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Stem Cell Research & Therapy Nov 2023Inherited retinal diseases (IRDs) can induce severe sight-threatening retinal degeneration and impose a considerable economic burden on patients and society, making... (Review)
Review
Inherited retinal diseases (IRDs) can induce severe sight-threatening retinal degeneration and impose a considerable economic burden on patients and society, making efforts to cure blindness imperative. Transgenic animals mimicking human genetic diseases have long been used as a primary research tool to decipher the underlying pathogenesis, but there are still some obvious limitations. As an alternative strategy, patient-derived induced pluripotent stem cells (iPSCs), particularly three-dimensional (3D) organoid technology, are considered a promising platform for modeling different forms of IRDs, including retinitis pigmentosa, Leber congenital amaurosis, X-linked recessive retinoschisis, Batten disease, achromatopsia, and best vitelliform macular dystrophy. Here, this paper focuses on the status of patient-derived iPSCs and organoids in IRDs in recent years concerning disease modeling and therapeutic exploration, along with potential challenges for translating laboratory research to clinical application. Finally, the importance of human iPSCs and organoids in combination with emerging technologies such as multi-omics integration analysis, 3D bioprinting, or microfluidic chip platform are highlighted. Patient-derived retinal organoids may be a preferred choice for more accurately uncovering the mechanisms of human retinal diseases and will contribute to clinical practice.
Topics: Animals; Humans; Induced Pluripotent Stem Cells; Retina; Retinal Degeneration; Retinitis Pigmentosa; Organoids
PubMed: 38012786
DOI: 10.1186/s13287-023-03564-5 -
Stem Cell Research Dec 2023X-linked retinoschisis (XLRS) is one of the most common retinal genetic diseases with progressive visual impairment in childhood affecting males. It is manifested with...
X-linked retinoschisis (XLRS) is one of the most common retinal genetic diseases with progressive visual impairment in childhood affecting males. It is manifested with macular and/or peripheral schisis in neural retinas with no effective treatment. Previously, we successfully generated a human-induced pluripotent stem cell (iPSC) line from an XLRS patient carrying the hemizygous RS1 c. 304C > T (p.R102W) mutation. Here, we corrected the c.304C > T mutation in the RS1 gene using CRISPR/Cas9 technology to generate an isogenic control. This cell line is valuable for the study of XLRS.
Topics: Male; Humans; Retinoschisis; Induced Pluripotent Stem Cells; Mutation; Retina; Cell Line; Eye Proteins
PubMed: 38011758
DOI: 10.1016/j.scr.2023.103263 -
Translational Vision Science &... Nov 2023This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV). (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV).
METHODS
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched systematically for controlled or non-controlled interventional gene therapy studies using key words related to retinal diseases, gene therapy, and AAV vectors. The primary outcome measure was safety, based on ocular severe adverse events (SAEs). Secondary outcome measures evaluated efficacy of the therapy based on best corrected visual acuity (BCVA) and improvements in visual sensitivity and systemic involvement following ocular delivery. Pooling was done using a DerSimonian Laird random effects model. Risk of bias was assessed using the Cochrane Risk of Bias Tool, version 1.
RESULTS
Our search identified 3548 records. Of these, 80 publications met eligibility criteria, representing 28 registered clinical trials and 5 postmarket surveillance studies involving AAV gene therapy for Leber congenital amaurosis (LCA), choroideremia, Leber hereditary optic neuropathy (LHON), age-related macular degeneration (AMD), retinitis pigmentosa (RP), X-linked retinoschisis, and achromatopsia. Overall, AAV therapy vectors were associated with a cumulative incidence of at least one SAE of 8% (95% confidence intervals [CIs] of 5% to 12%). SAEs were often associated with the surgical procedure rather than the therapeutic vector itself. Poor or inconsistent reporting of adverse events (AEs) were a limitation for the meta-analysis. The proportion of patients with any improvement in BCVA and visual sensitivity was 41% (95% CIs of 31% to 51%) and 51% (95% CIs of 31% to 70%), respectively. Systemic immune involvement was associated with a cumulative incidence of 31% (95% CI = 21% to 42%).
