ARVO poster area B. Roughly 1,000 new posters are displayed every day of ARVO.
See my notes from Sunday and Monday.
Patient Engagement in Ophthalmology Research
This special interest group discussed current methods of patient involvement in research and explored new ways this could be improved. A special emphasis was put on international policies, specifically in Europe and Canada. BC SUPPORT is one of the branches of the SPOR initiative across Canada meant to include patients and caregivers in research design. BC SUPPORT partnered with 42 different organizations (from hospitals to patient groups) to better achieve this goal.
Alastair Denniston highlighted the steps he takes to be a clinician who puts patients first. He always asks patients these two questions: “What would you like to get out of your visit today?” and “How are you doing?” Denniston encouraged ophthalmologists to acknowledge the power imbalance in the doctor-patient interaction. The default for some patients is to just say “I’m fine” because they feel uncomfortable. He wrote a great article titled “The patient is speaking”: Discovering the Patient Voice in Ophthalmology that I recommend checking out.
Leslie Low spoke next as a patient caregiver to three triplets who suffered from retinoblastoma. Her story is a difficult one, but she highlighted the importance of being an active participant in research and a resource for other parents of children with retinoblastoma. Sometimes patients do not want to be involved, potentially because they do not feel qualified to contribute or they do not want to bring back bad memories (both of which are perfectly valid reasons).
Another panelist talked about the difficulties in entering an underserved community and trying to help. Researchers should not go in and say “let me help you this way”, instead they should ask “how can we help you?”
Variable Nonsense mediated decay in CHM patients points to a prognostic indicator for nonsense suppression therapy - Mariya Moosajee
~30% of CHM mutations are nonsense mutations. This study sought to determine levels of CHM mRNA and if there is any pattern to the nonsense mediated decay in the patients. There was a high amount of variability even in patients with the same mutation.
Posters
Intravitreal Delivery of rAAV2 Vectors to the 13-Lined Ground Squirrel Retina - Benjamin S. Sajdak
This group used an engineered rAAV2 vector to administer mCherry fluorescent protein under a ubiquitous or cone specific promoter to newborn and adolescent squirrels. They found greater levels of inflammation in adolescent squirrels. Transduction of cone photoreceptors was most efficient in adolescent mice using the ubiquitous CBA promoter.
Novel Recombinant AAV Transfects Photoreceptor Cells Following Intravitreal Injection in Sheep - Maya Ross
This group showed videos of sheep treated six years ago with an intravitreal injection that have sustained vision. In their work here they used an engineered AAV2-7m8 (similar to the ground squirrel poster) and compared intravitreal to subretinal injections. Intravitreal resulted in expression in the ganglion cell layer, while subretinal targeted the RPE and photoreceptors better when using a CAG promoter. Using a cone specific promoter resulted in expression in the cones of both subretinal and intravitreal injections.
Suprachoroidal injections of AAV8 for ocular gene delivery in the nonhuman primate - Glenn Yiu
100uL of AAV8-GFP was delivered to Rhesus macaques via subretinal, suprachoroidal, and intravitreal injections. GFP expression was checked at 1 week, 1 month, 2 months, and 3 months. Suprachoroidal resulted in GFP expression at one week that peaked at 1 month and declined. This method primarily transduced the peripheral retina and did not hit the macular region very well. Intravitreal also resulted in peripheral expression. Subretinal resulted in robust expression in most cell types. Loss of outer retinal layers was seen in the subretinal injected mice.
Vector shedding and immunology measures in a choroideremia gene therapy trial - Alun R. Barnard
Barnard reported immunology results in 9 patients from a phase 2 clinical trial. Saliva, urine, tears, and blood was collected and assessed for the presence of AAV genomes at baseline, 1 day, 1 week, and 1 month post subretinal injections. They also performed ELISpot assays and assayed AAV2 NaB levels with a cellular assay. Only 2 samples were positive for vector: tears from patients 2 and 3 at 1 day post surgery. 3 patients had positive baseline anti-AAV2 antibody titres, and 2 of them responded with increased titres. To summarized, 4/9 patients had some level of response, but no patients displayed systemic symptoms or inflammatory adverse events.