As we ring in what will be our 3rd full year of releasing episodes of Straight From The Cutter’s Mouth: A Retina Podcast, I would like to start by taking a moment to thank a few people who make possible our weekly episodes releases.

First, Dr. Louie Cai is our webmaster extraordinaire, incredible producer, and technological Swiss army knife who keeps our endeavor a well-oiled machine. It is not hyperbole to say that he is one of the most important people to ever enter my life. Angela Chang is an audio editing machine who is quiet and unassuming and deserves major credit for taking our moderate quality recordings and turning them into the polished product hitting your phone every week. Mike Venincasa handles our social media distribution on Facebook and is our main contributor to the blog, where he has started a new project with our latest recruit, Amy Kloosterboer. Many of our episodes would be impossible without frequent contributors like my colleagues Dr. Ajay Kuriyan (podcast MVP three years running), Dr. Daniel Chao, Dr. M. Ali Khan, Dr. Will Parke, and the others who I bother week after week to join me on conference calls at odd hours built around multiple busy retinal surgeon schedules. Finally, it may sound corny every time I state this at the end of each episode, but all of the people who listen and tell their friends, colleagues, and trainees to listen make this experience special. It is the ideas and thoughts of listeners that continue to keep us fresh and motivated with new and thoughtful episode ideas.

Listeners and others ask frequent questions about our podcast, and I will use this blog post to both answer some frequently asked questions (FAQs) and transparently address some of the recent changes surrounding our project:

Why did you start the podcast?

We have addressed this in a few of our ‘state of the podcast’ episodes, but to summarize: leaving fellowship I anticipated joining a job that involved significant commuting, as many surgical retina jobs do. As a newly minted podcast consumer in other disciplines, I searched for a retina resource that could be educational on the go and came up mostly empty. One of my faculty mentors suggested that I pursue such a project myself, but it was not until months later when my friend Dr. Will Parke suggested that I pursue it as a solo venture that we got started. I spent a week reading about podcasting and audio recording on the Internet, obtained the necessary equipment, website, and software, figured out how to release via iTunes and social media, and then released the first episode on November 1st, 2016. It became immediately apparent that a completely solo venture would be impossible as my clinical and academic obligations continued to evolve, and within two weeks Louie Cai was on board running the website and producing the episodes. The rest is history as both our team and listener base have grown steadily over two plus years.

What about money? Who pays you to do the podcast?

Nobody. Making money off the podcast is a concept many friends and colleagues have asked me about, but it was never a primary motivation. Our team has discussed this issue multiple times, and to this point we unanimously have agreed to keep the podcast focused on a different goal: releasing useful, educational, consumable, permanent content that can be both a current resource and a repository of retina knowledge for years to come.

What about your costs?

Maintaining the website is roughly $100/year, software/audio licenses another approximate $250/year, and equipment averages $500/year to this point. Recently we have added legal protections with costs of about $3000. There are certainly major times costs to what we do as well. I have independently covered these costs through the end of 2018.

What about Retinal Physician, ASRS, and AAO? How are they supporting you?

We have been extremely grateful to these organizations for their support, but to answer a common question, none of that support has been or will be financial. Retinal Physician provides us their article proofs in advance so we can record periodic episodes that are different than our normal journal club episodes in allowing our contributors to take discussion in different and more creative directions. The American Society of Retinal Specialists (ASRS) generously offered to upload our episodes in a special podcast section of their website for members as a resource. The American Academy of Ophthalmology (AAO) is uploading and posting our episodes on their website as a free resource as well, with the upcoming added benefit of continuing medical education (CME) credits for certain episodes.

When will the CME be available? What about financial disclosures?

Probably early in 2019. The team at AAO has worked tremendously hard to obtain CME not only for the new episodes but for past episodes that qualify. As soon as we have details we will post prominently on the website and mention in the episodes themselves.

In preparation for the CME transition we are now including financial disclosures for all contributors to each podcast episode. Even if this was not required by CME, we were moving in this direction, as transparency in this day and age is paramount.

How do you plan to cover your costs going forward?

We are initiating a few new ventures. First, similar to Wikipedia and other free online resources we will soon be placing buttons on the website for people to contribute small dollar amounts either one time or monthly to support the podcast. Second, we are investigating making and selling podcast ‘swag’ including T-shirts and other apparel for the loyal supporters who have asked. Third, we will be rolling out limited advertisements before and after episodes, although I have an extremely strong preference to avoid ‘mid-roll’ advertisements that disrupt the flow of the episode/conversation.