CONCLUSIONS
AAV gene therapy vectors appear to be safe but the surgical procedure required to deliver them is associated with some risk. The large variability in efficacy can be attributed to the small number of patients treated, the heterogeneity of the population and the variability in dosage, volume, and follow-up.
TRANSLATIONAL RELEVANCE
This systematic review will help to inform and guide future clinical trials.
Topics: Humans; Retinal Degeneration; Dependovirus; Macular Degeneration; Retinitis Pigmentosa; Genetic Therapy
PubMed: 37982768
DOI: 10.1167/tvst.12.11.24 -
Asia-Pacific Journal of Ophthalmology...To describe the optic nerve head (ONH) abnormalities in nonpathologic highly myopic eyes based on swept-source optical coherence tomography (OCT) and the relationship...
PURPOSE
To describe the optic nerve head (ONH) abnormalities in nonpathologic highly myopic eyes based on swept-source optical coherence tomography (OCT) and the relationship with visual field (VF).
DESIGN
Secondary analysis from a longitudinal cohort study.
METHODS
Highly myopic patients without myopic maculopathy of category 2 or higher were enrolled. All participants underwent a swept-source OCT examination focused on ONH. We differentiated between 3 major types (optic disc morphologic abnormality, papillary/peripapillary tissue defect, and papillary/peripapillary schisis) and 12 subtypes of ONH abnormalities. The prevalence and characteristics of ONH abnormalities and the relationship with VF were analyzed.
RESULTS
A total of 857 participants (1389 eyes) were included. Among the 1389 eyes, 91.86%, 68.61%, and 34.92% of them had at least 1, 2, or 3 ONH abnormalities, respectively, which corresponded to 29.55%, 31.79%, and 35.67% of VF defects, respectively. Among the 12 subtypes of the 3 major types, peripapillary hyperreflective ovoid mass-like structure, visible retrobulbar subarachnoid space, and prelaminar schisis were the most common, respectively. Perimetric defects corresponding to OCT abnormalities were more commonly found in eyes with peripapillary retinal detachment, peripapillary retinoschisis, and peripapillary hyperreflective ovoid mass-like structure. Glaucoma-like VF defects were more common in eyes with deep optic cups (28.17%) and with optic disc pit/pit-like change (18.92%).
CONCLUSIONS
We observed and clarified the ONH structural abnormalities in eyes with nonpathologic high myopia. These descriptions may be helpful to differentiate changes in pathologic high myopia or glaucoma.
Topics: Humans; Optic Disk; Visual Fields; Longitudinal Studies; Myopia; Glaucoma; Eye Abnormalities; Tomography, Optical Coherence; Vision Disorders
PubMed: 37851563
DOI: 10.1097/APO.0000000000000636 -
Diagnostics (Basel, Switzerland) Sep 2023Inherited retinal dystrophies (IRDs) are a group of heterogeneous diseases caused by genetic mutations that specifically affect the function of the rod, cone, or bipolar... (Review)
Review
Inherited retinal dystrophies (IRDs) are a group of heterogeneous diseases caused by genetic mutations that specifically affect the function of the rod, cone, or bipolar cells in the retina. Electroretinography (ERG) is a diagnostic tool that measures the electrical activity of the retina in response to light stimuli, and it can help to determine the function of these cells. A normal ERG response consists of two waves, the a-wave and the b-wave, which reflect the activity of the photoreceptor cells and the bipolar and Muller cells, respectively. Despite the growing availability of next-generation sequencing (NGS) technology, identifying the precise genetic mutation causing an IRD can be challenging and costly. However, certain types of IRDs present with unique ERG features that can help guide genetic testing. By combining these ERG findings with other clinical information, such as on family history and retinal imaging, physicians can effectively narrow down the list of candidate genes to be sequenced, thereby reducing the cost of genetic testing. This review article focuses on certain types of IRDs with unique ERG features. We will discuss the pathophysiology and clinical presentation of, and ERG findings on, these disorders, emphasizing the unique role ERG plays in their diagnosis and genetic testing.
