The Medicine in the Digital Age BULLETIN 8 Convergence of Surgery of the Future and the Digital Age Aug / Sept 2018 Vol. 84 No. 2 by Raymond J. Lanzafame, MD, MBA, FACS

Published by 12 Emerging Technologies in the ER Monroe County Medical Society by Justin Mazzillo, MD 132 Allens Creek Rd., Rochester, NY 14618 (585) 473-7573 www.mcms.org 14 Changing Medicine One Tweet at a Time EDITORIAL COMMITTEE by Brian Teng, MD, FACS, FASCRS Stephen E. Presser, MD, Editor 16 Open Your Eyes! Gene Therapy is Here Jane Dodds, MPH, FACMPE Mark H. Goldgeier, MD by Matthew Witmer, MD David M. Newman, MD Jerry J. Svoboda, MD David A. Topa, MD STAFF Special Feature Christopher Bell, Executive Director Carol Burke, Managing Editor 18 Q&A With 23rd & 25th District Congressional Candidates

EXECUTIVE COMMITTEE OF THE MONROE COUNTY MEDICAL SOCIETY Surinder Devgun, MD, President Lisa Smith, MD, President-Elect Edith Grannum, MD, Secretary Features Susan Danahy, MD, Treasurer 25 Reporting Medical Practice Payments J. Chad Teeters, MD, Member-at-Large Balazs Zsenits, MD, Member-at-Large 30 Serving at Clinica Esperanza Peter Ronchetti, MD, Imm. Past President OFFICERS OF THE SEVENTH DISTRICT BRANCH, MSSNY Edward C. Tanner, MD (Monroe County) In Every Issue President 5 Letter From the Executive Director Werner K. Brammer, MD (Steuben County) First Vice President 7 President’s Column Daniel J. Koretz, MD (Wayne County) Secretary/Treasurer 26 MCMS Medical Memo 27 MCMS Physician Network Published in February, June, September and November by the Monroe County Medical Society and the Seventh District Branch of the Medical Society of the State of New York, The Park at Allens Creek, 132 Allens Creek Road, Rochester, 28 Upcoming Events NY 14618. Copyright 2018, MCMS. Advertising inquiries may be directed to (585) 473-7573 or [email protected]. 29 Ask An Attorney Postmaster: Please send address changes, undeliverable copies and all other communications to: The Bulletin, The Park at Allens Creek, 132 Allens Creek Road, Rochester, NY 14618. Periodicals postage paid at Rochester, NY. The Bulletin (USPS 384-130). The Bulletin is the official journal of Advertising Principles: The appearance of advertising in The Bulletin is not a MCMS guarantee or endorsement of the product or service or the claims made by the advertiser.

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Monroe County Medical Society l www.mcms.org 3 Open Your Eyes! Gene Therapy is Here BY MATTHEW WITMER, MD

