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Cold Spring Harbor Perspectives in... Sep 2023X-linked retinoschisis (XLRS) is an inherited vitreoretinal dystrophy causing visual impairment in males starting at a young age with an estimated prevalence of 1:5000... (Review)
Review
X-linked retinoschisis (XLRS) is an inherited vitreoretinal dystrophy causing visual impairment in males starting at a young age with an estimated prevalence of 1:5000 to 1:25,000. The condition was first observed in two affected brothers by Josef Haas in 1898 and is clinically diagnosed by characteristic intraretinal cysts arranged in a petaloid "spoke-wheel" pattern centered in the macula. When clinical electroretinogram (ERG) testing began in the 1960s, XLRS was noted to have a characteristic reduction of the dark-adapted b-wave amplitude despite normal or usually nearly normal a-wave amplitudes, which became known as the "electronegative ERG response" of XLRS disease. The causative gene, , was identified on the X-chromosome in 1997 and led to understanding the molecular and cellular basis of the condition, discerning the structure and function of the retinoschisin protein, and generating XLRS murine models. Along with parallel development of gene delivery vectors suitable for targeting retinal diseases, successful gene augmentation therapy was demonstrated by rescuing the XLRS phenotype in mouse. Two human phase I/II therapeutic XLRS gene augmentation studies were initiated; and although these did not yield definitive improvement in visual function, they gave significant new knowledge and experience, which positions the field for further near-term clinical testing with enhanced, next-generation gene therapy for XLRS patients.
Topics: Male; Humans; Animals; Mice; Retinoschisis; Mutation; Electroretinography; Phenotype; Genetic Therapy; Eye Proteins; Retina
PubMed: 36690462
DOI: 10.1101/cshperspect.a041288 -
Advances in Experimental Medicine and... 2018X-linked juvenile retinoschisis (XLRS) occurs exclusively in males and is characterized by visual loss that begins in early childhood; patients are usually school-age... (Review)
Review
X-linked juvenile retinoschisis (XLRS) occurs exclusively in males and is characterized by visual loss that begins in early childhood; patients are usually school-age and are experiencing visual disturbances, especially in reading. The prevalence is estimated to be 1 in 5000-25,000 men, worldwide. XLRS has complete penetrance but variable expressivity. Carrier females generally remain asymptomatic.
Topics: Child; Child, Preschool; Female; Genetic Diseases, X-Linked; Humans; Male; Retinoschisis
PubMed: 30578483
DOI: 10.1007/978-3-319-95046-4_10 -
Indian Journal of Ophthalmology Oct 2019
Topics: Humans; Male; Middle Aged; Ophthalmoscopy; Retina; Retinoschisis; Visual Acuity
PubMed: 31546543
DOI: 10.4103/ijo.IJO_193_19 -
Asia-Pacific Journal of Ophthalmology... 2018We present an updated clinical review of the pathophysiology, progression, and current treatments in pediatric patients with congenital X-linked retinoschisis (CXLRS).... (Review)
Review
We present an updated clinical review of the pathophysiology, progression, and current treatments in pediatric patients with congenital X-linked retinoschisis (CXLRS). CXLRS is an X-linked inherited retinal degeneration characterized by splitting of the superficial layers of the retina. Most recent classification divides CXLRS into 4 distinct clinical phenotypes: type 1, foveal; type 2, foveolamellar; type 3, complex; and type 4, foveoperipheral. The majority of retinoschisis cavities remain stable throughout life and may spontaneously collapse. However, a select number of patients progress to macula-involving peripheral retinoschisis, rhegmatogenous, and combined tractional-rhegmatogenous detachments that require further intervention. Although several advances have been made over the past several decades, medical therapy remains limited to case series‒based carbonic anhydrase therapy and prophylactic laser retinopexy. Recent advances in genetic-based clinical trials with the retinoschisis gene are promising. Vitreoretinal surgical approaches remain complex, case-based, and require careful planning depending on the configuration and location of the retinoschisis cavity.
