Conjunctival microcirculation imaging provides a non-invasive means for detecting hemodynamic alterations due to systemic and ocular diseases. However, reliable longitudinal monitoring of hemodynamic changes due to disease progression requires establishment of measurement variability over time. The purpose of the current study was to determine inter-visit variability of conjunctival microvascular hemodynamic measurements in non-diabetic control (NC, N = 7) and diabetic retinopathy (DR, N = 10) subjects. Conjunctival microvascular imaging was performed during 2 visits, which were 17 ± 12 weeks apart. Images were analyzed to determine vessel diameter (D), axial blood velocity (V), blood flow (Q), wall shear rate (WSR) and wall shear stress (WSS). The inter-visit variability was determined based on mean inter-visit differences. In NC, inter-visit variability of D, V, Q, WSR and WSS were 0.2 ± 0.5 µm, −0.01 ± 0.16 mm/s, −8 ± 46 pl/s, −3 ± 46 s−1 and −0.01 ± 0.10 dyne/cm2, respectively. Inter-visit variability of D, V, Q, WSR and WSS were beyond the normal 95% confidence limits in 60%, 20%, 40%, 20% and 20% of DR subjects, respectively. The variability of hemodynamic measurements over time was established in non-diabetic subjects, suggestive of the potential of the method for detecting longitudinal changes due to progression of DR.

The purpose of the current study was to investigate alterations in retinal oxygen delivery, metabolism, and extraction fraction and elucidate their relationships in an experimental model of retinal ischemia. METHODS. We subjected 14 rats to permanent bilateral common carotid artery occlusion using clamp or suture ligation, or they underwent sham procedure. Within 30 minutes of the procedure, phosphorescence lifetime imaging was performed to measure retinal vascular oxygen tension and derive arterial and venous oxygen contents, and arteriovenous oxygen content difference. Fluorescent microsphere and red-free retinal imaging were performed to measure total retinal blood flow. Retinal oxygen delivery rate (DO 2), oxygen metabolism rate (MO 2), and oxygen extraction fraction (OEF) were calculated. RESULTS. DO 2 and MO 2 were lower in ligation and clamp groups compared to the sham group, and also lower in the ligation group compared to the clamp group (P 0.05). OEF was higher in the ligation group compared to clamp and sham groups (P 0.03). The relationships of MO 2 and OEF with DO 2 were mathematically modeled by exponential functions. With moderate DO 2 reductions, OEF increased while MO 2 minimally decreased. Under severe DO 2 reductions, OEF reached a maximum value and subsequently MO 2 decreased with DO 2. CONCLUSIONS. The findings improve knowledge of mechanisms that can maintain MO 2 and may clarify the pathophysiology of retinal ischemic injury.

Creutzfeldt-Jakob Disease (CJD) is a neurodegenerative disease characterized by mutant PrP prion proteins, which accumulates and impairs the function of wild-type PrPc proteins. The interaction of prion proteins with wild-type proteins converts the PrPc proteins to mutant PrP proteins. These mutant prion proteins lead to neural tissue degradation and other nervous system problems that can eventually lead to death. The use of antibodies to target and destroy prion proteins can be used to decrease PrP levels that can stop CJD progression. The binding affinities of different anti-PrP Fab antibodies are analyzed to determine which antibody best binds to PrP proteins and targets them for destruction. Through antibody-based targeting of prion proteins, potential treatment methods could be developed for CJD. In addition, the use of drugs, such as quinacrine and doxycycline, also show short-term effects in decreasing the progression of CJD. These drugs extend the average lifespan of tested subjects with CJD but also lead to the development of drug-resistant prion proteins that eventually cause the death of the subject affected by CJD.

Purpose Diabetic retinopathy (DR) is a common cause of vision loss in working age adults and presents changes in retinal vessel oxygenation and morphology. The purpose of this study was to test the hypothesis that there is an association of retinal vessel oxygen saturation with vessel density (VD) and tortuosity in DR. Methods Ninety-five subjects were classified in the following groups: nondiabetic control ( N = 25), no DR ( N = 28), mild nonproliferative DR (NPDR; N = 21), moderate to severe NPDR ( N = 14), or treated proliferative DR (PDR; N = 7). Retinal oximetry was performed to measure arterial and venous oxygen saturation (SO 2A and SO 2V ) and calculate oxygen extraction fraction (OEF). Optical coherence tomography angiography (OCTA) was performed for measurements of VD and vessel tortuosity index (VTI). Results There were statistically significant differences in SO 2A and SO 2V among groups ( P < 0.004). SO 2A and SO 2V were higher in the PDR group compared to the control group and SO 2V was also higher in the moderate to severe NPDR group. VD differed significantly among groups ( P = 0.003), whereas VTI was not significantly different ( P = 0.22). Compared to the control group, VD was lower in moderate to severe NPDR and PDR groups. VD was also lower in the PDR group than that in the no DR group ( P = 0.03). There was a significant correlation of VTI with SO 2V (r = 0.32, P = 0.002) and OEF (r = −0.35, P = 0.001). Conclusions Retinal vessel morphology, oxygenation, and tissue oxygen extraction were associated with each other in a cohort of subjects with and without DR. Translational Relevance The findings of this study have the potential to improve clinical management of DR by providing better understanding of human disease pathophysiology and propelling future studies to identify multiple image-based biomarkers for improved disease diagnosis and monitoring.