Foveal Schisis Research Articles

Two macular holes due to choroidal neovascularization after pars plana vitrectomy with internal limiting membrane peeling

Introduction: To present a case of two macular holes (MHs) with myopic choroidal neovascularization (CNV) lesion. Case Presentation: A single case was evaluated. A 72-year-old woman presented with two small MHs in her left eye. One year ago, she had undergone vitrectomy for myopic foveal schisis, and a significant reduction of the schisis and a CNV lesion was observed after surgery. On examination, OCT (optical coherence tomography) showed the atrophic CNV and two MHs were located upper and lower close to the edge of the CNV. A PPV (pars plana vitrectomy) with two free ILM (internal limiting membrane) flaps implant was performed in her left eye. At 3 months after surgery, the two macular holes were both closed and the BCVA (best corrected visual acuity) was improved. Conclusions: Two MHs secondary to the regression of CNV after primary PPV combined with complete ILM peeling in eyes with macular schisis.

The features of dome-shape Macula and related complications in high myopia on optical coherence tomography.

This study used optical coherence tomography scanning and 3D reconstruction of the macular region in high myopia to examine more thoroughly and carefully the differences between high myopia-related macular complications with and without dome-shape macula (DSM) and to determine whether the DSM's fine structure has an effect on them. Retrospective analysis of the medical records of 345 eyes with high myopia who underwent an optical coherence tomography (OCT) examination. They were divided into the DSM group (69 eyes) and the group without DSM (276 eyes). Macular complications between the two groups were compared. The height of the DSM and the diameter of the dome base were measured. And then the association between DSM type, protrusion height and macular problems were analyzed. Epiretinal membrane (ERM) and extrafoveal schisis occurred more frequently in the DSM group, but the was no statistically significant difference in the frequency of foveal schisis between the two groups. The majority of eyes in the DSM categorization had a horizontal oval-shaped domain. In the DSM group, there was no evident difference in the percentage of eyes with macular complications in the groups below 150 um and above 150 um. OCT examination-based fine macular structure analysis reveals that DSM affects various macular problems in distinct ways. DSM could increase the risk of extrafoveal schisis and ERM while decreasing the risk of foveal schisis. The height of the DSM had no obvious impact on the prevalence of macular complications.

Single cell RNA sequencing confirms retinal microglia activation associated with early onset retinal degeneration

Mutations in the Membrane-type frizzled related protein (Mfrp) gene results in an early-onset retinal degeneration associated with retinitis pigmentosa, microphthalmia, optic disc drusen and foveal schisis. In the current study, a previously characterized mouse model of human retinal degeneration carrying homozygous c.498_499insC mutations in Mfrp (MfrpKI/KI) was used. Patients carrying this mutation have retinal degeneration at an early age. The model demonstrates subretinal deposits and develops early-onset photoreceptor degeneration. We observed large subretinal deposits in MfrpKI/KI mice which were strongly CD68 positive and co-localized with autofluorescent spots. Single cell RNA sequencing of MfrpKI/KI mice retinal microglia showed a significantly higher number of pan-macrophage marker Iba-1 and F4/80 positive cells with increased expression of activation marker (CD68) and lowered microglial homeostatic markers (TMEM119, P2ry13, P2ry13, Siglech) compared with wild type mice confirming microglial activation as observed in retinal immunostaining showing microglia activation in subretinal region. Trajectory analysis identified a small cluster of microglial cells with activation transcriptomic signatures that could represent a subretinal microglia population in MfrpKI/KI mice expressing higher levels of APOE. We validated these findings using immunofluorescence staining of retinal cryosections and found a significantly higher number of subretinal Iba-1/ApoE positive microglia in MfrpKI/KI mice with some subretinal microglia also expressing lowered levels of microglial homeostatic marker TMEM119, confirming microglial origin. In summary, we confirm that MfrpKI/KI mice carrying the c.498_499insC mutation had a significantly higher population of activated microglia in their retina with distinct subsets of subretinal microglia. Further, studies are required to confirm whether the association of increased subretinal microglia in MfrpKI/KI mice are causal in degeneration.

