The 2022 Annual Grant Scheme is open and accepting applications
Closing Date 31st of October 2022
For application & eligibility criteria, please contact the email@example.com
An important aspect of the Research Foundation’s work is to nurture and support young doctors in the fields of Ophthalmology and Otolaryngology. It is with new research and innovations that we work towards novel treatments for disease. It is imperative that any project funded by the Research Foundation must have real and tangible translational benefits for patients and add to developments in the field.
Through its Annual Grant Scheme, the Research Foundation funds new and exciting projects being undertaken by young Royal Victoria researchers. Below are some details on these projects and their potential impact.
Annual Grant Scheme 2021
Haematopoietic stem cell transplantation (HSCT) is a potentially curative form of treatment for a wide range of haematological diseases, including lymphoma, leukaemia, immune-deficiency illnesses, congenital metabolic defects, hemoglobinopathies, and myelodysplastic and myeloproliferative syndromes. However, with the increase survival has come an increase in chronic complications, predominately that of graft versus host disease (GVHD).
Although GVHD can have a multitude of systemic manifestations in affected patients, ocular GVHD is one of the most frequent and long-term complications and is associated with significant morbidity and a marked reduction in quality of life. It can affect all parts of the eye, but occurs primarily on the ocular surface, resulting in dry eye disease (DED) or keratoconjunctivitis sicca. The pathogenesis is complex and incompletely understood. However, it has been observed that DED related GVHD evolves in a similar fashion to that of primary Sjogren’s syndrome, with the destruction and fibrosis of lacrimal glands and conjunctiva, leading to tear film deficiency and instability.
Our preliminary studies have indicated that miR expression is dysregulated at the ocular surface and is involved in the pathogenesis of DED observed in patients with primary Sjogren’s syndrome. In a similar fashion, we hypothesize that epigenetic mechanisms that regulate the interplay between inflammatory cytokine networks, innate immune cells and their mediators are dysregulated in ocular GVHD patients thereby contributing to disease pathology.
Although ocular GVHD is common, currently there are no widely accepted guidelines available for its management, and no suggested regime of treatment that is completely satisfactory. So far, prophylactic treatment strategies for ocular GVHD have yet to be developed and treatment is normally initiated based on symptoms and often after permanent ocular tissue changes and surface damage has occurred.
Annual Grant Scheme 2021
Adenoid cystic carcinomas (ACC) are rare salivary gland neoplasms identified within the major and minor salivary glands, predominantly the parotid gland and palate. ACC account for approximately 10% of all salivary gland neoplasms. Interestingly, ACC can occur at other anatomic sites outside the head and neck region including within breast tissue and the prostate gland. There are numerous factors associated with poorer outcomes for patients with ACC including older age at diagnosis, higher tumour stage, skull-based disease and perineural invasion. Approximately 50% of patients develop recurrence of their cancer despite surgery, radiation and/or chemotherapeutic treatment. The disease specific survival at 5 years is 89% but falls to 40% at 15 years.
Utilisation of next generation sequencing has illustrated genetic alterations which permit identification of molecular pathways initiating and sustaining tumorigenesis. A recent publication in 2019 by Ho et al. illustrated that NOTCH1 mutations were the most prevalent somatic mutation in both the primary ACC tumour, as well as the recurrent or metastatic tumour. Armed with the knowledge that NOTCH1 mutations are associated with a poor prognosis, A phase I trial treating individuals with Brontictuzumab for recurrent or refractory solid tumours, showed efficacy for this monoclonal antibody targeting NOTCH1. A Phase II trial, the ACCURACY trial, examining the utilisation of a Notch inhibitor inpatients with recurrent and/or metastatic ACC is ongoing.
In summary, this will be the first study to identify the prevalence of NOTCH1 (and other) mutations in salivary gland neoplasms within an Irish cohort. With the known poor prognostic implications of this activating mutation, identifying patients with this mutation can assist in stratifying these individuals for potential future targeted studies.
