AMD Research at Doheny

The retina of the eye contains millions of highly specialized cells. Some of the cells capture images (in the form of light) from the visual field. Others carry the information to the brain where it is translated into what we see. The cells are supported by a structured “floor” and nourished by a unique system of blood vessels that also carry away cellular waste products. The varieties of retinal cells are confined, for the most part, to distinct retinal layers and are affected differently by retinal disorders. Some disorders affect the light capturing cells. Others cause the brain-connecting cells to fail. Some do so by altering the floor or vasculature and others by disrupting the internal workings of the cells. Age-related macular degeneration (AMD) is one of the retinal disorders being studied by scientists at Doheny Eye Institute.

Researchers are finding new ways to prevent, treat, and cure retinal disorders. These range from nutritional therapies to stem cell therapies. The nutritional therapies, for some forms of AMD, help patients who are at a mid-range stage of the disease. The stem cell therapies are designed to repair the retinal floor, called the retinal pigment epithelium, which malfunctions in many retinal degenerative disorders.

A specialized program at Doheny Eye Institute called the Doheny Image Reading Center (DIRC) is critically important to the worldwide vision research community. DIRC receives photographic images of the retinas of patients with retinal disorders at various stages; the DIRC scientists analyze and report on the images; the reports help scientists and medical doctors evaluate the effects of standard and experimental therapies on the progression of patients’ retinal disease.

Doheny AMD Researchers

Srinivas R. Sadda, MD

Sadda,SSrinivas R. Sadda, MD

President and Chief Scientific Officer

Dr. Sadda received his medical degree from The Johns Hopkins University in Baltimore, Maryland. After an internship at the William Beaumont Hospital in Royal Oak, Michigan, he returned to Johns Hopkins University and the Wilmer Eye Institute in Baltimore for an ophthalmology residency as well as neuro-ophthalmology and medical retina fellowships.

Dr Sadda’s major research interests include advanced retinal imaging technologies, image analysis algorithm development, retinal stem cells, translational research, clinical trial endpoint and biomarker development. Clinical disease interests include AMD, diabetic retinopathy, and retinal degenerations.

In pursuit of these interests, Dr. Sadda is or has been the Principal Investigator on more than 30 trials, including phase III studies of ranibizumab, preservative-free triamcinolone acetonide, and a dexamethasone posterior segment drug delivery system. He has more than 300 publications in peer-reviewed journals and over 300 published abstracts. He authored the first edition of the textbook Emerging Technologies in Retinal Disease, as well as 13 book chapters. As an invited lecturer, he has given more than 250 presentations around the country and the world. Dr. Sadda also serves as an editorial board member of Ophthalmic Surgery, Lasers & Imaging, Retina, and Ophthalmology. He is an editor of the 5th edition of the Ryan’s Retina textbook and also serves as the editor for the electronic edition of this text. In addition, he serves as an ad hoc scientific referee for Investigative Ophthalmology and Visual Science, Archives of Ophthalmology, American Journal of Ophthalmology, Experimental Eye Research, and the Center for Scientific Review at the National Institutes of Health. Among Dr. Sadda’s awards and honors are a Research to Prevent Blindness Physician-Scientist Award, a Senior Honor Award from the American Society of Retina Specialists, Silver Fellow designation from ARVO, an Achievement Award and a Secretariat Award from the American Academy of Ophthalmology, John H. Zumberge Research and Innovation Award, and the Macula Society Young Investigator Award. He has been named to the Best Doctors of America list for several consecutive years.

Zhihong (Jewel) Hu, PhD

Hu,Zhihong JewelZhihong (Jewel) Hu, PhD

Doheny Scientist

Dr. Hu received her Ph.D. in Electrical and Computer Engineering from the University of Iowa. She is the supervisor and lead software developer in the Doheny Image Analysis Laboratory (DIAL) at the Doheny Eye Institute. Dr. Hu’s overall research interests are in the fields of medical image processing, computer vision, machine learning, and video surveillance. Her latest research focuses on ophthalmic image processing and analysis, with the special attention in graph-based image segmentation, supervised pixel classification, deep learning, multi-object, multi-modality image segmentation, and uni-modal and multi-modal image registration.

When Dr. Hu worked in the University of Iowa, she specialized in the automated detection and analysis of the glaucomatous 3D eye structures involving the neural canal opening, optic cup, rim, and blood vessels, using 2D and 3D spectral domain optical coherence tomography (OCT) images. After she joined Doheny, she turned her attention to age-related macular degeneration (AMD).

Her research specializes in the automated detection and analysis of eye structures and lesions involving AMD using 2D and 3D OCT images. Dr. Hu has developed various automated algorithms to identify AMD structures and lesions to facilitate the understanding of the mechanism of AMD. For instance, Dr. Hu developed a graph-based algorithm to identify 11 retinal layers in OCT images. The automated multiple layer segmentation facilitates the analysis of the retinal layer thickness and reflectivity changes, which are believed to be the indicators/predictors of various eye diseases (e.g. AMD) and their progression. Recently, Dr. Hu developed a level-set-based algorithm and a pixel-wise-classification-based algorithm for the detection and quantification analysis of geographic atrophy (GA), the late stage of AMD. The preliminary GA segmentation and analysis results are promising and have resulted in the award of a research grant and an ARVO travel grant. Dr. Hu is also interested in the translation of her development to real-world applications and is pursuing the licensing of her development with OCT device companies.

An additional research interest of Dr. Hu’s is the development of manual graphical user interface (GUI) tools to facilitate retinal research. So far, the GUI tools can provide image data format conversion, visualization, registration, manual delineation (and manual correction of automated segmentation results), and quantitative analysis of retinal layer thickness, intensity and correlation with microperimetry sensitivity for 2D images and 3D macular OCT, which are important compensation for the automated algorithms.

Ram Kannan, PhD

Kannan,RRam Kannan, PhD

Doheny Scientist

Dr. Kannan received his Ph.D. in Organic Chemistry from Osmania University, India. His initial postdoctoral research in Europe was on lipid biochemistry and the role of fatty acids in cancer. After moving to the United States, he switched his field to ophthalmology and neuroscience with particular emphasis on the role of endogenous antioxidants in the eye and the brain.

Dr. Kannan‘s current major research interests are in elucidating protective mechanisms in the retina and retinal pigment epithelium; he is particularly interested in the prevention of damage caused by oxidative and other cellular stressors that are involved in the pathogenesis of age-related macular degeneration (AMD).

His research team at the Doheny Eye Institute has developed suitable animal models for geographic atrophic AMD and subretinal fibrosis and has elucidated the therapeutic potential of endogenous growth factors in preventing retinal pigment epithelium (RPE) degeneration in these models. Currently, Dr. Kannan’s research focuses on studying novel peptides (chaperone peptide aB–crystallin and mitochondrial-derived peptide Humanin) and strategies for their delivery by nanoparticles to RPE and retina in experimental models of atrophic AMD.

Dr. Kannan has published over 125 peer-reviewed research articles, 20 book chapters and reviews and has authored over 160 published abstracts. He serves as an ad hoc reviewer for a number of scientific journals including Investigative Ophthalmology and Visual Science, Experimental Eye Research, Molecular Vision and Graefe’s Archive for Clinical and Experimental Ophthalmology. Dr.Kannan’s research has received funding from NEI, the Department of Veteran’s Affairs (VA Merit Award) and the Arnold and Mabel Beckman Foundation. He has served as an ad hoc reviewer of an extramural NEI study section and an intramural Board of Scientific Counselors.