Genetic, morphological and electrophysiological findings in a patient with a rare pathogenic variant in the RS1 gene.

PURPOSE: In this study, we report a case of a young adult with X-linked juvenile retinoschisis (XLRS) with a rare pathogenic variant in the RS1 gene (c.522 + 2 T > A). METHODS: Ophthalmological evaluation, optical coherence tomography, full-field and multifocal electroretinograms and extensive genetic screening of genes related to visual loss were carried out in the participant. RESULTS: Clinical ophthalmological exams revealed a mild to moderate impairment of visual acuity. Retinal imaging showed bilateral foveal schisis, as well as normal a-wave, reduction in the b-wave amplitudes in dark- and light- adapted full-field electroretinograms, and abnormal oscillatory potentials. We found also diffuse amplitude reduction in multifocal electroretinogram arrays. A canonical splice variant was identified in the RS1 gene (c.522 + 2 T > A). CONCLUSION: A rare pathogenic variant of the RS1 gene was associated with diffuse retinal involvement (central and peripheral retina), probably in inner retina, and mild to moderate visual acuity impairment. The phenotypical characterization of rare mutations is relevant to provide information about the disease.

A patient with X-linked retinoschisis and exudative retinal detachment associated with a pathogenic hemizygous variant c.304c>T in RS1.

BACKGROUND: X-linked retinoschisis (XLRS) is a rare retinal dystrophy due to pathogenic variants in the RS1 gene. The hallmark of the disease is a foveal spoke-wheel appearance. The purpose of this report is to expand the phenotypic spectrum of XLRS reporting a patient with atypical phenotype of XLRS associated with Coats-like phenotype. MATERIALS AND METHODS: This is a case report of a patient diagnosed with XLRS who underwent ophthalmologic multimodal imaging and next-generation sequencing panel. RESULTS: The proband is a 14-year-old male patient who presented at Instituto Suel Abujamra with a history of Coats Disease in the right eye treated with retinal laser in both eyes two years ago. His best-corrected visual acuity was count finger at 1 foot in the right eye and 20/40 in the left eye. Fundus exam showed an extensive area of exudation and retinal detachment in the right eye and cystic change at the fovea in a spoke-wheel pattern in the left eye. The next-generation sequencing panel targeting inherited retinal diseases with 236 genes found a pathogenic hemizygous variant c.304C>T (p.Arg102Trp) in RS1 that has already been reported. CONCLUSIONS: The association of peripheral vascular incompetence and XLRS has already been described. Retinal exudation in the setting of XLRS is probably the result of vascular disruption and compromise. The loss of retinoschisin function that leads to foveal retinoschisis may also lead to vascular anomalies.

STELLATE UNILATERAL NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS: A MULTIMODAL IMAGING ANALYSIS AND CASE REPORT.

PURPOSE: To describe a case of stellate nonhereditary idiopathic foveomacular retinoschisis in a middle-aged woman and to depict the classic retinal fluorangiography (FA) findings, structural characteristics using macular spectral-domain optical coherence tomography angiographic data of vascular and perfusion density using optical coherence tomography angiography (OCT-A), and standardized multifocal electroretinography (mfERG) findings. METHODS: This is a case report of a 53-year-old ophthalmologist who was incidentally diagnosed with unilateral idiopathic foveomacular retinoschisis. Stellate nonhereditary idiopathic foveomacular retinoschisis is defined as a foveal elevation without alternative explanation for retinoschisis. FA, spectral-domain optical coherence tomography, optical coherence tomography angiography, and multifocal electroretinography were used as tools to obtain an integral multimodal diagnosis of this entity. RESULTS: Clinical examination and multimodal imaging were able to detect unilateral idiopathic retinoschisis, revealing a stellate pattern of retinal concentric cysts with minimal changes in vascular and perfusion density metrics and confirming the absence of bridging vessels. There were consistent FA findings, with almost unaltered foveal changes. Multifocal electroretinography depicted a subtle reduction in dark-adapted a-wave and b-wave amplitudes. CONCLUSION: Improvements and innovations in technology for ophthalmic diagnosis have revolutionized our capacity for diagnostic decision-making. Spectral-domain optical coherence tomography and optical coherence tomography angiography are useful tools for diagnosis and follow-up assessment. This fortuitous case gives a window on the importance of a routine specialized ophthalmic examination and how multimodal imaging can depict important and specific findings not evident from a clinical point of view. The subtle but important changes observed in optical coherence tomography angiography and multifocal electroretinography will help better define this clinical entity.

