Outcomes of Descemet Stripping Only Without Postoperative Use of Topical Rho-associated Protein Kinase Inhibitors.

PURPOSE: Descemet Stripping Only (DSO) is a promising surgical option for select patients with Fuchs endothelial dystrophy (FED). There is growing support for the use of topical Rho-associated protein kinase inhibitors (ROCKi) to optimize DSO outcomes. However, in many settings, ROCKi are either unavailable or not approved to treat corneal diseases. This study sought to characterize patient outcomes after DSO in the absence of ROCKi and potentially broaden the settings where DSO can be offered to patients. METHODS: Single-center retrospective case series of 15 eyes/11 patients (66 years; 52-74) that underwent DSO, alone or combined with cataract surgery, by one surgeon between August 2020 and January 2023. Patients included in analyses had FED with central guttae, no clinical evidence of corneal edema, and a clinically healthy peripheral corneal endothelium. RESULTS: Mean follow-up time was 14 months (2-34). Fourteen of 15 eyes achieved corneal clearance (93.3%). Mean time to clearance was 8.5 weeks (3-23). Eleven eyes (73%) achieved corrected distance visual acuity of ≤0.2 with a significant postoperative improvement at 4 to 8 months (P < 0.05) and sustained improvements at >12 months. No significant astigmatism was introduced by the procedure. Two eyes developed cystoid macular edema postoperatively. A trend toward earlier clearance was observed in the <65 years old group. CONCLUSIONS: Despite a longer time to corneal clearance in this cohort compared with the few studies using ROCKi, the overall success rate and visual outcomes for the patients in our cohort supports the use of DSO in settings where ROCKi are not readily available.

Plastic vs. glass: the effect of the synthetic material in contact with DMEK tissue during staining on endothelial cell loss.

PURPOSE: Endothelial cell loss (ECL) during Descemet membrane endothelial keratoplasty (DMEK) graft preparation has been shown to affect graft survival and the need for re-grafting. The purpose of this study was to quantitatively assess the impact of the plastic and glass mediums in contact with DMEK donor tissue during intra-operative graft staining on ECL. METHODS: Retrospective study that included patients who underwent DMEK surgery between January 2019 and June 2021 at Hôpital Maisonneuve-Rosemont and the Jewish General Hospital in Montreal, Canada. DMEK grafts were stained with 0.06% Trypan blue ophthalmic solution (VisionBlue®, Dutch Ophthalmic, USA, Exeter, NH) for 120 s in either a plastic or glass medium prior to delivery into the recipient's eye. The ECL was compared between the two groups 12-30 months post-operatively. RESULTS: ECL at 12-30 months was significantly less in the eyes that had received grafts stained in a plastic medium compared to those stained in a glass medium. Graft survival and re-bubbling was higher in the glass group however this difference was not statistically significant. CONCLUSION: Staining of the DMEK graft in a plastic medium caused less ECL compared to the glass medium.

A quantitative approach to the spread of variance in translational research using Monte Carlo simulation.

The translation of promising preclinical research into successful trials often fails. One contributing factor is the "Princess and the Pea" problem, which refers to how an initially significant effect size dissipates as research transitions to more complex systems. This work aimed to quantify the effects of spreading variability on sample size requirements. Sample size estimates were performed by Monte Carlo simulation. To simulate the process of progressing from preclinical to clinical studies, nested sigmoidal dose-response transformations with modifiable input parameter variability were used. The results demonstrated that adding variabilty to the dose-response parameters substantially increases sample size requirements compared to standared calculations. Increasing the number of consecutive studies further increases the sample size. These results quantitatively demonstrate how the spread of variability in translational research, which is not typically accounted for, can result in drastic increases in the sample size required to maintain a desired study power.

Nimodipine Reduces Dysfunction and Demyelination in Models of Multiple Sclerosis.

OBJECTIVE: Treatment of relapses in multiple sclerosis (MS) has not advanced beyond steroid use, which reduces acute loss of function, but has little effect on residual disability. Acute loss of function in an MS model (experimental autoimmune encephalomyelitis [EAE]) is partly due to central nervous system (CNS) hypoxia, and function can promptly improve upon breathing oxygen. Here, we investigate the cause of the hypoxia and whether it is due to a deficit in oxygen supply arising from impaired vascular perfusion. We also explore whether the CNS-selective vasodilating agent, nimodipine, may provide a therapy to restore function, and protect from demyelination in 2 MS models. METHODS: A variety of methods have been used to measure basic cardiovascular physiology, spinal oxygenation, mitochondrial function, and tissue perfusion in EAE. RESULTS: We report that the tissue hypoxia in EAE is associated with a profound hypoperfusion of the inflamed spinal cord. Treatment with nimodipine restores spinal oxygenation and can rapidly improve function. Nimodipine therapy also reduces demyelination in both EAE and a model of the early MS lesion. INTERPRETATION: Loss of function in EAE, and demyelination in EAE, and the model of the early MS lesion, seem to be due, at least in part, to tissue hypoxia due to local spinal hypoperfusion. Therapy to improve blood flow not only protects neurological function but also reduces demyelination. We conclude that nimodipine could be repurposed to offer substantial clinical benefit in MS. ANN NEUROL 2020 ANN NEUROL 2020;88:123-136.

Hyperspectral Imaging of the Hemodynamic and Metabolic States of the Exposed Cortex: Investigating a Commercial Snapshot Solution.

Hyperspectral imaging (HSI) systems have the potential to retrieve in vivo hemodynamic and metabolic signals from the exposed cerebral cortex. The use of multiple narrow wavelength bands in the near infrared (NIR) range theoretically allows not only to image brain tissue oxygenation and hemodynamics via mapping of hemoglobin concentration changes, but also to directly quantify cerebral metabolism via measurement of the redox states of mitochondrial cytochrome-c-oxidase (CCO). The aim of this study is to assess the possibility of performing hyperspectral imaging of in vivo cerebral oxyhemoglobin (HbO2), deoxyhemoglobin (HHb) and oxidized CCO (oxCCO) using commercially available HSI devices. For this reason, a hyperspectral snapshot solution based on Cubert GmbH technology (S185 FireflEYE camera) has been tested on the exposed cortex of mice during normoxic, hypoxic and hyperoxic conditions. The system allows simultaneous acquisition of 138 wavelength bands between 450 and 998 nm, with spectral sampling and resolution of ~4 to 8 nm. From the hyperspectral data, relative changes in concentration of hemoglobin and oxCCO are estimated and hemodynamic and metabolic maps of the imaged cortex are calculated for two different NIR spectral ranges. Spectroscopic analysis at particular regions of interest is also performed, showing typical oxygen-dependent hemodynamic responses. The results highlight some of the potentials of the technology, but also the limitations of the tested commercial solution for such specific application, in particular regarding spatial resolution.

Assessing alexithymia and related emotional ability constructs using multiple methods: interrelationships among measures.

This study examined relationships among various measures of emotional ability reflecting different methods of assessment: self-report, clinical interview, collateral report, and emotion-relevant performance. On 140 young adults, the authors assessed self-reported alexithymia, emotional approach coping, and trait metamood skills; observer-reported alexithymia; interviewer-rated alexithymia; emotional awareness in response to vignettes; and emotional intelligence test performance. There were moderate magnitude correlations among the self-report measures, but correlations among other measures were relatively low. Confirmatory factor analyses supported a 3-factor model in which explicit self, implicit self, and explicit other measures were differentiated. These emotional ability measures do not form a unitary construct but differ as a function of the person providing the information and whether the measure is explicit or implicit.