Expanding the genetic landscape of Usher syndrome type IV caused by pathogenic ARSG variants.

Usher syndrome (USH) is the most common cause of deafblindness. USH is autosomal recessively inherited and characterized by rod-cone dystrophy or retinitis pigmentosa (RP), often accompanied by sensorineural hearing loss. Variants in >15 genes have been identified as causative for clinically and genetically distinct subtypes.

Unilateral Melanoma-Associated Retinopathy Case Report.

In this report, we present a case of unilateral melanoma-associated retinopathy in a 72-year-old woman. The patient's main symptoms were decreased vision and positive dysphotopsia. Unilateral electronegative electroretinogram (ERG) was suggestive for melanoma retinopathy.

Paediatric cataract surgery with 27G vitrectomy instrumentation: the Ghent University Hospital Experience.

Objective: To describe a cohort of paediatric patients who underwent unilateral or bilateral lens extractions at Ghent University hospital using the Dutch Ophthalmic Research Center (D.O.R.

Multi-omics approach dissects cis-regulatory mechanisms underlying North Carolina macular dystrophy, a retinal enhanceropathy.

North Carolina macular dystrophy (NCMD) is a rare autosomal-dominant disease affecting macular development. The disease is caused by non-coding single-nucleotide variants (SNVs) in two hotspot regions near PRDM13 and by duplications in two distinct chromosomal loci, overlapping DNase I hypersensitive sites near either PRDM13 or IRX1. To unravel the mechanisms by which these variants cause disease, we first established a genome-wide multi-omics retinal database, RegRet.

Association between near viewing and acute acquired esotropia in children during tablet and smartphone use.

We investigated a possible association between the acute onset of esotropia and tablet or smartphone use in children. We characterized the clinical aspects of esotropia associated with tablet or smartphone use. The medical records of 10 children aged between 5 and 15 years old with presumably tablet or smartphone associated esotropia were reviewed regarding orthoptic examination and cycloplegic refraction.

The Retina in Patients With Triple A Syndrome: A Window Into Neurodegeneration?

Objective: Experimental evidence suggests that the clinical manifestations of Triple A syndrome result from oxidative stress. Several conditions caused by oxidative stress display retinal involvement. Our objective was to assess the retina and optic nerve involvement in children with Triple A syndrome.

Genetics in primary congenital glaucoma: Implications in disease management and counseling.

Primary congenital glaucoma is an important cause of visual impairment in children. It can develop both pre- and postnatally. Angle surgery is the first line treatment modality.

Expanding the clinical spectrum and management of Traboulsi syndrome: report on two siblings homozygous for a novel pathogenic variant in .

Background: Traboulsi syndrome is a very rare, syndromic form of ectopia lentis that is potentially sight-threatening at a young age. It is characterized by typical facial, skeletal and ocular signs.

Materials And Methods: Two siblings, born to consanguineous parents, with a clinical phenotype consistent with Traboulsi syndrome, underwent extensive ophthalmic imaging and exome-based genetic testing.

Two siblings with Heimler syndrome caused by PEX1 variants: follow-up of ophthalmologic findings.

Background: Heimler syndrome (OMIM number #234580 and #616617) is a rare condition comprising sensorineural hearing loss (SNHL), nail abnormalities and amelogenesis imperfecta. In addition, patients with this syndrome can have retinal dystrophies. Heimler syndrome is caused by bi-allelic pathogenic variants in the or gene.

Congenital stationary night blindness in a patient with mild learning disability due to a compound heterozygous microdeletion of 15q13 and a missense mutation in .

The complete form of congenital stationary night blindness (cCSNB) represents a non-progressive retinal disorder characterized by night vision problems and often congenital nystagmus, reduced vision, high myopia, strabismus and normal fundus appearance. Clinically this form of CSNB can be diagnosed by full-field electroretinogram. The mode of inheritance can be X-linked and autosomal recessive with mutations in genes coding for proteins mainly present at the dendritic tips of ON-bipolar cells.

CLINICAL CHARACTERISTICS AND NATURAL HISTORY OF RHO-ASSOCIATED RETINITIS PIGMENTOSA: A Long-Term Follow-Up Study.

Purpose: To investigate the natural history of RHO-associated retinitis pigmentosa (RP).

Methods: A multicenter, medical chart review of 100 patients with autosomal dominant RHO-associated RP.

Results: Based on visual fields, time-to-event analysis revealed median ages of 52 and 79 years to reach low vision (central visual field <20°) and blindness (central visual field <10°), respectively.

Microcoria due to first duplication of 13q32.1 including the GPR180 gene and maternal mosaicism.

Congenital microcoria (MCOR) is an eye anomaly characterized by a pupil with diameter below 2 mm, and is caused by underdevelopment or absence of the dilator muscle of the pupil. Two types have been described: a recessive, syndromic (Pierson syndrome OMIM 609049) and a dominant, isolated form (MCOR syndrome OMIM 156600). Fares-Taie and colleagues described inherited microdeletions in chromosome band 13q32.

Three cases of molecularly confirmed Knobloch syndrome.

Knobloch syndrome (OMIM 267750) is a rare autosomal recessive disorder due to genetic defects in the gene. The triad of high myopia, occipital defect, vitreoretinal degeneration has been described as pathognomonic for this condition. Patients with Knobloch syndrome have also extraocular problems as brain and kidney malformations.

MULTIMODAL IMAGING IN HELLP-RELATED CHORIORETINOPATHY.

Purpose: To illustrate with multimodal imaging a case of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) complicated by bilateral multifocal serous retinal detachments, subretinal exudation, and papilledema.

Methods: Case report. Fundus photography, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography, and indocyanine green angiography were performed at presentation and the day after.

The majority of autosomal recessive nanophthalmos and posterior microphthalmia can be attributed to biallelic sequence and structural variants in MFRP and PRSS56.

This study aimed to genetically and clinically characterize a unique cohort of 25 individuals from 21 unrelated families with autosomal recessive nanophthalmos (NNO) and posterior microphthalmia (MCOP) from different ethnicities. An ophthalmological assessment in all families was followed by targeted MFRP and PRSS56 testing in 20 families and whole-genome sequencing in one family. Three families underwent homozygosity mapping using SNP arrays.

Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration.

Objective: Age-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy.

Where are the missing gene defects in inherited retinal disorders? Intronic and synonymous variants contribute at least to 4% of CACNA1F-mediated inherited retinal disorders.

Inherited retinal disorders (IRD) represent clinically and genetically heterogeneous diseases. To date, pathogenic variants have been identified in ~260 genes. Albeit that many genes are implicated in IRD, for 30-50% of the cases, the gene defect is unknown.

ABCA4-associated disease as a model for missing heritability in autosomal recessive disorders: novel noncoding splice, cis-regulatory, structural, and recurrent hypomorphic variants.

Purpose: ABCA4-associated disease, a recessive retinal dystrophy, is hallmarked by a large proportion of patients with only one pathogenic ABCA4 variant, suggestive for missing heritability.

Methods: By locus-specific analysis of ABCA4, combined with extensive functional studies, we aimed to unravel the missing alleles in a cohort of 67 patients (p), with one (p = 64) or no (p = 3) identified coding pathogenic variants of ABCA4.

Results: We identified eight pathogenic (deep-)intronic ABCA4 splice variants, of which five are novel and six structural variants, four of which are novel, including two duplications.

Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect.

Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.