Autoimmune Retinopathies and Paraneoplastic Retinopathies
Cancer-associated retinopathy (CAR) presents with bilateral progressive vision loss (which may be unilateral or asymmetric in onset) and impaired color vision. Associated symptoms include photopsias, nyctalopia (night blindness), impaired dark adaptation, ring scotoma, and peripheral and/or central visual field loss. Symptoms progressively worsen over weeks to months, often before the underlying malignancy is identified. The most common cause is small-cell lung carcinoma, although other lung, 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 ONHs atrophic. Vision loss is typically severe. When CAR is suspected, the patient should be tested for the presence of antibodies against retinal proteins (ideally by both Western blot and immunohistochemical analysis). Serum antiretinal antibody testing is now commercially available. However, antibodies against recoverin, the best-characterized antibody, are found in only a minority of patients with CAR. If clinical suspicion of CAR remains high but the antibody testing is negative, the ophthalmologist should look for an underlying cancer. Empiric treatment with various combinations of corticosteroids, plasmapheresis, and intravenous immunoglobulin has been reported; in general, however, the prognosis for vision is poor.
Melanoma-associated retinopathy (MAR) is a rare syndrome that involves primarily 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. 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 it may show RPE irregularity, retinal arteriolar attenuation, or ONH pallor. Full-field ERG response shows rod dysfunction. The multifocal ERG pattern is relatively preserved; MAR affects rod function, and the multifocal ERG measures photopic responses. Unlike CAR, visual function may remain stable and nonprogressive in MAR. No treatment has proven effective, but anecdotal success with intravenous immunoglobulin has been reported.
Braithwaite T, Holder GE, Lee RW, Plant GT, Tufail A. Diagnostic features of the autoimmune retinopathies. Autoimmun Rev. 2014;13(4–5):534–538.
Gordon LK. Paraneoplastic syndromes in neuro-ophthalmology. J Neuroophthalmol. 2015; 35(3):306–314.
Nonparaneoplastic autoimmune retinopathy
Nonparaneoplastic autoimmune retinopathy (NpAIR) has a more variable presentation that may include decreased visual acuity, peripheral visual field loss, positive visual phenomenon, or nyctalopia. NpAIR is associated with autoimmune disease in approximately 50% of patients. ERG findings are highly variable but usually demonstrate cone-system dysfunction, either macular or generalized, with postphototransduction involvement. The clinician should diagnose NpAIR only following comprehensive systemic investigation to exclude occult malignancy. NpAIR-associated antibody targets overlap with those of CAR, with the exception of recoverin, which has not been reported in NpAIR to date.
Excerpted from BCSC 2020-2021 series: Section 5 - Neuro-Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.