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DEPARTMENT OF OPHTHALMOLOGY KECK SCHOOL OF MEDICINE OF USC 40 YEARS INSIGHT DEPARTMENT OF OPHTHALMOLOGY KECK SCHOOL OF MEDICINE OF USC Keck School of Medicine of USC Department of Ophthalmology USC Eye Institute 1450 San Pablo Street Los Angeles, CA 90033-4682 (800) USC-CARE KeckMedicine.org eye.usc.edu ©2015 Keck Medicine of USC 40 YEARS INSIGHT 10 USC Eye Institute TOP ACCOLADES AND ACHIEVEMENTS FOR 20 YEARS Ophthalmology U.S. News & World Report 2014-2015 • Ranked among the nation’s top 10 ophthalmology programs for 20 years by U.S. News & World Report. • Ranked among the nation’s top 10 ophthalmology programs by Ophthalmology Times. • Ranked in the top 10 for research funding by the National Eye Institute. • Headquarters of two California Institute of Regenerative Medicine (CIRM) grants since 2012. USC leads the development of a translational stem cell-based treatment for age-related macular degeneration. CIRM funds stem cellbased research at institutions throughout California with the goal of developing new therapies for diseases and disorders. • Headquarters of the National Science Foundation (NSF) Biomimetic MicroElectronic Systems Engineering Research Center since 2003. USC leads an NSF-funded national center for developing electronic devices that can be implanted to treat diseases, conditions and injuries of the eye. • Headquarters of the Department of Energy (DOE) Artificial Retina Project (2002-2012). USC leads a DOEfunded consortium whose goal is to develop a bioelectronic retinal implant to restore sight to the blind. INSIGHT • António Champalimaud Vision Award in 2012 for outstanding scientific research in the field of vision science — Carmen A. Puliafito, MD, MBA, dean of the Keck School of Medicine of USC. 2014 ANNUAL REPORT •One of the nation’s top one percent of ophthalmologists in 2012 by U.S. News & World Report — Mark S. Humayun, MD, PhD. • Top Doctors for 2014: USC ophthalmologists named America’s Top Doctors - Los Angeles (Castle Connolly) 8; Pasadena Magazine 11; Hollywood Reporter 8. • 17 current United States ophthalmology chairs are former faculty members and graduates of Keck School of Medicine of USC Department of Ophthalmology training programs. About the Cover: Image of brain connectivity from the Human Connectome Project, led by USC. Research on neural connections may help advance the development of new types of visual prostheses. 40 Years of Innovation 8 Patient Care 11 Research 16 Clinical Education 36 RETINITIS PIGMENTOSA CELLS 1 History has honed our skills and capabilities. This year, we celebrate 40 years of life-changing research, compassionate care, and leadership in education. The future inspires hard work and compassion. We envision a world where one of humankind’s greatest fears — loss of vision — is a thing of the past. How will we get there? With insights we have learned over four decades: Insight in Research: An outside-the-box, innovative research program that tackles the toughest of challenges — from diagnosing and treating imperiled eyesight in utero to putting stem cells to work to solve age-related macular degeneration to building a working artificial retina that will restore sight to the blind. Insight in Patient Care: A commitment to taking care of people and to crafting the very best solutions to the challenges our patients face. Good enough is never good enough. Bench scientist, front-line physician, staff — we all collaborate across disciplines to deliver the gift of sight. Insight in Education: More than 400 young physicians applied for six spots in our residency program. Our program is widely known as among the toughest in the country. We attract the best, the brightest and the fiercely dedicated. No wonder that USC Eye Institute thrives in supplying the world with the next generation of leaders. After 40 years, these are our insights; and like true Trojans, we will fight on until we achieve our mission: Vision for all. We invite you to join us. With your support and your advocacy, we see a clear path to success. “ Although the research, care and education we deliver is complex, our mission is very simple. Our physicians and researchers come to work every day with a single goal: to transform the lives of people facing loss of vision or blindness.” Sincerely, Rohit Varma, MD, MPH Grace and Emery Beardsley Professor Chair, Department of Ophthalmology, Keck School of Medicine of USC Director, USC Eye Institute Rohit Varma. Director (from left) Carmen A. Puliafito,MD, MBA, Dean, Keck School of Medicine of USC Rohit Varma, MD, MPH, Director, USC Eye Institute Tom Jackiewicz, MPH, Senior Vice President and Chief Executive Officer, Keck Medicine of USC 2 3 Vision is Our Mission PROTECTING USC Eye Institute leads major research in the epidemiology of eye disease to help prevent blindness. PRESERVING USC Eye Institute diagnoses, treats and manages the most complex eye conditions, from in utero to advanced age. RESTORING USC Eye Institute integrates and applies emerging technologies to develop new methods to restore sight to the blind. Fulfillment of our mission is best expressed in the remarkable triumphs of our patients. Read their stories in the pages ahead. 4 5 40 YEARS OF INNOVATION Major Breakthroughs by USC Department of Ophthalmology Faculty 1974-2014 INSIGHT 40 Years of Innovation 1974 Founded the USC Department of Opthalmology 1978 Developed a laboratory model of penetrating eye injuries that influences the management of trauma in humans Since its founding 40 years ago, the Department of Ophthalmology of the Keck School of Medicine of USC has pioneered many discoveries that have contribute to the advancement of vision science and clinical ophthalmology. 1979 Developed a laboratory model of choroidal neovascularization now widely used to study pathogenesis and treatment of subretinal neovascularization 1987 Implanted the first artificial cornea in a pediatric patient Our faculty has a long tradition of seeking and sharing knowledge to help protect, preserve and restore precious eyesight. 1987 Identified the gene that causes retinoblastoma In the pages that follow, we highlight significant achievements by current and former USC Department of Ophthalmology faculty members. 1991 Pioneered optical coherence tomography 1992 Addressed vision complications from AIDS by diagnosing and developing treatments for opportunistic eye infections and Kaposi’s sarcoma 1998 Developed the Baerveldt® glaucoma implant for preserving vision in glaucoma patients by reducing eye pressure 1999 Developed a noninvasive glucose-monitoring system using Raman spectrum signals from the aqueous humor 2000 Began the Los Angeles Latino Eye Study, the world’s largest investigation into eye disease in Latinos PIONEERING BREAKTHROUGHS, THEN AND NOW Optical coherence tomography, pioneered by Carmen A. Puliafito, dean of the Keck School of Medicine of USC, is an essential diagnostic tool used worldwide. Hyperspectral imaging, being developed by USC Eye Institute researchers, is providing images of the retina that reveal its spectroscopic features in unprecedented detail. ARTIFICIAL RETINA IMPLANT 6 7 2002 Implanted the first artificial retina in a patient after beginning collaboration with the U.S. Department of Energy Office of Science in 1999 2014 Discovered which retinal cells mutate to become retinoblastoma 2005 Pioneered use of ultra-high speed Fournier domain optical coherence tomography (OCT) to improve glaucoma diagnosis INSIGHT Patient Care 2007 Implanted first Argus II Retinal Prosthesis System in the United States 2009 Identified the unique mechanism of uptake in lacrimal gland for adenovirus 5 that may facilitate drug delivery 2010 Developed a Web-accessible visual field test and analysis system for multicenter studies and touchpad device access 2011 Began first clinical trials for an experimental therapeutic agent to treat Leber’s Hereditary Optic Neuropathy, a mitochondrial disease 2013 Received Argus II Retinal Prosthesis System approval by the United States Food and Drug Administration for patients with retinitis pigmentosa In 2014, USC Eye Institute had the privilege of treating many thousands of patients who were facing the possibility of loss of vision or blindness. People from all walks of life with a full spectrum of eye conditions relied on us to provide the most advanced care possible. The programmable micropump implanted by USC physicians 2014 Implanted a programmable micropump smart device that delivers precise small doses of medications into the eyes of patients with diabetic macular edema, in the first-in-man clinical trial PIONEERING BREAKTHROUGHS, THEN AND NOW The Baerveldt® glaucoma implant, developed at USC, has become the global standard for glaucoma surgery. 8 The gel stent, developed by USC Eye Institute researchers, is implanted through a minimally invasive injection and has been shown to reduce intraocular pressure from glaucoma. RETINAL STEM CELLS 9 Abe Spigner Ocular Laceration, Retinal Detachment OCULAR HISTORY 3/16/14 Ocular laceration OS resulting in open globe, traumatic cataract and vitreous hemorrhage. Presented with LP vision and at risk for permanent blindness. TREATMENT •3/16/14 Primary closure surgery. •3/18/14 Evaluation revealed hyphema, traumatic cataract and vitreous hemorrhage. When a wine glass shattered and sent a shard slicing into his left eye, Abe Spigner expected to lose his sight. Abe was rushed to USC Verdugo Hills Hospital and then transferred to LAC+USC Medical Center for primary surgical repair of his eye. Two days later at the USC Eye Institute, retinal specialist Lisa Olmos de Koo, MD, and cornea surgeon J. Martin Heur, MD, PhD, planned and performed successful surgery to save Abe’s left eye. A month later, the vision in Abe’s left eye suddenly worsened and he returned to the USC Eye Institute. Diagnosed with a retinal detachment, he underwent surgery that included inserting a gas bubble into his eye to hold the retina in place as it healed. Required to remain face down for seven days following surgery to keep the bubble in the proper position, Abe occupied himself •3/31/14 Planned surgery: vitrectomy and lensectomy and AC washout by building a radio-controlled truck. In the process, he •4/28/14 Sudden vision change. Diagnosed with macula-sparing retinal detachment. Detachment was repaired emergently with scleral buckle, vitrectomy and gas tamponade. Anterior wound revision was performed concurrently. from his childhood. •Poor candidate for rigid gas permeable and soft contact lenses due to severe dry eye and irregular corneal shape. Abe contributed to a very positive outcome — and rekindled a hobby In the months since surgery, Abe’s left eye has healed fully and he now has 20/25 vision corrected vision. J. Martin Heur, MD, PhD, associate professor of clinical ophthalmology, worked with retinal specialist Lisa Olmos de Koo, MD, MBA, assistant professor of ophthalmology, to save Abe Spigner’s left eye. OUTCOME In preliminary tests with prosthetic replacement of the ocular surface ecosystem (PROSE) therapy, custom scleral device improved vision to 20/25. Left eye fundus taken approx. seven months after detachment repair shows the retina is attached and healthy. The 360-degree indentation of the encircling buckle with laser marks on the crest is evident. A small amount of pre-retinal fibrosis superotemporal to the disc is apparent, but clinically insignificant. 10 11 PATIENT CARE Comprehensive Clinical Services A full spectrum of highly specialized eye care for patients of all ages. CORNEAL AND EXTERNAL DISEASES Comprehensive corneal evaluations, medical diagnostic services and computerized topography can often be performed during a single visit. Available diagnostic services include pachymetry, potential acuity measurement, microbiological studies and assessment of corneal topography using computerized corneal modeling technology. GLAUCOMA Targeted and Culturally Personalized Care Linda Lam, MD, specializes in medical and surgical treatment of retinal diseases. She also specializes in ensuring that the USC Eye Institute reaches patients where they live and addresses their specific needs. The composition of the team of specialists and subspecialists in Arcadia reflects the residents’ greater susceptibility to myopia, narrow angle glaucoma, cataracts, dry eye, diabetic retinopathy and age-related macular degeneration. OCULAR ONCOLOGY Specialists provide a broad range of diagnostic, medical and surgical services with access to cancer specialists from USC Norris Comprehensive Cancer The team can also address patients fluently in Mandarin, Cantonese, Vietnamese, Korean, Hindi, as well as Spanish and German. To make it easier for patients to see eye specialists and keep their appointments, the new clinic is located in the center of the city, adjacent to a soon-to-be-built Metro station. 