Pilot Study Assessing the Safety and Acceptance of a Novel Virtual Reality System to Improve Visual Function.

PURPOSE: To assess the feasibility of the clinical use of a novel Virtual Reality (VR) training software designed to be used for active vision therapy in amblyopic patients by determining its preliminary safety and acceptance on the visual function of healthy adults. METHODS: Pilot study enrolling 10 individuals (3 men, 7 women, mean age: 31.8 ± 6.5 years) with a best-corrected visual acuity (BCVA) of ≥ .90 (decimal) in both eyes were evaluated before and after 20 minutes of exposure to the NEIVATECH VR system using the HTC Vive Pro Eye head mounted display. Visual function assessment included near (40 cm) and distance (6 m) cover test (CT), stereopsis, binocular accommodative facility (BAF), near point of convergence (NPC), near point of accommodation (NPA), accommodative-convergence over accommodation (AC/A) ratio and positive and negative fusional vergences. Safety was assessed using the VR Sickness Questionnaire (VRSQ) and acceptance using the Technology Acceptance Model ;(TAM). Changes in all these variables after VR exposure were analyzed. RESULTS: Short-term exposure to the NEIVATECH VR system only induced statistically significant changes in distance phoria (p = .016), but these changes were not clinically relevant. No significant changes were observed in VRSQ oculo-motricity and disorientation scores after exposure (p = .197 and .317, respectively). TAM scores showed a good acceptance of the system in terms of perceived enjoyment and perceived ease of use, although some concerns were raised in relation to the intention-to-use domain. CONCLUSION: Exposure to the NEIVATECH VR system does not seem to adversely affect the visual function in healthy adults and its safety and acceptance profile seems to be adequate for supporting its potential use in other populations, such as amblyopic patients.

Imaging Biomarkers and Prevalence of Complex Aortic Plaque in Cryptogenic Stroke: A Systematic Review.

BACKGROUND: Complex aortic plaque (CAP) is a potential embolic source in patients with cryptogenic stroke (CS). We review CAP imaging criteria for transesophageal echocardiogram (TEE), computed tomography angiography (CTA), and magnetic resonance imaging and calculate CAP prevalence in patients with acute CS. METHODS AND RESULTS: PubMed and EMBASE databases were searched up to December 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Two independent reviewers extracted data on study design, imaging techniques, CAP criteria, and prevalence. The Cochrane Collaboration tool and Guideline for Reporting Reliability and Agreement Studies were used to assess risk of bias and reporting completeness, respectively. From 2293 studies, 45 were reviewed for CAP imaging biomarker criteria in patients with acute CS (N=37 TEE; N=9 CTA; N=6 magnetic resonance imaging). Most studies (74%) used ≥4 mm plaque thickness as the imaging criterion for CAP although ≥1 mm (N=1, CTA), ≥5 mm (N=5, TEE), and ≥6 mm (N=2, CTA) were also reported. Additional features included mobility, ulceration, thrombus, protrusions, and assessment of plaque composition. From 23 prospective studies, CAP was detected in 960 of 2778 patients with CS (0.32 [95% CI, 0.24-0.41], I2=94%). By modality, prevalence estimates were 0.29 (95% CI, 0.20-0.40; I2=95%) for TEE; 0.23 (95% CI, 0.15-0.34; I2=87%) for CTA and 0.22 (95% CI, 0.06-0.54; I2=92%) for magnetic resonance imaging. CONCLUSIONS: TEE was commonly used to assess CAP in patients with CS. The most common CAP imaging biomarker was ≥4 mm plaque thickness. CAP was observed in one-third of patients with acute CS. However, high study heterogeneity suggests a need for reproducible imaging methods.

Influence of non-osteoporotic treatments in patients on active anti-osteoporotic therapy: evidence from the OSTEOMED registry.

