Effective gene therapy of Stargardt disease with PEG-ECO/ nanoparticles.

Stargardt disease (STGD) is the most common form of inherited retinal genetic disorders and is often caused by mutations in . Gene therapy has the promise to effectively treat monogenic retinal disorders. However, clinically approved adeno-associated virus (AAV) vectors do not have a loading capacity for large genes, such as .

TOPICAL CARBONIC ANHYDRASE INHIBITORS IN THE LONG-TERM TREATMENT OF JUVENILE X-LINKED RETINOSCHISIS.

Purpose: To describe the response to long-term topical dorzolamide treatment in patients with juvenile X-linked retinoschisis and cystic-like foveal lesions.

Methods: This was a retrospective interventional case series that included 18 eyes of 10 patients with genetically confirmed juvenile X-linked retinoschisis examined at the Cleveland Clinic Cole Eye Institute, a tertiary referral center, between 2005 and 2021. Patients were treated with topical 2% dorzolamide two to three times daily in both eyes.

Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia.

Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been associated with ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6), the majority of these being implicated in the cone phototransduction cascade. CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors and is one of the major disease-associated genes for ACHM.

Profiling of visual acuity and genotype correlations in RP2 patients: a cross-sectional comparative meta-analysis between carrier females and affected males.

Background: X-linked retinitis pigmentosa (XLRP) is the most severe form of retinitis pigmentosa (RP) and accounts for 15-20% of all RP cases. In this study, we investigated the progression of visual acuity loss across age groups in female carriers and compared it to affected males.

Methods: A PubMed literature search was conducted, and RP2 cases were included based on specific inclusion criteria.

Mitochondrial DNA A3243G variant-associated retinopathy: a meta-analysis of the clinical course of visual acuity and correlation with systemic manifestations.

Purpose: The mitochondrial DNA A3243G (m.3243A>G) variant causes a wide spectrum of phenotypes, with pigmentary retinopathy as the most common ocular finding. We undertook this meta-analysis to investigate the clinical course of visual acuity (VA) in patients with m.

Mitochondrial DNA A3243G variant-associated retinopathy: Current perspectives and clinical implications.

Cellular function and survival are critically dependent on the proper functionality of the mitochondrion. Neurodegenerative cellular processes including cellular adenosine triphosphate production, intermediary metabolism control, and apoptosis regulation are all mitochondrially mediated. The A to G transition at position 3243 in the mitochondrial MTTL1 gene that encodes for the leucine transfer RNA (m.

Sector retinitis pigmentosa: Report of ten cases and a review of the literature.

Purpose: To describe the genotypes and phenotypes of ten patients with sector retinitis pigmentosa (RP). We also review previously reported mutations associated with sector RP and provide a discussion of possible underlying pathophysiological mechanisms.

Methods: Patients underwent detailed ophthalmologic examinations, fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (SD-OCT), as well as visual field and electroretinographic testing.

Survey of practice patterns for the management of ophthalmic genetic disorders among AAPOS members: report by the AAPOS Genetic Eye Disease Task Force.

To better understand AAPOS member pediatric ophthalmologists' knowledge and needs regarding genetic eye disorders, the AAPOS Genetic Eye Disease Task Force developed a 16-question survey that was circulated to national and international AAPOS members. Responses to questions on practice patterns, baseline knowledge, and educational interests regarding patients with suspected ophthalmic genetic disorders were collected. A majority of respondents (93%) evaluate patients with suspected genetic disorders.

Identification of a mutation in CNNM4 by whole exome sequencing in an Amish family and functional link between CNNM4 and IQCB1.

We investigated an Amish family in which three siblings presented with an early-onset childhood retinal dystrophy inherited in an autosomal recessive fashion. Genome-wide linkage analysis identified significant linkage to marker D2S2216 on 2q11 with a two-point LOD score of 1.95 and a multi-point LOD score of 3.

Identification and population history of CYP4V2 mutations in patients with Bietti crystalline corneoretinal dystrophy.

To identify known and novel CYP4V2 mutations in patients with Bietti crystalline cornea (BCD), expand the spectrum of CYP4V2 mutations, and characterize the population history of the c.802-8_810del17insGC mutation common in Asian populations, genomic DNA was isolated from peripheral blood samples from 58 unrelated patients with clinical diagnoses of BCD. Exons and flanking intronic regions of the CYP4V2 gene were dideoxy DNA sequenced.

Genetic Analysis of 'PAX6-Negative' Individuals with Aniridia or Gillespie Syndrome.

We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1.

Ophthalmological findings in 74 patients with mitochondrial disease.

Background: Mitochondrial disease often manifests with ophthalmologic signs and symptoms. Due to the important role of mitochondria in aerobic metabolism, the eyes are among the more preferentially involved organs. The clinical diagnosis of mitochondrial disease can be facilitated by an improved knowledge of the types and magnitude of their various manifestations.

Corneal Deformation Response and Ocular Geometry: A Noninvasive Diagnostic Strategy in Marfan Syndrome.

Purpose: To evaluate corneal air-puff deformation responses and ocular geometry as predictors of Marfan syndrome.

Design: Prospective observational clinical study.

Methods: Sixteen investigator-derived, 4 standard Ocular Response Analyzer (ORA), and geometric variables from corneal tomography and optical biometry using Oculus Pentacam and IOL Master were assessed for discriminative value in Marfan syndrome, measuring right eyes of 24 control and 13 Marfan syndrome subjects.

A Novel KCNJ13 Nonsense Mutation and Loss of Kir7.1 Channel Function Causes Leber Congenital Amaurosis (LCA16).

Mutations in the KCNJ13 gene that encodes the inwardly rectifying potassium channel Kir7.1 cause snowflake vitreoretinal degeneration (SVD) and leber congenital amaurosis (LCA). Kir7.

Mutations in ASPH cause facial dysmorphism, lens dislocation, anterior-segment abnormalities, and spontaneous filtering blebs, or Traboulsi syndrome.

We have previously described a syndrome characterized by facial dysmorphism, lens dislocation, anterior-segment abnormalities, and spontaneous filtering blebs (FDLAB, or Traboulsi syndrome). In view of the consanguineous nature of the affected families and the likely autosomal-recessive inheritance pattern of this syndrome, we undertook autozygosity mapping and whole-exome sequencing to identify ASPH as the disease locus, in which we identified two homozygous mutations. ASPH encodes aspartyl/asparaginyl β-hydroxylase (ASPH), which has been found to hydroxylate aspartic acid and asparagine residues on epidermal growth factor (EGF)-domain-containing proteins.

Congenital abnormalities of the optic nerve: from gene mutation to clinical expression.

Optic nerve malformations are common causes of congenital blindness and are recognized with increasing prevalence. The importance of identifying these malformations lies not only in determining the cause and level of visual impairment, but also in looking for associated treatable or life threatening systemic conditions. A number of genetic mutations have been identified in the development of optic disc anomalies, such as ones in PAX2 or PAX6.