SC-10 Among our patients with anti enolase drusen those with

Among our patients with anti-enolase drusen, those with a relatively short duration from the onset of visual symptoms to the first visit tended to have normal structure of photoreceptors with preserved visual function, despite the presence of drusen-related RPE abnormalities (Cases 1-3 and 8). In contrast, the patients with longer duration before the first visit tended to suffer from visual and anatomic impairments with the loss of the macular ellipsoid zone (Cases 4, 7, 11, and 12). Indeed, these observations were firmly validated by the negative correlation detected between the a-wave amplitude and the presumed disease duration in the drusen group. Moreover, combined rod and cone system responses on both standard and strong-flash ERGs showed lower a-wave amplitudes in the degeneration group than in the drusen group (Table 4). From these results, we inferred that the photoreceptor impairment stemmed secondarily from the RPE damage in patients with anti-enolase drusen. This is further supported by the present (Figure 6) and previous immunohistochemical data on the positive staining of α-enolase in RPE cells, suggesting this cell type as a potential cellular target of anti-α-enolase antibody. However, it remains largely unknown why approximately a half of our anti-enolase AIR patients exhibited multiple drusen, a distinctly different phenotype compared with previously reported cases.10, 12, 13, 14, 21, 22 One possible explanation is a racial difference between pigmented and nonpigmented populations, in terms that requirement of this glycolytic enzyme in metabolically active RPE SC-10 may be more prominent in Japanese patients, resulting in vulnerability of this cell type against anti-α-enolase antibody. In our case series, eyes with retinal degeneration or normal fundus unexceptionally demonstrated structural and functional photoreceptor abnormalities corresponding to the funduscopic and/or perimetric lesions, even though the RPE layer was intact (Figure 5). By stark contrast to eyes with multiple drusen, photoreceptor cells appeared to be primarily affected in these subtypes. Our immunohistochemical results suggested that both of the cell types immunoreactive for α-enolase could be impaired in anti-enolase AIR, casting a fundamentally important question of why there seemed to be no overlap between cases where the potential primary target was RPE cells (drusen group) or photoreceptors (degeneration/normal group). Importantly, anti-α-enolase antibody from sera of anti-enolase CAR patients was previously shown to harbor different labeling patterns for retinal cells based on its antigenic specificity. Furthermore, significant differences in the antigen epitope of α-enolase and the antibody-mediated cytotoxicity were detected between anti-enolase CAR patients and healthy subjects seropositive for anti-enolase antibody without visual symptoms. Therefore, we deduced that different antigenic specificity for this antibody might have determined which cell type was more susceptible, thus leading to the separately distinct funduscopic and functional features in the current case series. Despite our systemic screening applied here, 70% of the patients with anti-enolase AIR exhibited no association of tumor, in consistence with the previously reported rate of 67%. Basically, the pathogenesis of nonparaneoplastic AIR remains incompletely understood; however, excessive autoimmune reaction combined with some tissue damage may theoretically be a causative mechanism, given the presumably higher chance of antigen exposure of this ubiquitously expressed glycolytic enzyme. Another possibility is the presence of occult tumor controlled by potent immune surveillance and thus clinically undetectable. Indeed, we previously experienced a case of seropositive anti-recoverin AIR with a complicating tumor undetectable in the first place but later detected and excised, whose surgical specimens were shown to be immunoreactive for the corresponding retinal antigen.