12 NEURO-OPHTHALMOLOGY, ORBITAL AND ADULT STRABISMUS Specializing in disorders of the optic nerve, chronic papilledema and orbital trauma, our physicians provide consultations, and medical and surgical services. Available diagnostic testing includes fluorescein angiography, ultrasonography, visual fields and electrophysiology. As medical director of the recently relocated and expanded ophthalmology clinic in Arcadia, CA, Lam is attuned to the clinical and cultural nuances of the predominantly Asian neighborhood . Effective, personalized care is based on welcoming patients, meeting their needs and removing barriers to care. The Arcadia location expansion is the latest example of how the USC Eye Institute is achieving this goal. Glaucoma specialists provide comprehensive consultative, diagnostic, medical and surgical services. Faculty members are involved in a National Eye Institute sponsored, multicenter clinical trial studying the efficacy and safety of early surgery in the treatment of glaucoma. Center as needed. We specialize in the treatment of choroidal melanoma and other ocular tumors in adults, treatment of retinoblastoma and other ocular tumors in children and new treatment methodologies for intraocular tumors. OPHTHALMIC PATHOLOGY We provide macroscopic, microscopic and ultrastructural analysis of diseased eye tissues to aid in diagnosis. Advanced genomic, proteomic and cytogenetic techniques are also used to diagnose diseases at a molecular level. OPHTHALMIC PLASTICS, ORBITAL AND RECONSTRUCTIVE SURGERY Our physicians specialize in tissues surrounding the eyeball that affect the appearance or function of the eye. This includes diseases of the eyelids, the lacrimal system, the orbit and the facial areas adjacent to the eye. Ophthalmic plastic surgeons are board-certified ophthalmologists who have completed several years of additional, highly specialized training in plastic surgery. OPTOMETRY AND CORNEAL PROSTHESIS We have expertise in fitting specialty contact lenses, and offer innovative prosthetic replacement of the ocular surface ecosystem (PROSE). PEDIATRIC OPHTHALMOLOGY A full range of diagnostic and treatment methodologies are available through USC Department of Ophthalmology Patient Volumes Linda A. Lam, MD, associate professor of ophthalmology and vice chair, satellite clinical affairs Year Total Visits Total Surgeries 2013 95,000 4,700 2014 114,000 5,480 Totals include Keck Medicine of USC, Children’s Hospital Los Angeles, LAC+USC Medical Center and VA Greater LA Healthcare System Children’s Hospital Los Angeles, including the ability to measure visual acuity in infants and preverbal children. Our specialists have expertise in diagnosis and treatment of ocular oncology, neuro-ophthalmology, retinal disorders and strabismus. REFRACTIVE SURGERY We were one of the few ophthalmic centers in the country involved in the U.S. Food and Drug Administration supervised clinical trial testing of the efficacy of the excimer laser, and continue to be at the forefront of developments in refractive surgery. UVEITIS AND OCULAR INFLAMMATION Our specialists evaluate the functional status of the immune system and detect infectious causes or neoplastic processes. Electron microscopic and immunohistochemical techniques often lead to diagnosis of rare diseases. Highly specialized services dealing with AIDSrelated cytomegalovirus (CMV) retinitis are also available. VITREORETINAL SURGERY AND RETINAL DISEASE We specialize in the repair of complex retinal detachments, offering advanced techniques such as silicone oil, perfluorocarbon liquids and SF6 and C3F8 gases. Our specialists have the surgical and research experience to repair penetrating trauma. Laser treatment of the retina for diabetic retinopathy can be performed with the argon, krypton, diode, or double frequency YAG laser. FOR REFERRING PHYSICIANS To consult with an ophthalmologist from the USC Eye Institute, or to schedule appointments, please call (323) 442-6335. 13 Ruby Chan Bilateral Retinoblastoma MEDICAL HISTORY Premature birth. Diagnosed with retinoblastoma before she was barely term. Ruby Chan was born prematurely and diagnosed with cancer in both of her eyes. She began treatment at Children’s Hospital Los Angeles with Jesse L. Berry, MD, USC Eye Institute specialist in ocular oncology. Ruby’s parents, Michael and Nellie, took Nellie for chemotherapy for the first four months after diagnosis, and continue with appointments for laser therapy. Ruby has made great progress. Both of Ruby’s eyes were saved, and her left eye is expected to have good vision. Germline mutation places her at greater risk for cancers. Ruby OCULAR HISTORY Bilateral retinoblastoma, the right eye involves the macula. TREATMENT Chemotherapy and laser therapy every 3-4 weeks since birth. OUTCOME Both eyes saved from cancer. Near Ruby’s family includes her parents, Michael and Nellie, and her older brother, Rock. normal vision expected in the left eye. Image of the right eye shows a central scar involving the macula after laser consolidation for group B retinoblastoma, and a new tumor adjacent to the nerve. 14 Jesse L. Berry, MD, assistant professor of clinical ophthalmology, and Jonathan Kim, MD, associate professor of clinical ophthalmology, often collaborate to treat vision problems in young patients at Children’s Hospital Los Angeles. 15 RESEARCH INSIGHT Research USC Eye Institute clinician-scientists drive fundamental and translational research to advance patient care by establishing relationships that foster innovation. Our clinician-scientists conduct bench clinical trials and train the next generation of ophthalmologists at clinical locations where patient-centered collaboration improves vision and fuels the development of new therapies. Delivering Precise Drug Therapy for Retinal Disease Effective treatment for eye diseases often depends on adherence to a carefully planned regimen of eye drops. Unfortunately, many patients are unable to stay on schedule or provide the correct dosage. Our research moves from patient to bench to bedside to meet the real needs of patients and enhance their lives. To improve patient compliance, researchers at USC Eye Institute developed a “smart” device to control medical dosing. A tiny, implantable pump delivers precise amounts of medication as required at proper intervals directly into the eye. It is refillable, and is programmed and recharged wirelessly. Originally developed for treating glaucoma, the second-generation micropump system is designed for retinal disease. It is smaller, has a greater reservoir volume and offers the possibility of multiple chambers for more than one medication. For retinal patients, localized delivery of medications into the eye has the advantage of eliminating possible systemic side effects. In 2014, USC Eye Institute physicians performed noninvasive surgery for the first-in-man implant of the novel ophthalmic medication-delivery system in patients with diabetic macular edema. The clinical trial is to verify the device’s feasibility for controlled drug delivery for chronic diseases of the retina. Further investigations will evaluate its effectiveness and be used to fine-tune its operation. The micropump is practical and convenient to use. The medication reservoir can be refilled with up to 100 microliters within two minutes via a thin 31-gauge needle. It stores up to 12 months of medication before requiring a refill. The device has been shown to function effectively for up to seven years. This second-generation micropump holds the promise of delivering microdoses of medication to an exact schedule so patients with diabetic macular edema experience optimal outcomes from therapy — without being concerned about putting drops in their eyes. The World Health Organization estimates that only half of patients in developed countries follow treatment recommendations. This tiny pump has the potential for a huge impact. USC Eye Institute retinal specialists Mark S. Humayun, MD, PhD, professor of ophthalmology and biomedical engineering, and Damien Rodger, MD, PhD, assistant professor of clinical ophthalmology as of August 2015 (current fellow), are leading the development of the micropump. NORMAL RETINAL CELLS 16 17 Sheila Papayans Age-related Macular Degeneration (AMD) OCULAR HISTORY Family history and long personal history of dry AMD in both eyes. Presented emergently after one day of distorted vision of left eye. Diagnosed with early wet macular degeneration of the left eye. Sheila Papayans watched helplessly as AMD took away her sister’s eyesight. Sheila had the same condition and was anticipating the same outcome. Attuned to any changes in her vision, Sheila noticed a sudden distortion in what she saw with her left eye. Wasting no time, she came to the USC Eye Institute. Lisa Olmos de Koo, MD, a retinal specialist, confirmed that Sheila had early wet macular degeneration of the left eye and prescribed a regimen of therapeutic injections. Sheila agreed to start that very same day. Treatment was highly successful, most likely because Sheila TREATMENT noticed symptoms early and responded immediately. Sheila also Treated with intravitreal injections of anti-Vascular Endothelial Growth Factor therapy to her left eye (ranibizumab then aflibercept). Initial treat and extend protocol soon switched to therapy as needed. Had eight injections in left eye over approx. 2.5 years. Took Age-Related Eye Disease study formula antioxidant eye vitamins to reduce the chances that the right eye would convert from dry to wet. began taking age-related eye disease formula vitamins to reduce Sheila the risk of developing wet AMD in her right eye. Two years later, Sheila has no further symptoms of wet AMD in her left eye. Her right eye, highly susceptible to wet AMD, remains dry. Now enjoying good vision in both eyes, Sheila remains vigilant and grateful. OUTCOME Maintains excellent vision in both eyes, despite developing a potentially blinding retinal disease. Right eye has remained dry. Annual therapy of three injections per year is far below the national average. Vision is currently 20/25 in each eye. Initial OCT image shows subtle findings of wet macular degeneration, confirmed by subsequent fluorescein angiography. Lisa Olmos de Koo, MD, MBA, assistant professor of clinical ophthalmology, specializes in medical and surgical treatment of complex retinal diseases. She is also the primary investigator on clinical trials for the Argus II artificial retina. 18 19 RESEARCH Currently Active Fundamental Research Funding: Department of Ophthalmology, Keck School of Medicine of USC as of January 2015 PROJECT SOURCE PRINCIPAL INVESTIGATOR Snapshot Retinal Imaging Mueller Matrix Polarimeter NIH Amir Kashani, MD, PhD Molecular Remedy of Mitochondrial Defects NIH Biju Thomas, PhD Restoring vision by sheet transplants of retinal progenitors and retinal pigment epithelium (RPE) derived from human embryonic stem cells (hESCs) CIRM Biju Thomas, PhD An Experimental Approach to Masculopathy NIH David Hinton, PhD Zebrafish Model of Human Corneal Development and Disease NIH J. Martin Heur, MD, PhD Research to Prevent Blindness (RPB) Career Development Award RPB J. Martin Heur, MD, PhD Experimental and Clinical Investigations of Retinal Stimulation NIH James Weiland, PhD Novel Ultra-Flexible Hybrid Circuits for Intraocular Retinal Prostheses NIH James Weiland, PhD U.S. Army James Weiland, PhD INSPIRE: Bioelectronic Systems for Investigating Neural Plasticity NSF James Weiland, PhD EAGER: Neural Plasticity Driven by Electrical Stimulation of the Retina NSF James Weiland, PhD Biocompatible Hermetic Coatings, High Density Feedthroughs, and Hermeticity Test Chips for Implantable Biomedical Devices DARPA James Weiland, PhD VRPI Thermoresponsive Reversibly Attachable Patch for Temporary Intervention in Ocular Trauma U.S. Army Mark Humayun, MD, PhD Harrington Discovery Institute Mark Humayun, MD, PhD Retinal Nanophotoswitch NSF Mark Humayun, MD, PhD Phase 1 Safety Assessment of CPCB-RPE1, hESC-derived RPE Cell Coated Parylene Membrane Implants, in Patients with Advanced Dry Age-Related Macular Degeneration CIRM Mark Humayun, MD, PhD A Novel Treatment for Retinal Ischemia NIH Mark Humayun, MD, PhD An Engineering Research Center for Biomimetic Microelectronic Systems NSF Mark Humayun, MD, PhD Mexican–American Glaucoma Genetic Study NIH Rohit Varma, MD, MPH Primary Open Angle African-American Glaucoma Genetics NIH Rohit Varma, MD, MPH African–American Eye Disease Study NIH Rohit Varma, MD, MPH Los Angeles Latino Eye Study NIH Rohit Varma, MD, MPH Wearable Visual Aid as Treatment for TBI Associated Visual Dysfunction A Novel Treatment for Major Blinding Diseases 20 A layer of hESC-derived polarized RPE stem cells grown on the supporting parylene membrane (white) is shown implanted in the subretinal space. Implanting Stem Cells to Overcome AMD Researchers at the USC Eye Institute are working to restore vision to patients with advanced age-related macular degeneration (AMD). By growing thin sheets of stem cell-derived cells and surgically implanting them into the eye to replace diseased tissue, they hope to restore the retina’s