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Figure 1. Findings at the initial visit and 8 months after the onset of symptoms. A, Fundus photographs at the initial visit. Narrowed retinal arteries and swollen optic discs were obvious despite vitreous haziness. B, At the initial visit, full-field electroretinographic studies (International Society for Clinical Electrophysiology of Vision Standards) revealed normal rod electroretinographic results (first and second rows) but nonrecordable cone electroretinographic results (third and fourth rows) in both eyes. C, Eight months after the onset of symptoms, fundus photography and fluorescein angiography showed bilateral macular atrophy with a bull’s-eye appearance.

Figure 1. Findings at the initial visit and 8 months after the onset of symptoms. A, Fundus photographs at the initial visit. Narrowed retinal arteries and swollen optic discs were obvious despite vitreous haziness. B, At the initial visit, full-field electroretinographic studies (International Society for Clinical Electrophysiology of Vision Standards) revealed normal rod electroretinographic results (first and second rows) but nonrecordable cone electroretinographic results (third and fourth rows) in both eyes. C, Eight months after the onset of symptoms, fundus photography and fluorescein angiography showed bilateral macular atrophy with a bull’s-eye appearance.

Figure 2. Rhesus monkey retina incubated with the patient's serum. The cone outer segments are specifically labeled by the patient's antibodies (arrows) directed against a single neuronal protein of 42 kDa.

Figure 2. Rhesus monkey retina incubated with the patient's serum. The cone outer segments are specifically labeled by the patient's antibodies (arrows) directed against a single neuronal protein of 42 kDa.

1.
Cogan DG, Kuwabara T, Currie J, Kattah J. Paraneoplastic retinopathy simulating cone dystrophy with achromatopsia [in German].  Klin Monbl Augenheilkd. 1990;197(2):156-158PubMedArticle
2.
Campo E, Brunier MN, Merino MJ. Small cell carcinoma of the endometrium with associated ocular paraneoplastic syndrome.  Cancer. 1992;69(9):2283-2288PubMedArticle
3.
MacKay CJ, Gouras P, Roy M, Saeki M, Kupersmith M, Odel J. Paraneoplastic cone dystrophy.  Invest Ophthalmol Vis Sci. 1994;35(4):2119
4.
Jacobson DM, Thirkill CE. Paraneoplastic cone dysfunction: an unusual visual remote effect of cancer.  Arch Ophthalmol. 1995;113(12):1580-1582PubMedArticle
5.
Rios RJ, Odel JG, Hiron M, Mojon D. Rod-sparing paraneoplastic retinopathy, opsoclonus, and peripheral neuropathy due to a small cell lung carcinoma.  Neuro-Ophthalmology. 1997;17(2):101-105ArticleArticle
6.
Cross SA, Salomao DR, Parisi JE,  et al.  Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG.  Ann Neurol. 2003;54(1):38-50PubMedArticle
Research Letters
May 2012

Unusual Paraneoplastic Cause of Vision Loss: Combined Paraneoplastic Cone Dystrophy and Optic Neuropathy

Author Affiliations

Author Affiliations: Unit of Neuroophthalmology, Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland (Drs Finger and Borruat); and Eye Research Center, Davis Medical Center, University of California, Sacramento (Dr Thirkill).

Arch Ophthalmol. 2012;130(5):660-662. doi:10.1001/archophthalmol.2011.1814

Paraneoplastic cone dystrophy is a very rare condition with only a few cases reported in the literature.15 Paraneoplastic optic neuropathy is also a rare cause of cancer-associated visual disturbance. We describe a patient with subacute bilateral vision loss resulting from combined optic neuropathy and cone dystrophy of paraneoplastic origin (occult lung small cell carcinoma). The patient's serum contained antibodies reactive with a novel 42-kDa retinal antigen.

Report of a Case

A 55-year-old man had slight photophobia, photopsias, progressive loss of color perception, and slightly diminished visual acuity in both eyes over a month. Seven days before his initial visit, he developed massive painless vision loss in both eyes over a few hours. His medical history revealed active smoking and alcohol abuse as well as the removal of in situ epidermoid oropharyngeal carcinoma 1 month earlier.

On examination, best-corrected visual acuity was counting fingers at 2 ft OU. Color vision was abolished in both eyes. Slitlamp biomicroscopy showed 2+ cells in the vitreous of both eyes. Fundus examination revealed slightly pallid, swollen optic discs and narrowed arteries in both eyes (Figure 1A). Lumbar puncture revealed an elevated level of cells (9/μL) and proteins (855 mg/L) in cerebrospinal fluid with normal opening pressure. Brain magnetic resonance imaging was unrevealing. Full-field electroretinography showed bilateral nondetectable cone function but normal rod function (Figure 1B). Paraneoplastic retinopathy was suspected and a chest computed tomographic scan disclosed parahilar lymph nodes. Biopsy revealed metastasis of a neuroendocrine lung small cell carcinoma. Radiotherapy and systemic chemotherapy were initiated.

