-
Translational Vision Science &... Jun 2022The purpose of this study was to investigate the clinical characteristics of paravascular abnormalities (PVAs) and retinoschisis, and their associations with choroidal...
PURPOSE
The purpose of this study was to investigate the clinical characteristics of paravascular abnormalities (PVAs) and retinoschisis, and their associations with choroidal thickness (ChT) in young highly myopic (HM) adults.
METHODS
A total number of 645 eyes were included. Paravascular microfolds (PMs), paravascular cystoid spaces (PCs), paravascular lamellar holes (PLHs), and retinoschisis were detected using swept-source optical coherence tomography. Their associations with macular ChT and risk factors were analyzed.
RESULTS
PMs, PCs, and PLHs were detected in 203 (31.5%), 141 (21.9%), and 30 (4.7%) eyes, respectively. Retinoschisis was found in 50 (7.8%) eyes, 43 (86.0%) of which were located around the retinal vessels surrounding the optic disc. A decreasing trend of macular ChT (P < 0.001) was observed in the eyes with PMs only, with both PCs and PMs, and with PLHs, PCs, and PMs. After adjustments for age, sex, and axial length (AL), the presence of PCs, PLHs, or retinoschisis around the optic disc was negatively associated with macular ChT (all P < 0.05). Eyes with longer AL, incomplete posterior vitreous detachment (PVD), and myopic atrophic maculopathy (MAM) were more likely to have PCs (all P < 0.01) and retinoschisis around the optic disc (all P < 0.05).
CONCLUSIONS
PVAs were observed in approximately one third of the young HM adults in this study. The presence of PCs, PLHs, or retinoschisis around the optic disc was associated with thinner macular ChT. Eyes with longer AL, incomplete PVD, and MAM may be at risk of developing PVAs and retinoschisis around the optic disc.
TRANSLATIONAL RELEVANCE
PCs, PLHs, and retinoschisis around the optic disc could serve as early indicators for myopia progression.
Topics: Adult; Choroid; Humans; Myopia, Degenerative; Retinal Vessels; Retinoschisis; Tomography, Optical Coherence; Vitreous Detachment
PubMed: 35727187
DOI: 10.1167/tvst.11.6.18 -
American Journal of Ophthalmology Case... Jun 2022To determine whether the Mizuo-Nakamura phenomenon, which is an important diagnostic sign of Oguchi's disease, also occurs in patients with genetically proven X-linked...
PURPOSE
To determine whether the Mizuo-Nakamura phenomenon, which is an important diagnostic sign of Oguchi's disease, also occurs in patients with genetically proven X-linked retinoschisis (XLRS).
METHODS
We examined three patients with a clinical and genetic diagnosis of XLRS and one patient who was clinically diagnosed with Oguchi's disease, with an emphasis on the Mizuo-Nakamura phenomenon. We obtained color fundus photographs, especially in the fully dark-adapted state, using the non-mydriatic mode on a digital retinal camera and infrared observation monitor to avoid the bleaching effects caused by the viewing light, which alters the fundus color in a short time.
RESULTS
The Mizuo-Nakamura phenomenon was observed in all patients with molecularly proven XLRS, similar to that in the patient with Oguchi's disease. The sets of photographs were obtained in the light- and dark-adapted states using our newly devised techniques needed to witness the Mizuo-Nakamura phenomenon.
CONCLUSIONS AND IMPORTANCE
The Mizuo-Nakamura phenomenon was identified in three patients with genetically proven XLRS. To the best of our knowledge, this study provided the first genetic evidence of the Mizuo-Nakamura phenomenon in a patient with molecularly proven XLRS without the causative genetic abnormalities for Oguchi's disease. Our findings suggest that XLRS is responsible for the Mizuo-Nakamura phenomenon and its presence in XLRS is not a rare exception but may be a consistent manifestation of XLRS.
