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International Journal of Molecular... Mar 2024Aland island eye disease (AIED), an incomplete form of X-linked congenital stationary night blindness (CSNB2A), and X-linked cone-rod dystrophy type 3 (CORDX3) display...
Aland island eye disease (AIED), an incomplete form of X-linked congenital stationary night blindness (CSNB2A), and X-linked cone-rod dystrophy type 3 (CORDX3) display many overlapping clinical findings. They result from mutations in the gene encoding the α subunit of the Cav1.4 channel, which plays a key role in neurotransmission from rod and cone photoreceptors to bipolar cells. Case report: A 57-year-old Caucasian man who had suffered since his early childhood from nystagmus, nyctalopia, low visual acuity and high myopia in both eyes (OU) presented to expand the diagnostic process, because similar symptoms had occurred in his 2-month-old grandson. Additionally, the patient was diagnosed with protanomalous color vision deficiency, diffuse thinning, and moderate hypopigmentation of the retina. Optical coherence tomography of the macula revealed retinoschisis in the right eye and foveal hypoplasia in the left eye. Dark-adapted (DA) 3.0 flash full-field electroretinography (ffERG) amplitudes of a-waves were attenuated, and the amplitudes of b-waves were abolished, which resulted in a negative pattern of the ERG. Moreover, the light-adapted 3.0 and 3.0 flicker ffERG as well as the DA 0.01 ffERG were consistent with severely reduced responses OU. Genetic testing revealed a hemizygous form of a stop-gained mutation (c.4051C>T) in exon 35 of the gene. This pathogenic variant has so far been described in combination with a phenotype corresponding to CSNB2A and CORDX3. This report contributes to expanding the knowledge of the clinical spectrum of -related disease. Wide variability and the overlapping clinical manifestations observed within AIED and its allelic disorders may not be explained solely by the consequences of different mutations on proteins. The lack of distinct genotype-phenotype correlations indicates the presence of additional, not yet identified, disease-modifying factors.
Topics: Male; Humans; Child, Preschool; Infant; Middle Aged; Retinoschisis; Calcium Channels, L-Type; Genetic Diseases, X-Linked; Retinal Diseases; Retina; Mutation; Night Blindness; Myopia; Albinism, Ocular; Retinitis Pigmentosa; Eye Diseases, Hereditary
PubMed: 38474172
DOI: 10.3390/ijms25052928 -
BMC Ophthalmology Mar 2024Myopic traction maculopathy (MTM) is a complication of pathological myopia and encompasses various pathological conditions caused by tractional changes in the eye. These... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myopic traction maculopathy (MTM) is a complication of pathological myopia and encompasses various pathological conditions caused by tractional changes in the eye. These changes include retinoschisis, foveal retinal detachment, and lamellar or full-thickness macular holes (FTMHs). This meta-analysis evaluated the safety and efficacy of novel surgical for treating MTM.
METHODS
To compare the outcomes of different surgical approaches for MTM, multiple databases, including Web of Science, PubMed, Scopus, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, and the Meta-Register of Controlled Trials, were comprehensively searched. The meta-analysis was performed using RevMan 5.1.
RESULTS
Nine comparative studies involving 350 eyes were included in this meta-analysis. There were significant differences between fovea-sparing internal limiting membrane peeling (FSIP) and standard internal limiting membrane peeling (ILMP). Preoperative best-corrected visual acuity BCVA (standard mean difference (SMD): -0.10, 95% CI: -0.32 to 0.12) and central foveal thickness CFT (SMD: 0.05, 95% CI: -0.22 to 0.33) were not significantly different (p = 0.39 and p = 0.71, respectively). However, the postoperative BCVA improved significantly (SMD = - 0.47, 95% CI: - 0.80, - 0.14, p = 0.006) in the FSIP group compared to the standard ILMP group. Postoperative CFT did not differ significantly between the two groups (p = 0.62). The FSIP group had a greater anatomical success rate than the other groups, although the difference was not statistically significant (p = 0.26). The incidence of postoperative macular hole formation was significantly lower (OR = 0.19, 95% CI = 0.07-0.54; p = 0.05) in the FSIP group than in the standard ILMP group. The unique characteristics of highly myopic eyes, such as increased axial length and structural changes, may have contributed to the greater incidence of FTMH in the ILMP group.
