Seven human donor eye globes underwent corneal cross-linking using theranostic UV-A device with accessory corneal iontophoresis system for patterned delivery of a 0.22% riboflavin solution. Theranostic-guided UV-A light illumination assessed riboflavin distribution and treated corneas at 10 mW/cm2 for 9 min with a 5.0-mm beam size. Corneal topography maps were taken at baseline and 2-h post-treatment. Analysis utilized corneal topography elevation data, with results showing controlled riboflavin delivery led to a consistent gradient, with 40% higher levels centrally (248 ± 79 μg/cm3) than peripherally (180 ± 72 μg/cm3 at ±2.5 mm from the center). Theranostic-guided UV-A light irradiation resulted in significant changes in corneal topography, with a decrease in best-fit sphere value (-0.7 ± 0.2 D; p < 0.001) and consistent downward shift in corneal elevation map (-11.7 ± 3.7 μm). The coefficient of variation was 2.5%, indicating high procedure performance in achieving significant and reliable corneal flattening.

To assess the feasibility of theranostics to determine the riboflavin concentration in the cornea using clinically available ophthalmic formulations during epithelium-off (epi-off) and transepithelial (epi-on) corneal cross-linking procedures. Thirty-two eye bank human donor corneas were equally randomized in eight groups; groups 1 to 3 and groups 4 to 8 underwent epi-off and epi-on delivery of riboflavin respectively. Riboflavin ophthalmic solutions were applied onto the cornea according to the manufacturers’ instructions. The amount of riboflavin into the cornea was estimated, at preset time intervals during imbibition time, using theranostic UV-A device (C4V CHROMO4VIS, Regensight srl, Italy) and expressed as riboflavin score (d.u.). Measurements of corneal riboflavin concentration (expressed as µg/cm3) were also performed by spectroscopy absorbance technique (AvaLight-DH-S-BAL, Avantes) for external validation of theranostic measurements. At the end of imbibition time in epi-off delivery protocols, the average riboflavin score ranged from 0.77 ± 0.38 (the average corneal riboflavin concentration was 213 ± 190 µg/cm3) to 1.79 ± 0.07 (554 ± 103 µg/cm3). In epi-on delivery protocols, the average riboflavin score ranged from 0.17 ± 0.01 to 0.67 ± 0.19 (corneal riboflavin concentration ranged from 6 ± 5 µg/cm3 to 122 ± 39 µg/cm3) at the end of imbibition time. A statistically significant linear correlation (P ≤ 0.05) was found between the theranostic and spectrophotometry measurements in all groups. Real-time theranostic imaging provided an accurate strategy for assessing permeation of riboflavin into the human cornea during the imbibition phase of corneal cross-linking, regardless of delivery protocol. A large variability in corneal riboflavin concentration exists between clinically available ophthalmic formulations both in epi-off and epi-on delivery protocols.

Early identification of Neurodevelopmental Disorders (NDD) allows for faster intervention, which in turn improves clinical outcomes and reduces the individual and societal costs associated with the diagnosis. The aims of the study were to 1) investigate the use of the DeepLabCut (DLC) toolbox to automatically analyze the motor patterns of infants at Low Risk (LR) and High Risk (HR) for Autism Spectrum Disorder (ASD); and 2) define the critical time window in which atypical motor patterns discriminate between typically developing infants and those diagnosed with ASD or NDD. The DLC toolbox was used to train a model capable of tracking the movements of both LR and HR infants longitudinally at the ages of 10 days, 6 weeks, 12 weeks, 18 weeks, and 24 weeks. 226 videos of 87 infants (45 females), collected within the Italian Network for Early Detection of Autism Spectrum Disorder (NIDA), were analyzed. Using the Percentage of Correct Key-points (PCKh) accuracy metric, the DLC’s tracking performance was verified by comparing the obtained 2D hands and feet coordinates with those extracted by the Movidea software. Furthermore, motor features were computed and fed to three classifiers: Fine Tree, RUSBoosted Trees, and Narrow Neural Network to investigate their usefulness in terms of early NDD prediction. Satisfactory PCKh results were obtained for both hands and feet (left foot: 96.6%, right foot: 96.2 %, left hand: 80.9%, right hand: 82.8%). The best classification results were obtained with the RUSBoosted classifier at the ages of 10 days and 6 weeks. The 5-fold cross-validation accuracy was 81.4%, with a true negative rate of 80.0% and true positive rate 87.5%. Our data confirm the usefulness of DLC as a low-cost approach to track infant movements during the writhing period. Early motor behavior at the ages of 10 days and 6 weeks carries valuable information that has the potential to be suitable in predicting the diagnosis of NDD.

