The second article I wrote about ARVO 2018.

CRF Special Interest Group at ARVO 2018

The CRF organized and hosted a special session at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) to discuss Choroideremia. This special session, organized by CRF president Dr. Chris Moen, was attended by over 100 researchers and clinicians. The discussion featured a panel consisting of Dr. Jacque Duncan, Dr. David Birch, Dr. Ian MacDonald, Dr. Robert MacLaren, and Randy Wheelock, and was moderated by Dr. Mark Pennesi. The inclusion of a patient representative, Randy Wheelock, on a panel at ARVO shows that the organization is taking steps to further include patients in the conversation about treatments and the goals of those treatments. Short talks were given by each panelist as a jumping off point for the main discussion. The question at hand was “What are the most reliable and meaningful measurements to use in patients with Choroideremia to determine the success of a clinical trial?” The discussion was nuanced with the upsides and drawbacks for different techniques brought up.

Clinical Endpoints

The current primary measurement that has been used in clinical trials is visual acuity (how many letters you can read on an eye chart.) This has proved especially useful when treating older men with more severe vision loss. Because their visual acuity is less than 20/20, improvements can be measured and the untreated eye usually loses some acuity over the measurement period. This measurement has also been historically accepted by the FDA, so there isn’t a need to validate a new protocol. The downside of using visual acuity as a measurement should be obvious to anyone with CHM or with a family member affected by CHM. The first and main cause of disability is the loss of peripheral vision, which begins to deteriorate early on in life. The eventual loss of visual acuity is also catastrophic, but this occurs much later in life. If clinical trials are going to accept younger patients with good (close to 20/20) visual acuity then researchers will need another technique to measure the effectiveness of a therapy. The general consensus was that visual acuity can’t continue to be the one and only clinical trial endpoint, while Dr. MacLaren emphasized its importance in moving current clinical trials forward. He encouraged researchers to not lose focus of the goal of moving the treatment through clinical trials and into patients.

Randy Wheelock, science advisor to the CRF, has long been a champion of using anatomic endpoints in clinical trials. Anatomic endpoints can be measured using specialized cameras to image the retina and determine what areas are healthy and what areas have died. This is an objective way to measure the effectiveness of treatments, but it doesn’t come without its limitations. Areas of healthy retina correlate with vision (since you can’t see without a retina) so if the retina is preserved then vision should be preserved as well. There are advanced techniques, called adaptive optics, which enables researchers to images individual cells and determine how many remain. This specific technique is limited by availability and uniformity, since there are only a handful of these systems in the US, and they are mostly custom built.

Another way to measure the progression of disease is to test the patient’s functional visual field. This is usually done by shinning a small light around a bowl and having the patient trigger when he can see the dot. This reveals the size and shape of the blind spots in a patient’s field of view. Over time these blind spots increase in size and tunnel vision develops, so researchers should be able to see if a therapy halts this progression.

Anatomic measurements and visual field tests are great tool, but they are not without their limitations which were discussed. If the same person was tested multiple days in a row there is a substantial amount of variability. The visual field test is somewhat subjective and can fluctuate depending on how the patient is feeling. Additionally, if a subretinal injection is used to deliver a therapy some damage is likely to occur in the retina. If anatomical measurements are used, this surgery-induced loss of cells could cause the clinical trial to fail, even if the patient’s visual field is preserved and they have an increased quality of life.

These issues were discussed between panelists and audience members over the period of an hour. The discussion was open-ended and no consensus was reached, however it was still a very productive meeting. From a patient’s perspective, the attention that was given by all of these researchers on a rare disease was exciting to watch.