PubMed: 35479517
DOI: 10.1016/j.ajoc.2022.101529 -
Experimental Eye Research Jan 2023PITX2 and FOXC1 are the most common pathogenic genes associated with Axenfeld-Rieger syndrome (ARS). In this study, we aimed to explore the variation spectrum of PITX2... (Review)
Review
PITX2 and FOXC1 are the most common pathogenic genes associated with Axenfeld-Rieger syndrome (ARS). In this study, we aimed to explore the variation spectrum of PITX2 and FOXC1 and their associated phenotype based on data from our study and previously reported literatures. Whole exome sequencing was performed on eight probands in our study. Multistep bioinformatic and co-segregation analyses were performed to detect pathogenic variants. Genotype-phenotype correlations of PITX2 and FOXC1 and the differences between them were determined. We detected three variants of FOXC1 and two variants of PITX2 in five unrelated families with ARS. Macular retinoschisis had been observed in AR1 with variant in PITX2 and it is not reported before. Additionally, a review of published literature and our study led to the identification of 593 families with variants of PITX2 or FOXC1, including 316 families with heterozygous variants in FOXC1, 251 families with heterozygous variants in PITX2, 13 families with variants in double genes, seven families with homozygous or compound heterozygous variants in FOXC1, and six families with variants in ADAMTS17, PRDM5, COL4A1 or CYP1B1. Significant differences were observed between the prevalence of missense and in-frame, truncation, and large deletion variants in PITX2 (32.00%, 42.67%, and 25.33%, respectively) and FOXC1 (34.49%, 35.13%, 30.38%, respectively) (p = 1.16E-43). Enrichment and frequency analyses revealed that missense variants were concentrated in the forkhead domain of FOXC1 (76.14%) and homeodomain of PITX2 (87.50%). The percentage of Caucasians with variants in FOXC1 was significantly higher than that of PITX2 (p = 2.00E-2). Significant differences between PITX2 and FOXC1 were observed in glaucoma (p = 3.00E-2), corectopia (p = 3.050E-6), and polycoria (p = 5.21E-08). Additionally, we observed a significant difference in best-corrected visual acuity (BCVA) between FOXC1 and PITX2 (p = 3.80E-2). Among all the family members with PITX2 or FOXC1 variants, the prevalence of systemic abnormalities was significantly higher in PITX2 than in FOXC1 (89.16% vs. 58.77%, p = 5.44E-17). In conclusion, macular retinoschisis as a novel phenotype had been observed in patient with variant in PITX2. Significant differences were detected in phenotypes and genotypes between PITX2 and FOXC1.
Topics: Humans; Anterior Eye Segment; Eye Abnormalities; Eye Diseases, Hereditary; Forkhead Transcription Factors; Genetic Association Studies; Homeodomain Proteins; Mutation; Pedigree; Retinoschisis; Homeobox Protein PITX2
PubMed: 36442680
DOI: 10.1016/j.exer.2022.109307 -
Ophthalmology Feb 2022To describe the natural course, phenotype, and genotype of patients with X-linked retinoschisis (XLRS).
PURPOSE
To describe the natural course, phenotype, and genotype of patients with X-linked retinoschisis (XLRS).
DESIGN
Retrospective cohort study.
PARTICIPANTS
Three hundred forty patients with XLRS from 178 presumably unrelated families.
METHODS
This multicenter, retrospective cohort study reviewed medical records of patients with XLRS for medical history, symptoms, visual acuity (VA), ophthalmoscopy, full-field electroretinography, and retinal imaging (fundus photography, spectral-domain [SD] OCT, fundus autofluorescence).
MAIN OUTCOME MEASURES
Age at onset, age at diagnosis, severity of visual impairment, annual visual decline, and electroretinography and imaging findings.
RESULTS
Three hundred forty patients were included with a mean follow-up time of 13.2 years (range, 0.1-50.1 years). The median ages to reach mild visual impairment and low vision were 12 and 25 years, respectively. Severe visual impairment and blindness were observed predominantly in patients older than 40 years, with a predicted prevalence of 35% and 25%, respectively, at 60 years of age. The VA increased slightly during the first 2 decades of life and subsequently transitioned into an average annual decline of 0.44% (P < 0.001). No significant difference was found in decline of VA between variants that were predicted to be severe and mild (P = 0.239). The integrity of the ellipsoid zone (EZ) as well as the photoreceptor outer segment (PROS) length in the fovea on SD OCT correlated significantly with VA (Spearman's ρ = -0.759 [P < 0.001] and -0.592 [P = 0.012], respectively). Fifty-three different RS1 variants were found. The most common variants were the founder variant c.214G→A (p.(Glu72Lys)) (101 patients [38.7%]) and a deletion of exon 3 (38 patients [14.6%]).
