BACKGROUND: X-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.
METHODS: hiPSCs 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.
RESULTS: ROs 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.
CONCLUSIONS: The RS1 (E72K) mutation results in the photoreceptor development delay in ROs and can be partially rescued by the RS1 gene augmentation therapy.

BACKGROUND: Macular retinoschisis (MRS) and myopic macular neovascularization (mMNV) are both potentially blinding complications of high myopia. In this case report, we highlight the progression of MRS after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for mMNV, as well as an extensive review of the literature on this topic.
METHODS: A 49-year-old woman presented with two weeks of recent onset blurring and metamorphopsia in her right eye. She had high myopia in both eyes (right eye - 20/60 with - 16D, left eye - 20/20 with - 13D). Slit-lamp ophthalmoscopy found a normal anterior segment in both eyes. On fundus examination, features of pathological myopia with posterior staphyloma and peripapillary atrophy were observed in both eyes. An active mMNV, as well as intraretinal fluid, minimal perifoveal inner and outer MRS, and focal posterior vitreous traction along the inferotemporal retinal arcade, were detected on optical coherence tomography (OCT) of the right eye. The patient received an intravitreal injection of Aflibercept (2 mg/0.05 ml).
RESULTS: OCT scans at two- and four-month follow-up visits revealed regressed mMNV with a taut epiretinal membrane, progressive worsening of outer MRS, and the development of multiple perifoveal retinal detachment inferior to the fovea. Pars plana vitrectomy surgery was performed for the progressive MRS with good anatomical (resolved MRS) and functional outcome (maintained visual acuity at 20/60) at the last one-month post-surgery visit.
CONCLUSIONS: Intravitreal anti-VEGF injections for mMNV can cause vitreoretinal interface changes, exacerbating MRS and causing visual deterioration. Vitrectomy for MRS could be one of several treatment options.

暂无摘要。

X-linked retinoschisis (XLRS) is a monogenic recessive inherited retinal disease caused by defects in retinoschisin (RS1). It manifests clinically as retinal schisis cavities and a disproportionate reduction of b-wave amplitude compared with the a-wave amplitude. Currently there is no approved treatment. In the last decade, there has been major progress in the development of gene therapy for XLRS. Previous preclinical studies have demonstrated the treatment benefits of hRS1 gene augmentation therapy in mouse models. However, outcomes in clinical trials have been disappointing, and this might be attributed to dysfunctional assembly of RS1 complexes and/or the impaired targeted cells. In this study, the human synapsin 1 gene promoter (hSyn) was used to control the expression of hRS1 to specifically target retinal ganglion cells and our results confirmed the specific expression and functional assembly of the protein. Moreover, our results demonstrated that a single intravitreal injection of rAAV2-hSyn-hRS1 results in architectural restoration of retinal schisis cavities and improvement in vision in a mouse model of XLRS. In brief, this study not only supports the clinical development of the rAAV2-hSyn-hRS1 vector in XLRS patients but also confirms the therapeutic potential of rAAV-based gene therapy in inherited retinal diseases.

BACKGROUND: Retinal cysts are rare lesions of the fundus that are essentially fluid-filled cavities located or originating in the retina, with a diameter larger than the normal retinal thickness. To date, there have been few case reports of giant retinal cyst hemorrhage with retinoschisis.
METHODS: A 32-year-old woman with no other medical history complained of decreased vision for 3 days after a severe cough. The best-corrected visual acuity in the right eye was 0.5. A comprehensive ophthalmological examination including slit-lamp fundoscopy, ultrasound scan of the eye, optical coherence tomography scan, and orbital magnetic resonance imaging was performed. Ophthalmological examination revealed grade III anterior chamber blood cells and grade III vitreous hemorrhage in the right eye and a large herpetic cyst on the nasal side of the retina. The cyst projected into the vitreous, with a large amount of hemorrhage vaguely visible within it. The cyst was clearly visible, and a superficial retinal limiting detachment was observed around it. Ultrasound showed a retinal cyst with retinal detachment in the right eye. Laboratory test results were unremarkable. After 3 months of conservative treatment, the patient\'s intracystic hemorrhage was significantly absorbed, but the size of the cyst cavity did not show any significant change. Scleral buckling with external compression combined with external drainage of the intracystic fluid was performed, the patient\'s visual acuity was gradually restored to a normal 1.0 after the operation, and the retina appeared flattened. The patient was finally diagnosed with a giant retinal cyst with retinoschisis in the right eye. The presumed cause was heavy coughing leading to rupture and hemorrhage of the retinal cyst, similar to the mechanism of rupture of an arterial dissection. To the best of our knowledge, this case of retinal cyst rupture and hemorrhage caused by heavy coughing with good recovery after external surgical treatment has never been reported before.
CONCLUSIONS: Giant cystic retinal hemorrhage with retinoschisis is very rare. Orbital magnetic resonance imaging and ocular B-scan ultrasound are essential for its diagnosis, and the selection of an appropriate surgical procedure is necessary to maximize the benefit for affected patients.

