BUSNA Supported Research
BUSNA raises funds for Birdshot specific research from direct donations, Giving Tuesday contributions, T-shirt sales and from Facebook Birthday fundraisers. Many thanks to those in our community who have made valuable contributions.
Since its inception in 2020, BUSNA has contributed a total of $41,915 to various Birdshot research studies
Dr. Jennifer E. Thorne Update - December 2024
Birdshot Research Fund
Meredith Cross, was diagnosed with birdshot chorioretinitis in 2012 and generously established the Birdshot Research Fund in 2013 to begin to address the problem that birdshot research dollars are as rare as the disease. With more than 250 donations from 122 donors to date, Dr. Thorne and her colleagues at the Wilmer Eye Institute use the funds for birdshot research projects, including many in collaboration with birdshot experts at other universities around the world.
Projects Supported:
IMAGING STUDIES
We have been collaborating with five centers and have collected imaging data on 95 patients. We are correlating retinal findings on imaging with patient symptoms and demographics, treatment, visual function, and clinical exam findings. These papers were published in the IOVS. We are thrilled to have moved forward on a newer imaging modality, called OCT-angiography, which is a way to analyze blood vessels in the retina and choroid without injecting dye into patients. Our first investigation was published in Ocular Immunity and Inflammation (OII). We are now working with other collaborators to expand on earlier findings. With our Paris collaborators we have submitted a paper investigating a finding around the optic nerve called peripapillary atrophy which has been underreported in birdshot disease but occurs in nearly 100% of patients with more than 5 years of disease duration. Furthermore, a new international project that aims to standardize the imaging used in a variety of posterior uveitic diseases including birdshot is underway and will further define birdshot characteristics using multimodal imaging and to distinguish these findings from other “white spot” diseases; thus, speeding diagnosis of birdshot and improving our understanding of which imaging modalities are best for monitoring birdshot. The consensus meeting for this project occurred in Singapore in November of this year. The first paper is accepted in OII and a series of 5 papers are being prepared for inclusion in the American Journal of Ophthalmology(AJO).
PARIS COLLABORATIONS
We continue to collaborate with birdshot specialists in Paris to examine the visual outcomes, treatment outcomes, visual field analyses, imaging analyses, quality of life, and natural history of the birdshot disease. This is a unique opportunity in the study of birdshot given the long duration of observation. This collaboration has and will continue to dramatically increase our understanding of the natural history and pathogenesis of birdshot, which should enable us to make real progress in the successful treatment of patients. We published a paper in OII describing the visual outcomes of patients over the age of 80, many of whom had birdshot for more than 30 years. Fortunately, 75% of patients retained driving vision over the age of 80. We have now published the quality-of-life outcomes of the same patients aged 80 and above in OII and found that most patients maintained a good enough visual acuity to support the majority of activities of daily living. Another paper, in revision at the British Journal of Ophthalmology (BJO), explores the visual acuity and visual field outcomes of patients at various stages of disease duration. Our next paper aims to describe a very small subset of patients with birdshot—those that don’t require any systemic therapy and appear to not have progression of their disease. Understanding this group of patients more may help us better determine who requires aggressive treatment and who does not. The analyses of this paper are completed and hopefully the paper will be completed in the upcoming months. Finally, the BJO has invited us to write a review of birdshot chorioretinitis that we have begun drafting.
GENOMICS
Our team is diligently looking for genetic markers other than HLA-A29 in birdshot. This involves a massive amount of data to be analyzed, and so we are very happy to be collaborating with doctors from Harvard and our Paris collaborators. We are currently collecting data from our patients with added help from BUSNA—a patient-run support group of patients with birdshot whose enthusiasm for this project has been invaluable. Our Paris collaborators have a paper in press describing the patients that have inherited HLA-A29 from both parents. They have found that these patients were at higher risk of developing birdshot than those patients that inherited A29 from only one parent, BUT their disease was not more severe.
