Seeking new treatments for vision loss

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Carl Camras Center for Innovative Clinical Research in Ophthalmology:
Diana V. Do, MD (Director and Vice Chair for Education)  

The Carl Camras Center for Innovative Clinical Research in Ophthalmology is a Center dedicated to bringing novel and state-of-the-art clinical therapies to patients. The center allows ophthalmologists, optometrists, and vision scientists to bring medical breakthroughs to patients through the laboratory to the individual patients through clinical studies. The research team has expertise in conducting clinical studies that lead to novel therapies for a variety of eye diseases such as uveitis, diabetic eye disease, age-related macular degeneration (AMD), glaucoma, thyroid eye disease, and meibomian gland disease

In RETINA RESEARCH, clinician-scientists are evaluating new therapies for wet AMD, dry AMD, diabetic eye disease, and ocular inflammation. Using state-of-the-art imaging and diagnostic testing, clinicians are able to view and treat a variety of conditions that affect the retina.

The Truhlsen Eye Institute is one of the largest centers conducting uveitis clinical trials. Investigational drug therapies and novel drug delivery systems are evaluated for safety, tolerability, and effectiveness on non-infectious uveitis. Drs. Quan Nguyen and Diana Do lead the uveitis clinical trials.

Research has contributed to the development of vascular endothelial growth factor (VEGF) blockers to stop abnormal blood vessel growth and bleeding inside the eye in patients with retinopathy. VEGF blockers are the most effective treatment available for wet AMD and diabetic swelling in the retina. The retina research team is exploring new drugs to stop the progression of wet AMD such as: 1) mono-or adjunct therapy with VEGF blockers to minimize inflammatory, angiogenic, and fibrotic responses, 2) drugs that block T-cell activation, and 3) drugs that bind to antibodies to inhibit ocular inflammatory response. Drs. Quan Nguyen, Diana Do, and Eyal Margalit are conducting clinical trials in macular degeneration and diabetic macular edema.

In the near future, our center will be conducting clinical trials for dry AMD, another common cause of vision loss.

The following clinical trials in Retina Researchinclude:

·       Open-Label, Safety and Tolerability Study of Suprachoroidal Triamcinolone Acetonide via Microneedle in Subjects with Non-Infectious Uveitis

·       A Phase III, Multinational, Multicenter, Randomized, Double-Masked, Study Assessing the Safety and Efficacy of Intravitreal Injections of DE-109 (three doses) for the Treatment of Active, Non-Infectious Uveitis of the Posterior Segment of the Eye

·       Version 3

·       A Randomized, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Gevokizumab in the Treatment ofActiveNon-Infectious Intermediate, Posterior, or Pan-Uveitis, X052130

·       Sirolimus as a Therapeutic Approach for Uveitis: A Phase 2, Open-Label, Randomized Study to Assess the Safety, Tolerability, and Bioactivity of Two Doses of Intravitreal Injection of Sirolimus in Patients with Non-Infectious Uveitis

·        A Randomized, Multi-center, Phase II Study of the Safety, Tolerability and Bioactivity of Repeated Intravitreal Injections of iCo-007 as Monotherapy or in Combination with Ranibizumab or Laser Photocoagulation in the Treatment of Diabetic Macular Edema with Involvement of FoveAL Center

·       PSV-FAI-001: A Phase III, Multi-National, Multi-Center, Randomized, Masked, Controlled, Safety and Efficacy Study of a Fluocinolone Acetonide Intravitreal (FAI) Insert in Subjects with Chronic Non-Infectious Uveitis Affecting the Posterior Segment of the Eye

·       Study of the Safety, Tolerability, and Bioactivity of Tocilizumab on Patients with Non-infectious Uveitis

·       A phase 2a, multi-center, masked, randomized, comparator-controlled study evaluating isonep (Sonepcizumab[lt1009]) as either monotherapy or adjunctive therapy to Lucentis, Avastin or Eylea versus Lucentis, Avastin or Eylea alone in the treatment of subjects with choroidal neovascularization secondary to age-related macular degeneration

·       A phase 2a, multi-center, masked, randomized, comparator-controlled study evaluating isonep (Sonepcizumab[lt1009]) as either monotherapy or adjunctive therapy to Lucentis, Avastin or Eylea versus Lucentis, Avastin or Eylea alone in the treatment of subjects with choroidal neovascularization secondary to age-related macular degeneration

·       A randomized, double-masked and placebo-controlled study to evaluate the efficacy and safety of sarilumab administered subcutaneously every 2 weeks in patients with Non-infectious, Intermediate, Posterior or Pan-Uveitis (NIU)

·       A Randomized, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Gevokizumab in the Treatment of Subjects with Non-infectious Intermediate, Posterior, or Pan-Uveitis Currently Controlled with Systemic Treatment, X052131

·       A Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab and Ranibizumab for Diabetic Macular Edema

·       A Phase II Evaluation of Topical NSAIDs in Eyes with Non Central Involved DME

In GLAUCOMA RESEARCH, Carol Toris, PhD, Shan Fan, MD and Vikas Gulati, MD are conducting ongoing research studies of intraocular pressure (IOP) and aqueous humor dynamics (AHD) to: 1) identify differences in AHD between healthy teen-aged children and genetically related healthy adults among Caucasian and African American populations, 2) identify eye pressure responses to glaucoma medication based on genetic markers, and 3) determine the effects of anti-VEGF drugs (bevacizumab, ranibizumab or aflibercept) on AHD in patients with retinal vascular disease. 

