Background: (I) To describe the development and components of the automobile simulator driving behavior evaluation system developed by CRIR-Institut Nazareth et Louis-Braille; (II) to present the preliminary results of the content evaluation of the driving behavior evaluation grid.

Methods: The evaluation system consists of five components: (I) the VS500M Car Simulator (Virage Simulation); (II) four VS500M driving scenarios, modified to minimize the occurrence of simulator sickness and expose subjects to commonly encountered driving situations on highways and city boulevards; (III) the Tobii Pro Glasses 2 eye tracking device; (IV) a car simulator driving behavior observation grid (DBOG); (V) a software application used during the behaviour evaluation phase, where synchronized video tracking, certain data from the simulator (e.g., speed) and the DBOG grid are presented. Initially, the expected safe driving behaviors were identified, including 235 of a visual nature, supported by literature data and consultation of the project steering committee and an expert in driving assessment. Driving behaviors were assessed in 22 subjects without visual impairment (mean age 55±20 years). Subsequently, the items were revised to determine their relevance based on their importance in terms of road safety or on the frequency with which behaviors were observed among participants. For analysis purpose, the items of the DBOG were grouped according to their content, by type of expected driving behavior (e.g., following a stop, look to the left and right before crossing the intersection) or element to be detected (e.g., pedestrians).

Results: Some visual behaviors are difficult to observe with the eye tracker device because they are more dependent on peripheral than central vision. Others are rarely observed, possibly because they are little or not realized in daily life or the representation of reality on the simulator does not stimulate their adoption. On the other hand, the visual detection behaviors expected in a situation where safety can be compromised are mostly carried out (e.g., detection of oncoming vehicles, side mirror verification when changing lanes).

Conclusions: This first phase of the study has made possible to better target the items to be kept in the car simulator driving behavior observation grid, and those that will have to be removed as they are too difficult to observe or too rarely adopted by the participants. Content validity and inter-rater reliability will be assessed from the simplified grid.

Background: (I) To describe the development and components of the automobile simulator driving behavior evaluation system developed by CRIR-Institut Nazareth et Louis-Braille; (II) to present the preliminary results of the content evaluation of the driving behavior evaluation grid.

Methods: The evaluation system consists of five components: (I) the VS500M Car Simulator (Virage Simulation); (II) four VS500M driving scenarios, modified to minimize the occurrence of simulator sickness and expose subjects to commonly encountered driving situations on highways and city boulevards; (III) the Tobii Pro Glasses 2 eye tracking device; (IV) a car simulator driving behavior observation grid (DBOG); (V) a software application used during the behaviour evaluation phase, where synchronized video tracking, certain data from the simulator (e.g., speed) and the DBOG grid are presented. Initially, the expected safe driving behaviors were identified, including 235 of a visual nature, supported by literature data and consultation of the project steering committee and an expert in driving assessment. Driving behaviors were assessed in 22 subjects without visual impairment (mean age 55±20 years). Subsequently, the items were revised to determine their relevance based on their importance in terms of road safety or on the frequency with which behaviors were observed among participants. For analysis purpose, the items of the DBOG were grouped according to their content, by type of expected driving behavior (e.g., following a stop, look to the left and right before crossing the intersection) or element to be detected (e.g., pedestrians).

Results: Some visual behaviors are difficult to observe with the eye tracker device because they are more dependent on peripheral than central vision. Others are rarely observed, possibly because they are little or not realized in daily life or the representation of reality on the simulator does not stimulate their adoption. On the other hand, the visual detection behaviors expected in a situation where safety can be compromised are mostly carried out (e.g., detection of oncoming vehicles, side mirror verification when changing lanes).

Conclusions: This first phase of the study has made possible to better target the items to be kept in the car simulator driving behavior observation grid, and those that will have to be removed as they are too difficult to observe or too rarely adopted by the participants. Content validity and inter-rater reliability will be assessed from the simplified grid.

Background: The perceptions surrounding assistive technology have been shown to be increasingly stigmatizing in older adult populations. This stigmatization can lead individuals to the abandonment of the assistive device. Until now, the methods of identifying or predicting the stigma surrounding assistive technology has mostly been qualitative in nature. Here we present a novel quantitate and qualitative research study that uses neuro-cognitive (psychophysics and EEG) and eye tracking technology, in addition to a new questionnaire to investigate the stigma associated with assistive devices. Therefore, this approach plays a major role in understanding and predicting the neural and physiological correlates associated to stigma.

