Multimodal imaging and electroretinography analysis of end-stage presentations of X-linked retinoschisis

Document Type


Publication Date



Purpose : Patients with X-linked retinoschisis (XLRS) presenting at end-stage of disease are difficult to diagnose when severe macular atrophy is present without intraretinal fluid. The purpose of this study is to characterize late presentations of XLRS with retinal imaging and electrophysiology in patients without pathognomonic fundus exam or OCT findings.

Methods : Three unrelated male patients presented by referral to the Harkness Eye Institute electrophysiology clinic for evaluation of severe retinal degenerations of unknown etiology. Ocular exam findings, SD-OCT, fundus autofluorescence (FAF), full-field electroretinography (ffERG), and genetic testing results were retrospectively reviewed.

Results : All three patients (average age, 62; range, 58-70) described chronic, progressive bilateral vision loss and exhibited decreased visual acuity and central macular atrophy in both eyes on exam. In each patient (6 eyes), SD-OCT confirmed marked atrophy affecting all retinal layers with no evidence of cystoid changes. FAF imaging revealed a hyperautofluorescent ring between the vascular arcades of all eyes, containing an inner region of heterogenous signal and confluent patches of hypoautofluorescence consistent with loss of retinal pigment epithelium. Disease severity and FAF/OCT phenotype was symmetric between eyes of all patients. FfERGs were performed in two patients and both showed decreased scotopic b-wave and photopic 30 Hz-flicker amplitudes, with electronegative maximum scotopic responses. RS1 mutations were identified in each patient: c.286T>C, (p.Trp96Arg), c.416delA (p.Gln139Argfs*10), and c.445A>C (p.Thr149Pro) respectively, confirming the diagnosis of XLRS.

Conclusions : Patients with undiagnosed late-stage XLRS may present with profound macular atrophy but without the classic ‘spoke-wheel’ appearance of the fundus or characteristic foveal schisis, thus delaying accurate diagnosis. Patients suspected to have an inherited retinal dystrophy that exhibit severe macular degeneration and electronegative responses on ffERG may warrant screening with candidate RS1 gene testing as a first diagnostic step.

Publication Title

investigative ophthalmology & visual science






presented at the 2019 ARVO Annual Meeting, Vancouver, Canada, April 28 - May 2, 2019.

This document is currently not available here.

Open Access