Anna Brouwer

arthritis or other retinal diseases including diabetic retinopathy, retinal dystrophy, family history of retinal dystrophy, myopic degeneration, or severe media opacities were excluded. Ethical approval was requested and obtained from the Medical Ethical Research Committee of the University Medical Center Utrecht. This study was conducted in compliance with the ethical principles of the declaration of Helsinki. ERG measurement ERGs were measured according to an extended protocol, with more flash strengths than the standard International Society for Clinical Electrophysiology of Vision (ISCEV) protocol. 11 For the light-adapted (LA) ERG this protocol comprised 0.3, 1.0, 3.0 and 10.0 cds/m 2 flash strengths and a 30 Hz flicker response. Dawson-Trick-Litzkow (DTL) electrodes were used as active electrodes, and an Espion E3 system with Colordome stimulator (Diagnosys LLC, Cambridge, UK) for flash stimulation. We defined the cone b-IT as prolonged when two or more consecutive flash strengths from the LA ERG were above the 95 th percentile of the implicit times of a normal population. 5,11 Our reference values, and ERG results have been previously described. 5,6 OCT retinal layer analysis OCT images were made with Carl Zeiss Cirrus HD-OCT model 5000 (Carl Zeiss Meditec AG, Germany). C-scans were 200 x 200 x 1024 voxels and were analyzed using the Iowa Reference Algorithms (Retinal Image Analysis Lab, Iowa Institute for Biomedical Imaging, Iowa City, IA). 7,12,13 This program automatically defines the borders of ten retinal layers and calculates the mean (SD) thickness of these retinal layers per retinal region. Figure 1givesanoverviewof the ten retinal layersas seenonOCT: the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), inner segment/ outer segment (IS/OS), outer segment layer (OSL), outer segment photoreceptors/ retinal pigment epithelium complex (OPR) and retinal pigment epithelium (RPE). The nine regions of which the thickness were analyzed were those of the Early Treatment Diabetic Retinopathy Study (ETRDRS) grid. Statistical analysis R Studio (R studio, 2019, version 3.6.0) was used for statistical analyses. The distribution of the automatically segmented thickness analysis was evaluated with Shapiro-Wilk tests, Q-Q plots, histograms and boxplots. Extreme outliers (Tukey’s k = 3) were 96 Chapter 4