Nora Foster* was seeing things. For a month, the 44-year-old woman was bothered by bright, swirling lights that spun in a clockwise motion, “like a pinwheel.” The lights did not change in size or intensity, and they persisted when she closed her eyes.
Many years earlier, Ms. Foster had been diagnosed with ocular migraines, which consisted of “zigzag” lines in her peripheral vision followed by severe headaches. The migraines had clear hormonal triggers. When she consulted us about the pinwheel lights, she was adamant that these new episodes were different and unrelated to her menstrual cycle.
We Get a Look
Ms. Foster’s medical history was significant for Hodgkin’s lymphoma. The disease was diagnosed and treated 20 years previously and she was considered to be in remission.
Her visual acuity was 20/20 in her right eye and 20/15 in her left. Ishihara color vision testing was normal in both eyes. Humphrey visual fields revealed bilateral enlarged blind spots, with superior and inferior arcuate scotomas in her left eye.
Caption: Visual fields revealed bilateral enlarged blind spots in both eyes, with
superior and inferior arcuate scotomas in the left eye (right image).
Ms. Foster’s pupils were equal, round and briskly reactive to light. There was a mild 0.6 to 0.9 log unit relative afferent pupillary defect in her left eye. Photostress recovery test was normal (10 seconds in her right eye and 19 seconds in her left). The slit-lamp examination was unremarkable. The funduscopic examination revealed normal-appearing macula and pink discs with sharp margins and small cups. Marked arteriolar narrowing was present bilaterally (Fig. 3). The remainder of her neurologic exam was unremarkable.
Our differential diagnosis included optic neuritis, migraine headaches, autoimmune-related retinopathy and optic neuropathy (ARRON), retinitis pigmentosa and occipital lobe seizures.
Electrophysiologic testing was performed. Visual evoked potentials were normal in both eyes. Electroretinography was normal for both amplitude and implicit time in the right eye, but the left showed subnormal responses for amplitude.
An MRI of the brain and orbits was performed; it was unremarkable, as were carotid studies.
Serum was sent to the Ocular Hypersensitivity Laboratory at the University of California, Davis, to be evaluated for antiretinal and antioptic nerve antibodies, including the 23 kilodalton (kD) antibody responsible for cancer-associated retinopathy (CAR). While Ms. Foster did not show evidence of CAR, her serum contained a 57-60 kD autoantibody; this was felt to indicate activity against the retinal nerve fiber layer extending into the ganglion cell layer.
We recommended an oncology consultation to evaluate for occult malignancy. The complete medical and radiologic workup revealed only an enlarged supraclavicular lymph node. A biopsy of this node revealed no evidence of recurrent lymphoma.
The Cancer Connection
Although these cases often are bilateral, in instances such as this one—with an atypical, asymmetric retinal degeneration in a patient with a prior history of cancer—the patient should be evaluated for paraneoplastic retinal disease.
Several well-defined paraneoplastic retinopathies exist. The two best-described such retinopathies are CAR and MAR (melanoma-associated retinopathy).
In 1987, Thirkill et al. defined the 23 kD antibody for CAR.1 This syndrome is most commonly found in patients with small-cell lung cancer. However, it has also been diagnosed in patients with other malignancies, including ovarian, endometrial, cervical and breast cancer. It is characterized by painless loss of vision, photopsias, ring scotoma and altered photoreceptor function as shown on ERG.2 The visual loss often precedes the diagnosis of cancer.
MAR is the result of autoantibodies against retinal bipolar cells in patients with a history of malignant cutaneous melanoma.3 Patients typically note acute onset of shimmering lights and nyctalopia several years following the treatment for melanoma. These patients have ERG changes similar to congenital stationary night blindness.
ARRON is associated with antiretinal and/or antioptic nerve antibodies in the absence of a demonstrable cancer.
Ms. Foster was diagnosed with ARRON and started on oral steroids. The photopsias resolved and the visual field changes markedly improved, and she was weaned off of the medication.
In more than five years of follow-up, she has experienced several episodes of photopsias with concomitant blind spot enlargement, which has been worse in the left eye than in the right. It is of note that this case of ARRON has behaved like recurrent acute big blind spot syndrome.4 Each episode has been successfully treated with steroids with near complete resolution of her symptoms.
At her last examination, Ms. Foster’s visual acuity was 20/20 in both eyes. Color plates were full, her pupils were briskly reactive without afferent defect and the visual fields indicated minimally enlarged blind spots bilaterally. She currently remains in remission, with no evidence that the lymphoma has recurred.
* Patient name is fictitious.
1 Arch Ophthalmol 1987;105:372–375.
2 Goldstein, S. M. et al. Arch Ophthalmol 1999;117:1641–1645.
3 Weinstein, J. M. et al. Ophthalmology 1994;101:1236–1243.
4 Fletcher, W. A. et al. Arch Ophthalmol 1988;106(1):44–49.
Dr. Spirn is a vitreoretinal fellow at the University of British Columbia. Dr. Turbin is assistant professor and Dr. Frohman is associate professor and vice-chairman of ophthalmology; both are at the New Jersey Medical School of the University of Medicine and Dentistry of New Jersey.