A Pilot Study Assessing Retinal Blood Flow Dysregulation in Glaucoma Using Erythrocyte Mediated Velocimetry.

Purpose: The purpose of this study was to compare autoregulation of retinal arteriolar and venular blood flow in patients with glaucoma, glaucoma suspect participants, and control participants using erythrocyte mediated velocimetry. Methods: This prospective cohort pilot study included 7 eyes of 5 participants with glaucoma, 15 eyes of 8 glaucoma suspect participants, and 11 eyes of 6 control participants. Mean erythrocyte velocity in retinal arterioles and venules was measured using erythrocyte mediated velocimetry at room air and after oxygen supplementation. Change in erythrocyte velocity was compared among all groups using generalized estimating equations. Results: In total, 64 vessels (18 with glaucoma, 31 that were glaucoma suspect, and 15 controls) of 33 eyes of 19 participants were analyzed. There was no significant difference in baseline velocities in arterioles or venules among the three groups. With induction of hyperoxia, mean arterial erythrocyte velocity decreased in glaucoma (-7.2 ± 13.7%), which differed from controls and glaucoma suspects where erythrocyte velocity increased with hyperoxia by 4.6 ± 13.3% (P = 0.002) and 7.2 ± 21.7% (P = 0.03), respectively. A higher baseline arteriolar velocity (ß = -3.9% per mm/s, P = 0.002), glaucoma diagnosis (ß = -21.1%, P = 0.03), and White race (ß = -20.0%, P = 0.01) were associated with decreased velocity in response to arterial hyperoxia. Conclusions: Hyperoxia increased erythrocyte velocity in control and glaucoma suspect participants, but decreased erythrocyte velocity in glaucoma participants, possibly due to impaired autoregulation. Baseline velocity, glaucoma diagnosis, and White race were associated with a decrease in velocity with induction of hyperoxia. Translational Relevance: The European Medicines Agency (EMA) permits precision measurements of blood flow which may aid in the development of biomarkers of glaucoma-related dysregulation of blood flow.

Differences in visual field loss pattern when transitioning from SITA standard to SITA faster.

Swedish Interactive Threshold Algorithm (SITA) Faster is the most recent and fastest testing algorithm for the evaluation of Humphrey visual fields (VF). However, existing evidence suggests that there are some differences in global measures of VF loss in eyes transitioning from SITA Standard to the newer SITA Faster. These differences may be relevant, especially in glaucoma, where VF changes over time influence clinical decisions around treatment. Furthermore, characterization of differences in localizable VF loss patterns between algorithms, rather than global summary measures, can be important for clinician interpretation when transitioning testing strategies. In this study, we determined the effect of transitioning from SITA Standard to SITA Faster on VF loss patterns in glaucomatous eyes undergoing longitudinal VF testing in a real-world clinical setting. Archetypal analysis was used to derive composition weights of 16 clinically relevant VF patterns (i.e., archetypes (AT)) from patient VFs. We found switching from SITA Standard to SITA Faster was associated with less preservation of VF loss (i.e., abnormal AT 2-4, 6-9, 11, 13, 14) relative to successive SITA Standard exams (P value < 0.01) and was associated with relatively greater preservation of AT 1, the normal VF (P value < 0.01). Eyes that transition from SITA Standard to SITA Faster in a real-world clinical setting have an increased likelihood of preserving patterns reflecting a normal VF and lower tendency to preserve patterns reflecting abnormal VF as compared to consecutive SITA Standard exams in the same eye.

Predicting Flow Rate Escalation for Pediatric Patients on High Flow Nasal Cannula Using Machine Learning.

Background: High flow nasal cannula (HFNC) is commonly used as non-invasive respiratory support in critically ill children. There are limited data to inform consensus on optimal device parameters, determinants of successful patient response, and indications for escalation of support. Clinical scores, such as the respiratory rate-oxygenation (ROX) index, have been described as a means to predict HFNC non-response, but are limited to evaluating for escalations to invasive mechanical ventilation (MV). In the presence of apparent HFNC non-response, a clinician may choose to increase the HFNC flow rate to hypothetically prevent further respiratory deterioration, transition to an alternative non-invasive interface, or intubation for MV. To date, no models have been assessed to predict subsequent escalations of HFNC flow rates after HFNC initiation. Objective: To evaluate the abilities of tree-based machine learning algorithms to predict HFNC flow rate escalations. Methods: We performed a retrospective, cohort study assessing children admitted for acute respiratory failure under 24 months of age placed on HFNC in the Johns Hopkins Children's Center pediatric intensive care unit from January 2019 through January 2020. We excluded encounters with gaps in recorded clinical data, encounters in which MV treatment occurred prior to HFNC, and cases electively intubated in the operating room. The primary study outcome was discriminatory capacity of generated machine learning algorithms to predict HFNC flow rate escalations as compared to each other and ROX indices using area under the receiver operating characteristic (AUROC) analyses. In an exploratory fashion, model feature importance rankings were assessed by comparing Shapley values. Results: Our gradient boosting model with a time window of 8 h and lead time of 1 h before HFNC flow rate escalation achieved an AUROC with a 95% confidence interval of 0.810 ± 0.003. In comparison, the ROX index achieved an AUROC of 0.525 ± 0.000. Conclusion: In this single-center, retrospective cohort study assessing children under 24 months of age receiving HFNC for acute respiratory failure, tree-based machine learning models outperformed the ROX index in predicting subsequent flow rate escalations. Further validation studies are needed to ensure generalizability for bedside application.

Measurement of Retinal Microvascular Blood Velocity Using Erythrocyte Mediated Velocimetry.

Changes in retinal blood flow may be involved in the pathogenesis of glaucoma and other ocular diseases. Erythrocyte mediated velocimetry (EMV) is a novel technique where indocyanine green (ICG) dye is sequestered in erythrocyte ghosts and autologously re-injected to allow direct visualization of erythrocytes for in vivo measurement of speed. The purpose of this study is to determine the mean erythrocyte speed in the retinal microvasculature, as well as the intravisit and intervisit variability of EMV. Data from 23 EMV sessions from control, glaucoma suspect, and glaucoma patients were included in this study. In arteries with an average diameter of 43.11 µm ± 6.62 µm, the mean speed was 7.17 mm/s ± 2.35 mm/s. In veins with an average diameter of 45.87 µm ± 12.04 µm, the mean speed was 6.05 mm/s ± 1.96 mm/s. Intravisit variability, as measured by the mean coefficient of variation, was 3.57% (range 0.44-9.68%). Intervisit variability was 4.85% (range 0.15-8.43%). EMV may represent reliable method for determination of retinal blood speed, potentially allowing insights into the effects of pharmacologic agents or pathogenesis of ocular diseases.