PURPOSE: To evaluate the effect of different non-osteoporotic drugs on the increase or decrease in the risk of incident fragility fractures (vertebral, humerus or hip) in a cohort of patients diagnosed with osteoporosis on active anti-osteoporotic therapy. METHODS: For this retrospective longitudinal study, baseline and follow-up data on prescribed non-osteoporotic treatments and the occurrence of vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression models. The drugs evaluated with a possible beneficial effect were thiazides and statins, while the drugs evaluated with a possible harmful effect were antiandrogens, aromatase inhibitors, proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, GnRH agonists, thyroid hormones, and oral and inhaled corticosteroids. RESULTS: Logistic regression analyses indicated that no treatment significantly improved fracture risk, with the only treatments that significantly worsened fracture risk being letrozole (OR = 0.18, p-value = 0.03) and oral corticosteroids at doses ≤ 5 mg/day (OR = 0.16, p-value = 0.03) and > 5 mg/day (OR = 0.27, p-value = 0.04). CONCLUSION: The potential beneficial or detrimental effects of the different drugs evaluated on fracture risk are masked by treatment with anabolic or antiresorptive drugs that have a more potent action on bone metabolism, with two exceptions: letrozole and oral corticosteroids. These findings may have important clinical implications, as patients receiving these treatments are not fully protected by bisphosphonates, which may imply the need for more potent anti-osteoporotic drugs such as denosumab or teriparatide.

Randomised placebo-controlled clinical trial evaluating the impact of a new visual rehabilitation program on neuroadaptation in patients implanted with trifocal intraocular lenses.

PURPOSE: To evaluate the efficacy of a new visual training program for improving the visual function in patients implanted with trifocal intraocular lenses (IOLs). METHODS: Randomised placebo-controlled clinical trial enrolling 60 subjects (age, 47-75 years) undergoing cataract surgery with implantation of trifocal diffractive IOL. Home-based active visual training was prescribed immediately after surgery to all of them (20 sessions, 30 min): 31 subjects using a serious game based on Gabor patches (study group) and 29 using a placebo software (placebo group). Visual acuity, contrast sensitivity (CS), and perception of visual disturbances (QoV questionnaire) were evaluated before and after training. Likewise, in a small subgroup, resting-state functional magnetic resonance imaging (rs-fMRI) analysis was performed. RESULTS: No significant differences were found between groups in compliance time (p = 0.70). After training, only significant improvements in monocular uncorrected intermediate visual acuity were found in the study group (p ≤ 0.01), although differences between groups did not reach statistical significance (p ≥ 0.11). Likewise, significantly better binocular far CS values were found in the study group for the spatial frequencies of 6 (p = 0.01) and 12 cpd (p = 0.03). More visual symptoms of the QoV questionnaire experienced a significant change in the level of bothersomeness in the study group. Rs-fMRI revealed the presence significant changes reflecting higher functional connectivity after the training with the serious game. CONCLUSIONS: A 3-week visual training program based on the use of Gabor patches after bilateral implantation of trifocal diffractive IOLs may be beneficial for optimising the visual function, with neural changes associated suggesting an acceleration of neuroadaptation. Trial registration ClinicalTrials.gov, NCT04985097. Registered 02 August 2021, https://clinicaltrials.gov/(NCT04985097 ).

Amblyopia Treatment through Immersive Virtual Reality: A Preliminary Experience in Anisometropic Children.

The use of digital devices provides a wide range of possibilities for measuring and improving visual function, including concepts such as perceptual learning and dichoptic therapy. Different technologies can be used to apply these concepts, including, in recent years, the introduction of virtual reality (VR) systems. A preliminary experience in treating anisometropic amblyopia through an immersive VR device and using prototype software is described. A total of 4 children were treated by performing 18 office-based sessions. Results showed that distance VA in amblyopic eyes remained constant in two subjects, whereas the younger subjects improved after the training. Near VA improved in three subjects. All subjects showed an increase in the stereopsis of at least one step, with three subjects showing a final stereopsis of a 60 s arc. A total of three subjects showed an increase of approximately 0.5 CS units for the spatial frequency of 3 cpd after the training. Results from this pilot study suggest that visual training based on perceptual learning through an immersive VR environment could be a viable treatment for improving CS, VA, and stereopsis in some children with anisometropic amblyopia. Future studies should support these preliminary results.

Randomized Controlled Trial Evaluating the Benefit of a Novel Clinical Decision Support System for the Management of COVID-19 Patients in Home Quarantine: A Study Protocol.

