The Natural History of Congenital X-Linked Retinoschisis and Conversion between Phenotypes over Time.

PURPOSE: To evaluate the natural history of congenital X-linked retinoschisis (CXLRS) and to assess disease stability or progression over time. DESIGN: Retrospective case series at a single-center, tertiary care, pediatric retina practice. PARTICIPANTS: One hundred two eyes of 51 patients with CXLRS. METHODS: The clinical examinations, fundus photographs, and OCT images of all patients with CXLRS were assessed. Eyes that initially demonstrated combined retinoschisis-retinal detachments and those with large, centrally overhanging schisis cavities were excluded from the analysis (n = 49) because they underwent surgery, which precluded observation of the natural disease course. MAIN OUTCOME MEASURES: Stability or conversion of CXLRS phenotype over time. RESULTS: Fifty-three eyes met inclusion criteria for observation of natural disease history over time. At the time of diagnosis, 7.5% of eyes showed type 1 disease (n = 4), 17% showed type 2 disease (n = 9), 66% showed type 3 disease (n = 35), and 9.5% showed type 4 disease (n = 5). Mean length of follow-up was 7.4 years. A total of 7.5% of eyes demonstrated a combined retinoschisis-retinal detachment requiring surgery (n = 4), whereas 1.8% demonstrated a large, centrally overhanging schisis cavity requiring surgery (n = 1). Overall, 83% of eyes (n = 44) remained the same type without conversion or development of a complication requiring surgery. The remaining 17% of eyes (n = 9) experienced some type of change from their baseline diagnosis, with 7.5% (n = 4) converting between phenotypes and 9.5% (n = 5) demonstrating a complication requiring surgery; 3.75% of eyes (n = 2) converted from type 2 to 3 and 7.5% of eyes (n = 4) converted from type 3 to a combined retinoschisis-retinal detachment with mean time to conversion of 4.07 years. CONCLUSIONS: This longitudinal study conveyed the natural history of CXLRS. Congenital X-linked retinoschisis displayed long-term stability in 83% of eyes with conversion or progression of the disease to a more severe phenotype in the remaining cases. Type 3 CXLRS was a risk factor for the development of a combined retinoschisis-retinal detachment and may benefit from closer follow-up.

Congenital X-Linked Retinoschisis: An Updated Clinical 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.

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.

Different foveal schisis patterns in each retinal layer in eyes with hereditary juvenile retinoschisis evaluated by en-face optical coherence tomography.

PURPOSE: To analyze the structures of schisis in eyes with hereditary juvenile retinoschisis using en-face optical coherence tomography (OCT) imaging. METHODS: In this retrospective observational study, we reviewed the medical records of patients with hereditary juvenile retinoschisis who underwent comprehensive ophthalmic examinations including swept-source OCT. RESULTS: OCT images were obtained from 16 eyes of nine boys (mean age ± standard deviation, 10.6 ± 4.0 years). The horizontal OCT images at the fovea showed inner nuclear layer (INL) schisis in one eye (6.3 %), ganglion cell layer (GCL) and INL schisis in 12 eyes (75.0 %), INL and outer plexiform layer (OPL) schisis in two eyes (12.5 %), and GCL, INL, and OPL schisis in one eye (6.3 %). En-face OCT images showed characteristic schisis patterns in each retinal layer, which were represented by multiple hyporeflective holes in the parafoveal region in the GCL, a spoke-like pattern in the foveal region, a reticular pattern in the parafoveal region in the INL, and multiple hyporeflective polygonal cavities with partitions in the OPL. CONCLUSIONS: Our results using en-face OCT imaging clarified different patterns of schisis formation among the GCL, INL, and OPL, which lead to further recognition of structure in hereditary juvenile retinoschisis.

COMPLICATED CONGENITAL RETINOSCHISIS.

