 Rene is presenting in absentia. Rene Choi is another of our senior residents. He is not here at the moment but did take care to have his presentation videotaped and he's going to give it in absentia. Rene is going to talk to us about fish oil supplementation in Stargardt's and Rene is off to do a UBI to fellowship at the Oregon Health Sciences University in Portland next year. Hello everyone. I apologize for not being able to be there today but I'm still excited to be able to present my research to you all through this prior recording. The title of my talk is long-term follow-up of autosomal dominant Stargardt macular disher fee subjects enrolled in a fish oil supplement interventional trial. To begin my talk I'd first like to briefly go over what exactly are the Stargardt macular disher fees. They are a group of early onset disorders characterized by macular atrophy and subretinal flex that lead to central visual loss typically in the first or second decade of life. Autosomal recessive Stargardt macular disher fee is the most common form and it is due to mutations in the ABCA4 gene whose protein product is involved in the transport of retinoids from the rod outer segments. There is another type of Stargardt known as autosomal dominant Stargardt macular disher fee. It is clinically indistinguishable from the autosomal recessive form as it is characterized by loss of central vision in the first and second decades of life. Progressive macular atrophy with or without yellowish fundus flex. There's a large phenotypically diverse range from near normal to pattern disher fee to a classic Stargardt appearance. This disease entity was first described by three independent research groups as resulting from dominant mutations in the ELOVL4 gene. So what exactly is ELOVL4 responsible for? Well it codes for a protein that is involved in the elongation of fatty acids. Thus it in turn stands for elongation of very long chain fatty acids. The ELOVL4 gene has been shown to be expressed abundantly in photoreceptor cells of the retina and to a lesser extent in the brain, testes and skin. Now to understand the importance of ELOVL4 in dominant Stargardts we have to cover what exactly very long chain polyunsaturated fatty acids are. I'll be referring to these as PUFAs for the remainder of my talk. So they are defined as cellular lipids that contain 28 to 40 carbons. They are found exclusively in the retina and testes. In the retina studies have shown that PUFAs are involved in photoreceptor membrane fluidity and structural integrity of its discs. Now PUFAs are considered essential fatty acids because they must be obtained from dietary sources. Thus a PUFAs such as Dekosa hexanoic acid or DHA can either be obtained as preformed dietary DHA or elongated in the body from shorter chain PUFAs such as Icosa pentanoic acid or EPA and this is done by the enzyme ELOVL4. Studies have shown that ELOVL4 dysfunction and loss of the PUFAs occurs in dominant Stargardts. Of note PUFAs have also been shown to be depleted in eyes afflicted with macular degeneration. A prior study performed by our group showed that in patients part of a kindred with the ELOVL4 mutation there was an inverse correlation in phenotypic severity of dominant Stargardts and blood levels of DHA and EPA as well as fish consumption. Thus the observations from this study showed that individuals who consumed fish regularly had the mildest phenotype. Another case study showed that dietary DHA supplementation transiently improved the multifocal ERG and visual acuity in a 14-year-old patient with dominant Stargardts. Therefore we naturally asked does increasing DHA and EPA consumption using fish oil slow the progression of dominant Stargardts disease? To help answer this question we enrolled 11 adult patients with dominant Stargardts in an 8-year open label prospective study. They were instructed to take a thousand milligrams daily of fish oil supplement containing EPA and DHA. Each year we performed a complete eye exam, blood serum lipid analysis, a questionnaire, contrast sensitivity testing, multifocal ERG and retinal imaging including color fundus photos, fundus autofluorescence, as well as OCT. At this point of my talk I'd like to report that we unfortunately had issues with compliance. Three subjects never followed up after the initial visit. The other eight subjects returned whenever they wanted over an eight-year period and only four subjects reported that they took fish oil supplements regularly. Considering the global lack of compliance there still was no significant change in best corrected visual acuity over the eight years. This was also the case for contrast sensitivity testing. And our serum markers for fish oil ingestion were highly variable and here are the results of the red blood cell EPA levels with time. And here are the results for the red blood cell DHA levels with time. These results are consistent with the lack of compliance in the majority of our patients. All of our patients showed varying levels of an attenuated response in the macula of both eyes at the beginning of our study as measured by multifocal ERG. And we were able to track progressive worsening of the disease using multimodal imaging. Here the fundus autofluorescence images highlight the increase in the number of flecks and progressive enlargement of the area of the macular atrophy over time. Here is another fundus autofluorescence image showing progressive enlargement of the area of macular atrophy over time as well. So in summary we were not able to draw conclusions about fish oils impact on the progression of dominant stargarts due to marginal compliance, irregular follow-up visits, small sample size and inability to randomize the patients as none of the patients wanted to join the study if they had the chance of being in the control group. However we are able to confidently state that the fundus findings including macular atrophy and paraphovial whitish flecks are consistent with the results from a recent study that used multimodality imaging to characterize dominant stargarts. We have no future clinical trials planned. However, gleaning from our previous studies we do still recommend that dominant stargarts patients focus on improving fish consumption in the next generation before macular pathology becomes apparent. As the old proverb states, give a man a fish and you feed him for a day. Teach a man to fish and you feed him for a lifetime. I'd like to conclude by saying, give an adult patient with dominant stargarts a fish or fish oil and he still won't eat it but teach a child with dominant stargarts to eat fish or fish oil and he might not go blind. Before I finish I'd like to briefly go over my QI project. I'm developing an electronic sign-out program for follow-up studies and tasks in the VA neurophomology clinic. The reason being there's no mechanism for sign-out at the VA and patients have pending labs and imaging studies that need close follow-up. This is especially important at the VA where there is a high turnover of residents. We have completed the design of the program and we'll be installing the program until all resident computers. The primary goal of this study is to improve continuity of care for our VA patients. Here are my references. I'd like to thank Dr. Bernstein for allowing me to be part of this project as well as Dr. Garcipputi for her help with the lipid analysis and lastly but not least Ethan Peterson for allowing this prior video recording to happen. Thank you. Thank you very much for your time and consideration guys and I'd be happy to take any questions via email. Thank you again.