PURPOSE:To validate the ability of theranostic imaging biomarkers in assessing corneal cross-linking (CXL) efficacy in flattening the maximum keratometry (Kmax) index. DESIGN:Prospective, randomized, multicenter, masked clinical trial (ClinicalTrails.gov identifier, NCT05457647). PARTICIPANTS:Fifty patients with progressive keratoconus. INTERVENTION:Participants were stratified to undergo epithelium-off (25 eyes) and epithelium-on (25 eyes) CXL protocols using an ultraviolet A (UV-A) medical device with theranostic software. The device controlled UV-A light both for performing CXL and assessing the corneal riboflavin concentration (riboflavin score) and treatment effect (theranostic score). A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epithelium-off and epithelium-on protocols, respectively. All eyes underwent 9 minutes of UV-A irradiance at 10 mW/cm2. MAIN OUTCOME MEASURES:The primary outcome measure was validation of the combined use of theranostic imaging biomarkers through measurement of their accuracy (proportion of correctly classified eyes) and precision (positive predictive value) to classify eyes correctly and predict a Kmax flattening at 1 year after CXL. Other outcome measures included change in Kmax, endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction and central corneal thickness 1 year after CXL. RESULTS:Accuracy and precision of the theranostic imaging biomarkers in predicting eyes that had >0.1 diopter (D) of Kmax flattening at 1 year were 91% and 95%, respectively. The Kmax value significantly flattened by a median of -1.3 D (IQR, -2.11 to -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 logarithm of the minimum angle of resolution (logMAR; IQR, -0.3 to 0.0 logMAR [P < 0.001] and -0.2 to 0.0 logMAR [P < 0.001], respectively). No significant changes in endothelial cell density (P = 0.33) or central corneal thickness (P = 0.07) were noted 1 year after surgery. CONCLUSIONS:The study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epithelium-off and epithelium-on CXL protocols. Concentration of riboflavin and its UV-A light mediated photoactivation in the cornea are the primary factors determining CXL efficacy. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

This study investigated the effect of a theranostic-guided UV-A light corneal photo-reshaping technique on corneal elevation and wavefront aberration (WA) in human donor eyes. A specialized platform, combining UV-A light with corneal iontophoresis for controlled, patterned, riboflavin delivery, was used for both distribution assessment and concentration-driven photopolymerization of corneal proteins. In all cases, a consistent riboflavin concentration gradient, with lower levels in the central prepupillary zone, was recorded. Corneal topography and WA measurements showed significant corneal steepening and smooth wavefront shaping, respectively, with a delay in the central 2.0 mm of the WA and advancement in the surrounding zone, as well as a 50% reduction in corneal spherical aberration over a 5.0 mm pupil size. Notably, the corneal optical quality, measured via modulation transfer function (MTF), remained stable. This incision-free approach demonstrated the potential to extend focal range without compromising distance vision, presenting a new solution for presbyopia correction.