CONCLUSIONS
Large variabilities in phenotype and natural course of XLRS were seen in this study. In most patients, XLRS showed a slow deterioration starting in the second decade of life, suggesting an optimal window of opportunity for treatment within the first 3 decades of life. The integrity of EZ as well as the PROS length on SD OCT may be important in choosing optimal candidates for treatment and as potential structural end points in future therapeutic studies. No clear genotype-phenotype correlation was found.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blindness; Child; Child, Preschool; Electroretinography; Eye Proteins; Female; Follow-Up Studies; Genetic Association Studies; Humans; Infant; Male; Middle Aged; Ophthalmoscopy; Optical Imaging; Retina; Retinal Photoreceptor Cell Outer Segment; Retinoschisis; Retrospective Studies; Tomography, Optical Coherence; Vision, Low; Visual Acuity
PubMed: 34624300
DOI: 10.1016/j.ophtha.2021.09.021 -
American Journal of Ophthalmology Case... Mar 2022To report a case of preretinal hemorrhage from extraretinal neovascularization related to capillary non-perfused retina within a large schisis in a pediatric patient...
PURPOSE
To report a case of preretinal hemorrhage from extraretinal neovascularization related to capillary non-perfused retina within a large schisis in a pediatric patient with X-linked retinoschisis (XLRS).
OBSERVATIONS
A 4-year old male with an mutation and XLRS presented with preretinal and vitreous hemorrhage in the right eye. Retinal imaging, including wide angle fluorescein angiography (FA) and optical coherence tomography (OCT), showed vitreoretinal traction on extraretinal neovascularization and capillary non-perfused retina in the schisis cavity. Laser treatment to the non-perfused retina within the schisis was successful in reducing extraretinal neovascularization.
CONCLUSIONS
Vitreous hemorrhage is a well-known occurrence in XLRS. Imaging using wide angle FA and OCT were helpful to determine the causes of hemorrhage in order to develop a management plan.
PubMed: 35198819
DOI: 10.1016/j.ajoc.2022.101395 -
Journal of Vitreoretinal Diseases 2022The rapid and noninvasive nature of optical coherence tomography angiography (OCTA) makes it a potentially valuable tool for imaging the retina in children. With the... (Review)
Review
PURPOSE
The rapid and noninvasive nature of optical coherence tomography angiography (OCTA) makes it a potentially valuable tool for imaging the retina in children. With the optimization of tabletop systems and the development of experimental handheld OCTA devices, there is expanded potential for OCTA in the clinic and the operating room. This article reviews the utility of OCTA in some of the most common pediatric retinal disorders.
METHODS
A thorough computerized PubMed search was performed to review relevant published journal articles to contextualize and identify the role of OCTA in common retinal disorders with vascular involvement affecting children. Pertinent results and findings from original investigations and case reports were summarized.
RESULTS
The ability to quickly collect both qualitative and quantitative information about retinal microvasculature, in both the clinic and operating room settings, with OCTA, has led to the uncovering of microvascular features and morphologic changes in many pediatric retinal disorders such as Coats Disease, familial exudative vitreoretinopathy, incontinentia pigmenti, sickle cell retinopathy, Stargardt Disease, X-linked juvenile retinoschisis, retinopathy of prematurity, diabetic retinopathy in type 1 diabetes, pediatric retinal tumors, and choroidal neovascularization.
CONCLUSIONS
OCTA is a relevant tool to aid early detection, guide intervention, monitor treatment response, and understand pathogenesis in a number of pediatric retinal disorders.
PubMed: 37008546
DOI: 10.1177/24741264221083873 -
Ophthalmic Genetics Oct 2020Kearns-Sayre Syndrome (KSS) is characterized by pigmentary retinopathy, external ophthalmoplegia and heart block. We report on a now 24-year-old male with clinical...
BACKGROUND
Kearns-Sayre Syndrome (KSS) is characterized by pigmentary retinopathy, external ophthalmoplegia and heart block. We report on a now 24-year-old male with clinical retinoschisis and molecularly confirmed KSS.
MATERIALS AND METHODS
Physical and complete ophthalmic examination, molecular diagnosis.
