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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 -
Journal of Clinical Medicine Jul 2023Peripapillary intrachoroidal cavitation (PICC) is a yellow-orange lesion, located at the outer border of the myopic conus. First described as a localized detachment of... (Review)
Review
Peripapillary intrachoroidal cavitation (PICC) is a yellow-orange lesion, located at the outer border of the myopic conus. First described as a localized detachment of the retinal pigment epithelium, its intrachoroidal location was later revealed, justifying its current name. PICC is related to other myopic complications such as posterior staphyloma, but its pathogenesis is not clear to date. Although it has been considered a benign condition, most eyes with PICC show visual field defects, which leads to diagnostic uncertainty as these deficits resemble those seen in glaucoma. Furthermore, eyes with PICC may develop macular detachment with retinoschisis. Finally, misdiagnosis of PICC as a metastatic choroidal tumor may lead to unnecessary and anxiety-inducing investigations. Advances in optical coherence tomography (OCT) imaging have improved the visualization of ocular structures, contributing to the understanding of PICC. Recently, high optic nerve sheath traction forces during eye movements in highly myopic eyes have been suggested as promoters of PICC, renewing interest around this condition. However, a review of PICC is still lacking. Therefore, we aimed to provide a concise yet comprehensive overview of the current state of the art, focusing on OCT illustrations, pathophysiology and potential future perspectives based on the biomechanics of the optic nerve.
PubMed: 37510829
DOI: 10.3390/jcm12144712 -
Drug Delivery Dec 2023Ocular posterior segment diseases such as uveitis, X-linked juvenile retinoschisis, or age-related macular degeneration usually result in progressive and irreversible... (Review)
Review
Ocular posterior segment diseases such as uveitis, X-linked juvenile retinoschisis, or age-related macular degeneration usually result in progressive and irreversible vision loss. Although intravitreal injection is the main way to deliver drugs to the posterior eye, it still has shortcomings as an invasive operation. Nanocontrolled drug delivery technology is a promising option to avoid frequent injections. Due to the particularity of the human intraocular structure, drugs have unique pharmacokinetic characteristics in the eye. Various nanoparticles have been successfully investigated in experimental studies for vitreous injection, with advantages and drawbacks. Here, we introduce an ideal nanopolymer modifier to build nanodelivery systems in vitreous cavities. Hyaluronic acid (HA) is a natural polysaccharide with a broad molecular weight range, negatively charged surface, ligand-receptor binding capabilities, and hyaluronidase breakdown capability. Advances in CD44 receptor targeting for HA-based nanoparticles can improve mobility and penetration in the vitreous and retina, stabilize the nanoparticles, and regulate drug release. This review summarizes the intravitreal administration of nanoplatforms based on HA and the benefits of HA in drug delivery systems.
Topics: Humans; Hyaluronic Acid; Pharmaceutical Preparations; Retina; Drug Delivery Systems; Nanoparticles
PubMed: 37194147
DOI: 10.1080/10717544.2023.2204206 -
Retinal Cases & Brief Reports Nov 2023To present two cases of concomitant retinal neovascularization (RNV) in acquired peripheral retinoschisis and analyze its characteristics on optical coherence tomography... (Review)
Review
PURPOSE
To present two cases of concomitant retinal neovascularization (RNV) in acquired peripheral retinoschisis and analyze its characteristics on optical coherence tomography angiography and based on a literature review.
METHODS
This was an observational, retrospective case study.
RESULTS
Case 1 presented with bullous retinoschisis and RNV near the schisis cavity. Optical coherence tomography angiography revealed no angioflow into the retinal arterioles of the cavity. An arterial filling delay to the retinoschisis with extensive leakage from the RNV was noted on fluorescein angiography. Case 2 involved the superficial retinoschisis and telangiectatic vessels inside the schisis cavity. Optical coherence tomography angiography revealed damage to the superficial capillary plexus of the cavity, absence of angioflow to the inner schisis layer, and increased angioflow to the RNV. Fluorescein angiography showed focal leakage from the RNV and diffuse leakage from telangiectasia. No vision-threatening complications were identified in either patient up to the last follow-up, subsequent to laser photocoagulation.
CONCLUSION
Acquired peripheral retinoschisis is associated with RNV. Inner retinal ischemia caused by hemodynamic resistance or a damaged superficial capillary plexus can interrupt angioflow to the inner schisis retinal layer on optical coherence tomography angiographic findings and develop RNV inside or outside the retinoschisis.