critical light-sensitive cells. USC stem cell researchers identified a stem cell line that contains the characteristics of normal adult retinal pigment epithelium (RPE) cells. USC bioengineers developed a material that can act as a scaffold for RPE cells to allow them to function normally. Their collaborative advancements will be at the center of Phase I clinical trials expected to begin within one year. Retinal-cell implants have the potential to improve the lives of an estimated 1.75 million people in the United States who have AMD — the leading cause of vision loss and blindness among the elderly. David Hinton, MD, associate dean for vision science, and Mark Humayun, MD, PhD, professor of ophthalmology and bioengineering, are principal investigators for a $19 million grant from the California Institute for Regenerative Medicine to develop a stem cell-based treatment for AMD. 21 RESEARCH DISCOVERING AMERICANS’ VISION RISKS LATINOS CHINESE-AMERICANS Among Latinos with Type 2 A study is underway to obtain diabetes, Native-American ancestry prevalence estimates of visual is a significant risk factor for impairment, refractive error, diabetic retinopathy, the leading diabetic retinopathy, open-angle cause of blindness in working- and angle-closure glaucoma, lens age adults in the United States, opacities, and age-related macular affecting more than 4 million degeneration in Chinese-Americans. Americans, age 40 and older. CHILDREN AFRICAN-AMERICANS Myopia (nearsightedness) and African-Americans bear a heavier hyperopia (farsightedness) vary burden of diabetic macular edema widely among children of different (DME), one of the leading causes ethnic groups. For example, of blindness in diabetic patients in African-American children are the United States. Although Latinos most likely to have myopia but have the highest incidence of least likely to have hyperopia, diabetes, more African-Americans compared to Latino and non- suffer from its vision complications. Hispanic white children. Major Studies of Minority Populations USC Eye Institute research about the prevalence and impact of eye diseases in many vulnerable populations includes: • Los Angeles Latino Eye Study (LALES), 1999–2014 • Multi-Ethnic Pediatric Eye Disease Study (MEPEDS), 2003-2011 • Chinese-American Eye Study (CHES), 2008-2013 • African-American Eye Disease Study (AFEDS), 2013-2018 Image of perifoveal region of a fetal-week 19 retina shows retinoblastoma suppressor protein (stained in red) expressed at especially high levels in nuclei of cone precursors (stained in green). Leukocoria, a white reflection from within the eye, is often the first sign of a growing retinoblastoma tumor. Identifying the Cause of Retinoblastoma Retinoblastoma is an eye cancer that usually affects children one to two years of age. Although rare, it is the most common malignant tumor of the eye in children. Left untreated, retinoblastoma can be fatal or result in blindness. USC Eye Institute faculty researcher David E. Cobrinik, MD, PhD, and his colleagues made a major breakthrough in 2014 by identifying the type of cell and signaling pathways that lead to the development of retinoblastoma. Protecting Vision through Community Health Research Through an ongoing series of comprehensive studies, principal investigator USC Eye Institute epidemiologists Xuejuan Jiang, PhD, assistant professor of research, and Rohit Varma, MD, MPH, professor and chair, USC Department of Ophthalmology, lead community health research. Cobrinik’s research discovered that retinoblastomas originate in immature cone photoreceptor cells that have not fully differentiated. When the RB1 gene in those cells mutates, it no longer encodes a tumor suppressor protein (Rb) that prevents excessive cell growth, resulting in the development of retinoblastoma tumors. Rohit Varma, MD, MPH, director of the USC Eye Institute, is defining important These findings significantly advance the understanding of cancer differences in eye disease among various ethnic groups. because they more generally imply that cancers can develop through Many of the studies, the first of their kind ever conducted, are identifying major risk factors. This new knowledge leads to improvements in vision care and informs the government in setting effective goals for preventive eye care and treatment. the collaboration between a cancer-causing mutation — in this case, inactivation of the RB1 gene — and the circuitry of the cell of origin that sensitizes Rb protein loss. Ultimately, Cobrinik and his research team aim to characterize the cell typespecific signaling pathways that collaborate with RB1 inactivation to identify therapeutic targets for retinoblastoma and other cancers. 22 USC Eye Institute faculty involved in retinoblastoma research include Alan Linn Murphree, MD, (top left) who identified the RB1 gene, David Cobrinik, MD, PhD, (top right), Jonathan Kim, MD, (bottom left) and Jesse Berry, MD, (bottom right) 23 Harry Svoboda Advanced Glaucoma Harry Svoboda’s glaucoma went undiagnosed for many years because it presented in just one eye and had not caused any discomfort. When Harry’s right eye became MEDICAL HISTORY irritated consistently, she sought help and was finally was Advanced primary open-angle glaucoma, right eye. Unaffected left eye. diagnosed with glaucoma. Wanting the best of care, Harry drove more than two hours to the OCULAR HISTORY USC Eye Institute for an appointment with glaucoma-specialist Elevated intraocular pressure to 40 mmHg in the right eye despite maximum medical therapy including Diamox. No evidence of ocular ischemic syndrome (carotid duplex negative). No CNS pathology. No evidence of trauma. No inflammation or steroid use. Alena Reznik, MD. Initially, Reznik prescribed a regimen of eye drops. When that proved ineffective, she performed a specialized procedure that included injection of an anti-scarring agent. Harry’s eye pressure soon decreased to normal levels. Reznik Harry checks Harry’s eye pressures on a regular basis, so Harry can continue to enjoy life to its fullest. Glaucoma Under Control Right Eye IOP: Harry Svoboda TREATMENT Trabeculectomy with subconjunctival injection of Mitomycin-C prior to surgery, resulting in less trauma and greater diffusion. DATE PRESSURE NOTES 8/15/14 39 Initial presentation OUTCOME 9/12/14 24 All topical drops, oral Diamox 10/13/14 39 Despite all topical drops, unable to tolerate Diamox 10/24/14 20 No drops/No Diamox POD 1 after trabeculectomy with subconjunctival injection of Mitomycin C 11/17/14 12 No drops/No Diamox Right eye IOP reduced from 39 to 12. Alena Reznik, MD, assistant professor of clinical ophthalmology, is a glaucoma specialist. 24 25 RESEARCH James D. Weiland, PhD, professor of ophthalmology and biomedical engineering, is deputy director of the Biometric MicroElectronic Systems Engineering Center at USC. TOP 10 PUBLICATIONS BY USC EYE INSTITUTE FACULTY PRIMARY INVESTIGATORS David Cobrinik, MD, PhD 1. X u XL, Singh HP, Wang L, Qi DL, Poulos BK, Abramson DH, Jhanwar SC, Cobrinik D. Rb suppresses human cone-precursor-derived retinoblastoma tumours. Nature. Oct 16, 2014; 514(7522):385-8. Cheryl Craft, PhD 2. R ebrik TI Botchkina I, Craft CM, Korenbrot, JI. CNG-Modulin: the elusive modulator of cone photoreceptor cGMP-gated channel. Journal of Neuroscience. Feb 29 2012;32(9):314253 and Cover. Mark Humayun, MD, PhD and James Weiland, PhD 3. N anduri D, Horasager A, Boynton G, Humayun MS, Greenberg RJ, Weiland JD. Frequency and Amplitude Modulation Have Different Effects on the Percepts Elicited by Retinal Stimulation. Invest Ophthalmol Vis Sci. Jan 20, 2012; 53 (1) 205-214. 4. W eiland JD, Faraji B, Greenberg RJ, Humayun MS, Shellock F. Assessment of MRI issues for the Argus II retinal prosthesis. Magn Reson Imaging. Apr 30, 2012;3, 382-389. Amir Kashani, MD, PhD 5. L opez-Jamie GR, Kashani AH, Saati S, Martin G, Chader G, Humayun, MS. Acute Variations in Retinal Vascular Oxygen Content in a Rabbit Model of Retinal Venous Occlusion. PLOS ONE. Nov 6, 2012;7 (11), e50179. Carmen A. Puliafito, MD, MBA 6. D ai C, Liu X, Zhang HF, Puliafito CA, Jiao S. Absolute retinal blood flow measurement with a dual-beam Doppler optical coherence tomography. Invest Ophthalmol Vis Sci. Dec 9, 2013; 54(13):7998-8003. Arthur Toga, PhD 7. N ovak NM, Stein JL, Medland SE, Hibar DP, Thompson PM, Toga AW. EnigmaVis: Online interactive visualization of The complete list of 2014 publications by USC Eye Institute faculty is on page 43. 26 genome-wide association studies of the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium. Twin Res Hum Genet. 2012; 15(3):414-8. 8. T oga AW, Clark KA, Thompson PM, Shattuck DW, Van Horn JD. Mapping the human connectome. Neurosurgery. 2012; 71(1):1-5. Rohit Varma, MD, MPH 9. V arma R, Bressler NM, Doan QV, Gleeson M, Danese M, Bower JK, Selvin E, Dolan C, Fine J, Colman S, Turpcu A. Prevalence of and Risk Factor for Diabetic Macular Edema in the United States. JAMA Ophthalmol. 2014; 132(11):1334-1340. 10. Xie JZ, Tarczy-Hornoch K, Lin J, Cotter SA, Torres M, Varma R. Color vision deficiency in preschool children: the multi-ethnic pediatric eye disease study. Ophthalmology. July 2014; 121(7):1469-1474. After implanting, the soft stent conforms to eye tissue and provides subconjuctival drainage of fluid. Reinventing Glaucoma Treatment For glaucoma patients who no longer respond to medications or laser trabeculoplasty, trabeculectomy and tube shunt procedures are the most effective treatments because they rapidly lower intraocular pressure (IOP). For decades, they have been the most-performed glaucoma surgeries worldwide. Approximately the width of a human hair, the stent is injected into the eye through a small, self-sealing corneal incision. It creates a gentle outflow of fluid from the eye’s anterior chamber into the surrounding subconjuctival tissue. This pathway for drainage has been proven effective and is preferred by physicians worldwide. Despite their proven effectiveness, trabeculectomies and tube shunts are highly invasive and have a oneyear complication rate as high as 50 percent for high-risk glaucoma patients. Outcomes also have shown a high degree of variability that can lead to too little or too much IOP reduction. Over time, shunts can become less effective and require replacement. The gel stent is pliable, noninflammatory and conforms to eye tissue, which is likely to minimize issues with migration, erosion and corneal endothelial damage often seen with synthetic materials. The preloaded injector enables standardized minimally invasive insertion of the stent. International clinical trials have shown that the gel stent significantly and safely lowers intraocular pressure. Researchers at USC Eye Institute have developed a more effective alternative — a soft stent made of permanent, collagen-derived gelatin. The gel stent is approved in Europe for primary open angle glaucoma where other treatment methods have failed. In the United States, it is an investigational device, awaiting approval by the U.S. Food and Drug Administration. This breakthrough holds the promise to prevent glaucoma-related vision loss through a broadly adoptable 10-minute procedure. Glaucoma is the world’s No. 2 cause of blindness and affects more than 60 million people worldwide. USC Eye Institute glaucoma specialists Alena Reznik, MD, assistant professor of clinical ophthalmology, and Rohit Varma, MD, MPH, professor and chair, Department of Ophthalmology, are leading gel stent development. 