[Analysis of the therapeutic efficacy of pars plana vitrectomy without intraocular tamponade in the treatment of high myopic eyes with myopic foveoschisis and central foveal detachment].

Objective: To investigate the efficacy of pars plana vitrectomy (PPV) without intraocular tamponade in the treatment of high myopic eyes with myopic foveoschisis (MF) accompanied by foveal detachment (FD). Methods: A retrospective case series study was conducted. The medical records of patients diagnosed with unilateral MF accompanied by FD at the Eye & ENT Hospital of Fudan University between May 2018 and December 2021 were collected. All patients underwent 23-gauge PPV with posterior vitreous cortex clearance, and no intraocular tamponade was applied. The cases were divided into groups based on whether the internal limiting membrane was peeled during surgery or retained. Follow-up was conducted for at least 12 months. The main outcome measures included postoperative best-corrected visual acuity (BCVA, converted to logarithm of the minimum angle of resolution), central foveal thickness (CFT), MF resolution, and complications. Statistical analyses were performed using t-tests, chi-square tests, Fisher's exact tests, and univariate and multivariate linear regression. Results: A total of 40 patients (40 eyes) with MF and FD were included in the study, with 30.0% being male and 70.0% female. The mean age was (56.9±11.7) years, and the axial length of the eyes was (29.1±1.9) mm. At 12 months postoperatively, BCVA improved from baseline 1.15±0.58 to 0.73±0.39 (t=6.11, P<0.001), and CFT decreased from baseline (610.1±207.2) µm to (155.9±104.1) µm (t=13.47, P<0.001). Complete resolution of MF with foveal reattachment was observed in 80.0% of eyes, with a median time of 6 (5, 8) months. There was no significant difference in BCVA and CFT between the internal limiting membrane peeled group and retained group [0.68±0.39 vs. 0.79±0.40, t=0.85, P=0.403; (148.3±63.8)vs.(164.3±137.2)um,t=0.48, P=0.634]. One eye experienced macular hole and another eye developed retinal detachment postoperatively. Correlation analysis showed a positive correlation between BCVA at 12 months postoperatively and baseline BCVA (ß=0.433, P<0.001). Conclusions: Pars plana vitrectomy without intraocular tamponade is effective in treating MF accompanied by FD. The choice between internal limiting membrane peeling and retention does not significantly affect visual prognosis.

Surgical management of a case of double optic disc pits with maculopathy.

BACKGROUND: Double optic disc pit maculopathy is a rare entity. It can be difficult to manage because of excessive leakage and chronic maculopathy. PURPOSE: To describe surgical management in a case of double optic disc pits with maculopathy. SYNOPSIS: A 42-year-old male presented with double optic disc pits with macular detachment in the left eye. The best-corrected visual acuity (BCVA) was 20/60, N12. Preoperative OCT showed the presence of two disc pits. The macular region had large retinoschisis and subretinal fluid (SRF) with a central foveal thickness of 879 microns and loss of the ellipsoid zone. A shallow communication from the temporal aspect of the disc to the submacular area was also noted. Among the options of observation, laser photocoagulation, and surgery, the patient opted for surgical management. SURGICAL TECHNIQUE: A standard-3 port 23-gauge pars plana vitrectomy was done. After staining the ILM with brilliant blue, ILM peeling was done with the help of forceps and Finesse loop. ILM flaps were inverted over to cover the optic disc pits and sealed with a drop of fibrin glue. Next, 20% SF6 gas was used for tamponade. Pre- and post-surgery parameters such as visual acuity and OCT were evaluated. POSTOPERATIVE EVALUATION: After 6 weeks, left eye BCVA was 20/40 with OCT showing reduced SRF and reduced intraretinal schisis with a foveal thickness of 546 microns. At 3 months of follow-up, the vision in the left eye had improved to 20/30 with further reduction in the retinoschisis and foveal thickness of 482 microns. HIGHLIGHTS: In this interesting case, we demonstrate a unique way of sealing the defect surgically by vitrectomy and inverted ILM flap with fibrin glue over the disc pits. Despite sealing the maculopathy is slow to resolve. VIDEO LINK: https://youtu.be/s9nY5UPe1s4.

Intraocular Pressure Lowering Associated With Worsening Optic Pit-Like Retinoschisis.

