The electrophysiological features of X-linked juvenile retinoschisis in a young male: a case report

This case report describes the detailed electrophysiological features and the corresponding relationship with the structural changes in a case of X-linked juvenile retinoschisis (XLRS). A 25-year-old male presented with a history of several years of decreased visual acuity in both eyes. The best corrected visual acuity was 20/200 in oculus dexter (OD) and 20/80 in oculus sinister. Retinoschisis was found in the macula by optical coherence tomography, which was more severe in OD. Electroretinogram revealed a similar electronegative waveform in both eyes. Visual evoked potential detected a reduced amplitude and delayed phase in P100-wave, which was worse in OD. The patient was diagnosed as XLRS and advised to undergo continuous medical observation. He was followed up for the next year, with no significant change in retinal function and structure being observed. These current findings suggest that electrophysiology permits the detailed analysis of the clinical picture of XLRS and helps to gain a deeper understanding of the pathogenesis.

Clinical and Genetic Study of X-Linked Juvenile Retinoschisis in the Czech Population

The aim of this study was to identify RS1 pathogenic variants in Czech patients with X-linked retinoschisis (XLRS) and to describe the associated phenotypes, including natural history, in some cases. Twenty-one affected males from 17 families were included. The coding region of RS1 was directly sequenced and segregation of the identified mutations was performed in available family members. In total, 12 disease-causing variants within RS1 were identified; of these c.20del, c.275G>A, c.[375_379del; 386A>T], c.539C>A and c.575_576insT were novel, all predicted to be null alleles. The c.539C>A mutation occurred de novo. Three patients (aged 8, 11 and 19 years) were misdiagnosed as having intermediate uveitis and treated with systemic steroids. Repeat spectral domain optical coherence tomography examinations in four eyes documented the transition from cystoid macular lesions to macular atrophy in the fourth decade of life. Four individuals were treated with topical dorzolamide and in two of them, complete resolution of the cystic macular lesions bilaterally was achieved, while one patient was noncompliant. Rebound phenomenon after discontinuation of dorzolamide for 7 days was documented in one case. Misdiagnosis of XLRS for uveitis is not uncommon; therefore, identification of disease-causing variants is of considerable benefit to the affected individuals.

Rs1h−/y exon 3-del rat model of X-linked retinoschisis with early onset and rapid phenotype is rescued by RS1 supplementation

Animal models of X-linked juvenile retinoschisis (XLRS) are valuable tools for understanding basic biochemical function of retinoschisin (RS1) protein and to investigate outcomes of preclinical efficacy and toxicity studies. In order to work with an eye larger than mouse, we generated and characterized an Rs1h−/y knockout rat model created by removing exon 3. This rat model expresses no normal RS1 protein. The model shares features of an early onset and more severe phenotype of human XLRS. The morphologic pathology includes schisis cavities at postnatal day 15 (p15), photoreceptors that are misplaced into the subretinal space and OPL, and a reduction of photoreceptor cell numbers by p21. By 6 mo age only 1–3 rows of photoreceptors nuclei remain, and the inner/outer segment layers and the OPL shows major changes. Electroretinogram recordings show functional loss with considerable reduction of both the a-wave and b-wave by p28, indicating early age loss and dysfunction of photoreceptors. The ratio of b-/a-wave amplitudes indicates impaired synaptic transmission to bipolar cells in addition. Supplementing the Rs1h−/y exon3-del retina with normal human RS1 protein using AAV8-RS1 delivery improved the retinal structure. This Rs1h−/y rat model provides a further tool to explore underlying mechanisms of XLRS pathology and to evaluate therapeutic intervention for the XLRS condition.

Case series of clinical features in siblings with X-linked juvenile retinoschisis

X-linked juvenile retinochisis (XLRS) is a rare inherited bilateral vitreoretinal dystrophy which usually affects males early in life. We describe the clinical findings, outcome, and challenges in treatment of three siblings diagnosed with XLRS. Three siblings with ages ranging from 5 to 9 years old presented with reduced visual acuity (VA) and posterior segment showing varying degrees of vitreous veil and spoke-wheel maculopathy. Optical coherence tomography (OCT) of the macula was performed, revealing retinoschisis in all eyes. All three siblings were diagnosed with XLRS and were started on topical brinzolamide twice daily. OCT was repeated at 6 months and 18 months. At 18 months, three eyes showed stable VA and three eyes showed improved in VA. One out of the three eyes with stable VA showed improved retinoschisis while the other two eyes showed worsening retinoschisis. On the other hand, one out of the three eyes with improved VA had improved retinoschisis and the other two had worsening retinoschisis. We demonstrated that the VA of patients with retinoschisis is not directly proportional to the degree of splitting of the neurosensory retina. Retinoschisis treatment is challenging, as there is no one proven effective treatment up to date.

Optical coherence tomography analyses based segmentation and relative intensity evaluation of outer retinal layers in patients affected with X-linked juvenile retinoschisis

Purpose: We aim to provide a description of the optical coherence tomography findings in the outer macula hyperreflective bands of our patients with X-linked juvenile retinoschisis. Also to categorize these changes and to quantitatively and qualitatively correlate their reflectivity levels with visual function. Methods: We manually segmented the borders, and depicted relative intensity of the inner segment ellipsoid band, and quantified the volume of edema. Results: The average relative intensity of the ellipsoid zone, ISe band, for the control subject was 14.864, our patient’s, with the mild disease was, 28.238 and 34.943 in OD and OS, respectively, and for the patient with severe disease was, 44.442 and 40.154 for OD and OS respectively. Thresholding showed a significant difference in edema volume between mild disease (~20%), and severe form (~50%). Relative intensity analyses are indicative of homogeneity variability. High standard deviation value illustrates the high dispersion of data values and is a safe marker of ellipsoid zone homogeneity. Conclusion: Data suggested that both anatomic and functional characteristic of outer macula hyperreflective bands were notably associated with the pathogenesis cascade in the photoreceptor cells. External limiting membrane line disruption is initiated by the volume of macular edema and followed by disorganization of the three lines in a stepwise pattern, first at the ellipsoid zone, followed by the cone outer segment tips zone and finally at the External limiting membrane.

A case of X-linked juvenile retinoschisis in the outpatient settings

The article considers the case of observation of a child with X-linked hereditary retinoschisis in the outpatient settings. The differential diagnosis and treatment of X-linked retinoschisis is examined on the example of this child. The article reflects the clinical picture and diagnostic methods necessary for the diagnosis. Key words: X-linked juvenile retinoschisis, children, optical coherence tomography, electroretinogram.