27 Emily Mangel Complex Corneal Disease Emily Emily Mangel was born with congenital varicella syndrome, a rare disease that causes various abnormalities of the body. For Emily, the disease affected her MEDICAL HISTORY right eye, right leg, and left arm and hand. Over many years of Fetal varicella affected right eye, right leg, and left arm/hand. treatment at Children’s Hospital Los Angeles (CHLA), Emily made tremendous progress in overcoming her challenges. OCULAR HISTORY For her right eye, Emily began treatment at age five with Mark Keratoconjunctivitis sicca, neurotrophic keratitis, perforated cornea, penetrating keratoplasty and tarsorrhaphy. specialists. Using medications, they preserved Emily’s corneal Borchert, MD, and Jonathan Song, MD, USC Eye Institute corneal surface from repeated thinning and healing until she reached her early twenties, when multiple perforations led them to perform a TREATMENT Prosthetic replacement of the ocular surface ecosystem (PROSE). OUTCOME Best corrected vision improved from 20/200 to 20/30 in the right eye with PROSE device. Enhanced comfort and ocular surface protection. Emily began treatment with USC Eye Institute specialists when she was 5 years old, shown here in a Peter Pan costume for Halloween. corneal transplant. To protect the corneal surface, Emily’s right eye was sewn shut for several months. When it was reopened, Emily’s vision markedly improved. To protect her corneal surface and further improve her vision, Emily took advantage of an innovative treatment — prosthetic replacement of the ocular surface ecosystem, or PROSE. Gloria Chiu, OD, fitted Emily with the customized device and helped her learn how to apply and remove it, despite limitations with her left hand. Emily now wears the PROSE device on a daily basis and experiencing improvements in eye comfort, vision and protection of the cornea. The gas-permeable PROSE device creates a smooth optical surface above the cornea and bathes the ocular surface with a reservoir of sterile saline. A trio of USC Eye Institute specialists have provided 22 years of continuous care for Emily’s complex vision challenges. Mark Borchert, MD, (left), Gloria Chiu, OD, (center), Jonathan Song, MD, (right) 28 29 RESEARCH Advancing Imaging of the Retina Clinician-scientists at the USC Eye Institute, longtime innovators in ocular imaging, continue to develop new technologies to advance diagnosis and treatment of eye disease. Jeannie Chen, PhD, M. Elizabeth Fini, PhD, Scott Fraser PhD, and Sarah Hamm-Alvarez, PhD, are among the USC Eye Institute research collaborators who published major papers in 2014. TOP 10 PUBLICATIONS BY USC EYE INSTITUTE FACULTY COLLABORATORS Jeannie Chen, PhD 1. M oaven H, Koike Y, Jao C, Gurevich VV, Langen R, Chen J. Visual arrestin interactions with clathrin adaptor AP2 regulates photoreceptor cell survival. Proc Natl Acad Sci. 2013; 110:9463-9468. Scott Fraser, PhD 2. K im DY, Finglera J, Zawadzki RJ, Park SS, Morse LS, Schwartz DM, Fraser SE, Werner JS. Optical imaging of the chorioretinal vasculature in the living human eye. Proc Natl Acad Sci. Aug 27, 2013;110(35); 14354-14359. Elizabeth Fini, PhD 3. J eong S, Ledee DR, Gordon GM, Itakura T, Patel N, Martin A, Quinn J, Fini ME. Interaction of clusterin (CLU) and matrix metalloproteinase-9 (MMP-9): implications for epithelial homeostasis and inflammation. American Journal of Pathology. 2012;180:2028-39. 4. S antos ARC, Corredor RG, Obeso BA, Wang Y, Trakhtenberg EF, Ponmattam J, Dvoriantchikova G, Ivanov D, Shestopalov VI, Goldberg JL, Fini ME (co-senior author), Bajenaru ML. Beta1 integrin-focal adhesion kinase (FAK) signaling modulates retinal ganglion cell survival. PLOS ONE, 2012, 7(10):e48332. Sarah Hamm-Alvarez, PhD 5. X u S, Ma L, Evans E, Okamoto T, Hamm-Alvarez SF. Polymeric immunoglobulin A receptor traffics through two distinct apically-targeted pathways in primary lacrimal gland acinar cells. J Cell Sci. 2013; 126:2704-2717. 6. H amm-Alvarez SF, Janga SR, EdmanWoolcott MC, Madrigal S, Shah M, Frousiakis S, Renduchintala K, Zhu J, Bricel S, Silka K, Bach D, Heur M, Christianakis S, Arkfeld DA, Stohl W. Tear Cathepsin S-A candidate biomarker for Sjögren’s syndrome. Arthritis Rheumatol. Jul 2014; 66(7):1872-81 Huizong Tao, PhD 7. L i YT, Ibrahim LA, Liu BH, Zhang LI, Tao HW. Linear transformation of thalamocortical input by intracortical excitation. Nat Neurosci. 2013;16:1324-1330. The complete list of 2014 publications by USC Eye Institute faculty is on page 43. 30 Bosco S. Tjan, PhD 8. N andy AS, Tjan BS. Saccadeconfounded image statistics explain visual crowding. Nature Neuroscience. 2012;15(3), 463–469. David Hinton, MD, PhD 9. S reekumar PG, Chothe P, Sharma KK, Baid R, Kompella U, Spee C, Kannan N, Manh C, Ryan SJ, Ganapathy V, Kannan R, Hinton DR. Antiapoptotic properties of alpha-crystallin-derived peptide chaperones and characterization of their uptake transporters in RPE cells. Invest Ophthalmol Vis Sci. 2013; 54:2787-2798. F eatured in the Investigative Ophthalmology and Visual Science Journal as “Research Highlight”: Stern JH. Mini-Chaperones for Early AMD. Invest Ophthalmol Vis Sci. 2013; 54:2799. 10.Zhou P, Kannan R, Spee C, Sreekumar PG, Dou G, Hinton DR. Protection of retina by aB crystallin in sodium iodate induced retinal degeneration. PLOS ONE. May, 29 2014;9(5):e98275. OCT angiography image of the retina shows changes that occur in diabetic retinopathy. OCT angiography eliminates need for dye injection To assess the health of blood vessels in the retina, physicians commonly use fluorescein angiography — injecting dye into a patient’s arm vein and taking photographs of the eye with a special camera that highlights the dye as it circulates in the retinal vessels. USC Eye Institute researchers are eliminating the need for dye injections when visualizing fine retinal capillaries through advanced technology called OCT angiography. This non-invasive method works by isolating the reflected light from the retina and identifying the changes in the phase and intensity of light that are associated with the movement of blood. Pre-clinical pilot studies show that OCT angiography can reveal the changes that occur in diseases such Hyperspectral images from the camera built by the USC Eye Institute to measure the oxygen levels inside the retinal vessels. as diabetic retinopathy and retinal vein occlusion much like fluorescein angiography, but without the risk or discomfort of any injection procedure. Once FDA approved, it is likely that OCT angiography will become an important tool to help diagnose and treat retinal diseases in the future. Hyperspectral imaging provides unprecedented detail Through collaboration with optical engineers and other scientists, USC Eye Institute researchers have built a camera that can measure the spectroscopic features of the retina in unprecedented detail. The camera acquires images in seconds without injections or other invasive procedures. Using hyperspectral imaging, studies demonstrated that patients with advanced forms of diabetic retinopathy have significant changes in the amount of oxygen in the retinal blood vessels. This may suggest that the retina is not receiving the appropriate amount of oxygen in this disease. The information available from hyperspectral imaging holds great promise for expanding the understanding of retinopathy, retinal vein occlusions, choroidal nevi and melanoma, leading to advancements in diagnosis and treatment. Carmen A. Puliafito, MD, MBA, dean, Keck School of Medicine, professor of ophthalmology, and Amir Kashani, MD, PhD, assistant professor of clinical ophthalmology, are leading retinal imaging research at the USC Eye Institute. 31 Margaret Hanopulus Adult Strabismus OCULAR HISTORY Margaret Hanopulus was born with strabismus. The alignment of her eyes was corrected with surgeries when she was a toddler and a teenager. Since then, her eyes gradually drifted out of alignment. Infantile esotropia requiring previous strabismus surgeries in 1958 and 1970. After suffering a stroke and then successfully undergoing surgery Developed large exotropia and hypertropia over the years, with significant deviation. eye surgery was not as scary as she had previously thought. TREATMENT using an adjustable suture technique that enables exceptional Exploration, resection of scar tissue and advancement of previously recessed medial recti (bilaterally) with adjustable suture technique. for an aneurysm, Margaret decided that having corrective She consulted Vivek Patel, MD, a neuro-ophthalmology specialist at the USC Eye Institute. Patel performed strabismus surgery precision and long-term maintenance of correct position. Margaret Now Margaret’s eye alignment is the same as it was in her teenage years. OUTCOME Pre-operative measurements of 35 PD XT and 12 PD LHT improved to 4 PD ET and no hypertropia. She does not experience diplopia and will continue to improve over time. The adjustable suture technique affords remarkable precision and safety for patients who have experienced multiple strabismus surgeries in the past. Vivek Patel, MD, associate professor of clinical ophthalmology, is director of neuro-ophthalmology and adult strabismus at the USC Eye Institute. 32 33 RESEARCH USC Eye Institute Collaborators To advance vision science and clinical ophthalmology, USC Eye Institute collaborates with many other research organizations. We are grateful for their partnership and acknowledge their efforts in a variety of major initiatives. INDIVIDUALS Bioengineering Initiative COLLABORATOR Theodore Berger, PhD Robert Chow, MD, PhD Scott E. Fraser, PhD Malancha Gupta, PhD Hossein Hashemi, PhD Laurent Itti, PhD Gianluca Lazzi, PhD Mark Liker, MD Gerard Medioni, PhD Ellis Meng, PhD Alapakkam Sampath, PhD Kirk Shung, PhD Dong Song, PhD Armand Tanguay, PhD ORGANIZATION USC (Biomedical Engineering) USC (Zhilka Institute) USC (Biomedical Engineering) USC (Materials Science) USC (Electrical Engineering) USC (Computer Science) University of Utah, UT USC (Neurosurgery) USC (Computer Science) USC (Biomedical Engineering) UCLA, CA USC (Biomedical Engineering) USC (Biomedical Engineering) USC (Electrical Engineering) Human Connectome Project COLLABORATOR James T. Becker, PhD Adam L. Boxer, MD, PhD Kyle Chard, PhD Kristi Clark, PhD Eric Deutsch, PhD Ivo Dinov, PhD James Duncan, PhD Jerome Engel, MD Ian Foster, PhD Giovanni Frisoni, MD Gustavo Glusman, PhD Dana Goldman, PhD Gerig Guido, PhD Susan Hayflick, MD Scott Holland, PhD Leroy Hood, MD, PhD John Van Horn, PhD ORGANIZATION University of Pittsburgh, PA UCSF, CA University of Chicago, IL USC (Neurology) Institute for Systems Biology, WA University of Michigan, MI Yale University, CT UCLA, CA University of Chicago, IL IRCCS Fatebenefratelli, Italy Institute for Systems Biology, WA USC (Schaeffer Center for Health Policy and Economics) University of Utah, UT Oregon Health & Science University, OR Cincinnati Children’s Research Foundation, OH Institute for Systems Biology, WA USC (Neurology) COMPANIES •Abbott Medical Optics •Advanced Bionics •Alcon •Allergan •AqueSys •Bausch & Lomb •BioPhan •Boston Scientific •Carl Zeiss Meditech •Cell Traffix •Eli Lilly •Genentech •Harvest Precision Technologies 34 Carl Kesselman, PhD Richard Leahy, PhD Robert Scott Mackin, PhD Geoffrey T Manley, MD, PhD Tom Nichols, PhD Yuko Y. Palesch, PhD Nathan Price, PhD Bruce Rosen, MD, PhD Howard Rosen, MD Seth Seabury, PhD Yonggang Shi, PhD Olaf Sporns, PhD Michael Weiner, MD Wenle Zhao, PhD USC (Industrial and Systems Engineering) USC (Electrical Engineering) UCSF, CA UCSF, CA University of Warwick, United Kingdom Medical University of South Carolina, SC Institute for Systems Biology, WA Massachusetts General Hospital, MA UCSF, CA USC (Schaeffer Center for Health Policy and Economics) USC (Neurology) Indiana University, IN Northern California Institute for Research & Education, CA Medical University of South Carolina, SC Imaging Initiative COLLABORATOR Antonio Capone, MD Thomas Karnowski, PhD Michael Trese, MD George Williams, MD Mark Wong, PhD ORGANIZATION Oakland University, MI Oak Ridge National Labs, TN Oakland University, MI Oakland University, MI National Aeronautics and Space Administration, MD Ocular Epidemiology COLLABORATOR Stanley Azen, PhD Xiaoyi Gao, PhD James Gauderman, PhD Joanne Katz, ScD Ronald Klein, MD, MPH Roberta McKean-Cowdin, PhD Joan M. O’Brien, MD Jeremy Rotter, PhD Kristina Tarczy-Hornoch, MD Tien Wong, MD, PhD ORGANIZATION USC (Preventive Medicine) University of Illinois at Chicago, IL USC (Preventive Medicine) Johns Hopkins University, MD University of Wisconsin-Madison, WI USC (Preventive Medicine) University of Pennsylvania, PA Los Angeles Biomedical Institute, CA Seattle Children's Hospital, WA National University of Singapore, Singapore USC EYE INSTITUTE COLLABORATORS •Iridex •MCNC •Medtronic •Morgan Technical Ceramics •NOCO •Nanodynamics •National Semiconductor •OProbe •Premitec •Product Development Technologies •Quallion •Reichert Technologies •Replenish Inc. •Santen, Inc. •Second Sight •St. Jude ANS •Stryker •SurModics •Synergetics •Texas Instruments •Ventrex •Virginia Technologies 09% U.S. Research Institutions within California 46% U.S. Research Institutions outside California 04% International Research Institutions 41% University of Southern California: Other Departments Argus II is comprised of an eyeglass-mounted camera that sends signals to an implanted 60-electrode receiver, which transmits them to the retina. Signals travel the optic nerve to the brain where they can be interpreted as a visual picture. During months of follow-up testing, Lisa will train her brain to see in a new way, interpreting the signals sent by Argus II. Fulfilling the Promise of Sight for the Blind The world’s first retinal prosthesis reached another milestone in 2014. Lisa Kulik, blinded by retinitis pigmentosa, became the first person on the West Coast to be implanted with the recently FDA-approved Argus II.