Dr. Jesse Berry is Associate Professor of Ophthalmology, Clinical Scholar, and the Associate Director of Ocular Oncology at the USC Eye Institute at the University of Southern California and Children’s Hospital Los Angeles. In addition to having previously served as Associate Residency Program Director for the Los Angeles County + University of Southern California (LAC+USC) Ophthalmology Residency Program until 2018. Dr. Berry specializes in ocular oncology and has additional surgical expertise in cataract and comprehensive ophthalmology. She is the founder of WOO, Women in Ocular Oncology, and is a member of the Society of Heed Fellows. Dr. Berry received her undergraduate and medical degrees from Harvard University in Massachusetts.
Can you give us an overview of the amazing research you are doing on using the aqueous humor as a surrogate tumor biopsy for Retinoblastoma?
A liquid biopsy is when you use fluid, not tumor tissue, as a biopsy to evaluate for either circulating tumor cells or, as is the case with the aqueous humor, cell-free DNA which is shed from tumor cells. Most frequently, when you hear about a liquid biopsy, you hear people talking about blood. There are liquid biopsies for breast cancer, lung cancer and kidney cancer. You can also use urine for bladder cancer. So the idea that we’ve been exploring is whether or not you can use the aqueous humor, which is the clear fluid in the front of the eye in a separate compartment for where the retinoblastoma tumors form, in order to serve as a liquid biopsy or a surrogate tumor biopsy for retinoblastoma.
This is really important because most other tumors in adults and children can safely be biopsied. You can put in either a small needle or surgically do a biopsy on the tumors. You get the tumor tissues, the cells, and of course anything that goes along with that (DNA, RNA, other tumor markers). But with retinoblastoma, you can not directly biopsy the tumor. It is not safe to do so for the child because you can pull viable retinoblastoma cells outside of the eye. In fact, previous studies have shown that either purposeful (or more often inadvertent) biopsies of retinoblastoma tumors can cause the tumor to spread outside the eye which is a danger to the child’s life. So in general, we consider any direct biopsy of retinoblastoma to be unsafe and contraindicated. However, if the aqueous continues to show the promise that it has to serve as a liquid biopsy or a surrogate biopsy it would allow us to have access to tumor DNA and other tumor markers without ever touching the retinoblastoma tumor itself.
What are you looking for in the aqueous humor?
To date, everything that we’ve looked at in depth has been DNA-based. DNA is packaged into pairs of chromosomes inside the nucleus of cells. Normal cells have a pair of each of the chromosomes and we know that cancer cells can show changes in their chromosomal pairs. Tumor cells can have too much of some small parts of the chromosome (that’s called a copy number gain – indicating there are more than there should be) and some chromosomal regions can instead show a loss. Those gains and losses can actually drive tumor behavior. In our work we found a very interesting marker – a known region of chromosomal gain on chromosome 6p – which in our early studies has correlated with aggressive behavior clinically. More work needs to be done before identification of this marker in a patient can give a more clear prognosis to parents but it shows early promise. We are also looking at the retinoblastoma tumor suppressor gene mutations. In the future we hope to look at RNA and microRNA but for right now everything’s been DNA-based.
Where did the idea come from?
It was mostly serendipitous. I work at Children’s Hospital Los Angeles (CHLA) which is one of the largest retinoblastoma centers in the country – we see a lot of patients which is important given how rare the disease is. We were doing an injection of chemotherapy on a patient and one of the first preparatory steps to make the procedure safe is to remove a small amount of the aqueous humor fluid from the front of the eye to help ensure the proper balance of pressure in the eye once the chemotherapy is injected. I was explaining to one of our trainees how amazing this is and how novel it is and how much it has changed our field that we can now place a needle directly into the eye with retinoblastoma and inject the chemotherapy as a treatment for vitreous seeds at the back of the eye.
While I was talking, we discarded the aqueous fluid into the biospecimen container and I suddenly had this idea that perhaps we could find more information regarding the tumor in the aqueous? So we’ve been studying it and there’s all sorts of fascinating data in the aqueous. We’re finding a lot out about how retinoblastoma behaves in these eyes because of the aqueous.
What do you see as the long term potential for the Liquid Biopsy procedure for children with RB and beyond?
