Month: November 2019

Mark Humayun, MD, PhD and Amir Kashani, MD, PhD featured in Voice of America “VOA/TEK” episode highlighting their mission to restore sight

By Alexandra Demetriou

Anna Kuehl, a USC Roski Eye Institute patient featured on Voice of America's
USC Ginsburg Institute researchers were featured for their innovations to restore sight in a recent episode of Voice of America’s “VOA/TEK” (Image: still from “VOA/TEK” episode)

 Mark Humayun, MD, PhD and Amir Kashani, MD, PhD were featured on Voice of America’s “VOA/TEK,” a news program dedicated to highlighting the most cutting-edge technologies and medical breakthroughs around the world. The episode details the strides Humayun and his team have made in their mission to restore sight, the lasting impact of their innovations on patients’ lives and the research that continues to evolve at the Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics.

The episode opened with a feature on Anna Kuehl, a patient who regained her eyesight after receiving a stem cell-based retinal implant as part of a study at the USC Roski Eye Institute. Kuehl had suffered from progressive vision loss due to age-related macular degeneration (AMD), a disease that affects approximately 11 million Americans. She was diagnosed with the dry form of AMD, which causes a layer of cells called the retinal pigment epithelium (RPE) to die off. RPE cells are responsible for nurturing photoreceptor cells in the eye that enable proper eyesight. The loss of functional RPE and photoreceptor cells gradually blinds patients like Kuehl and, historically, there was little doctors could do to help.

Kuehl was one of a handful of people who participated in a clinical trial led by Kashani at the USC Roski Eye Institute, which used stem cells to grow new RPE cells for dry AMD patients. Kashani and Humayun implanted the brand-new cells, grown in a single layer on a biocompatible membrane, to replace the dying RPE cells in Kuehl’s retina.

“When they’re just-formed RPE cells, they’re as young and vibrant as they can get,” Humayun explains in the episode. “They’re incredibly resistant to stressors in the environment, which otherwise would kill older RPE cells. These vibrant, tough cells that we put in Anna’s eye were put in a very destructive environment –– of course, because that environment had killed her cells ­­–– so the question was, would these cells survive?”

The cells did better than survive. They restored Kuehl’s eyesight to the point that she could clearly see the faces of her loved ones once again. During her interview with “VOA/TEK,” Kuehl recalls the moment she first realized she was able see whole faces after the surgery, while she was watching TV: “I jumped back! I was so excited,” she recounts with a laugh.

Kuehl is one of hundreds of patients who have benefitted from the innovations Humayun and his colleagues continue to develop at the USC Ginsburg Institute. Another such patient is Terry Byland, the only person in the world to have two “bionic eyes.”

Byland has a genetic form of blindness called retinitis pigmentosa (RP), which initially causes tunnel vision and eventually leads to complete vision loss. The disease left him in total darkness for 26 years until he received an Argus I and later an Argus II implant, which feed visual information from a camera to the optic nerve to restore some eyesight. The tiny implants are placed inside the eye along the retina and allow patients like Byland to perceive some light and basic motions. The implants offer Byland practical benefits, such as noticing a car in front of him, as well as invaluable gifts, such as the opportunity to see the outline of his now 30-year-old son –– a sight Byland had last witnessed when the boy was only five.

There’s no doubt these implants have brought immeasurable benefits to patients’ lives, but they didn’t arrive at the clinic without challenges. Humayun describes creating the implant as “skiing uphill” because of the immense difficulty of the entire process, from determining what kind of electrical stimulation would produce vision to figuring out how to mount an implant in the tiny, delicate retina. It took an impressive feat of ingenuity and perseverance to develop the implants in the first place, and Humayun is determined to keep making progress. Recently, Argus patients in Korea have begun reporting that they can see the top letter on an eye chart –– a development Humayun finds promising and exciting.

In addition to enhancing the previously described implants, a brain implant based on the Argus platform is also in the works. This device, called Orion, sits directly on the surface of the brain to stimulate a region called the visual cortex. It is intended for patients who have damage to the nerve connecting the eye to the rest of the brain. A patient wears glasses with a tiny camera mounted on the bridge, similar to the glasses and camera used with the Argus retinal implant. As the wearer turns his or her head to take in the surroundings, the camera, instead of transmitting visual information to the implant on the retina, now directly transfers it to the brain implant.