PURPOSE:The aim of this study was to assess accuracy of the mean corneal stiffness ( kc , N/m) parameter to discriminate between patients with keratoconus and age-matched healthy subjects. METHODS:Dynamic Scheimpflug imaging tonometry was performed with Corvis ST (Oculus Optikgeräte GmbH, Germany) in patients with keratoconus (n = 24; study group) and age-matched healthy subjects (n = 32; control). An image processing algorithm was developed to analyze the video sequence of the Corvis ST air-puff event and to determine the geometric and temporal parameters that correlated with the corneal tissue biomechanical properties. A modified 3-element viscoelastic model was used to derive the kc parameter, which represented the corneal tissue resistance to deformation under load. Receiver operating characteristic curves were used to assess the overall diagnostic performance for determining the area under the curve, sensitivity, and specificity of the kc in assessing the corneal tissue deformation to the Corvis ST air-puff event in keratoconus and control eyes. The Corvis Biomechanical Index ( CBI ) was analyzed for external validation. RESULTS:The kc parameter was significantly different between keratoconus and controls ( P < 0.001), ranging from 24.9 ±3.0 to 34.2 ±3.5 N/m, respectively. It was highly correlated with CBI (r = -0.69; P < 0.001); however, the kc parameter had greater specificity (94%) than CBI (75%), whereas the 2 biomarkers had similar area under the curve (0.98 vs. 0.94) and sensitivity (96% vs. 92%) in predicting the occurrence of keratoconus. CONCLUSIONS:The kc parameter extracted by video processing analysis of dynamic Scheimpflug tonometry data was highly accurate in discriminating patients with clinically manifest keratoconus compared with controls.

Purpose: To assess predictability of tissue biomechanical stiffening induced by UV-A light-mediated real-time assessment of riboflavin concentration during corneal crosslinking (CXL) of human donor tissues. Setting: Studio Italiano di Oftalmologia, Rome, Italy. Design: Laboratory study. Methods: 20 sclerocorneal tissues were randomly stratified to undergo CXL with either the epithelium intact (n = 12) or removed (n = 8). Samples underwent corneal soaking with 0.22% riboflavin formulation (RitSight) with dosing time of t = 10 minutes and t = 20 minutes in epithelium-off and epithelium-on protocols, respectively. All tissues underwent 9-minute UV-A irradiance at 10 mW/cm2 using theranostic device (C4V CHROMO4VIS). The device used controlled UV-A light irradiation to induce both imaging and treatment of the cornea, providing a real-time measure of corneal riboflavin concentration and treatment efficacy (ie, theranostic score) during surgery. Tissue biomechanics were assessed with an air-puff device (Corvis), which was performed before and after treatment. A 3-element viscoelastic model was developed to fit the corneal deformation response to air-puff excitation and to calculate the mean corneal stiffness parameter (kc). Results: Significant corneal tissue stiffening (P < .05) was induced by the theranostic UV-A device in either CXL treatment protocol. Significant correlation was found between the theranostic score and the increase in kc (R = 0.75; P = .003). The score showed high accuracy (94%) and precision (94%) to predict correctly samples that had improved tissue biomechanical strengthening. Conclusions: Real-time assessment of corneal riboflavin concentration provided a predictive and precise approach for significant improvement of tissue strength on individual corneas, regardless of CXL treatment protocol.

Non-invasive solutions (no sensors nor markers) appear the most appealing for assessment of body movements and facial dynamics in order to predict Neurodevelopmental disorders (NDD) even in the first days of life. To this aim, recent advances in machine learning applied could be effectively exploited on visual data framing the children, but they suffer from the scarcity of annotated data for training the algorithms. In order to fill this gap, in this paper, a semi-automatic tool specifically designed for labelling videos of children in cribs is introduced. It consists of a Graphical User Interface allowing to select: 1) videos, or static images, to be processed and 2) the desired annotation goal achieved by state-of-the-art deep learning based neural architectures.

Theranostics is an emerging therapeutic paradigm of personalized medicine; the term refers to the simultaneous integration of therapy and diagnostics. In this work, theranostic‐guided corneal cross‐linking was performed on 10 human sclero‐corneal tissues. The samples were soaked with 0.22% riboflavin formulation and underwent 9 minutes UV‐A irradiance at 10 mW/cm2 using theranostic device, which provided both a measure of corneal riboflavin concentration and a theranostic score estimating treatment efficacy in real time. A three‐element viscoelastic model was developed to fit the deformation response of the cornea to air‐puff excitation of dynamic tonometry and to calculate the mean corneal stiffness parameter before and after treatment. Significant correlation was found between the theranostic score and the increase in mean corneal stiffness (R = 0.80; P < .001). Accuracy and precision of the theranostic score in predicting the induced corneal tissue stiffening were both 90%. The riboflavin concentration prior to starting the UV‐A photo‐therapy phase was the most important variable to allow corneal cross‐linking to be effective. Theranostic UV‐A light mediated imaging and therapy enables the operator to adopt a precise approach for achieving highly predictable biomechanical strengthening on individual corneas.

