Christina Gerth-Kahlert

Purpose Toxoplasmosis is the most common cause of infectious uveitis of the posterior segment. Current literature regarding this parasitic ocular infection in children is sparse. In this study, we focused on localisation of retinal infiltration and visual outcome in children and adolescents. Material and Methods Single-centre, retrospective study from 2012 to 2021. Patients were divided into three subgroups depending on foveal involvement: (1) direct foveal infiltrate, (2) with extrafoveal infiltrate, either with or (3) without fovea-involving inflammation. The primary outcome was visual acuity (VA) improvement (Snellen, decimal). The secondary outcome was the VA outcome depending on foveal involvement. Wilcoxon signed rank test (SPSS Statistics 26) was used for statistical analysis. Results Data of 144 paediatric uveitis cases were identified, with active ocular toxoplasmosis in 21 (14.5%) patients. Data analysis was permitted in 20/21 patients. Oral antibiotic and prednisone therapy and additional topical steroids were initiated if deemed necessary. Overall, VA improved from first presentation (mean 0.5, range hand motion to 1.0) to last follow-up (mean 0.7, range counting fingers to 1.0; p = 0.001). Focusing on the subgroups, the most substantial VA improvement was reported in group 1 (0.042 to 0.30; p = 0.028) and in group 2 (0.62 to 0.9; p = 0.078). Conclusion In children in adolescence, VA improves the symptoms of in children of fovea involving ocular toxoplasmosis. Direct foveal infiltrate is associated with the lowest visual acuity outcome but also with the most substantial VA improvement.

Purpose Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune disease affecting the central nervous system, frequently manifesting with optic neuritis (ON). Despite often favourable functional visual recovery, structural retinal changes may persist. This prospective study assessed the utility of functional and structural visual outcome measures in paediatric MOGAD. Methods Children with serologically confirmed MOGAD were recruited from across Switzerland, alongside age-matched healthy controls. All participants underwent pattern-reversal visual evoked potentials (VEP; 15′ and 60′ check sizes), spectral-domain optical coherence tomography (OCT), high- and low-contrast distance visual acuity (VA), near VA, and colour vision testing. VEP outcomes were P100 peak times, and OCT outcomes were peripapillary retinal nerve fibre layer (pRNFL) thickness (global, temporal, nasal, and papillomacular bundle (PMB)), macular volume, and central retinal thickness. Discriminative performance was assessed using receiver operating characteristic (ROC) analysis. Results Twelve paediatric MOGAD patients (10.9 ± 3.1 years) and twelve age-matched controls (11.5 ± 2.8 years) were included. VEP P100 peak times were generally comparable between patients and controls. pRNFL thickness appeared lower in patients than controls. ROC analysis showed excellent to outstanding discrimination for global, PMB, temporal, and nasal pRNFL sectors, both overall and in ON+ and ON– subgroups. VEP P100 peak times exhibited fair or poor discrimination overall, however 15′ check sizes showed excellent discrimination between ON+ and control eyes. Conclusions In our cohort, OCT-derived pRNFL thickness differentiated MOGAD from controls with high accuracy, including in eyes without prior ON. VEPs showed limited utility, supporting OCT as a more sensitive marker of subclinical structural involvement.

Background: One of the key factors for enhancing outcomes in neurorehabilitation of patients with congenital or acquired brain injury is optimal sensory function and identification of possible visual dysfunctions. Awareness of visual dysfunctions including cerebral visual impairment (CVI) is therefore of utmost importance in the rehabilitation process. The purpose was to investigate the frequency and nature of vision disorders in children admitted to a rehabilitation centre over a 5‐year period. Methods: This is a retrospective analysis of patients at the Swiss Children’s Rehab who received an ophthalmological consultation between January 2019 and December 2024. Electronic chart review was performed in patients with consent for the study. Analysed Data: Referral diagnoses leading to admission to the rehabilitation centre, corresponding ophthalmological findings, therapeutic interventions and demographics. The study was approved by the local ethics committee. Results: A total of 229 consultations from 163 patients were reviewed. The two most common causes for admission were traumatic (41/163) and inflammatory (36/163) conditions. Congenital disease was present in 30 patients. Most of the children had an acquired disorder (133/163). Pathological ophthalmological findings were present in 101/163 (62%) children examined. The most common findings were reduced vision (26/163) followed by CVI (22/163) and refractive errors (20/163). Traumatic causes were most often associated with oculomotor disorders (10/41) or CVI (6/41). CVI was prevalent in 22% of the pathological findings in this study. Conclusions: Ophthalmological assessment is recommended for all children with suspected visual dysfunction as part of the rehabilitation process.