CONCLUSION
Based on the findings of this meta-analysis, FSIP is the initial surgical approach for early-stage MTM and has shown promising outcomes. However, to establish the safest and most efficient surgical technique for treating different MTM stages, further comparative studies, specifically those focusing on ILMP and FSIP, are necessary.
TRIAL REGISTRATION
Retrospectively registered.
Topics: Humans; Fovea Centralis; Macular Degeneration; Myopia, Degenerative; Retinal Detachment; Retinal Perforations
PubMed: 38443856
DOI: 10.1186/s12886-024-03374-0 -
Scientific Reports Mar 2024We evaluated the distribution and types of retinal hemorrhages (RHs) and other damages in eyes with abusive head trauma (AHT). This retrospective, consecutive case...
We evaluated the distribution and types of retinal hemorrhages (RHs) and other damages in eyes with abusive head trauma (AHT). This retrospective, consecutive case series of AHT and non-AHT conditions involved 54 children with AHT, 43 children with head bruises, and 49 children with blunt eye trauma, each of non-AHT supported by reliable witness accounts. RHs and other damage were evaluated using ophthalmoscopy and wide-field fundus photography. A variety of RH types and other damage were identified in the AHT group but not in the non-AHT group. RHs in AHT extended from the posterior pole to the far periphery in 77% of eyes and on/near the veins in 86% and arteries in 85%, most of which were in the far periphery. Retinoschisis, white-dot lesions, and retinal folds were seen even in the far periphery. RHs on/near the veins and arteries, retinoschisis, and retinal folds suggest a traumatic mechanism of the tractional force of the vitreous that is attached to the entire retinal surface. Identifying the distribution and arterio and venous origins of RHs is a key factor in determining the association with trauma. Thus, wide-field fundus photography is useful to record and evaluate the origin of the RHs and other retinal damage.
Topics: Child; Humans; Retinal Hemorrhage; Retinoschisis; Retrospective Studies; Craniocerebral Trauma; Retinal Diseases; Eye Injuries; Retina
PubMed: 38438406
DOI: 10.1038/s41598-024-54664-y -
Frontiers in Medicine 2024X-linked retinoschisis (XLRS), due to loss-of-function mutations in the retinoschisin () gene, is characterized by a modest to severe decrease in visual acuity. Clinical...
PURPOSE
X-linked retinoschisis (XLRS), due to loss-of-function mutations in the retinoschisin () gene, is characterized by a modest to severe decrease in visual acuity. Clinical trials for XLRS utilizing intravitreal (IVT) gene therapy showed ocular inflammation. We conducted a subretinal dose-response preclinical study using rAAV2tYF-CB-h utilizing the knockout (-KO) mouse to investigate short- and long-term retinal rescue after subretinal gene delivery.
METHODS
-KO mice were subretinally injected with 2 μL of rAAV2tYF-CB-h vector with 8E9 viral genomes (vg)/eye, 8E8 vg/eye, 8E7 vg/eye, or sham injection, and compared to untreated eyes. Reconstitution of human RS1 protein was detected using western blotting. Analysis of retinal function by electroretinography (ERG) and structural analysis by optical coherence tomography (OCT) were performed at 1, 2, 3, 5, 7, and 12 months post injection (MPI). Immunohistochemistry (IHC) was performed to evaluate cone rescue on the cellular level. Functional vision was evaluated using a visually guided swim assay (VGSA).