VITRECTOMY FOR STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS ASSOCIATED WITH OUTER RETINAL LAYER DEFECT.

PURPOSE: To describe a case of stellate nonhereditary idiopathic foveomacular retinoschisis associated with outer retinal layer defect treated with pars plana vitrectomy, internal limiting membrane removal, and C3F8 tamponade. METHODS: Spectral-domain optical coherence tomography (Heidelberg Engineering, Heidelberg, Germany) scans of a 46-year-old woman with unilateral stellate nonhereditary idiopathic foveomacular retinoschisis were acquired at baseline and 1, 3, 6, and 12 months after surgery. RESULTS: Pars plana vitrectomy was performed after phacoemulsification. The vitreous was circumcised, and the internal limiting membrane was removed with a Tano brush, releasing tangential forces. The patient experienced progressive recovery of the outer retinal layers and improvement of visual acuity during follow-up. CONCLUSION: Stellate nonhereditary idiopathic foveomacular retinoschisis may be associated with outer retinal layer defect and severe vision loss. Pars plana vitrectomy with internal limiting membrane removal and C3F8 infusion seems to be a safe and feasible treatment in such cases, with potentially good anatomical and functional outcome.

Retinosquisis ligada al cromosoma X: presentación de un caso clínico y análisis del diagnóstico genético / X-linked Retinoschisis: a case report and genetic diagnosis analysis / Retinosquise ligada ao X: a presentação de um caso clínico e análise do diagnóstico genético

La Retinosquisis ligada al X, que se presenta fundamentalmente en varones, es una enfermedad genética caracterizada por agudeza visual reducida debido a degeneración macular. Su prevalencia es de 1/5000 varones en todo el mundo. Se manifiesta desde la primera década de la vida con pérdida de la visión que progresa hasta la adolescencia y se mantiene estable hasta la 4ta década de la vida, momento en que presenta un declive importante. El fondo de ojo suele mostrar esquisis. Las mujeres portadoras rara vez presentan síntomas. El gen involucrado es RS1, codifica para Retinosquina, proteína que participa en la integridad estructural y funcional de la retina. El mismo presenta diferentes mutaciones que generan pérdida de función de la proteína. La sospecha diagnóstica se basa en la clínica y los antecedentes familiares, y se apoya en la paraclínica confirmándose en la mayoría de los casos mediante secuenciación del gen. El tratamiento consiste en control periódico oftalmológico y cirugía de las complicaciones. Presentamos el caso de un niño de 2 años con episodios reiterados de desprendimiento de retina, con antecedentes familiares de Retinosquisis por línea materna en individuos de sexo masculino. Estos fueron estudiados demostrándose que son portadores de la variante probablemente patogénica c.466A>C (Arg156Gly) en el gen RS1 la cual había sido reportada previamente en una familia de origen chino. Se demostró que nuestro paciente presenta la mutación familiar en hemicigosis, por lo que esta es la segunda familia en que se confirma la segregación de esta variante con Retinosquisis.

X-linked Retinoschisis is a genetic disease characterized by reduced visual acuity mainly in men due to juvenile macular degeneration. Its prevalence is 1/5000 men worldwide. It manifests from the first decade of life with loss of vision that progresses to adolescence and then remains stable until the 4th decade of life, when it may present a significant decline. The fundus exam usually shows schism. Carrier women rarely have symptoms. The gene involved is RS1 (Xp22.13), which encodes for Retinoschisin, a protein that participates in the structural and functional integrity of the retina. In affected cases, mutations that generate loss of protein function were demonstrated. The diagnosis is based on the clinical and family history, and is supported by ophthalmology evaluation; in most cases it can be confirmed by sequencing of the gene. The treatment consists of periodic ophthalmological control and surgery of the complications. We describe the case of a 2 year old boy with repeated episodes of retinal detachment and who has a family history of Retinoschisis by maternal line in male individuals. These were studied, and it was shown that they are carriers of the probably pathogenic variant c.466A> C (Arg156Gly) in the RS1 gene, which had been reported previously in a family of Chinese origin. It was shown that our patient presents the family mutation in hemizygous state, so this is the second family in which the segregation of this variant with Retinoschisis is confirmed.