The ongoing clinical studies in Glaucomainclude:

·       Effect of Vascular Endothelial Growth Factor Blockers on Aqueous Humor Dynamics

·       Aqueous Humor Dynamic Components that Determine Intraocular Pressure Variance

·        Aqueous Humor Dynamics and Biometric Parameters in Eyes of Children

THYROID EYE DISEASE (TED) research focuses on the active phase of TED and potential ways to minimize its severity and duration. The study is conducted by Dr. James Gigantelli. The study is:

·       A Multicenter, Double-Masked, Placebo-Controlled, Efficacy And Safety Study of RV 001, an Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antagonist Antibody (Fully Human), Administered Every 3 Weeks (Q3W) By Intravenous (IV) Infusion in Patients Suffering From Active Thyroid Eye Disease (TED)

MEIBOMIAN GLAND DYSFUNCTION is being studied by Dr. John Halgren and his research team of James Gigantelli, MD, Frank Graf, OD, and Patti Fries, OD. Specifically the team is studying the cause of the dysfunction as a result of testosterone deficiency. The study is entitled:

·       Ophthalmic AGN-195263 for the Treatment of Meibomian Gland Dysfunction to evaluate the safety and efficacy of AGN-195263 (0.01%, 0.03%, and 0.1%) ophthalmic emulsion twice daily ocular topical administration compared to vehicle in patients with meibomian gland dysfunction (MGD)

The Carl Camras Center for Innovative Clinical Research in Ophthalmology at the Truhlsen Eye Institute has allowed the Department of Ophthalmology and Visual Sciences at UNMC to rapidly expand its research activities since the center opened one year ago. The Center is led by Diana V. Do, MD (Director) with the assistance of research coordinators (Lisa Greer, Donna Neely, Kristi Miller, and Sylvie Sim) and research assistant (Brooke Dworak). The future of research in the TEI is looking brighter than ever.

Laboratory Research:

The Department of Ophthalmology and Visual Sciences is one of the collaborating departments with the Medical Sciences Interdisciplinary Area (MSIA) graduate programs for students who want to pursue graduate studies in vision research.

Dr. Margalit's research interests are in the field of visual rehabilitation of individuals blind from retinal diseases. He divides his research efforts between basic science projects in collaboration with Dr. Thoreson (electrophysiology of the retina during electrical stimulation), translational studies focusing on assembling a retinal prosthesis for patients blind from retinitis pigmentosa and age related macular degeneration, and clinical trials (steroid intraocualr injections for the treatment of branch and central vein occlusion, intraocular injections of non-steroidal anti-inflammatory drugs for the treatment of intraocular inflammation, new antibiotic drugs for the treatment of intraocular infections etc.). One of his goals is to involve residents and fellows with his research projects, to expand their medical education. Thus, residents and fellows participate and play major roles in most of the projects discussed above.

The glaucoma research team includes Drs. Rai, Gulati, Fan, and Toris. For many years, one area of their intensive research efforts has included prostaglandins, which have become the leading treatment for glaucoma throughout the world. Four prostaglandin analogs currently are commercially available to treat glaucoma. The group has evaluated the mechanisms by which prostaglandins reduce eye pressure and induce iris color darkening. They use a fluorophotometric method to determine how prostaglandin analogs and other drugs affect eye pressure. They have compared the efficacy, safety and mechanism of action of different prostaglandin analogs. They developed a unique model for iris color darkening in rabbit eyes in which input from a particular part of the nervous system is severed. This model has been useful in studying mechanisms by which prostaglandins cause iris color darkening. In collaboration with the Department of Pharmaceutical Sciences and the Department of Internal Medicine, Dr. Toris is studying diabetes and its effects on fluid transport and pressure in the eye.

Dr. Thoreson's laboratory is among the most productive of those utilizing electrophysiologic methods to study early mechanisms in vision. Dr. Thoreson and his colleagues have made significant progress in unraveling the mechanisms employed by rods and comes to signal their responses to other retinal neurons.

Dr. Ahmad’s is one of the leading labs studying the regulation of ocular stem cells, and using emerging information for regenerative medicine for blindness. His lab is identifying alternate sources of retinal progenitors in embryonic stem cells, and by reprogramming adult stem cells to facilitate ex-vivo stem cell therapy. His lab has shown that Muller glia, the support cells in the adult retina, are latent stem cells that can be potentially activated to treat retinal degeneration from within. In addition, they have identified a potential therapeutic target in a signaling pathway, known as the Notch signaling, to treat wet age-related macular degeneration (AMD), which accounts for most of the AMD-related vision loss.

Drs. Shinohara and Singh have studied retinal development and cataract formation when they were previously at Harvard Medical School. They are currently studying a novel growth factor called lens epithelium-derived growth factor (LEDGF). Although initially discovered in the eye, LEDGF is found throughout the body. Among other properties, LEDGF helps cells survive stressful conditions and thus holds promise as a possible therapeutic adjuvant for treating a variety of different eye diseases.