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Chapter 6184In 22q11.2DS, thinning of RNFL segments with increasing age are consistent with findings of a study in adults in the general population.34 In that study, retinal layer thinning increasing with age was mainly found in the macular RNFL and the retinal ganglion cell layer. In Parkinson’s disease, loss of retinal ganglion cells and axons has been found, with thinning of the peripapillary RNFL in the inferotemporal segments,35 which is in line with our findings in adults with 22q11.2DS. ImplicationsTogether, findings of this study, and considering the consistency with previous studies in community-based schizophrenia spectrum and neurodegenerative disorders,16, 20, 34, 35 suggest that retinal FD and tortuosity may be useful biomarkers for psychotic disorders, and FD and RNFL thickness for (early) neurodegenerative processes in 22q11.2DS. Similarly, it may aid in our understanding of disease trajectories in other genetic neurodevelopmental disorders.36 An example may be found in a study in adults with Down syndrome that observed thinning of macular RNFL to be related to early Alzheimer’s disease pathology.37 To account for the earlier discussed factors that may contribute to retinal vessel morphology, and the medical complexity, adequately powered longitudinal studies are needed to better understand the changes that may occur within patients with 22q11.2DS.Mechanisms underlying retinovascular and retinoneural abnormalities in 22q11.2DSPotential biological mechanisms that may play a role in retinovascular and retinoneural abnormalities in 22q11.2DS include genetic variants, excessive mitophagy, cardiovascular abnormalities, and tissue oxygenation changes.29, 38, 39 One candidate gene for retinal vascular abnormalities that lies within the LCR22A-LCR22B region is TBX1, encoding a T-box transcription factor. TBX1 is important for cardiovascular development and regulates the vascular endothelial growth factor receptor 3-gene VEGFR3in brain endothelial cells.40-42 Studies in mice have indicated an important role for VEGFR3 in regulating angiogenesis and controlling branching of blood vessels in the retina and hindbrain.43 Inactivation of tbx1 in mice has shown to result in vascular abnormalities, impaired vascular functioning, and insufficient oxygenation in affected brain regions.40 Another gene that has been postulated to be involved in retinal abnormalities in 22q11.2DS,