® Lisa Olmos de Koo, MD, MBA, performed the four-hour procedure at the Keck Medical Center of USC. On the first day of activation, Lisa was already ahead of expectations as she was able to see spots of light. At a 4th of July celebration, she was thrilled to see the light and movement of fireworks. Progress continues as Lisa learns to interpret the signals sent by Argus ll. Confident that her participation in Argus II research is leading toward a cure for blindness, Lisa also participates in a study to determine whether partial restoration of vision has an impact on how the brain processes information. She returns to USC periodically for magnetic imaging resonance (MRI) tests, as well as testing with the Argus II. Retinitis pigmentosa is a genetic disease affecting nearly 100,000 people in the United States. As the disease progresses, patients experience night blindness, tunnel vision, blurring and difficulty adjusting from dark to light environments. Eventually their vision is reduced to shadows and most victims are declared legally blind. For these patients, the improvement of vision provided by Argus II would be nothing short of a miracle. USC Eye Institute retinal specialists Lisa Olmos de Koo, MD, MBA, assistant professor of clinical ophthalmology, and Mark Humayun, MD, PhD, professor of ophthalmology and bioengineering, are leading further development of Argus II. 35 CLINICAL EDUCATION Exceptional Clinical Education The USC Eye Institute provides a residency and fellowship training experience with unique clinical and research opportunities. INSIGHT Clinical Education Clinical education is one of the defining principles at the USC Eye Institute. Visiting professor Joseph Miller, MD, MPH, professor and head, Ophthalmology and Vision Science from the University of Arizona College of Medicine, lectures residents. Our tradition of academic excellence in training leading clinicians and researchers in ophthalmology is well documented. Among current United States ophthalmology chairs, 17 are former faculty members and graduates of Keck School of Medicine of USC Department of Ophthalmology training programs. Priority is on training, mentoring and inspiring future leaders in four diverse and highly acute clinical and surgical settings: · USC Eye Institute at Keck Medical Center of USC, ranked as a top 10 program by U.S. News & World Report for 20 years The USC Eye Institute is proud to be training the next generation of leaders. · Children’s Hospital Los Angeles (CHLA), ranked among the top five children’s hospitals in the U.S. · Los Angeles County (LAC) + USC Medical Center, one of nation’s largest public hospitals · VA Greater Los Angeles Healthcare System, serving the needs of generations of veterans. As one of the most funded eye institutes in the world, the USC Eye Institute collaborates across CORNEAL ENDOTHELIUM CELLS 36 disciplines with a wide variety of industries and institutions. It is an ideal interdisciplinary environment for physicians who have a passion to be an important part of internationally recognized, cutting-edge vision science. Medical Education Keck School of Medicine of USC has 27 basic science and academic departments with more than 1,500 full-time faculty members. Future physicians receive comprehensive training from an ophthalmology faculty that has been ranked in the top 10 nationally by U.S. News & World Report for 20 years. USC Eye Institute faculty who oversee clinical ophthalmology education, from top left, include Malvin Anders, MD, chief of ophthalmology, LAC+USC Medical Center; Jesse Berry, MD, associate residency program director; Vivek Patel, MD, residency program director; Neda Shamie, MD, director of medical education; Rohit Varma, MD, MPH; chair, department of ophthalmology; and Carmen A. Puliafito, MD, MBA, dean, Keck School of Medicine, professor of ophthalmology. 37 Stan Bard Uveitis OCULAR HISTORY Referred for two weeks of uveitis of unclear etiology, found to have Without warning, both of Stan Bard’s eyes suddenly became red and his vision began to blur. He thought the problem was temporary irritation that would go away, but it became worse. Stan consulted several eye specialists, but none was able to offer lasting relief. He became increasingly alarmed when he could neither focus on objects at arm’s length, nor read. a multifocal serpiginoid pattern of After two weeks, Stan’s search for an answer led him to the USC chorioretinal inflammation in both Eye Institute. He consulted with Narsing Rao, MD, Director of eyes thought to be of herpetic origin. the Ophthalmic Pathology Laboratory and Uveitis Service, and TREATMENT Treated with antivirals with dramatic improvement in two days then started Damien Rodger, MD, PhD. The uveitis specialists made a thorough evaluation and decided on a treatment plan that included antiviral medications, followed by a course of oral steroids. on oral steroids. Upon treatment, Stan’s eyes showed marked improvement within OUTCOME its normal state: 20/25 in his right eye and 20/20 in his left eye. Vision improved from 20/70 to 20/25 in the right eye and 20/100 to 20/20 in the left eye. Stan several days. The redness disappeared and his vision returned to UPON PRESENTATION AFTER TWO DAYS OF TREATMENT Widefield fundus images of the right and left eyes below show the dramatic resolution of uveitis. Narsing Rao, MD, professor of ophthalmology and pathology, and Damien Rodger, MD, PhD, a vitreoretinal surgery fellow who will become an assistant professor in 2015, worked together to restore Stan’s vision. 38 39 CLINICAL EDUCATION USC Eye Institute Full-time Faculty, Residents and Fellows 2014-15 Faculty, Fellows and Residents Residents Each year, the USC Eye Institute recruits exceptional residents. The incoming six residents for 2014-15 were accepted from more than 400 applicants. 3RD YEAR Lloyd Cuzzo, MD Co-Chief Resident Tova Mannis, MD Co-Chief Resident Sahar Bedrood, MD, PhD Andrew Browne, MD, PhD Yohko Murakami, MD Saloomeh Saati, MD Mica Bergman, MD, PhD Lilangi Ediriwickrema, MD, MS Esther Lee Kim, MD Sun Young Lee, MD, PhD Benjamin Xu, MD, PhD Dagny Zhu, MD Jiun L. Do, MD, PhD Stavros Moysidis, MD Billy Pan, MD Kelly Rue, MD Grace Shih, MD Philip Storey, MD, MPH Hossein Ameri, MD Vitreoretinal Surgery Meena George, MD Vitreoretinal Surgery Daniel Greene, MD Cornea & External Disease Luxme Hariharan MD, MPH, Pediatric Cornea, Cataract & Glaucoma Hossein Nazari, MD Medical Retina Grace Richter, MD, MPH Damien Rodger, MD, PhD Vitreoretinal Surgery Namita Sagar, MD Glaucoma Hangxiu Xu, MD, PhD Neuro-ophthalmology 2ND YEAR 1ST YEAR Fellows and Clinical Instructors The USC Eye Institute offers clinical fellowship training in six subspecialty areas, including cornea and external disease, glaucoma, neoophthalmology, ophthalmic plastic surgery, retina and uveitis. Informal research fellowships are also awarded by each service and laboratory independently. USC attracts promising academic ophthalmologists from around the world who spend one or two years participating in research programs. Many return to their home countries where they assume positions of national or international leadership. 40 41 CLINICAL EDUCATION USC Eye Institute Full-time Faculty Secondary, Tertiary and Joint Appointment Faculty Hossein Ameri, MD Assistant Professor (as of July 2015) Malvin Anders, MD Associate Professor Jesse Berry, MD Assistant Professor Mark Borchert, MD Professor Angela Buffenn, MD, MPH Assistant Professor Gloria Chiu, OD Assistant Professor David Cobrinik, PhD Associate Professor • • • • • • Joseph Cocozza, Assistant Professor J eannie Chen, PhD, Cell & Neurobiology M. Elizabeth Fini, PhD, Cell & Neurobiology Sarah Hamm-Alvarez, PhD, Pharmacology Shikun He, MD, Pathology David Hinton, MD, Pathology Florence Hofman, PhD, Pathology •Eun Jin Lee, PhD, Biomedical Engineering •Austin K. Mircheff, PhD, Physiology •Maria E. Sibug Saber, MD, Pathology •Joel E. Schechter, PhD, Cell & Neurobiology •Huizhong W. Tao, PhD, Cell & Neurobiology USC Collaborating Faculty • S cott Fraser, PhD, Biomedical Engineering • Judith Hirsch, PhD, Neurobiology • Aaron McGee, PhD, Pediatrics • Bosco Tjan, PhD, Psychology Biju Thomas, PhD, assistant professor of clinical ophthalmology Cheryl Craft, PhD Professor Charles Flowers,MD Associate Professor Henry Fong, PhD Associate Professor J. Martin Heur, MD, PhD Associate Professor Mark Humayun, MD, PhD Professor Veronica Isozaki, OD Assistant Professor Shunwu Jeong, PhD Assistant Professor Xuejuan Jiang, PhD Assistant Professor 2014 Publications 1. Cheung AY, Kashani AH, Drenser KA. Subretinal peripapillary neovascularization associated with persistent fetal vasculature. Retin Cases Brief Rep. 2014 Winter;8(1):83-6 Amir Kashani, MD, PhD Assistant Professor Jonathan Kim, MD Associate Professor Linda Lam, MD Associate Professor Carlos Lastra, MD Clinical Instructor Thomas Lee, MD Associate Professor Debbie Mitra, PhD Assistant Professor Andrew Moshfeghi, MD Associate Professor Arlanna Moshfeghi, MD, MBA Assistant Professor 2. Wu DM, Fawzi AA, Recasens MA, Bertoni B, Chopra V, Rao NA, Eliott D. Good visual outcome after repair of a very large macular hole with neurosensory retinal operculum. Retin Cases Brief Rep. 2014 Spring;8(2):138-40 3. Samimi DB, Chiu GB, Burnstine MA. Prose scleral lens: A novel aid for staged eyelid reconstruction. Ophthal Plast Reconstr Surg. 2014 Sep-Oct;30(5):e119-21 4. Ameri H. Retinal prosthesis, potential future approaches. Clin Experiment Ophthalmol. 2014 Sep-Oct;42(7):599-600 Alan Linn Murphree, MD Professor Grace Richter, MD, MPH Assistant Professor (as of Aug 2015) Rohit Varma, MD, MPH, Professor 42 Sudha Nallasamy,MD Assistant Professor Damien Rodger, MD, PhD Assistant Professor (as of Aug 2015) Dandan Wang, MD Clinical Instructor Lisa Olmos de Koo, MD, MBA Assistant Professor Neda Shamie, MD Associate Professor James Weiland, PhD Professor Vivek Patel, MD Associate Professor Jonathan Song, MD Associate Professor Andrew Weitz, PhD Assistant Professor Carmen Puliafito, MD, MBA Professor Biju Thomas, PhD Assistant Professor John Whalen, PhD Assistant Professor Narsing Rao, MD Professor Paul Thompson, PhD, Professor Sandy ZhangNunes, MD Assistant Professor Bibiana Reiser, MD Assistant Professor Arthur Toga, PhD Provost Professor Alena Reznik, MD Assistant Professor Lernik Torossian, OD Assistant Professor 5. Valenzuela F, Browne A, Srur M, Nieme C, Zanolli M, Lopez-Solis R, Traipe L. Combined phacoemulsification and ahmed glaucoma drainage implant surgery for patients with refractory glaucoma and cataract. J Glaucoma. 2014 Sep 26 6. Saeed S, Quintin J, Kerstens HH, Rao NA, Aghajanirefah A, Matarese F, Cheng SC, Ratter J, Berentsen K, van der Ent MA, Sharifi N, Janssen-Megens EM, Ter Huurne M, Mandoli A, van Schaik T, Ng A, Burden F, Downes K, Frontini M, Kumar V, Giamarellos-Bourboulis EJ, Ouwehand WH, van der Meer JW, Joosten LA, Wijmenga C, Martens JH, Xavier RJ, Logie C, Netea MG, Stunnenberg HG. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science. 2014 Sep 26;345(6204):1251086 7. Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, Giamarellos-Bourboulis EJ, Martens JH, Rao NA, Aghajanirefah A, Manjeri GR, Li Y, Ifrim DC, Arts RJ, van der Meer BM, Deen PM, Logie C, O’Neill LA, Willems P, van de Veerdonk FL, van der Meer JW, Ng A, Joosten LA, Wijmenga C, Stunnenberg HG, Xavier RJ, Netea MG. Mtor- and hif-1alphamediated aerobic glycolysis as metabolic basis for trained immunity. Science. 2014 Sep 26;345(6204):1250684 8. Zhang-Nunes SX, Dang S, Garneau HC, Hwang C, Isaacs D, Chang SH, Goldberg R. Characterization and outcomes of repeat orbital decompression for thyroid-associated orbitopathy. Orbit. 2014 Sep 22:1-9 9. Babiloni C, Del Percio C, Boccardi M, Lizio R, Lopez S, Carducci F, Marzano N, Soricelli A, Ferri R, Triggiani AI, Prestia A, Salinari S, Rasser PE, Basar E, Fama F, Nobili F, Yener G, Emek-Savas DD, Loreto G, Mundi C, Thompson PM, Rossini PM, Frisoni GB. Occipital sources of resting-state alpha rhythms are related to local gray matter density in subjects with amnesic mild cognitive impairment and alzheimer’s disease. Neurobiol Aging. 2014 Sep 21 10. Lee JG, Heur M. Interleukin-1beta-induced wnt5a enhances human corneal endothelial cell migration through regulation of cdc42 and rhoa. Mol Cell Biol. 2014 Sep 15;34(18):3535-45 11. Riverol M, Becker JT, Lopez OL, Raji CA, Thompson PM, Carmichael OT, Gach HM, Longstreth Jr WT, Fried L, Tracy RP, Kuller LH. Relationship between systemic and cerebral vascular disease and brain structure integrity in normal elderly individuals. J Alzheimers Dis. 2014 Sep 11 12. Narendra DP, Wang N, Erkkinen MG, Jagadeesan J, Lee TC, Zimmerman EE, Klein JP. An anomalous developmental venous anomaly. Neurology. 2014 Sep 9;83(11):1033-4 13. Puliafito CA. Oct angiography: The next era of oct technology emerges. Ophthalmic Surg Lasers Imaging Retina. 2014 Sep 1;45(5):360 14. Adogwa O, Huang MI, Thompson PM, Darlington T, Cheng JS, Gokaslan ZL, Gottfried ON, Bagley CA, Anderson GD, Isaacs RE. No difference in postoperative complications, pain, and functional outcomes up to 2 years after incidental durotomy in lumbar spinal fusion: A prospective, multi-institutional, propensity-matched analysis of 1,741 patients. Spine J. 2014 Sep 1;14(9):1828-34 15. Thomas JB, Brier MR, Bateman RJ, Snyder AZ, Benzinger TL, Xiong C, Raichle M, Holtzman DM, Sperling RA, Mayeux R, Ghetti B, Ringman JM, Salloway S, McDade E, Rossor MN, Ourselin S, Schofield PR, Masters CL, Martins RN, Weiner MW, Thompson PM, Fox NC, Koeppe RA, Jack CR, Jr., Mathis CA, Oliver A, Blazey TM, Moulder K, Buckles V, Hornbeck R, Chhatwal J, Schultz AP, Goate AM, Fagan AM, Cairns NJ, Marcus DS, Morris JC, Ances BM. Functional connectivity in autosomal dominant and late-onset alzheimer disease. JAMA Neurol. 