Principal Investigators: Dr. Ramulu & Dr. Quigley

Project 1:  Angle closure glaucoma is a leading cause of blindness worldwide with limited evidence supporting current treatments.  The team will:

Continue an ongoing study of laser iridotomy to prevent angle closure glaucoma in persons at risk.  This study being conducted in Guangzhou, China is the largest clinical trial in this field and has been underway for over two years with close to 1,000 participants being followed. It has an international collaborative advisory committee consisting of members from University College, London, from Singapore, and from China.

Funding for additional follow-up will be required and we estimate the total cost to fully fund this effort at $500,000.

Expand work with our collaborators at Singapore National Eye Center to define more clearly the mechanisms of angle closure and to prospectively monitor outcomes in persons with different underlying mechanisms. During the past 5 years, our research in this program has developed an important new diagnostic approach using anterior segment optical coherence tomography, whose prototype instrument and design modifications depended on our group. The collaboration of Dr David Silver of Wilmer and the Applied Physics Lab have been vital in this work. A longitudinal followup cohort is now being assembled to validate whether diagnostic risk factors that have been developed will be validated prospectively.

The additional funding needed to monitor this group is estimated at $250,000.

Project 2:  Glaucoma care in the developing world is limited and most patients are diagnosed only when the disease has led to severe vision loss.  Identifying ways to integrate glaucoma care into the care of patients in these regions will be a key component of preventing glaucoma related blindness. 

The GCE will establish ongoing training opportunities at Wilmer for ophthalmologists at large institutions in the developing world in order to improve the management of glaucoma in their environment. Collaboration with the School of Public Health, including Kay Dickersin are important to this work.

Funding for this will require $30,000 per person trained and equipped, plus equipment costs.

The GCE will actively engage in producing models of screening for and detecting glaucoma in hospitals that are already seeing a high volume of patients in the developing world.  Currently these patients are largely undiagnosed or treated ineffectively.  This research effort will likely start in India with colleagues at the Aravind Eye Hospital and will be expanded to other regions as a clear model is developed.

The cost to initiate this process is $50,000.

Principal Investigators: Dr. Ramulu, Dr. Boland & Dr. Jampel

The GCE’s common goal is to increase the quality of life of glaucoma patients at Wilmer and beyond. To that end, we have an active research program into how glaucoma impacts activities of daily living, such as reading, driving, and mobility. The outcomes will be recommendations about how to live more safely, especially avoiding falls and motor vehicle accidents. We collaborate with visual rehabilitation specialists to develop methods for better reading and walking in patients with advanced glaucoma. This research uses existing GCE patients, as well as population-based databases.

Initial collaborations with Wilmer Dana Center epidemiologists have shown that patients with early glaucoma are more likely to stop driving, that patients with moderately severe glaucoma walk more slowly and more often bump into objects, and that patients with advanced glaucoma read for shorter periods of time. Ongoing investigations study travel outside the home, measure physical activity, and have developed new tests to evaluate the ability to read books.

Based on present research results and anticipating findings in these areas, we propose to develop patient education materials to be used in our new patient care approach (priority area 6). This will raise awareness for both physicians and patients of quality of life issues and take important steps towards avoiding driving and walking-related injuries.

The program will have costs for development of the teaching materials and for a nurse—counselor to work full time testing the methods objectively ($50,000 per year).

The GCE project will determine which visual rehabilitation approaches most effectively enable our patients to complete their life goals. Amazingly, not a single study has focused on rehabilitation efforts to decrease disability among glaucoma patients.

We seek funding of $100,000 to support such research initiatives, to formalize protocols for rehabilitating glaucoma patients and to evaluate their outcomes in collaboration with the Wilmer Lions Vision Center as well as geriatric specialists at Bayview.

Principal Investigators: Dr. Zack, Dr. Quigley & Dr. Welsbie

The ultimate cause of visual dysfunction and blindness in glaucoma is the dysfunction and death of retinal ganglion cells (RGCs), nerve cells that carry information from the eye to the brain. In advanced glaucoma, the patient does not see because RGCs die, and information is not communicated from the eye to the brain. The higher the eye pressure, the more RGC death from glaucoma, and lowering pressure slows the damage, but not completely. Thus, a protective strategy for RGCs (neuroprotection) that directly promotes the health and survival of RGCs has the potential to improve vision preservation for glaucoma. Such a therapy would likely be used in conjunction with current IOP-lowering drugs.

