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Frontiers in Medicine 2024Previous studies have reported Caspase-1 () is upregulated in mouse models of Juvenile X-linked Retinoschisis (XLRS), however no functional role for in disease...
PURPOSE
Previous studies have reported Caspase-1 () is upregulated in mouse models of Juvenile X-linked Retinoschisis (XLRS), however no functional role for in disease progression has been identified. We performed electroretinogram (ERG) and standardized optical coherence tomography (OCT) in mice deficient in the Retinoschisin-1 () and and Caspase-11 genes (-KO ) to test the hypothesis that may play a role in disease evolution and or severity of disease. Currently, no studies have ventured to investigate the longer-term effects of on phenotypic severity and disease progression over time in XLRS, and specifically the effect on electroretinogram.
METHODS
-KO; mice were generated by breeding -KO mice with mice. OCT imaging was analyzed at 2-, 4-, and 15-16 months of age. Outer nuclear layer (ONL) thickness and adapted standardized cyst severity score were measured and averaged from 4 locations 500 μm from the optic nerve. Adapted standardized cyst severity score was 1: absent cysts, 2: <30 μm, 3: 30-49 μm, 4: 50-69 μm, 5: 70-99 μm, 6: >99 μm. Electroretinograms (ERG) were recorded in dark-adapted and light-adapted conditions at 2 and 4 months. Results obtained from -KO and -KO; eyes were compared with age matched WT control eyes at 2 months.
RESULTS
Intraretinal schisis was not observed on OCT in WT eyes, while schisis was apparent in most -KO and -KO; eyes at 2 and 4 months of age. There was no difference in the cyst severity score from 2 to 4 months of age, or ONL thickness from 2 to 16 months of age between -KO and -KO; eyes. ERG amplitudes were similarly reduced in -KO and -KO; compared to WT controls at 2 months of age, and there was no difference between KO and -KO; eyes at 2 or 4 months of age, suggesting no impact on the electrical function of photoreceptors over time in the absence of .
CONCLUSION
Although has been reported to be significantly upregulated in KO mice, our preliminary data suggest that removing does not modulate photoreceptor electrical function or alter the trajectory of the retinal architecture over time.
PubMed: 38938378
DOI: 10.3389/fmed.2024.1347599 -
Eye (London, England) Jun 2024
PubMed: 38849597
DOI: 10.1038/s41433-024-03158-2 -
Investigative Ophthalmology & Visual... Jun 2024The purpose of this study was to evaluate self-reported functional vision (FV) and the impact of vision loss in patients with USH2A-associated retinal degeneration using... (Observational Study)
Observational Study
PURPOSE
The purpose of this study was to evaluate self-reported functional vision (FV) and the impact of vision loss in patients with USH2A-associated retinal degeneration using a patient-reported outcome (PRO) measure, the Michigan Retinal Degeneration Questionnaire (MRDQ), to correlate MRDQ scores with well-established visual function measurements.
DESIGN
An observational cross-sectional study (n = 93) of participants who had Usher Syndrome Type 2 (USH2, n = 55) or autosomal recessive non-syndromic retinitis pigmentosa (ARRP; n = 38) associated with biallelic variants in the USH2A gene.
METHODS
The study protocol was approved by all ethics boards and informed consent was obtained from each participant. Participants completed the MRDQ at the 48-month study follow-up visit. Disease duration was self-reported by participants. One-way ANOVA was used to compare subgroups (clinical diagnosis, age, disease duration, and full-field stimulus threshold [FST] Blue-Red mediation) on mean scores per domain. Spearman correlation coefficients were used to assess associations between MRDQ domains and visual/retinal function assessments.
RESULTS
Of the study sample, 58% were female participants and the median disease duration was 13 years. MRDQ domains were sensitive to differences between subgroups of clinical diagnosis, age, disease duration, and FST Blue-Red mediation. MRDQ domains correlated with static perimetry, microperimetry, full-field stimulus testing, and best-corrected visual acuity (BCVA).
CONCLUSIONS
Self-reported FV measured by the MRDQ, when applied to USH2 and ARRP participants, had good distributional characteristics and correlated well with visual function tests. MRDQ adds a new dimension of understanding on vision-related functioning and establishes this PRO tool as an informative measure in evaluating USH2A outcomes.
Topics: Humans; Female; Male; Cross-Sectional Studies; Middle Aged; Visual Acuity; Extracellular Matrix Proteins; Adult; Self Report; Usher Syndromes; Surveys and Questionnaires; Retinal Degeneration; Aged; Young Adult; Quality of Life; Adolescent; Retinitis Pigmentosa
PubMed: 38833260
DOI: 10.1167/iovs.65.6.5 -
Stem Cell Research & Therapy May 2024X-linked juvenile retinoschisis (XLRS) is an inherited disease caused by RS1 gene mutation, which leads to retinal splitting and visual impairment. The mechanism of...