PURPOSE: To describe the treatment and natural history of a patient with complicated congenital retinoschisis. METHODS: A retrospective case report. A 10-month-old boy with congenital retinoschisis presented with tractional retinal detachments and foveal schisis in both eyes. RESULTS: On presentation, vision was decreased in both eyes with presumed amblyopia of the left eye. Funduscopic examination revealed bilateral foveal schisis and tractional retinal detachment involving the macula. Follow-up examination revealed superior retinal dragging and peripheral ischemia on fluorescein angiogram in both eyes. Nine months after presentation, combined rhegmatogenous and tractional retinal detachment developed in the right eye and was treated by scleral buckle. After vitrectomy for nonclearing vitreous hemorrhage in the left eye, a combined rhegmatogenous and tractional retinal detachment developed. Vitrectomy and lensectomy with silicone oil was performed. At 6 years of follow-up, both retinas were attached and foveal schisis had resolved. CONCLUSION: Sight threatening complications of congenital retinoschisis include retinal detachment and vitreous hemorrhage. Vitrectomy and/or scleral buckling may prevent progression of vision loss and promote resolution of schisis.

Surgical treatment for complications of congenital retinoschisis.

This study examined the clinical features of complications of congenital retinoschisis and the clinical efficacy of vitreoretinal surgery in the treatment of these complications. The clinical efficacy of surgical treatments was retrospectively analyzed in 10 patients with congenital retinoschisis (10 eyes) complicated with rhegmatogenous retinal detachment (n=5), vitreous hemorrhage (n=2) and macula- involving schisis (n=1). All the patients suffered foveal and peripheral schisis. They were treated with scleral buckling (n=1) or vitrectomy (n=9). After the surgical treatment, the retina was reattached in patients with rhegmatogenous retinal detachment; the refractive media became transparent in those with vitreous hemorrhage; the visual acuity in 80% of patients was improved; no remarkable progression of schisis was found; no severe operative complications occurred. It was concluded that vitreoretinal surgery in the treatment of complications of congenital retinoschisis is safe and effective, and helps improve and maintain the visual function.

Analysis of optic coherence tomography for congenital macular retinoschisis.

PURPOSE: To investigate the pathological characteristics of congenital macular retinoschisis by optic coherence tomography (OCT). METHODS: The data of 7 cases (14 eyes) with congenital macular retinoschisis were collected. Electroretinogram (ERG), fundus fluorecein angiography (FFA) and OCT examination were performed, respectively. RESULTS: The OCT images showed schisis cavity in all eyes. Schisis was confined to the fovea and parafovea in 2 eyes (1 patient). Schisis was involved in entire macular area in 12 eyes (6 patients). Inner nuclear layer (INL) schisis was seen in all eyes. Schisis was located at both INL and outer nuclear layer (ONL)/outer plexiform layer (OPL) in 2 of the 14 eyes. Besides the schisis cavity, small cysts within ganglion cell layer were found in 3 eyes. The small cysts were confined to parafoveal area. The OCT images of both eyes in one patient were similar but not exactly the same or symmetrical. CONCLUSION: Morphology, extension and schisis location in congenital macular retinoschisis have respective diversity.

Long-term 12 year follow-up of X-linked congenital retinoschisis.

PURPOSE: To investigate the retinal structure and function during the progression of X-linked retinoschisis (XLRS) from childhood to adulthood. METHODS: Ten patients clinically diagnosed with XLRS were investigated at 6-15 years of age (mean age 9 years) with a follow-up 8 to 14 years later (mean 12 years). The patients underwent regular ophthalmic examination as well as testing of best corrected visual acuity (BCVA), visual field (VF) and assessment of full-field electroretinography (ERG) during their first visit. During the follow-up, the same clinical protocols were repeated. In addition, macular structure and function was examined with multifocal electroretinography (mfERG) and optical coherence tomography (OCT). The patients were 18-25 years of age (mean age 21 years) at the follow-up examination. All exons and exon-intron boundaries of RS1-gene were sequenced for gene mutations in 9 out of the 10 patients. RESULTS: Best corrected VA and VF were stable during this follow-up period. No significant progression in cone or rod function could be measured by full-field ERG. Multifocal electroretinography and OCT demonstrated a wide heterogeneity of macular changes in retinal structure and function at the time of follow-up visit. Three different mutations were detected in these nine patients, including a known nonsense mutation in exon 3, a novel insertion in exon 5 and an intronic mutation at 5' splice site of intron 3. CONCLUSIONS: Clinical follow-up (mean 12 years) of ten young XLRS patients (mean age of 9 years) with a typical congenital retinoschisis phenotype revealed no significant decline in retinal function during this time period. MfERG and OCT demonstrated a wide variety of macular changes including structure and dysfunction. The XLRS disease was relatively stable during this period of observation and would afford opportunity for therapy studies to judge benefit against baseline and against the fellow eye.

