Caitlin Rook

Rapid, High-Accuracy Detection of Strabismus and Amblyopia Using the Pediatric Vision Scanner

Purpose. The Pediatric Vision Scanner (PVS) detects strabismus by identifying ocular fixation in both eyes simultaneously. This study was undertaken to assess the ability of the PVS to identify patients with amblyopia or strabismus, particularly anisometropic amblyopia with no measurable strabismus. Methods. The PVS test, administered from 40 cm and requiring 2.5 seconds of attention, generated a binocularity score (BIN, 0%-100%). We tested 154 patients and 48 controls between the ages of 2 and 18 years. BIN scores of amblyopic children and controls were measured, and 21 children received sequential PVS measurements to detect any changes in BIN resulting from amblyopia treatment. Results. With the pass/refer threshold set at BIN 60%, sensitivity and specificity were 96% for the detection of amblyopia or strabismus. Assuming a 5% prevalence of amblyopia or strabismus, the inferred positive and negative predictive values of the PVS were 56% and 100%, respectively. Fixation accuracy was significantly reduced in amblyopic eyes. In anisometropic amblyopia patients treated successfully, the BIN improved to 100%. Conclusions. The PVS identified children with amblyopia or strabismus with high sensitivity and specificity, while successful treatment restored normal BIN scores in amblyopic patients without strabismus. The results support the hypothesis that the PVS detects strabismus and amblyopia directly. Future strategies for screening by nonspecialists may thus be based on diagnostic detection of amblyopia and strabismus rather than the estimation of risk factors, allowing for rapid, accurate identification of children with amblyopia early in life when it is most amenable to treatment.

IN VIVO ASSESSMENT OF MOLECULAR AGING BY QUASI-ELASTIC LIGHT SCATTERING IN HUMAN LENS

lipidated and quickly catabolized (2) APOE4 particles are themselves toxic. During the disease progression Ab exists as monomer, soluble Ab oligomers and fibrillar Ab. There is increasing evidence that Ab oligomers are the most toxic species, contributing to AD related cognitive decline, synaptic dysfunction and inhibition of long-term potentiation. We hypothesize that APOE4 interaction with Ab diminishes the formation of toxic oligomeric species and alleviates its deleterious effects. Methods: Electron microscopy and western and dot blotting were used to characterize complexes, resulting from co-incubating monomeric Ab with APOE3 or APOE4 at oligomer forming conditions. Utilizing primary mouse neuronal cultures we determined the effect of Ab oligomers +/APOE particles on transcriptome profiles. We also examined the impact of these co-incubations on synaptic markers and structure utilizing Sholl analysis. Lastly, we infused Ab oligomers +/APOE particles into the hippocampi of WT mice and examined their impact on cognitive performance utilizing novel object recognition and fear conditioning. Results:We demonstrate that ApoE3 and ApoE4 particles decrease Ab oligomer formation. Furthermore, treatment of neurons with APOE-Ab complexes significantly impacts the transcriptome and neuronal structurewhen compared to Ab oligomers alone. Hippocampal infusion of Ab oligomers significantly decreased cognitive performance in WT mice in two memory paradigms. Lastly, APOE3 and APOE4 when used at equal concentrations are equally protective against deleterious effects of Ab oligomers on cognitive function. Conclusions: This study demonstrates the importance of oligomeric Ab in AD related cognitive decline and the ability of APOE to influence oligomeric Ab toxicity. Moreover, this study provides further support of APOE as a potential therapeutic target for AD.

Monitoring Molecular Aging of Lens Proteins using Noninvasive Quasi-Elastic Light Scattering

Post-translational modifications of lens proteins during aging can be monitored with quasi-elastic light scattering. Here, we show the ability of the technique to detect these changes both ;in vitro and ;in vivo.

Noninvasive detection of Alzheimer's disease lens pathology in down syndrome by quasi-elastic light scattering

In Down syndrome there is increased deposition of Alzheimer’s disease-related Amyloid-β protein in the brain and lens. Here we use quasi-elastic light scattering to noninvasively detect Alzheimer’s disease lens pathology in subjects with Down syndrome.