Optical Coherence Tomography: Retinal Imaging Contributes to the Understanding of Brain Pathology in Classical Galactosemia.

It remains unresolved whether central nervous system involvement in treated classical galactosemia (CG) is a progressive neurodegenerative process. This study aimed to investigate retinal neuroaxonal degeneration in CG as a surrogate of brain pathology. Global peripapillary retinal nerve fibre layer (GpRNFL) and combined ganglion cell and inner plexiform layer (GCIPL) were analysed in 11 CG patients and 60 controls (HC) using spectral-domain optical coherence tomography. Visual acuity (VA) and low-contrast VA (LCVA) were acquired to test visual function. GpRNFL and GCIPL did not differ between CG and HC (p > 0.05). However, in CG, there was an effect of intellectual outcome on GCIPL (p = 0.036), and GpRNFL and GCIPL correlated with neurological rating scale scores (p < 0.05). A single-case follow-up analysis showed GpRNFL (0.53-0.83%) and GCIPL (0.52-0.85%) annual decrease beyond the normal aging effect. VA and LCVA were reduced in CG with intellectual disability (p = 0.009/0.006), likely due to impaired visual perception. These findings support that CG is not a neurodegenerative disease, but that brain damage is more likely to occur early in brain development. To clarify a minor neurodegenerative component in the brain pathology of CG, we propose multicenter cross-sectional and longitudinal studies using retinal imaging.

Optical Coherence Tomography to Assess Neurodegeneration in Phenylalanine Hydroxylase Deficiency.

In phenylalanine hydroxylase (PAH) deficiency, an easily feasible method to access the progression of neurodegeneration is warranted to contribute to current discussions on treatment indications and targets. The objective of the present study was to investigate whether optical coherence tomography (OCT) measures as markers of neurodegeneration differ between patients with PAH deficiency and healthy controls (HCs) according to phenotype and metabolic control. In this single-center cross-sectional study, 92 patients with different phenotypes of PAH deficiency [PAH deficiency not requiring treatment, early treated phenylketonuria (ETPKU), and late-diagnosed phenylketonuria (PKU)] compared with 76 HCs were examined using spectral-domain OCT. Indices of phenylalanine elevation and variability were correlated with OCT parameters. Late-diagnosed PKU patients showed reduced peripapillary retinal nerve fiber layer (pRNFL) thickness and combined ganglion cell and inner plexiform layer (GCIPL) volume. Adult ETPKU patients were found to have lower GCIPL volume (p = 0.016), which correlated with the indices of phenylalanine control. In pediatric ETPKU patients with poor metabolic control, pRNFL was significantly reduced (p = 0.004). Patients with PAH deficiency not requiring treatment did not exhibit retinal degeneration. Inner nuclear layer (INL) was significantly increased in the pediatric ETPKU patients, driven by those with current poor metabolic control (p = 0.006). Our data provide evidence of retinal neuroaxonal degeneration and INL swelling, depending on the phenotype, current age, and metabolic control. These findings suggest that OCT is suitable to investigate neurodegeneration in PKU and we propose OCT as a sensitive, reliable, safe, low-burden, and low-cost examination for future multicenter studies.