(1) Background: We present the protocol of a randomized controlled trial designed to evaluate the benefit of a novel clinical decision support system for the management of patients with COVID-19. (2) Methods: The study will recruit up to 500 participants (250 cases and 250 controls). Both groups will receive the conventional telephone follow-up protocol by primary care and will also be provided with access to a mobile application, in which they will be able to report their symptoms three times a day. In addition, patients in the active group will receive a wearable smartwatch and a pulse oximeter at home for real-time monitoring. The measured data will be visualized by primary care and emergency health service professionals, allowing them to detect in real time the progression and complications of the disease in order to promote early therapeutic interventions based on their clinical judgement. (3) Results: Ethical approval for this study was obtained from the Drug Research Ethics Committee of the Valladolid East Health Area (CASVE-NM-21-516). The results obtained from this study will form part of the thesis of two PhD students and will be disseminated through publication in a peer-reviewed journal. (4) Conclusions: The implementation of this telemonitoring system can be extrapolated to patients with other similar diseases, such as chronic diseases, with a high prevalence and need for close monitoring.

Visual perception alterations in COVID-19: a preliminary study.

AIM: To compare the visual perception (color and chromatic-achromatic contrast vision) of a small cohort of COVID-19 patients at the time of infection and after 6mo with that of a healthy population matched for sex and age. METHODS: A total of 25 patients (9 females, 16 males, mean age: 54±10y) with COVID-19 hospitalized in the COVID-19 Unit of the University Clinical Hospital of Valladolid were recruited for this preliminary study. Visual perception, as determined by monocular measurement of contrast sensitivity function (CSF) and color vision was assessed in each patient using the Optopad test. The results obtained were then compared with those of a sample of 16 age- and sex-matched healthy controls (5 females, 11 males, mean age: 50±6y) in which the same measurement procedure was repeated. Statistically significant differences between groups were assessed using the Mann-Whitney U test. Measurements were repeated after a minimum follow-up period of 6mo and statistically significant differences between the two time points in each group were assessed using the Wilcoxon signed rank test. RESULTS: Discrimination thresholds (color and chromatic-achromatic contrast vision) and their corresponding sensitivity, calculated as the inverse of the discrimination threshold, were evaluated. Analysis of the data revealed higher contrast threshold results (i.e., worse contrast sensitivity) in the COVID-19 group than in the control group for all spatial frequencies studied in the Optopad-CSF achromatic test and most of the spatial frequencies studied in the Optopad-CSF chromatic test for the red-green and blue-yellow mechanisms. In addition, color threshold results in the COVID-19 group were also significantly higher (i.e., worse color sensitivity) for almost all color mechanisms studied in the Optopad-Color test. At 6mo, most of the differences found between the groups were maintained despite COVID-19 recovery. CONCLUSION: The present results provide preliminary evidence that visual perception may be impaired in COVID-19, even when the infection has passed. Although further research is needed to determine the precise causes of this finding, analysis of CSF and color vision could provide valuable information on the visual impact of COVID-19.

Comorbidity and osteoporotic fracture: approach through predictive modeling techniques using the OSTEOMED registry.

PURPOSE: To examine the response to anti-osteoporotic treatment, considered as incident fragility fractures after a minimum follow-up of 1 year, according to sex, age, and number of comorbidities of the patients. METHODS: For this retrospective observational study, data from baseline and follow-up visits on the number of comorbidities, prescribed anti-osteoporotic treatment and vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression and an artificial network model. RESULTS: Logistic regression showed that the probability of reducing fractures for each anti-osteoporotic treatment considered was independent of sex, age, and the number of comorbidities, increasing significantly only in males taking vitamin D (OR = 7.918), patients without comorbidities taking vitamin D (OR = 4.197) and patients with ≥ 3 comorbidities taking calcium (OR = 9.412). Logistic regression correctly classified 96% of patients (Hosmer-Lemeshow = 0.492) compared with the artificial neural network model, which correctly classified 95% of patients (AUC = 0.6). CONCLUSION: In general, sex, age and the number of comorbidities did not influence the likelihood that a given anti-osteoporotic treatment improved the risk of incident fragility fractures after 1 year, but this appeared to increase when patients had been treated with risedronate, strontium or teriparatide. The two models used classified patients similarly, but predicted differently in terms of the probability of improvement, with logistic regression being the better fit.

