|dc.description.abstract||Purpose. Children with visual impairment may be referred for ERG and OCT testing to aid in diagnosis and monitoring, particularly those with suspected retinal diseases. To establish if a result is abnormal, knowledge of typical development of retinal structure and function is essential to detect, monitor, and understand pathological processes that may affect the pediatric retina. The purpose of the first study was to investigate the development of the ERG waveforms from childhood until adulthood in healthy children of European descent to better understand how retinal function changes with age. Additionally, the study aimed to provide a pediatric normative dataset for the standard ERGs to be used for clinical interpretations for children with suspected retinal diseases. The purpose of the second study was to investigate the maturation of the retinal structure from childhood until adulthood. Also, the study aimed to provide a pediatric normative dataset of retinal layer thickness maps measurements for each of the seven layers that were automatically generated by SD-OCT in the retinal regions defined by the Early Treatment of Diabetic Retinopathy Study (EDTRS) (Heidelberg Spectralis) in the same population (children of European descent). The additional purpose was to provide reference values for each sector of the peripapillary RNFL thickness. Adults were included in both studies for comparison.
Methods. For the first cross-sectional study (ERG study), thirty-two participants of European descent with normal ocular and general health were recruited. The sample included 12 children between 7 and 11 years, 10 older children and adolescents between 12 and 15 years and 10 adults between 20 and 33 years. Full-field ERGs were recorded simultaneously in each eye from thread electrodes (DTL® fiber) using the Espion E3 system with fully dilated pupils (0.5% tropicamide). Stimuli were ISCEV standard dark-adapted ERGs (DA 0.01, DA 3, DA 10) as well as a light-adapted ERG series with flash strengths of 0.3, 1.0, 3.0, 10 & 24 cd.s.m2 (which includes the standard LA 3.0). We measured a- and b-wave amplitudes and implicit times using the average of the right and left eye values to compare age groups.
For the cross–sectional second study (OCT study), thirty-six participants of European descent with normal ocular and general health were recruited. The sample included 6 children between 4 and 7 years, 9 children between 8 and 11 years and 10 adolescents between 12 and 15 years and 11 adults between 20 and 33 years. SD-OCT scans centered on the fovea were acquired with fully dilated pupils (0.5% tropicamide). Retinal thickness values were measured for the ETDRS regions for each of the seven layers that were automatically generated by SD-OCT (Heidelberg Spectralis, Eye Explorer software version 18.104.22.168). The peripapillary RNFL thickness measurements were calculated using the Spectralis OCT device. The influence of age on the foveal subfield, inner ring, and outer ring of the ETDRS maps, as well as on the peripapillary RNFL thickness was determined using parametric or ranked correlations. Adjusted Bonferroni correction was applied to correct for multiple comparisons.
Results. For the first study, both DA a- and- b-wave implicit times were significantly positively correlated with age for all stimuli except for the b-wave of the DA 3.0 ERG i.e., implicit times were shorter for children compared to adults. Rank correlations of a-wave with age were r=0.573, p = 0.001 for the DA 3.0 ERG, r = 0.570, and p < 0.001 for the DA 10 ERG. DA b-wave implicit times were correlated with age for the weak and strong flash stimuli but not for the LA standard 3.0 ERG (DA 0.01 ERG [r = 0.596, p< 0.001] or DA 10 ERG [r = 0.434, p< 0.013]). With respect to the LA ERGs, a-wave implicit times did not correlate with age except for the LA 0.3 ERG (r = 0.548, p = 0.001). LA b-wave implicit times did not correlate with age except for the LA 1.0 ERG time age (r = 0.363, p= 0.041). In contrast, none of the ERG DA and LA amplitudes for both a- and b-waves were significantly correlated with age.
For the second study, average global peripapillary RNFL thickness was 104.86 +/- 9.43µm. The peripapillary RNFL thickness was not significantly correlated with age except for the nasal superior sector where it thinned with age (r = -0.379, p = 0.023). Regarding the ETDRS regions, the total retinal thickness was positively correlated with age in the foveal subfield (r = 0.487, p = 0.003) but not in the other ETDRS rings. All the individual inner retinal layers thickened with age in some regions, except for the ganglion cell layer. While the retinal nerve fiber layer was significantly positively correlated with age in the fovea (r = 0.557, p<0.001) and parafovea (0.474, p = 0.004), the inner plexiform layer was only influenced by age in the parafoveal area (0.495, p= 0.002). In contrast, the inner nuclear layer was positively influenced by age only at the fovea (r = 0.452, p= 0.006). The individual outer retinal layers were associated with age in some regions except for the outer nuclear layer. While the outer plexiform layer thinned significantly with age in the parafoveal area (r = -0.394, p = 0.017), the retinal pigment epithelium thickened with age (r = 0.387, p = 0.020) in the foveal area.
In Chapter 5 examples of OCTs and ERGs from children with retinopathy due to HARS syndrome are compared qualitatively with the present results.
Conclusion. The present study provides evidence that the functional and morphological development of the retina may not be mature for children aged from 4 to 15 years. So that, the implicit times of both DA a- and b-waves and some of the LA ERGs (0.3[a-wave], 1.0 [b-wave]) increase with age to approach the adult values. Similarly, the OCT findings of the present study indicate that both the inner and outer retinal layers were influenced by age except for the ganglion cells and outer nuclear layers. Nevertheless, the peripapillary RNFL thickness measurements were not affected by age except for the nasal superior sector such that the thickness values decrease with age. In this study, we were able to obtain OCT scans using standard instruments for children as young as 4 years, and as young as 7 years for ERG. For the quantitative measurements from these techniques to be most beneficial in detecting and monitoring retinal disorders in pediatric patients, they have to be compared to an age-matched database. Age-norms and ranges were therefore calculated for those measures that were correlated with age, and overall means/medians and 95% ranges for those that were not correlated with age. These normative values can be used as a reference against which to compare for children with suspected retinal diseases.||en