Project 1: As a first step towards developing a safe and effective neuroprotective drug, the GCE has created several High Content Screening (HCS) assays that can directly assess the ability of various small molecules to promote RGC survival, pointing to areas in which drugs could be developed. These assays use RGCs in culture, an approach that allows mass screening while remaining biologically relevant.

We have screened over 7,000 compounds, identifying a number of candidate RGC neuroprotective compounds. Collaborating with a team of chemists from Hopkins and outside, we will customize these compounds to make them suited for safe and effective human use. In parallel, we are testing the currently available compounds in well-characterized rodent models of glaucoma and RGC injury. Initial studies in these models confirm one compound with neuroprotective activity in animals. Further animal studies that should be predictive of eventual applicability to humans are also underway. In addition, the drug discovery work is being complemented by a number of ongoing studies in our labs that are analyzing the molecular mechanisms by which RGCs die in glaucoma.

This rational and logical pathway for the development of neuroprotective drugs for glaucoma is uniquely being used at the GCE. Although we have been fortunate to have received “start-up” funds from the National Institutes of Health to initiate the drug development work, along with our success comes an increasing demand for financial support, since chemical optimalization and animal testing are expensive. We are negotiating with pharmaceutical firms to collaborate in this work. Increased philanthropic support will allow us to extend and accelerate our drug development efforts. We expect that this work will lead to more effective and safer options for the prevention of glaucoma visual damage. Collaboration with Dr Nick Marsh-Armstrong of the Kennedy—Krieger Institute is important in our ganglion cell studies.

Additional funding of $250,000 is being sought.

Project 2: We recently developed a new model of glaucoma in mice that duplicates its more important features. Using this model that causes elevated eye pressure through obstruction of outflow by microbeads, we are not positioned to test a variety of factors using genetically and biochemically altered mice, in a way that is not feasible in any other species.

One major area of this work is to test the hypothesis that alteration in the biomechanical behavior of the sclera and its rheology will be protective for glaucoma. These experiments involve collaboration with engineers at both the Homewood and Medical School. Dr. Vicky Nguyen of the Mechanical Engineering Department collaborates with the Quigley lab to measure the stress—strain behavior of the mouse eye. We have determined that older age and certain biochemical treatments lead to stiffer sclera response. We will next test whether having a stiffer response to induced eye pressure elevation is beneficial in glaucoma. If so, treatments of human eyes to make the sclera stiffer are already being tested in corneal disease and could be made practical for glaucoma.

A second area is to breed mice with the equivalent of axial myopia and to test whether these are more susceptible to glaucoma, as are humans with axial myopia. The collaboration of Dr. Hal Dietz of the Department of Pediatrics is key to this work, as he has a strain of myopic mice that mimic the Marfan syndrome. We also are testing 5 other strains of mice from a variety of labs worldwide. The bead-induced mouse glaucoma model will be used in these experiments.

A third area of collaboration is with the Justin Hanes group, with whom we are working to measure the penetration of nanoparticles through the sclera. Scleral rheology has never been quantified, and this is quite important both to changes that may be induced by glaucoma, as well as delivery of drugs to the eye through the sclera.

Funding to underpin these projects could involve costs of $200,000.

Principal Investigators: Dr. Boland & Dr. Ramulu

Members of the GCE are developing and expanding a new approach to research that has been successfully begun in pediatric and retinal ophthalmic research. Even the largest glaucoma studies have been carried out at a relatively small number of institutions, allowing tight control but restricting the number and types of patients who are able to participate.  It is also inefficient for each study to create its own research infrastructure (staff, space, equipment) only to have it dismantled after the study is complete. To overcome these problems, we will create a permanent network of research infrastructure distributed across the United States and around the world.

When fully implemented, the Glaucoma Research Network (GRN) will consist of a coordinating center at the Wilmer Eye Institute and many participating institutions, both academic and private practices. The coordinating center will include the GRN principal investigators as well as the staff needed for the day-to-day operations of clinical trials and the information technology to collect, store, and analyze research data. The computer infrastructure will play the key role of allowing geographically distributed sites to be connected to the coordinating center, thereby facilitating broad-based collaboration.

