Visuele functies bij 5-jarige kinderen in relatie tot een zeer laag geboortegewicht en/of een zeer korte zwangerschapsduur

Uit eerder onderzoek verricht op de afdeling Fysiologie I van de Erasmus Universiteit Rotterdam is gebleken dat kinderen, waarvan het geboortegewicht zeer laag was ( <1500 g, VLBW) een verhoogde kans hebben op stoornissen van de visuele ontwikkeling. Zeker 50% van de VLBW kinderen bleken in het eerste levensjaar afwijkingen te hebben in de ontwikkeling van de gezichtsscherpte, gezichtsvelden en/of binoculaire of monoculaire optokinetische nystagmus (OKN). Deze visuele stoornissen leken in verband te staan met perinataal cerebraal letsel. Het percentage VLBW kinderen met een visuele stoornis was het hoogst wanneer visueel onderzoek verricht werd op de leeftijd van 6 maanden. Na deze leeftijd (tussen de leeftijd van 6 maanden en 2 ½ jaar) bleek het percentage visueel gestoorde kinderen af te nemen. Deze resultaten wijzen erop dat de visuele ontwikkeling bij VLBW kinderen vertraagd kan verlopen. Anderzijds was het percentage visuele stoornissen op 2 ½-jarige leeftijd nog steed verhoogd. Het was onbekend of VLBW kinderen ook een verhoogde kans hebben op blijvende stoornissen van het zien. Om deze reden werden visuele functies onderzocht bij 450 5-jarige kinderen, waarvan het geboortegewicht minder dan 1500 gram was en/of de zwangerschapsduur korter dan 32 weken (in het huidige onderzoek risico kinderen genoemd). Ter vergelijking werden tevens 201 5-jarige controle kinderen onderzocht, waarvan het geboortegewicht tussen 2500 en 4500 gram was en de zwangerschapsduur tussen 37 en 42 weken

Strabismus in very low birth weight and/or very preterm children: Discrepancy between age of onset and start of treatment

Present medical care is not sufficient for early detection and treatment of strabismus in at-risk children. Our results suggest that the optimal screening age for early detection of persistent strabismus in VLBW children is at 9 months of age. Because strabismus can also develop after this age, it is important to repeat examination of visual functions in at risk-children at regular intervals after 1 year of age

LONGITUDINAL STUDY OF RPE65-ASSOCIATED INHERITED RETINAL DEGENERATIONS

PURPOSE: To study the disease course of RPE65-associated inherited retinal degenerations (IRDs) as a function of the genotype, define a critical age for blindness, and identify potential modifiers. METHODS: Forty-five patients with IRD from 33 families with biallelic RPE65 mutations, 28 stemming from a genetic isolate. We collected retrospective data from medical charts. Coexisting variants in 108 IRD-associated genes were identified with Molecular Inversion Probe analysis. RESULTS: Most patients were diagnosed within the first years of life. Daytime visual function ranged from near-normal to blindness in the first four decades and met WHO criteria for blindness for visual acuity and visual field in the fifth decade. p.(Thr368His) was the most common variant (54%). Intrafamilial variability and interfamilial variability in disease severity and progression were observed. Molecular Inversion Probe analysis confirmed all RPE65 variants and identified one additional variant in LRAT and one in EYS in two separate patients. CONCLUSION: All patients with RPE65-associated IRDs developed symptoms within the first year of life. Visual function in childhood and adolescence varied but deteriorated inevitably toward blindness after age 40. In this study, genotype was not predictive of clinical course. The variance in severity of disease could not be explained by double hits in other IRD genes

Diagnostic exome sequencing in 266 Dutch patients with visual impairment

Inherited eye disorders have a large clinical and genetic heterogeneity, which makes genetic diagnosis cumbersome. An exome-sequencing approach was developed in which data analysis was divided into two steps: the vision gene panel and exome analysis. In the vision gene panel analysis, variants in genes known to cause inherited eye disorders were assessed for pathogenicity. If no causative variants were detected and when the patient consented, the entire exome data was analyzed. A total of 266 Dutch patients with different types of inherited eye disorders, including inherited retinal dystrophies, cataract, developmental eye disorders and optic atrophy, were investigated. In the vision gene panel analysis (likely), causative variants were detected in 49% and in the exome analysis in an additional 2% of the patients. The highest detection rate of (likely) causative variants was in patients with inherited retinal dystrophies, for instance a yield of 63% in patients with retinitis pigmentosa. In patients with developmental eye defects, cataract and optic atrophy, the detection rate was 50, 33 and 17%, respectively. An exome-sequencing approach enables a genetic diagnosis in patients with different types of inherited eye disorders using one test. The exome approach has the same detection rate as targeted panel sequencing tests, but offers a number of advantages. For instance, the vision gene panel can be frequently and easily updated with additional (novel) eye disorder genes. Determination of the genetic diagnosis improved the clinical diagnosis, regarding the assessment of the inheritance pattern as well as future disease perspective

Screening for suppresion in young children: the Polaroid-Suppression-Test

Background: Assessment of monocular visual impairment during screening of young children is often hampered by lack of cooperation. Because strabismus, amblyopia, or anisometropia may lead to monocular suppression during binocular viewing conditions, a test was developed to screen far suppression in young children. Methods: Children were invited to look through two polaroid filters of different polarization direction at two pictures covered with polaroid filters of opposite polarization direction. In this way, each eye could only see one of the two pictures. in cases of suppression, only one picture would be visible. Acuity measurements in 201 B-year-old children were compared with the Polaroid Suppression test (PST) results. Results: The PST had a high success rate (99.5%) and testing time was under 1 minute. Specificity of the PST for acuity impairments was 91%. The low sensitivity of 60% was caused mainly by the fact that some children with binocular acuity impairments were not detected with the PST. However, the PST was highly sensitive for significant interocular acuity differences. Conclusion: The PST has been found to be a useful screening method for amblyogenic factors in young children. The test can be carried out without occlusion of one eye. The apparatus is portable, the test duration is short, and the costs are low. The results indicate that the PST is a very promising tool to use in clinical conditions and for screening large numbers of young children

Screening for suppression in young children: the Polaroid Suppression test

Background: Assessment of monocular visual impairment during screening of young children is often hampered by lack of cooperation. Because strabismus, amblyopia, or anisometropia may lead to monocular suppression during binocular viewing conditions, a test was developed to screen far suppression in young children. Methods: Children were invited to look through two polaroid filters of different polarization direction at two pictures covered with polaroid filters of opposite polarization direction. In this way, each eye could only see one of the two pictures. in cases of suppression, only one picture would be visible. Acuity measurements in 201 B-year-old children were compared with the Polaroid Suppression test (PST) results. Results: The PST had a high success rate (99.5%) and testing time was under 1 minute. Specificity of the PST for acuity impairments was 91%. The low sensitivity of 60% was caused mainly by the fact that some children with binocular acuity impairments were not detected with the PST. However, the PST was highly sensitive for significant interocular acuity differences. Conclusion: The PST has been found to be a useful screening method for amblyogenic factors in young children. The test can be carried out without occlusion of one eye. The apparatus is portable, the test duration is short, and the costs are low. The results indicate that the PST is a very promising tool to use in clinical conditions and for screening large numbers of young children