A retinosquise ligada ao X, que ocorre principalmente em homens, é uma doença genética caracterizada pela redução da acuidade visual devido à degeneração macular. Sua prevalência é de 1/5000 homens em todo o mundo. Manifesta-se desde a primeira década de vida com perda da visão que progride até a adolescência e permanece estável até a 4ª década de vida, época em que apresenta declínio significativo. O fundo geralmente mostra esquise. Portadoras do sexo feminino raramente apresentam sintomas. O gene envolvido é o RS1, que codifica a Retinosquina, proteína que participa da integridade estrutural e funcional da retina. Apresenta diferentes mutações que geram perda de função da proteína. A suspeita diagnóstica baseia-se na história clínica e familiar, e na paraclínica, sendo confirmada na maioria dos casos pelo sequenciamento gênico. O tratamento consiste em acompanhamento oftalmológico periódico e cirurgia para complicações. Apresentamos o caso de um menino de 2 anos com episódios repetidos de descolamento de retina, com história familiar de retinosquise materna no sexo masculino. Estes foram estudados mostrando que são portadores da variante provavelmente patogênica c.466A> C (Arg156Gly) no gene RS1, que havia sido relatado anteriormente em uma família de origem chinesa. Foi demonstrado que nosso paciente apresenta a mutação familiar em hemizigose, sendo esta a segunda família em que se confirma a segregação desta variante com Retinosquise.

Late ophthalmology findings in a X-linked juvenile retinoschisis patient / Achados oftalmológicos tardios em um paciente portador de retinosquise juvenil ligada ao cromossomo X

ABSTRACT X-linked juvenile retinoschisis (XLRS) is a vitreoretinal degeneration caused by mutations in the RS1 gene, generally characterized by bilateral maculopathy and peripheral retinoschisis leading to progressive visual loss during the first 2 decades of life and complications like retinal detachment and vitreous hemorrhage. Herein, we present late ophthalmology findings in a XLRS patient.

RESUMO A retinosquise juvenil ligada ao cromossomo X (XLRS) é uma degeneração vitreorretiniana causada por mutações no gene RS1, geralmente caracterizada por maculopatia bilateral e retinosquise periférica, levando à perda visual progressiva durante as primeiras 2 décadas de vida e complicações como descolamento de retina e hemorragia vítrea. Apresentamos aqui achados oftalmológicos tardios em um paciente com XLRS.

A hybrid coloboma and optic disc pit associated with macular retinoschisis.

BACKGROUND: To report and describe an unusual case of a patient with optic disc pit in one eye and optic disc coloboma with a focal pit associated with macular retinoschisis in the other eye. CASE PRESENTATION: A 21-year-old woman presented with optic disc pit in the right eye and optic disc coloboma with a focal pit like excavation in the left eye. Macular spectral domain optical coherence tomography (SD-OCT) of the left eye revealed macular retinoschisis, without serous detachment. CONCLUSIONS: Proper monitoring of patients with disc anomalies associated with maculopathy is mandatory. The use of OCT imaging during follow-up can help to identify involvement of the fovea or enlargement of the retinoschisis area.

Foveosquisis miópica asociada al Síndrome de Straatsma / Myopic foveoschisis associated with Straatsma's syndrome

RESUMEN Este reporte describe la presentación concomitante de foveosquisis miópica y fibras de mielina en una paciente con miopía elevada. La primera puede ser un hallazgo incidental, pero no infrecuente en pacientes con miopía elevada, y causa pérdida visual central severa. La segunda es infrecuente, y en casos muy raros se presenta asociada a miopía ipsilateral y estrabismo. Ambas entidades deben incluirse en el diagnóstico diferencial de un paciente alto miope con disminución de la visión central. La tomografía de coherencia óptica es el medio auxiliar de elección(AU)

ABSTRACT This case report describes the concomitant presentation of myopic foveoschisis and myelinated retinal nerve fibers in a patient with elevated myopia. The myopic foveoschisis may be an incidental but not uncommon finding in highly myopic eyes, leading to severe central vision loss. Myelinated retinal nerve fibers are infrequent and in rarely cases they are associated with ipsilateral myopia and strabismus. Both entities should be including as differential diagnosis of central vision loss in high myopia, and optic coherence tomography is the leading as auxiliary test(AU)