OBJECTIVE: To utilize ultra-widefield multimodal imaging (Optos PLC) to describe novel findings in degenerative retinoschisis.
METHODS: This retrospective, non-comparative case series of degenerative retinoschisis received a waiver of consent from Advarra IRB, Protocol 00066379. Initial ultra-widefield pseudocolour, colour-separated, autofluorescence, and peripheral OCT imaging were analysed for characterizing features.
RESULTS: In total, 139 eyes were included. A hyporeflective reticular pattern associated with retinoschisis was seen on pseudocolour images in 39% of cases, but visible in 53% on green-separated images. Fine hyper-reflective foci were observed in 49%. In 27%, retinoschisis was confirmed with OCT.
CONCLUSIONS: Ultra-widefield pseudocolour and green-separated images are valuable for the diagnosis and characterization of degenerative retinoschisis. The findings described may prompt the evaluation of subtle retinoschisis with peripheral OCT.

X-linked retinoschisis (XLRS) is an early onset degenerative retinal disease characterized by cystic lesions in the middle layers of the retina. These structural changes are accompanied by a loss of visual acuity and decreased contrast sensitivity. XLRS is caused by mutations in the gene Rs1 which encodes the secreted protein Retinoschisin 1. Young Rs1-mutant mouse models develop key hallmarks of XLRS including intraretinal schisis and abnormal electroretinograms. The electroretinogram (ERG) comprises activity of multiple cellular generators, and it is not known how and when each of these is impacted in Rs1 mutant mice. Here we use an ex vivo ERG system and pharmacological blockade to determine how ERG components generated by photoreceptors, ON-bipolar, and Müller glial cells are impacted in Rs1 mutants and to determine the time course of these changes. We report that ERG abnormalities begin near eye-opening and that all ERG components are involved.

Aland island eye disease (AIED), an incomplete form of X-linked congenital stationary night blindness (CSNB2A), and X-linked cone-rod dystrophy type 3 (CORDX3) display many overlapping clinical findings. They result from mutations in the CACNA1F gene encoding the α1F subunit of the Cav1.4 channel, which plays a key role in neurotransmission from rod and cone photoreceptors to bipolar cells. Case report: A 57-year-old Caucasian man who had suffered since his early childhood from nystagmus, nyctalopia, low visual acuity and high myopia in both eyes (OU) presented to expand the diagnostic process, because similar symptoms had occurred in his 2-month-old grandson. Additionally, the patient was diagnosed with protanomalous color vision deficiency, diffuse thinning, and moderate hypopigmentation of the retina. Optical coherence tomography of the macula revealed retinoschisis in the right eye and foveal hypoplasia in the left eye. Dark-adapted (DA) 3.0 flash full-field electroretinography (ffERG) amplitudes of a-waves were attenuated, and the amplitudes of b-waves were abolished, which resulted in a negative pattern of the ERG. Moreover, the light-adapted 3.0 and 3.0 flicker ffERG as well as the DA 0.01 ffERG were consistent with severely reduced responses OU. Genetic testing revealed a hemizygous form of a stop-gained mutation (c.4051C>T) in exon 35 of the CACNA1F gene. This pathogenic variant has so far been described in combination with a phenotype corresponding to CSNB2A and CORDX3. This report contributes to expanding the knowledge of the clinical spectrum of CACNA1F-related disease. Wide variability and the overlapping clinical manifestations observed within AIED and its allelic disorders may not be explained solely by the consequences of different mutations on proteins. The lack of distinct genotype-phenotype correlations indicates the presence of additional, not yet identified, disease-modifying factors.