Neurodevelopmental disorders (NDD) are impairments of the growth and development of the brain and/or central nervous system. In the light of clinical findings on early diagnosis of NDD and prompted by recent advances in hardware and software technologies, several researchers tried to introduce automatic systems to analyse the baby's movement, even in cribs. Traditional technologies for automatic baby motion analysis leverage contact sensors. Alternatively, remotely acquired video data (e.g., RGB or depth) can be used, with or without active/passive markers positioned on the body. Markerless approaches are easier to set up and maintain (without any human intervention) and they work well on non-collaborative users, making them the most suitable technologies for clinical applications involving children. On the other hand, they require complex computational strategies for extracting knowledge from data, and then, they strongly depend on advances in computer vision and machine learning, which are among the most expanding areas of research. As a consequence, also markerless video-based analysis of movements in children for NDD has been rapidly expanding but, to the best of our knowledge, there is not yet a survey paper providing a broad overview of how recent scientific developments impacted it. This paper tries to fill this gap and it lists specifically designed data acquisition tools and publicly available datasets as well. Besides, it gives a glimpse of the most promising techniques in computer vision, machine learning and pattern recognition which could be profitably exploited for children motion analysis in videos.

The Assessment of theranostic guided riboflavin/UV-A corneal cross-linking for treatment of keratoconus (ARGO; registration number NCT05457647) clinical trial tests the hypothesis that theranostic-guided riboflavin/UV-A corneal cross-linking (CXL) can provide predictable clinical efficacy for halting keratoconus progression, regardless of treatment protocol, i.e., either with or without epithelial removal. Theranostics is an emerging therapeutic paradigm of personalized and precision medicine that enables real-time monitoring of image-guided therapy. In this trial, the theranostic software module of a novel UV-A medical device will be validated in order to confirm its accuracy in estimating corneal cross-linking efficacy in real time. During CXL procedure, the theranostic UV-A medical device will provide the operator with an imaging biomarker, i.e., the theranostic score, which is calculated by non-invasive measurement of corneal riboflavin concentration and its UV-A light mediated photo-degradation. ARGO is a randomized multicenter clinical trial in patients aged between 18 and 40 years with progressive keratoconus aiming to validate the theranostic score by assessing the change of the maximum keratometry point value at 1-year postoperatively. A total of 50 participants will be stratified with allocation ratio 1:1 using a computer-generated stratification plan with blocks in two treatment protocols, such as epithelium-off or epithelium-on CXL. Following treatment, participants will be monitored for 12 months. Assessment of safety and performance of theranostic-guided corneal cross-linking treatment modality will be determined objectively by corneal tomography, corneal endothelial microscopy, visual acuity testing and slit-lamp eye examination.

Within the context of telerehabilitation, serious games have a significant role, but creating software for serious games is resource demanding. We present Proteo, a modular and open-source framework for developing serious games from scratch. We also present two serious game implementation examples with analysis of end user and therapist/researcher satisfaction. By involving a group of 11 specialized therapists and 9 end users we analyzed the Proteo’s user satisfaction. We found that both groups scored high for the level of involvement, and the therapists scored also high for the level of suitability. More in depth, both groups showed significant differences between positive and negative feelings, with positive feelings scoring higher than negative ones. Finally, the user level of suitability was reported as high while the difficulty of the system and the difficulty of the task were reported as low. Proteo has proven to be a useful tool to develop serious games for telerehabilitation and has been well accepted by the users involved in the evaluation tests.