Preliminary Evaluation of the Clinical Benefit of a Novel Visual Rehabilitation Program in Patients Implanted with Trifocal Diffractive Intraocular Lenses: A Blinded Randomized Placebo-Controlled Clinical Trial.

The authors of this study evaluated the potential benefit on visual performance of a novel 3 week visual rehabilitation program based on the use of Gabor patches in patients undergoing bilateral cataract surgery with the implantation of two models of trifocal diffractive intraocular lens (IOL). A total of 30 patients were randomly assigned to two groups: a study group (15 patients) that used a videogame based on Gabor patches and a placebo group (15 patients) that used a videogame without specific stimuli for improving visual performance. No statistically significant differences between groups were found in distance, intermediate, and near post-training visual acuity (p ≥ 0.15). Significantly better distance contrast sensitivity (CS) was found for the spatial frequencies of 6 (p = 0.02) and 12 cpd (p = 0.01) in the study group. Likewise, significantly better values of near CS were found in the study group compared to the placebo group for the spatial frequency of 1.5 cpd (p = 0.02). In conclusion, a 3 week visual rehabilitation program based on the use of Gabor patches in the immediate postoperative period after the bilateral implantation of trifocal diffractive IOLs seems to be beneficial for improving both distance and near visual performance achieved with the implant.

Stimuli Characteristics and Psychophysical Requirements for Visual Training in Amblyopia: A Narrative Review.

Active vision therapy using perceptual learning and/or dichoptic or binocular environments has shown its potential effectiveness in amblyopia, but some doubts remain about the type of stimuli and the mode and sequence of presentation that should be used. A search was performed in PubMed, obtaining 143 articles with information related to the stimuli used in amblyopia rehabilitation, as well as to the neural mechanisms implied in such therapeutic process. Visual deficits in amblyopia and their neural mechanisms associated are revised, including visual acuity loss, contrast sensitivity reduction and stereopsis impairment. Likewise, the most appropriate stimuli according to the literature that should be used for an efficient rehabilitation of the amblyopic eye are described in detail, including optotypes, Gabor's patches, random-dot stimuli and Vernier's stimuli. Finally, the properties of these stimuli that can be modified during the visual training are discussed, as well as the psychophysical method of their presentation and the type of environment used (perceptual learning, dichoptic stimulation or virtual reality). Vision therapy using all these revised concepts can be an effective option for treating amblyopia or accelerating the treatment period when combining with patching. It is essential to adapt the stimuli to the patient's individual features in both monocular and binocular training.

Quantified ischemic core's radiological hypodensity and risk of parenchymal hematoma in > 4.5 h-window stroke thrombectomy.

We aimed to study the relationship between the ischemic core's (IC) radiological hypodensity and the risk of parenchymal haematoma after endovascular therapy (EVT) in acute ischemic stroke (AIS) presenting > 4.5 h from onset. We studied AIS patients with a proximal anterior circulation occlusion > 4.5 h from symptoms onset treated with primary EVT. The IC regions of interest (ROI) were manually delineated on pretreatment CT within the affected hemisphere and their specular ROIs on the unaffected side. IC hypodensity ratio was calculated by dividing mean Hounsfield Unit (HU) value from all ROIs in affected/unaffected hemisphere. Primary endpoint: parenchymal hematoma (PH) type hemorrhagic transformation. Secondary: poor long-term clinical outcome. From May 2015 to November 2018, 648 consecutive AIS patients received reperfusion therapies and 107 met all inclusion criteria. PH after EVT was diagnosed in 33 (31%) patients. In bivariate analyses, IC hypodensity ratio (p < 0.001) and minimum HU value (p = 0.008) were associated with PH. A lower IC hypodensity ratio [OR < 0.001 (< 0.001-0.116) p 0.016] predicted PH but not poor clinical outcome in multivariable logistic regression models. A lower IC radiological density predicted a higher risk of PH in > 4.5 h-window AIS patients treated with primary EVT, although it was not independently associated with a worse clinical outcome.

Brain Atrophy and the Risk of Futile Endovascular Reperfusion in Acute Ischemic Stroke.