OTHER COLLABORATIONS
Our team collaborated with doctors from across the US to describe the occurrence of optic nerve swelling as a presenting sign of birdshot disease—a finding that is commonly underreported and overlooked. The paper was published in the Journal of Neuroophthalmology. Lastly, we have completed our data collection for a multicentered study looking at the outcomes of an injectable corticosteroid called Yutiq in the treatment of birdshot chorioretinitis and look forward to working on the manuscript once the data analyses are completed.
Dr. Shilpa Kodati
Dr. Shilpa Kodati’s research group at the Kellogg Eye Center, University of Michigan, is studying mechanisms underpinning inflammatory eye diseases. Using techniques such as single-cell RNA sequencing, immune repertoire profiling, bulk RNA sequencing and proteomics, her group aims to characterize different uveitic diseases on the basis of their molecular signatures, understand why some patients respond to a given treatment and others do not, and study the role of the gut microbiota in uveitis.
To address these questions and ultimately develop precision medicine approaches to treating uveitis, Dr. Kodati has set up a dedicated biorepository to collect blood and fecal samples from patients with uveitis.
Specific projects include:
- Characterizing changes in the retinal microvasculature using optical coherence tomography angiography (OCT-A) in Birdshot Chorioretinopathy. These findings were recently published in Ophthalmology Science (Ophthalmol Sci. 2024 Jun 17;4(6):100559. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334704). Our results demonstrated a decrease in vessel density in eyes with birdshot chorioretinopathy compared to healthy volunteers and a greater decrease was observed in those with longer disease duration. These findings suggest the vessel density may be helpful in monitoring disease severity.
- Investigating changes in the gut microbiota and metabolome in non-infectious uveitis. The contribution of the gut microbiome and their metabolites to the development of autoimmune diseases is increasingly being recognized. Recent evidence suggests that alterations in the gut microbiota in certain systemic autoimmune diseases are associated with disease flares, and that restoration of altered microbiome composition occurs following treatment of the disease. Like autoimmune diseases affecting the body, the gut-eye axis has been implicated as an important factor in eye inflammation. However, comparatively less is known about the gut microbiome in the development of uveitis, and to date, longitudinal studies are lacking. Thus, the overall goal of this study is to investigate how the gut microbiome and metabolome change with disease activity in non-infectious uveitis, including in diseases such as Birdshot Chorioretinopathy. An improved understanding of these changes will inform precision medicine approaches in uveitis and potentially facilitate modulation of the gut microbiota as a therapeutic strategy.
- T cell receptor profiling in Birdshot Chorioretinopathy. Using single-cell sequencing with immune repertoire profiling of blood samples, we are aiming to identify the specific populations of self-reactive T-cells in Birdshot Chorioretinopathy with a goal of ultimately selectively targeting these self-reactive T-cells to treat this disease.
Dr. Lynn Hassman
Dr. Lynn Hassman is a clinician-scientist who focuses on developing precision medicine approaches for uveitis, a complex group of inflammatory eye diseases. Her research combines advanced techniques like single-cell RNA sequencing, immune receptor profiling, and genetic analysis to uncover the immune and molecular causes of uveitis and related eye disorders. Her team was the first to perform single-cell RNA sequencing on immune cells from the eye, revealing distinct immune mechanisms across different forms of the disease. Dr. Hassman has built a biorepository of clinical data and biospecimens from over 1,500 uveitis patients, which is essential for her translational research efforts. Currently, her lab is working on creating recombinant antibodies from patient samples to identify the antigens that trigger inflammation in the eye. She also leads a collaborative project with Dr. Isaac Harley, a rheumatologist-geneticist, to explore the genetic risk factors for uveitis in diverse populations. Specifically, her team is working on identifying genetic differences between patients with birdshot uveitis and their unaffected family members. Dr. Hassman has published her work in leading journals such as Nature and Ophthalmology Science and is a frequent speaker at national and international conferences, including the International Ocular Immunology Society and the American Uveitis Society. In addition, she mentors early-career clinicians and scientists.
