Mesenchymal stem cell based therapies for uveitis: a systematic review of preclinical studies.

Cell therapy has shown promising results for treating uveitis in preclinical studies. As the field continues to grow towards clinical translation, it is important to review and critically appraise existing studies. Herein, we analysed and critically appraised all preclinical studies using cell therapy or cell derived extracellular vesicles (EVs) for uveitis, and provided insight into mechanisms regulating ocular inflammation. We used PubMed, Medline, and Embase to search for preclinical studies examining stem cell therapy (e.g., mesenchymal stem cells [MSC]) and secreted EVs. All included studies were assessed for quality using the SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) checklist. Sixteen preclinical studies from 2011 to 2022 were analysed and included in this review of which 75% (n = 12) focused only on cell therapy, 18.7% (n = 3) studies focused on EVs, and 6.3% (n = 1) study focused on both cells and EVs. MSCs were the most common type of cells used in preclinical studies (n = 15) and EVs were commonly isolated from MSCs (n = 3). Overall, both MSCs and EVs showed improvements in ocular inflammation (seen on fundoscopy/slit lamp and histology) and electroretinogram outcomes. Overall, MSC and MSC-derived EVs shown great potential as therapeutic agents for treating uveitis. Unfortunately, small sample size, risk of selection/performance bias, and lack of standardized cell harvesting or delivery protocols are some factors which limits clinical translation. Large scaled, randomized preclinical studies are required to understand the full potential of MSCs for treating uveitis.

Development and validation of the first Canadian Aboriginal syllabics visual acuity chart.

OBJECTIVE: To design and validate the first visual acuity (VA) chart in the Canadian Aboriginal syllabics (CAS) alphabet. DESIGN: Prospective, nonrandomized, within-subjects cross-sectional study. PARTICIPANTS: Twenty Latin- and CAS-reading subjects were recruited from Ullivik, a residence in Montreal for Inuit patients. METHODS: VA charts were made in Latin and in CAS using letters conserved across Inuktitut, Cree, and Ojibwe languages. Fonts were similar in style and size between charts. Each chart was made for a viewing distance of 3 m, with 11 lines of VAs from 20/200 to 20/10. Charts were created using LaTeX to ensure proper formatting and optotype sizing and displayed to scale on an iPad Pro. Each participant had his or her best-corrected VA for each eye measured using the Latin and CAS charts sequentially for a total of 40 eyes. RESULTS: Median best-corrected VAs were 0.04 logMAR (range, -0.06-0.54) and 0.07 logMAR (range, 0-0.54) for the Latin and CAS charts, respectively. Median difference between CAS and Latin charts was 0 logMAR (range, -0.08-0.1). Mean ± SD difference between charts was 0.01 ± 0.03 logMAR. Pearson's r correlation between groups was 0.97. The two-tailed paired t test between groups was p = 0.26. CONCLUSIONS: We demonstrate here the first VA chart in Canadian Aboriginal syllabics for Inuktitut-, Ojibwe-, and Cree-reading patients. The CAS VA chart has highly similar measurements to the standard Snellen chart. Testing VA for Indigenous patients in their native alphabet may provide patient-centred care and accurate VA measurements for Indigenous Canadians.

Addressing healthcare barriers faced by asylum seekers and refugees through an interprofessional symposium.

In this work, we describe an interprofessional healthcare symposium driven by the challenges faced by the local asylum-seeking/refugee population in Montreal. McGill University medical, nursing, dietetics, and social work students partnered with local experts to provide attendees with tools to better meet the needs of Montreal's migrant population. This student-led initiative, unique in its interdisciplinary and comprehensive nature, increased awareness of the needs of an underserved population while promoting student engagement in health advocacy and interprofessional collaboration. It also enhances the development of skills essential to provide culturally sensitive care.