Currently, the implants only sit on one of the brain’s hemispheres and transmit signals through 60 electrodes –– a small quantity compared to the number of signals the estimated 140 million neurons in one’s visual cortex can carry. Second Sight, the company that manufactured the Argus and Orion implants, hopes to eventually increase the number of electrodes, implant devices in both hemispheres and add features like heat vision to help patients identify their family, friends and pets. Six patients have received the Orion implants so far, and they are working with researchers and doctors to retrain their brains to adapt to this new modality of visual information.

“It’s been exciting because every time I come here, I get to see something,” says Benjamin Spencer, one of the Orion implant recipients, during one of his post-implantation testing visits. “It may not be full vision yet, but it’s something, and for someone who hasn’t seen anything in 25 ½ years, that is a huge accomplishment.”

To watch the full “VOA/TEK” episode, click here.

 

Disclosures:

Mark Humayun, MD, PhD, is a co-inventor of the Argus implant series.  He is a minority equity owner in Second Sight Medical Products, Inc. and receives royalty payment. 

The technology to produce the stem cell–based retinal implant is exclusively licensed to Regenerative Patch Technologies LLC from the University of Southern California, the California Institute of Technology and the University of California, Santa Barbara. Humayun has an equity interest in and is a consultant for Regenerative Patch Technologies LLC.

 

Economic analysis shows treatment for wet age-related macular degeneration generates billions of dollars in societal value

By Alexandra Demetriou

Researchers at the University of Southern California have developed an economic model to quantify the benefits of treatment for wet age-related macular degeneration (wAMD), the leading cause of blindness in western countries. Their work signals a step forward in the way ophthalmologists audit their practices to define the worth of modern treatments both to patients and society at large.

The study, led by Karen Mulligan, PhD of the Sol Price School of Public Policy and the USC Schaeffer Center for Health Policy & Economics, Seth Seabury, PhD, director of the Keck-Schaeffer Initiative for Population Health Policy and associate professor in the USC School of Pharmacy, and Mark Humayun, MD, PhD, director of the Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics and co-director of the USC Roski Eye Institute, was published on November 14th in the Journal of the American Medical Association (JAMA). This research represents the first analysis to quantitatively compare the economic benefits of therapeutic injections for wAMD to their costs and assess the value they bring to society. The researchers’ model showed that treating wAMD can generate $5.1 to $8.2 billion in patient benefit and $0.9 to $3 billion in societal benefit in three years based on the value of vision gains alone –– not including other potential benefits such as reductions in medical expenditure or caregiver burden. These numbers are poised to climb even higher if future innovations in health care can boost treatment initiation and adherence rates.

QUANTIFYING THERAPEUTIC VALUE

Wet age-related macular degeneration is a progressive form of blindness caused by the abnormal growth of blood vessels underneath the retina. A molecule called vascular endothelial growth factor (VEGF) drives this blood vessel formation, and doctors can treat the disease with a targeted therapy against that molecule to block blood vessel growth and restore patients’ eyesight for up to five years. Anti-VEGF therapy is largely successful when injected into the eye regularly, yet many people with wAMD never initiate therapy and studies based on Medicare beneficiaries have shown that approximately 53-58% of wAMD patients receiving treatment discontinue within the first year.1,2 Cost, fear of discomfort related to the injection process and the time-consuming nature of follow-up care all contribute to this problem, prompting many doctors to modify treatment schedules to minimize the number of injections a patient must receive without drastically compromising effectiveness.

Finding the balance between providing enough treatment and minimizing the burden on patients can be tricky, and until now it was made even harder by the fact that no one had previously quantified the benefits that anti-VEGF therapy provides for patients and society in exchange for the costs associated with treatment. In an era when health care expenditure is growing at an unsustainable rate and policymakers are looking to cut costs where possible, this situation highlights the importance of quantifying which therapies are most worth their investments.