Dr. Jennifer E. Thorne
Meredith Cross, who was diagnosed by Dr. Jennifer Thorne with Birdshot in 2012, established the Birdshot Research Fund in 2013 to begin to address the problem that Birdshot research dollars are as rare as the disease. With more than 105 donors to date, Dr. Thorne and her colleagues at the Wilmer Eye Institute use the funds to conduct a variety of Birdshot Research projects, including many in collaboration with Birdshot experts at other universities.
Supported research:
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Through collaboration with five centers, we have collected imaging data on 95 patients and are correlating retinal findings on imaging with patient symptoms and demographics, treatment, visual function, and clinical exam findings. We are optimistic that the results of this research will benefit Birdshot patients in the future by providing enhanced imaging that will allow treating ophthalmologists to see active inflammation sooner in the disease course and treat the inflammation more aggressively and completely in the disease’s earliest stages.
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We are collaborating with Birdshot specialists in Paris to examine the visual outcomes, treatment outcomes, visual field analyses, imaging analyses, quality of life, and natural history of the disease. This is a unique opportunity in the study of Birdshot given the long duration of observation. We hope that this collaboration will dramatically increase our understanding of the natural history and pathogenesis of Birdshot, which should enable us to make real progress in the successful treatment of patients.
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Our team is investigating the likelihood of drug-free remission in Birdshot. We presented these results at the Association for Research in Vision and Ophthalmology (ARVO) meeting in Vancouver this year.
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Our team is diligently looking for genetic markers other than HLA-A29 in Birdshot. This involves a massive amount of data to be analyzed, but while the progress is slow, it has been steady. Although similar to searching for needles in haystacks, this is among the most exciting work being done at Johns Hopkins, and hopefully, we will be able to add to the knowledge in this arena.
Dr. Larissa Derzko-Dzulynsky
Dr. Larissa Derzko-Dzulynsky and her colleagues at the University of Toronto Department of Ophthalmology and Vision Sciences (DOVS) aim to apply single-cell RNA sequencing, (scRNAseq), in their investigations. This technology enables discovery of disease-relevant cells for immune-mediated diseases like BSCR. They look for cells that are important for BSCR by comparing scRNAseq profiles of immune cells from people with active disease and those with remission of BSCR. In order to understand the behavior of immune cells, they also measure cytokine levels in these same blood samples.
Dr. Lynn Hassman
The goal of the Hassman’s Uveitis Lab at Washington University is to characterize patient- and disease-specific mechanisms of eye inflammation with the goal of developing precision medicine treatment strategies. Dr. Lynn M. Hassman and her colleagues use advanced molecular tools (like single cell RNA-Sequencing) to analyze the immune cells and molecules from their patients.
Washington University in St. Louis School of Medicine - Ophthalmology research
Dr. Lucia Sobrin
Dr. Lucia Sobrin and her colleagues at Massachusetts Eye and Ear are committed to research to further understand and better treat birdshot uveitis. Their projects are focused on Fluorescein angiography leakage patterns in birdshot uveitis and genetic risk factors for birdshot patients.
Dr. Sobrin’s study protocol allows patients from outside of Massachusetts Eye and Ear to provide a blood sample for DNA extraction. If you are interested in participating in the study, details are included in the research summary.
Harvard Medical, Massachusetts Eye and Ear, and Massachusetts General Hospital research
Dr. Marie-Josée Aubin
Dr. Marie-Josée Aubin and her colleagues at the University of Montreal Department of Ophthalmology are studying how ERG and OCT can be used to detect early signs of Birdshot chorioretinopathy. This could allow doctors to initiate treatment earlier and better monitor treatment response to limit damages to the vision of birdshot patients. They are also establishing a Biobank for Uveo-Retinal Diseases