Single Center Experience with Voretigene Neparvovec Gene Augmentation Therapy in RPE65 Mutation-Associated Inherited Retinal Degeneration in a Clinical Setting.

Purpose: To assess the impact of baseline data on psychophysical and morphological outcomes of subretinal voretigene neparvovec (VN) (Luxturna, Spark Therapeutics, Inc.) treatment.

Design: Single-center, retrospective, longitudinal, consecutive case series.

Artificial intelligence predicts delirium following cardiac surgery: A case study.

Delirium is a highly relevant complication of surgical interventions. Current research indicates that despite increased awareness for delirium, it is often overlooked. We implemented an AI-based tool to monitor delirium in cardiac surgery patients in our specialist clinic.

Biallelic mutations in L-dopachrome tautomerase (DCT) cause infantile nystagmus and oculocutaneous albinism.

Infantile nystagmus syndrome (INS) denominates early-onset, involuntary oscillatory eye movements with different etiologies. Nystagmus is also one of the symptoms in oculocutaneus albinism (OCA), a heterogeneous disease mainly caused by defects in melanin synthesis or melanosome biogenesis. Dopachrome tautomerase (DCT, also called TYRP2) together with tyrosinase (TYR) and tyrosin-related protein 1 (TYRP1) is one of the key enzymes in melanin synthesis.

Biallelic mutation of human encoding the taurine transporter TAUT is linked to early retinal degeneration.

We previously reported that inactivation of the transmembrane taurine transporter (TauT or solute carrier 6a6) causes early retinal degeneration in mice. Compatible with taurine's indispensability for cell volume homeostasis, protein stabilization, cytoprotection, antioxidation, and immuno- and neuromodulation, mice develop multisystemic dysfunctions (hearing loss; liver fibrosis; and behavioral, heart, and skeletal muscle abnormalities) later on. Here, by genetic, cell biologic, H-magnetic resonance spectroscopy and molecular dynamics simulation studies, we conducted in-depth characterization of a novel disorder: human TAUT deficiency.

Splitting of the lateral rectus muscle with medial transposition to treat oculomotor palsy: a retrospective analysis of 29 consecutive cases.

Purpose: The lateralis splitting technique has been an interesting option for treating large-angle exotropia due to complete 3rd nerve paralysis since its inception in the early 1990s. The purpose of this study is to report on our experience regarding the effectiveness and complications of this method.

Methods: Retrospective analysis of a consecutive series of 29 patients operated by one single experienced surgeon and examined according to a specific operative and perioperative protocol.

[The Phenotypic Spectrum of Ophthalmic Changes in CEP290 Mutations].

Purpose: Inherited retinal diseases (IRDs) may be caused by variations in genes affecting the connecting cilium of photoreceptor cells and intraflagellar transport, manifested as ciliopathies. is frequently mutated in non-syndromic, but also syndromic IRDs. In preparation for clinical treatment trials, detailed phenotypic work-up including longitudinal follow-up is mandatory.

The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene.

Purpose: To delineate the natural history of visual parameters over time in individuals with biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD); describe the range of causative mutations; determine potential genotype/phenotype relationships; and describe the variety of clinical diagnoses.

Design: Global, multicenter, retrospective chart review.

Methods: Study Population: Seventy individuals with biallelic RPE65 mutation-associated IRD.

Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290.

Purpose: To describe the phenotypic spectrum of retinal disease caused by the c.2991+1655A>G mutation in CEP290 and to compare disease severity between homozygous and compound heterozygous patients.

Methods: Medical records were reviewed for best-corrected visual acuity (BCVA), age of onset, fundoscopy descriptions.

Unexpected Genetic Cause in Two Female Siblings with High Myopia and Reduced Visual Acuity.

In daily life, myopia is a frequent cause of reduced visual acuity (VA) due to missing or incomplete optical correction. While the genetic cause of high myopia itself is not well understood, a significant number of cases are secondary to hereditary malfunctions or degenerations of the retina. The mechanism by which this occurs remains yet unclear.

[Overview of Congenital Stationary Night Blindness with Predominantly Normal Fundus Appearance].

Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous group of non-progressive retinal disorder with largely normal fundus appearance. The mode of inheritance can be autosomal dominant (adCSNB), autosomal recessive (arCSNB) or X-chromosomal (XLCSNB). Additional ocular signs can be myopia, hyperopia, strabismus, nystagmus and reduced visual acuity.

Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: copy number variations, phenocopies, a predominant target for translational read-through, and mutated in Heimler syndrome.