2014 Sep;71(9):1111-22 16. Khan MA, DeCroos FC, Storey PP, Shields JA, Garg SJ, Shields CL. Outcomes of anti-vascular endothelial growth factor therapy in the management of choroidal neovascularization associated with choroidal osteoma. Retina. 2014 Sep;34(9):1750-6 17. Kashani AH, Lopez Jaime GR, Saati S, Martin G, Varma R, Humayun MS. Noninvasive assessment of retinal vascular oxygen content among normal and diabetic human subjects: A study using hyperspectral computed tomographic imaging spectroscopy. Retina. 2014 Sep;34(9):1854-60 18. Gao X, Gauderman WJ, Marjoram P, Torres M, Chen YD, Taylor KD, Rotter JI, Varma R. Native american ancestry is associated with severe diabetic retinopathy in latinos. Invest Ophthalmol Vis Sci. 2014 Sep;55(9):6041-5 19. Cavedo E, Pievani M, Boccardi M, Galluzzi S, Bocchetta M, Bonetti M, Thompson PM, Frisoni GB. Medial temporal atrophy in early and lateonset alzheimer’s disease. Neurobiol Aging. 2014 Sep;35(9):2004-12 20.Prasad G, Joshi AA, Feng A, Toga AW, Thompson PM, Terzopoulos D. Skull-stripping with machine learning deformable organisms. J Neurosci Methods. 2014 Oct 30;236:114-24 43 CLINICAL EDUCATION 21. Xu XL, Singh HP, Wang L, Qi DL, Poulos BK, Abramson DH, Jhanwar SC, Cobrinik D. Rb suppresses human cone-precursor-derived retinoblastoma tumours. Nature. 2014 Oct 16;514(7522):385-8 22. Shen KK, Rose S, Fripp J, McMahon KL, de Zubicaray GI, Martin NG, Thompson PM, Wright MJ, Salvado O. Investigating brain connectivity heritability in a twin study using diffusion imaging data. Neuroimage. 2014 Oct 15;100:628-41 23. Jin Y, Shi Y, Zhan L, Gutman BA, de Zubicaray GI, McMahon KL, Wright MJ, Toga AW, Thompson PM. Automatic clustering of white matter fibers in brain diffusion mri with an application to genetics. Neuroimage. 2014 Oct 15;100:75-90 24. Hill RH, 3rd, Czyz CN, Kandapalli S, ZhangNunes SX, Cahill KV, Wulc AE, Foster JA. Evolving minimally invasive techniques for tear trough enhancement. Ophthal Plast Reconstr Surg. 2014 Oct 8 25. Ching CR, Hua X, Hibar DP, Ward CP, Gunter JL, Bernstein MA, Jack CR, Jr., Weiner MW, Thompson PM. Does mri scan acceleration affect power to track brain change? Neurobiol Aging. 2014 Oct 7 26. Storey P, Alshareef R, Khuthaila M, London N, Leiby B, DeCroos C, Kaiser R. Pars plana vitrectomy and scleral buckle versus pars plana vitrectomy alone for patients with rhegmatogenous retinal detachment at high risk for proliferative vitreoretinopathy. Retina. 2014 Oct;34(10):1945-51 27. Raji CA, Erickson KI, Lopez OL, Kuller LH, Gach HM, Thompson PM, Riverol M, Becker JT. Regular fish consumption and age-related brain gray matter loss. Am J Prev Med. 2014 Oct;47(4):444-51 28. Pan BX, Yee KM, Ross-Cisneros FN, Sadun AA, Sebag J. Inner retinal optic neuropathy: Vitreomacular surgery-associated disruption of the inner retina. Invest Ophthalmol Vis Sci. 2014 Oct;55(10):6756-64 29. Xiang S, Yuan L, Fan W, Wang Y, Thompson PM, Ye J. Bi-level multi-source learning for heterogeneous block-wise missing data. Neuroimage. 2014 Nov 15;102p1:192-206 30.Dennis EL, Jahanshad N, Braskie MN, Warstadt NM, Hibar DP, Kohannim O, Nir TM, McMahon KL, de Zubicaray GI, Montgomery GW, Martin NG, Toga AW, Wright MJ, Thompson PM. Obesity gene negr1 associated with white matter integrity in healthy young adults. Neuroimage. 2014 Nov 15;102 Pt 2:548-57 31. Couvy-Duchesne B, Blokland GA, Hickie IB, Thompson PM, Martin NG, de Zubicaray GI, McMahon KL, Wright MJ. Heritability of head motion during resting state functional mri in 462 healthy twins. Neuroimage. 2014 Nov 15;102 Pt 2:424-34 32. Patel VR, Zee DS. The cerebellum in eye movement control: Nystagmus, coordinate 44 frames and disconjugacy. Eye (Lond). 2014 Nov 14 33. Tai AX, Song JC. Surgical outcomes of baerveldt implants in pediatric glaucoma patients. J aapos. 2014 Nov 12 34. Cunningham SI, Weiland JD, Bao P, LopezJaime GR, Tjan BS. Correlation of vision loss with tactile-evoked v1 responses in retinitis pigmentosa. Vision Res. 2014 Nov 3 35. Matsunaga D, Yi J, Puliafito CA, Kashani AH. Oct angiography in healthy human subjects. Ophthalmic Surg Lasers Imaging Retina. 2014 Nov 1;45(6):510-5 36. Warstadt NM, Dennis EL, Jahanshad N, Kohannim O, Nir TM, McMahon KL, de Zubicaray GI, Montgomery GW, Henders AK, Martin NG, Whitfield JB, Jack CR, Jr., Bernstein MA, Weiner MW, Toga AW, Wright MJ, Thompson PM. Serum cholesterol and variant in cholesterol-related gene cetp predict white matter microstructure. Neurobiol Aging. 2014 Nov;35(11):2504-13 37. Varma R, Bressler NM, Doan QV, Gleeson M, Danese M, Bower JK, Selvin E, Dolan C, Fine J, Colman S, Turpcu A. Prevalence of and risk factors for diabetic macular edema in the united states. JAMA Ophthalmol. 2014 Nov;132(11):1334-40 38. Renteria ME, Hansell NK, Strike LT, McMahon KL, de Zubicaray GI, Hickie IB, Thompson PM, Martin NG, Medland SE, Wright MJ. Genetic architecture of subcortical brain regions: Common and region-specific genetic contributions. Genes Brain Behav. 2014 Nov;13(8):821-30 39. Mah FS, Davidson R, Holland EJ, Hovanesian J, John T, Kanellopoulos J, Shamie N, Starr C, Vroman D, Kim T. Current knowledge about and recommendations for ocular methicillinresistant staphylococcus aureus. J Cataract Refract Surg. 2014 Nov;40(11):1894-908 40.40.Kashani AH, Brown KT, Chang E, Drenser KA, Capone A, Trese MT. Diversity of retinal vascular anomalies in patients with familial exudative vitreoretinopathy. Ophthalmology. 2014 Nov;121(11):2220-7 41. Nugent AK, Paulus YM, Chan A, Kim JW, Schwartz EJ, Moshfeghi DM. Multiple myeloma recurrence with optic nerve infiltration diagnosed by vitrectomy, immunohistochemistry, and in situ hybridization. Eur J Ophthalmol. 2014 MayJun;24(3):446-8 42. Roussotte FF, Gutman BA, Madsen SK, Colby JB, Thompson PM. Combined effects of alzheimer risk variants in the clu and apoe genes on ventricular expansion patterns in the elderly. J Neurosci. 2014 May 7;34(19):6537-45 45. Prasad G, Joshi SH, Thompson PM. Optimizing brain connectivity networks for disease classification using epic. Proc IEEE Int Symp Biomed Imaging. 2014 May;2014:834-7 46. Pirotta E, Brookes KL, Graham IM, Thompson PM. Variation in harbour porpoise activity in response to seismic survey noise. Biol Lett. 2014 May;10(5):20131090 47. Hurtz S, Woo E, Kebets V, Green AE, Zoumalan C, Wang B, Ringman JM, Thompson PM, Apostolova LG. Age effects on cortical thickness in cognitively normal elderly individuals. Dement Geriatr Cogn Dis Extra. 2014 May;4(2):221-7 48. Gadelkarim JJ, Ajilore O, Schonfeld D, Zhan L, Thompson PM, Feusner JD, Kumar A, Altshuler LL, Leow AD. Investigating brain community structure abnormalities in bipolar disorder using path length associated community estimation. Hum Brain Mapp. 2014 May;35(5):2253-64 49.Cannon TD, Sun F, McEwen SJ, Papademetris X, He G, van Erp TG, Jacobson A, Bearden CE, Walker E, Hu X, Zhou L, Seidman LJ, Thermenos HW, Cornblatt B, Olvet DM, Perkins D, Belger A, Cadenhead K, Tsuang M, Mirzakhanian H, Addington J, Frayne R, Woods SW, McGlashan TH, Constable RT, Qiu M, Mathalon DH, Thompson P, Toga AW. Reliability of neuroanatomical measurements in a multisite longitudinal study of youth at risk for psychosis. Hum Brain Mapp. 2014 May;35(5):2424-34 50. Borchert M, Garcia-Filion P, Fink C, Geffner M, Nelson M. Re: Ramakrishnaiah et al.: Reliability of magnetic resonance imaging for the detection of hypopituitarism in children with optic nerve hypoplasia (ophthalmology 2014;121:387-91). Ophthalmology. 2014 May;121(5):e26-7 51. Roussotte FF, Jahanshad N, Hibar DP, Thompson PM. Altered regional brain volumes in elderly carriers of a risk variant for drug abuse in the dopamine d2 receptor gene (drd2). Brain Imaging Behav. 2014 Mar 16 52. Yehoshua Z, de Amorim Garcia Filho CA, Nunes RP, Gregori G, Penha FM, Moshfeghi AA, Zhang K, Sadda S, Feuer W, Rosenfeld PJ. Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: The complete study. Ophthalmology. 2014 Mar;121(3):693-701 53. Wang M, Lu AT, Varma R, Schuman JS, Greenfield DS, Huang D. Combining information from 3 anatomic regions in the diagnosis of glaucoma with time-domain optical coherence tomography. J Glaucoma. 2014 Mar;23(3):129-35 43. Wong SC, Lee TC, Heier JS, Ho AC. Endoscopic vitrectomy. Curr Opin Ophthalmol. 2014 May;25(3):195-206 54. Nir TM, Jahanshad N, Busovaca E, Wendelken L, Nicolas K, Thompson PM, Valcour VG. Mapping white matter integrity in elderly people with hiv. Hum Brain Mapp. 2014 Mar;35(3):975-92 44.Weiland JD, Humayun MS. Retinal prosthesis. IEEE Trans Biomed Eng. 2014 May;61(5):1412-24 55. Haas BW, Sheau K, Kelley RG, Thompson PM, Reiss AL. Regionally specific increased volume of the amygdala in williams syndrome: Evidence from surface-based modeling. Hum Brain Mapp. 2014 Mar;35(3):866-74 56. Dennis EL, Thompson PM. Functional brain connectivity using fmri in aging and alzheimer’s disease. Neuropsychol Rev. 2014 Mar;24(1):49-62 57. Chen K, Weiland JD. Discovery of retinal elastin and its possible role in age-related macular degeneration. Ann Biomed Eng. 2014 Mar;42(3):678-84 58. Weiner MW, Veitch DP, Hayes J, Neylan T, Grafman J, Aisen PS, Petersen RC, Jack C, Jagust W, Trojanowski JQ, Shaw LM, Saykin AJ, Green RC, Harvey D, Toga AW, Friedl KE, Pacifico A, Sheline Y, Yaffe K, Mohlenoff B. Effects of traumatic brain injury and posttraumatic stress disorder on alzheimer’s disease in veterans, using the alzheimer’s disease neuroimaging initiative. Alzheimers Dement. 2014 Jun;10(3 Suppl):S226-35 59. Van Horn JD, Toga AW. Human neuroimaging as a “big data” science. Brain Imaging Behav. 2014 Jun;8(2):323-31 60.Thompson PM, Stein JL, Medland SE, Hibar DP, Vasquez AA, Renteria ME, Toro R, Jahanshad N, Schumann G, Franke B, Wright MJ, Martin NG, Agartz I, Alda M, Alhusaini S, Almasy L, Almeida J, Alpert K, Andreasen NC, Andreassen OA, Apostolova LG, Appel K, Armstrong NJ, Aribisala B, Bastin ME, Bauer M, Bearden CE, Bergmann O, Binder EB, Blangero J, Bockholt HJ, Boen E, Bois C, Boomsma DI, Booth T, Bowman IJ, Bralten J, Brouwer RM, Brunner HG, Brohawn DG, Buckner RL, Buitelaar J, Bulayeva K, Bustillo JR, Calhoun VD, Cannon DM, Cantor RM, Carless MA, Caseras X, Cavalleri GL, Chakravarty MM, Chang KD, Ching CR, Christoforou A, Cichon S, Clark VP, Conrod P, Coppola G, Crespo-Facorro B, Curran JE, Czisch M, Deary IJ, de Geus EJ, den Braber A, Delvecchio G, Depondt C, de Haan L, de Zubicaray GI, Dima D, Dimitrova R, Djurovic S, Dong H, Donohoe G, Duggirala R, Dyer TD, Ehrlich S, Ekman CJ, Elvsashagen T, Emsell L, Erk S, Espeseth T, Fagerness J, Fears S, Fedko I, Fernandez G, Fisher SE, Foroud T, Fox PT, Francks C, Frangou S, Frey EM, Frodl T, Frouin V, Garavan H, Giddaluru S, Glahn DC, Godlewska B, Goldstein RZ, Gollub RL, Grabe HJ, Grimm O, Gruber O, Guadalupe T, Gur RE, Gur RC, Goring HH, Hagenaars S, Hajek T, Hall GB, Hall J, Hardy J, Hartman CA, Hass J, Hatton SN, Haukvik UK, Hegenscheid K, Heinz A, Hickie IB, Ho BC, Hoehn D, Hoekstra PJ, Hollinshead M, Holmes AJ, Homuth G, Hoogman M, Hong LE, Hosten N, Hottenga JJ, Hulshoff Pol HE, Hwang KS, Jack CR, Jr., Jenkinson M, Johnston C, Jonsson EG, Kahn RS, Kasperaviciute D, Kelly S, Kim S, Kochunov P, Koenders L, Kramer B, Kwok JB, Lagopoulos J, Laje G, Landen M, Landman BA, Lauriello J, Lawrie SM, Lee PH, Le Hellard S, Lemaitre H, Leonardo CD, Li CS, Liberg B, Liewald DC, Liu X, Lopez LM, Loth E, Lourdusamy A, Luciano M, Macciardi F, Machielsen MW, Macqueen GM, Malt UF, Mandl R, Manoach DS, Martinot JL, Matarin M, Mather KA, Mattheisen M, Mattingsdal M, Meyer-Lindenberg A, McDonald C, McIntosh AM, McMahon FJ, McMahon KL, Meisenzahl E, Melle I, Milaneschi Y, Mohnke S, Montgomery GW, Morris DW, Moses EK, Mueller BA, Munoz Maniega S, Muhleisen TW, Muller-Myhsok B, Mwangi B, Nauck M, Nho K, Nichols TE, Nilsson LG, Nugent AC, Nyberg L, Olvera RL, Oosterlaan J, Ophoff RA, Pandolfo M, Papalampropoulou-Tsiridou M, Papmeyer M, Paus T, Pausova Z, Pearlson GD, Penninx BW, Peterson CP, Pfennig A, Phillips M, Pike GB, Poline JB, Potkin SG, Putz B, Ramasamy A, Rasmussen J, Rietschel M, Rijpkema M, Risacher SL, Roffman JL, Roiz-Santianez R, RomanczukSeiferth N, Rose EJ, Royle NA, Rujescu D, Ryten M, Sachdev PS, Salami A, Satterthwaite TD, Savitz J, Saykin AJ, Scanlon C, Schmaal L, Schnack HG, Schork AJ, Schulz SC, Schur R, Seidman L, Shen L, Shoemaker JM, Simmons A, Sisodiya SM, Smith C, Smoller JW, Soares JC, Sponheim SR, Sprooten E, Starr JM, Steen VM, Strakowski S, Strike L, Sussmann J, Samann PG, Teumer A, Toga AW, Tordesillas-Gutierrez D, Trabzuni D, Trost S, Turner J, Van den Heuvel M, van der Wee NJ, van Eijk K, van Erp TG, van Haren NE, van ‘t Ent D, van Tol MJ, Valdes Hernandez MC, Veltman DJ, Versace A, Volzke H, Walker R, Walter H, Wang L, Wardlaw JM, Weale ME, Weiner MW, Wen W, Westlye LT, Whalley HC, Whelan CD, White T, Winkler AM, Wittfeld K, Woldehawariat G, Wolf C, Zilles D, Zwiers MP, Thalamuthu A, Schofield PR, Freimer NB, Lawrence NS, Drevets W. The enigma consortium: Large-scale collaborative analyses of neuroimaging and genetic data. Brain Imaging Behav. 