What about these future advertisements? Isn’t that a conflict of interest?

Industry is critical to the development and advancement of our field, and myself and many others who contribute on the podcast have industry ties and disclosures. That being said, we have and still will continue to try and avoid any industry (pharmaceutical or surgical device) advertisements on our program. One of the things that makes doing the podcast so enjoyable is the freedom of discussion and we think staying industry-free helps maintain that environment.

We will be rolling out our first ever paid episode advertisement in Episodes 148-151 on behalf of a retina-only private practice looking for a new associate on partnership track. The practice approached us with the idea and I accepted. I felt comfortable with this decision for a couple of reasons. First, a job recruiting advertisement has no effect or influence on the resulting discussion. Second, the practice has a positive reputation and may actually represent a great opportunity for one of our listeners. Will we pursue similar advertisements in the future? Probably and hopefully, but I think that those decisions will be made on a case by case basis.

What if your new revenue streams exceed your costs? Who pockets the surplus?

Nobody. Surplus revenue will be directed towards either improving or adding to our recording equipment to allow us for more creative episodes (for example, high quality group interviews at major meetings) or future travel grants/scholarship opportunities for residents and fellows to attend major meetings.

So how many people listen now? What other podcast-related activities are you pursuing?

We have tremendously fortunate to see a steady and ascending base that listens to our episodes consistently. For the first few episodes we averaged 50-100 unique listeners/episode. At the end of 2017 it was closer to 300 listeners/episode. But now at the end of 2018 we are up to about 1000 listeners/episode. Given how niche and specialized our program is, that is a tremendous number! More encouraging is that if we examine the statistics for ‘old’ episodes unique listeners keep going back and listening, meaning we are achieving our goal of releasing content that is current but still useful months to years later.

We have written a couple of upcoming papers on our podcast data and a survey we collected last year. We will also be collecting a larger survey this year and will be presenting research at major meetings such as the AAO annual meeting and AUPO annual meeting (Mike Venincasa), the Innovations in Medical Education conference (myself), and others pending acceptance (Louie Cai, Angela Chang). We believe that our experience has reinforced what other medical specialties had discovered before us: podcasts and mobile audio learning are the present, not the future. Our research is designed to emphasize that.

My co-resident loves your podcast but is going into glaucoma. Will you do a podcast about glaucoma? What about cornea?

I have been asked this multiple times and am always honest that my relative knowledge base would limit my ability to host a topical and interesting show and ask guests the right questions. We are investigating the possibility of a producing a ‘sister’ anterior segment show, but it has to have the right host, environment, and consistency to not dilute from what we are doing on the retina side. TBD!

Hopefully that answers many of the questions that have come up and will come up going forward. Happy new year and thank you!

                                                                                                                                         Jay Sridhar

(Left) Dr. Elizabeth Sargent and (Right) Isabel Hayes Chapin Barrows. Image Credit: https://www.aaojournal.org/article/S0161-6420(14)01093-8/fulltext

            In this week’s Episode (LINK), Jay was joined by Drs. Zelia Correa, Geeta Lalwani, and Ashvini Reddy for a panel discussion about the job and contract negotiation process, with a special focus on maternity and sick leave. Therefore, we thought it would be fitting to discuss some of the first female ophthalmologists in our field.

            Although female physicians began to receive training following the graduation of Elizabeth Blackwell from Geneva Medical College in 1849 and the establishment of the Women’s Medical College in Philadelphia in 1850, there was still a great amount of push-back when it came to training in a surgical specialty (the AMA did not admit women until 1915). Despite these set-backs, the two first female ophthalmologists – Isabel Hayes Chapin Barrows and Elizabeth Sargent – completed their training near the end of the 19th century. Both physicians spent time learning at the University of Zurich, where women studied medicine as early as 1833 and were admitted as medical students starting in 1864, and at Howard University in the United States, which was founded on similar principles in 1867.

