The multifocal electroretinogram in X-linked juvenile retinoschisis

To measure and compare the multifocal electroretinography in normal control and X-linked juvenile retinoschisis, 13 cases (13 right eyes) of normal control and nine cases (17 eyes) of X-linked juvenile retinoschisis were measured with VERIS Science 4.0. Four cases (eight eyes) out of the nine retinoschisis cases were tested with Ganzfeld ERG at the same day. The results showed statistically significant difference of average response densities and latencies in six ring retinal regions between the normal control and retinoschisis. The trace array and 3-D topography of multifocal ERG showed multi-area amplitude decrease with absence or reduction of central peak amplitude in patients with retinoschisis. The P₁/N₁ ratio of multifocal ERG average response densities in six ring retinal regions was different from the b/a ratio of Ganzfeld ERG. The multifocal ERG and Ganzfeld ERG each had its advantage in the diagnosis of retinoschisis.     

A carrier state of X-linked juvenile retinoschisis

The carrier state of X-linked juvenile retinoschisis has not been known to be associated with any fundus abnormalities. We report a case where there are funduscopic changes and mild visual acuity changes in one eye of a carrier.     

X连锁遗传性视网膜劈裂症的分子遗传学与治疗研究进展

X连锁遗传性视网膜劈裂症(XLRS,OMIM#312700)是一种较少见的X连锁隐性遗传病,主要累及双侧视网膜,造成神经纤维层和神经节细胞层之间的劈裂,患者具有典型的车轮状中心凹劈裂和视网膜电图b/a比值下降的特征性电生理改变,是由于XLRS1基因发生突变而导致的一种遗传性眼底疾病.就XLRS的发病机制、动物实验和临床治疗的研究进展进行综述.     

先天性视网膜劈裂发生严重并发症的手术疗效观察

目的:评价玻璃体视网膜手术治疗先天性视网膜劈裂症(X-linked congenital retinoschisis,XLRS)的有效性。方法:回顾性分析近年来我院手术治疗的出现严重并发症的XLRS患者,所有纳入研究的25例31眼患者术前OCT检查均存在黄斑区异常伴/不伴周边视网膜劈裂。我们根据患眼术前有无进行激光治疗将其分成A,B两组。A组15眼在术前已行视网膜激光治疗;B组16眼术前未行视网膜激光治疗。入组的全部31眼均行经扁平部玻璃体切割手术,内界膜剥除,气体或硅油填充。A组视术前光凝情况补/不补激光,B组均在注气或注油前行视网膜光凝治疗。术后随访3a,分析术后解剖复位情况和视功能结果。使用SPSS 13.0软件对手术前后平均视力数据进行统计分析,行配对t检验。A,B两组手术前后平均视力组间变化值差异,行单因素方差分析。结果:末次随访中,玻璃体积血者术后屈光间质透明,视网膜脱离者术后视网膜复位良好,视力提高者23眼,占所有病例74.2%;术后平均视力0.24±0.16,与治疗前平均视力(0.13±0.08)比较,差异具有统计学意义(t=-5.354,P=0.000)。A组平均视力由术前0.11±0.08提高至0.22±0.15(t=-4.391,P=0.000),B组由术前0.14±0.08提高到0.26±0.15(t=-4.488,P=0.000),差异均具有统计学意义。但比较两组的平均视力提高值,两组间手术前后变化无明显统计学差异(F=4.055,P=0.069)。随访期间有3眼出现并发症,1眼在术后3mo并发白内障,另2眼分别在术后10,12mo发生牵引性视网膜脱离。其中1眼发生于A组患者,2眼发生于B组患者,经再次手术,预后良好,且视网膜劈裂无明显进展。结论:玻璃体视网膜手术用于治疗先天性视网膜劈裂症眼后段并发症,能有效阻止劈裂腔进一步发展,有助于改善和稳定视功能,恢复视网膜解剖结构。     

X-linked retinoschisis maculopathy treated with topical dorzolamide, and relationship to genotype

Purpose

To correlate the response of topical dorzolamide (Trusopt; Merck) in patients with X-linked retinoschisis (XLRS) with genotype.

Methods

We carried out a retrospective evaluation of four patients (seven eyes) with XLRS, treated with topical dorzolamide. The change in best-corrected visual acuity (VA) and central macular thickness (CMT; central 1 mm subfield thickness) from optical coherence tomography (OCT) was analysed over the follow-up period, using Student''s t-test. Each patient also had genetic analysis for mutations in the retinoschisisgene (RS1).