Annual Grant Scheme 2020
Uveal Melanoma (UM) is the most common intraocular malignancy in adults with an annual incidence in Ireland estimated at 9.5 cases per million people. Almost 50% of patients with UM will develop metastases, the average survival after detection of metastases being only 10 months.
Detecting those patients who are at increased risk of developing metastases is important for clinical management, as metastases are not usually detectable at the time of treatment of the primary tumour and have often reached an advanced stage by the time they cause symptoms. The ability to stratify patients into high risk or low risk for metastases based on the cytogenetic profile of their tumour will allow us to reassure those patients who are at low risk of metastatic disease. Conversely, those at high risk can undergo more regular surveillance and might also be considered for adjuvant therapies.
A clinical study of prophylactic chemotherapy would also be desirable; however, regarding the side-effects of chemotherapy, identification of a high-risk group is regarded as a prerequisite for such a study.
Although several clinical and histopathologic parameters serve as established prognostic factors in UM, none of them have been regarded as sufficient for a clear definition of clinically relevant subgroups of patients. The understanding of the role which various genetic anomalies play in UM tumorigenesis may finally lead to risk-adjusted therapy strategies.
C-myc is one such marker that could act as a prognostic indicator in UM. C-Myc is a nuclear oncogene involved in cellular proliferation, and its expression is linked with the ability of cells to proceed through the cell cycle. Aberrant expression of C-myc has been related to the deregulation of proliferation in several tumour types.
Overexpression of the C-myc protein has independent prognostic significance in a variety of primary and metastatic cutaneous melanomas which suggests a possible role for this gene in uveal melanoma genesis. The gene for C-Myc is located on chromosome 8q24.1 and chromosomal abnormalities involving amplification of 8q material have been associated with poor prognosis in uveal melanoma also.
To date, only a limited number of studies have examined the role of C-myc in uveal melanoma. The results from these studies have varied with one paper demonstrating improved survival and another, decreased survival with increasing levels of C-myc expression.
The aim of the study is to assess C-myc positivity in uveal melanoma samples obtained at RVEEH between 2010 and 2020. We will determine any significant association between C-myc positivity and survival. It would also determine the association between C-myc positivity and a number of putative clinicopathological tumour characteristics.
Annual Grant Scheme 2020
It is well established that human papilloma virus (HPV) associated oropharyngeal cancer (OPC) carries a favourable prognosis compared to non-HPV associated OPC. This is reflected in the most recent (8th) edition of the American Joint Committee on Cancer (AJCC) staging manual wherein HPV+OPC has a distinct TNM classification. Thus there exists potential for less intense treatment regimens for HPV+OPC; reducing associated morbidity while maintaining efficacy. However, a minority of HPV+OPC patients still have a poor prognosis. Therefore, there is a need for further prognostic indicators within the HPV+ cohort.
Tumour infiltrating T-lymphocytes (TILs) have been identified in recent studies as potential prognostic biomarkers for HPV+OPC. In this respect, TILs show promise in informing decision making and improving patient treatment but further research is needed to ensure this is a robust prognostic indicator.
Similarly, the presence of Programmed Death Ligand-1 (PD-L1), a cell surface protein that can be highly expressed on neoplastic cells, has correlated with improved survival in HPV+OPC patients in recent studies. However, as with TILs, further research is required to ensure its validity in clinical use.
Hence, this project draws on novel research and the addition of our data will help to further the understanding of HPV+OPC. Ultimately, this will enable improved treatment and outcomes for patients with HPV+OPC.
Annual Grant Scheme 2020
Dry eye disease (DED) is an extremely common condition, affecting 5-50% of the worldwide population. For those affected, symptoms can be chronic and progressive ranging from mild irritation, grittiness and stinging to debilitating painful and potentially sight threatening. Furthermore, currently available medications used to treat DED fall short of providing a cure or any long-term relief and are often accompanied with a myriad of side effects. Thus, our research focus has been the identification of the molecular pathways driving the pathogenesis of DED, and subsequently, the provision of targeted treatment strategies to restore homeostasis to the ocular surface.