In this article, we present a case of optic pit-like macular retinoschisis in the absence of advanced glaucomatous cupping. Intraocular pressure (IOP)-lowering therapy, which was started due to an early concern for glaucoma, caused a worsening of the retinoschisis, which subsequently resolved on discontinuation of the IOP-lowering therapy. Lower IOP likely triggered intraretinal fluid accumulation by facilitating a translaminar gradient from the subarachnoid to intraretinal space. [Ophthalmic Surg Lasers Imaging Retina 2024;55:100-102.].

Foveal Microstructure and Visual Outcomes after Pars Plana Vitrectomy in Patients with Different Types of Epiretinal Membrane Foveoschisis.

INTRODUCTION: The aim of this study was to evaluate the clinical characteristics and surgical outcomes of the epiretinal membrane foveoschisis (ERM-FS) with different morphological types. METHODS: This retrospective observational study reviewed 44 consecutive ERM-FS patients who underwent ERM surgery. According to the optical coherence tomography images, ERM-FS was classified into three groups: group A, FS crossed the fovea with the foveola elevated; group B, FS located at the foveal edges with a near-normal central foveal point thickness; and group C, FS with undermined foveal edges with a near-normal central foveal point thickness. RESULTS: There were 10 eyes in group A, 20 eyes in group B, and 14 eyes in group C. Preoperatively, eyes in group A had the best best-corrected visual acuity (BCVA), the thickest central foveal point thickness, and the highest ellipsoid zone (EZ) intact rate among the three groups. After surgery, a resolution of foveoschisis was observed in 40.0%, 45.0%, and 50.0% of the eyes in group A, group B, and group C (p = 0.928), respectively. BCVA was significantly improved postoperatively. Although there was no significant difference in BCVA among the three groups at 1 month postoperatively, BCVA of group A was the best at 4 and 10 months. Correlation analysis indicated that the type of ERM-FS, baseline BCVA, central foveal point thickness, and postoperative EZ continuity (all p < 0.05) were important factors for the final BCVA. CONCLUSIONS: The damage to the retinal structure and visual function was milder in group A ERM-FS. Our study emphasized the necessity of OCT-based subtyping in patients with ERM-FS.

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

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

The Road towards Gene Therapy for X-Linked Juvenile Retinoschisis: A Systematic Review of Preclinical Gene Therapy in Cell-Based and Rodent Models of XLRS.

X-linked juvenile retinoschisis (XLRS) is an early-onset progressive inherited retinopathy affecting males. It is characterized by abnormalities in the macula, with formation of cystoid retinal cavities, frequently accompanied by splitting of the retinal layers, impaired synaptic transmission of visual signals, and associated loss of visual acuity. XLRS is caused by loss-of-function mutations in the retinoschisin gene located on the X chromosome (RS1, MIM 30083). While proof-of-concept studies for gene augmentation therapy have been promising in in vitro and rodent models, clinical trials in XLRS patients have not been successful thus far. We performed a systematic literature investigation using search strings related to XLRS and gene therapy in in vivo and in vitro models. Three rounds of screening (title/abstract, full text and qualitative) were performed by two independent reviewers until consensus was reached. Characteristics related to study design and intervention were extracted from all studies. Results were divided into studies using (1) viral and (2) non-viral therapies. All in vivo rodent studies that used viral vectors were assessed for quality and risk of bias using the SYRCLE's risk-of-bias tool. Studies using alternative and non-viral delivery techniques, either in vivo or in vitro, were extracted and reviewed qualitatively, given the diverse and dispersed nature of the information. For in-depth analysis of in vivo studies using viral vectors, outcome data for optical coherence tomography (OCT), immunohistopathology and electroretinography (ERG) were extracted. Meta-analyses were performed on the effect of recombinant adeno-associated viral vector (AAV)-mediated gene augmentation therapies on a- and b-wave amplitude as well as the ratio between b- and a-wave amplitudes (b/a-ratio) extracted from ERG data. Subgroup analyses and meta-regression were performed for model, dose, age at injection, follow-up time point and delivery method. Between-study heterogeneity was assessed with a Chi-square test of homogeneity (I2). We identified 25 studies that target RS1 and met our search string. A total of 19 of these studies reported rodent viral methods in vivo. Six of the 25 studies used non-viral or alternative delivery methods, either in vitro or in vivo. Of these, five studies described non-viral methods and one study described an alternative delivery method. The 19 aforementioned in vivo studies were assessed for risk of bias and quality assessments and showed inconsistency in reporting. This resulted in an unclear risk of bias in most included studies. All 19 studies used AAVs to deliver intact human or murine RS1 in rodent models for XLRS. Meta-analyses of a-wave amplitude, b-wave amplitude, and b/a-ratio showed that, overall, AAV-mediated gene augmentation therapy significantly ameliorated the disease phenotype on these parameters. Subgroup analyses and meta-regression showed significant correlations between b-wave amplitude effect size and dose, although between-study heterogeneity was high. This systematic review reiterates the high potential for gene therapy in XLRS, while highlighting the importance of careful preclinical study design and reporting. The establishment of a systematic approach in these studies is essential to effectively translate this knowledge into novel and improved treatment alternatives.