Results

The mean age at the start of treatment was 14.7±11 years, and mean follow-up duration was 21.7±7.7 months. Mean CMT at the final follow-up was significantly better than at baseline (291±123 vs352±119 μm, P=0.007); however, mean VA was worse (0.38±0.25 vs0.31±0.24 logMAR score, P=0.041). All four patients had a mutation in the RS1gene; there was no apparent association between the type of mutation and the response to topical dorzolamide.

Conclusion

Topical dorzolamide may have some effect in reducing central macular thickness in patients with XLRS, but this does not necessarily correlate with improvement in VA. In our case series, genotypic information did not predict the response to this treatment.     

Evaluation of focal retinal function using multifocal electroretinography in patients with X-linked retinoschisis

Objective: To evaluate focal retinal function in patients presenting with features of X-linked retinoschisis (XLRS), with the use of multifocal electroretinography (mfERG).Design: Consecutive observational case-control study.Participants: Eighteen eyes of 9 patients who presented to the retina clinic of Sankara Nethralaya from 2005 to 2008.Methods: XLRS was diagnosed clinically and corroborated with full-field electroretinogram (ffERG), mfERG, and optical coherence tomography. ffERG and mfERG recordings were done with VERIS 5.2.2X according to International Society for Clinical Electrophysiology of Vision standards. The mfERG stimulus consisted of 103 hexagons flickered at a 75 Hz frame rate, subtended 35° horizontally and 31° vertically at a viewing distance of 53 cm. The amplitudes and implicit times of ffERG and first-order kernels of mfERG were analyzed and compared with those of the controls.Results: P1 and N1 amplitudes were reduced and P1 and N1 implicit times were prolonged significantly in patients with XLRS, compared with controls.Conclusions: mfERG helps estimate focal retinal function in patients with XLRS.     

Clinical observations of vitreoretinal surgery for four different phenotypes of X-linked congenital retinoschisis

AIM: To evaluate the outcomes of vitreoretinal surgery for four different phenotypes of X-linked retinoschisis (XLRS). METHODS: This study included thirty-one eyes of 25 patients who developed XLRS with severe complications. Among the 31 eyes, there were 7 eyes with vitreous hemorrhage, 8 eyes with retinal detachment and vitreous hemorrhage, and 16 eyes with rhegmatogenous retinal detachment. All of the patients underwent standard three-port pars plana vitrectomy. All of the eyes were divided into 4 groups before surgery according to a modified classification scheme, with the first three groups as follows: group A, with foveal cystic schisis; group B with macular lamellar schisis; and group C with foveolamellar changes. Peripheral schisis was not present in these 3 groups; however, group D was a complex group with both macular and peripheral changes. One year after surgery, we analyzed the best corrected visual acuity and postoperative anatomical and functional outcomes of these 4 groups. RESULTS: There were 7 eyes in group A (22.6%), 1 eye in group B (3.2%), 15 eyes in group C (48.4%) and 8 eyes in group D (25.8%). Postoperative anatomical and functional outcomes were satisfactory at the last visit, while the mean visual acuity was increased to 0.27±0.11, with a significant difference (t=-1.049, P=0.000) compared with the results before surgery (0.1±0.08). Visual acuity was improved in 23 eyes (74.2%). Complications were found in three eyes: two eyes with proliferative vitreoretinopathy and traction retinal detachment 10 and 12mo after surgery, respectively; and one eye with vitreous hemorrhage 15mo after surgery. These eyes were in groups C and D. The retinas remained attached in these 3 eyes after reoperation. CONCLUSION: We should pay greater attention to XLRS with foveolamellar changes because it is the most changeable phenotype. Once complications occur, vitreoretinal surgery can significantly improve visual acuity and restore the anatomic structure of the retina.     

X-linked juvenile retinoschisis: phenotypic and genetic characterization

Juvenile X-linked retinoschisis (XLRS, MIM#312700) belongs to a group of the vitreoretinal dystrophies. We aimed to describe the phenotype-genotype correlation of three XLRS cases in juveniles with different novel mutations from the Lithuanian population. The patients demonstrated macular retinoschisis and typical cyst-like cavities on spectral-domain optical coherence tomography (SD-OCT) images. The mean central foveal thickness was 569.7 μm. Two patients presented with peripheral retinoschisis. Flash electroretinogram demonstrated a reduced b/a ratio (<1.0) in all patients. RS1 (NM_000330.3) gene coding exons Sanger sequencing was performed. RS1 c.599G>T (p.R200L) mutation was detected in one case, showing to be pathogenic in silico analysis. c. (92_97) insC (p.W33fs) mutation was identified for another patient, indicating the variant is possibly damaging in silico analysis. The third case was identified with a pathogenic mutation c.422C>G (p.R141H), HGMD CM981753. These are the first cases of XLRS in the Lithuanian population confirmed by molecular genotyping. Presented patients had a different genotype but similar phenotypic traits.     