Dans cet article, nous décrivons un symposium en santé interprofessionnel adressant les défis auxquels font face la population locale de demandeurs d'asile/réfugiés à Montréal. Les étudiants en médecine, en sciences infirmières, en diététique et en travail social de l'Université McGill ont fait appel à des experts locaux pour fournir aux futur professionnels de la santé des outils leur permettant de mieux répondre aux besoins de la population migrante de Montréal. Cette initiative unique dans sa nature interdisciplinaire et globale, a accru la sensibilisation aux besoins d'une population mal desservie tout en favorisant l'engagement des étudiants dans la promotion de la Santé, la collaboration Interprofessionnelle et l'offre de soins culturellement adaptés.

Research and residency match: a near-peer online webinar.

Medical students have a wide range of opinions and expectations about research and face many challenges when pursuing it. Online research webinars have the potential to teach medical students about the value of research for various competitive and non-competitive specialties, while also providing them with the opportunity to network with recent medical graduates. When hosted virtually, these events have the potential to reach medical student across multiple provinces and provide them with insight on the different facets of research.

Les étudiants en médecine ont des opinions et des attentes très diversifiées en ce qui concerne la recherche et ils sont confrontés à de nombreux défis lorsqu'ils s'y lancent. Les webinaires sur la recherche peuvent renseigner les étudiants sur l'intérêt de la recherche dans diverses spécialités à forte concurrence ou non, tout en leur donnant l'occasion de réseauter avec des diplômés récents. Ce type d'activités, lorsqu'elles sont tenues virtuellement, ont le potentiel de toucher les étudiants en médecine de plusieurs provinces et de leur donner un aperçu des différentes facettes de la recherche.

Incidence of ophthalmologic pathology and associated risk factors in orbital fractures at a level I trauma centre.

OBJECTIVE: To estimate the incidence of ophthalmologic pathology at presentation of patients with orbital fracture to a level I trauma centre and the most significant associated risk factors. METHODS: A total of 244 patients with 278 fractured orbits over a 2-year period at a level I trauma centre were reviewed. The primary outcome was the incidence of urgent ophthalmologic pathology, defined as requiring attention without delay. Patient demographics, history, findings on radiographic imaging, and physical examination findings at initial and follow-up examinations were recorded. Odds ratios with 95% confidence intervals were calculated. RESULTS: On initial examination and follow-up, 9.7% of orbits had ophthalmologic pathology. Only 3 patients (1.1%) had urgent pathology, including orbital compartment syndrome and globe rupture, whereas 22 patients (7.9%) had semiurgent pathology and 4 patients (1.4%) had nonurgent pathology. Subjective decreased vision (odds ratio [OR] = 3.5; p = 0.021), assault-related injuries (OR = 2.4; p = 0.036), work-related injuries (OR = 7.7; p = 0.004), afferent pupillary defect (OR = 19.2; p = 0.017), anisocoria (OR = 7.8; p = 0.001), and symmetrical extraocular movement limitation (OR = 5.2; p = 0.003) and fixed pupil (OR = 16.9; p < 0.001) had statistically significant odds ratios associated with pathology. Patient sex, eye involved, intoxication, anticoagulation, and antiplatelets, as well as previous ocular surgery, were not associated with pathology. CONCLUSIONS: Most orbital fractures do not present with ophthalmologic pathology. Subjective vision loss, history of assault or work trauma, and pupil abnormalities on examination were the greatest risk factors for pathology. Our results highlight the most important factors on patient presentation that should prompt first responders to seek urgent ophthalmologic consultation.

Significance of subconjunctival hemorrhage in predicting ocular pathology for patients with orbital fracture.

