Retinoschisis

The dark-adapted human electroretinogram (ERG) response to a standard bright flash includes a negative-going a-wave followed by a positive-going b-wave that crosses the baseline. An electronegative waveform (or negative ERG) results when the b-wave is selectively reduced such that the ERG fails to cross the baseline following the a-wave. In the context of a normally sized a-wave, it indicates a site of retinal dysfunction occurring after phototransduction (commonly at the photoreceptor to bipolar cell synapse). This is an important finding. In genetic disease, the pattern of ERG abnormality can point to variants in a small group of genes (frequently those associated with congenital stationary night blindness and X-linked retinoschisis, but negative ERGs can also be seen in other conditions including syndromic disease). In acquired disease, there are numerous causes, but specific features may point to melanoma-associated retinopathy (MAR). In some cases, the visual symptoms precede the diagnosis of the melanoma and so the ERG findings can initiate investigations facilitating early detection and treatment. Negative ERGs can occur in other paraneoplastic conditions, and in a range of other diseases. This review will outline the physiological basis for the negative ERG, report prevalences in the literature from different cohorts, discuss the range of causes, displaying examples of a number of ERG phenotypes, highlight features of a clinical approach to patients, and briefly discuss further insights relating to current flows shaping the a-wave trough and from single-cell transcriptome analysis.

PurposeTo investigate the structural and clinical characteristics of peripapillary retinoschisis observed in glaucomatous eyes using spectral-domain optical coherence tomography (SD-OCT).MethodsCircumpapillary retinal nerve fiber layer (cpRNFL) and macular cross-hair SD-OCT scans and infrared fundus images of the glaucoma patients from the Investigating Glaucoma Progression Study (IGPS) and healthy volunteers were reviewed. Optic disc images obtained using enhanced depth imaging (EDI) SD-OCT were also evaluated. The structural characteristics and clinical course of the retinoschisis associated with glaucoma were investigated.ResultsTwenty-five retinoschisis areas were found in 22 of the 372 patients (5.9%) included in the IGPS, and in 1 area in 1 of 187 healthy control subjects (0.5%). In the 22 glaucomatous eyes with retinoschisis, the schisis was attached to the optic disc and overlapped with the retinal nerve fiber layer (RNFL) defect. The RNFL was the layer most commonly affected by the retinoschisis, either alone or together with other deeper layers. Acquired optic disc pit was identified in 8 eyes on disc photography and/or B-scan images obtained by EDI SD-OCT. Spontaneous resolution of this condition was observed in nine eyes. No retinal detachment or macular involvement of the retinoschisis was observed in any of the eyes. Multivariate analysis showed a significant influence of a higher intraocular pressure at SD-OCT scanning on the presence of retinoschisis (Odds ratio = 1.418, P = 0.001).ConclusionsThe present study investigated 22 cases of peripapillary retinoschisis in glaucomatous eyes. The retinoschisis was attached to the optic nerve and topographically correlated with RNFL defect. It often resolved spontaneously without causing severe visual disturbance. Care should be taken not to overestimate the RNFL thickness in eyes with retinoschisis, and also not to misinterpret the resolution of retinoschisis as a rapid glaucomatous RNFL deterioration.

BackgroundMyopic foveoschisis (MF) is among the leading causes of visual loss in high myopia. However, it remains controversial whether internal limiting membrane (ILM) peeling or gas tamponade is necessary treatment option for MF.MethodsPubMed, EMBASE, CBM, CNKI, WANFANG DATA and VIP databases were systematically reviewed. Outcome indicators were myopic foveoschisis resolution rate, visual acuity improvement and postoperative complications.ResultsNine studies that included 239 eyes were selected. The proportion of resolution of foveoschisis was higher in ILM peeling group than non-ILM peeling group (OR = 2.15, 95% CI: 1.06-4.35; P = 0.03). The proportion of postoperative complications was higher in Tamponade group than non-Tamponade group (OR = 10.81, 95% CI: 1.26-93.02; P = 0.03). However, the proportion of visual acuity improvement (OR = 1.63, 95% CI: 0.56-4.80; P = 0.37) between ILM peeling group and non-ILM peeling group and the proportion of resolution of foveoschisis (OR = 1.80, 95% CI: 0.76-4.28; P = 0.18) between Tamponade group and non-Tamponade group were similar.ConclusionsVitrectomy with internal limiting membrane peeling could contribute to better resolution of myopic foveoschisis than non-peeling, however it does not significantly influence the proportion of visual acuity improvement and postoperative complications. Vitrectomy with gas tamponade is associated with more complications than non-tamponade and does not significantly influence the proportion of visual acuity improvement and resolution of myopic foveoschisis.

BackgroundX-linked juvenile retinoschisis (XLRS) is an inherited disease caused by RS1 gene mutation, which leads to retinal splitting and visual impairment. The mechanism of RS1-associated retinal degeneration is not fully understood. Besides, animal models of XLRS have limitations in the study of XLRS. Here, we used human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) to investigate the disease mechanisms and potential treatments for XLRS.MethodshiPSCs reprogrammed from peripheral blood mononuclear cells of two RS1 mutant (E72K) XLRS patients were differentiated into ROs. Subsequently, we explored whether RS1 mutation could affect RO development and explore the effectiveness of RS1 gene augmentation therapy.ResultsROs derived from RS1 (E72K) mutation hiPSCs exhibited a developmental delay in the photoreceptor, retinoschisin (RS1) deficiency, and altered spontaneous activity compared with control ROs. Furthermore, the delays in development were associated with decreased expression of rod-specific precursor markers (NRL) and photoreceptor-specific markers (RCVRN). Adeno-associated virus (AAV)-mediated gene augmentation with RS1 at the photoreceptor immature stage rescued the rod photoreceptor developmental delay in ROs with the RS1 (E72K) mutation.ConclusionsThe RS1 (E72K) mutation results in the photoreceptor development delay in ROs and can be partially rescued by the RS1 gene augmentation therapy.