先天性视网膜劈裂症基因突变的分析

目的 研究先天性视网膜劈裂症（XLRS）家系的XLRS1基因突变情况及其发病机制，为建立基因诊断的方法提供理论依据。 方法 采用聚合酶链反应（PCR）和DNA直接测序方法对两个家系的XLRS1基因编码区进行突变的筛选及检测。 结果 在家系1中发现Pro193Ser突变。 结论 在XLRS家系中发现XLRS1基因突变。本研究结果可直接应用于XLRS 的遗传咨询和产前基因诊断。 （中华眼底病杂志，2004，20：149-151）     

The treatment of refractory angle-closure glaucoma in a patient with X-linked juvenile retinoschisis

X-Linked Retinoschisis (XLRS) is a common genetically determined form of macular degeneration affecting young males. XLRS is due to mutations in the RS1 gene located on chromosome Xp22 which codes for retinoschisin and is estimated to affect between 1:5000 to 1:20000 individuals worldwide.

We report a case of refractory angle-closure glaucoma in a thirty-nine-year-old Caucasian man with atypical XLRS. The patient presented with a two-day history of left eye pain, acutely reduced vision and a nine-month history of hemicranial pain. Examination identified left intraocular pressure (IOP) of 52mmHg. Gonioscopy confirmed complete angle closure.

Following failure of medical management and persistently raised left IOP (43-46mmHg), the patient underwent left phacoemulsification and intraocular lens insertion without complication. After surgery, his IOP reduced to 10-14mmHg on all follow up examinations without the need for glaucoma drops. His iridocorneal angle remained open and vision improved to 20/100.

Our case demonstrates the additional role of lens surgery in the treatment of secondary angle-closure glaucoma in the presence of an inherited retinal dystrophy. All patients with inherited retinopathy presenting with a headache or eye pain should undergo gonioscopic examination to exclude angle-closure glaucoma.     

Electrophysiological similarities between two eyes with X-linked recessive retinoschisis

Electroretinograms (ERG) and electro-oculograms (EOG) were studied in 88 eyes of 44 male patients with X-linked recessive retinoschisis. Differences of fundus appearance, ERG, and EOG between the eyes of each patient were analyzed. Fundus abnormalities were symmetrical in 77.3% of the cases. The amplitude of the ERG a-wave was normal in 26.1% and was abnormally low in 73.9%. The amplitude of the b-wave was below normal in all eyes; thus a small b-wave/a-wave ratio, which is characteristic of X-linked recessive retinoschisis, was observed in every case. The light peak to dark trough (LP/DT) ratio of the EOG was normal in 90.8% of the cases. The relative electrophysiological differences between the two eyes were calculated and showed that a-wave amplitude was not different between eyes in 75.0% of the cases; b-wave amplitude was not different in 77.3% of the cases; b-wave/a-wave ratio was symmetrical in 93.2% of the cases; and the LP/DT ratio was consistent between eyes in 86.8% of the cases. These results suggest that in most cases of X-linked recessive retinoschisis the fundus appearance, ERG, and EOG are similarly affected in both eyes of the patient.     

A novel mutation in the XLRS1 gene in a Korean family with X-linked retinoschisis

PURPOSE: To report a novel missense mutation in the XLRS1 gene in a Korean family with X-linked retinoschisis. METHODS: Observation case report of a family with a proband with X-linked retinoschisis underwent complete ophthalmologic examination. Genomic DNA was excluded from the family's blood and all exons of the XLRS1 gene were amplified by polymerase chain reaction and analyzed using a direct sequencing method. RESULTS: A novel Leu103Phe missense mutation was identified. CONCLUSIONS: A novel Leu103Phe mutation is an additional missense mutation which is responsible for the pathogenesis of X-linked retinoschisis.     

Molecular analysis of the XLRS1 gene in 4 females affected with X-linked juvenile retinoschisis

Background: X-linked juvenile retinoschisis (XLRS) is the most common cause of juvenile macular degeneration in males. Because of its X-linked mode of transmission, the disease is rare in females. In this article, we describe a mutation screen conducted on a family in which 4 female patients affected with XLRS presented with an unusually severe phenotype.Methods: DNA was extracted from peripheral blood, and the XLRSI gene was amplified on DNA samples of all the available family members. The mutation screen was conducted by performing direct DNA sequencing using an MJ Research PTC-225 Peltier Thermal Cycler.Results: A novel mutation, 588-593ins.C, was identified in exon 6 of the gene. The affected father was found to be heterozygous for the mutation, whereas all the female patients were homozygous for this mutation. The homozygosity of the mutation in the affected females led to severe phenotypes. The defective allele was expressed in infancy in 1 patient, whereas the disease manifested itself at variable ages in the other patients, reflecting a variation in the phenotype.Interpretation: This report describes a novel mutation in a family in which consanguinity has led to XLRS in 4 females. A variation in the phenotype of the disease is consistent with the published literature and suggests the involvement of genetic modifiers or environmental factors in influencing the clinical severity of the disease.     