RESULTS
Western blotting analysis showed human RS1 protein expression in a dose-dependent manner. Quantification of western blotting showed that the RS1 protein expression in mice treated with the 8E8 vg dose was near the wild-type (WT) expression levels. ERG demonstrated dose-dependent effects: At 1 MPI the 8E8 vg dose treated eyes had higher light-adapted (LA) ERG amplitudes in 3.0 flash and 5 Hz flicker compared to untreated ( < 0.0001) and sham-treated eyes ( < 0.0001) which persisted until the 12 MPI endpoint, consistent with improved cone function. ERG b-wave amplitudes were higher in response to dark-adapted (DA) 0.01 dim flash and 3.0 standard combined response (SCR) compared to sham-treated ( < 0.01) and untreated eyes ( < 0.001) which persisted until 3 MPI, suggesting short-term improvement of the rod photoreceptors. All injections, including sham-treated, resulted in a cyst severity score of 1 (no cavities), with significant reductions compared to untreated eyes up to 3 MPI ( < 0.05). The high and low dose groups showed inconsistent ERG improvements, despite reduced cyst severity, emphasizing the dose-dependent nature of gene augmentation's efficacy and the tenuous connection between cyst reduction and ERG improvement. IHC data showed a significant cone rescue in eyes treated with the 8E8 vg dose compared to sham-treated and untreated eyes. VGSA showed better functional vision in 8E8 vg dose treated mice. Eyes treated with the highest dose showed occasional localized degeneration in the outer nuclear layer.
CONCLUSION
Our data suggest that a dose of 8E8 vg/eye subretinally improves retinal function and structure in the -KO mouse. It improves cone function, rod function, and reduces cyst severity. Sham treatment resolves schisis cysts, but 8E8 vg/eye is needed for optimal retinal electrical function rescue. These findings offer a promising path for clinical translation to human trials.
PubMed: 38414621
DOI: 10.3389/fmed.2024.1304819 -
Therapeutic Advances in Ophthalmology 2024X-linked retinoschisis (XLRS) is an inherited retinal degeneration affecting males, characterized by splitting of the retinal layers. We herein present the outcomes of...
Early recurrence of macular schisis in X-linked retinoschisis treated with vitrectomy for rhegmatogenous retinal detachment under silicone oil: case report and brief literature review.
X-linked retinoschisis (XLRS) is an inherited retinal degeneration affecting males, characterized by splitting of the retinal layers. We herein present the outcomes of surgical treatment in a case of XLRS complicated by rhegmatogenous retinal detachment (RRD). A 22-year-old male presented to the emergency department due to decreased visual acuity and visual field defect in his left eye Oculus Sinister (OS) of 1 week duration. The patient reported an early onset retinal degeneration and decreased visual acuity in both eyes since childhood in his past ocular history. Upon presentation, best corrected visual acuity (BCVA) was 6/30 on the right eye Oculus Dexter (OD) and 6/120 OS. Fundus examination revealed areas of peripheral retinal schisis, and the characteristic spoke wheel pattern on the macula of both eyes. In OS, a temporal RRD involving the macula was identified. The patient underwent surgical treatment with pars plana vitrectomy with internal limiting membrane (ILM) peeling, endolaser, and silicone oil (SO) tamponade. BCVA in OS improved to 6/60 and schistic cavities resolution was observed in the immediate postoperative period. The patient's BCVA further improved to 6/19 at 1 month, as foveal anatomy showed relative improvement. However, there was a rapid reappearance of schisis spaces in the macular area at this point, which was also followed by progressive deterioration of foveal schisis by 3 months post-operatively. The resorption and recurrence of lamellar macular schisis changes after ILM peel and presence of SO, highlights that although XLRS findings can temporarily improve upon surgical intervention, the pathogenetic mechanisms contributing to disease phenotype remain to be elucidated.
PubMed: 38406626
DOI: 10.1177/25158414241232261 -
Journal of Ayub Medical College,... 2023Optic disc pits are hypothesized to form because of failure of embryonic fissure closure, which can also present with congenital defects in the choroid, RPE, and... (Review)
Review
Optic disc pits are hypothesized to form because of failure of embryonic fissure closure, which can also present with congenital defects in the choroid, RPE, and neurosensory retina. It is also associated with serous macular detachment. We present a case report of a 32-year-old man with an optic disc pit and independent choroidal coloboma below the inferior peripapillary area in the left eye, associated with macular retinoschisis with serous detachment.