A Rare Case of Juvenile X-Linked Retinoschisis

Abstract Aim: To present a rare clinical case of X-linked retinoschisis, confirmed clinically, electrophysiologically and genetically. Material and methods: A 12-year-old boy underwent detailed ophthalmic examination including fundus photography, full-field, multifocal and pattern electroretinography, visual field testing, optical coherence tomography, which established the clinical diagnosis, confirmed also genetically. Results: The clinical findings included a slight loss of vision, central and paracentral scotomas, a characteristic spoke-wheel pattern appearance of the macula in fundoscopy and the pathognomic appearance of splitting of the retinal layers in the macula with foveal schisis with cystic spaces on OCT. Reduced cone and rod ERG responds were detected with the characteristic decreasing of b-ware near the isoelectric line. The genetic analysis found that the patient was hemizygous for the missense mutation c.598G>A (p.Arg200Cys) of RS1 gene, coming from his asymptomatic mother. Conclusion: The comprehensive clinical, electrophysiological and genetic testing of patients with rare hereditary retinal dystrophies is essential for the correct diagnosis and the choice of therapeutic approach.

A novel mutation in the RS1 gene in a Chinese family with X-linked congenital retinoschisis.

The purpose of the present study was to assess the clinical characteristics of X-linked retinoschisis (XLRS) in a Chinese family over a 7-year period with the aim of identifying possible genetic mutations associated with this disease. A total of 2 male siblings from a family with XLRS were followed up for 7 years and the best-corrected visual acuity and data obtained using slit-lamp microscopy, indirect ophthalmoscopy, fundus photography, spectral domain-optical coherence tomography (OCT), fundus autofluorescence and fundus fluorescence (FFA) and multifocal electroretinograms (ERG) were examined. The coding regions of the retinoschisin 1 (RS1) gene were amplified by PCR and sequenced directly. The proband exhibited blurred vision at 12 years old and was indicated to exhibit a typical phenotype of XLRS at 30 years old. The elder brother exhibited blurred vision at 11 years old and was diagnosed with XLRS at 33 years old. There was no change in the best-corrected visual acuities in the two patients over the 7 years. The OCT results suggested that there were intraretinal cysts and macular atrophy in the eyes of the older sibling, whilst a ‘spoke-wheel’ pattern was present in the macula of the younger sibling. In addition, OCT examination revealed foveal schisis. FFA analysis indicated a hyperfluorescent signal in the central macula. Multifocal ERG recordings indicated that responses were markedly reduced in the central and outer rings bilaterally. The central retinal thickness of the younger sibling increased but the central retinal thickness of the older sibling was not changed during the 7 years. Sequencing analysis revealed that the mutation was c.366G>A (p.Trp122*) in exon 5 of Xp22.1. Gene mutation analysis indicated that the affected male siblings harbored a Trp122* (c.366G>A) mutation, while the patients' mother was demonstrated to be a heterozygous carrier of the pathogenic mutation. To conclude, the present study discovered a novel XLRS mutation in a Chinese family, where the Trp122* mutation caused a significant change in the function of the RS1 protein. Over the 7 years of observation, although the vision was not significantly impaired in the two patients examined, the central retinal thickness of the younger sibling increased but the central retinal thickness of the older sibling was not altered.

Fovea-Sparing versus Standard Internal Limiting Membrane Peeling for Myopic Traction Maculopathy: A Study of 102 Consecutive Cases