OBJECTIVE: Subconjunctival hemorrhage (SCH) is a common presentation in patients with orbital trauma and often warrants investigation of underlying ocular pathology. Our study aims to assess the significance of SCH severity, graded in a spatial 0-360° manner, as a predictor for ocular pathology in patients with orbital fracture. DESIGN: Retrospective chart review. PARTICIPANTS: Patients with fractured orbits (n = 265) presenting to a level 1 trauma centre between August 2015 and January 2018. METHODS: Key elements of ophthalmic assessment, including visual acuity, SCH (0-360°), anterior- and posterior-segment examination, Hertel exophthalmometry, and ocular pathology, were recorded. Simple logistic regression assessed for association between SCH severity and ocular pathology. Odds ratios (ORs) were calculated with 95% CI. RESULTS: Among the 265 fractured orbits, 158 (59.6%) presented with no SCH, and 107 (40.4%) had some degree of SCH. Ocular pathology was noted in 24 fractured orbits (9%). Most common pathologies included entrapment (22.2%), hyphema (16.7%), traumatic optic neuropathy (8.3%), and commotio retinae (8.3%). Simple logistic regression revealed a higher incidence of ocular pathology with increasing severity of SCH from 0-360° (OR = 1.004; 95% CI 1.001-1.007; p = 0.0085). In addition, χ2 analysis demonstrated a higher proportion of ocular pathology in 181-270° (25.0%; p = 0.0466) and 271-360° SCH subgroups (26.3%; p = 0.0031) compared with the 0° SCH subgroup (6.3%). CONCLUSIONS: Our findings suggest that there is some correlation between the extent of SCH and ocular pathology. However, patient care and investigations should continue to be directed by a full clinical assessment of patients with orbital trauma.

Clinical correlations of extraocular motility limitation pattern in orbital fracture cases: a retrospective cohort study in a level 1 trauma centre.

PURPOSE: Ocular pathology (OP) following orbital fracture can vary vastly in complexity and severity. Extra-ocular motility (EOM) limitations are frequently present in orbital trauma cases, with patterns of duction limitations being symmetrical or asymmetrical. The aim of this study was to identify if there was any association between increased OP following orbital fracture cases based on the pattern of EOM deficits. METHODS: This is a retrospective cohort study of patients with fractured orbits presenting with or without EOM limitations to a level 1 trauma center between August 2015 to January 2018. All pertinent elements of the ophthalmic examination were recorded. Outcome measures: Chi-square analyses assessed for association between symmetrical or asymmetrical EOM limitation and OP. Odds ratios were calculated with 95% confidence interval. RESULTS: 278 orbits with wall fractures were included in this study. A significant correlation between EOM limitation and increased OP following orbital trauma was found (p = 0.000081). Cases with symmetrical and asymmetrical EOM limitation were 7.9 (95%CI: 2.3-27.2) and 5.22 (95%CI: 1.9-13.9) times more likely to have OP than cases with no EOM limitation, respectively. With extraocular muscle entrapment excluded, cases with symmetrical limitations had a significantly higher incidence of OP than cases with asymmetrical limitations (p = 0.0161). CONCLUSIONS: OP is frequently observed in cases of orbital fracture. While any EOM limitations should prompt the clinicians to anticipate OP, intra-ocular injury may be more likely in cases of symmetrical EOM limitation. Future prospective studies are needed to further elucidate the relationship between EOM symmetricity and OP following orbital trauma.

Cemiplimab for metastatic squamous cell carcinoma of the orbit, periocular adnexa, and thigh.

The current case presentation highlights the potential of cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, as first-line treatment for periocular metastatic cutaneous squamous cell carcinoma (SCC) without requiring curative surgery or radiotherapy. A 64-year-old male presented with a progressing 4.5 × 3.0 cm left upper eyelid lesion initially diagnosed as psoriasis. Work-up revealed cutaneous SCC with tumor invasion into extraconal fat and lacrimal gland, and metastasis to the left parotid lymph node. The patient also presented with a suspicious lesion on his left medial thigh found to be a second primary on pathology. To avoid orbital exenteration and treat the multifocal disease, the patient was started on intravenous cemiplimab immunotherapy. Following six doses, repeated FGD-PET-CT revealed a complete response of the left eyelid lesion and residual low-grade hypermetabolic activity of the left medial thigh lesion. Biopsy confirmed chronic inflammation and fibrosis with no signs of malignancy. This unique case with dual primary cutaneous SCC provides support for cemiplimab in treating locally invasive periocular SCC, and potentially abrogating the need for highly morbid exenteration procedures to preserve binocular vision.

Uveal melanoma incidence trends in Canada: 1992-2010 vs. 2011-2017.