Pathogenic variants in ADAMTSL4 are an important cause of isolated ectopia lentis with an increasing number of genetically confirmed cases internationally. We sought to better describe ocular features seen with pathogenic variants in ADAMTSL4 . We performed a retrospective, multicenter study examining the phenotypic and genotypic spectrum of ADAMTSL4 ‐associated ocular disease. We identified 41 individuals from 32 families with genetically confirmed ADAMTSL4 ‐related disease across six tertiary referral centers across Europe. Identified participants had a young age of diagnosis (median 1.3 years) and a highly myopic refractive error (mean SE −10.27 D). A diagnosis of ectopia lentis et pupillae was made in a third of cases, with a younger age at diagnosis (median 0.5 years). Subluxation tended to be in the inferior direction (~33%). Zonules were noted to be missing or absent in the majority of cases. Sixteen different pathogenic variants in ADAMTSL4 were reported. A previously reported 20‐bp deletion (c.767_786del) was highly prevalent in this cohort (23/32), and all ectopia lentis et pupillae cases carried this variant. ADAMTSL4 ‐related disease tends to present at a younger age and be associated with higher myopia than other forms of ectopia lentis (such as FBN1 ). Early identification of typical phenotypic features alongside genetic testing can aid early, precise diagnosis and prevent unnecessary investigations.

Congenital cataracts (CCs) are a leading cause of preventable childhood blindness, with genetic factors playing a crucial role in their etiology. Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder associated with CCs but is often underdiagnosed due to variable expressivity, particularly in female carriers. Objective: This study aimed to explore the genetic landscape of CCs in a Swiss cohort, focusing on two novel NHS and one novel GJA8 variants and their phenotypic presentation. Methods: Whole-exome sequencing (WES) was conducted on 20 unrelated Swiss families diagnosed with CCs. Variants were analyzed for pathogenicity using genetic databases, and segregation analysis was performed. Clinical data, including cataract phenotype and associated systemic anomalies, were assessed to establish genotype–phenotype correlations. Results: Potentially pathogenic DNA sequence variants were identified in 10 families, including three novel variants, one in GJA8 (c.584T>C) and two NHS variants (c.250_252insA and c.484del). Additional previously reported variants were detected in CRYBA1, CRYGC, CRYAA, MIP, EPHA2, and MAF, reflecting genetic heterogeneity in the cohort. Notably, NHS variants displayed significant phenotypic variability, suggesting dose-dependent effects and X-chromosome inactivation in female carriers. Conclusions: NHS remains underdiagnosed due to its variable expressivity and the late manifestation of systemic features, often leading to misclassification as isolated CC. This study highlights the importance of genetic testing in unexplained CC cases to improve early detection of syndromic forms. The identification of novel NHS and GJA8 variants provides new insights into the genetic complexity of CCs, emphasizing the need for further research on genotype–phenotype correlations.

Peters anomaly (PA) is a rare congenital disorder within the anterior segment dysgenesis (ASD) spectrum, characterized by corneal opacity, iridocorneal adhesions, and potential systemic involvement. The genetic basis of PA and related syndromes are complex and incompletely understood. This study investigates novel genetic variants and their clinical impact in two unrelated individuals diagnosed with PA spectrum disorder. Whole-exome sequencing (WES), long-range PCR, and breakpoint analysis were applied to identify pathogenic variants. In the first patient, a heterozygous ~1.6 Mb deletion was detected, spanning the genes PEX2 and ZFHX4 (GRCh37 chr8:g.76760782_78342600del). The second patient carried a heterozygous FOXC1 variant (NM_001453.3:c.310A>G), classified as likely pathogenic. Both variants were confirmed by Sanger sequencing and considered de novo, as they were not present in the biological parents. Clinical evaluations revealed phenotypic variability, with the first patient displaying both ocular and systemic anomalies as in a Peters plus-like syndrome phenotype, while the second patient had isolated ocular manifestations as in a PA type 1 phenotype. These findings expand the genetic landscape of PA, underscoring the importance of comprehensive genomic analysis in subclassifying ASD disorders. Further studies are needed to elucidate the functional consequences of these variants and improve diagnostic and therapeutic strategies.

