DIDS kinase Recoverin is a kDa retinal protein that
Recoverin is a 23-kDa retinal protein that binds to calcium. It regulates the DIDS kinase of rhodopsin during visual transduction within photoreceptor cells. Since the pathogenicity of anti-recoverin antibody is potent, anti-recoverin CAR patients often have progressive visual impairments, characterized by decreased cone and rod responses, resulting in a poor visual prognosis., However, this antibody was detected only in approximately 10% of CAR patients.
Enolase is a ubiquitously expressed 46-kDa glycolytic enzyme that is found in many systemic and cancer tissues. Anti-α-enolase antibody is the most frequent antibody in seropositive CAR patients, with a detection rate of approximately 30% and labeled retinal ganglion cells, Müller glial cells, and cone and rod photoreceptors on immunohistochemistry., , However, it remains largely unknown whether this antibody affects the retinal pigment epithelium (RPE).
There are several reports regarding patients with anti-α-enolase antibody–positive (anti-enolase) AIR, either paraneoplastic or nonparaneoplastic in origin., , , , , , In a previous case series, the clinical features of 12 anti-enolase AIR patients were as follows: (1) funduscopically normal appearance in 58% of the patients, with the remaining 42% exhibiting some degenerative changes in the fundus; (2) perimetry showing central scotoma in 50% of the cases; (3) ERG demonstrating global or central cone dysfunction with modest or no rod involvement in 67% of the cases; (4) slowly or hardly progressive visual dysfunction for years; and (5) cancer detected in 33% of the cases. To the best of our knowledge, however, the clinical features of Japanese anti-enolase AIR patients have not been reported.
Here we investigated the clinical features of Japanese patients with anti-enolase AIR and identified a peculiarly striking subtype of “multiple drusen”, in addition to the “normal” and “degenerative” findings also described in the literature. To seek a possible interpretation of this previously undocumented phenotype, we further examined tissue localization of α-enolase in an enucleated eye of 1 patient in this case series.
Patients and Methods
Discussion A comparison of the clinical features of anti-enolase AIR between Japanese patients in the present study and Caucasian patients in a previous study is shown in Table 5. The common features to both studies are the mean age at first visit, sex ratio, the frequency of central visual impairments, the rate of complicating systemic tumors, and the number of patients with a slowly progressive or stable clinical course during the follow-up. However, we found a much higher frequency (48% vs 8%) of patients with drusen in our study. Importantly, in the literature as well, there has been no particular description of drusen in anti-enolase AIR patients,10, 13, 14, 21, 22 except for 1 patient with fine foveal macular drusen in the case series involving Caucasian subjects, suggesting a strikingly unique feature of the drusen subtype in our Japanese patients with anti-enolase AIR. SD-OCT scans revealed hyperreflective to isoreflective materials at the sub-RPE level corresponding to the different-sized white-yellow deposits in our anti-enolase AIR patients, and FAF demonstrated miscellaneous appearances of hyper- or hypoautofluorescence depending on cases. These observations suggested the diversity of the currently seen drusen, which would be attributable to the degree of atrophic changes in the lipofuscin-laden RPE cells and the composition rate of excreted lipofuscin in the drusen component. Actually, drusen findings on FAF are variable and thus elusive in several drusen-associated diseases, such as autosomal dominant radial drusen (honeycomb retinal dystrophy or malattia leventinese) and large colloid drusen, both characterized by hyperautofluorescence, but in contrast, cuticular drusen (basal laminar drusen) basically showing hypoautofluorescence. In general, age-related hard (small) drusen are hypoautofluorescent, whereas soft (larger) drusen typically seen in AMD are more diverse in carrying hypo- to hyperautofluorescence, in accordance with our FAF findings of anti-enolase AIR-related drusen (hereafter referred to as “anti-enolase drusen”) in various sizes ranging from small deposits to vitelliform-like accumulations.