Retinosquise peripapilar e descolamento seroso de retina neuro-sensorial após esclerectomia profunda não penetrante / Peripapillary retinoschisis and serous detachment of neurosensory retina after a non-penetrating deep sclerectomy

Resumo Relato de caso de um paciente de 46 anos com glaucoma juvenil de controle clínico insatisfatório, portador de retinosquise peripapilar que, após ser submetido à esclerectomia profunda não penetrante, evoluiu com descolamento seroso da retina neuro-sensorial. A associação entre retinosquise peripapilar e o descolamento seroso pós cirurgia filtrante é de ocorrência rara, tendo sido descrito apenas um caso na literatura. A partir deste relato temos por objetivo, além de enfatizar a raridade da associação, mostrar a importância de investigar retinosquise peripapilar em pacientes glaucomatosos, em especial se associada a camada de fibras nervosas, e a importância da explanação adequada aos pacientes de um possível descolamento seroso de retina no pós-operatório de cirurgia filtrante.

Abstract Case report of a 46-year-old patient with unsatisfactory clinical controlled juvenile glaucoma and peripapillary retinoschisis who, after being submitted to non-penetrating deep sclerectomy, evolved with serous detachment of the neurosensory retina. The association between peripapillary retinoschisis and serous detachment after filtering surgery is rare and only one case has been described in the literature. The purpose of this report is, besides to emphasize the rarity of the association, to show the importance of investigating peripapillary retinoschisis in glaucomatous patients, especially if associated with retinal nerve fiber layer, and the importance of adequate explanation to patients of possible serous detachment of retina in the postoperative of filtering surgery.

En face and OCT angiography findings in macular retinoschisis

Abstract The diagnosis of macular retinoschisis is often complex and demands complementary exams to be confirmed. This is the report of a case of a 27 years old man diagnosed with macular retinoschisis, in which En face OCT and OCT angiography were used to identify and demonstrate the typical patterns of the disease, as well as distinguish them from the findings of cystoid macular edema.

Optical coherence tomography and congenital retinoschisis: three case reports / Tomografia de coerência óptica e retinosquise congênita: relato de três casos

Abstract Congenital retinoschisis is an X-linked recessive inherited disease. It causes the splitting of the retina's neurosensory layers from the remaining of the sensory retina, presenting itself as a "stellate" or "bicycle-wheel" maculopathy, vitreous hemorrhage and retinal detachment. We report three cases of congenital retinoschisis, two of them brothers. optical coherence tomography was used when evaluating the cases. It was impossible to differentiate retinoschisis from retinal detachment in one of the cases through optical coherence tomography due to lack of patient collaboration. We then performed laser photocoagulation to mark and follow-up the affected area.

Resumo A retinosquise congênita é uma doença autossômica recessiva ligada ao X. Resulta em separação da camada de fibras nervosas do restante da retina sensorial, e manifesta-se como maculopatia estriada, hemorragias vítreas e descolamento de retina. Relatamos três casos de retinosquise congênita, sendo dois deles irmãos. Utilizou-se a tomografia de coerência óptica na avaliação dos casos. Em um, não foi possível efetuar o diagnóstico diferencial com descolamento de retina através da tomografia de coerência óptica, devido a não cooperação no exame, optando-se pela realização de fotocoagulação com laser para demarcação e seguimento da área.

Retinosquise juvenil ligada ao X / X-linked juvenile retinoschisis

Relatar o caso de um paciente masculino de 28 anos que foi encaminhado ao Centro de Estudos e Pesquisas Oculistas Associados (RJ) para avaliação de retina e apresentou os achados típicos de retinosquise juvenil ligada ao cromossomo X: maculopatia cistóide com formação de cistos na fóvea e retinosquise periférica. Foi realizado o manejo conservador, com atenção para as complicações.

Report the case of a male 28 years-old patient, who was referred to Centro de Estudos e Pesquisas Oculistas Associados – RJ, to retina assessment and presented the tipical findings of the X-Linked Juvenile Retinoschisis: A cystoid maculopathy with formation of foveal cysts and schisis of the peripheral retina. It was carried out the conservative management, with attention to the complications.