To investigate the long-term outcomes of pars plana vitrectomy (PPV) with fovea-sparing internal limiting membrane (ILM) peeling (FSIP) and standard ILM peeling for myopic traction maculopathy (MTM). Retrospective case series. A total of 102 eyes of 96 consecutive patients who underwent primary PPV for MTM and were followed up for at least 12 months. We compared the outcomes of eyes that underwent vitrectomy with FSIP from October 2012 to March 2017 with those of eyes that underwent vitrectomy with standard ILM peeling from June 2008 to September2012. Best-corrected visual acuity (BCVA) at 12 months and the final follow-up visit after surgery, time to MTM resolution, and postoperative complications such as macular hole (MH) formation. There were 26 and 76 eyes in the FSIP and standard ILM peeling groups, respectively. In both groups, the mean visual acuity (VA) at the 12-month follow-up was significantly improved relative to the mean preoperative VA (P < 0.001 for both groups). The preoperative and postoperative BCVA (logarithm of the minimum angle of resolution) showed no significant between-group differences (preoperative: 0.60±0.35 in the FSIP group and 0.61±0.39 in the standard ILM peeling group, P= 0.935; postoperative BCVA: 0.32 ± 0.43 in the FSIP group and 0.37 ± 0.38 in the standard ILM peeling group, P= 0.281). The mean time to the resolution of foveal retinal detachment and schisis was also comparable between groups (8.9 ± 4.8 months in the FSIP group and 6.9 ± 4.6 months in the standard ILM peeling group, P= 0.084). None of the eyes in the FSIP group and 6 eyes (8%) in the standard ILM peeling group developed postoperative MH. Consequently, the BCVA at 12 months deteriorated by 3 or more lines for 4 eyes (5%) in the standard ILM peeling group; this deterioration was not observed for any eye in the FSIP group. Risk factors for postoperative MH formation were worse preoperative visual acuity (P = 0.035) and thinner choroidal thickness (P = 0.025). The visual and anatomic improvements after vitrectomy with FSIP may be comparable to those after vitrectomy with standard ILM peeling, with FSIP showing the ability to prevent postoperative MH formation and a consequent impairment in vision.

Clinical outcome in acquired retinoschisis

Introduction: Retinoschisis is defined as splitting of the neurosensory layer of retina. It can be congenital, acquired or secondary type. Clinically, the patients show typically a cystic space stellate maculopathy or a foveal schisis. Methods: This study was a retrospective case series. The inclusion criteria were either sex, no systemic disorder, and ready for subsequent follow ups. Through clinical history of the patient was taken. Visual acuity, intraocular pressure measurement, anterior segment examination and fundoscopy were performed. Optical Coherence Tomography of the suspected eye was done. Results: Based on clinical and Optical Coherence Tomography findings, the diagnosis of acquired retinoschisis was made. Conclusion: The clinical presentation of the patient and understanding of retinal anatomy is important in diagnosis of retinoschisis. Early diagnosis helps in management and reduces the risk of permanent visual loss.

Optic disc pit maculopathy: tamponade of maculoschisis.

PurposeTo present rapid and safe closure of the pit-macula communication (PMC) by core vitrectomy and adequate duration gas tamponade as our preferred method of resolving optic disc pit (ODP) maculopathy and to define the term “maculoschisis” in ODP maculopathy as an alternative to the term “schisis-like.”Patient and methodsA twenty-four-year-old female presented with an optical coherence tomography (OCT) confirmed ODP and a “giant” communicating maculoschisis cavity. Central macular thickness (CMT) measured 906 microns, and macular volume was twice normal, at 20.8 mm3. Snellen corrected visual acuity was 20/70. Two months after initial vitrectomy performed elsewhere with short-term gas tamponade (SF6 20%), CMT and visual acuity were not significantly improved. Combined lens extraction/intraocular lens placement and repeat vitrectomy with C3F8 15% gas tamponade were performed, with one supplemental (office) gas injection.ResultsOCT imaging six weeks postoperatively showed definitive closure of the PMC with CMT reduced by 405 microns. Sequestered from its ODP source, foveal schisis fluid then resolved by 12 weeks postoperatively. At final follow-up 3.4 years postoperatively, the macula remained dry with a CMT of 322 microns and a concave foveal contour. Macular volume was reduced to (a normal) 10.2 mm3 and visual acuity had improved to 20/25.ConclusionNo report heretofore has documented rapid, sustained closure of the PMC by gas tamponade as the preferred method of expeditiously resolving ODP maculopathy. However, tamponade PMC closure sequesters ODP fluid and uniquely provides early assurance of ultimate maculopathy resolution. In all other techniques, PMC closure is a trailing phenomenon and success remains uncertain during months to a year or more of (unsequestered) fluid resolution. We suggest that more invasive techniques (laser barrier application to the peripapillary choroid, vitreoretinal interface maneuvers, and pit-plugging) be withheld unless a recurrence is detected during subsequent examinations.

Refractory macular edema in X-linked juvenile retinoschisis

X-linked juvenile retinoschisis (XLRS) is one of the most common X-linked inherited, bilateral vitreoretinal dystrophies affecting males in the first two decades of life. In this article, we present a case report of a young man who presented with gradual decrease in visual acuity in both eyes that was attributed to macular edema and foveal schisis in the inner retinal layers. He was investigated by appropriate ocular images which were consistent with a diagnosis of XLRS. He was treated by anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection, dorzolamide eye drops and intravitreal steroids injection without improvement.