Vitreomacular traction in diabetic retinopathy.

PURPOSE: Vitreomacular traction (VMT) has unique presentations in eyes with diabetic retinopathy (DR). This study aimed to investigate the characteristics and clinical course of VMT in DR. STUDY DESIGN: A retrospective case series. METHODS: Thirty eyes from 30 patients with DR and concurrent VMT were retrospectively enrolled. Baseline and final best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) characteristics were reported. Linear regression models were used to analyze the correlating factors for visual outcome. RESULTS: Of the 30 eyes, a thickened posterior hyaloid membrane was noted in all cases and multi-layered traction from different directions in 14 eyes (46.7%). Twenty-one eyes (70%) had tractional macular retinoschisis, seven (23.3%) had foveal detachment, five (16.7%) had a lamellar macular hole, and three (10%) had a full-thickness macular hole, including two with macular hole retinal detachment. Three eyes had spontaneous release of the VMT within 3 months of observation. For the remaining 27 eyes receiving operations, the VMT, full-thickness macular hole, and serous foveal detachment all resolved postoperatively with residual macular schisis in 6 eyes (22.2%) only. None of the baseline OCT characteristics were associated with postoperative BCVA (P > .05). CONCLUSIONS: VMT in DR had a thickened posterior hyaloid, and many of them had multi-layered traction and/or concurrent macular retinoschisis. Lamellar macular hole, full-thickness macular hole, or concurrent retinal detachment may also occur. Spontaneous resolution of VMT rarely occurred, and those who underwent operation for VMT had improved vision and macular structures with resolution of the macular hole and retinal detachment.

Retinal Detachments in Pediatric Patients With X-Linked Retinoschisis: Characteristics and Surgical Outcomes.

BACKGROUND AND OBJECTIVE: Retinal detachments (RDs) are a complication of X-linked retinoschisis (XLRS) with a poor prognosis. This study aims to report outcomes of XLRS-RD repair in pediatric patients. MATERIALS AND METHODS: The study is a retrospective analysis of pediatric patients undergoing vitreoretinal surgery for XLRS-RDs from 2000 to 2022. RESULTS: Nine patients (11 eyes) met inclusion criteria. All patients were boys, with a mean age of 8 years. Most RDs arose inferiorly (64%). Seven (64%) detachments were macula-involving. Seven (64%) detachments were repaired with combined scleral buckling and vitrectomy, two (18%) detachments were repaired with vitrectomy alone, one (9%) detachment underwent a primary scleral buckling procedure, and one (9%) asymptomatic detachment with a pigment demarcation line was observed. Silicone oil was used in eight of nine (89%) eyes undergoing vitrectomy. Final visual acuity was 20/200 or better in eight (73%) eyes. One eye that underwent surgical intervention remained unattached at follow-up. CONCLUSION: Surgical repair in patients with XLRSRDs was associated with successful reattachment, although visual prognosis varied. [Ophthalmic Surg Lasers Imaging Retina 2023;54:574-579.].

Concurrent Foveoschisis and Atrophy in a Patient With X-Linked Retinoschisis and Type 1 Diabetes Mellitus.

We report the case of a 28-year-old man with X-linked retinoschisis (XLRS) and type I diabetes mellitus. The patient had bilateral foveoschisis with a tractional retinal fold in the right eye. Optical coherence tomography (OCT) revealed hyperreflective material within the inner nuclear and outer plexiform layers, photoreceptor atrophy, and retinal pigment epithelium irregularities in both eyes. Fluorescein angiography showed hyperfluorescent foveal spots corresponding to the hyperreflective material observed on OCT. This is a unique presentation of XLRS, with concurrent foveoschisis and photoreceptor atrophy in both eyes. The hyperreflective material on OCT serves as a distinctive feature of XLRS. [Ophthalmic Surg Lasers Imaging Retina 2023;54:603-606.].

Stellate nonheritable idiopathic foveomacular retinoschisis in juveniles: case report.