Background/aims: Uveal melanoma is the most common type of non-cutaneous melanoma and the most common ocular malignancy in the adult population, especially affecting Caucasians (98% of cases). Despite its low incidence rate, we have noted increasing incidence trends in recent years. Methods: We analyzed uveal melanoma incidence data using the Canadian Cancer Registry (CCR) for 2011-2017 years. The data was examined using the International Classification of Diseases for Oncology, Third Edition, codes for all uveal melanoma subtypes. The data for 2011-2017 was then compared to previously published work by our research group for uveal melanoma incidence in Canada between 1992 and 2010 using the same methodology. Results: Between 2011 and 2017, 1,215 patients were diagnosed with uveal melanoma, 49% of whom were females. The percentage distribution of uveal melanoma between the sexes was similar between 1992-2010 and 2011-2017, whereby of the 2,215 diagnoses of uveal melanoma in 1992-2010, 47.9% were females. The change in the incidence rate for this cancer has doubled between 1992-2010 and 2011-2017, from 0.074 to 0.15 cases per million individuals per year. Our study documents that the Canadian 2011-2017 age-standardized incidence rate (ASIR) for uveal melanoma against the World Health Organization (WHO) 2000-2025 world population standard was 5.09 cases per million individuals per year (95% confidence interval, 4.73-5.44), as compared with the 1992-2010 rate of 3.34 cases per million individuals per year (95% confidence interval, CI 3.20 to 3.47). Conclusion: This work demonstrates an ongoing, steady increase in uveal melanoma incidence in Canada in recent years.

Impact of COVID-19 on Canadian Medical Education: Pre-clerkship and Clerkship Students Affected Differently.

The coronavirus pandemic (COVID-19) has altered the undergraduate learning experience for many students across Canada. Medical education is no exception; clinical programs, in-person lectures, and mandatory hands-on activities have been suspended to adhere to social distancing guidelines. As remote teaching becomes the forefront of education, medical curricula have been forced to adapt accordingly in order to fulfill the core competencies of medical training and to provide quality education to medical students. With that in mind, the COVID-19 crisis offers a unique opportunity to evaluate the current "continuity plans" in medical education as they stand. This paper provides the perspective of medical students on how medical education is changing for both pre-clerkship and clerkship students, using their experience at McGill University as an example for the Canadian medical education system. Additionally, we discuss the accommodations put forth by the undergraduate medical education (UGME) office, and reflect on the limitations and sustainable solutions in supporting quality medical education.

Peptide-modified methacrylated glycol chitosan hydrogels as a cell-viability supporting pro-angiogenic cell delivery platform for human adipose-derived stem/stromal cells.

Cell-based therapies involving the injection of adipose-derived stem/stromal cells (ASCs) within rationally designed biomaterials are a promising approach for stimulating angiogenesis. With this focus, the current work explored the effects of incorporating integrin-binding RGD or IKVAV peptides within in situ-gelling N-methacrylate glycol chitosan (MGC) hydrogels on the response of encapsulated human ASCs. Initial studies focused on hydrogel characterization to validate that the MGC, MGC-RGD, and MGC-IKVAV hydrogels had similar biomechanical properties. ASC viability following encapsulation and culture under 2% O2 was significantly impaired in the MGC-IKVAV group relative to the MGC and MGC-RGD groups. In contrast, sustained viability, along with enhanced cell spreading and metabolic activity were observed in the MGC-RGD group. Investigation of angiogenic transcription suggested that the incorporation of the peptide groups did not substantially alter the pro-angiogenic gene expression profile of the encapsulated ASCs after 7 days of culture under 2% O2. Consistent with the in vitro findings, preliminary in vivo characterization following subcutaneous implantation into NOD/SCID mice showed that ASC retention was enhanced in the MGC-RGD hydrogels relative to the MGC-IKVAV group at 14 days. Further, the encapsulated ASCs in the MGC and MGC-RGD groups promoted murine CD31+ endothelial cell recruitment to the peri-implant region. Overall, the results indicate that the MGC-RGD and MGC hydrogels are promising platforms for ASC delivery, and suggest that strategies that support long-term ASC viability can augment in vivo angiogenesis through paracrine mechanisms. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 571-585, 2019.