Ataxic syndromes include several rare, inherited and acquired conditions. One of the main issues is the absence of specific, and sensitive automatic evaluation tools and digital outcome measures to obtain a continuous monitoring of subjects' motor ability.Gait evaluation was performed by Kinect v2 in a cohort of young participant affected by ataxia syndrome. The dataset is composed of the spatio-temporal parameters calculated by the skeleton acquired by the Kinect sensor, by the diagnosis of each participant, and by the total score of the clinical scale SARA. These parameters have been previously validated and corrected as requested by the Bland-Altman test.

BACKGROUND:Ataxic syndromes include several rare, inherited and acquired conditions. One of the main issues is the absence of specific, and sensitive automatic evaluation tools and digital outcome measures to obtain a continuous monitoring of subjects' motor ability.OBJECTIVES:This study aims to test the usability of the Kinect system for assessing ataxia severity, exploring the potentiality of clustering algorithms and validating this system with a standard motion capture system.METHODS:Gait evaluation was performed by standardized gait analysis and by Kinect v2 during the same day in a cohort of young patient (mean age of 13.8±7.2). We analyzed the gait spatio-temporal parameters and we looked at the differences between the two systems through correlation and agreement tests. As well, we tested for possible correlations with the SARA scale as well. Finally, standard classification algorithm and principal components analysis were used to discern disease severity and groups.RESULTS:We found biases and linear relationships between all the parameters. Significant correlations emerged between the SARA and the Speed, the Stride Length and the Step Length. PCA results, highlighting that a machine learning approach combined with Kinect-based evaluation shows great potential to automatically assess disease severity and diagnosis.CONCLUSIONS:The spatio-temporal parameters measured by Kinect cannot be used interchangeably with those parameters acquired with standard motion capture system in clinical practice but can still provide fundamental information. Specifically, these results might bring to the development of a novel system to perform easy and quick evaluation of gait in young patients with ataxia, useful for patients stratification in terms of clinical severity and diagnosis.

BACKGROUND AND OBJECTIVE:Early onset ataxias (EOAs) are a heterogeneous group of neurological conditions, responsible for severe motor disability in paediatric age, which still lack reliable outcome measures. Available scales to assess ataxia, such as the Scale for Assessment and Rating of Ataxia (SARA), are based on subjective assessment of specific motor and language tasks by an examiner, and therefore is age dependent and lacks accuracy in detecting small variations in disease severity. In last years, novel technologies, including computer interfaces and videogames, have emerged for clinical applications and the advent of Internet of Medical Things and of Information Communication Technology have allowed the remote control of such technologies. This pilot study describes a newly developed tool (SaraHome) for the assessment at home of EOA evaluating its feasibility and acceptability on a small sample of children.METHODS:Ten EOA children and ten caregivers have been enrolled for a preliminary outpatient evaluation. The Microsoft Kinect 2.0 and Leap Motion Controller (LMC) connected to a personal computer with an ad hoc software have been set-up, for the acquisition of standardized motor tasks performed by the patients with the caregivers' assistance. Acceptance and practicability have been tested by QUEST 2.0 and IMI questionnaires in caregivers and patients respectively.RESULTS:The SaraHome software was developed, based on a collection of services provided by a complex architecture that consists of a Restful interface, which enables to access a series of plugins for the execution of different tasks. A graphical user interface allows the acquisition of the patient movements while performing a motor task. A protocol of standard tasks inspired by SARA was established, and a system of video-assisted instruction provided. The set-up for the optimal acquisition of such protocol by Kinect and LMC has been defined. Both patients and caregivers accomplished the SaraHome assessment with good feedback at the technology acceptance questionnaires.CONCLUSIONS:SaraHome represents a newly developed tool for the assessment of ataxia in patients, resulting from the integration of low-cost and easy-accessible technologies. This pilot application highlighted the feasibility and the acceptability of the system, suggesting the potential use in clinical practice.