Observational study of clinical characteristics of dome-shaped macula in Chinese Han with high myopia at Zhongshan Ophthalmic Centre

PurposeTo evaluate the prevalence of dome-shaped macula (DSM) in highly myopic eyes among Chinese Han and to detect the correlation with myopic maculopathy and macular complications.MethodsA total of 736 Chinese...

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

To evaluate the outcomes of vitreoretinal surgery for four different phenotypes of X-linked retinoschisis (XLRS). 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. 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. 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.

Identification of XLRS1 gene mutation (608C>T) in a Portuguese family with juvenile retinoschisis.

To characterize electroretinogram (ERG) and molecular genetic findings in a family with XLRS1 mutation. The authors present two cases of a Portuguese family with juvenile retinoschisis with a mutation in exon 6. Two brothers and their parents, grandmother, and uncle underwent a full ophthalmic examination. The two brothers with ophthalmic disease were evaluated with color fundus photography, fluorescein angiography, optical coherence tomography (OCT), molecular genetic study (Group VI of Retinoschisis Consortium), pattern visual evoked potential (PVEP), and full field ERG. Both patients presented funduscopic manifestations of vitre o retinal degeneration. They presented peripheral schisis and retinal detachment. However, foveal schisis had never been observed at funduscopy. A negative ERG was recorded in both. Six months after that, the younger brother showed a typical foveal schisis at fundus examination. A retinoschisis gene (XLRS1) mutation with transition of cytosine by thymine at position 608 (608C>T) had been identified in both. Negative ERG is the most secure clinical marker to establish the diagnosis of juvenile retinoschisis. XLRS1 gene 608C>T mutation was described for the first time in a Portuguese family. (Eur J Ophthalmol 2005; 15: 638-40 ).

Enhanced S-Cone Syndrome (Goldmann-Favre Syndrome).

In enhanced S-cone syndrome (ESCS), rods and red and green cone receptors are degenerated, but S-cones are enhanced (increased in number). Patients have increased sensitivity to blue light, with night blindness from an early age (from birth) and impaired central vision. The fundus shows characteristic nummular pigmentary changes along the vascular arcades at the level of the retinal pigment epithelium (RPE). (In retinitis pigmentosa [RP], pigment is deposited within the retina.) Sometimes, there are white-yellow dots at the level of the RPE along the vascular arcades, along with focal hyperpigmentation within the arcades (Figs. 28.1 and 28.2). Patients may also have foveal schisis. (Goldmann-Favre syndrome consists of foveal schisis plus peripheral degeneration.) Fundus autofluorescence (FAF) shows a decrease or lack of AF outside the arcades, possibly due to loss of photoreceptors in this region; a ring of hyperautofluorescence (hyperAF) is seen in the transition zone between the region of absent AF beyond the arcade and the central zone of spoke-like, relatively increased AF, centered on the fovea; increased AF may be related to lipofuscin accumulation secondary to RPE-photoreceptor dysfunction in that area. Electroretinograms (ERGs) in ESCS are pathognomonic and show extinguished rod response and a similar wave form in both scotopic and photopic conditions. The 30 Hz flicker responses are markedly delayed and are of lower amplitude. (Normally, flicker amplitude lies between that of the photopic a- and b-waves, but in ESCS, it is less than that of the photopic a-wave.) With orange background (suppressing red and green cones), increased response to short wavelength (blue) is elicited, suggestive of functioning of S-cones. The multifocal ERG (mfERG) shows preservation of central responses, though somewhat delayed. ESCS is a slowly progressive disorder that often leads to severe visual loss in adults.

