Panorama view from Whistler Mountain.
These notes from Thursday May 2, the last day of ARVO 2019. The conference had thinned out a bit as some people had to leave, but there were still some presentations of interest. You can read a summary or my notes from the other days here: Friday, Sunday, Monday, Tuesday, and Wednesday.
Subfoveal gene augmentation therapy for choroideremia: One-year results from a Phase I/II trial of AAV2-hCHM - Rachel M. Huckfeldt
Dr. Huckfeldt presented results from an extension of the clinical trial which Thomas Aleman presented on Wednesday. They treated 5 more patients (between the ages of 20 and 32) with better vision than Aleman’s cohort with a high dose of virus. This study unfortunately had a serious surgery related complication in one patient. During the surgery he developed a macular hole which caused his central vision to decrease from 20/20 to 20/80 at 1.5 years from surgery. Subretinal injections are “safe” most of the time, but this is a sobering reminder that there is always a risk. Everyone involved hates to see an event like this particularly in a patient this young. A slow degenerative disease like choroideremia is a rough thing to go through, but this shows that we still do have something to lose when enrolling in clinical trials. My heart goes out to they young guy involved in this clinical trial.
Besides this unfortunate complication, the rest of the trial was safe without any inflammation in the patients. Visual acuity change between treated/untreated eyes and baseline was almost identical (-0.6 and -0.5 letters respectively). The same was found during microperimetry. Further monitoring is needed to determine if the gene therapy has any effect.
Quantification of RPE changes in choroideremia using a Photoshop-based protocol - Yi Zhai
In this study fundus autofluorescence area was measured using the Photoshop quick selection tool. I am always in favor of new, easy ways to study the disease, but I do worry a little that this method is not exactly reproducible. Software is often a moving target so I don’t expect there to always be perfect reproducibility, but it would have been good to at least include the version of Photoshop that was used for this analysis. The difference between graders was was 0.46 (+/- 0.99) mm2. They found an intraclass correlation coefficient of 0.980 between RPE areas as determined by the 2 graders.
Development of a Rapid and Cost-Effective CRISPR-based Molecular Detection Platform for a Novel Myocilin Mutation in Rural Philippines - Edward Ryan Collantes
This was an interesting poster showing the use of CRISPR as a diagnosis tool (termed SHERLOCK by its creators.) This method of diagnosis is a little limited in that you need to know the mutation you are looking for beforehand. Regardless it is always exciting to see cutting edge research being applied in an extremely cost-efficient manner (overall cost was $2) to help in a real way. Too much of research is theoretical and does not end up having a real impact. This method of diagnosis is useful in remote areas where a full diagnostic laboratory is not available.
During a discussion on the immune system and gene therapy, the topic of empty viral capsids came up. Peter Francis from 4D Molecular Therapeutics had the opinion that you want to minimize the amount of empty capsids to reduce inflammation. Paul Sieving cited Kathy Hyde’s opinion that empty capsids are actually a good thing and reduce the immune response during gene therapy. I had not heard this opinion before and want to dig into it more. I will most likely write something in the future about what I find.