The GRN currently consists of investigators from The Wilmer Eye Institute and five other major eye centers along the East coast.  The six initial institutions are working on two projects to demonstrate the benefits of this model for research. First, we have created the largest database of visual field tests ever assembled, to better understand how glaucoma produces visual damage. Second, we are conducting a randomized, controlled clinical trial comparing two devices commonly employed in glaucoma implant surgery.  These studies are, individually, important contributions, but will permit development of a research network for continued future collaboration.  Third, the other priority research areas of the GCE will utilize the GRN as a mechanism to broaden the reach of research projects.

The initial GRN has been funded by $150,000 in donated funds to the GCE, and we seek funding to expand the network and to carry out the next phase of projects. 

Ongoing infrastructure costs in the initial phases are estimated at $200,000 per year. 

Support for the GRN represents a leveraged investment in the future of glaucoma knowledge as the network will soon make initial applications for support of its mechanism and initial projects from N.I.H.

Principal Investigator: Dr. Boland

The current national push for Electronic Health Records (EHRs) is motivated by the desire to improve the quality and safety of patient care by better using information that is currently obscured by being confined to a paper chart. GCE physicians have been documenting patient encounters using computerized systems for 10 years and have recently upgraded to a fully functional EHR. This means that the important information about each patient visit is stored electronically to improve quality and efficiency of patient care.

Our EHR improves care by ensuring that all information is available at every care site, by avoiding dangerous drug interactions and allergies, and by displaying information in ways that help physicians make better clinical decisions.  The medical information is only available to those who need access. The EHR used in the GCE also facilitates evaluation of the quality of care that we provide and assesses the effect of changes in visits or testing.  The GCE is the first group within the Wilmer Eye Institute and among in all of Johns Hopkins Medicine to make this quality improvement

In keeping with our commitment to research that improves patient care, we are evaluating the impact of the EHR on our practice.  Since the EHR is now involved in all portions of a patient encounter, such impact is important and our results will help other physicians, not just glaucoma specialists as they transition to electronic records.  These studies will evaluate how frequently testing should be done, how well physicians interpret and use exams and tests, and how doctors make decisions on treatment. The studies will directly test the effect of presenting doctors with risk calculation data so that their choices to treat or how to treat are informed by electronically generated data, as well as clinical judgment.

This research will be conducted nationally through the Glaucoma Research Network that is outlined here.

Principal Investigator: Dr. Jampel

Some doctors see glaucoma patients 4 times a year and other doctors see them once or twice.  Testing frequency varies widely and how the tests are used to make decisions is highly variable. Visits for glaucoma are a huge cost to Medicare and the health system, and new imaging tests are the most rapidly growing feature of health care costs. The GCE proposes to study cost-effectiveness of glaucoma care both through national studies and within the GCE itself in two project areas.

Project 1:  The national study, implemented through the Glaucoma Research Network proposed here, will study new testing centers that are convenient for patients with centralized grading of data. Physicians will assign visit frequency based on risk assessment data. The project will compare present visit/doctor approach to the newer method in the outcomes: patient satisfaction, eye pressure control, glaucoma worsening, and overall cost.

This is new model of care will take up to 2 years initially to implement and to test.  We anticipate more attention will be given to managing the impact of glaucoma on the patient (through social workers, low vision specialists and support personnel), while physicians will have regular access to the best technology for their patients and will spend more time to spend with those patients who require careful monitoring or a change in care.

This project will initially need $200,000 to establish a team to develop the care model and to engage the healthcare system, and likely will require additional funding as the program expands.

Project 2: The strategy of visits and testing for glaucoma patients, although endorsed by expert panels, is based on habit not data. Diagnostic tests are probably unnecessarily often for some and too infrequent in others. Actual time of communication between physician and patient is modest, and possibly inadequate. Patients generally have a poor (or untested) understanding of their disease, impeding their ability to fully participate in their care. Both are contributing factors in suboptimal patient adherence with the prescribed therapeutic regimen. The GCE has led the world in both observational and interventional studies of adherence with glaucoma eyedrop taking. Collaboration with Eric Bass, a specialist in public health assessment of medical interventions is important in this work.

To have each member of the health care team perform the functions they do best, the GCE will evaluate a scheme of care for patients to increase cost-effectiveness, improve adherence with eyedrops, and raise patient satisfaction.  All new patients will receive a comprehensive evaluation by the glaucoma specialist with the formulation of a therapeutic plan. In addition, the patients will be asked about visual limitations on their reading, walking, and driving, since these are key functions that matter to glaucoma patients.  Brief tests of reading and ambulation refined at Wilmer will be administered. A baseline evaluation of the patient’s satisfaction with their vision and understanding of the disease will be performed.