            Dr. Isabel Hayes Chapin Barrows was the daughter of a family doctor, and so grew up surrounded by the medical field. After she suffered through a miscarriage and her husband died of diphtheria, she decided to pursue a medical education. However, life continued to place strains on her education, which was placed on hold as took over her second husband’s stenography job when he fell ill with typhoid fever. Finally, Dr. Barrows graduated from the Women’s Medical College of the New York Infirmary for Women and Children. She then moved to Zurich and Vienna, where she fell in love with the eye and learned the art of cataract surgery with Professor Eduard Jaeger. After completing her training, Dr. Barrows returned to Washington, DC to purchase 100 dollars worth of ophthalmology equipment and to become the first woman to have a private practice in medicine in the city.

            From a young age, Dr. Elizabeth Sargent (who was the daughter of a politician father and an activist mother) was an advocate for women’s rights and worked for the women’s suffrage. Like Dr. Barrows, she also attended Howard University before obtaining her medical degree, and she also traveled to Zurich for her training in ophthalmology. When she returned to San Francisco, Dr. Sargent continued her women’s suffrage work and began a practice in pediatric ophthalmology. She became a leader both at home and around the world, donating to keep her women and children’s hospital open and even representing the AMA’s Section on Ophthalmology at an international meeting.

”News” from The Ophthalmic Record: A Monthly Review of the Progress of Ophthalmology, Volume 9

            Together, Drs. Barrows and Sargent helped to pave the way for future female ophthalmologists, and future female physicians in general. Although there is always progress to be made, these first steps were important and these physicians deserve particular recognition today. For more information about Drs. Barrows and Sargent, you may like to read this AAO article (LINK) by Alice R. McPherson and Daniel M. Albert, on which this text is based. We hope that you enjoyed today’s reading!

            -Michael Venincasa

In last week’s episode, Jay was joined by Dr. Yoshi Yonekawa and Dr. Will Parke for Journal Club. The three publications discussed involved pediatric retinal detachment surgery, open label extension of RISE and RIDE, and blood pressure fluctuations during intravitreal injections. 

One of the articles discussed during Journal Club centered around the treatment for diabetic retinopathy. Diabetes is one of the most common chronic diseases in the United States, with the CDC estimating that more than 100 million people in the US have either diabetes or prediabetes. Currently, it is expected that 2 out of 5 Americans will develop type 2 diabetes in their lifetime. This disease carries the risk of many complications, including vision loss, neuropathy, nephropathy, skin problems and more. Importantly, it is the leading cause of vision loss in patients between 25 and 74 years of age. Because of the great global burden of diabetes and its impact on vision loss, in this post we wanted to review the classifications of diabetic retinopathy, and how the use of a monoclonal antibody can aid in treatment of this condition.  

Diabetic retinopathy is the most common microvascular complication of diabetes and it is classified into either nonproliferative or proliferative subtypes. Nonproliferative DR represents the first visible changes seen in the retina due to diabetes. In this stage microaneurysms begin to appear as well as dot intraretinal hemorrhages, and retinal ischemia or infarction represented by “cotton wool” spots. Proliferative DR represents the end stage in the natural history of DR and presents with angiogenesis, or the formation of new blood vessels. In this stage there is severe hypoxia that stimulates the production of angiogenic factors, including VEGF. 

(Left) Image Credit: https://www.researchgate.net/figure/Moderate-non-proliferative-diabetic-retinopathy-with-no-diabetic-macular-edema_fig2_310612920

(Right) Image Credit: http://retinavitreous.com/diseases/dm_pdr.php

The RIDE and RISE Studies are long-term clinical studies looking at the use of Ranibizumab, a monoclonal antibody fragment, to treat proliferative diabetic retinopathy. This monoclonal antibody is designed to inhibit VEGF and prevent angiogenesis. VEGF, or Vascular Endothelial Growth Factor, is a protein produced by cells that stimulates the formation of blood vessels and endothelial cell growth, and causes the breakdown of the blood-retinal barrier. The state of severe hypoxia seen in proliferative DR induces the production of this molecule, which leads to retinal neovascularization. These new blood vessels are fragile, prone to bleeding, and can grow into the vitreous body. Thus, sight-affecting complications include vitreous hemorrhage and tractional retinal detachment. Monoclonal antibodies like Ranibizumab have been developed to prevent this progression by inhibiting VEGF. 