Background and Purpose- We aimed to evaluate the impact of brain atrophy on long-term clinical outcome in patients with acute ischemic stroke treated with endovascular therapy, and more specifically, to test whether there are interactions between the degree of atrophy and infarct volume, and between atrophy and age, in determining the risk of futile reperfusion. Methods- We studied consecutive patients with acute ischemic stroke with proximal anterior circulation intracranial arterial occlusions treated with endovascular therapy achieving successful arterial recanalization. Brain atrophy was evaluated on baseline computed tomography with the global cortical atrophy scale, and Evans index was calculated to assess subcortical atrophy. Infarct volume was assessed on control computed tomography at 24 hours using the formula for irregular volumes (A×B×C/2). Main outcome variable was futile recanalization, defined by functional dependence (modified Rankin Scale score >2) at 3 months. The predefined interactions of atrophy with age and infarct volume were studied in regression models. Results- From 361 consecutive patients with anterior circulation acute ischemic stroke treated with endovascular therapy, 295 met all inclusion criteria. Futile reperfusion was observed in 144 out of 295 (48.8%) patients. Cortical atrophy affecting parieto-occipital and temporal regions was associated with futile recanalization. Total global cortical atrophy score and Evans index were independently associated with futile recanalization in an adjusted logistic regression. Multivariable adjusted regression models disclosed significant interactions between global cortical atrophy score and infarct volume (odds ratio, 1.003 [95%CI, 1.002-1.004], P<0.001) and between global cortical atrophy score and age (odds ratio, 1.001 [95% CI, 1.001-1.002], P<0.001) in determining the risk of futile reperfusion. Conclusions- A higher degree of cortical and subcortical brain atrophy is associated with futile endovascular reperfusion in anterior circulation acute ischemic stroke. The impact of brain atrophy on insufficient clinical recovery after endovascular reperfusion appears to be independently amplified by age and by infarct volume.

Potential of video games for the promotion of neuroadaptation to multifocal intraocular lenses: a narrative review.

Multifocal intraocular lenses (IOLs) are currently usually implanted for the treatment of cataracts because they have been proved to be superior to monofocal IOLs with respect to spectacle independence. In turn, they are associated with a higher prevalence of dysphotopsia symptoms that is one of the most common causes of patient dissatisfaction. Neuroadaptation seems to play a major role in the optimal adaptation to multifocal IOLs. In this context, the development of strategies that facilitate the neuroadaptation process to multifocality might be an effective strategy to reduce patients' dissatisfaction. Video games have been proved to be effective for the improvement of visual acuity and for the promotion of neuroplasticity in elderly subjects and other populations with cortical-related visual impairment. This narrative review highlights the physiological potential of video games as a perceptual strategy to improve visual acuity and promote neuroplasticity in patients using multifocal IOLs, although research is still needed to confirm these benefits in this specific population, with only one comparative study to this date providing evidence of them.

Dependability of pachymetry measurements after myopic advanced surface ablation using scanning-slit topography and specular microscopy.

PURPOSE: To assess the repeatability, intersession and interobserver reproducibility, and agreement of central corneal thickness (CCT) measurements obtained by scanning-slit topography (SST) and noncontact specular microscopy (NCSM) after advanced surface ablation (ASA). METHODS: To analyze repeatability, one examiner measured 63 post-myopic ASA eyes five times successively using both techniques randomly. To calculate interobserver reproducibility a second examiner obtained another CCT measurement in a random fashion. To study intersession reproducibility, the first operator obtained CCT measurements from another 24 eyes during two sessions 1 week apart. RESULTS: With regard to intrasession repeatability, SST and NCSM within-subject standard deviation (S(w)) and intraclass correlation coefficient (ICC) were 7.35 and 3.81 µm, and 0.97 and 0.99, respectively. For interobserver reproducibility, SST measurement variability showed correlation with CCT magnitude (r(s) = -0.38; P = 0.002), whereas NCSM did not. NCSM S(w) and ICC were 3.83 µm and 0.99, respectively. For intersession reproducibility, no difference in CCT measurements was found for any technique; S(w) and ICC estimates for SST and NCSM were 12.2 and 8.37 µm, and 0.94 and 0.95, respectively. We found a tendency for the difference (mean SST-NCSM = 13.39 µm) to increase in thicker corneas (r(s) = 0.45, P = 0.001). CONCLUSIONS: Both noncontact pachymetry techniques provided highly repeatable and quite reproducible CCT measurements in post-ASA patients having no clinically significant corneal haze, except for SST interobserver reproducibility, which decreased in thinner corneas. However, the techniques were not interchangeable. The estimates provided should help clinicians differentiate real CCT change from noncontact pachymetry measurement variability after ASA.