Following the visit with the glaucoma specialist the patient will be randomized to either current pattern of care or a new pattern of care. The new method consists of a comprehensive annual doctor visit with quarterly visits including technician testing and a meeting with an ophthalmic nurse, who reviews adherence and medication side effects. Quarterly visit data are reviewed by the glaucoma specialist and discussed with the patient by phone or in person where changes are required.

The program will be formally evaluated annually for 5 years. The primary outcomes will be visual acuity, visual field testing, optic disc imaging, quality of life and patient satisfaction assessment, disease understanding questionnaire results, as well as functional tests of reading and mobility. The direct costs of care for both arms will be also be determined.

The program has need for a full-time nurse—educator who will also serve as the research coordinator for data collection, at an annual cost of $100,000.

Principal Investigators: Dr. Ramulu & Dr. Quigley

Teaching resident ophthalmologists in training is a primary focus of the GCE, but current methods inadequately incorporate advances in technology and are out-of-step with how young doctors now learn. We are developing modern teaching approaches and studying the outcomes of these new teaching methods. We anticipate that our new, evidence-based methods for teaching will serve as a model for how to best train doctors both within and beyond Johns Hopkins. The program has been developed with initial collaboration with Dr Harry Goldberg of the Johns Hopkins Medical School Dean’s office.

Project 1: First, we will transform passive, lecture-format education by making residents into active participants. Daily lectures often conflict with the other responsibilities of trainees, so that only a minority attend. Faculty too infrequently update their lectures, fueling the perception that there is nothing new. Learning styles vary among students, so single approaches fail to encompass help for some.

To make teaching information more accessible and interactive, we are testing elimination of lectures and replacing them with a single intensive weekly 3 hour learning session. Lectures slides with overlying audio have been pre-recorded by GCE faculty and posted online to be viewed prior to the learning session, and passwords identify which residents accessed the material. The in-class learning session will be an interactive interchange using clinical case material on the relevant subject. Trainees will be given an opportunity to “order tests” or ask for more information about the patient’s history or exam findings. They will then meet in small groups mixing individuals with differing levels of clinical experience, and finally reviewed with faculty.

To improve the surgical teaching of resident physicians, the GCE instituted an introductory wetlab experience for all residents beginning their glaucoma rotation. Residents review faculty surgical videos, view slides on instruments and sutures, then spends 3 hours of one-on-one time with a faculty member performing operations on pig eyes under operating microscope conditions.

Learning will be assessed through objective responses to a pre-test and post-test at the sessions. We will then compare the improvement in post-test scores for lectures given in the classic format, to the improvement seen with the new learning format.

For this program, educational software that permits each student to be assessed during the sessions is commercially available and we seek funding to purchase and implement this using each student’s own laptop or wireless device. The cost is estimated at $100,000.

Project 2: The American College of Graduate Medical Education has called for objective evaluation of resident knowledge and performance, yet few specialties have actual methods to accomplish this important goal. The GCE has 3 methods to assess resident performance. First, residents complete an oral exam involving management of 6 clinical cases. Second, the GCE performed actual chart review on resident-managed glaucoma patients at Wilmer and Bascom Palmer Institute, comparing the care to faculty patient charts. Third, GCE faculty has developed online modules for education in the diagnostic and management skills needed in glaucoma care. The present 4 modules teach and assess skills in gonioscopy, disc and nerve fiber layer exams, and visual field test interpretation. Each takes one hour to conduct and has a pre- and post-test to assess learning and progress.

To extend this educational initiative, we are seeking funds for a research coordinator to evaluate the quality of learning and to support the effort to evaluate and publish research on resident learning and care. While we have studied whether tests are or are not performed, the more important question is whether tests or examinations, when performed, are interpreted correctly. New web-based modules are needed on glaucoma surgery, laser treatment, and medical management.

Each of these costs approximately $25,000 in time and materials/programming.

A commercial firm (Eyemaginations, Inc, Towson MD) is licensed to market these, and license fees will ultimately pay for the program and provide income in the long-term.  Once modules for glaucoma are constructed, the framework to expand to all ophthalmic subspecialties is ready to use. A research coordinator for this program requires $50,000 per year.