Machine learning approach for ambient-light-corrected parameters and the Pupil Reactivity (PuRe) score in smartphone-based pupillometry.

Introduction: The pupillary light reflex (PLR) is the constriction of the pupil in response to light. The PLR in response to a pulse of light follows a complex waveform that can be characterized by several parameters. It is a sensitive marker of acute neurological deterioration, but is also sensitive to the background illumination in the environment in which it is measured. To detect a pathological change in the PLR, it is therefore necessary to separate the contributions of neuro-ophthalmic factors from ambient illumination. Illumination varies over several orders of magnitude and is difficult to control due to diurnal, seasonal, and location variations. Methods and results: We assessed the sensitivity of seven PLR parameters to differences in ambient light, using a smartphone-based pupillometer (AI Pupillometer, Solvemed Inc.). Nine subjects underwent 345 measurements in ambient conditions ranging from complete darkness (<5 lx) to bright lighting (≲10,000 lx). Lighting most strongly affected the initial pupil size, constriction amplitude, and velocity. Nonlinear models were fitted to find the correction function that maximally stabilized PLR parameters across different ambient light levels. Next, we demonstrated that the lighting-corrected parameters still discriminated reactive from unreactive pupils. Ten patients underwent PLR testing in an ophthalmology outpatient clinic setting following the administration of tropicamide eye drops, which rendered the pupils unreactive. The parameters corrected for lighting were combined as predictors in a machine learning model to produce a scalar value, the Pupil Reactivity (PuRe) score, which quantifies Pupil Reactivity on a scale 0-5 (0, non-reactive pupil; 0-3, abnormal/"sluggish" response; 3-5, normal/brisk response). The score discriminated unreactive pupils with 100% accuracy and was stable under changes in ambient illumination across four orders of magnitude. Discussion: This is the first time that a correction method has been proposed to effectively mitigate the confounding influence of ambient light on PLR measurements, which could improve the reliability of pupillometric parameters both in pre-hospital and inpatient care settings. In particular, the PuRe score offers a robust measure of Pupil Reactivity directly applicable to clinical practice. Importantly, the formulae behind the score are openly available for the benefit of the clinical research community.

Vascular density and macular sensitivity in eyes after scleral buckling surgery for macula-on rhegmatogenous retinal detachment.

PURPOSE: To investigate the structure and function of the retina after scleral buckling (SB) surgery due to macula-on rhegmatogenous retinal detachment (RRD). METHODS: Twenty eyes with repaired macula-on RRD and 20 fellow eyes were included. All patients within 6-12 months of the procedure, were examined to evaluate retinal structure using spectral domain optical coherence tomography (SD-OCT) and vessel density (VD) by OCT angiography (OCTA). Best corrected visual acuity (BCVA) and microperimetry (MP) tests were used to assess retinal function. RESULTS: Analysis of the microvascular network using OCTA between the operated and healthy fellow eyes showed a significant reduction on VD in superficial vascular plexus (SVP), deep vascular plexus (DVP) and radial peripapillary capillaries (RPC) (p< 0.001, p = 0.019 and p = 0.008, respectively). Comparison of retinal structure in SD-OCT showed no significant differences on thickness in ganglion cell complex (GCC) and peripaillary retinal nerve fiber layer (pRNFL) (p> 0.05) between examined eyes. Retinal function analysis by MP examination showed a decrease of retinal sensitivity (p = 0.0013) whereas postoperative BCVA showed no differences (p = 0.62) in the operated eyes. Significant Pearson's correlations were observed between retinal sensitivity and VD in SVP, RPC (p< 0.05). CONCLUSION: In the eyes after SB surgery due to macula-on RRD, changes in retinal sensitivity were accompanied by impairment of the microvascular network assessed by the OCTA.

Alterations in Fixation Indices in Primary Open-Angle Glaucoma by Microperimetry.

The aim of this study was to determine whether primary open-angle glaucoma (POAG) is associated with changes in fixation stability parameters assessed by microperimetry (MP) and whether the severity of glaucoma is related to a deterioration in these indicators. This study analyzed fixation stability using MP macular analyzer integrity assessment (MAIA) in patients with mild and moderate/severe POAG and healthy controls. The resulting fixation indices were correlated with parameters used to assess retinal function with MP and standard automated perimetry (SAP) and retinal structure with optical coherence tomography (OCT) and OCT angiography (OCTA). We enrolled 54 eyes in the POAG groups (32 eyes with mild POAG and 22 eyes with moderate/severe POAG) and 24 eyes in the healthy group. It was shown that fixation stability in POAG eyes deteriorated with increasing disease severity, and significant differences in bivariate contour ellipse area (BCEA) including 95% of fixation points were observed among groups (p = 0.042). Quantitative analysis of structural and functional retinal parameters also showed significant deterioration with the progression of glaucoma (p < 0.001). Correlations among fixation parameters and abnormalities in the retinal structure and function were confirmed. We concluded that POAG is associated with disturbances in the fixation pattern, which worsen as the disease progresses and can be effectively assessed by performing a MP test.