Carbonic anhydrase inhibitors in patients with X-linked retinoschisis: effects on macular morphology and function

Background: Currently there is no medical treatment for X-linked retinoschisis (XLRS). In many retinal dystrophies, carbonic anhydrase inhibitors (CAIs) are effectively used to reduce cystoid macular edema. Prospective studies investigating the effect of CAIs in patients with XLRS are needed for the evaluation of their efficacy in this disease. The purpose of our work is to investigate the effects on macular morphology and function of oral CAIs used for the treatment of foveal lesions in patients with XLRS.

Methods: Nineteen patients with a clinical diagnosis of XLRS were enrolled and prescribed oral CAIs for six months. We evaluated the therapeutic effect of CAIs with: best-corrected visual acuity (BCVA), spectral-domain optical coherence tomography, microperimetry (MP) and multifocal electroretinography (mfERG).

Results: We observed a significant improvement of BCVA (p-value = 0.013), central retinal thickness (p-value = 0.004) and macular sensitivity (p-value<0.001). Moreover, in regards to mfERG responses, an increase of P1 wave amplitude was observed in three of the six rings.

Conclusions: Our data supports the efficacy of oral CAIs for the treatment of macular cyst-like lesions in XLRS patients. The recovery of a normal retinal anatomy by means of oral CAIs could be useful to create the optimal circumstances for gene therapy. The increase in macular sensitivity and in P1 wave amplitude confirmed that MP and mfERG provide with an unbiased and more sensitive understanding of how macular function may respond to the use of CAIs. Therefore, we recommend the use of MP and mfERG to assess the effect of therapy in XLRS.     

Surgical management of a large retinal cyst in X-linked retinoschisis with internal drainage: Report of an unusual case

Although X-linked retinoschisis is a common retinal degeneration condition, the presence of a large retinal cyst obscuring the visual axis in an infant is a rare presentation. Herein, we describe such a case of a child who presented to us with the diagnosis of retinal detachment in both the eyes. However, following multimodal imaging and electrophysiology, the child was found to have bilateral juvenile retinoschisis with a large retinoschisis cyst involving the visual axis seen intraoperatively in the left eye. A limbal approach followed by lensectomy was used to excise the inner retinal layer of the cyst. The intracystic fluid was then drained and the stretched retinal vessels were endocauterized and severed without causing any iatrogenic outer retinal breaks and retinal detachment. The correct diagnosis and meticulous preoperative planning of the surgical procedure helped us manage this challenging case with a favorable anatomical and functional outcome.     

中心性浆液性脉络膜视网膜病变的多焦视网膜电图改变

目的 测试并比较中心性浆液性脉络膜视网膜病变(CSCR)患者和正常人的多焦视网膜电图，探讨CSCR患者的视网膜功能。方法 应用EDI公司生产的VERIS系统对8例CSCR12只眼和14例正常人的16只眼进行检测，检测结果进行Mann—Whitney检验。结果 CSCR患者1环、2环的P1波反应密度下降，与正常对照组相比差异有显著性意义。结论 多焦视网膜电图可对CSCR患者的视功能进行定量检测且具有较好的重复性。     

Multifocal electroretinograms in X-linked retinoschisis

PURPOSE: To study local retinal cone function in patients with X-linked retinoschisis (XLRS) by multifocal ERGs (mfERGs). METHODS: mfERGs were recorded from seven eyes of seven patients with XLRS (mean age +/- SD, 22.1 +/- 3.2 years; range, 18 to 25 years). Five eyes had microcystic changes in the macula and two eyes had nonspecific macular degeneration. Two eyes had peripheral retinoschisis, and some of the stimuli fell on this area. The stimulus array consisted of 103 hexagons and the total recording time was set at approximately 4 minutes. The amplitudes and implicit times of both focal and summed responses for the first- and second-order kernels were analyzed. RESULTS: The amplitudes of the first-order kernel were markedly reduced in the central retina in all eyes. A large variation was observed in the amplitudes outside the fovea. The amplitudes of the focal cone ERGs at the peripheral retinoschisis did not differ from those recorded from adjacent retinal loci without the retinoschisis. The implicit times of the first-order kernel were significantly delayed, and the amplitudes of the second-order kernels were more affected than the first-order kernels across the whole field in all XLRS eyes. CONCLUSIONS: The cone-mediated retinal responses were more impaired in the central than peripheral retina in eyes with XLRS. Delayed implicit times of the first-order kernel and reduced second-order kernel across the whole testing field in all XLRS eyes suggest that there is widespread cone-system dysfunction in XLRS.     