The best of the best: a review of select retina case reports published in 2015

This review article highlights 4 case reports published in 2015 that provided substantive contributions to the field of retina. The first describes postoperative hemorrhagic occlusive retinal vasculitis, a newly described and visually devastating complication of cataract surgery. The second discusses ocriplasmin as a novel treatment for foveal schisis in patients with X-linked retinoschisis. The third describes a case of retinal toxicity from sertraline, a common psychiatric drug often sold as name brand Zoloft (Pfizer Inc, New York, NY). The last article shares 10-year results from a blind patient who received the Argus I retinal prosthesis. The study of vitreoretinal disease is both complex and fascinating. Case reports and case series are a means by which clinicians can share clinical experiences in managing retinal disease. By sharing our clinical experiences from individual patients, we begin the process of describing new diseases, new medications, and new surgical techniques. To obtain a list of published reports, we performed a MEDLINE search for case reports with the keyword retina. In 2015 there were 195 publications meeting these criteria. We selected 4 articles that highlight interesting developments in the field of retina.

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

To analyze the structures of schisis in eyes with hereditary juvenile retinoschisis using en-face optical coherence tomography (OCT) imaging. 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. OCT images were obtained from 16 eyes of nine boys (mean age ± standard deviation, 10.6 ± 4.0years). 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. 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.

Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family.

BackgroundJuvenile X-linked retinoschisis (RS1, OMIM: 312700) is a hereditary vitreoretinal dystrophy characterized by bilateral foveal schisis and, in half of the patients, splitting through the nerve fiber layer in the peripheral retina. In the first decade of life, patients usually develop a decrease in visual acuity. Long-term visual outcomes can be poor due to the limited number of known successful treatments.PurposeThe purposes of this study were to present, for the first time, a p.Arg197Cys missense mutation in the RS1 gene (OMIM: 300839) in a four-generation Italian family with RS1 and to examine the clinical response to the treatment with acetazolamide tablets alone or in combination with dorzolamide eye drops as assessed by spectral-domain optical coherence tomography (SD-OCT).MethodsEleven individuals, including two brothers with RS1 (patients 1 and 2), underwent a full medical history examination and a comprehensive ocular assessment that involved SD-OCT, fluorescein angiography, electroretinography and DNA analysis. Each RS1 patient received oral acetazolamide (375 mg daily) during the first three months. Thereafter, patient 1 continued only with dorzolamide eyedrops three times a day for a period of three months, while patient 2 spontaneously stopped both medications.ResultsSequence analysis of the RS1 gene identified a hemizygous c.589C>T (p.Arg197Cys) missense mutation in exon 6, which has not been previously reported in an Italian family. A different response to the medical therapy was observed in the four eyes of the two affected brothers hemizygous for this abnormality. Of note, after acetazolamide interruption, a rebound effect on cystoid macular edema reduced the beneficial effects of the initial therapy for RS1 from p.Arg197Cys mutation. Indeed, a minimal rebound effect on cystoid macular edema, and an improvement in visual acuity, was observed in patient 1 during the six months of treatment. Conversely, in patient 2, an initial improvement in cystoid macular edema was not associated with visual acuity changes, followed by a marked rebound effect.ConclusionThis study showed that the sequential use of acetazolamide tablets and dorzolamide eye drops should be considered and studied further as a possible treatment for macular edema and visual impairment in patients with RS1 from a hemizygous p.Arg197Cys mutation.

Phenotypic characterization of X-linked retinoschisis: Clinical, electroretinography, and optical coherence tomography variables.

Aims:To study the phenotypic characteristics of X-linked retinoschisis (XLRS) and report the clinical, electroretinogram (ERG), and optical coherence tomography (OCT) variables in Indian eyes.Design:A retrospective study.Materials and Methods:Medical records of 21 patients with retinoschisis who were genetically confirmed to have RS1 mutation were reviewed. The phenotype characterization included the age of onset, best-corrected visual acuity, refractive error, fundus findings, OCT, and ERG.Statistical Analysis Used:Data from both the eyes were used for analysis. A P < 0.05 was set as statistical significance. Data were not normally distributed (P < 0.05, Shapiro wilk); hence, nonparametric tests were used for statistical analysis.Results:All were males whose mean age of presentation was 9 years. Visual acuity was moderately impaired (median 0.6 logMAR, interquartile range: 0.47, 1) in these eyes with a hyperopic refractive error of median +1.75 Ds (interquartile range: +0.50 Ds, +4.25 Ds). About 54.7% of the eyes had both foveal and peripheral schisis, isolated foveal schisis was seen in 28.5% of the eyes, and schisis with retinal detachment was seen in 16.6% of the eyes. The inner nuclear layer was found to be commonly involved in the schisis, followed by outer nuclear and plexiform layers as evident on OCT. On ERG, a- and b-wave amplitudes were significantly reduced in eyes with foveal and peripheral schisis when compared to the eyes with only foveal schisis (P < 0.05).Conclusions:XLRS has phenotypic heterogeneity as evident on OCT, ERG, and clinical findings.

