Retinal and Vitreous Changes Associated with Spontaneous Improvement in Myopic Macular Schisis.

PURPOSE: To describe the retinal and vitreous changes in eyes showing myopic macular schisis (MMS) improvement when vitrectomy was not performed and identify triggering factors. DESIGN: Retrospective observational study. SUBJECTS: Patients with nonoperated MMS. METHODS: The records of patients with MMS who were followed without performing surgery for >6 months were retrospectively reviewed, and the eyes showing an anatomic improvement were included. Myopic macular schisis evolution was analyzed quantitatively (central foveal thickness [CFT], parafoveal thickness, maximum height) and qualitatively (presence/absence of foveal detachment, lamellar hole, epiretinal membrane, choroidal neovascularization, inner and outer retinoschisis, vitreous status) at baseline and at the final visit. An anatomic improvement was defined as a decrease in CFT by ≥50 µm. MAIN OUTCOME MEASURES: The rate of anatomic improvement of MMS without performing vitrectomy and the morphological changes observed in these cases. RESULTS: In a cohort of 74 nonoperated eyes with MMS, MMS improved in 14 eyes (19%) after a mean follow-up of 55 ± 38 months (range, 8-138). In these improved cases, the mean decrease in CFT was 153 ± 166 µm (range, 24-635; P = 0.005) and a complete resolution of MMS was observed in 9 eyes (64%). In 9 eyes (64%), the improvement was associated with visible vitreous changes in the macular area on the OCT scans. The mean visual acuity, which was already good at baseline (20/50, 0.4 ± 0.2 logarithm of the minimum angle of resolution), increased at the last visit (20/40, 0.3 ± 0.3 logarithm of the minimum angle of resolution) but without reaching significance. CONCLUSIONS: This long-term follow-up analysis showed that almost 20% of MMS in eyes without indication for surgery could improve over time. In most cases, the improvement was associated with an apparent resolution of vitreous tensions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical and Genetic Features of NR2E3-Associated Retinopathy: A Report of Eight Families with a Longitudinal Study and Literature Review.

(1) Background: NR2E3 encodes a nuclear receptor transcription factor that is considered to promote cell differentiation, affect retinal development, and regulate phototransduction in rods and cones. This study aimed to analyze the clinical characteristics and observe the prognosis of autosomal dominant retinopathy (ADRP) and autosomal recessive retinopathy (ARRP) associated with NR2E3; (2) Methods: NR2E3 variants were collected from our exome sequencing data and identified per the American College of Medical Genetics and Genomics criteria. Data from our cohort and a systemic literature review were conducted to explore the NR2E3 variants spectrum and potential genotype-phenotype correlations; (3) Results: Nine pathogenic variants/likely pathogenic variants in NR2E3, including five novel variants, were detected in eight families (four each with ADRP and ARRP). Follow-up data showed schisis/atrophy in the macula and retinal degeneration initiation around the vascular arcades with differences in ADRP and ARRP. A systemic literature review indicated patients with ADRP presented better visual acuity (p < 0.01) and later onset age (p < 0.0001) than did those with ARRP; (4) Conclusions: Macular schisis and retinal degeneration around vascular arcades may present as the prognosis of NR2E3-retinopathy, dominant, or recessive. Our data might further enrich our understanding of NR2E3 variants and associated inherited retinopathy.

Inverted ILM Flap Technique in Optic Disc Pit Maculopathy.

Purpose: To present the outcome of optic disc pit maculopathy (ODPM) managed successfully with an inverted internal limiting membrane (ILM) flap over the optic disc. A narrative review of ODPM pathogenesis and surgical management techniques are also provided. Case Report: This prospective interventional case series included three eyes of three adult patients (25-39 years old) with unilateral ODPM and a mean duration of unilaterally decreased visual acuity of 7.33 ± 2.40 months (4-12 months). The pars plana vitrectomy with posterior vitreous detachment induction was performed on eyes, followed by an inverted ILM flap insertion over the optic disc and gas tamponade. Patients were followed for 7-16 weeks postoperatively; best-corrected visual acuity (BCVA) improved dramatically in one patient from 2/200 to 20/25. BCVA in other patients improved two and three lines - to 20/50 and 20/30, respectively. A significant anatomical improvement was achieved in all three eyes, and no complication was detected throughout the follow-up period. Conclusion: Vitrectomy with inverted ILM flap insertion over the optic disc is safe and can yield favorable anatomical improvement in patients with ODPM.

Myopic macular schisis: Insights into distinct morphological subtypes and novel biomechanical hypothesis.