2014 Jun;8(2):153-82 61. Shen L, Thompson PM, Potkin SG, Bertram L, Farrer LA, Foroud TM, Green RC, Hu X, Huentelman MJ, Kim S, Kauwe JS, Li Q, Liu E, Macciardi F, Moore JH, Munsie L, Nho K, Ramanan VK, Risacher SL, Stone DJ, Swaminathan S, Toga AW, Weiner MW, Saykin AJ. Genetic analysis of quantitative phenotypes in ad and mci: Imaging, cognition and biomarkers. Brain Imaging Behav. 2014 Jun;8(2):183-207 62. Roussotte FF, Gutman BA, Madsen SK, Colby JB, Narr KL, Thompson PM. The apolipoprotein e epsilon 4 allele is associated with ventricular expansion rate and surface morphology in dementia and normal aging. Neurobiol Aging. 2014 Jun;35(6):1309-17 63. Roussotte FF, Daianu M, Jahanshad N, Leonardo CD, Thompson PM. Neuroimaging and genetic risk for alzheimer’s disease and addictionrelated degenerative brain disorders. Brain Imaging Behav. 2014 Jun;8(2):217-33 64. Peng DX, Kelley RG, Quintin EM, Raman M, Thompson PM, Reiss AL. Cognitive and behavioral correlates of caudate subregion shape variation in fragile x syndrome. Hum Brain Mapp. 2014 Jun;35(6):2861-8 65. Pefkianaki M, Westcott M, Liew G, Lee R, Pavesio C, Rao NA, Gupta A, Bansal R, Khairallah M, Kahloun R. Diagnostic and therapeutic challenges. Retina. 2014 Jun;34(6):1247-52 66.Nazari H, Karakousis PC, Rao NA. Replication of mycobacterium tuberculosis in retinal pigment epithelium. JAMA Ophthalmol. 2014 Jun;132(6):724-9 67. Medland SE, Jahanshad N, Neale BM, Thompson PM. Whole-genome analyses of whole-brain data: Working within an expanded search space. Nat Neurosci. 2014 Jun;17(6):791-800 68.Dinov ID, Petrosyan P, Liu Z, Eggert P, Zamanyan A, Torri F, Macciardi F, Hobel S, Moon SW, Sung YH, Jiang Z, Labus J, Kurth F, Ashe-McNalley C, Mayer E, Vespa PM, Van Horn JD, Toga AW. The perfect neuroimaging-genetics-computation storm: Collision of petabytes of data, millions of hardware devices and thousands of software tools. Brain Imaging Behav. 2014 Jun;8(2):311-22 69.Chen K, Rowley AP, Weiland JD, Humayun MS. Elastic properties of human posterior eye. J Biomed Mater Res A. 2014 Jun;102(6):2001-7 70. Nicholson LB, Kim BT, Jardon J, TownsendPico W, Santos C, Moshfeghi AA, Albini TA, Eliott D, Sobrin L. Severe bilateral ischemic retinal vasculitis following cataract surgery. Ophthalmic Surg Lasers Imaging Retina. 2014 Jul-Aug;45(4):338-42 71. Kashani AH, Cheung AY, Robinson J, Williams GA. Longitudinal optical density analysis of subretinal fluid after surgical repair of rhegmatogenous retinal detachment. Retina. 2014 Jul 30 72. Braskie MN, Boyle CP, Rajagopalan P, Gutman BA, Toga AW, Raji CA, Tracy RP, Kuller LH, Becker JT, Lopez OL, Thompson PM. Physical activity, inflammation, and volume of the aging brain. Neuroscience. 2014 Jul 25;273:199-209 73. Kochunov P, Jahanshad N, Sprooten E, Nichols TE, Mandl RC, Almasy L, Booth T, Brouwer RM, Curran JE, de Zubicaray GI, Dimitrova R, Duggirala R, Fox PT, Elliot Hong L, Landman BA, Lemaitre H, Lopez LM, Martin NG, McMahon KL, Mitchell BD, Olvera RL, Peterson CP, Starr JM, Sussmann JE, Toga AW, Wardlaw JM, Wright MJ, Wright SN, Bastin ME, McIntosh AM, Boomsma DI, Kahn RS, den Braber A, de Geus EJ, Deary IJ, Hulshoff Pol HE, Williamson DE, Blangero J, van ‘t Ent D, Thompson PM, Glahn DC. Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling. Neuroimage. 2014 Jul 15;95:136-50 74. West SK, Moncada J, Munoz B, Mkocha H, Storey P, Hardick J, Gaydos CA, Quinn TC, Schachter J. Is there evidence for resistance of ocular chlamydia trachomatis to azithromycin after mass treatment for trachoma control? J Infect Dis. 2014 Jul 1;210(1):65-71 75. Schwarz CG, Reid RI, Gunter JL, Senjem ML, Przybelski SA, Zuk SM, Whitwell JL, Vemuri P, Josephs KA, Kantarci K, Thompson PM, Petersen RC, Jack CR, Jr. Improved dti registration allows voxel-based analysis that outperforms tractbased spatial statistics. Neuroimage. 2014 Jul 1;94:65-78 45 CLINICAL EDUCATION 76. Guillaume B, Hua X, Thompson PM, Waldorp L, Nichols TE. Fast and accurate modelling of longitudinal and repeated measures neuroimaging data. Neuroimage. 2014 Jul 1;94:287-302 77. Xie JZ, Tarczy-Hornoch K, Lin J, Cotter SA, Torres M, Varma R. Color vision deficiency in preschool children: The multi-ethnic pediatric eye disease study. Ophthalmology. 2014 Jul;121(7):1469-74 78. Shi Y, Lai R, Wang DJ, Pelletier D, Mohr D, Sicotte N, Toga AW. Metric optimization for surface analysis in the laplace-beltrami embedding space. IEEE Trans Med Imaging. 2014 Jul;33(7):1447-63 79. Nguyen P, Rue K, Heur M, Yiu SC. Ocular surface rehabilitation: Application of human amniotic membrane in high-risk penetrating keratoplasties. Saudi J Ophthalmol. 2014 Jul;28(3):198-202 80.Heur M, Bach D, Theophanous C, Chiu GB. Prosthetic replacement of the ocular surface ecosystem scleral lens therapy for patients with ocular symptoms of chronic stevens-johnson syndrome. Am J Ophthalmol. 2014 Jul;158(1):49-54 81. Hamm-Alvarez SF, Janga SR, Edman MC, Madrigal S, Shah M, Frousiakis SE, Renduchintala K, Zhu J, Bricel S, Silka K, Bach D, Heur M, Christianakis S, Arkfeld DG, Irvine J, Mack WJ, Stohl W. Tear cathepsin s as a candidate biomarker for sjogren’s syndrome. Arthritis Rheumatol. 2014 Jul;66(7):1872-81 82. Chiu GB, Bach D, Theophanous C, Heur M. Prosthetic replacement of the ocular surface ecosystem (prose) scleral lens for salzmann’s nodular degeneration. Saudi J Ophthalmol. 2014 Jul;28(3):203-6 83. Garcia Filho CA, Yehoshua Z, Gregori G, Nunes RP, Penha FM, Moshfeghi AA, Zhang K, Feuer W, Rosenfeld PJ. Change in drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration. Ophthalmic Surg Lasers Imaging Retina. 2014 Jan-Feb;45(1):18-31 84.Cabrera M, Gonzalez A, Albini TA, Rowaan C, Aguilar M, Lee W, Fortun JA, Moshfeghi AA, Flynn HW, Jr., Parel JM. Differential flow rate of commercially available triamcinolone with and without preservative through small-gauge needles. Ophthalmic Surg Lasers Imaging Retina. 2014 Jan-Feb;45(1):54-7 85. Prestia A, Cavedo E, Boccardi M, Muscio C, Adorni A, Geroldi C, Bonetti M, Thompson PM, Frisoni GB. Hippocampal and amygdalar local structural differences in elderly patients with schizophrenia. Am J Geriatr Psychiatry. 2014 Jan 22 86.Merchant ND, Pirotta E, Barton TR, Thompson PM. Monitoring ship noise to assess the impact of coastal developments on marine mammals. Mar Pollut Bull. 2014 Jan 15;78(1-2):85-95 87. Luders E, s Thompson PM. Why size matters: Differences in brain volume account for apparent sex differences in callosal anatomy: The sexual dimorphism of the corpus callosum. Neuroimage. 2014 Jan 1;84:820-4 46 88. Williams ME, Fink C, Zamora I, Borchert M. Autism assessment in children with optic nerve hypoplasia and other vision impairments. Dev Med Child Neurol. 2014 Jan;56(1):66-72 89.Storey P, Dollin M, Pitcher J, Reddy S, Vojtko J, Vander J, Hsu J, Garg SJ. The role of topical antibiotic prophylaxis to prevent endophthalmitis after intravitreal injection. Ophthalmology. 2014 Jan;121(1):283-9 90.Labus JS, Dinov ID, Jiang Z, Ashe-McNalley C, Zamanyan A, Shi Y, Hong JY, Gupta A, Tillisch K, Ebrat B, Hobel S, Gutman BA, Joshi S, Thompson PM, Toga AW, Mayer EA. Irritable bowel syndrome in female patients is associated with alterations in structural brain networks. Pain. 2014 Jan;155(1):137-49 91. Kashani AH, Learned D, Nudleman E, Drenser KA, Capone A, Trese MT. High prevalence of peripheral retinal vascular anomalies in family members of patients with familial exudative vitreoretinopathy. Ophthalmology. 2014 Jan;121(1):262-8 92. He M, Abdou A, Ellwein LB, Naidoo KS, Sapkota YD, Thulasiraj RD, Varma R, Zhao J, Kocur I, Congdon NG. Age-related prevalence and met need for correctable and uncorrectable near vision impairment in a multi-country study. Ophthalmology. 2014 Jan;121(1):417-22 93. Dean DC, 3rd, Jerskey BA, Chen K, Protas H, Thiyyagura P, Roontiva A, O’Muircheartaigh J, Dirks H, Waskiewicz N, Lehman K, Siniard AL, Turk MN, Hua X, Madsen SK, Thompson PM, Fleisher AS, Huentelman MJ, Deoni SC, Reiman EM. Brain differences in infants at differential genetic risk for late-onset alzheimer disease: A cross-sectional imaging study. JAMA Neurol. 2014 Jan;71(1):11-22 94.Browne AW, Osher RH. Optimizing precision in toric lens selection by combining keratometry techniques. J Refract Surg. 2014 Jan;30(1):67-72 95. Zingg B, Hintiryan H, Gou L, Song MY, Bay M, Bienkowski MS, Foster NN, Yamashita S, Bowman I, Toga AW, Dong HW. Neural networks of the mouse neocortex. Cell. 2014 Feb 27;156(5):1096-111 96.Looi JC, Velakoulis D, Walterfang M, GeorgiouKaristianis N, Macfarlane MD, Power BD, Nilsson C, Styner M, Thompson PM, Van Westen D, Wilkes FA, Wahlund LO. The australian, us, scandinavian imaging exchange (aussie): An innovative, virtually-integrated health research network embedded in health care. Australas Psychiatry. 2014 Feb 19;22(3):260-5 97. Dubey R, Zhou J, Wang Y, Thompson PM, Ye J. Analysis of sampling techniques for imbalanced data: An n = 648 adni study. Neuroimage. 2014 Feb 15;87:220-41 98.Blokland GA, McMahon KL, Thompson PM, Hickie IB, Martin NG, de Zubicaray GI, Wright MJ. Genetic effects on the cerebellar role in working memory: Same brain, different genes? Neuroimage. 2014 Feb 1;86:392-403 99.Weitz AC, Behrend MR, Ahuja AK, Christopher P, Wei J, Wuyyuru V, Patel U, Greenberg RJ, Humayun MS, Chow RH, Weiland JD. Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses. J Neural Eng. 2014 Feb;11(1):016007 109.Kim JW, Ngai LK, Sadda S, Murakami Y, Lee DK, Murphree AL. Retcam fluorescein angiography findings in eyes with advanced retinoblastoma. Br J Ophthalmol. 2014 Dec;98(12):1666-71 100.Shan ZY, Wright MJ, Thompson PM, McMahon KL, Blokland GG, de Zubicaray GI, Martin NG, Vinkhuyzen AA, Reutens DC. Modeling of the hemodynamic responses in block design fmri studies. J Cereb Blood Flow Metab. 2014 Feb;34(2):316-24 110.Kempen JH, Sugar EA, Varma R, Dunn JP, Heinemann MH, Jabs DA, Lyon AT, Lewis RA. Risk of cataract among subjects with acquired immune deficiency syndrome free of ocular opportunistic infections. Ophthalmology. 2014 Dec;121(12):2317-24 101.Dennis EL, Thompson PM. Reprint of: Mapping connectivity in the developing brain. Int J Dev Neurosci. 2014 Feb;32:41-57 111.Clark KA, Helland T, Specht K, Narr KL, Manis FR, Toga AW, Hugdahl K. Neuroanatomical precursors of dyslexia identified from prereading through to age 11. Brain. 2014 Dec;137(Pt 12):3136-41 102.Cetingul HE, Wright MJ, Thompson PM, Vidal R. Segmentation of high angular resolution diffusion mri using sparse riemannian manifold clustering. IEEE Trans Med Imaging. 2014 Feb;33(2):301-17 103.Bressler NM, Varma R, Doan QV, Gleeson M, Danese M, Bower JK, Selvin E, Dolan C, Fine J, Colman S, Turpcu A. Underuse of the health care system by persons with diabetes mellitus and diabetic macular edema in the united states. JAMA Ophthalmol. 2014 Feb;132(2):168-73 112.Bressler NM, Varma R, Suner IJ, Dolan CM, Ward J, Ehrlich JS, Colman S, Turpcu A. Visionrelated function after ranibizumab treatment for diabetic macular edema: Results from ride and rise. Ophthalmology. 2014 Dec;121(12):2461-72 113.Prasad G, Joshi SH, Nir TM, Toga AW, Thompson PM. Brain connectivity and novel network measures for alzheimer’s disease classification. Neurobiol Aging. 2014 Aug 30 104.Ameri H, Liu H, Liu R, Ha Y, Paulucci-Holthauzen AA, Hu S, Motamedi M, Godley BF, Tilton RG, Zhang W. Tweak/fn14 pathway is a novel mediator of retinal neovascularization. Invest Ophthalmol Vis Sci. 2014 Feb;55(2):801-13 114.Nir TM, Jahanshad N, Toga AW, Bernstein MA, Jack CR, Jr., Weiner MW, Thompson PM. Connectivity network measures predict volumetric atrophy in mild cognitive impairment. Neurobiol Aging. 2014 Aug 30 105.Lam LA, Rodger DC. Bilateral macular detachments, venous stasis retinopathy, and retinal hemorrhages as initial presentation of multiple myeloma: A case report. Retin Cases Brief Rep. 2014 Fall;8(4):240-4 115.Madsen SK, Rajagopalan P, Joshi SH, Toga AW, Thompson PM. Higher homocysteine associated with thinner cortical gray matter in 803 participants from the alzheimer’s disease neuroimaging initiative. Neurobiol Aging. 2014 Aug 30 106.Chalavi S, Vissia EM, Giesen ME, Nijenhuis ER, Draijer N, Cole JH, Dazzan P, Pariante CM, Madsen SK, Rajagopalan P, Thompson PM, Toga AW, Veltman DJ, Reinders AA. Abnormal hippocampal morphology in dissociative identity disorder and post-traumatic stress disorder correlates with childhood trauma and dissociative symptoms. Hum Brain Mapp. 2014 Dec 29 107.Palmer ND, Goodarzi MO, Langefeld CD, Wang N, Guo X, Taylor KD, Fingerlin TE, Norris JM, Buchanan TA, Xiang AH, Haritunians T, Ziegler JT, Williams AH, Stefansovski D, Cui J, Mackay AW, Henkin LF, Bergman RN, Gao X, Gauderman J, Varma R, Hanis CL, Cox NJ, Highland HM, Below JE, Williams AL, Burtt NP, Aguilar-Salinas CA, Huerta-Chagoya A, Gonzalez-Villalpando C, Orozco L, Haiman CA, Tsai MY, Johnson WC, Yao J, Rasmussen-Torvik L, Pankow J, Snively B, Jackson RD, Liu S, Nadler JL, Kandeel F, Chen YI, Bowden DW, Rich SS, Raffel LJ, Rotter JI, Watanabe RM, Wagenknecht LE. Genetic variants associated with quantitative glucose homeostasis traits translate to type 2 diabetes in mexican americans: The guardian (genetics underlying diabetes in hispanics) consortium. Diabetes. 