BACKGROUND
X-linked juvenile retinoschisis (XLRS) is an inherited disease caused by RS1 gene mutation, which leads to retinal splitting and visual impairment. The mechanism of RS1-associated retinal degeneration is not fully understood. Besides, animal models of XLRS have limitations in the study of XLRS. Here, we used human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) to investigate the disease mechanisms and potential treatments for XLRS.
METHODS
hiPSCs reprogrammed from peripheral blood mononuclear cells of two RS1 mutant (E72K) XLRS patients were differentiated into ROs. Subsequently, we explored whether RS1 mutation could affect RO development and explore the effectiveness of RS1 gene augmentation therapy.
RESULTS
ROs derived from RS1 (E72K) mutation hiPSCs exhibited a developmental delay in the photoreceptor, retinoschisin (RS1) deficiency, and altered spontaneous activity compared with control ROs. Furthermore, the delays in development were associated with decreased expression of rod-specific precursor markers (NRL) and photoreceptor-specific markers (RCVRN). Adeno-associated virus (AAV)-mediated gene augmentation with RS1 at the photoreceptor immature stage rescued the rod photoreceptor developmental delay in ROs with the RS1 (E72K) mutation.
CONCLUSIONS
The RS1 (E72K) mutation results in the photoreceptor development delay in ROs and can be partially rescued by the RS1 gene augmentation therapy.
Topics: Retinoschisis; Humans; Induced Pluripotent Stem Cells; Eye Proteins; Genetic Therapy; Organoids; Mutation; Retina; Male; Cell Differentiation
PubMed: 38816767
DOI: 10.1186/s13287-024-03767-4 -
The British Journal of Ophthalmology May 2024Choroidal neovascularisation (CNV) in patients with X-linked retinoschisis (XLRS) has been poorly documented. This study aims to investigate the prevalence and clinical...
AIMS
Choroidal neovascularisation (CNV) in patients with X-linked retinoschisis (XLRS) has been poorly documented. This study aims to investigate the prevalence and clinical characteristics of CNV in patients with XLRS, as well as analyse the preliminary genotype-phenotype correlation.
METHODS
A retrospective case series of patients with genetically confirmed XLRS was included. Demographic, clinical and genetic features were analysed, with a comparison between CNV and non-CNV eyes.
RESULTS
Among 185 eyes of 129 patients with XLRS, the prevalence of CNV was 8.1% (15/185). The mean diagnostic age of all patients with CNV is 5.1±2.56 years. CNV eyes exhibited a mean best-corrected visual acuity (BCVA) (logarithm of the minimal angle of resolution) of 1.37±0.74. All CNVs were classified as subretinal and active. Peripapillary CNVs accounted for 80.0% (12/15), while subfoveal CNVs accounted for 20.0% (3/15). In CNV eyes, the prevalence of macular atrophy (5/15, 33.3%, p=0.013) and bullous peripheral schisis (14/15, 93.3%, p=0.000) was higher compared with non-CNV eyes. Additionally, CNV eyes exhibited poorer integrity of the outer retina and BCVA (p=0.007) compared with non-CNV eyes. All 15 eyes with CNV underwent anti-vascular endothelial growth factor (anti-VEGF) therapy. Genotype analysis revealed that 7 of 10 patients (70.0%, 10 eyes) were predicted to have missense variants, while 3 of 10 patients (30.0%, 5 eyes) exhibited severe variants.
CONCLUSIONS
The prevalence of CNV in XLRS eyes was found to be 8.1%. All CNVs secondary to XLRS were active and classified as type 2. CNV eyes demonstrated poorer visual function and compromised retinal structures. Anti-VEGF therapy demonstrated effectiveness in treating XLRS-CNVs. No significant genotype-phenotype correlation was established.
PubMed: 38811052
DOI: 10.1136/bjo-2023-324165 -
BMC Ophthalmology May 2024Macular retinoschisis (MRS) and myopic macular neovascularization (mMNV) are both potentially blinding complications of high myopia. In this case report, we highlight... (Review)
Review
BACKGROUND
Macular retinoschisis (MRS) and myopic macular neovascularization (mMNV) are both potentially blinding complications of high myopia. In this case report, we highlight the progression of MRS after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for mMNV, as well as an extensive review of the literature on this topic.
CASE DESCRIPTION
A 49-year-old woman presented with two weeks of recent onset blurring and metamorphopsia in her right eye. She had high myopia in both eyes (right eye - 20/60 with - 16D, left eye - 20/20 with - 13D). Slit-lamp ophthalmoscopy found a normal anterior segment in both eyes. On fundus examination, features of pathological myopia with posterior staphyloma and peripapillary atrophy were observed in both eyes. An active mMNV, as well as intraretinal fluid, minimal perifoveal inner and outer MRS, and focal posterior vitreous traction along the inferotemporal retinal arcade, were detected on optical coherence tomography (OCT) of the right eye. The patient received an intravitreal injection of Aflibercept (2 mg/0.05 ml).