PURPOSE: To analyze the features of myopic macular schisis (MMS) in different retinal layers and to explore the role of Müller cells in the pathophysiology of such condition. METHODS: Spectral-domain optical coherence tomography (SD-OCT) images of myopic eyes with staphyloma and macular schisis were reviewed. The morphological features of MMS were analyzed and correlated with their geographical location in the parafoveal and perifoveal region. A biomechanical model was adopted to explain MMS morphological differences. The effect of the different schisis subtypes with best corrected visual acuity (BCVA) was also explored. RESULTS: A total of 36 eyes from 26 patients were included in this study. MMS was classified into inner, middle and outer retinal subtypes. The prevalence of middle retinal schisis was significantly lower in the parafovea, within a central 3 mm-diameter circle (p < 0.001) centered at the fovea . The prevalence of inner retinal schisis was significantly higher outside the central 3-mm diameter circle, in the perifoveal region (p < 0.001). No significant differences were noted in the prevalence of outer retinal schisis for these two locations (p = 0.475). The presence of middle retinal schisis within the central 3-mm diameter circle showed a weak association with lower BCVA (p = 0.058). The presence of outer retinal schisis within the central 3-mm diameter circle was significantly related with lower BCVA (p = 0.024). CONCLUSION: Three major forms of MMS are distinguished: inner, middle and outer retinal schisis. This classification may have clinical importance as only the outer grade of schisis was associated with vision loss.

Characterization and diagnosis of retinoschisis and schisis detachments using spectral domain optical coherence tomography.

PURPOSE: To characterize retinoschisis in a large series using spectral domain optical coherence tomography (SD-OCT), including rates of schisis detachment and macular involvement in cases of peripheral retinoschisis. METHODS: In this retrospective, cross-sectional, descriptive study, consecutive patients with diagnosis of retinoschisis in at least one eye were identified using billing codes between January 2012 and May 2021. Charts were reviewed to verify diagnosis of retinoschisis or schisis detachment. SD-OCT and clinical examination was used to identify frequency of macular schisis, peripheral schisis, and schisis detachment, and characteristics of retinoschisis including frequency of inner and outer wall breaks, distribution of layers split, and location of involvement of peripheral pathology. SD-OCT images of insufficient quality were excluded from the pertinent analysis. RESULTS: 281 eyes of 191 patients were included. 195 (69.4%) eyes had peripheral retinoschisis, 15 (5.3%) had schisis detachment, 66 (23.5%) had macular retinoschisis alone, and 5 (1.8%) had combined macular and peripheral retinoschisis. Of the eyes without macular retinoschisis, 7.0% had schisis detachment. Of the remainder, 4 (2.1%) had inner wall breaks, and 24 (12.3%) had outer wall breaks. In eyes with peripheral retinoschisis, splitting occurred in the outer plexiform layer in 58.9%, the retinal nerve fiber layer in 8.9%, a combination of layers in 26.8%, and indeterminate in 5.4%. Location of peripheral involvement was inferotemporal in 58.5%, superotemporal in 14.1%, temporal in 13.7%, and inferior in 12.2%. CONCLUSION: SD-OCT helped to identify the presence of schisis detachment and breaks, confirmed diagnosis in challenging cases, and demonstrated the layer of splitting within the neurosensory retina. This series represents the largest such study to date.

The effect of vitrectomy combined total versus fovea-sparing peeling of internal limiting membrane for myopic foveoschisis / 中华眼底病杂志

Objective:To systematically evaluate the effect of pars plana vitrectomy (PPV) combined total peeling of internal limiting membrane (ILM) versus fovea-sparing peeling of ILM for myopic foveoschisis.Methods:A evidence-based medicine study. Chinese and English as search terms for myopic foveoschisis, vitrectomy, and peeling of internal limiting membrane were used to search literature in China National Knowledge Infrastructure, Wanfang database, VIP database, PubMed of National Library of Medicine, Medline, Embase, and Cochrane Library. The high myopic macular schisis was selected as the research object, the intervention method was PPV combined with complete ILM peeling and combined with foveal preservation ILM peeling surgery clinical control study between Jan 1, 2010, and Jun 31, 2021. Incomplete or irrelevant literature and review literature were excluded. The method of Newcastle-Ottawa Scale system was used to evaluate the included literature. The literature was meta-analyzed by RevMan5.3 software. The mean difference ( MD) and a confidence interval ( CI) of 95% were used to describe the effect sizes of continuous data, fixed effects model was performed. The data including the best corrected visual acuity (BCVA), central fovea thickness (CFT), and postoperative macular hole (MH) were analyzed. Results:In those databases, 232 articles based search stratery were totally retrieved, and 10 articles (417 eyes) were finally included for meta-analysis with 245 eyes for PPV combined total peeling of ILM and 172 eyes for PPV combined fovea-sparing peeling of ILM. Meta-analysis results showed there was no significant difference in BCVA and CFT between the two groups (BCVA: MD=0.05, 95% CI 0.00-0.11; P>0.05; CFT: MD=-4.79, 95% CI -18.69-9.11, P>0.05). It was compared with the incidence of MH, the difference was statistically significant (odds ratio=5.70, 95% CI 2.22-14.61, P<0.05). Conclusion:BCVA and CFT could be improved by PPV combined total and fovea-sparing peeling of ILM for myopic foveoschisis; compared with complete ILM peeling, the incidence of MH was lower after foveal-sparing ILM peeling.

