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. Two female siblings, 4 y and 2 y, respectively, from a consanguineous Pakistani family were referred to our department for reduced VA and strabismus. Both girls were highly myopic and hence were further examined using standard clinical tests and electroretinography (ERG). The latter confirmed confounded electrical coupling of photoreceptors and bipolar cells. Further inquiry and testing confirmed a similar condition for the father including impaired night vision, reduced VA, photophobia, and an equally characteristic ERG. Findings in the mother were unremarkable. Subsequent genetic analysis of autosomal recessive and X-linked genes for congenital stationary night blindness (CSNB) revealed a novel homozygous splice site mutation in CACNA1F in the two girls transmitted from both the father and the mother. While in males the above clinical constellation is a frequent finding, this report, to the authors' knowledge, is the first demonstrating biallelic mutations at the CACNA1F locus in females.

[Handheld Optical Coherence Tomography in Paediatric Ophthalmology: Experience of the Department of Ophthalmology in Giessen]. / Handgehaltene optische Kohärenztomografie in pädiatrischer Ophthalmologie: Erfahrung der Gießener Universitätsaugenklinik.

Introduction: Optical coherence tomography is an important tool for the imaging and analysis of retinal structures. The usability of conventional table-top devices is limited in children. We report on our experiences with a handheld Spectral Domain Optical Coherence Tomography (HH-SD-OCT, Bioptigen™) in infants and young children in our daily practice. Methods: Between October 2014 and April 2016, we investigated 259 patients. Indications and diagnoses were assessed. Individual examples are shown to demonstrate the advantages and disadvantages of the novel technique. Results: It was possible to examine 259 children of at least 7 weeks of age (median: 1.59 years; ± 1.32 SD) with a mean investigation time of 18.3 minutes (± 8.3 SD). The most frequent indication was retinal assessment in prematures (32.8 %). Nystagmus, retinal dystrophies, reduced visual acuity and albinism amounted to additional 37.4 % of all indications. Conclusions: Handheld OCT is a beneficial complement for diagnosis of diseases in paediatric ophthalmology. As a complement to established methods like wide-field fundus photography, HH-SD-OCT allows the physician to assess and follow-up new objective structural information. As the Bioptigen does not have an eye tracker, it is challenging to orient the scan in the posterior retinal pole, in particular in case of instable fixation. This complicates follow-up investigations, which can only be performed with additional high programming and analysis effort.

Correlation of central visual function and ROP risk factors in prematures with and without acute ROP at the age of 6-13†years: the Giessen long-term ROP study.

AIM: To correlate light increment sensitivity (LIS) and visual acuity (VA) with birth weight (BW), gestational age (GA) and stage of acute retinopathy of prematurity (ROP) (STG) in premature children at school age. METHODS: 180 children (150 former prematures and 30 age-matched term-born children) were enrolled at age 6-13 years. Former prematures were categorised by the results of the initial ROP screening based on digital wide-field fundus imaging: absence of ROP (n=100) and spontaneously resolved ROP (n=50). The latter group was further subdivided according to their STG (Stg 1; Stg 2; Stg 3). Both groups were categorised into sectors by BW (<1000 g; 1000-1500 g; >1500 g), and GA (≤28 weeks; >28<32 weeks; ≥32 weeks). VA was assessed with Early Treatment of Diabetic Retinopathy Study letters, LIS was measured at 0°, 2.8° and 8° in the visual field (Microperimeter MP1, Nidek Technologies), and spherical equivalent refraction assessed with a Nidek autorefractor (Nidek, Italy). RESULTS: Central and pericentral LIS (0° and 2.8°) and VA were significantly lower in all groups and sectors compared with term-born controls except for BW >1500 g for LIS and GA >28 to <32 W for VA. No significant differences were found for LIS at 8° in all groups. No correlation was found between LIS and VA on an individual basis. CONCLUSIONS: Low BW, GA and increasing severity of spontaneously resolving ROP were associated with significantly decreased central visual function. In addition to VA, LIS measurement further describes foveal function and is a unique parameter to assess parafoveal function.

[Autosomal recessive bestrophinopathy (ARB): a clinical and molecular description of two patients at childhood]. / Autosomal-rezessive Bestrophinopathie (ARB): klinische und molekulare Beschreibung zweier Patienten im Kindesalter.

BACKGROUND: Autosomal recessive bestrophinopathy (ARB) is associated with mutations in BEST1. ARB is rarely diagnosed compared to BEST1-associated autosomal dominant (a. d.) juvenile vitelliform macular degeneration (Morbus Best, VMD). This is not only due to its low prevalence, but also to the phenotypic appearance. This paper describes typical features in two patients and discusses novel findings using improved ophthalmological diagnostic tools. MATERIAL AND METHODS: Two unrelated boys with reduced visual acuity as well as five further relatives underwent a comprehensive ophthalmological examination including electroretinography (ERG) and electrooculography (EOG) according to ISCEV standard, fundus autofluorescence (FAF) and spectral-domain optic coherence tomography (SD­OCT). BEST1 was screened for mutations based on the clinical diagnosis. RESULTS: Visual acuity ranged between 0.2 and 0.5 in the patients. Multifocal yellowish paramacular and peripheral lesions were visible in the fundus correlating with spots of increased FAF. The lesions correlated with thickening of the RPE layer. Especially in the inner nuclear layer hyporeflective areas were visible, reminiscent of retinoschisis but without changes of FAF. In both patients the ganzfeld ERG was within the normal range and the mfERG presented obvious reductions of amplitudes in the central area. The EOG did not show a light peak. Goldmann perimetry was normal for isopters III/4e and I/4e. The fundus controlled perimetry revealed a central sensitivity loss. Molecular genetic analysis identified four (two novel) mutations in BEST1, in the compound heterozygous state in both patients. The screened relatives carried one of the mutations in the heterozygous state and were ophthalmologically unremarkable apart from age-related changes. CONCLUSION: ARB is a rare disease, presenting with obvious differences to a.d. Mobus Best. The phenotype can easily be identified by the extramacular multifocal yellowish lesions with increased FAF and accompanied by early loss of visual acuity. Specific diagnostic tests like OCT, FAF recordings and electrophysiology support the diagnosis. Molecular genetic screening confirms the diagnosis and the autosomal recessive inheritance.