Topics: Humans; Retinoschisis; Retinal Neovascularization; Tomography, Optical Coherence; Retrospective Studies; Retinal Diseases; Fluorescein Angiography; Ischemia
PubMed: 35594561
DOI: 10.1097/ICB.0000000000001292 -
American Journal of Ophthalmology Feb 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.
PubMed: 38401851
DOI: 10.1016/j.ajo.2024.02.016 -
Medicina 2024
Topics: Humans; Male; Retinoschisis; Tomography, Optical Coherence; Adult
PubMed: 38683539
DOI: No ID Found -
Graefe's Archive For Clinical and... Apr 2024Circumscribed choroidal hemangioma is a rare vascular hamartoma of the choroid, presenting as a red-orange mass at the posterior pole on fundoscopic examination. Despite... (Review)
Review
Circumscribed choroidal hemangioma is a rare vascular hamartoma of the choroid, presenting as a red-orange mass at the posterior pole on fundoscopic examination. Despite its benign origin, associated complications such as subretinal fluid, serous retinal detachment, retinoschisis and neovascular glaucoma may lead to serious visual impairment in more than half patients. Because of its similarity to amelanotic choroidal melanoma and choroidal metastasis, differential diagnosis is still challenging for specialists. Multimodal imaging such as ultrasonography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography guides the clinician to the correct diagnosis and the proper follow-up. Treatment is indicated in symptomatic cases in order to resolve exudation and improve visual acuity. Treatment options include photocoagulation, transpupillary thermotherapy, radiation therapy, photodynamic therapy and anti-vascular endothelial growth factor therapy. Currently, photodynamic therapy is the treatment of choice due to its effectiveness and safety. The purpose of this review is to describe the latest knowledge in the etiopathogenesis of the circumscribed choroidal hemangioma, the most recent multimodal imaging findings, and the available treatment options.
Topics: Humans; Hemangioma; Choroid Neoplasms; Photochemotherapy; Choroid; Fluorescein Angiography; Tomography, Optical Coherence
PubMed: 37505277
DOI: 10.1007/s00417-023-06179-x -
Graefe's Archive For Clinical and... Nov 2023To investigate the changes in macular cystic schisis (MCS) and sensitivity during the day in X-linked retinoschisis (XLRS) patients.
BACKGROUND
To investigate the changes in macular cystic schisis (MCS) and sensitivity during the day in X-linked retinoschisis (XLRS) patients.
METHODS
Treatment-naïve patients with genetically verified XLRS underwent best-correlated visual acuity (BCVA) testing with ETDRS charts, spectral domain optical coherence tomography, and microperimetry (MP) twice a day, at 9 a.m. and 4 p.m., to measure changes in central retinal thickness (CRT), macular volume (MV), average threshold (AT), and fixation stability parameters (P1 and P2).
RESULTS
At baseline, the BCVA of the 14 eyes of 8 patients amounted 0.73 (± 0.23) LogMAR. Between timepoints, the BCVA increased in 3.21 letters (p = .021), the AV improved in 1.84 dB (p = .03, 9.73%), the CRT decreased in 24.43 µm (p = .007, - 4.05%), and the MV dropped in 0.27 µm (p = .016, - 2.68%). P1 and P2 did not variate. The collapse of the MCS led to the reduction of macula thickness. CRT at baseline correlated with the decrease of CRT (Spearman's ρ: - 0.83 [p = .001]). Age and change of BCVA, CRT, and AV did not correlate among one another. Eyes with disrupted ellipsoid zone showed a more prominent change in CRT (p = .050). Photoreceptor outer segment length and integrity of the external limiting membrane and cone outer segment tips were not associated with BCVA, AT, or CRT variation.
CONCLUSION
Eyes of treatment-naïve XLRS patients show diurnal macular thickness and function changes. Eyes with pronounced macular thickness show a greater reduction of the MCS. These results should be taken into consideration in upcoming clinical trials in XLRS.
TRIAL REGISTRATION NUMBER
Institutional Review Board of the Hamburg Medical Chamber (Ethik-Kommission der Ärztekammer Hamburg): 2020-10,328.