Methods: Thirty-four older adults (>50 years) took part in the study. To determine the psychophysiological predictors of stigma surrounding assistive technologies, we monitored brain activity using EEG, heart rate and eye movements using an eye-tracker while participants viewed a series of images containing either an older or younger individual in different social scenarios (e.g., talking to doctor, at coffee shop). In each scenario, the individual uses either no assistive device, a low stigmatizing device (e.g., iPad), or a high stigmatizing device (e.g., electronic magnifier).

Results: Here we present preliminary analysis of the eye movement data. Analysis shows that in comparison to images that contained a low stigmatizing device, in images that contain high stigmatizing devices, the latency to fixate the device is shorter, first fixation duration is longer, and the total number of fixations on the device are higher. The environment that the devices is used in has no effect on eye movement metrics.

Conclusions: Although the sample size is small, and based on a healthy older-adult population, these initial observations would indicate that latency to fixate and first fixation duration are predictors of stigma associated with assistive devices. Future research should expand this prediction to those actively using assistive devices, and how the measures predict abandonment over time.

Background: The perceptions surrounding assistive technology have been shown to be increasingly stigmatizing in older adult populations. This stigmatization can lead individuals to the abandonment of the assistive device. Until now, the methods of identifying or predicting the stigma surrounding assistive technology has mostly been qualitative in nature. Here we present a novel quantitate and qualitative research study that uses neuro-cognitive (psychophysics and EEG) and eye tracking technology, in addition to a new questionnaire to investigate the stigma associated with assistive devices. Therefore, this approach plays a major role in understanding and predicting the neural and physiological correlates associated to stigma.

Methods: Thirty-four older adults (>50 years) took part in the study. To determine the psychophysiological predictors of stigma surrounding assistive technologies, we monitored brain activity using EEG, heart rate and eye movements using an eye-tracker while participants viewed a series of images containing either an older or younger individual in different social scenarios (e.g., talking to doctor, at coffee shop). In each scenario, the individual uses either no assistive device, a low stigmatizing device (e.g., iPad), or a high stigmatizing device (e.g., electronic magnifier).

Results: Here we present preliminary analysis of the eye movement data. Analysis shows that in comparison to images that contained a low stigmatizing device, in images that contain high stigmatizing devices, the latency to fixate the device is shorter, first fixation duration is longer, and the total number of fixations on the device are higher. The environment that the devices is used in has no effect on eye movement metrics.

Conclusions: Although the sample size is small, and based on a healthy older-adult population, these initial observations would indicate that latency to fixate and first fixation duration are predictors of stigma associated with assistive devices. Future research should expand this prediction to those actively using assistive devices, and how the measures predict abandonment over time.

Background: This infrastructure delivers biological material necessary for several research projects to Vision Health Research Network investigators (VHRN).

Methods: Héma-Québec is the organism in charge obtaining consent and retrieving donor eyes for patient treatment or for research. In Quebec City, donor eyes are sent to the eye bank of the “Centre Universitaire d’Ophtalmologie” (CUO) of Saint-Sacrement hospital. Technicians at the eye bank evaluate the quality of the tissues. Those unfit for graft are transferred to the infrastructure where the coordinator encodes samples prior to their distribution.

Results: Between 2013 and 2017, 27 fundamental investigators, clinical investigators and collaborators supported by 60 students, trainees and laboratory assistants used this infrastructure to move forward their projects. Since 2013, results from those projects generated 21 scientific publications and 232 presentations. The infrastructure helped VHRN investigators obtain near 4 million dollars in grants from many organisms (CIHR, NSERC, Foundations, etc.). These grants allowed recruitment and formation of highly qualified personnel. Last year (April 2016 to March 2017), 189 corneas and 23 eyes transited through the infrastructure.

Conclusions: This infrastructure is available for all investigators that are members of the VHRN. Many original projects have been elaborated thanks to the human ocular tissues provided by this infrastructure. These projects will advance our knowledge in vision health. A better understanding of eye functions will lead to new treatments for eye diseases.

Background: This infrastructure delivers biological material necessary for several research projects to Vision Health Research Network investigators (VHRN).