Comparison of Retinal Microvasculature in Patients With Alzheimer's Disease and Primary Open-Angle Glaucoma by Optical Coherence Tomography Angiography.

Purpose: Comparison of retinal microvasculature within the macula and the optic nerve head in the eyes of patients with Alzheimer's disease (AD), primary open-angle glaucoma (POAG), and in a healthy control (HC) group, using optical coherence tomography angiography (OCTA). Methods: In this cross-sectional study, 27 patients with AD, 27 with POAG, and 27 healthy controls were enrolled. The Mini-Mental State Examination test was used to assess cognitive function. Ophthalmic examination included OCTA, which was used for the imaging of vascular flow within the layer of radial peripapillary capillaries (RPCs), and also in the superficial vascular plexus (SVP) and deep vascular plexus (DVP) of the retina. Results: In the AD group, the density of vessels in DVP was significantly reduced and the foveal avascular zone was increased when compared to POAG and HC groups (P < 0.001). Patients with POAG had a significantly reduced vessel density in RPCs and SVP as compared to AD and HC groups (P < 0.001). The average thickness of peripapillary retinal nerve fiber layer was correlated with the vessel density in SVP in patients with POAG (Pearson's r = 0.66; P = 0.0002) and was significantly lower in POAG and AD groups than in the HC group (P < 0.001). Conclusions: AD and POAG are neurodegenerative diseases associated with apoptosis of nerve cells and impairment of microvasculature. Despite the fact that in both diseases there are abnormalities of the entire retinal vascular system, significant microcirculatory impairment in POAG patients affects superficial vessels, whereas in AD patients it affects vessels located in the deeper retinal layers.

Peripapillary Retinal Nerve Fiber Layer Thickness in Patients with Alzheimer's Disease: A Comparison of Eyes of Patients with Alzheimer's Disease, Primary Open-Angle Glaucoma, and Preperimetric Glaucoma and Healthy Controls.

BACKGROUND The aim of this study was to assess and compare peripapillary retinal nerve fiber layer (RNFL) thickness in patients with Alzheimer's disease (AD), primary open-angle glaucoma (POAG), preperimetric glaucoma (PPG), and healthy controls with the use of Spectral Domain Optical Coherence Tomography (SD-OCT). MATERIAL AND METHODS Thirty patients with AD, 30 patients with POAG, 30 patients with PPG, and 30 healthy controls were enrolled in this cross-sectional study. Only 1 randomly selected eye of each patient was analyzed. Every subject underwent a thorough ophthalmological examination and OCT of the optic disc. The peripapillary RNFL thickness in each of the 6 sectors and globally was analyzed. RESULTS The RNFL was thinnest in patients with POAG. The mean RNFL thickness value was 60.97±12.97 µm and it was significantly lower than in healthy controls (106.30±8.95 µm), patients with PPG (93.20±12.04 µm), and AD patients (95.73±13.52 µm). Mean RNFL thickness in patients with AD was significantly lower when compared to healthy controls, and was higher compared to eyes with POAG, while there were no significant differences compared to patients with PPG. CONCLUSIONS Neuronal damage in the central nervous system (CNS) also affects to retinal axons. A major problem is to distinguish the cause for a moderate decrease in the RNFL thickness. This is particularly true for patients with glaucoma who have not been diagnosed with changes in the visual field. It is not possible to distinguish the cause of a mild decrease in the RNFL thickness based on the SD-OCT. This may result in misdiagnosis of glaucoma, unnecessary use of anti-glaucoma eye drops, and a delayed diagnosis of AD.

Oxygenation of alkylzinc complexes with pyrrolylketiminate ligand: access to alkylperoxide versus oxo-encapsulated complexes.

By variation of the zinc bonded alkyl group significantly different post-oxygenation products, the novel zinc alkylperoxide and the tetranuclear zinc oxo-encapsulated cluster, were derived from the controlled oxygenation of the corresponding alkylzinc complexes with a pyrrolylketiminate ligand.