If you have been thinking that gene mobility test at increasingly dimmer levels of light. The therapy is science fiction that will take effects of the treatment showed durability throughout 3 decades to achieve clinical relevance, years. Patients that have undergone the treatment have think again. During December of described life-changing experiences after the treatment 2017, the FDA approved the first gene including the ability to see stars at night, recognize faces, therapy for a genetic disease when it and improve their mobility. approved LUXTURNA™ (voretigene neparvovec-rzyl) (Spark Therapeutics, Why the Eye? Philadelphia, PA) (Figure 1) for the The eye has long been thought to hold promise as a treatment of an inherited retinal primary site for gene therapy success. There are several disease. The medication is indicated for reasons for this, which include: the treatment of patients with confirmed biallelicRPE65 mutation-associated retinal dystrophy. These patients 1. there are many inherited causes of blindness that are have typically previously been clinically diagnosed mediated by a single gene, which could be targeted as either Leber’s congenital with gene therapy vectors; amaurosis (LCA) (Figure 2A) or retinitis pigmentosa (RP) 2. the eye is an immune privileged site because the (Figure 2B) and undergone vitreous humor contains relatively few antigen genetic testing to confirm their presenting cells and immune factors that could genotype. The approval of gene initiate a severe immune response; therapy for the eye was the Leber’s congenital amaurosis culmination of decades of basic 3. the eye is a paired organ which allows for a potential science and clinical research and control eye and treatment eye in clinical trials; was proof that gene therapy is a legitimate avenue for clinical 4. the monitoring of disease progression or regression therapies. is readily available with current imaging modalities that can assess treatment response in terms of form Retinitis pigmentosa (RP) What is Gene or function. Optical coherence tomography creates Therapy? images of the retina that now approach histology and Gene therapy is the transplantation of normal genes functional vision can be assessed in several different into cells in place of missing or defective ones in order manners; and to correct genetic disorders. This transfer of genetic material can be achieved using viral vectors. In the case 5. the eye provides a readily accessible organ for of biallelic RPE65 mutation-associated retinal dystrophy, surgical manipulation by standard operating the RPE65 gene encodes an important enzyme in the techinques. These are the same techniques that I use visual cycle that catalyzes the isomerization of 11-trans- each time I am in the operating room. retinyl esters into the chromophore 11-cis-retinal. The loss of function of this gene can cause an inherited retinal Why the Adeno-Associated Virus as a disease that is progressive and blinding. LUXTURNA™ Vector (AAV)? (voretigene neparvovec-rzyl) works by using an adeno- Adeno-associated virus is a 25-nm nonenveloped virus associated virus (AAV) to transfer the gene into the containing a linear-stranded DNA genome. This virus is retinal cells. A phase 3 clinical trial with the medication commonly selected for gene therapy trials because of revealed improved ability for the patient to complete a it low immunogenicity and high tolerability. The virus is 16 The Bulletin l Aug / Sept 2018 particularly valuable for gene therapy in the eye because patient does not sufficiently improve. In addition, the of its high retinal affinity. The virus also demonstrates manufacuturer has allowed insurance companies to durability while present in the nucleus. purchase the medication directly rather than having treatment centers purchase it first. How does it work? Luxturna delivers a functional copy of the RPE65 gene Future Directions to cells that contain mutated versions of this gene. The The advent of clinically available gene therapy treatments AAV serotype 2 delivers this is monumental. This new functional copy of the RPE65 age will change the way we gene to retinal pigment epithelial manage patients with inherited (RPE) cells. It is estimated that retinal diseases. Patients with 1-2,000 people in the U.S. may be certain phenotypes consistent eligible for this therapy. with inherited retinal disease associated with RPE65 loss now How is it done? merit genetic testing because LUXTURNA™ (voretigene this could influence treatment neparvovec-rzyl) is administered decisions. In addition, patients by subretinal injection during a with other retinal dystrophies vitreoretinal surgical procedure. may be eligible for several of The surgery consists of a the ongoing clinical trials using standard vitrectomy in order Figure 3 gene therapy. There are currently to gain access to the subretinal gene therapy clinical trials for the space. The preparation of the treatment of variety of retinal medication is under sterile conditions. Among others, they conditions and the medication include: must be administered within 4 hours of preparation. Once • choroideremia the pars plana vitrectomy is • X-linked retinitis completed, a subretinal cannula pigmentosa is introduced into the eye and the site of the injection is identified • Stargardt’s disease (Figure 3). The recommended • Usher syndrome site is along the superior vascular • Achromatopsia arcade, at least 2 mm distal to the center of the fovea (Figure 4). The • X-linked retinoschisis goal is avoid direct contact with the retinal vasculature or with Figure 4 It is only a matter of time areas of pathologic features, such as until additional gene therapy atrophy and scarring. 0.3 ml of volume is then injected treatments become approved and are available to subretinally. The surgery is concuded with a fluid-air improve the lives of our patients. exchange to fill the eye with an air bubble. Dr. Witmer is a vitreoretinal specialist in private practice at Retina Associates What does it cost? of Western New York. His office is A central question with the advent of clinical gene located in Brighton, NY. His practice therapy remains the price of such incredible innovations. consists of the medical and surgical Spark Therapeutics set the price of LUXTURNA™ treatment of diseases that affect the (voretigene neparvovec-rzyl) at $425,000 per eye. retina. He is originally from Rochester, Such an exorbitant price requires creative solutions to NY. find a way to pay for this. This includes that the cost of the medication would be rebated if the sight of the

Monroe County Medical Society l www.mcms.org 17