Precision of a commercial hartmann-shack aberrometer: limits of total wavefront laser vision correction.

PURPOSE: To assess the intrasession and intersession precision of higher-order aberrations (HOAs) measured using a commercial Hartmann-Shack wavefront sensor (Zywave; Bausch & Lomb) in refractive surgery candidates. DESIGN: Prospective, experimental study of a device. METHODS: To analyze intrasession repeatability, 1 experienced examiner measured 30 healthy eyes 5 times successively. To study intersession reproducibility, the same clinician obtained measurements from another 30 eyes in 2 consecutive sessions at the same time of day 1 week apart. RESULTS: For intrasession repeatability, excellent intraclass correlation coefficients (ICCs) were obtained for total ocular aberrations, total HOAs, and second-order terms (ICC, > 0.94). The ICCs for third-order terms also were high (ICCs, > 0.87); however, fourth-order ICCs varied from 0.71 to 0.90 (Z(4)(0) = 0.90); and fifth-order ICCs were less than 0.85. For intersession reproducibility, only total ocular aberrations, total ocular HOAs, second-order terms, Z(4)(0), Z(3)(1), and Z(3-)(3) had ICCs of 0.90 or more. Bland-Altman analysis showed that the limits of agreement (were clinically too wide for most higher-order Zernike terms, especially for the third-order terms (> 0.21 µm). CONCLUSIONS: Total ocular aberrations, total HOAs, and second-order terms can be measured reliably by Zywave aberrometry without anatomic recognition. Third-order terms and Z(4)(0) are repeatable, but not as reproducible between visits. Fourth-order terms, except for Z(4)(0), and fifth-order terms are not sufficiently reliable for clinical decision making or treatment. Because the variability of Zywave can be a major limitation of a truly successful wavefront-guided excimer laser procedure, surgeons should consider treating HOA magnitudes that are more than the intrasession repeatability values (2.77 × S(w)) as those presented in this study.

Comparison of central corneal thickness using optical low-coherence reflectometry and spectral-domain optical coherence tomography.

PURPOSE: To assess intraobserver and interobserver reliability of central corneal thickness (CCT) measurements using optical low-coherence reflectometry (OLCR) technology and its agreement with spectral-domain optical coherence tomography (SD-OCT). SETTING: Rio Hortega University Hospital, Valladolid, Spain. DESIGN: Evaluation of diagnostic technology. METHODS: To analyze OLCR intraobserver repeatability, 1 examiner obtained 4 successive measurements. To study interobserver reproducibility, a different examiner obtained another CCT measurement. To determine agreement with SD-OCT, the first examiner also obtained CCTs. Intraobserver and interobserver within-subject standard deviation (S(w)), coefficient of variation (CV(w)), and limits of agreement (LoA) were obtained for OLCR reliability analysis; for study agreement, data were analyzed using the paired-sample t test and the LoA were calculated. RESULTS: For OLCR intraobserver repeatability, the S(w) and precision (1.96×S(w)) were 2.33 and 4.56 µm, respectively. The intraobserver CV(w) was 0.42%. For interobserver reproducibility, the S(w) and precision were 11.59 and 22.71 µm, respectively; the CV(w) was 2.10%. The mean difference between observers was -1.35 µm (95% confidence interval [CI], -3.97 to 1.26). The width of the LoA was 45.27 µm. The mean CCT difference between OLCR and SD-OCT was 5.68±11.46 µm (95% CI, 8.29-3.08 µm; P=.0001), and the width of the LoA was 44.93 µm. CONCLUSIONS: Optical low-coherence reflectometry technology provided reliable intraobserver and interobserver CCT measurements. Although OLCR underestimated the pachymetry by less than 6 µm compared with SD-OCT, its interchangeability fell within the range of interobserver reproducibility. Both noncontact pachymetry measurements seem to be clinically useful and may be used interchangeably with minimum calibration adjustment. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.