On follow-up visits, photophobia remained severe, visual acuity was counting fingers OU, and the visual field was markedly constricted under photopic conditions bilaterally. However, under very dim illumination, visual acuity improved to 20/400 OU and the visual field expanded in each eye. Vitreous cells disappeared and bilateral optic disc atrophy ensued. After 8 months, bilateral macular atrophy with a bull’s-eye appearance was obvious in both eyes (Figure 1C). The patient's condition remained stable for 4 years with unchanged visual acuity, visual fields, and full-field electroretinographic results. He eventually died of recurrence of his primary lung cancer. No autopsy was performed.

Findings on serum analyses were negative for all of the paraneoplastic antibodies known at the time (1996), including antirecoverin antibody. Serum was sent for further analysis (by C.E.T.), and antibody activity directed toward a 42-kDa retinal antigen was detected. When incubated with fresh rhesus monkey retina, these antibodies specifically labeled the retinal cone outer segments (Figure 2), providing evidence for a mechanism explaining the cone dysfunction.

Comment

Within 1 month, the patient had experienced a sudden acute and profound bilateral vision loss defined by swollen discs, vitreous cells, and inflammatory spinal fluid related to a paraneoplastic optic neuropathy.

Typical features of an acquired cone dystrophy (decreased visual acuity better with sunglasses, loss of color vision, photopsias, and suppressed photopic response on electroretinography) were initially present. Later, a bull’s-eye maculopathy developed and abnormal antibody activity involving the cone pedicles appeared in the patient's serum.

The unique combination of paraneoplastic cone dystrophy and optic neuropathy in our patient was associated with the presence of antibody activity involving a 42-kDa retinal antigen. Indirect fluorescent antibody assays on sectioned rhesus monkey eye associated this antibody activity with the cone outer segments, representing a previously unknown paraneoplastic reaction. The nature of the 42-kDa antigen is not known.

Combined paraneoplastic vision loss (retinopathy and optic neuropathy) has recently been reported in 5 of 16 patients with collapsin response-mediated protein 5 antibodies.6 Nine of the 16 patients exhibited vitreous cells, and 15 of the 16 had swollen optic discs.

This case expands the spectrum of clinical entities capable of producing paraneoplastic vision loss.

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Article Information

Correspondence: Dr F.-X. Borruat, Unit of Neuroophthalmology, Jules-Gonin Eye Hospital, Avenue de France 15, CH-1004 Lausanne, Switzerland (francois.borruat@fa2.ch).

Financial Disclosure: None reported.

Funding/Support: This work was supported by an unrestricted grant from Research to Prevent Blindness and core grant 1 P30 EY12576-6 from the National Eye Institute (Dr Thirkill).

Previous Presentation: This paper was presented as a poster at the 2011 Meeting of the Swiss Society of Ophthalmology; September 1-3, 2011; Interlaken, Switzerland.

References
1.
Cogan DG, Kuwabara T, Currie J, Kattah J. Paraneoplastic retinopathy simulating cone dystrophy with achromatopsia [in German].  Klin Monbl Augenheilkd. 1990;197(2):156-158PubMedArticle
2.
Campo E, Brunier MN, Merino MJ. Small cell carcinoma of the endometrium with associated ocular paraneoplastic syndrome.  Cancer. 1992;69(9):2283-2288PubMedArticle
3.
MacKay CJ, Gouras P, Roy M, Saeki M, Kupersmith M, Odel J. Paraneoplastic cone dystrophy.  Invest Ophthalmol Vis Sci. 1994;35(4):2119
4.
Jacobson DM, Thirkill CE. Paraneoplastic cone dysfunction: an unusual visual remote effect of cancer.  Arch Ophthalmol. 1995;113(12):1580-1582PubMedArticle
5.
Rios RJ, Odel JG, Hiron M, Mojon D. Rod-sparing paraneoplastic retinopathy, opsoclonus, and peripheral neuropathy due to a small cell lung carcinoma.  Neuro-Ophthalmology. 1997;17(2):101-105ArticleArticle
6.
Cross SA, Salomao DR, Parisi JE,  et al.  Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG.  Ann Neurol. 2003;54(1):38-50PubMedArticle
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