Author Affiliations: Department of Ophthalmology, Duke University Eye Center, Durham, North Carolina (Dr Grunwald); and Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania (Mr Kligman and Dr Shields).
Paraneoplastic retinopathy occurs when autoantibodies against cancer cross-react with normal retinal antigens and lead to retinal degeneration and subsequent vision loss.1 Two main categories of paraneoplastic retinopathies have been described, including cancer-associated retinopathy and melanoma-associated retinopathy.2 Cancer-associated retinopathy is found most often in patients with small cell lung carcinoma and affects both rod and cone function, while melanoma-associated retinopathy occurs with metastatic cutaneous or uveal melanoma and affects primarily rod function.1 Autoantibodies against recoverin and bipolar cells are typically found in cancer-associated retinopathy and melanoma-associated retinopathy, respectively, although other retinal antigens have also been described.1,3 Herein, we illustrate a case of a more recently recognized paraneoplastic retinopathy, termed acute exudative polymorphous paraneoplastic vitelliform maculopathy (AEPPVM).
A 69-year-old woman noted gradually progressive blurred vision in both eyes over 2 years. Three months previously, she experienced subjective loss of peripheral vision bilaterally. Other symptoms included mild decreased night vision and photopsia. Stage I breast cancer was diagnosed 5 years prior and treated with excisional biopsy and radiotherapy. She had a second cancer, stage IV lung cancer with liver metastasis, that was diagnosed 2 years prior and was treated with chemotherapy.
On examination, best-corrected visual acuity was 20/80 OD and 20/70 OS. The anterior segment, optic disc, and retinal vessels were unremarkable bilaterally. Fundus examination revealed multiple small, round, amelanotic (vitelliform) lesions approximately 500 μm in diameter in the postequatorial region bilaterally that superficially appeared like choroidal metastasis or retinal pigment epithelial detachments (Figure 1). There was no vitritis. Ultrasonography showed multifocal regions of chorioretinal thickening. Optical coherence tomography revealed multiple areas of localized subretinal fluid with debris overlying flat retinal pigment epithelium (Figure 2). Autofluorescence disclosed hyperautofluorescence corresponding to the serous retinal detachments (Figure 1), whereas fluorescein angiography demonstrated hypofluorescence of these regions with no leakage (Figure 2). The patient refused electroretinography testing.
Figure 1. Fundus photographs of the right (A) and left (B) eyes show numerous subtle hypopigmented subretinal lesions (arrows) corresponding to multifocal serous detachments of the neurosensory retina. Autofluorescence of the right (C) and left (D) eyes reveals hyperautofluorescence (arrows) in the area of the serous retinal detachment.
Figure 2. Optical coherence tomographic image and fluorescein angiograms. A, Optical coherence tomography shows multiple serous neurosensory retinal detachments with optically dense debris. Fluorescein angiograms show hypofluorescence of the lesion in early frames in the right (B) and left (C) eyes and late frames in the right (D) and left (E) eyes.
This case illustrates an unusual cause of vision loss in a patient with systemic cancer, namely AEPPVM. This condition manifests with multiple vitelliform lesions and is considered an atypical subset of cancer-associated retinopathy or melanoma-associated retinopathy or a separate paraneoplastic entity. Several authors have associated this entity with underlying cutaneous and choroidal melanoma, but not carcinoma.3- 6 Previous reports have labeled this condition as Vogt-Koyanagi-Harada–like syndrome, melanoma-associated retinopathy syndrome variant, vitelliform maculopathy with skin melanoma, vitelliform paraneoplastic retinopathy associated with melanoma, and AEPPVM.3- 6 While most previously reported cases have occurred in patients with skin or eye melanoma, we are unaware of reports of this condition with carcinoma, as in our case.
Clinicians should be aware of AEPPVM. Differentiation from choroidal metastasis can be made by clinical examination and more specifically by optical coherence tomography in that the choroid is flat in AEPPVM, whereas it is elevated with choroidal metastases. In our case, optical coherence tomography showed elevated retina and flat choroid, consistent with AEPPVM. Superficially, the optical coherence tomography changes resembled pigment epithelial detachment, but close scrutiny disclosed flat retinal pigment epithelium and subretinal fluid with dense debris.
Symptoms from paraneoplastic retinopathy can occur before or after the discovery of the primary malignant neoplasm.1,2 Systemic evaluation for primary cancer, particularly cutaneous or uveal melanoma, is indicated. In our case, systemic evaluation showed no sign of melanoma, and the previously diagnosed carcinomas were confirmed. There is a remote possibility that our patient could have had a regressed cutaneous melanoma or undetected visceral melanoma.
In summary, we describe an unusual paraneoplastic syndrome, namely AEPPVM. This condition should be recognized by clinicians, and systemic evaluation for the primary malignant neoplasm should be performed owing to the high association with cutaneous and choroidal melanoma and, now, carcinoma.1
Correspondence: Dr C. L. Shields, Ocular Oncology Service, Ste 1440, Wills Eye Institute, 840 Walnut St, Philadelphia, PA 19107 (email@example.com).
Financial Disclosure: None reported.
Funding/Support: This work was supported by the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (Dr Shields).
Thank you for submitting a comment on this article. It will be reviewed by JAMA Ophthalmology editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 7
Customize your page view by dragging & repositioning the boxes below.
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.