However, developing safe, effective and patient-acceptable drug products is an expensive and lengthy process with high risk of failure at different stages along the development lifecycle. As such, the creation of robust biopharmaceutical tools replicating disease states to test potential therapeutics is crucial to prevent a stagnation of innovation along the drug development pipeline.
Herein, we propose through collaboration with the Tissue Engineering Research Group in RCSI, to adapt a hyperosmolar model using primary conjunctival epithelial cells, creating a 3-dimensional disease model of DED. In this we hope to better recapitulate an in vivo response to optimise our novel, targeted therapeutic aimed at re-establishing ocular surface homeostasis. Furthermore, the creation of such a facility will enable other researchers to reliably test drug efficacy, model therapeutic mechanisms of action, study off-target activity and resistance and thus improve in vitro-in vivo correlations of drug response, bridging the gap between pre-clinical DED therapeutics and patients care.
Dry eye disease (DED) is the most common patient presentation that ophthalmologists encounter, affecting 5-30% of the population aged 50 and over worldwide – this is more than that of Type II Diabetes, cancer, and heart-related problems.
In its mildest form, DED can cause discomfort, irritation and vision distortion. In its severest form it can cause ulceration, corneal damage and loss of sight. Regardless of severity, like many other eye conditions, DED has a serious adverse effect on the quality of life of patients.
This is a study of the network of small molecules (microRNA) on the surface of the eye which can inhibit the production of cellular proteins which cause inflammation.
With what we will learn from this research, combined with a newly formulated nanocarrier formulation already developed as part of this study, it is planned to develop a antagomir, or ‘blocker’ to prevent the production of the inflammation causing proteins and also encourage ocular repair.
Emily Greenan, Joan Ni Gabhann, Prof Conor Murphy and Christine Goodchild.
You can read more about the study.
Age-related macular degeneration (AMD) is the leading cause of central retinal vision loss worldwide. Over 100,000 people in Ireland, over the age of 50, suffer with AMD. New cases of AMD are diagnosed at rate of 7,000 per year and it is the country’s leading cause of sight loss.
The retina at the back of the eye allows you to perceive light and to convert light into a form of energy that allows our brain to form images. Essentially, the retina can be considered as an accessible part of the brain. Similar to the brain, the retina requires a constant supply of oxygen enriched blood and has an intricate network of blood vessels. These blood vessels are easy to see when an eye doctor examines your eye. The study being proposed will allow us to determine how these blood vessels may differ in integrity at various times of the day and how this might relate to the development of the common form of blindness in the elderly, namely, age-related macular degeneration (AMD). We hypothesize that discrete changes in these blood vessels with age, may pre-dispose some people to developing AMD during their lifetime. In understanding the basic mechanisms underlying this disease, we may be better able to develop new forms of therapy.
Dr. Alan Hopkins Dr. Alan Hopkins and Dr. Natalie Hudson presenting at ARVO 2019
There are an estimated 5000 patients in Ireland suffering from an inherited retinal disease (IRD). The goal of our collaborative study ‘Target 5000’, through genetic diagnosis, to better enable these 5000 individuals to obtain a clearer understanding of their condition and improved access to potentially life changing therapies.
There are up to 800 people living in Ireland with juvenile onset Stargardts disease, an IRD, is one of the leading causes of blindness in under 18’s worldwide and causes progressive loss of central vision.
It is most commonly associated with mutations in what is known as the ABCA4 gene. During the course of the Target 5000 study, researchers have identified many people who have mutations in ABCA4, however analysis has shown many of these do not correlate with the established pattern of well characterised Stargardts Disease previously known.
This exciting and important piece of research aims to combine the comprehensive clinical study of a patient’s genotype (from the inherited gene) and phenotype (a genetic reaction to an environment) to represent the full spectrum if ABCA4 disease in Irish patients.
Studies of this type are vital to developing a greater understanding of each syndrome and are crucial to ongoing pursuit of new genetic therapies for inherited conditions.
Dr. Niamh Wynne presenting a poster on her ABCA4 Study at ARVO 2019