Methods: Héma-Québec is the organism in charge obtaining consent and retrieving donor eyes for patient treatment or for research. In Quebec City, donor eyes are sent to the eye bank of the “Centre Universitaire d’Ophtalmologie” (CUO) of Saint-Sacrement hospital. Technicians at the eye bank evaluate the quality of the tissues. Those unfit for graft are transferred to the infrastructure where the coordinator encodes samples prior to their distribution.

Results: Between 2013 and 2017, 27 fundamental investigators, clinical investigators and collaborators supported by 60 students, trainees and laboratory assistants used this infrastructure to move forward their projects. Since 2013, results from those projects generated 21 scientific publications and 232 presentations. The infrastructure helped VHRN investigators obtain near 4 million dollars in grants from many organisms (CIHR, NSERC, Foundations, etc.). These grants allowed recruitment and formation of highly qualified personnel. Last year (April 2016 to March 2017), 189 corneas and 23 eyes transited through the infrastructure.

Conclusions: This infrastructure is available for all investigators that are members of the VHRN. Many original projects have been elaborated thanks to the human ocular tissues provided by this infrastructure. These projects will advance our knowledge in vision health. A better understanding of eye functions will lead to new treatments for eye diseases.

Background: The purpose of this infrastructure is to provide to the Network researchers a database and diverse related tools for the anatomical and functional analysis of the normal, pathological and surgical cornea.

Methods: This database is composed of normal and pathological individuals, totaling more than 36,000 patients. It includes anatomical and functional imaging data, physiological optics data, psychometric and clinical data (medical history, surgical parameters, acuteness, etc.). Various corneal topography tools were added, giving the database a unique character: tools for analyzing individual maps, average map tools for the study and comparison of populations, 3D modeling and visualization tools, statistical tools, etc. There are also screening tools for detecting various corneal conditions (LASIK, PRK, RK, keratoconus) and for secure data exchange between colleagues.

Results: Several studies were made in recent years thanks to this common infrastructure. For example, this database has provided important information regarding the evolution of the 3D shape of the normal cornea with age and ametropia and has confirmed the mirror symmetry of corneas for the right and the left eyes (enantiomorphism). The different stages of Fuchs’ dystrophy were also characterized to provide essential knowledge for surgery of the posterior layer of the cornea. Our database also allowed studying the anatomy of the wounds and the shape of the cornea before and after a transfixing transplant or an endothelial transplant (DSAEK and DSEK). The data on the characterization of experimentally transplanted corneas with corneal equivalents generated by tissue engineering and the recent addition of clinical data on the replacement of a diseased cornea with a synthetic corneal equivalent (keratoprosthesis) also resulted in several publications. More recently, the database has allowed to develop innovative algorithms to determine the optimal shape of an implant according to the clinical parameters of the recipient. On the other hand, we also demonstrated that the 3D shape of the cornea can be used as a biometric characteristic (such as fingerprints) for identification of individuals for various applications ranging from forensics to secure border crossings. Consequently, a new multimodal database (cornea + iris + eventually retina) was created for the purpose of biometric identifications. This database provides a unique set of anatomical and functional tools for the analysis of the cornea. It is characterized by the scientific quality and large quantity of accumulated information on the cornea and the high-level tools to exploit its content.

Conclusions: The common infrastructure is easily accessible to all VHRN members on request. The database will also be accessible online in 2018 (see http://cvl.concordia.ca for more information).

Background: The purpose of this infrastructure is to provide to the Network researchers a database and diverse related tools for the anatomical and functional analysis of the normal, pathological and surgical cornea.

Methods: This database is composed of normal and pathological individuals, totaling more than 36,000 patients. It includes anatomical and functional imaging data, physiological optics data, psychometric and clinical data (medical history, surgical parameters, acuteness, etc.). Various corneal topography tools were added, giving the database a unique character: tools for analyzing individual maps, average map tools for the study and comparison of populations, 3D modeling and visualization tools, statistical tools, etc. There are also screening tools for detecting various corneal conditions (LASIK, PRK, RK, keratoconus) and for secure data exchange between colleagues.