Heads-up Digitally Assisted Surgical Viewing with Intraoperative Optical Coherence Tomography for Myopic Schisis Repair.

PURPOSE: To describe the surgical approach with a screen-based heads-up, three-dimensional (3-D) digital viewing with intraoperative optical coherence tomography (I-OCT) for the successful repair of a myopic macular schisis (MMS) case. CASE REPORT: A 62-year-old woman with vision loss in the left eye was scheduled for pars plana vitrectomy (PPV) and MMS repair. Surgery was performed using the NGENUITYⓇ system for surgical viewing, and foveal-sparing internal limiting membrane (fs-ILM) peeling was performed without gas tamponade, after confirming the absence of iatrogenic macular hole with I-OCT. There were no intraoperative or postoperative complications. Visual acuity improved to 20/40 and the subfoveal macular thickness improved from 706 µm (preoperative) to 221 µm after seven months of follow-up. CONCLUSION: Heads-up digitally assisted viewing technology with I-OCT may be useful or preferred for patients requiring vitreoretinal surgery in the setting of MMS.

Optic pit-like maculopathy in a patient without any detectable disc anomalies.

Macular schisis is the splitting of the inner retinal layers at macula, with or without associated detachment. The acquired form of macular schisis is frequently associated with optic disc pit maculopathy, although it could be accompanied by several conditions such as tractional maculopathies, cystoid macular edema, veno-occlusive disease, and shaken baby syndrome. However, a small number of cases of retinoschisis without optic disc pit have been reported elsewhere. Here, we present a patient with acquired macular schisis without high myopia and optic disc abnormality in funduscopic examination and imaging. Macular optical coherence tomography of her left eye revealed schisis of the inner and outer retinal layers and subretinal fluid and choroidal thickness of 426 µm (pachychoroid). Although the optic disc of this patient appeared normal, the probable presumption is that small junctions existed between the macular neuroretinal tissue and the vitreous cavity. Further studies are required to survey the other probable mechanisms of retinoschisis without optic pit with more subjects.

Evolution of macular hole in enhanced S-cone syndrome.

PURPOSE: To describe the stages of development and natural course of a full-thickness macular hole (FTMH) in a patient with enhanced S-cone syndrome (ESCS). METHODS: This study reported the serial ophthalmologic examinations and macular spectral-domain optical coherence tomography (SD-OCT) imaging over a period of 6 years in a 29-year-old man with ESCS confirmed by electroretinography (ERG) and NR2E3 molecular genetic analysis. RESULTS: At presentation, patient had night blindness and visual acuity (VA) of 20/300 in the right eye (OD) and 20/100 in the left eye (OS). Examination showed bilateral retinal midperipheral pigmentary deposits and a macular schisis in OD. Electroretinography and NR2E3 genetic analysis confirmed ESCS. A year later, a lamellar MH (LMH) appeared at the fovea in OD. SD-OCT confirmed it as inner retinal layer LMH with outer retinal preservation and displayed, on the temporal side of the LMH, prominent splitting between the inner and outer retinal layers. At 2 years, a focal defect in the ellipsoid zone appeared on SD-OCT, followed by split in the outer retinal layer creating a progressively expanding outer LMH. The latter had rolled edges which then fused with the inner LMH margins creating a single full-thickness FTMH. Over the next 4 years, enlargement of the FTMH with increased adjacent retinal splitting continued. No visible vitreous abnormalities or vitreoretinal traction forces were identified at any stage during follow-up. VA OD remained unchanged. CONCLUSION: This case illustrates that the clinical evolution of FTMH in ESCS may be progressive and likely involves degeneration and intraretinal, rather than vitreoretinal, traction. This should be kept in mind when considering surgical intervention in these cases.

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.