Case report: pneumatic retinopexy for the treatment of progressive retinal detachment in senile retinoschisis.

Retinoschisis is an abnormal separation of the retinal layers and is asymptomatic in most cases. Enlargement of the area of retinoschisis and retinal tear and detachment are possible complications of the disease, and the treatment of retinoschisis is controversial. In this case report, we present a case of retinal detachment associated with senile retinoschisis in which pneumatic retinopexy was chosen as the treatment of choice and was performed successfully in one of the eyes. After a literature review on retinoschisis and pneumatic retinopexy for the treatment of associated retinal detachment, we found only one case that was successfully treated without drainage of subretinal fluid, using air as the filler. However, no previous reports have been found in the literature on the effectiveness of pneumatic retinopexy using C3F8 as the sole treatment for progressive retinal detachment in senile retinoschisis.

Case report: pneumatic retinopexy for the treatment of progressive retinal detachment in senile retinoschisis / Relato de caso: retinopexia pneumática no tratamento do descolamento de retina associado à retinosquise senil

Retinoschisis is an abnormal separation of the retinal layers and is asymptomatic in most cases. Enlargement of the area of retinoschisis and retinal tear and detachment are possible complications of the disease, and the treatment of retinoschisis is controversial. In this case report, we present a case of retinal detachment associated with senile retinoschisis in which pneumatic retinopexy was chosen as the treatment of choice and was performed successfully in one of the eyes. After a literature review on retinoschisis and pneumatic retinopexy for the treatment of associated retinal detachment, we found only one case that was successfully treated without drainage of subretinal fluid, using air as the filler. However, no previous reports have been found in the literature on the effectiveness of pneumatic retinopexy using C3F8 as the sole treatment for progressive retinal detachment in senile retinoschisis.

Retinosquise significa uma separação anormal das camadas da retina e, na maioria dos casos, é assintomática. Aumento da área de retinosquise, roturas e descolamento de retina são possíveis complicações da doença, sendo seus tratamentos controversos. Nesse relato, apresentamos um caso de descolamento de retina associado à retinosquise senil em que foi optado pela retinopexia pneumática como primeiro tratamento, com sucesso em um dos olhos tratados. Revisada literatura sobre retinosquises e retinopexia pneumática para tratamento de descolamento de retina associado, foi encontrado apenas um caso tratado com sucesso, sem drenagem de líquido sub-retiniano, utilizando-se ar como agente tamponante. Não existem relatos na literatura de retinopexia pneumática efetiva utilizando C3F8 como tratamento único para descolamento de retina progressivo na retinosquise senil.

Evaluación y conducta recomendada en presencia de precursores vítreorretinianos del desprendimiento de retina / Evaluation and recommended behavior in presence of vitreous retinal precursors of the retinal detachment

Los cambios y las variaciones anatómicas vítreorretinianas predisponen al desprendimiento de retina regmatógeno, por lo que su conocimiento es de vital importancia para el tratamiento adecuado de los pacientes. Por ello se decidió realizar una revisión acerca de los elementos más importantes al respecto, con el objetivo de actualizar los conocimientos existentes sobre el tema. Estos precursores comprenden tres entidades que, por su fisiopatología, pueden estar presentes en la historia natural de esta afección: Desprendimiento de vítreo posterior, degeneraciones periféricas y desgarro de retina (sintomáticos y asintomáticos). Además, algunas situaciones de riesgo como la cirugía de catarata, la capsulotomía posterior con YAG-láser, los traumatismos y la miopía alta pueden favorecer también al desprendimiento de retina. Estos precursores, por lo general, se hacen más evidentes después de los 40 años, sin predilección por sexo o características raciales y están muy relacionadas con cambios vítreos o su licuefacción. El conocimiento básico y actualizado de estas entidades, así como de los factores de riesgo asociados al desprendimiento de retina es importante para el adecuado manejo y el control de las complicaciones. En la revisión se describen con claridad los pilares fundamentales para el diagnóstico y tratamiento de este tipo de situaciones clínicas