Topics: Adult; Humans; Male; Coloboma; Eye Abnormalities; Optic Disk; Retinal Detachment; Retinoschisis
PubMed: 38404105
DOI: 10.55519/JAMC-03-11574 -
American Journal of Ophthalmology Jul 2024To evaluate the severity and related factors of macular retinoschisis (MRS) and paravascular retinoschisis (PVRS) in high myopia (HM) using ultra-wide-field optical...
PURPOSE
To evaluate the severity and related factors of macular retinoschisis (MRS) and paravascular retinoschisis (PVRS) in high myopia (HM) using ultra-wide-field optical coherence tomography (UWF-OCT) and a novel Gaussian curvature (K).
DESIGN
A cross-sectional study.
METHODS
Patients diagnosed with HM in Peking Union Medical College Hospital were recruited between January 2022 and November 2022. The presence and severity of retinoschisis, along with the three highest K values, were assessed using UWF-OCT and en face images. Logistic regressions were employed to identify factors associated with MRS, PVRS, and the severity of retinoschisis in the 24 × 20 mm scan region.
RESULTS
A total of 108 HM eyes from 55 patients were recruited. The highest Gaussian curvature (K1) was predominantly found in the vascular arcade (43, 40%). Multivariable logistic regression found that age and PVRS were significant risk factors for MRS occurrence (P < .05), while MRS and higher K1 were significantly associated with the presence of PVRS in HM patients (P < .05). The axial length (AL) and spherical equivalent were associated with the severity of MRS, while AL and K1 values were associated with the severity of retinoschisis in the 24 × 20 mm scan region (P < .05).
CONCLUSIONS
An association existed between large Gaussian curvature and the presence of MRS and PVRS, as well as the severity of retinoschisis in a wide field of view. UWF-OCT, which enables visualization of the central and peripheral retinal areas, holds promise as an imaging technique for the early detection of extrafoveal retinoschisis.
Topics: Humans; Tomography, Optical Coherence; Retinoschisis; Male; Cross-Sectional Studies; Female; Middle Aged; Myopia, Degenerative; Adult; Visual Acuity; Macula Lutea; Aged
PubMed: 38401851
DOI: 10.1016/j.ajo.2024.02.016 -
Frontiers in Medicine 2023X-linked retinoschisis (XLRS) is a potential target for gene supplementation approaches. To establish potential structural and functional endpoints for clinical trials,...
INTRODUCTION
X-linked retinoschisis (XLRS) is a potential target for gene supplementation approaches. To establish potential structural and functional endpoints for clinical trials, a comprehensive understanding of the inter-eye symmetry, relationship between structural and functional parameters, and disease progression is vital.
METHODS
In this retrospective multicentre study, 118 eyes of 59 XLRS patients with mutations were assessed. Information from center databases included: variant; age at presentation; best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume (MV) at presentation and at the last follow up; full-field electroretinogram (ERG) findings; presence of peripheral retinoschisis and complications (vitreous hemorrhage, retinal detachment); treatment with systemic or topical carbonic anhydrase inhibitors (CAI).
RESULTS
Inter-eye symmetry revealed strong correlation in CRT ( = 0.77; < 0.0001) and moderate correlations in MV ( = 0.51, < 0.0001) and BCVA ( = 0.49; < 0.0001). Weak or no correlations were observed between BCVA and structural parameters (CRT, MV). Peripheral retinoschisis was observed in 40 (68%), retinal detachment in 9 (15%), and vitreous hemorrhage in 5 (8%) patients, respectively. Longitudinal examinations (mean, 4.3 years) showed no BCVA changes; however, a reduction of the CRT ( = 0.02), and MV ( = 0.01) was observed. Oral and/or topical CAI treatment did not significantly alter the CRT ( = 0.34).
DISCUSSION
The XLRS phenotype demonstrates a strong CRT symmetry between the eyes within individual patients and stable BCVA over several years. BCVA exhibits a weak correlation with the morphological parameters of retinal thickness (CRT MV). In our cohort, longitudinal functional changes were not significant, likely attributed to the short average follow-up period. Furthermore, CAI treatment didn't influence both morphological and functional outcomes.