X-linked juvenile retinoschisis

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.

Optical Coherence Tomography Retinal Thickness and Volume Measurements in X-Linked Retinoschisis

To analyze retinal thickness and volume measurements of X-linked retinoschisis patients by spectral-domain optical coherence tomography (SD OCT) and correlate these findings with visual acuity and patient age. Retrospective comparative case series. Sixty-three eyes of 33 male patients with X-linked retinoschisis were gleaned from a SD OCT database at the University of Illinois at Chicago. Forty-one eyes of 21 patients with low refractive error, no visualimpairment, and no known retinal disease served as age-similar controls. The mean age of the retinoschisis patients was 26.4 years. The mean age of patient controls was 30.0 years. Full-thickness, inner and outer retina thickness, and volume measurements were determined by SD OCT. Foveal schisis was observed in 81% of retinoschisis patients. Patients with foveal schisis tended to be younger than patients lacking foveal schisis. Inner and outer foveal thickness and volume measurements were increased in retinoschisis patients compared to controls. Outer retinal perifoveal and parafoveal thicknesses and volumes were consistently increased in retinoschisis patients relative to controls. In contrast, inner retinal perifoveal and parafoveal thickness and volume measurements were decreased in retinoschisis patients compared to controls. Worse visual acuity correlated with thinning of the temporal perifoveal inner retina and thickening of the inner fovea. Full-thickness measurements and inner retina and outer retina thickness and volume measurements tended to decrease with patient age. Increased inner retinal foveal thickness and decreased perifoveal inner retinal thickness correlates with worse visual acuity and overall retinal thickness decreases with age in X-linked retinoschisis.

A Phenotype–Genotype Correlation Study of X-Linked Retinoschisis

To compare the clinical phenotype and detailed electroretinographic parameters in X-linked retinoschisis (XLRS). Retrospective, comparative study. Fifty-seven patients (aged 1-67 years) with molecularly confirmed XLRS were clinically ascertained. Pattern electroretinography (PERG) and full-field electroretinography (ERG), incorporating international standard recordings, were performed in 44 cases. Thirteen patients, mostly pediatric, were tested using a simplified ERG protocol. On-Off and S-cone ERGs were performed in most adults. Fundus autofluorescence (FAF) imaging and optical coherence tomography (OCT) were available in 17 and 21 cases, respectively. The clinical and electrophysiologic data associated with different types of mutation in the RS1 gene. Forty-three patients had missense changes (group A), and 14 patients had nonsense, splice-site, or frame-shifting mutations in the RS1 gene (group B). The mean best-corrected visual acuity was better in group A than in group B (0.34 and 0.21, respectively). Fundus examination revealed foveal schisis in approximately half of both groups. The bright-flash dark-adapted (DA) ERG (11.0 candela.sec.m(-2)) waveform was electronegative in 62% of group A eyes and 100% of group B eyes. The photopic 30-Hz flicker ERG was delayed in all group B eyes and all except 6 group A eyes. On-Off ERG b-waves were subnormal in 39% of group A and 89% of group B eyes; d-waves were delayed in 14 eyes (group A = 10, group B = 4). S-cone ERGs were abnormal in 50% of both groups. The PERG was abnormal in 88% of group A and 100% of group B eyes. A spoke-wheel pattern of high and low intensity was the most common FAF abnormality observed. The OCT showed intraretinal schitic cavities in the majority of eyes. There is profound phenotypic variability in patients with XLRS. Most patients have DA bright-flash ERGs with a low b:a ratio in keeping with inner retinal dysfunction. Generalized cone system dysfunction is common and associated with an abnormal On-response and less frequent additional Off-response involvement. Nonsense, splice-site, or frame-shifting mutations in RS1 consistently caused electronegative bright-flash ERG, delayed flicker response, and abnormal PERG; missense mutations result in a wider range of ERG abnormalities.