Topics: Diagnostic Imaging; Disease Management; Genetic Testing; Genetic Therapy; Humans; Retinoschisis
PubMed: 29633586
DOI: 10.22608/APO.201803 -
Survey of Ophthalmology 2022Degenerative retinoschisis is a common condition characterized by elevation of the inner layers of the peripheral retina. While uncomplicated retinoschisis (i.e., with... (Review)
Review
Degenerative retinoschisis is a common condition characterized by elevation of the inner layers of the peripheral retina. While uncomplicated retinoschisis (i.e., with no associated retinal layer breaks) is almost invariably a benign process, retinal detachment associated with isolated outer layer breaks (termed schisis-detachment) is fairly common. Historically, schisis-detachment has been treated with a variety of interventions, ranging from retinopexy to intraocular surgery. Based on published descriptions of the natural history of the disease, these interventions are likely unnecessary in many cases and may place the patient's vision at unnecessary risk. Progressive symptomatic schisis-related retinal detachment, on the other hand, is a vision threatening condition that requires intervention. While clinical examination remains the mainstay of diagnosis, recent advances in multimodal imaging can provide supplemental information in subtle cases and may prove valuable for long-term disease monitoring. When evaluating patients with peripheral retinal elevation, it is important for ophthalmologists to make an accurate diagnosis and to understand the risk-benefit ratio associated with intervention. Thus, we summarize the current literature on the natural history, clinical and imaging diagnosis, and surgical management of degenerative retinoschisis and its related complications.
Topics: Humans; Retina; Retinal Detachment; Retinal Perforations; Retinoschisis
PubMed: 34896193
DOI: 10.1016/j.survophthal.2021.12.004 -
Indian Journal of Ophthalmology Jan 2020
Topics: Adult; Eye Proteins; Humans; Male; Retina; Retinoschisis; Tomography, Optical Coherence
PubMed: 31856528
DOI: 10.4103/ijo.IJO_1521_19 -
Indian Journal of Ophthalmology Jul 2022
Review
Topics: Humans; Macular Degeneration; Retinoschisis; Visual Acuity
PubMed: 35791214
DOI: 10.4103/ijo.IJO_2090_21 -
Ophthalmic Genetics Feb 2023X-linked juvenile retinoschisis (×LRS) is an X-linked vitreoretinal degenerative disease that consists of variable phenotypes ranging from severe early-onset defects to... (Review)
Review
BACKGROUND
X-linked juvenile retinoschisis (×LRS) is an X-linked vitreoretinal degenerative disease that consists of variable phenotypes ranging from severe early-onset defects to subtle abnormalities diagnosed in elderly patients. XLRS is caused by a loss of function of the protein Retinoschisin (RS1), which is essential to preserve retinal integrity and function of photoreceptor-bipolar synapse. The literature data so far mostly agree on the absence of a clear genotype-phenotype correlation in XLRS. We reviewed clinical and molecular characteristics of a cohort of Italian pediatric XLRS patients to assess the presence of a correlation between genotype and phenotype severity.
MATERIALS AND METHODS
We retrospectively examined clinical and genetic features of a cohort of 27 XLRS patients. In this study we included patients with a diagnosis of XLRS confirmed by fundus photography, spectral domain optical coherence tomography, and molecular analysis and with an onset of less than 10 years of age. We sorted RS1 variants according to their effect of RS1 structure and function in three separate groups.
RESULTS
According to previous studies, we did not observe a conclusive genotype-phenotype correlation in our cohort; nevertheless, we noticed that patients harboring RS1 variants leading to RS1-secreted mutants show a more homogeneous phenotype, with an overall good visual acuity, compared to the other two groups.
CONCLUSIONS
Our data support the hypothesis that secretion profile of RS1 could influence the severity of the phenotype. More extensive and functional studies are needed to acquire notions in view of the opportunity of gene replacement therapy for XLRS patients.
Topics: Humans; Retinoschisis; Retrospective Studies; Electroretinography; Mutation; Phenotype; Genotype; Eye Proteins; Tomography, Optical Coherence
PubMed: 36377647
DOI: 10.1080/13816810.2022.2141790 -
Archivos de La Sociedad Espanola de... Dec 2022X-linked retinoschisis (XLR) is a cause of retinal degeneration that affects males at an early age. X-linked disorders classically affect only males. We present the case...
X-linked retinoschisis (XLR) is a cause of retinal degeneration that affects males at an early age. X-linked disorders classically affect only males. We present the case of a 10-year-old female with the full spectrum of the pathology. BCVA 0.7 OU. Optical coherence tomography (OCT) showed bilateral foveal alteration with cystic appearance. The genetic study identified the variant c.644A>T (p.Glu215Gly) in the RS1 gene in homozygosis, associated with retinoschisis with X-linked recessive mode of inheritance. XLR is a condition that has a great variety in the severity of the disease and there is no correlation between the latter and the progression of the pathology. The disease has been described in a limited number of females mainly in families with high degree of consanguinity.
Topics: Male; Female; Humans; Child; Retinoschisis; Fovea Centralis; Tomography, Optical Coherence
PubMed: 36341910
DOI: 10.1016/j.oftale.2022.09.002 -
International Ophthalmology Clinics Oct 2021
Topics: Eye Proteins; Genetic Therapy; Humans; Retinoschisis; Tomography, Optical Coherence
PubMed: 34584055
DOI: 10.1097/IIO.0000000000000373