An antibody molecule consists of four different polypeptide chains that join together to form a “Y” shape. Each antibody consists of two identical heavy chains and two identical light chains. Both polypeptides have a constant region and a variable region, and it is this variable region that binds to an antigen. A monoclonal antibody fragment, like the one used in the RIDE and RISE studies, only contains the antigen-binding fragment (Fab region) which is composed of both a heavy and a light chain with constant and variable regions. The loss of the Fc region makes this monoclonal antibody smaller allowing it to penetrate the retina more easily. Once in the retina, this antibody can bind to and inhibit VEGF, which prevents the molecule from binding to its receptor and thus helps to limit the progression of proliferative DR. 

-Amy Kloosterboer

(Left) Image Credit: https://bxcell.com/antibody-structure/

(Right) Image Credit: https://www.scoop.it/t/victrelis-boceprevir-merck-fda-review-approval/p/4069081506/2016/09/13/scfv-fab-construction-and-purification-fab-creative-biolabs

During Episode 142, Jay was joined by Dr. Ed Ryan of Minneapolis, MN to discuss the design of devices to improve surgical techniques, advances in vitrectomy, and scleral buckling. Central to this discussion was the idea that while scleral buckling may be falling out of favor, it is a technique that must not be forgotten and should be considered as the primary intervention in certain cases. Today’s blog post is from a new name on our team: Amy Kloosterboer, a third-year medical student at the University of Miami’s Miller School of Medicine. Today, we present the history of scleral buckling and some of the basic principles behind this surgery.  

Retinal detachment occurs when the retina separates from the underlying retinal pigment epithelium (RPE) and choroid. This can occur actively, as seen with diabetic traction retinal detachment, or passively due to accumulation of fluid between the two layers. The inner layers depend on the outer layers for delivery of nutrients and oxygen, and so this detachment can lead to damage to and even death of the cells in the neurosensory retinal layer. 

Image Credit:

(Left) http://www.shreeramkrishnanetralaya.com/retinal_detachment.html

(Top Right) https://www.lehp.org.au/Training%20Course/pages/conditions.html

(Bottom Right) http://www.fairvieweyecenter.com/Education/Conditions/RetinalDetachment/tabid/3103/Default.aspx

One of the options to treat retinal detachment is a scleral buckle. The principle behind this surgery is to collapse the space created between the detached retinal layer and its supporting layers. This is done by applying a band-like device onto the exterior of the globe, which causes inward indentation of the sclera to create a ridge (or buckle) that functionally closes the breaks. This allows the separated layers to come together once more.

Image Credit: https://www.texomaretina.com/services-2/common-treatments/scleral-buckle/

The first successful treatment of retinal detachment occurred in 1920 by Swiss ophthalmologist, Dr. Jules Gonin. His technique involved closure of the break using trans-scleral cauterization. Since the patient subsequently recovered vision, this showed that retinal breaks were the main cause of retinal detachments, and that successful treatment involved sealing those breaks. Many different techniques were developed after 1920, but it was not until 1949 that the first scleral buckle surgery was reported. Dr. Erns Custodis, a German ophthalmologist and professor, performed the first scleral buckling procedure that included a retained exoplant. He sutured a polyviol material to the sclera, and effectively indented the eye wall at the area of the break to close the gap between the retinal layer and the RPE. In 1956, Dr. Charles L. Schepens, inventor of the binocular indirect ophthalmoscope, modified this technique to use an encircling polyethylene tube. With the help of the indirect ophthalmoscope, Dr. Schepens was able to localize the retinal break and correctly position this tube to seal the break between the layers. Today, there are a variety of materials can be used as a buckle, and the most common is silicone as it is nontoxic, nonallergenic, and can be molded as needed by the surgeon. This last property allows for great variability between operations, giving the surgeon the flexibility to adapt the technique to the patient and to choose between a localized scleral buckle to an encircling circumferential buckle. 

-Amy Kloosterboer

Last week, we began a new blog feature with one of our medical students offers his or her perspective on the current week’s episode. For this week’s podcast episode, we were joined by Dr. Audina Berrocal for a discussion on a number of topics in pediatric retinal surgery. Of these, one in particular that has received special attention in the media and in ophthalmology communities has been the use of gene therapy to treat children with hereditary retinal diseases such as Leber congenital amaurosis (LCA). The most common hereditary retinal disease is retinitis pigmentosa (RP) and there are current trials ongoing in the United States looking at gene therapy for RP. For our listeners and readers who may be patients, parents, or simply curious, we wanted to provide a basic overview of RP and how this treatment can be used to save some patients’ sight.

