macular pigmentation. As the disease progresses, the macular RPE becomes atrophic in a central oval region. A “bull’s-eye” pattern of depigmentation may be present, similar to that observed in late chloroquine-induced maculopathy. Findings on fluorescein angiography and fundus autofluorescence may highlight these abnormalities before they become clinically apparent. Full-field ERG results may be normal initially but eventually show markedly depressed photopic (cone) response and less prominently affected scotopic (rod) response. Multifocal ERG studies show central depression. OCT scans may show thinning of outer macular layers.

Paraneoplastic Syndromes

Cancer-associated retinopathy

Cancer-associated retinopathy (CAR) presents with constant photopsias, nyctalopia, impaired dark adaptation, dimming, ring scotoma, and peripheral and/or central visual field loss. Symptoms progressively worsen over weeks to months, often (in 50% of cases) before the underlying malignancy is identified. The most common cause is small cell lung carcinoma, although other lung tumors and breast, uterine, and cervical malignancies have been reported. The fundus may initially appear normal, but the ERG response shows markedly reduced amplitudes. As the disease progresses, the retinal arterioles become attenuated, the RPE thinned and mottled, and the optic discs atrophic. Vision loss is typically severe.

The underlying tumor most likely expresses an antigen that is homologous to a 23-kDa retinal photoreceptor protein. Originally termed the CAR antigen, this protein has now been identified as the calcium-binding protein recoverin. Circulating autoantibodies against the tumor-associated antigen presumably cross-react with retinal recoverin to produce immune-mediated photoreceptor degeneration of rods and cones. Treatment of the inciting tumor has an unclear effect on retinal function. Treatment benefit may occur with various combinations of corticosteroids, plasmapheresis, and intravenous immunoglobulin; in general, however, the prognosis for vision is poor.

Melanoma-associated retinopathy

Melanoma-associated retinopathy (MAR) is an extremely rare syndrome that primarily involves rod bipolar cells, with corresponding symptoms of photopsia, nyctalopia, and bilateral peripheral visual field loss. MAR usually develops rapidly over weeks to months but may have a sudden onset. Visual symptoms typically develop in patients with previously diagnosed melanoma, and investigation of vision loss often reveals recurrence or metastasis. Visual acuity, color vision, and the central visual field are often initially normal with prominent peripheral visual field loss. The fundus may appear normal or may show RPE irregularity, retinal arteriolar attenuation, and optic disc pallor. Full-field ERG response shows rod dysfunction. The mfERG pattern is relatively preserved because MAR affects rod function and the mfERG measures photopic responses. Visual function may remain stable and nonprogressive in MAR (unlike for CAR). No treatment has proven effective, but isolated success with intravenous immunoglobulin has been reported.

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