Comparison of macular buckling and vitrectomy for the treatment of macular schisis and associated macular detachment in high myopia: a randomized clinical trial.

OBJECTIVE: To compare the efficacy and safety of macular buckling and vitrectomy for myopic traction maculopathy showing macular schisis (MS) and associated macular detachment (MD) but without full-thickness macular hole (FTMH). DESIGN: Prospective, randomized, parallel, open-label study. METHODS: Patients were randomly assigned to either buckling or vitrectomy group. Macular buckling and intravitreal C3F8 gas injection were performed in the buckling group. Small gauge vitrectomy, internal limiting membrane peeling (ILMP) and C3F8 gas tamponade were performed in the vitrectomy group. The patients were followed for 12 months. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at 12 months. RESULTS: A total of 85 patients were randomized, 80 eyes were included (41 receiving buckling, 39 received vitrectomy), and 78 patients completed the study. There were less eyes determined as surgical failure and required a second surgery in the buckling group than vitrectomy the group (2.4% versus 18.4%, p = 0.021). After surgery, macular buckling achieved more improvement in BCVA (+21.7 versus +4.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, p = 0.002). FTMH development was observed in only 1 (2.4%) eye, after removing of the implant due to recurrent conjunctival erosion, in the buckling group and 10 (26.3%) eyes (seven with-, three without MD) in the vitrectomy group (p < 0.001). More eyes developed cataracts in the vitrectomy group than did in the buckling group (28.9% versus 7.5%, p = 0.014). Macular buckling-associated strabismus (esotropia), binocular diplopia and implant exposure were observed in limited cases. CONCLUSIONS AND RELEVANCE: Macular buckling is superior to vitrectomy with ILM peeling plus gas injection for surgical treatment of MS and associated MD in high myopia.

Intrafamilial heterogeneity of congenital optic disc pit maculopathy.

BACKGROUND: Optic disc pit is a very rare clinical entity. The main complication of this condition is the maculopathy. Report of cases: A 40-year-old Caucasian man and his 6-year-old daughter underwent a complete ophthalmological examination. In both cases ophthalmoscopy examination showed a bilateral white-yellow oval depression in the optic disc. Optical coherence tomography showed maculopathy with different degrees of severity in the two cases. Microperimetry and multifocal-electroretinography showed different degrees of retinal dysfunction in both cases. Molecular genetic analysis was performed and the possible pathogenic role of the MIR204 gene was excluded. DISCUSSION: The findings of our familial cases support the hypothesis that optic disc pit associated with maculopathy could be a genetic disease with an autosomal dominant inheritance pattern. Optical coherence tomography is the most helpful diagnostic tool to assess maculopathy associated with optic disc pit. Microperimetry and multifocal-electroretinography are useful for the diagnosis of macular dysfunction in the early stages, and for the prognosis and follow-up of optic disc pit-maculopathy which is the main cause of visual impairment in these patients. Furthermore, in consideration of the variable expressivity and disease severity reported in our cases, genetic anticipation may be hypothesized.

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

BACKGROUND: Juvenile 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. PURPOSE: The 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). METHODS: Eleven 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. RESULTS: Sequence 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. CONCLUSION: This 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.

Vitrectomy for bilateral macular schisis without apparent optic disc anomalies.

A 78-year-old man complained of bilateral visual acuity loss. Optical coherence tomography examination showed bilateral macular schisis with fluid accumulation in the external retinal layers without vitreous traction. Fundus examination and fluorescein angiography were normal in both eyes. Both eyes were treated by phacoemulsification, intraocular lens implantation, and vitrectomy without laser, gas exchange, or retinal fenestration. Slow and progressive fluid resorption and improvement in VA were observed in both eyes. Macular schisis similar to the one associated with optic disc anomalies is a possibility in patients without apparent disc anomalies. Vitrectomy without laser, gas, or retinal fenestration may be a good therapeutic option even in patients with a PVD preoperatively.

Spectral domain optical coherence tomography imaging in optic disk pit associated with outer retinal dehiscence.

A 37-year-old Bangladeshi male presented with an inferotemporal optic disk pit and serous macular detachment in the left eye. Imaging with spectral domain optical coherence tomography (OCT) revealed a multilayer macular schisis pattern with a small subfoveal outer retinal dehiscence. This case illustrates a rare phenotype of optic disk maculopathy with macular schisis and a small outer retinal layer dehiscence. Spectral domain OCT was a useful adjunct in delineating the retinal layers in optic disk pit maculopathy, and revealed a small area of outer retinal layer dehiscence that could only have been detected on high-resolution OCT.