Results: Several studies were made in recent years thanks to this common infrastructure. For example, this database has provided important information regarding the evolution of the 3D shape of the normal cornea with age and ametropia and has confirmed the mirror symmetry of corneas for the right and the left eyes (enantiomorphism). The different stages of Fuchs’ dystrophy were also characterized to provide essential knowledge for surgery of the posterior layer of the cornea. Our database also allowed studying the anatomy of the wounds and the shape of the cornea before and after a transfixing transplant or an endothelial transplant (DSAEK and DSEK). The data on the characterization of experimentally transplanted corneas with corneal equivalents generated by tissue engineering and the recent addition of clinical data on the replacement of a diseased cornea with a synthetic corneal equivalent (keratoprosthesis) also resulted in several publications. More recently, the database has allowed to develop innovative algorithms to determine the optimal shape of an implant according to the clinical parameters of the recipient. On the other hand, we also demonstrated that the 3D shape of the cornea can be used as a biometric characteristic (such as fingerprints) for identification of individuals for various applications ranging from forensics to secure border crossings. Consequently, a new multimodal database (cornea + iris + eventually retina) was created for the purpose of biometric identifications. This database provides a unique set of anatomical and functional tools for the analysis of the cornea. It is characterized by the scientific quality and large quantity of accumulated information on the cornea and the high-level tools to exploit its content.

Conclusions: The common infrastructure is easily accessible to all VHRN members on request. The database will also be accessible online in 2018 (see http://cvl.concordia.ca for more information).

Background: Because of its superficial anatomical localization, the cornea is particularly vulnerable to abrasive forces and various traumas, which can lead to significant visual impairments. Upon injury of the corneal epithelium, there are important changes that occur in the composition of the underlying extracellular matrix (ECM). Those changes are perceived by the integrins that recognize the ECM components as their ligand and activate different intracellular signalling pathways, ultimately leading to reepithelialisation and reorganization of the injured epithelium, both of which are necessary in order to restore the visual properties of the cornea. The goal of this study was to analyse the impact of the pharmacological inhibition of specific signal transduction mediators of integrin-dependant signalling pathways on corneal wound healing using both monolayers of hCECs and tissue-engineered human corneas (hTECs) as in vitro models.

Methods: hTECs were produced by the self-assembly approach and wounded with a 8-mm diameter biopsy punch. Total RNA and proteins were isolated from the wounded and unwounded hTECs to conduct gene profiling analyses and protein kinase arrays. The wounded tissues were then incubated with the WNK1 inhibitor WNK463 and wound healing was monitored over a period of 6 days. Control corneas were incubated with the vehicle alone (DMSO). The impact of WNK1 inhibition on hCECs monolayers was determined using a scratch wound assay.

Results: Gene profiling analyses and protein kinases arrays revealed important alterations in the expression and activity of several mediators from the integrin-dependent signalling pathways in response to the ECM changes taking place during corneal wound healing. Among these, WNK1 is considerably activated through phosphorylation during corneal wound healing. The pharmacological inhibition of WNK1 by WNK463 significantly reduced the dynamic of corneal wound closure in our hTECs and hCECs monolayers compared to their respective negative controls.

Conclusions: These results allowed the identification of WNK1 kinase as an important player for a proper healing of the cornea. Also, these results allowed for a better understanding of the cellular and molecular mechanisms involved in corneal wound healing and they may lead to the identification of new therapeutic targets in the field of corneal wounds.

Background: Because of its superficial anatomical localization, the cornea is particularly vulnerable to abrasive forces and various traumas, which can lead to significant visual impairments. Upon injury of the corneal epithelium, there are important changes that occur in the composition of the underlying extracellular matrix (ECM). Those changes are perceived by the integrins that recognize the ECM components as their ligand and activate different intracellular signalling pathways, ultimately leading to reepithelialisation and reorganization of the injured epithelium, both of which are necessary in order to restore the visual properties of the cornea. The goal of this study was to analyse the impact of the pharmacological inhibition of specific signal transduction mediators of integrin-dependant signalling pathways on corneal wound healing using both monolayers of hCECs and tissue-engineered human corneas (hTECs) as in vitro models.

Methods: hTECs were produced by the self-assembly approach and wounded with a 8-mm diameter biopsy punch. Total RNA and proteins were isolated from the wounded and unwounded hTECs to conduct gene profiling analyses and protein kinase arrays. The wounded tissues were then incubated with the WNK1 inhibitor WNK463 and wound healing was monitored over a period of 6 days. Control corneas were incubated with the vehicle alone (DMSO). The impact of WNK1 inhibition on hCECs monolayers was determined using a scratch wound assay.