BACKGROUND: Stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) is a rare type of retinoschisis with a spoke-like splitting that occurs in the outer plexus layer. We present a case of stellate nonhereditary idiopathic foveomacular retinoschisis in a juvenile, in which two eyes show different development trends and macular retinoschisis could be associated with mechanical force in the Henle fibre layer. The removal of mechanical force can partially restore vision. CASE PRESENTATION: A 14-year-old girl with bilateral SNIFR was diagnosed and followed up with spectral-domain optical coherence tomography (SD-OCT). During the two follow-up visits, vitreous adhesion was released in the left eye, and visual acuity improved. Neuroepithelial detachment was aggravated in the right eye, and visual acuity decreased. Therefore, vitrectomy was performed on the right eye. After surgery, the patient's retina was reattached, and her vision was partially restored. CONCLUSIONS: We reported a juvenile with bilateral SNIFR. Each of her eyes showed different development trends, so we adopted different treatment methods for each eye. Vitrectomy was performed on the patient to address progressive vision loss, which improved the patient's vision. It was further confirmed that the Henle layer of SNIFR patients was susceptible to posterior vitreous membrane adhesion.

Vitreous Hemorrhage in Pediatric Patients With X-Linked Retinoschisis: Characteristics and Outcomes.

OBJECTIVE: To report the management and outcomes of vitreous hemorrhage in pediatric patients with X-linked retinoschisis (XLRS). MATERIALS AND METHODS: Retrospective case series of pediatric patients with XLRS with vitreous hemorrhage between January 2000 and January 2022 at the Bascom Palmer Eye Institute. RESULTS: Nine patients (12 eyes) met inclusion criteria. The average age at presentation was 5.75 years and mean follow-up time was 6 years. All eyes (58.3%) that underwent fluorescein angiography exhibited peripheral capillary dropout. Six of 12 eyes (50%) were observed without intervention. Four of 12 eyes (33.3%) underwent intravitreal injection of bevacizumab and 2 (16.6%) underwent vitreoretinal surgery. Seven of 12 eyes (58.3%) had documented recurrence of vitreous hemorrhage during follow-up. All retinas were attached and had clear media at final follow-up. CONCLUSION: Fluorescein angiography is a helpful tool to evaluate the vascular phenotype in XLRS. Favorable anatomic outcomes were noted in this cohort, but recurrence of vitreous hemorrhage was common. [Ophthalmic Surg Lasers Imaging Retina 2023;54:513-518.].

Severe macular complications in glaucoma: high-resolution multimodal imaging characteristics and review of the literature.

PURPOSE: To describe imaging characteristics of severe macular complications occurring in glaucoma and discuss available treatments. METHODS: Retrospective case series of glaucomatous patients with macular retinoschisis (MR) and/or serous retinal detachment (SRD). Patients underwent a complete ophthalmological examination and multimodal imaging including retinography, SD-OCT, fluorescein and indocyanine green angiography (FA & ICGA) and adaptive optics (AO). RESULTS: Ten eyes (8 patients) were included. Initial BCVA was 1.04 ± 1.12 logMAR and IOP was 24.0 ± 9.3mmHg. All eyes presented with MR while SRD was present in 5 eyes (5 patients), with a central macular thickness of 573 ± 152 µm. FA and ICGA allowed to exclude leakage in all cases. A focal lamina cribrosa defect (LCD) was found in four eyes (4 patients) using OCT, with AO providing en-face visualization of the defect in one eye. Outer retinal hole was present in 3 eyes (3 patients). No visual improvement or resolution of the macular retinoschisis was observed in eyes with medical or surgical IOP control (N = 9). Vitrectomy with internal membrane limiting peeling and gas tamponade was performed in one eye with good visual results. CONCLUSIONS: Multimodal high-resolution imaging is essential to diagnose severe macular complications associated with advanced glaucoma.

Identification and molecular characterization of two recurrent missense mutations in the RS1 gene in two families with X-linked retinoschisis from North India.

X-linked retinoschisis (XLR) is a rare medical condition that involves in the splitting of neurosensory layers and the impairment of vision in the retina. In majority of the XLR cases, pathogenic variants in Retinoschisin 1 (RS1) gene have been implicated in males with an early age of onset during early childhood. In the present study, we have recruited two North Indian families having multiple affected male members, who were diagnosed with XLR. The entire protein-coding region of RS1 was screened by PCR-Sanger sequencing and two recurrent pathogenic variants (p.I81N and p.R102Q) were unraveled. The in vitro study of these variants demonstrated the aggregation of mutant RS1 within the endoplasmic reticulum. Furthermore, mutant forms of this protein showed significant intracellular retention, which was evident by the absence of retinoschisin protein fractions in the extracellular media. These inferences were also supported by extensive bioinformatics analysis of the mutants, which showed dramatic conformational changes in the local structure of retinoschisin. Thus, our study suggests that the identified pathogenic variants interfere with proper protein folding, leading to anomalous structural changes ultimately resulting in intracellular retention of retinoschisin within the retina.