While it is still solidly in the research stage, I hope that in time it will serve as a prognostic tool for retinoblastoma. It is my hope that we will continue to find more markers of aggressive disease, possibly even markers of invasive disease – something that can be very hard to determine clinically, and I’m hoping that markers will be help us determine how we treat these kids and how likely these eyes are to respond to certain therapies. That is my overall goal, and I will tell you that I already have secondary goals of diagnosing every RB1 mutation(s) from the tumor as well. We’ve already had some tremendous success with that, but I’d like to be successful in every kid every time. Also in the future, if we do really elucidate some good markers of aggressive disease, that could allow us to start to look at the mechanism – Why is one tumor more aggressive than another tumor? That will allow us to think about new methods and new targets for retinoblastoma treatment as well.
You’re on the Program Committee for the International Society for Ocular Oncology (ISOO) Conference 2019…What does this conference mean for families out there being treated for RB?
My partner, Dr. Jonathan Kim, and I bid in 2017 in Australia to run the International Society for Ocular Oncology conference in Los Angeles. We were elected by our peers in the society to do so and we have spent the last two years planning this very exciting conference. It brings together nearly 400 actively practicing ocular oncologists, medical oncologists, pathologists, and ophthalmologists from around the world. There are 40 countries represented this year and we received a record number of 350 abstracts submitted which has been great. We focus on all ocular and periocular tumors, but of course, we have a specific focus on retinoblastoma. In the five-day conference, we dedicate one entire day to it. We talk about the new science that’s emerging and we’re able to share clinical techniques with our colleagues from all around the world. We discuss difficult and unique cases and bring expertise from the whole globe together to specifically discuss these diseases.
You’ve been a big supporter of Know The Glow for years. As a physician, but also as a mother-to-be, how important is sharing awareness about the Glow and how beneficial is early detection for your patients?
Know The Glow (KTG) serves a very important role in the retinoblastoma and glow-related disease communities because you talk directly to the people who most often make the initial diagnosis of retinoblastoma and that is parents! Parents are most often the ones that first notice that there’s a change or a glow in the eye.
Because of KTG, more parents have been exposed to the PSAs and the important information about the glow. More parents know that there is something that is not normal about a child who exhibits a glow (scientifically termed “leukocoria”) in either photos or dim lighting and they then bring their children in for care sooner. I’m always so grateful when I have a parent who says, “I heard about the glow, I heard that it was abnormal, I saw it in my child and I brought him in.” I do think in just the last few years of my practice, I’ve noticed more and more parents coming and saying, “we heard about the glow” and “we want our child checked because we’re noticing something funny that keeps occuring in their eye.”
Like many diseases, early diagnosis can be extraordinarily helpful for the patient and that is definitely true for retinoblastoma. The smaller the tumor, the easier it is for us to treat. The faster these parents are able to have their children seen the better. We still often see advanced disease in eyes, but they’re not as advanced as they would otherwise be.
As a mother to be, I can say that this kind of critical health-related information can’t be undervalued or underestimated. The power that parents have in terms of being healthcare advocates for their children is really striking and so the more KTG can do to get that word out, the better it is for us as doctors charged with taking care of these patients because the kids will receive care earlier and parents will be better educated about exactly what is happening with their child’s eyes.
What do you like most about being an ocular oncologist?
One of the things that I absolutely love about being an ocular oncologist is that I get to treat adults and children and I get to operate on different parts of the eye. That’s really exciting for me. Obviously, I am incredibly fascinated with retinoblastoma. I absolutely love treating this patient population. These kids are incredible, resilient and responsive, and you develop a really special long-lasting relationship with these families. I’m very appreciative of that.
You would never find me in a place where I couldn’t be actively treating retinoblastoma because of how much I love the work and how exciting I think the future is for this field, particularly with some of the current liquid biopsy research. Additionally It is also really special to have the opportunity to operate on adults and perform surgeries and procedures from the front of the eye to the back of the eye. It makes ocular oncology really exciting, challenging and rewarding.
I really do love what I do. I say that all the time that you’ll be happiest in your career if you love what you do and I take that to heart because I think it’s what keeps me going every day. I am very very passionate about the work that I do both in the lab and in the OR and I leave work every day knowing I’ve made a real difference in the lives of each of my current patients and also knowing I am making an impact in this field as we prepare for tomorrow’s children.