RESULTS
Over nine years of follow-up, the subject manifested progressive signs and symptoms of KSS, including external ophthalmoplegia/strabismus, ptosis, pigmentary retinopathy, corneal edema, Type I diabetes mellitus, gut dysmotility, sensorineural deafness and heart block. At age 21 he was incidentally found to have retinoschisis on optical coherence tomography that remained stable over three years follow-up. Sequencing of the gene revealed no pathogenic variants, effectively ruling out co-existing X-linked retinoschisis.
CONCLUSIONS
These findings suggest retinoschisis may be a rare manifestation of KSS. A trial of a carbonic anhydrase inhibitor was frustrated by coexisting corneal edema associated with the condition.
Topics: Adult; Humans; Kearns-Sayre Syndrome; Male; Prognosis; Retinoschisis; Tomography, Optical Coherence; Young Adult
PubMed: 32787478
DOI: 10.1080/13816810.2020.1799416 -
Expert Opinion on Biological Therapy Jan 2018The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight... (Review)
Review
INTRODUCTION
The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity.
AREAS COVERED
This review covers Leber's congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, Stargardt disease, Leber's hereditary optic neuropathy, Achromatopsia, and X-linked retinoschisis.
EXPERT OPINION
Despite great potential, gene therapy for IRD raises many questions, including the potential for less invasive intravitreal versus subretinal delivery, efficacy, safety, and longevity of response, as well as acceptance of novel study endpoints by regulatory bodies, patients, clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will require widespread genetic screening to identify and diagnose patients based on genotype instead of phenotype.
Topics: Choroideremia; Clinical Trials as Topic; Color Vision Defects; Dependovirus; Genetic Therapy; Genetic Vectors; Humans; Lentivirus; Macular Degeneration; Nerve Degeneration; Stargardt Disease; Usher Syndromes; cis-trans-Isomerases
PubMed: 29057663
DOI: 10.1080/14712598.2018.1389886 -
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 -
Frontiers in Medicine 2021To investigate the relationship between myopic tractional maculopathy (MTM) and myopic atrophy maculopathy (MAM). Two hundred and six eyes with definitive myopic...
To investigate the relationship between myopic tractional maculopathy (MTM) and myopic atrophy maculopathy (MAM). Two hundred and six eyes with definitive myopic retinoschisis were assessed in the retrospective observational case series study and the atrophic and tractional features were further evaluated. Atrophic changes were analyzed according to the atrophic component in the ATN classification and the occurrence of gamma zones and delta zones. Tractional changes were evaluated based on different retinoschisis layers, the location and range of outer retinoschisis, retinal detachment, inner lamellar macular hole (ILMH), outer lamellar MH (OLMH), full-thickness MH (FTMH), and paravascular abnormalities. Of all the eyes, 29.6, 42.7, 19.4, and 8.3% presented MAM grades with A1, A2, A3, and A4, respectively. The three layers of retinoschisis and the entire macular retinoschisis had the highest incidences in A2 (38.6%; 54.5%). The numbers of retinoschisis layers and the grades of outer retinoschisis had a weak negative correlation with MAM ( = -0.138, = 0.048; = -0.139, = 0.047). All the eyes had gamma zones, and 82.52% of eyes also had delta zones. The incidence of retinal detachment and OLMH reached the peak in A2 and then decreased gradually. With MAM aggravation, the prevalence of ILMH decreased. Eyes with A1 and A2 were more likely to have OLMH, and those with A3 and A4 were more likely to have FTMH ( = 0.028; OR, 3.423; 95% CI, 1.144-10.236; = 0.004; OR, 7.752; 95% CI, 1.951-30.803). With the MAM grades growing, the types of paravascular abnormalities increased ( = 0.165, = 0.018). Diffuse chorioretinal atrophy was the dominant MAM grade in eyes with MTM. In the study, 72.3% of eyes with MTM presented with diffuse chorioretinal atrophy and a tessellated fundus. Over 80% of eyes with MTM had both gamma zones and delta zones. Diffuse chorioretinal atrophy might be a complicated stage for MTM with the highest rate of three layers of retinoschisis, the entire macular retinoschisis, RD, and OLMH. Atrophic progression might involve the development of MH. When MTM combines with well-defined atrophy, the occurrence of FTMH should be noted.
PubMed: 34490288
DOI: 10.3389/fmed.2021.679192