Genotypic and phenotypic spectrum of X-linked retinoschisis in Australia

BACKGROUND: X-linked retinoschisis (XLRS), an X-linked recessive inherited degenerative retinopathy, is characterized by splitting in the nerve fibre layer and is caused by alterations in the RS1 gene. The aim of the present study was to review both the phenotypic features of XLRS and the mutation spectrum of the RS1 gene in an Australian cohort. METHODS: Patients were recruited from ophthalmic and paediatric hospitals as well as private ophthalmic clinics across Australia. A cohort of 18 presumably unrelated families was identified. Twenty-two affected patients underwent clinical examination. Following DNA extraction all six exons of the RS1 gene were sequenced. RESULTS: The median age at diagnosis was 8 years (range 1-43 years); the median age at review was 14 years (range 5-63 years). The median best-corrected visual acuity upon review was 6/24 (range 6/6-1/36). Typical foveal schisis was found in 90.1% eyes examined (39/43) while peripheral schisis was present in 30% of eyes (13/43). The scotopic blue b-wave amplitude ranged between 2% and 82% of the mean normal amplitude. Five novel mutations (61G-->T, Gly21X; 103C-->T, Gln35X; 327-329del, Cys110del; 527T-->C, Phe176Ser; 573Gdel, Pro192fs) and six previously identified missense mutations (304C-->T, Arg102Trp; 305G-->A, Arg102Gln; 336G-->C, Trp112Cys; 418G-->A, Gln140Arg; 598C-->T, Arg200Cys; 625C-->T, Arg209Cys) were found. The mutations present in codons 21 and 102 were each identified in two presumably unrelated pedigrees. One previously described point deletion (416Adel) was identified. Two pedigrees contained affected individuals where exons 2 or 3, respectively, were unable to be amplified, indicating the likely presence of a significant deletion. No mutation was found in the RS1 gene in two affected individuals from different pedigrees. CONCLUSION: Population genetic studies of XLRS have not previously been conducted in Australia. The phenotype associated with these mutations varied. The identification of each pedigree's specific mutation allows future determination of female carrier status for genetic counselling purposes. Further study into the refinement of the XLRS phenotype as well as the degree of intrafamilial phenotypic variation is required.     

Neovascular Glaucoma in a Patient with X-linked Juvenile Retinoschisis

Purpose: To report the rubeosis iridis and neovascular glaucoma findings in one patient of X-linked juvenile retinoschisis(XLRS). Methods: Color fundus photography, fluorescein angiography (FFA), OCT and B-scan were performed in a patient with X-linked juvenile retinoschisis complicated with neovascular glaucoma. Result: Color fundus photography, fluorescein angiography (FFA), OCT and B-scan unveiled a rare condition of XLRS complicated with neovascular glaucoma. Conclusion: XLRS may complicate with neovascular glaucoma. It is necessary to test OCT, FFA, ERG and carefully examine the fundus of the follow eye when it comes to uncertain neovascular glaucoma of youth and child. And only in this way, can we exclude XLRS. Eye Science 2005; 21:140-141.     

Diurnal variations of foveoschisis by optical coherence tomography in patients with RS1 X-linked juvenile retinoschisis

Background: To evaluate diurnal variations in macular schisis cavities in patients with X-linked juvenile retinoschisis (XLRS) with pathogenic variants in the RS1 gene using spectral-domain optical coherence tomography (SD-OCT).

Methods: Three consecutive patients with a clinical diagnosis of XLRS and pathogenic variants in the RS1, treated with carbonic anhydrase inhibitors (CAIs).

Observational procedures: SD-OCT scans of the macula were acquired at 9 a.m., 1 p.m., and 4 p.m. within 24 h.

Results: All patients demonstrated increased measures of central foveal thickness in the morning with gradual decrease through the day (9–43%). Major changes were observed between 9 a.m. and 1 p.m. in the central foveal thickness.

Conclusion: The central foveal thickness varies during daytime hours in patients with XLRS. This finding may explain the inconsistent and heterogeneous responses to treatment with CAIs and necessitate standardization of measurement times in treatment trials for XLRS as well as in the routine ophthalmic evaluation of these patients.