Anti-EYS monoclonal antibody, clone 4H20.2

Background: To characterize the clinical phenotypes associated with previously-reported mutations of the eyes shut homolog (EYS) gene, including a truncating mutation, c. 4957_4958insA, which is a major causative mutation for retinitis pigmentosa (RP) in Japan. Materials and Methods: The study population comprised ten unrelated RP subjects with very likely pathogenic mutations in both alleles, four of them with a homozygous c. 4957_4958insA mutation. The phenotype analysis was based on ophthalmic examination, Goldmann perimetry, and digital fundus photography. Results: The study population included six men and four women aged 34-74 years. The average age at first visit was 31 years (range, 14-44 years), and the patients typically presented with night blindness as the initial symptom and subsequently developed progressive constriction of the visual field. Myopia was noted in 9/20 affected eyes. For most patients, central visual acuity was preserved relatively well up to their thirties, after which it deteriorated rapidly over the next two decades. The visual acuity of patients homozygous for the c. 4957_4958insA mutation was uniform. Visual fields were constricted symmetrically, and the extent of constriction seemed to be better correlated with age than visual acuity. The fundus displayed bone spicules, which increased in density with age, and attenuated retinal vessels. Conclusions: Although additional studies with more patients with mutations of the EYS gene are required, it appears that patients share a relatively uniform phenotype with near-normal central visual function up to their twenties. The patients homozygous for the c. 4957_4958insA mutation showed a uniform course of visual acuity changes.

Purpose To evaluate whether the length of the inner segment ellipsoid (ISe) band can be used as a prognostic factor for disease course in retinitis pigmentosa (RP) patients with EYS mutations by observation over a period of 5 years. Methods Twelve RP patients with EYS mutations were studied. The horizontal and vertical ISe length of the right eye was manually measured at five time points annually, using spectral domain optical coherence tomography. A regression line through the five points from baseline to the final measurement was drawn and the ratio of the length (%) at each point to the baseline length was calculated; the slope was defined as the rate of ISe shortening (%/year). The correlation between the rate of ISe shortening and age, visual acuity, and mean deviation (MD) value were evaluated. The intraclass correlation coefficient (ICC) for the measurements was calculated. Results The mean rate of ISe shortening was -4.65 +/- 2.89% per year and the decline was statistically significant. The rate of shortening was significantly negatively correlated with the baseline length (P= 0.046, r= 0.58), but not with the baseline age, visual acuity, and MD value. The ICC (2, 1) was 0.999. Conclusions ISe of all RP patients with EYS mutations shortened during the 5 years of annual observation. The measurement of the length of ISe is a simple and convenient method with high repeatability, and the length is a sensitive prognostic factor for the rate of ISe shortening in RP patients with EYS mutations.