Development and evaluation of Order of Magnitude (OM): a virtual reality-based visual field analyzer for glaucoma detection.

PURPOSE: This study introduces the Order of Magnitude (OM), a cost-effective, indigenous, virtual reality-based visual field analyzer designed for detecting glaucomatous visual field loss. METHODS: The OM test employs a two-step supra-thresholding algorithm utilizing stimuli of 0.43°diameter (equivalent to Goldmann size III) at low and high thresholds. A comparative analysis was conducted against the Humphrey visual field (HVF) test, considered the gold standard in clinical practice. Participants, including those with glaucoma and normal individuals, underwent comprehensive eye examinations alongside the OM and HVF tests between April and October 2019. Diagnostic sensitivity and specificity of the OM test were assessed against clinical diagnoses made by specialists. RESULTS: We studied 157 eyes (74 glaucomatous, 83 control) of 152 participants. Results demonstrated a high level of reliability for both OM and HVF tests, with no significant difference observed (P = 0.19, Chi-square test). The sensitivity and specificity of the OM test were found to be 93% (95% CI 86-100%) and 83% (95% CI 72.4-93%), respectively, while the HVF test showed sensitivity and specificity of 98% (95% CI 93.9-100%) and 83% (95% CI 73.9-92.8%), respectively. CONCLUSION: These findings suggest that the OM test is non-inferior to the reference standard HVF test in identifying glaucomatous visual field loss.

Effect of Light Intensity on the Relative Afferent Pupillary Defect in Unilateral Neuro-ophthalmic Pathology.

SIGNIFICANCE: Objective pupillometry with standardized light intensities allows a comprehensive assessment of the relative afferent pupillary defect in patients with unilateral neuro-ophthalmic pathology. PURPOSE: This study aimed to determine the impact of varying light intensities on the grade of relative afferent pupillary defect in unilateral neuro-ophthalmic pathology vis-à-vis healthy controls. METHODS: Monocular pupillary light reflexes of 20 controls (14 to 50 years) and 31 cases (12 to 72 years) with clinically diagnosed relative afferent pupillary defect were measured thrice using 1-second-long light pulses, followed by 3 seconds of darkness, at eight light intensities (6.4 to 1200 lux) using objective pupillometry. The relative afferent pupillary defect was quantified as the ratio of the percentage change in the direct light reflexes of the left and right eyes. Its change with light intensity was described using standard exponential fits. RESULTS: The median (25th to 75th interquartile range) defect score of 54.8% cases decreased from baseline values of 1.58 (1.25 to 1.87) for right eye pathology and 0.45 (0.39 to 0.55) for left eye pathology to saturation values of 1.18 (1.05 to 1.31) and 0.98 (0.95 to 1.06), respectively, at light intensities between 56.9 and 300.5 lux. Like controls (1.01 [1.00 to 1.06]), the defect scores of the remaining 45.2% cases were constant with light intensity at 1.23 (1.18 to 1.46) and 0.87 (0.86 to 0.89) for right and left eye pathologies, respectively. CONCLUSIONS: Relative afferent pupillary defects may decrease with test light intensity in a significant proportion of patients with unilateral neuro-ophthalmic pathology. This highlights the importance of objective pupillometry with standardization light intensities for clinical assessment of afferent pupillary defects.

Publisher Correction: Cerebral ischemia induces the aggregation of proteins linked to neurodegenerative diseases.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Cerebral ischemia induces the aggregation of proteins linked to neurodegenerative diseases.

Protein aggregation critically affects cell viability in neurodegenerative diseases, but whether this also occurs in ischemic brain injury remains elusive. Prior studies report the post-ischemic aggregation of ubiquitin, small ubiquitin-related modifier (SUMO) and ribosomes, however whether other proteins are also affected is unknown. Here we employed a proteomic approach to identify the insoluble, aggregated proteome after cerebral ischemia. Mice underwent transient middle cerebral artery occlusion or sham-surgery. After 1-hour reperfusion, prior to apparent brain injury, mice were sacrificed and detergent-insoluble proteins were obtained and identified by nanoLC-MS/MS. Naturally existing insoluble proteins were determined in sham controls and aggregated proteins after cerebral ischemia/reperfusion were identified. Selected aggregated proteins found by proteomics were biochemically verified and aggregation propensities were studied during ischemia with or without reperfusion. We found that ischemia/reperfusion induces the aggregation of RNA-binding and heat-shock proteins, ubiquitin, SUMO and other proteins involved in cell signalling. RNA-binding proteins constitute the largest group of aggregating proteins in ischemia. These include TDP43, FUS, hnRNPA1, PSF/SFPQ and p54/NONO, all of which have been linked to neurodegeneration associated with amyotrophic lateral sclerosis and frontotemporal dementia. The aggregation of neurodegeneration-related disease proteins in cerebral ischemia unveils a previously unappreciated molecular overlap between neurodegenerative diseases and ischemic stroke.