The changes and the vitreous retinal anatomical variations predispose to rhegmatogenous detachment of the retina, so knowing them is very important for the adequate treatment of patients. Therefore, it was decided to make a review on the most important elements, with the objective of updating the existing pieces of knowledge on the topic. These precursors include three entities that, because of their physiopathology, can be present in the natural history of this illness: detachment of posterior vitreous, peripheral degeneration and retinal tear (symptomatic and asymptomatic). Additionally, some risk situations such as cataract surgery, posterior capsulotomy with YAG-laser, traumas and high myopia may also favor the retinal detachment. These precursors became more evident after the 40's, without sex or race preferences, and they are closely related to vitreous changes or to their liquefaction. The basic updated knowledge about these illnesses as well as the risk factors associated to the retinal detachment is important to adequate management and control of complications. The review clearly described the fundamental pillars in diagnosis and treatment of this type of clinical situations

Prevalence of macular anatomic abnormalities in high myopia.

BACKGROUND AND OBJECTIVE: Macular anatomic abnormalities in high myopia are more frequent in the presence of posterior staphyloma. The objective was to determine the prevalence of foveoschisis, foveal detachment, vascular traction, epiretinal membrane (ERM), and macular hole (MH) in eyes with high myopia by spectral-domain optical coherence tomography. PATIENTS AND METHODS: Prospective, observational study. Eyes with myopia greater than 8 diopters (D) were included. Results were analyzed using chi-square and Student's t tests. RESULTS: The study included 116 eyes of 72 patients. Mean spherical equivalent: -15.04 ± 5.33 D. Mean axial length: 28.88 ± 2.31 mm. Foveoschisis was observed in 17 eyes (14.65%), vascular traction in 17 (14.65%), ERM in 13 (11.2%), lamellar MH in two (1.72%), and posterior staphyloma in 41 (35.34%). Presence of foveoschisis, vascular traction, and ERM was more frequent in eyes with posterior staphyloma (P = .0001). CONCLUSION: Macular anatomic abnormalities were observed in 22.41% of eyes with high myopia and in 53.65% of eyes with posterior staphyloma.

Retinosquisis juvenil y su rehabilitación visual / Juvenile retinoschisis and its visual rehabilitation

La retinosquisis es una distrofia vitreorretiniana caracterizada por la separación de las capas de la retina y la formación de quistes intrarretinianos. En la retinosquisis juvenil se describen alteraciones oftalmológicas que la distinguen de la retinosquisis adquirida. Con el objetivo de describir las características clínicas de un caso atípico de retinosquisis juvenil se realizó el estudio de un paciente varón de 8 años de edad, quien acudió a consulta por disminución de la visión y la posibilidad de ayuda óptica. Al examen del fondo de ojo se visualizó una esquisis a nivel macular y periférica con edema de ambas máculas. El electrorretinograma presentó una disminución en la amplitud de la onda b. La tomografía de coherencia óptica reveló la separación de la retina interna a nivel de la capa de fibras nerviosas y el edema macular quístico. El tratamiento realizado fue la corrección y la ayuda ópticas para la visión cercana. Se concluye que se trata de una enfermedad infrecuente y, a su vez, de un caso atípico donde se imbricaron diversos signos que orientaban hacia las dos formas clínicas de la enfermedad, pero independientemente de que aparezcan características de retinosquisis adquirida en un paciente joven, el tratamiento de rehabilitación visual con ayuda óptica sigue siendo el más indicado para lograr una mayor calidad visual

The retinoschisis is a vitreoretinal dystrophy characterized by the separation of the retina layers and the formation of intraretinal cysts, In juvenile retinoschisis are described ophthalmologic alterations distinguished of the acquired retinoschisis. The objective of present paper was to conduct a study to describe the clinical features of an atypical case of juvenile retinoschisis of a male patient aged 8 who came to consultation due to a decrease of vision and the possibility of optical help. At eye examination it was visualized a schisis at macular level and peripheral with edema ob both maculae. The electroretinogram showed a decrease in the b-wave amplitude. The tomography of optical coherence demonstrated the separation of the internal retina at level of the nervous fibers and the cystic macular edema. Treatment consisted of correction and optical help to the close vision. We conclude that it is a uncommon disease and at the same time, of a atypical case where are overlapped different signs directed towards the two clinical ways of the disease, but independently that appear characteristics of acquired retinoschisis in a young patient, the treatment of visual rehabilitation with optical help remains the more prescribed to achieve a great visual quality