PubMed: 38351967
DOI: 10.3389/fmed.2023.1331889 -
Biochemistry and Biophysics Reports Mar 2024Adeno-associated virus (AAV) vectors have been widely used in therapy to treat hereditary retinal diseases. But its transduction efficiency by intravitreal injection...
Adeno-associated virus (AAV) vectors have been widely used in therapy to treat hereditary retinal diseases. But its transduction efficiency by intravitreal injection still needs to be improved. In this study, we investigated the transduction efficiency of AAV-DJ (K137R)-GFP in different retinal cells of normal mice, as well as the therapy effection of AAV-DJ (K137R)-Rs1 on retinal function and structure in Rs1-KO mice. The intravitreal injection of AAV-DJ (K137R)-GFP demonstrated that this vector transduced cells in all layers of the retina, including the inner nuclear layer and photoreceptor layer. The intravitreal injection of AAV-DJ (K137R)-Rs1 found that 3 months post-injection of this vector improved retinal function and structure in Rs1-KO mice. Our conclusion is that AAV-DJ (K137R) vector can efficiently and safely penetrate the inner limiting membrane and transduce different layers of retinal cells in the long term, as well as being able to continuously and efficiently express target therapeutic proteins, making it a candidate therapeutic vector for X-linked retinoschisis (XLRS).
PubMed: 38333050
DOI: 10.1016/j.bbrep.2024.101646 -
Investigative Ophthalmology & Visual... Feb 2024This study investigated a three-dimensional indicator in spectral-domain optical coherence tomography (SD-OCT) and established phenotype-genotype correlation in X-linked...
PURPOSE
This study investigated a three-dimensional indicator in spectral-domain optical coherence tomography (SD-OCT) and established phenotype-genotype correlation in X-linked retinoschisis (XLRS).
METHODS
Thirty-seven patients with XLRS underwent comprehensive ophthalmic examinations, including visual acuity (VA), fundus examination, electroretinogram (ERG), and SD-OCT. SD-OCT parameters of central foveal thickness (CFT), cyst cavity volume (CCV), and photoreceptor outer segment length were assessed. CCV was defined as the sum of the areas of cyst cavities in uential B-scans, measured automatically by self-developed software (OCT-CCSEG). Structural changes of the protein associated with missense variants were quantified by molecular dynamics (MD). The correlation between genotype and phenotype was analyzed.
RESULTS
Twenty-seven different RS1 variants were identified, including a novel variant c.336_337insT(p.L113Sfs*8). The average age of onset was 14.76 ± 15.75 years, and the mean VA was 0.84 ± 0.43 logMAR. The mean CCV was 1.69 ± 1.87 mm3, correlating significantly with CFT (R = 0.66; P < 0.01). In the genotype-phenotype analysis of missense variants, CCV significantly correlated with the structural effect on the protein of mutational changes referred to as wild type, including root-mean-square deviation (R = 0.34; P = 0.04), solvent accessible surface area (R = 0.38; P = 0.02), and surface hydrophobic area (R = 0.37; P = 0.03). The amplitude of scotopic 3.0 ERG a-waves and b-waves significantly correlated with the percentage change of the β-strand in the secondary structure (a-wave: R = -0.58, P < 0.01; b-wave: R = -0.53, P < 0.01).
CONCLUSIONS
CCV is a promising indicator to quantify the structural disorganization of XLRS retina. The OCT-CCSEG software calculated CCV automatically, potentially facilitating prognosis assessment and development of personalized treatment. Moreover, MD-involved genotype-phenotype analysis suggests an association between protein structural alterations and XLRS severity measured by CCV and ERG.
Topics: Humans; Adolescent; Young Adult; Adult; Retinoschisis; Molecular Dynamics Simulation; Tomography, Optical Coherence; Retina; Cysts
PubMed: 38324300
DOI: 10.1167/iovs.65.2.17