Results: Gene profiling analyses and protein kinases arrays revealed important alterations in the expression and activity of several mediators from the integrin-dependent signalling pathways in response to the ECM changes taking place during corneal wound healing. Among these, WNK1 is considerably activated through phosphorylation during corneal wound healing. The pharmacological inhibition of WNK1 by WNK463 significantly reduced the dynamic of corneal wound closure in our hTECs and hCECs monolayers compared to their respective negative controls.

Conclusions: These results allowed the identification of WNK1 kinase as an important player for a proper healing of the cornea. Also, these results allowed for a better understanding of the cellular and molecular mechanisms involved in corneal wound healing and they may lead to the identification of new therapeutic targets in the field of corneal wounds.

Background: Congenital hereditary endothelial dystrophy (CHED) is characterized by blindness at birth or in early infancy resulting from bilateral corneal opacification, and is linked to mutation in the Slc4a11 gene. A Slc4a11 knockout (KO) mouse, generated by gene deletion (Vithana et al. Nat Genet 2006), was acquired in order to study this disease. To confirm the phenotype of this Slc4a11 KO mouse model as a function of age, using the wild type (WT) mouse as a control.

Methods: Genotyping was performed by PCR (REDExtract-N-AmpTM Tissue PCR Kit, Sigma-Aldrich, Oakville, ON). Slc4a11 WT and KO mice populations aged from 5 to 50 weeks were studied (n=5 animals per age group; 5-year age intervals). Slit lamp examination, anterior segment-ocular coherence tomography (OCT930SR; Thorlabs, Inc., Newton, NJ), corneal endothelial cell staining, and scanning (SEM) and transmission (TEM) electron microscopy were used to assess the morphological and cellular differences between the two groups. The expression of basolateral membrane transporter NaBC1 within the corneal endothelium was also assessed using immunohistochemistry.

Results: Diffuse and progressive corneal opacification was observed at the slit lamp in the Slc4a11 KO mice, starting at 10 weeks. The central corneal thickness (CCT) also increased progressively as a function of time. In comparison, Slc4a11 WT corneas remained clear over the entire study period. Early TEM results showed vacuole degeneration of the corneal endothelium in the 15-week KO mouse, which was not seen in the same age WT mouse.

Conclusions: The corneal phenotype of this Slc4a11 KO mouse is representative of the clinical manifestations of CHED in human subjects, confirming the usefulness of this model for studying pathophysiology and therapeutic alternatives for Slc4a11-associated corneal dystrophies.

Background: Congenital hereditary endothelial dystrophy (CHED) is characterized by blindness at birth or in early infancy resulting from bilateral corneal opacification, and is linked to mutation in the Slc4a11 gene. A Slc4a11 knockout (KO) mouse, generated by gene deletion (Vithana et al. Nat Genet 2006), was acquired in order to study this disease. To confirm the phenotype of this Slc4a11 KO mouse model as a function of age, using the wild type (WT) mouse as a control.

Methods: Genotyping was performed by PCR (REDExtract-N-AmpTM Tissue PCR Kit, Sigma-Aldrich, Oakville, ON). Slc4a11 WT and KO mice populations aged from 5 to 50 weeks were studied (n=5 animals per age group; 5-year age intervals). Slit lamp examination, anterior segment-ocular coherence tomography (OCT930SR; Thorlabs, Inc., Newton, NJ), corneal endothelial cell staining, and scanning (SEM) and transmission (TEM) electron microscopy were used to assess the morphological and cellular differences between the two groups. The expression of basolateral membrane transporter NaBC1 within the corneal endothelium was also assessed using immunohistochemistry.

Results: Diffuse and progressive corneal opacification was observed at the slit lamp in the Slc4a11 KO mice, starting at 10 weeks. The central corneal thickness (CCT) also increased progressively as a function of time. In comparison, Slc4a11 WT corneas remained clear over the entire study period. Early TEM results showed vacuole degeneration of the corneal endothelium in the 15-week KO mouse, which was not seen in the same age WT mouse.

Conclusions: The corneal phenotype of this Slc4a11 KO mouse is representative of the clinical manifestations of CHED in human subjects, confirming the usefulness of this model for studying pathophysiology and therapeutic alternatives for Slc4a11-associated corneal dystrophies.