SPONTANEOUS RESOLUTION OF RETINOSCHISIS IN THE SETTING OF NARROW-ANGLE GLAUCOMA: A CASE REPORT.

PURPOSE: To present a rare case of retinoschisis in the setting of narrow-angle glaucoma that demonstrated spontaneous resolution with conservative management. METHODS: Case report presentation from the Vitreous Retina Macula Specialists of Toronto in December 2020. RESULTS: A 65-year-old woman with previous bilateral laser peripheral iridotomies for narrow-angle glaucoma was referred to a tertiary retina clinic for the assessment of query macular edema in the left eye. The patient presented with a blunted foveal reflex in the left eye, and optical coherence tomography imaging demonstrated diffuse retinoschisis of outer retinal layers in the peripapillary region and nasal macula. The patient elected for conservative management, and by 10-month follow-up, her retinoschisis resolved spontaneously. CONCLUSION: Only seven cases of retinoschisis in the setting of narrow-angle glaucoma have been identified in the literature. This is the first case in this setting to demonstrate spontaneous resolution with conservative management. Although laser peripheral iridotomies have been shown to resolve retinoschisis in narrow-angle glaucoma patients, clinicians should be aware of a conservative management approach to yield a positive improvement in retinal integrity.

Macular Retinoschisis from Optic Disc without a Visible Optic Pit or Advanced Glaucomatous Cupping (No Optic Pit Retinoschisis [NOPIR]).

PURPOSE: To review eyes with peripapillary and macular retinoschisis without a visible optic pit or advanced glaucomatous optic atrophy, or No Optic Pit Retinoschisis (NOPIR). DESIGN: Retrospective multicenter case series. SUBJECTS: The study included 11 eyes of 11 patients. METHODS: Retrospective study of eyes with macular retinoschisis without a visible optic pit, advanced optic nerve head cupping, or macular leakage on fluorescein angiography. MAIN OUTCOME MEASURES: Visual acuity (VA), retinoschisis resolution, months to resolution, and recurrence of retinoschisis RESULTS: The mean age was 68.1 ± 17.6 years, mean intraocular pressure was 17.4 ± 3.8 mmHg, and the mean spherical equivalent refractive error was -3.1 ± 2.9 diopters. No subject had pathologic myopia. Seven subjects were treated for glaucoma, and 9 subjects had nerve fiber layer defects on OCT. All eyes had retinoschisis in the outer nuclear layer (ONL) in the nasal macula and extending to the edge of the optic disc, and 8 subjects had fovea-involving retinoschisis. Three nonfoveal and 4 fovea-involved eyes were observed, and 4 fovea-involved eyes with vision loss underwent surgery. Surgery involved preoperative juxtapapillary laser followed by vitrectomy and membrane and internal limiting membrane peeling with intraocular gas and face-down position. The mean baseline VA was significantly worse in the surgery group than that in the observation group (P = 0.020). Retinoschisis resolved and vision improved in all surgical cases. The mean resolution time for the surgery group was 2.75 ± 0.96 months, which was shorter than that for the observation group (28.0 ± 21.2 months; P = 0.014). No eye developed recurrence of the retinoschisis after surgery. CONCLUSIONS: Peripapillary and macular retinoschisis can develop in eyes without a visible optic pit or advanced glaucomatous cupping. Eyes without foveal involvement and those with foveal involvement but only mild decrease in vision can be observed for spontaneous resolution. If there is persistent foveal involvement with vision loss, surgery can improve vision by resolving the macular retinoschisis. Surgery for fovea-involved macular retinoschisis without a visible optic pit resulted in faster anatomic resolution and better vision recovery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Acute angle-closure in juvenile X-linked retinoschisis.

Juvenile X-linked retinoschisis (JXR), the most common inherited retinal disorder in young males, presents with a wide range of phenotypic variations. Acute angle closure in children with JXR has been reported in the literature only once before. We present a case of acute-angle closure, temporally associated with pharmacologic dilation, in a 12-year-old boy with JXR.