RESULTS
OCT scans at two- and four-month follow-up visits revealed regressed mMNV with a taut epiretinal membrane, progressive worsening of outer MRS, and the development of multiple perifoveal retinal detachment inferior to the fovea. Pars plana vitrectomy surgery was performed for the progressive MRS with good anatomical (resolved MRS) and functional outcome (maintained visual acuity at 20/60) at the last one-month post-surgery visit.
CONCLUSION
Intravitreal anti-VEGF injections for mMNV can cause vitreoretinal interface changes, exacerbating MRS and causing visual deterioration. Vitrectomy for MRS could be one of several treatment options.
Topics: Humans; Receptors, Vascular Endothelial Growth Factor; Female; Intravitreal Injections; Middle Aged; Retinoschisis; Recombinant Fusion Proteins; Myopia, Degenerative; Tomography, Optical Coherence; Visual Acuity; Angiogenesis Inhibitors; Disease Progression; Retinal Neovascularization; Fluorescein Angiography
PubMed: 38807066
DOI: 10.1186/s12886-024-03497-4 -
Genes May 2024Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of diseases which cause visual loss due to Mendelian mutations in over 250 genes,...
Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of diseases which cause visual loss due to Mendelian mutations in over 250 genes, making genetic diagnosis challenging and time-consuming. Here, we developed a new tool, CDIP (Cost-effective Deep-sequencing IRD Panel) in which a simultaneous sequencing of common mutations is performed. CDIP is based on simultaneous amplification of 47 amplicons harboring common mutations followed by next-generation sequencing (NGS). Following five rounds of calibration of NGS-based steps, CDIP was used in 740 IRD samples. The analysis revealed 151 mutations in 131 index cases. In 54 (7%) of these cases, CDIP identified the genetic cause of disease (the remaining were single-heterozygous recessive mutations). These include a patient that was clinically diagnosed with retinoschisis and found to be homozygous for -c.932G>A (p.R311Q), and a patient with RP who is hemizygous for an variant, c.292C>A (p.H98N), which was not included in the analysis but is located in proximity to one of these mutations. CDIP is a cost-effective deep sequencing panel for simultaneous detection of common founder mutations. This protocol can be implemented for additional populations as well as additional inherited diseases, and mainly in populations with strong founder effects.
Topics: Humans; High-Throughput Nucleotide Sequencing; Mutation; Retinal Diseases; Founder Effect; Male; Female; Genetic Testing; Cost-Benefit Analysis; Pedigree
PubMed: 38790275
DOI: 10.3390/genes15050646 -
Journal of Glaucoma May 2024Peripapillary retinoschisis may bias optical coherence tomography's monitoring of glaucoma progression. Its impact on glaucoma still remains uncertain. Only two out of...
PRCIS
Peripapillary retinoschisis may bias optical coherence tomography's monitoring of glaucoma progression. Its impact on glaucoma still remains uncertain. Only two out of the ten included studies illustrated a correlation between peripapillary retinoschisis and glaucoma progression.
PURPOSE
The frequent use of optical coherence tomography increased the detection of peripapillary retinoschisis, which poses challenges in the follow-up of glaucoma patients. This systematic review aims to summarize the literature regarding peripapillary retinoschisis in glaucoma, exploring its prevalence, impact on disease, and clinical management implications.
METHODS
We searched PubMed, Embase, Web of Science and Scopus with tailored search queries for each platform. All studies had to report peripapillary retinoschisis in glaucoma patients. Exclusion criteria included studies with less than 10 eyes, studies focusing on schisis outside the disc area, with concomitant retinal or optic nerve lesions, with animals, reviews, studies written in non-English language and congress abstracts.
RESULTS
Ten studies were included, of which 7 were case-control, one was a cohort study and two were case series.Six studies showed that peripapillary retinoschisis often overlapped pre-existing retinal nerve fiber layer defects. One study reported that the de novo development of peripapillary retinoschisis was more frequent in eyes with glaucoma progression than in eyes without progression.Visual field findings were inconsistent, with just one study (out of six) showing that glaucoma patients with peripapillary retinoschisis experienced faster visual field deterioration than those without it. Overall, solely two studies (out of seven) associated peripapillary retinoschisis with faster glaucoma progression.
CONCLUSIONS
Peripapillary retinoschisis biases optical coherence tomography analysis in glaucoma. Caution is needed against overestimation of retinal nerve fiber layer thickness when peripapillary retinoschisis develops, and misinterpretation of its resolution as rapid progression. Peripapillary retinoschisis' exact impact on glaucoma progression remains unclear.
