Advances in Ophthalmology

After decades of pioneering research and clinical achievements, Columbia ophthalmologists are making groundbreaking advances in Precision Ophthalmology™ that herald a new era in vision care. Defined as customized genetic, diagnostic, and translational clinical care, the burgeoning field of Precision Ophthalmology™ uses a patient’s own genetic profile to tailor a course of treatment specifically designed for him or her. At the Edward S. Harkness Eye Institute at NewYork-Presbyterian/Columbia University Irving Medical Center, our skilled and compassionate physicians are applying state-of-the-art genetic diagnostic and treatment methods to address the unmet needs of patients with the most challenging eye conditions. Bolstered by the vast clinical, scientific, and educational resources made possible by Columbia’s affiliation with NewYork-Presbyterian, ranked fourth in the nation and the top hospital in New York, we are uniquely poised to unlock the full potential of Precision Ophthalmology™ to enhance the vision and the very lives of our patients.

“We are undergoing a seismic shift in the way we think about genetics in ocular disease, and disease in general,” says Irene Maumenee, MD, Professor of Ophthalmology and Director of Clinical Ophthalmic Genetics at Columbia Vagelos College of Physicians and Surgeons. “A cataract isn’t just a cataract, but a genetic disease, and we have to bring that understanding into the forefront of patient care. Soon we will no longer treat ophthalmic diseases as surgical or medical conditions, but as genetic disorders. The future of the management of ocular conditions depends upon the integration of genetic concepts into eye care.”

Applied Genetics: Bringing Discoveries from the Lab to Clinical Practice

Through an abundance of discovery, Columbia scientists are applying the concept of precision medicine - the treatment and prevention of disease that considers individual variability in genes, environment, and lifestyle - to the nascent field of Precision Ophthalmology™. By sequencing genomes and their protein-coding parts, exomes, in thousands of patients with eye diseases, our scientists have been able to identify genetic variations causing single-gene eye diseases, such as Stargardt disease and retinitis pigmentosa, and complex, multifactorial diseases such as age-related macular degeneration and myopia. We have introduced these variants in mouse and cell-based models, enabling the development of precisely defined, genetics-based therapeutic approaches based on small molecules, stem cells, gene therapy and gene correction therapy.

In the Applied Genetics program in the Department of Ophthalmology at Columbia University Irving Medical Center, our physicians are leveraging the latest knowledge of the genome to diagnose, counsel and treat individuals with genetic eye disease. To create these individualized treatments, we are merging previously disparate bodies of scientific knowledge ranging from molecular and cellular biology to imaging, bio-informatics, and genomics in a team approach to medicine that combines the innovation of our researchers, the talents of our basic scientists and the clinical skills of our physicians. In this highly personalized, multiple specialists review each case to determine the most appropriate plan for care. Many of our physicians are involved in research, which enables us to recommend patients for clinical trials, many of which are based right here at Columbia.

Innovations in Precision Ophthalmology^™ at a Glance

• One of our world-renowned researchers is currently using translational genetics to study the way the eye is formed.
• Our investigators are unlocking the genetic basis of myopia and retinal degenerations, and are using these insights to develop novel therapies to prevent disease progression.
• Our researchers have developed a new genome surgery technique using the powerful gene editing tool CRISPR to restore retinal function in mice afflicted by a degenerative retinal disease, retinitis pigmentosa. This is the first time researchers have successfully applied CRISPR technology to a type of inherited disease known as a dominant disorder. This same tool might work in hundreds of diseases, including Huntington’s disease, Marfan syndrome, and corneal dystrophies
• In a New York State supported stem cell program, our researchers are examining embryonic stem cells to model and replace diseased human retinal cells.
• Our glaucoma scientists are combining novel insights into the cellular causes of this serious disease to propose new diagnostic and therapeutic paradigms.
• Our labs are genotyping over 800 patients with retinitis pigmentosa and juvenile macular degeneration who are awaiting FDA approval of gene therapy approaches to restore their ability to conduct activities of daily living.
• We are rapidly advancing our understanding of pediatric corneal diseases, some of which are the result of an interplay between genetic and environmental factors, and applying this knowledge in a dedicated monthly clinic for children with corneal disorders.
• With a grant from the National Eye Institute, our scientists are developing a topical tissue strengthening treatment for the progressive eye disease keratoconus that involves the application of cross-linking agents to the corneal surface. This treatment also has potential to address difficult-to-treat corneal infections involving multi-drug resistant organisms.
• Our scientist-clinicians are rapidly discovering genetic variants responsible for age-related macular degeneration (AMD), developing novel imaging techniques for earlier disease diagnosis, and providing vision-saving treatments to thousands of patients with AMD.
• We have launched a major Clinical Trials Unit to speed progress of new therapies.
• There are now at least six clinical trials underway studying gene therapy as a treatment for retinitis pigmentosa (RP), with two of those trials headquartered at Columbia. These trials focus on X-linked RP, an inherited condition caused by mutations in the RPGR gene that causes progressive vision loss in boys and young men. Another precision stem cell trial is in the planning phase, focused on patients with RP associated with mutations in the MERTK gene.
• Genetic analysis of uveal melanoma has revealed certain mutations that are predictive of developing metastatic disease. Our physicians are taking fine needle aspiration biopsy at time of primary tumor treatment to obtain the genetic information from the tumor and predict this risk. The genetic information can be used to adjust systemic screening schedules and permit eligibility into adjuvant clinical trials.

Driving the Future of Precision Ophthalmology^™

At Columbia, the robust interplay between basic and clinical science and precision ophthalmology was evident at the fourth Precision Ophthalmology Symposium, the annual conference of Columbia University Medical Center that highlights ground-breaking work and updates in ophthalmic sub-specialties, sponsored by Columbia Ophthalmology Alumni Society and the Edward S. Harkness Eye Institute. Focusing on applied genetics, the 2020 symposium provided a rich series of lectures and practical case studies demonstrating how we are taking genetic discoveries from the laboratory and moving them rapidly into clinical practice.

“At our first Precision Ophthalmology Symposium in 2016, the focus was primarily descriptive,” says Stephen Tsang, MD, PhD, Laszlo T. Bito Professor of Ophthalmology and Professor of Pathology and Cell Biology at Columbia University Medical Center, who presented a session on advances in genome surgery, including his own groundbreaking work. “The field has made so much progress in such a short time that the 2020 agenda was all about treatment. Many people still think of gene therapy as primarily the province of research, but we are rapidly moving forward to precision treatment in the clinic at the level of an individual DNA base pair.”

“At Columbia, we are positioning ourselves as the first institution in the tri-state area to offer both genomic medicine and gene surgery for the eye, which will happen within the next year,” he adds. “By the time we are ready for the 2021 Precision Ophthalmology Symposium, the agenda will be all about how we are improving gene therapy and gene surgery.”