Diagnosis and pathogenesis of congenital X-linked retinoschisis with optical coherence tomography.

This study shows how optical coherence tomography has been valuable in the diagnosis of congenital X-linked retinoschisis. An infant with convergent strabismus underwent serial optical coherence tomography examinations that helped to make the diagnosis of congenital X-linked retinoschisis. Optical coherence tomography is useful in the diagnosis of congenital X-linked retinoschisis and adds new information about pathogenesis. The authors recommend the use of optical coherence tomography in pediatric retinal disease, even if the macula appears normal on indirect ophthalmoscopy.

Elevated levels of cystatin C and tenascin-C in schisis cavities of patients with congenital X-linked retinoschisis.

PURPOSE: To describe the finding of tenascin C and cystatin-C in the intraschisis cavities of pediatric patients with intraretinal schisis cavities. METHODS: Three patients with congenital X-linked retinoschisis (CXLRS) and one girl with clinical retinoschisis underwent vitrectomy for vision-threatening schisis cavities. At the time of surgery undiluted samples of intraschisis fluid and vitreous fluid from four eyes (three male and one female) were obtained and analyzed by gel electrophoresis and protein sequencing for the presence of tenascin C and cystatin-C. RESULTS: Tenascin C and cystatin-C were found in all four samples of fluid from the intraschisis cavities, including a girl with a clinical presentation of CXLRS. The vitreous samples did not have detectable levels of either protein as determined by gel electrophoresis. CONCLUSIONS: Tenascin C and cystatin-C levels are elevated in intraschisis cavity fluid. Interestingly, this was also found in a girl not carrying a mutation in the retinoschisin gene, indicating that elevated concentrations of tenascin C and cystatin-C result from pathologic changes in the retina and not from the presence of aberrant retinoschisin.

Intraschisis cavity fluid composition in congenital X-linked retinoschisis.

PURPOSE: To describe the intraschisis cavity protein composition in congenital X-linked retinoschisis (CXLRS) from two eyes of one child. METHODS: The authors present a child with complex, Type 3 CXLRS who underwent bilateral surgical repair with autologous plasmin enzyme-assisted lens-sparing vitrectomy. Undiluted samples of intraschisis fluid and vitreous fluid from two eyes (one child) were obtained and used for protein analysis. RESULTS: The patient underwent successful schisis repair with plasmin-assisted lens-sparing vitrectomy and silicone oil. Two unique protein bands were identified in the intraschisis cavity sample of each eye by gel electrophoresis. The proteins were identified as tenascin-C, an extracellular matrix protein involved in wound healing, and cystatin C, a ubiquitous cysteine protease inhibitor implicated in inflammation. CONCLUSIONS: Tenascin-C has previously been described in its complex relationship with decorin and fibronectin in normal wound healing. Tenascin's upregulation in sites of inflammation and tenascin's role as an antiadhesive molecule may contribute to the pathogenesis of CXLRS. To the authors' knowledge, this is the first description of intraschisis cavity fluid.

Congenital retinoschisis: successful collapse with photocoagulation.

We report a case of progressive congenital retinoschis is where the schisis cavity collapsed following argon laser photocoagulation. Despite reports to the contrary, we feel that in the absence of significant vitreous or inner layer traction, photocoagulation applied as light burns in the schisis cavity may be beneficial in collapsing the cavity. Whether or not this collapse of the schisis cavity reduces the risk of rhegmatogenous retinal detachment is unclear.