Structure/Psychophysical Relationships in X-Linked Retinoschisis

Juvenile X-linked retinoschisis (XLRS) is a congenital macular degeneration affecting 1/5000 to 1/25,000 worldwide.1,–3 The gene associated with XLRS, Retinoschisin (RS1),4 translates to a retinoschisin protein (RS1), which assists in maintaining retinal structure by binding to the photoreceptors and bipolar cells. Patients are diagnosed in their primary school years with clinical characteristics of bilateral retinal splitting5–8 and an electronegative electroretinography (ERG) response with preserved a-wave.9 Best corrected visual acuity (BCVA) typically ranges from 20/50 to 20/120 (0.5–0.8 log minimum angle of resolution [logMAR]) and remains stable until the fifth or sixth decade of life when the cavities resolve and visual acuity decreases.10 Shape discrimination hyperacuity (SDH) and contour integration perimetry (CIP) in patients with intermediate AMD show significant deficits, with macular edema exacerbating the loss of the ability to detect distortions in circular shapes.11,12 These tests assess the global integration of visual stimuli over a large retinal area. The SDH tests parafoveal acuity, whereas the CIP determines retinal acuity outside of the central 3°. Due to the foveal edema in XLRS we hypothesize that the global integration measured by SDH/CIP may be affected, although some patients retain a relatively good BCVA. Spectral-domain optical coherence tomography (SDOCT) studies in XLRS have been reported,5,7,13,14 but rarely correlated with fundus-guided perimetry15 or shape discrimination. Clinical attributes of XLRS have been characterized, but concise relationships with structure and psychophysical function need further exploration. A multicenter natural history study of XLRS was designed to understand disease progression and determine suitable outcome measures for future gene therapy trials. The results reported here were obtained from a single visit. A subset of patients were tested with additional measures so that we could determine whether photoreceptor outer segment (OS) and/or total retina (TR) thickness could predict performance on visual tasks such as BCVA, fundus-guided perimetry, SDH, and CIP in patients with XLRS.