PubMed: 38771637
DOI: 10.1097/IJG.0000000000002437 -
Frontiers in Neurology 2024Highly myopic optic nerve head (ONH) abnormalities encompass a series of complications resulting from the stretching of papillary and peripapillary structures during... (Review)
Review
Highly myopic optic nerve head (ONH) abnormalities encompass a series of complications resulting from the stretching of papillary and peripapillary structures during significant axial elongation. The morphological changes in the ONH typically initiate with disk tilting or rotation, progressing to PHOMS and PPA. Tissue defects in each layer manifest as focal lamina cribrosa defects (FLDs), peripapillary intrachoroidal cavitations (PICCs), and acquired pits of the optic nerve (APON). Anterior vitreous/vascular traction and posterior scleral protrusion may lead to prelaminar schisis as well as paravascular cysts and holes, which can potentially develop into retinoschisis. Traditional color fundus photography (CFP) is often insufficient for visualizing most of these lesions, yet their description and quantification benefit significantly from the advancements in optical coherence tomography (OCT) and OCT angiography (OCTA), complemented by fundus autofluorescence (FAF), indocyanine green angiography (ICGA), and three-dimensional imaging. The effective diagnosis and classification of ONH abnormalities heavily rely on a comprehensive understanding of their multimodal imaging features, as outlined in this review. These findings provide valuable insights into optic neuropathy in high myopia, establishing a solid foundation for future endeavors in disease monitoring and treatment guidance.
PubMed: 38715686
DOI: 10.3389/fneur.2024.1366593 -
Ophthalmic & Physiological Optics : the... Jul 2024The aim of this study was to investigate the microcirculatory characteristics of the dome-shaped macula (DSM), its complications in highly myopic eyes and to explore the...
Evaluating the microcirculation of the dome-shaped macula and its complications in adults with highly myopic eyes by swept-source optical coherence tomography angiography.
PURPOSE
The aim of this study was to investigate the microcirculatory characteristics of the dome-shaped macula (DSM), its complications in highly myopic eyes and to explore the factors associated with a DSM.
METHODS
This cross-sectional case-control study included a total of 98 subjects (98 eyes): 49 eyes with DSM and 49 eyes without DSM. The axial length (AL) of the myopic eyes was matched 1:1 to eliminate the effect of AL differences on the results. Choroidal (CT) and scleral thickness (ST) and other structural parameters were assessed by swept-source optical coherence tomography (SS-OCT). OCT angiography was used to measure microcirculatory parameters in highly myopic eyes.
RESULTS
Subjects with DSM had thinner subfoveal choroidal thickness (46.01 ± 13.25 vs. 81.62 ± 48.26 μm; p < 0.001), thicker subfoveal scleral thickness (SFST; 331.93 ± 79.87 vs. 238.74 ± 70.96 μm; p < 0.001) and thinner foveal CT (66.86 ± 24.65 vs. 107.85 ± 52.65 μm; p < 0.001) compared to subjects without DSM. The foveal choroidal perfusion area (0.72 ± 0.04 vs. 0.76 ± 0.04 mm; p < 0.001) and foveal choroidal vascularity index (0.15 ± 0.04 vs. 0.33 ± 0.14; p < 0.001) were significantly lower in eyes with DSM. Retinoschisis (81.6% vs. 38.8%; p < 0.001) was more common in eyes with DSM. Eyes with horizontal DSM had worse best-corrected logMAR visual acuity than eyes with round DSM (0.34 ± 0.22 vs. 0.23 ± 0.22; p = 0.03). DSM height (98.95 ± 65.17 vs. 104.63 ± 44.62 μm; p = 0.05) was lower in the horizontal DSM. SFST (OR = 1.06, p = 0.04) and foveal choroidal vascularity index (OR = 0.711, p = 0.02) were significantly associated with DSM. DSM width (p < 0.001), foveal choroidal perfusion area (p = 0.01), foveal choriocapillaris perfusion area (p = 0.02) and parafoveal choroidal vascularity index (p = 0.03) were the most significantly associated factors with DSM height.
CONCLUSIONS
The microcirculatory characteristics of eyes with DSM differed from those without DSM. Microcirculatory abnormalities were significantly associated with a DSM. The height of the DSM was associated with decreased blood perfusion.
Topics: Humans; Tomography, Optical Coherence; Male; Female; Cross-Sectional Studies; Macula Lutea; Microcirculation; Case-Control Studies; Middle Aged; Adult; Fluorescein Angiography; Visual Acuity; Retinal Vessels; Myopia, Degenerative; Choroid; Fundus Oculi
PubMed: 38685756
DOI: 10.1111/opo.13314