PubMed: 37835784
DOI: 10.3390/diagnostics13193041 -
Diagnostics (Basel, Switzerland) Sep 2023X-linked juvenile retinoschisis (XLRS) is an inherited disorder characterized by retinal schisis cavities, which can be observed in optical coherence tomography (OCT)...
X-linked juvenile retinoschisis (XLRS) is an inherited disorder characterized by retinal schisis cavities, which can be observed in optical coherence tomography (OCT) images. Monitoring disease progression necessitates the accurate segmentation and quantification of these cavities; yet, current manual methods are time consuming and result in subjective interpretations, highlighting the need for automated and precise solutions. We employed five state-of-the-art deep learning models-U-Net, U-Net++, Attention U-Net, Residual U-Net, and TransUNet-for the task, leveraging a dataset of 1500 OCT images from 30 patients. To enhance the models' performance, we utilized data augmentation strategies that were optimized via deep reinforcement learning. The deep learning models achieved a human-equivalent accuracy level in the segmentation of schisis cavities, with U-Net++ surpassing others by attaining an accuracy of 0.9927 and a Dice coefficient of 0.8568. By utilizing reinforcement-learning-based automatic data augmentation, deep learning segmentation models demonstrate a robust and precise method for the automated segmentation of schisis cavities in OCT images. These findings are a promising step toward enhancing clinical evaluation and treatment planning for XLRS.
PubMed: 37835778
DOI: 10.3390/diagnostics13193035 -
BMC Ophthalmology Sep 2023Stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) is a rare type of retinoschisis with a spoke-like splitting that occurs in the outer plexus layer....
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.
Topics: Humans; Female; Adolescent; Retinoschisis; Retina; Macular Degeneration; Vitrectomy; Vitreous Body
PubMed: 37752454
DOI: 10.1186/s12886-023-03142-6 -
Cureus Aug 2023Stellate foveomacular retinoschisis is commonly associated with congenital X-linked retinoschisis, which is almost exclusively seen bilaterally in males. In the absence...
Stellate foveomacular retinoschisis is commonly associated with congenital X-linked retinoschisis, which is almost exclusively seen bilaterally in males. In the absence of a family history of retinoschisis and other related conditions, the term stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) is used. SNIFR constitutes a rather rare diagnosis and is usually observed unilaterally in myopic females. Within this context, we report a case of a non-myopic female patient with bilateral SNIFR detected with optical coherence tomography (OCT).
PubMed: 37664272
DOI: 10.7759/cureus.42805 -
Vitreous Hemorrhage in Pediatric Patients With X-Linked Retinoschisis: Characteristics and Outcomes.Ophthalmic Surgery, Lasers & Imaging... Sep 2023To report the management and outcomes of vitreous hemorrhage in pediatric patients with X-linked retinoschisis (XLRS).
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. .
Topics: Child; Humans; Bevacizumab; Retina; Retinoschisis; Retrospective Studies; Vitreous Hemorrhage
PubMed: 37642422
DOI: 10.3928/23258160-20230803-01 -
Frontiers in Medicine 2023X-linked retinoschisis is more common in male children and rare in females. Clinically, male patients mainly present with early onset visual impairment or vision loss,...
X-linked retinoschisis is more common in male children and rare in females. Clinically, male patients mainly present with early onset visual impairment or vision loss, and retinal retinoschisis due to division of the inner retina. We report a long-term observation of a female patient with familial foveal retinoschisis (FFR) caused by gene with complex heterozygotic mutation. The initial symptoms of the female patient reported in this study were very similar to some early manifestations of X-linked retinoschisis (XLRS) caused by mutations involving macular fovea. However, as time going on, the splitting height at retinal fovea of FFR gradually decreased, and the splitting extent at retinal fovea of FFR gradually decreased.
PubMed: 37636578
DOI: 10.3389/fmed.2023.1220075