This study is a randomized control trial aimed at testing the role of a human-assisted social robot as an intervention mediator in a socio-emotional understanding protocol for children with autism spectrum disorders (ASD). Fourteen children (4–8 years old) were randomly assigned to 10 sessions of a cognitive behavioural therapy (CBT) intervention implemented in a group setting either with or without the assistance of a social robot. The CBT protocol was based on Rational Emotive Behaviour Therapy (REBT) principles. Pre- and post-intervention assessments were conducted using the Test of Emotional Comprehension (TEC) and the Emotional Lexicon Test (ELT). Substantial improvements in contextualized emotion recognition, comprehension and emotional perspective-taking through the use of human-assisted social robots were attained.

The Internet of Medical Things (IoMT) is a sweeping revolution in the healthcare industry, with IoT quickly establishing itself as a critical part of modern healthcare. The rapid proliferation of such IoMT devices can bring limitations to the current Cloud-IoT centric infrastructures which are not designed to handle huge volumes and velocity of data generated. To address this problem, it is necessary to revisit the network architecture, pushing some data, processing and services directly on the edge nodes of the network where the data originates, away from the centralized Cloud. In this context, Osmotic Computing (OC) aims to provide a new paradigm for the integration between a centralized Cloud layer and Edge/IoT layers. The deployment and migration strategies through the Cloud and Edge layers depend on the infrastructures and applications requirements. This scientific work promotes the basic principles behind the OC paradigm and proposes a closed-loop OC flow model applied to a gamified cognitive rehabilitation use case. Moreover, the use case introduces the development of a customized virtual reality system based on a serious game which allows the patient to carry out physical and cognitive rehabilitation therapies using a natural user interface based on Microsoft Kinect. eas

Recent improvements in the field of assistive technologies have led to innovative solutions aiming at increasing the capabilities of people with disability, helping them in daily activities with applications that span from cognitive impairments to developmental disabilities. In particular, in the case of Autism Spectrum Disorder (ASD), the need to obtain active feedback in order to extract subsequently meaningful data becomes of fundamental importance. In this work, a study about the possibility of understanding the visual exploration in children with ASD is presented. In order to obtain an automatic evaluation, an algorithm for free (i.e., without constraints, nor using additional hardware, infrared (IR) light sources or other intrusive methods) gaze estimation is employed. Furthermore, no initial calibration is required. It allows the user to freely rotate the head in the field of view of the sensor, and it is insensitive to the presence of eyeglasses, hats or particular hairstyles. These relaxations of the constraints make this technique particularly suitable to be used in the critical context of autism, where the child is certainly not inclined to employ invasive devices, nor to collaborate during calibration procedures.The evaluation of children's gaze trajectories through the proposed solution is presented for the purpose of an Early Start Denver Model (ESDM) program built on the child's spontaneous interests and game choice delivered in a natural setting.

During the last decade, the healthcare topic has moved on the top of the development agenda not only for private organizations but also for public administrations. The information technology advances in the healthcare sector have designed an innovative model, the so-called eHealth, that leverages the Cloud Computing paradigm. Even more, with the medical devices (seen as IoT devices) proliferation, there have been introduced new challenges for the Cloud-IoT centric infrastructure. In this context, traditional Health Information Technology (HIT) systems present several limitations, such as scalability, fault-tolerance, interoperability, data management and so on. Starting from the experience reported at ISASI-CNR (ME), a healthcare and research center, in this paper, we motivate the need to move the traditional HIT systems into innovative infrastructures based on the Osmotic Computing paradigm. In particular, we introduce two real uses cases, Ataxia and Dyslexia projects.

We have introduced a new hybrid fabrication method for lab-on-a-chip devices through the combination of femtosecond laser micromachining and removable insert micro-injection molding. This method is particularly suited for the fast prototyping of new devices, while maintaining a competitive low cost. To demonstrate the effectiveness of our approach, we designed, fabricated, and tested a completely integrated flow cytometer coupled to a portable media device. The system operation was tested with fluorescent plastic micro-bead solutions ranging from 100 beads/μL to 500 beads/μL. We demonstrated that this hybrid lab-on-a-chip fabrication technology is suitable for producing low-cost and portable biological microsystems and for effectively bridging the gap between new device concepts and their mass production.