Retinitis Pigmentosa: Background

RP is a clinically and genetically heterogenous group of inherited (can be passed down from parent to child) retinal disorders, meaning that there is a good amount of variability between patients with respect to how they inherited the disease and how the disease affects their vision. In general, however, RP involves a progressive (worsening) retinal dysfunction, usually starting with the rod photoreceptors (the “night-vision” part of the retina) and later affecting the cones (for “day-vision”) and retinal pigment epithelium. Thus, patients with RP generally first experience night blindness (difficulty seeing in low-light settings), followed by progressive visual field loss (a sort of “tunnel vision” as shown below).

Image Credit: https://www.mesvision.com

Retinitis Pigmentosa: Genetics

There are no known risk factors for RP other than genetic predisposition. So what does this mean? We mentioned earlier that RP is “genetically heterogeneous” - indeed, RP can be inherited as an isolated sporadic disorder, or in an autosomal dominant, autosomal recessive, or X-linked pattern.

• Isolated Sporadic: a genetic mutation can be passed on, but in order for one to be present and available to be passed on, the mutation has to occur for the first timein some individual of a family. This is called “sporadic” since the mutation occurs, essentially, randomly.

• Autosomal Dominant: for most of your DNA, there exists a second “backup copy” for each gene (one from Mom, one from Dad). For autosomal dominant inheritance patterns, if one of the two copies is “bad,” the disease can occur. In general, the purpose of each gene is to make a certain protein that your body needs to function. Think of this as a two-person team at work; if one of your team-members refuses to do his/her work, you may not meet that deadline. In the same way, if one member of the two-protein team (two copies: one from Mom, one from Dad) isn’t cooperating, a disease process can occur.

• Autosomal Recessive: in this case, both copies need to be “bad” for the disease state to occur. In other words, one good copy is sufficient to prevent disease. Think of this as being like transportation to work: if your car is broken down but your spouse’s car is running, you can borrow the car and still make it to work on time. For autosomal recessive diseases, if one copy of the gene is “bad” and the other is “normal,” the patient will not have the disease (see image below).

• X-Linked: for these diseases, the important gene is located on a particular chromosome called the X-chromosome. For baby boys, they only receive an X-chromosome from their mother. For baby girls, they receive an X-chromosome from both their mother and their father. Since the boy would only have one X-chromosome, he wouldn’t have a “backup” copy in case the copy he received is “bad,” and so he would be more likely to be affected.

Image Credit: https://ghr.nlm.nih.gov/primer/inheritance/inheritancepatterns

Retinitis Pigmentosa and Gene Therapy

Now that we’ve finished our genetics lesson for the day, how does this relate to “gene therapy” treatments for RP? In the episode, Jay and Dr. Berrocal discuss use of RPE65 therapy for some children with LCA. Since this is an autosomal recessive disease, that means that both copies of the gene are “bad” and the so both copies of the protein that they are (supposed to be) making are “bad.”

Gene therapy is a way to allow the patient to create the “good” protein. A special virus (which carries a “good copy” of the RPE65 gene) is used to insert the “good” gene into cells of the patient’s retina. After that, the cells are are able to make the “good” protein, which helps preserve or improve vision!

Image Credit: http://www.retina-specialist.com/article/gene-therapy-the-new-frontier-for-inherited-retinal-disease

Image Credit: https://www.semanticscholar.org/paper/The-gene-therapy-revolution-in-ophthalmology.-Al-Saikhan/065a764404bda4440485b3f07a3109cffdd75e2e/figure/1

Looking To The Future

Although Jay and Dr. Berrocal only talked about one specific gene that is being targeted with gene therapy, there are others that are being targeted in current clinical trials (e.g. Dr. Berrocal’s patient with X-linked RP who received gene therapy at Bascom Palmer) or will be in the future. Gene therapy is a bright light for the future, and hopefully will improve the lives of countless patients with a number of ophthalmologic and non-ophthalmologic conditions.

-Michael Venincasa

#genetherapy #retinitispigmentosa #leberscongenitalamaurosis #rpe65 #ophthalmology