Autoimmune retinopathy (AR) can be divided into three different categories, paraneoplastic retinopathy, including recoverin-associated retinopathy and melanoma-associated retinopathy, non-paraneoplastic autoimmune retinopathy, combined paraneoplastic optic neuropathy and retinopathy (CAR). These conditions are characterised by circulating anti-retinal autoantibodies, possibly due to a cross-reaction between retinal proteins and cancer antigen. One such protein is carbonic anhydrase II (CA II), a zinc enzyme, that catalyses the reversible hydration of carbon dioxide, found in the retina in cones and Muller cells, and in many other tissues. Autoantibodies against CA II have been identified in other autoimmune conditions including Sjogren’s Syndrome, systemic lupus erythematosus (SLE) and type 1 diabetes. In this study sera from a large cohort of patients with AR, including CAR and healthy controls were analysed for CA II epitope recognition. Biotinylated 12-mer overlapping synthetic peptides covering the CA Il sequence were used to assess autoantibody titres by ELISA. The results showed three epitopes were common in AR, CAR and healthy controls (HC), but with different prevalence. AR patients recognised eipotpe 85-90, CAR autoantibodies recognised eipitope 218-22, while HC showed a different pattern. A patient who developed CAR two years after an initial diagnosis of AR, switched epitope profile from AR to CAR. These data show that antibodies target different regions of the same molecule depending on the form of AR, a finding that may be important in diagnosis.