2014 Dec 18 108.Toga AW, Thompson PM. Connectopathy in ageing and dementia. Brain. 2014 Dec;137(Pt 12):3104-6 116.Madsen SK, Gutman BA, Joshi SH, Toga AW, Jack CR, Jr., Weiner MW, Thompson PM. Mapping ventricular expansion onto cortical gray matter in older adults. Neurobiol Aging. 2014 Aug 30 121.Boyle CP, Raji CA, Erickson KI, Lopez OL, Becker JT, Gach HM, Longstreth WT, Jr., Teverovskiy L, Kuller LH, Carmichael OT, Thompson PM. Physical activity, body mass index, and brain atrophy in alzheimer’s disease. Neurobiol Aging. 2014 Aug 27 122.Prasad G, Joshi SH, Jahanshad N, Villalon-Reina J, Aganj I, Lenglet C, Sapiro G, McMahon KL, de Zubicaray GI, Martin NG, Wright MJ, Toga AW, Thompson PM. Automatic clustering and population analysis of white matter tracts using maximum density paths. Neuroimage. 2014 Aug 15;97:284-95 123.Wang B, Petrossians A, Weiland JD. Reduction of edge effect on disk electrodes by optimized current waveform. IEEE Trans Biomed Eng. 2014 Aug;61(8):2254-63 124.Shi J, Lepore N, Gutman BA, Thompson PM, Baxter LC, Caselli RJ, Wang Y. Genetic influence of apolipoprotein e4 genotype on hippocampal morphometry: An n = 725 surface-based alzheimer’s disease neuroimaging initiative study. Hum Brain Mapp. 2014 Aug;35(8):3903-18 125.Liu W, Rootman DB, Berry JL, Hwang CJ, Goldberg RA. Methicillin-resistant staphylococcus aureus dacryoadenitis. JAMA Ophthalmol. 2014 Aug;132(8):993-5 126.Hong BK, Khanamiri HN, Bababeygy SR, Rao NA. The utility of routine tuberculosis screening in county hospital patients with uveitis. Br J Ophthalmol. 2014 Aug;98(8):1091-5 127.Berry JL, Jubran R, Wong K, Lee TC, Murphree AL, Kim JW. Factors predictive of long-term visual outcomes of group d eyes treated with chemoreduction and low-dose imrt salvage: The children’s hospital los angeles experience. Br J Ophthalmol. 2014 Aug;98(8):1061-5 128.Sivakumar RR, Rao NA. Anterior segment ischemia in viper bite. Ocul Immunol Inflamm. 2014 Apr 30 117.Nir TM, Villalon-Reina JE, Prasad G, Jahanshad N, Joshi SH, Toga AW, Bernstein MA, Jack CR, Jr., Weiner MW, Thompson PM. Diffusion weighted imaging-based maximum density path analysis and classification of alzheimer’s disease. Neurobiol Aging. 2014 Aug 27 129.Zito G, Luders E, Tomasevic L, Lupoi D, Toga AW, Thompson PM, Rossini PM, Filippi MM, Tecchio F. Inter-hemispheric functional connectivity changes with corpus callosum morphology in multiple sclerosis. Neuroscience. 2014 Apr 25;266:47-55 118.Jahanshad N, Nir TM, Toga AW, Jack CR, Jr., Bernstein MA, Weiner MW, Thompson PM. Seemingly unrelated regression empowers detection of network failure in dementia. Neurobiol Aging. 2014 Aug 27 130.Chavarria MC, Sanchez FJ, Chou YY, Thompson PM, Luders E. Puberty in the corpus callosum. Neuroscience. 2014 Apr 18;265:1-8 119.Hibar DP, Stein JL, Jahanshad N, Kohannim O, Hua X, Toga AW, McMahon KL, de Zubicaray GI, Martin NG, Wright MJ, Weiner MW, Thompson PM. Genome-wide interaction analysis reveals replicated epistatic effects on brain structure. Neurobiol Aging. 2014 Aug 27 120.Gutman BA, Wang Y, Yanovsky I, Hua X, Toga AW, Jack CR, Jr., Weiner MW, Thompson PM. Empowering imaging biomarkers of alzheimer’s disease. Neurobiol Aging. 2014 Aug 27 131.Fink C, Borchert M, Simon CZ, Saper C. Hypothalamic dysfunction without hamartomas causing gelastic seizures in optic nerve hypoplasia. J Child Neurol. 2014 Apr 2 132.Wong BJ, Hong BK, Rao NA. Rapid progression of uveitis and alopecia syphilitica in aids. JAMA Ophthalmol. 2014 Apr 1;132(4):506-8 133.McHardy SF, Bohmann JA, Corbett MR, Campos B, Tidwell MW, Thompson PM, Bemben CJ, Menchaca TA, Reeves TE, Cantrell WR, Jr., Bauta WE, Lopez A, Maxwell DM, Brecht KM, Sweeney RE, McDonough J. Design, synthesis, and characterization of novel, nonquaternary reactivators of gf-inhibited human acetylcholinesterase. Bioorg Med Chem Lett. 2014 Apr 1;24(7):1711-4 134.Braskie MN, Thompson PM. A focus on structural brain imaging in the alzheimer’s disease neuroimaging initiative. Biol Psychiatry. 2014 Apr 1;75(7):527-33 135.Storey P, Murchison AP, Dai Y, Hark L, Pizzi LT, Leiby BE, Haller JA. Comparing methodologies for imputing ethnicity in an urban ophthalmology clinic. Ophthalmic Epidemiol. 2014 Apr;21(2):106-10 136.Roussotte FF, Jahanshad N, Hibar DP, Sowell ER, Kohannim O, Barysheva M, Hansell NK, McMahon KL, de Zubicaray GI, Montgomery GW, Martin NG, Wright MJ, Toga AW, Jack CR, Jr., Weiner MW, Thompson PM. A commonly carried genetic variant in the delta opioid receptor gene, oprd1, is associated with smaller regional brain volumes: Replication in elderly and young populations. Hum Brain Mapp. 2014 Apr;35(4):1226-36 137.Moysidis SN, Vajzovic L, Gregori G, Goldberg JL. Acute retinal pigment epithelium detachments after photocoagulation. Retina. 2014 Apr;34(4):749-60 138.Looi JC, Walterfang M, Nilsson C, Power BD, van Westen D, Velakoulis D, Wahlund LO, Thompson PM. The subcortical connectome: Hubs, spokes and the space between - a vision for further research in neurodegenerative disease. Aust N Z J Psychiatry. 2014 Apr;48(4):306-9 139.Li M, Luo XJ, Rietschel M, Lewis CM, Mattheisen M, Muller-Myhsok B, Jamain S, Leboyer M, Landen M, Thompson PM, Cichon S, Nothen MM, Schulze TG, Sullivan PF, Bergen SE, Donohoe G, Morris DW, Hargreaves A, Gill M, Corvin A, Hultman C, Toga AW, Shi L, Lin Q, Shi H, Gan L, Meyer-Lindenberg A, Czamara D, Henry C, Etain B, Bis JC, Ikram MA, Fornage M, Debette S, Launer LJ, Seshadri S, Erk S, Walter H, Heinz A, Bellivier F, Stein JL, Medland SE, Arias Vasquez A, Hibar DP, Franke B, Martin NG, Wright MJ, Su B. Allelic differences between europeans and chinese for creb1 snps and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility. Mol Psychiatry. 2014 Apr;19(4):452-61 140.Fears SC, Service SK, Kremeyer B, Araya C, Araya X, Bejarano J, Ramirez M, Castrillon G, GomezFranco J, Lopez MC, Montoya G, Montoya P, Aldana I, Teshiba TM, Abaryan Z, Al-Sharif NB, Ericson M, Jalbrzikowski M, Luykx JJ, Navarro L, Tishler TA, Altshuler L, Bartzokis G, Escobar J, Glahn DC, Ospina-Duque J, Risch N, Ruiz-Linares A, Thompson PM, Cantor RM, Lopez-Jaramillo C, Macaya G, Molina J, Reus VI, Sabatti C, Freimer NB, Bearden CE. Multisystem component phenotypes of bipolar disorder for genetic investigations of extended pedigrees. JAMA Psychiatry. 2014 Apr;71(4):375-87 47 PUBLISHED BY HEALTH SCIENCES PUBLIC RELATIONS & MARKETING KECK MEDICINE OF USC Editor Tom DeSanto Executive Director Creative Services Health Sciences Public Relations & Marketing Production Carol Sussman Production Coordinator Health Sciences Public Relations & Marketing Amir Kashani, MD, PhD, assistant professor of clinical ophthalmology Design Studio De Castro 141.Dennis EL, Jahanshad N, McMahon KL, de Zubicaray GI, Martin NG, Hickie IB, Toga AW, Wright MJ, Thompson PM. Development of insula connectivity between ages 12 and 30 revealed by high angular resolution diffusion imaging. Hum Brain Mapp. 2014 Apr;35(4):1790-800 142.Wong SC, Lee TC, Heier JS. 23-gauge endoscopic vitrectomy. Dev Ophthalmol. 2014;54:108-19 143.Wong BJ, Hong BK, Samrao D, Kim GH, Rao NA. A 49-year-old man with unilateral, nontender left eyelid swelling. Digit J Ophthalmol. 2014;20(1):15-9 144.Walterfang M, Luders E, Looi JC, Rajagopalan P, Velakoulis D, Thompson PM, Lindberg O, Ostberg P, Nordin LE, Svensson L, Wahlund LO. Shape analysis of the corpus callosum in alzheimer’s disease and frontotemporal lobar degeneration subtypes. J Alzheimers Dis. 2014;40(4):897-906 145.Stefanini FR, Maia M, Falabella P, Pfister M, Niemeyer M, Kashani AH, Humayun MS, Koss MJ. Profile of ocriplasmin and its potential in the treatment of vitreomacular adhesion. Clin Ophthalmol. 2014;8:847-56 146.Shi Y, Li J, Toga AW. Persistent reeb graph matching for fast brain search. Mach Learn Med Imaging. 2014;8679:306-13 48 of vogt-koyanagi-harada disease: In vivo documentation. J Ophthalmic Inflamm Infect. 2014;4:9 associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome. Front Behav Neurosci. 2014;8:393 151.Meintjes EM, Narr KL, der Kouwe AJ, Molteno CD, Pirnia T, Gutman B, Woods RP, Thompson PM, Jacobson JL, Jacobson SW. A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure. Neuroimage Clin. 2014;5:152-60 160.Gracanin A, Timmermans-Sprang EP, van Wolferen ME, Rao NA, Grizelj J, Vince S, Hellmen E, Mol JA. Ligand-independent canonical wnt activity in canine mammary tumor cell lines associated with aberrant lef1 expression. PLoS One. 2014;9(6):e98698 152.Lu PH, Lee GJ, Shapira J, Jimenez E, Mather MJ, Thompson PM, Bartzokis G, Mendez MF. Regional differences in white matter breakdown between frontotemporal dementia and earlyonset alzheimer’s disease. J Alzheimers Dis. 2014;39(2):261-9 161.Fulham WR, Michie PT, Ward PB, Rasser PE, Todd J, Johnston PJ, Thompson PM, Schall U. Mismatch negativity in recent-onset and chronic schizophrenia: A current source density analysis. PLoS One. 2014;9(6):e100221 153.Lu B, Tai YC, Humayun MS. Microdevicebased cell therapy for age-related macular degeneration. Dev Ophthalmol. 2014;53:155-66 154.Li J, Shi Y, Toga AW. Diffusion of fiber orientation distribution functions with a rotation-induced riemannian metric. Med Image Comput Comput Assist Interv. 2014;17(Pt 3):249-56 155.Li J, Shi Y, Toga AW. Rotational gradient field for interpolation of fiber orientation distribution in connectivity analysis. Proc IEEE Int Symp Biomed Imaging. 2014;2014:1051-4 147.Schneider C, Helmstaedter C, Luders E, Thompson PM, Toga AW, Elger C, Weber B. Relation of callosal structure to cognitive abilities in temporal lobe epilepsy. Front Neurol. 2014;5:16 156.Lee GJ, Lu PH, Mather MJ, Shapira J, Jimenez E, Leow AD, Thompson PM, Mendez MF. Neuroanatomical correlates of emotional blunting in behavioral variant frontotemporal dementia and early-onset alzheimer’s disease. J Alzheimers Dis. 2014;41(3):793-800 148.Sacchet MD, Prasad G, Foland-Ross LC, Joshi SH, Hamilton JP, Thompson PM, Gotlib IH. Structural abnormality of the corticospinal tract in major depressive disorder. Biol Mood Anxiety Disord. 2014;4:8 157.Kumar R, Farahvar S, Ogren JA, Macey PM, Thompson PM, Woo MA, Yan-Go FL, Harper RM. Brain putamen volume changes in newlydiagnosed patients with obstructive sleep apnea. Neuroimage Clin. 2014;4:383-91 149.Pfister M, Lue JC, Stefanini FR, Falabella P, Dustin L, Koss MJ, Humayun MS. Comparison of reaction response time between hand and foot controlled devices in simulated microsurgical testing. Biomed Res Int. 2014;2014:769296 158.Jiang X, Tseng CC, Bernstein L, Wu AH. Family history of cancer and gastroesophageal disorders and risk of esophageal and gastric adenocarcinomas: A case-control study. BMC Cancer. 2014;14:60 150.Nazari H, Hariri A, Hu Z, Ouyang Y, Sadda S, Rao NA. Choroidal atrophy and loss of choriocapillaris in convalescent stage 159.Jalbrzikowski M, Villalon-Reina JE, Karlsgodt KH, Senturk D, Chow C, Thompson PM, Bearden CE. Altered white matter microstructure is Photography Van Urfalian Printing Color Graphics 162.Dinov ID, Petrosyan P, Liu Z, Eggert P, Hobel S, Vespa P, Woo Moon S, Van Horn JD, Franco J, Toga AW. High-throughput neuroimaging-genetics computational infrastructure. Front Neuroinform. 2014;8:41 163.Bailey H, Brookes KL, Thompson PM. Assessing environmental impacts of offshore wind farms: Lessons learned and recommendations for the future. Aquat Biosyst. 2014;10:8 164.Ashbrook DG, Williams RW, Lu L, Stein JL, Hibar DP, Nichols TE, Medland SE, Thompson PM, Hager R. Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease. BMC Genomics. 2014;15:850 165.Apostolova LG, Hwang KS, Kohannim O, Avila D, Elashoff D, Jack CR, Jr., Shaw L, Trojanowski JQ, Weiner MW, Thompson PM. Apoe4 effects on automated diagnostic classifiers for mild cognitive impairment and alzheimer’s disease. Neuroimage Clin. 2014;4:461-72 Photo/Image Credits Cover image courtesy of the Laboratory of Neuro Imaging and Martinos Center for Biomedical Imaging, Consortium of the Human Connectome Project-www.humanconnectomeproject.org. Page 2-3 based on image from the lab of Eun Jin Lee, PhD, USC BME Center for Vision Science and Technology. Pages 4 upper left and 30 ©John Livzey. Nate Kaiser for Chan family photos on pages 4 and 14. Pages 9 lower right and 31 from the lab of Amir Kashani, MD. Page 10 left Abbott Medical Optics, right AqueSys, Inc. Pages 11 and 21 from the lab of David Hinton, MD. Page 16 from the lab of Jeannie Chen, PhD. Pages 17 and 27 Replenish, Inc. Page 21 right from the lab of Mark Humayun, MD, PhD. Page 23 Hardeep Singh, PhD, lab of David Cobrinik, MD, PhD. Page 29 BostonSight©. Page 32 Springer eBook, David G. Hunter. Page 35 left Second Sight. Page 36 based on image from the lab of J. Martin Heur, MD, PhD. 49