暂无摘要。

Objective: To investigate the efficacy of pars plana vitrectomy (PPV) without intraocular tamponade in the treatment of high myopic eyes with myopic foveoschisis (MF) accompanied by foveal detachment (FD). Methods: A retrospective case series study was conducted. The medical records of patients diagnosed with unilateral MF accompanied by FD at the Eye & ENT Hospital of Fudan University between May 2018 and December 2021 were collected. All patients underwent 23-gauge PPV with posterior vitreous cortex clearance, and no intraocular tamponade was applied. The cases were divided into groups based on whether the internal limiting membrane was peeled during surgery or retained. Follow-up was conducted for at least 12 months. The main outcome measures included postoperative best-corrected visual acuity (BCVA, converted to logarithm of the minimum angle of resolution), central foveal thickness (CFT), MF resolution, and complications. Statistical analyses were performed using t-tests, chi-square tests, Fisher\'s exact tests, and univariate and multivariate linear regression. Results: A total of 40 patients (40 eyes) with MF and FD were included in the study, with 30.0% being male and 70.0% female. The mean age was (56.9±11.7) years, and the axial length of the eyes was (29.1±1.9) mm. At 12 months postoperatively, BCVA improved from baseline 1.15±0.58 to 0.73±0.39 (t=6.11, P<0.001), and CFT decreased from baseline (610.1±207.2) μm to (155.9±104.1) μm (t=13.47, P<0.001). Complete resolution of MF with foveal reattachment was observed in 80.0% of eyes, with a median time of 6 (5, 8) months. There was no significant difference in BCVA and CFT between the internal limiting membrane peeled group and retained group [0.68±0.39 vs. 0.79±0.40, t=0.85, P=0.403; (148.3±63.8)vs.(164.3±137.2)um,t=0.48, P=0.634]. One eye experienced macular hole and another eye developed retinal detachment postoperatively. Correlation analysis showed a positive correlation between BCVA at 12 months postoperatively and baseline BCVA (β=0.433, P<0.001). Conclusions: Pars plana vitrectomy without intraocular tamponade is effective in treating MF accompanied by FD. The choice between internal limiting membrane peeling and retention does not significantly affect visual prognosis.
目的： 探讨不联合眼内填充的单纯玻璃体切除术治疗高度近视眼黄斑劈裂（MF）伴黄斑中心凹脱离（FD）的疗效。 方法： 回顾性病例系列研究。收集2018年5月至2021年12月在复旦大学附属眼耳鼻喉科医院诊断为单眼伴有FD的MF患者的病历资料。所有患者均行23G玻璃体切除术，术中清除玻璃体后皮质，所有患者均未进行眼内填充。根据术中是否剥除内界膜分为内界膜剥除组及内界膜保留组。术后至少随访12个月。主要评价指标为术后最佳矫正视力（BCVA，转换为最小分辨角的对数表示）、黄斑中心凹视网膜厚度（CFT）、MF愈合情况及并发症情况。采用t检验、卡方检验、Fisher精确检验、单因素线性及多因素线性回归分析进行统计学处理。 结果： 共40例（40只眼）MF伴FD的患者纳入研究，其中12例（30.0%）为男性，28例（70.0%）为女性；年龄为（56.9±11.7）岁，眼轴长度为（29.1±1.9）mm。术后12个月，BCVA由基线的1.15±0.58提高至0.73±0.39（t=6.11，P<0.001），CFT由基线的（610.1±207.2）μm下降至（155.9±104.1）μm（t=13.47，P<0.001），32只眼（80.0%）的视网膜劈裂完全恢复，劈裂完全好转所需的时间为6（5，8）个月。内界膜剥除组及内界膜保留组的BCVA（分别为0.68±0.39和0.79±0.40）及CFT［分别为（148.3±63.8）和（164.3±137.2）μm］差异无统计学意义（t=0.85，P=0.403；t=0.48，P=0.634）。术后分别有1只眼发生黄斑裂孔及视网膜脱离。相关性分析提示术后12个月BCVA与术前基线BCVA呈正相关（β=0.433，P<0.001）。 结论： 不联合眼内填充的单纯玻璃体切除术可有效治疗伴有FD的MF。内界膜剥除和保留的术式对视力预后影响无明显差别。.