Sir,

Paraneoplastic optic neuritis (PON) is an ocular manifestation of the paraneoplastic syndrome that is clinically characterized by subacute vision reduction, optic disc swelling, and neurological symptoms.1 Previously, the diagnosis was difficult because it was based only on the clinical signs and symptoms. Recently, a distinct IgG for the 62 kDa collapsin response-mediator protein-5 (CRMP-5-IgG) was demonstrated to be a serological marker for PON.1, 2

Case report

A 55-year-old woman noticed a subacute bilateral vision reduction and was referred to our hospital. She had a history of a lung adenocarcinoma resection at 46 years of age, but the cancer reappeared 3 years later. She also had occasional epileptic seizures beginning at 54 years of age.

On examination, her visual acuity was 20/400 in each eye. Her pupillary responses, eye movements, and anterior segments were normal. The critical fusion frequencies were markedly reduced. Funduscopic examination showed a mild swelling of both optic discs (Figure 1a). There were no inflammatory cells in the vitreous cavity. Fluorescein angiography revealed hyperfluorescence and leakage on the optic disc in accord with the swelling, but not in areas away from the disc. The arm–retina time was not delayed. Visual field examination showed a central scotoma and enlarged blind spot in both eyes (Figure 1b). Full-field cone and rod electroretinograms were within normal limits.

Figure 1
figure 1

Fundus photographs and visual fields of patient with PON. (a) Fundus photographs showing mild swelling of both optic discs (left, right eye; right, left eye). (b) Visual fields showing bilateral central scotoma and blind spot enlargement (left, left eye; right, right eye).

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Cranial computed tomography (CT) and magnetic resonance imaging showed neither metastatic cancer nor white matter lesions suggestive of multiple sclerosis. Cerebrospinal fluid examination revealed a slightly elevated protein level (64 mg/dl). Laboratory findings were normal except for an elevated carcinoembryonic antigen.

Methylprednisolone pulse treatment, 500 mg/day, was given for 3 days but the visual acuity and optic disc appearance did not improve. Chest CT showed nodular lesion at the apex of the right lung.

Based on these findings, a possibility of PON was considered. We performed Western blot analysis of her serum and detected a 62 kDa band corresponding to CRMP-5-IgG (Figure 2).

Figure 2
figure 2

Western blot analysis using soluble fraction of bovine optic nerve. The primary antibodies used were lane 1, anti-human CRMP-5 (1 : 3000 dilution, CHEMICON, Temecula, CA, USA); lane 2, serum IgG from the patient (1 : 15 dilution); lane 3 and 4, sera from age-matched healthy human subjects without any retinopathy and optic neuropathy (1 : 3000 dilution). A 62 kDa protein corresponding to full-length CRMP-5 is seen only in lanes 1 and 2 (Arrowhead). HRP-labelled anti-rabbit IgG or anti-human IgG (1 : 3000 dilution; Amersham, Piscataway, NJ, USA) was used as a second antibody. NS, nonspecific.

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Comment

Most of the previous cases of PON were associated with small-cell lung carcinoma, and a lung adenocarcinoma has been reported in only one case but without CRMP-5-IgG testing.1, 3 We are unaware of previous reports of PON caused by lung adenocarcinoma that was confirmed by CRMP-5-IgG testing.

The results of autopsy examinations of a previous case of PON associated with a lung adenocarcinoma showed a destruction of the optic nerves mainly around the chiasma.3 The optic discs in our case were swollen, but the swelling was milder than that in cases of PON associated with small-cell lung carcinoma. Therefore, further studies are required to determine if the optic disc appearance in cases of PON associated with lung adenocarcinoma is significantly different from that with small-cell lung carcinoma.

Immunosuppressive therapies are generally considered to be ineffective for PONs as in our case.1 This is probably because CRMP-5 may play a role in maintaining dendritic plasticity in the mature central nervous system,1 and PON results in irreversible damages such as demyelination of optic nerve and gliosis.3, 4, 5 Therefore, the CRMP-5-IgG testing can lead to an earlier and precise diagnosis, which would then enable earlier treatments of the original tumor(s) before irreversible damage of the optic nerve.