Other specialties have started a movement of quantifying treatment value and comparing benefits to costs, prompting Humayun to help pioneer this paradigm shift in ophthalmology by partnering with public policy experts like Mulligan and Seabury to audit the field’s own practices.

AN IMPRESSIVE RETURN ON INVESTMENT

Humayun and his team started by combing through scientific literature and accruing model data of wAMD patients treated with anti-VEGF therapy. They translated the patients’ changes in visual acuity over time to “quality-adjusted life years,” which is an economic measurement that reflects both quantity and quality of years lived and could be used as a variable in the team’s economic model.

“Our model assumes a person with perfect, 20/20 vision has a quality of life that is valued at $150,000 for a single year,” Mulligan explains, referencing a commonly used value in health economics. “For a person who is diagnosed with wAMD, their vision is worse –– reflecting that, their quality of life is valued at about $105,000 for a single year,” she continues. “However, if they are treated with anti-VEGFs, their vision gains translate into nearly $11,000 in value after one year.  Put another way, a patient with wAMD would be willing to pay $11,000 for the improved quality of life associated with better vision from the first year of anti-VEGF treatments,” she summarizes.

The model reflected multiple treatment scenarios, all compared back to a “No Treatment” control group: patients in the “Less Frequent Injections” group who received approximately 8 injections per year, those in the “More Frequent Injections” group who received on average 10.5 injections per year (a number closer to drug-label treatment suggestions), and several different treatment innovation scenarios to reflect the gains that might occur if more patients initiate and follow through with treatment.

After creating this model, the team used it to simulate a range of possible patient outcomes based on each scenario and compared the benefits of each outcome to its associated costs.

Their findings overwhelmingly point to the vast economic benefits anti-VEGF therapies bring to patients and society as a whole, even in light of the drugs’ relatively high costs. For example, a single patient receiving less frequent injections for a five-year period can benefit from approximately $49,558 in economic gains, and a patient receiving more frequent injections during that time could witness $84,873 worth in benefits from improved quality of life.

The study further bolsters the case for increasing the number of injections per year, providing that patients respond well and experience meaningful vision gains from treatment. Their analysis shows that receiving less frequent injections accrues $873 million in population-wide value over three years while more frequent injections add $2.1 billion to societal value in three years even after accounting for the higher costs of performing more injections. Importantly, the study points out that innovations to improve treatment adherence could generate an additional $1.2 to $3.7 billion in patient benefit and $59 million to $1.3 billion in societal value compared to current treatment scenarios, highlighting the fact that when patients follow through with necessary treatment, both individuals and society as a whole can reap the rewards.

The researchers also demonstrated that if 100% of patients who needed therapy actually initiated treatment and only 6% dropped out per year (the dropout rate in clinical trial data), patients could benefit 42% more compared to simply improving treatment adherence and 89% more than they benefit from the current “Less Frequent Injections” model. In fact, in this “best case” scenario reflecting high rates of both treatment uptake and adherence, the three-year benefits could reach as high as $9.7-$15.0 billion depending on whether patients receive less or more frequent injections respectively.

Finally, the team pointed out that while politicians often scorn the high costs of anti-VEGF treatments (in 2015, Medicare Part B payed out $3.0 billion between just two anti-VEGF drugs), the team showed that relying more on a less expensive type of anti-VEGF drug known as bevacizumab could reduce costs for the full population by as much as $1.8-$2.2 billion over three years. Findings like these point to the importance of using economics to quantify the value of different therapies and auditing common practices in ophthalmology to optimize the way doctors approach treatment in a way that benefits patients and society at large.
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  1. Curtis LH, Hammill BG, Qualls LG, et al. Treatment patterns for neovascular age-related macular degeneration: analysis of 284 380 medicare beneficiaries. Am J Ophthalmol. 2012;153(6):1116-1124.e1. doi:10.1016/j.ajo.2011.11.032
  2. Lad EM, Hammill BG, Qualls LG, Wang F, Cousins SW, Curtis LH. Anti-VEGF Treatment Patterns for Neovascular Age-Related Macular Degeneration Among Medicare Beneficiaries. American Journal of Ophthalmology. 2014;158(3):537-543.e2. doi:10.1016/j.ajo.2014.05.014