Background: Combined retinal degeneration and sensorineural hearing impairment is mostly due to autosomal recessive Usher syndrome (USH1: congenital deafness, early retinitis pigmentosa (RP); USH2: progressive hearing impairment, RP).

Methods: Sanger sequencing and NGS of 112 genes (Usher syndrome, nonsyndromic deafness, overlapping conditions), MLPA, and array-CGH were conducted in 138 patients clinically diagnosed with Usher syndrome.

Results: A molecular diagnosis was achieved in 97% of both USH1 and USH2 patients, with biallelic mutations in 97% (USH1) and 90% (USH2), respectively.

Spatially Resolved Spectral Sensitivities as a Potential Read-out Parameter in Clinical Gene Therapeutic Trials.

Purpose: Spatially resolved functional assessment of rods and cones under photopic and scotopic conditions is desirable to evaluate the treatment outcome of gene therapeutic applications in inherited retinal disorders, such as early- onset severe retinal dystrophy (EOSRD) or achromatopsia.

Methods: A sample of 3 healthy subjects, 6 patients with RPE65 deficiency (aged 11-45 years), and 3 patients with cone dysfunction disorders underwent spectral sensitivity testing (SST) under conditions of dark and light adaptation using a Humphrey Field Analyzer modified perimeter.

Results: SST in healthy subjects revealed sensitivity curves corresponding well with the CIE (International Commission on Illumination) standard fundamentals.

[Genotype-Phenotype Correlations in Patients with CRB1 Mutations].

Mutations in the gene were identified in patients with early-onset severe retinal dystrophy (EOSRD), childhood-onset and juvenile-onset rod-cone dystrophy. This study describes the phenotypic spectrum of disease-causing -mutations in the first two decades of life. Eight patients, aged three months to 20 years, underwent a full comprehensive ophthalmological examination including best corrected visual acuity testing (BCVA), color vision testing, funduscopy, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) recording.

[Segregation Analysis in Inherited Eye Disorders: An Academic Add-on or An Essential Effort?].

The knowledge of the genetic basis of many eye diseases is constantly increasing. Besides retinal degeneration, developmental defects of the anterior segment, cataracts, and the development of the basic structure are often associated with genetic defects. Moreover, a lot of genetic syndromes involve eye abnormalities.

Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family.

Background: Juvenile X-linked retinoschisis (RS1, OMIM: 312700) is a hereditary vitreoretinal dystrophy characterized by bilateral foveal schisis and, in half of the patients, splitting through the nerve fiber layer in the peripheral retina. In the first decade of life, patients usually develop a decrease in visual acuity. Long-term visual outcomes can be poor due to the limited number of known successful treatments.

Ocular morphology and function in juvenile neuronal ceroid lipofuscinosis (CLN3) in the first decade of life.

Purpose: CLN3 is a rare lysosomal storage disorder. The majority of the patients suffer from neurological degeneration in the first decade of life leading to death in the second or third decade. One of the first symptoms is a rapid visual decline from retinal degeneration.

Modelling human height and weight: a Bayesian approach towards model comparison.

Background/objectives: Given the availability of large longitudinal data sets on human height and weight, different modelling approaches are at hand to access quantities of interest relating to important diagnostic aims.

Subjects/methods: Statistical modelling frameworks for longitudinal data on human height and weight have to consider the issues of individual heterogeneity and time dependence to provide an accurate statistical characterisation. Further, missing values inevitably occurring within longitudinal data sets have to be addressed adequately to allow for valid inference.

[Albinism and the Range of Fundus Hypopigmentation, Macular Hypoplasia, and Nystagmus].

From the ophthalmological view, albinism is a disorder of reduced pigmentation of the retinal and irdial pigment epithelium and the iris and choroid stroma. The reduced pigmentation is accompanied by morphological changes in the retina and the optic nerve. The functional relationship of these morphological changes is not yet well understood.

Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark.

Leber congenital amaurosis (LCA) represents the most severe form of inherited retinal dystrophies with an onset during the first year of life. Currently, 21 genes are known to be associated with LCA and recurrent mutations have been observed in AIPL1, CEP290, CRB1 and GUCY2D. In addition, sequence analysis of LRAT and RPE65 may be important in view of treatments that are emerging for patients carrying variants in these genes.

Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies.

Autosomal-recessive optic neuropathies are rare blinding conditions related to retinal ganglion cell (RGC) and optic-nerve degeneration, for which only mutations in TMEM126A and ACO2 are known. In four families with early-onset recessive optic neuropathy, we identified mutations in RTN4IP1, which encodes a mitochondrial ubiquinol oxydo-reductase. RTN4IP1 is a partner of RTN4 (also known as NOGO), and its ortholog Rad8 in C.