Zusammenfassung: Hintergrund Die kongenitale Tränenwegstenose, eine häufige Erkrankung bei Neugeborenen, ist durch eine Verengung des Tränenwegsystems, häufig am Ductus nasolacrimalis, gekennzeichnet. In den meisten Fällen öffnet sich der Tränenweg spontan im 1. Lebensjahr, unterstützt durch Massagen. Bei fehlender Besserung kann eine operative Sondierung erforderlich sein. Ziel dieser Studie war die Analyse der Erscheinungsbilder und Ergebnisse operativ behandelter Tränenwegstenosen bei Kindern in unserer Klinik. Patienten und Methoden In einer retrospektiven Analyse wurden elektronische Krankenakten von Patienten unter 18 Jahren ausgewertet, die zwischen 2011 und 2023 wegen einer kongenitalen Tränenwegstenose behandelt wurden. Erfasst wurden demografische Daten, Symptome, Lokalisation der Stenose, operative Therapie und Ergebnisse. Zudem wurden Eltern der Patienten zur postoperativen Situation und Symptomatik befragt. Die Studie wurde von der Kantonalen Ethikkommission Zürich (BASEC2022-00830) genehmigt. Resultate Von insgesamt 147 identifizierten Patienten (39 weiblich, 62 männlich) konnte bei 69% eine Analyse mit vorliegendem Einverständnis erfolgen. Das Alter bei Erstuntersuchung lag zwischen 8 Monaten und 12 Jahren (median 27 Monate). Eine unilaterale Stenose wurde bei 69% und eine bilaterale bei 31% festgestellt. Die häufigsten Symptome waren Epiphora (95%), verklebte Zilien (68%), muköses Sekret (23%) und Rötung der Lider/Konjunktiva (19%). Bei 11% wurde intraoperativ eine Malformation festgestellt. Eine 2. Sondierung war bei 10% notwendig, wobei das Alter zwischen 18 und 69 Monaten lag (Median 38 Monate). Eine Dakryozystorhinostomie wurde bei 4% durchgeführt (Alter 92 – 145 Monate, median 113 Monate). Nach der Operation berichteten 70,5% subjektiv und/oder objektiv über Beschwerdefreiheit, 22,7% über anhaltende Epiphora und 6,8% über verkrustete Zilien. Bei 77/101 lag eine Beantwortung des Fragebogens vor. Hierbei berichteten 92%, dass das tränende Auge nicht mehr vorhanden war und 96% benötigten keine Therapie mehr. 97% gaben an, dass die Operation ohne Komplikationen verlief, 17% erlebten erneut tränende Augen, und 6% benötigten zusätzliche, nicht tränenwegbezogene Behandlungen. Fazit In den meisten Fällen ist eine alleinige Sondierung und Spülung zur Heilung ausreichend. Eine temporäre Sondeneinlage ist häufiger bei älteren Kindern notwendig. Eine Intervention nach dem 18. Lebensmonat beeinflusst die Heilung nicht negativ.

Background/Objectives: Neural retina leucine zipper (NRL) is a transcription factor involved in the differentiation of rod photoreceptors. Pathogenic variants in the gene encoding NRL have been associated with autosomal dominant retinitis pigmentosa and autosomal recessive clumped pigmentary retinal degeneration. Only a dozen unrelated families affected by recessive NRL-related retinal dystrophy have been described. The purpose of this study was to expand the genotypic spectrum of this disease by reporting clinical and genetic findings of two unrelated families. Methods: Index patients affected by retinal dystrophy were genetically tested by whole-exome sequencing (WES) and whole-genome sequencing (WGS). Segregation analysis within the families was performed for candidate variants. A minigene assay was performed to functionally characterize a variant suspected to affect splicing. Results: Variant filtering revealed homozygous NRL variants in both families. The variant in patient A was a small deletion encompassing the donor splice site of exon 1 of transcript NM_006177.3. The minigene assay revealed that this variant led to two aberrant transcripts that used alternative cryptic donor splice sites located in intron 1. In patient B, a stop-gain variant was identified in the last exon of NRL in a homozygous state due to maternal uniparental disomy of chromosome 14. Conclusions: Our study expands the genotypic spectrum of autosomal recessive NRL-related retinal dystrophy. Moreover, it underscores the importance of actively maintaining bioinformatic pipelines for variant detection and the utility of minigene assays in functionally characterizing candidate splicing variants.

Background/Objectives: Stargardt disease (STGD1) is an autosomal recessive disorder caused by pathogenic variants in ABCA4 that affects the retina and is characterised by progressive central vision loss. The onset of disease manifestations varies from childhood to early adulthood. Methods: Whole exome (WES), whole gene, and whole genome sequencing (WGS) were performed for a patient with STGD1. Results: WES revealed a heterozygous pathogenic missense variant in ABCA4, but no second pathogenic variant was found. ABCA4 whole-gene sequencing, subsequent WGS, and segregation analysis identified a complex deep-intronic allele (NM_000350.2(ABCA4):c.[1555-5882C>A;1555-5784C>G]) in trans to the missense variant. Minigene assays combined with nanopore sequencing were performed to characterise this deep-intronic complex allele in more detail. Surprisingly, the reference minigene revealed the existence of two pseudoexons in intron 11 of the ABCA4 gene that are included in low-abundance (ABCA4 intron 11, one of which was substantially increased by the complex allele.