PubMed: 37294434
DOI: 10.1007/s00417-023-06106-0 -
International Journal of Ophthalmology 2023To characterize the ophthalmic clinical phenotype of a family with retinitis pigmentosa (RP) and closed-angle glaucoma and to detect pathogenic genes and mutation sites...
AIM
To characterize the ophthalmic clinical phenotype of a family with retinitis pigmentosa (RP) and closed-angle glaucoma and to detect pathogenic genes and mutation sites causing RP in this family.
METHODS
Ophthalmic clinic performance was examined in detail in 8 enrolled family members. Genomic DNA was extracted from the peripheral blood of 4 family members for whole-exome sequencing (WES) to select potential genetic mutations whose structures were identified by bioinformatics analysis. Then, Sanger sequencing was used in 12 family members and control group members to validate and confirm the disease-causing mutation loci, and we analyzed the genotype-phenotype relationships.
RESULTS
The known c.512C>T (p.P171L) mutation in the () gene was only found in afflicted family members and was confirmed by WES and Sanger sequencing as the pathogenic mutation in this family. In addition to being diagnosed with RP, family member III:4 was found to have bilateral closed-angle glaucoma, high myopia, and concurrent cataracts, and family members II:2 and II:4 had pathological changes of anterior chamber angle narrowing. Family members IV:3 and IV:4 were found to have retinoschisis.
CONCLUSION
Glaucoma and related pathological changes, such as retinoschisis, in family members are preliminarily considered RP complications caused by mutation.
PubMed: 38111930
DOI: 10.18240/ijo.2023.12.07 -
Ophthalmology Dec 2023To describe the largest, most phenotypically and genetically diverse cohort of patients with inherited retinal disease (IRD)-related Coats-like vasculopathy (CLV).
PURPOSE
To describe the largest, most phenotypically and genetically diverse cohort of patients with inherited retinal disease (IRD)-related Coats-like vasculopathy (CLV).
DESIGN
Multicenter retrospective cohort study.
PARTICIPANTS
A total of 67 patients with IRD-related CLV.
METHODS
Review of clinical notes, ophthalmic imaging, and molecular diagnosis from 2 international centers.
MAIN OUTCOME MEASURES
Visual function, retinal imaging, management, and response to treatment were evaluated and correlated.
RESULTS
The prevalence of IRD-related CLV was 0.5%; 54% of patients had isolated retinitis pigmentosa (RP), 21% had early-onset severe retinal dystrophy, and less frequent presentations were syndromic RP, sector RP, cone-rod dystrophy, achromatopsia, PAX6-related dystrophy, and X-linked retinoschisis. The overall age of patients at CLV diagnosis was 30.7 ± 16.9 years (1-83). Twenty-one patients (31%) had unilateral CLV, and the most common retinal features were telangiectasia, exudates, and exudative retinal detachment (ERD) affecting the inferior and temporal retina. Macular edema/schisis was observed in 26% of the eyes, and ERD was observed in 63% of the eyes. Fifty-four patients (81%) had genetic testing, 40 of whom were molecularly solved. Sixty-six eyes (58%) were observed, 17 eyes (15%) were treated with a single modality, and 30 eyes (27%) had a combined approach. Thirty-five eyes (31%) were "good responders," 42 eyes (37%) were "poor responders," 22 eyes (19%) had low vision at baseline and were only observed, and 12 eyes (11%) did not have longitudinal assessment. Twenty-one observed eyes (62%) responded well versus 14 (33%) treated eyes. Final best-corrected visual acuity was significantly worse than baseline (P = 0.002); 40 patients (60%) lost 15 ETDRS letters or more over follow-up in 1 or both eyes, and 21 patients (31%) progressed to more advanced stages of visual impairment.
CONCLUSIONS
Inherited retinal disease-related CLV is rare, sporadic, and mostly bilateral; there is no gender predominance, and it can occur in diverse types of IRD at any point of the disease, with a mean onset in the fourth decade of life. Patients with IRD-related CLV who have decreased initial visual acuity, ERD, CLV changes affecting 2 or more retinal quadrants, and CRB1-retinopathy may be at higher risk of a poor prognosis.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Prevalence; Retrospective Studies; Retina; Retinal Detachment; Retinal Dystrophies; Retinitis Pigmentosa; Cone-Rod Dystrophies; Vision, Low; Eye Proteins; Membrane Proteins; Nerve Tissue Proteins
PubMed: 37544434
DOI: 10.1016/j.ophtha.2023.07.027