroretinopathy. There was no visible lesion within the inner nuclear layer despite electronegative-type ERG. Six months later, the patient presented with metastatic small cell carcinoma of the prostate. Tumour cells were immunopositive for glyceraldehyde-3-phosphate dehydrogenase, enolase and recoverin as well as neuroendocrine markers. The patient's serum reacted to cytoplasmic and nuclear antigens in the prostate biopsy and in human retina. Anti-retinal antibodies against several antigens were detected by both commercial and in-house western blots.
  
  
  
  A spectrum of autoreactive anti-retinal antibodies is associated with a unique phenotype of acute progressive paravascular placoid neuroretinopathy resulting in degeneration of photoreceptor cells, inner retinal dysfunction and classic electronegative ERG in paraneoplastic retinopathy. Detailed clinical, functional and immunological phenotyping of paraneoplastic retinopathy illustrated the complex mechanism of paraneoplastic syndrome.
authors.affiliation: Centre for Ophthalmology and Vision Science, The University of Western Australia, Perth, WA, Australia.|Lions Eye Institute, Perth, WA, Australia.|Department of Ophthalmology, Royal Perth Hospital, Perth, WA, Australia.
authors.forename: Fred K
authors.initials: FK
authors.lastname: Chen
authors.affiliation: Centre for Ophthalmology and Vision Science, The University of Western Australia, Perth, WA, Australia.|Lions Eye Institute, Perth, WA, Australia.
authors.forename: Avenell L
authors.initials: AL
authors.lastname: Chew
authors.affiliation: Lions Eye Institute, Perth, WA, Australia.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Lions Eye Institute, Perth, WA, Australia.
authors.forename: Shang-Chih
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, WA, Australia.
authors.forename: Enid
authors.initials: E
authors.lastname: Chelva
authors.affiliation: Lions Eye Institute, Perth, WA, Australia.
authors.forename: Erandi
authors.initials: E
authors.lastname: Chandrasekera
authors.affiliation: PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Perth, WA, Australia.
authors.forename: Eleanor M H
authors.initials: EMH
authors.lastname: Koay
authors.affiliation: Centre for Ophthalmology and Vision Science, The University of Western Australia, Perth, WA, Australia.|Lions Eye Institute, Perth, WA, Australia.|The Institute of Medical Sciences, The University of Aberdeen, Scotland, UK.
authors.forename: John
authors.initials: J
authors.lastname: Forrester
authors.affiliation: Centre for Ophthalmology and Vision Science, The University of Western Australia, Perth, WA, Australia. smclenachan@gmail.com.|Lions Eye Institute, Perth, WA, Australia. smclenachan@gmail.com.|Department of Ophthalmology, Royal Perth Hospital, Perth, WA, Australia. smclenachan@gmail.com.|Ocular Tissue Engineering Laboratory, Lions Eye Institute, 2 Verdun Street, Nedlands, WA, 6009, Australia. smclenachan@gmail.com.
authors.forename: Samuel
authors.identifier: 0000-0001-5732-7387
authors.initials: S
authors.lastname: McLenachan
mesh_terms: D000208:Acute Disease; D004596:Electroretinography; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D010257:Paraneoplastic Syndromes / Q000175:diagnosis*; D012160:Retina / Q000473:pathology*; D012164:Retinal Diseases / Q000175:diagnosis*
keywords: Anti-retinal antibodies; Autoimmunity; Cancer-associated retinopathy; Paraneoplastic retinopathy; Paravascular placoid neuroretinopathy; Small cell carcinoma