Retina Research Foundation Research

Retinal disease can cause blindness in everyone from newborns to the elderly. Until recently, no physician has been able to offer patients more than palliative treatment and preventive advice. Now, potential pharmacological cures are in sight which may revolutionize the practice of ophthalmology. Between the patients and their recovered vision, however, lie the hurdles of drug trials and FDA approval. Many individuals will wait with little hope of benefiting from these medications. Our goal is to provide adequate research facilities to bring them the best that science can offer. The sooner we do that, the less they will suffer.

Blindness in America

Retinal diseases are the leading causes of blindness in the United States and in all developed countries. Different retinal disorders affect different age groups, but they all share the same fundamental pathways to blindness. Abnormal new vessels grow, and increased permeability and fluid leakage lead to partial or complete blindness.

The leading cause of legal blindness is age related macular degeneration (ARMD). This disease affects primarily the retired population. Approximately 1.75 million elderly Americans suffer from ARMD and 200,000 new cases are diagnosed every year. When macular degeneration changes from the dry into the more devastating wet type, onset of blindness is often rapid, and quality of life degrades catastrophically. The patient is suddenly unable to drive, read or write. Grocery shopping becomes a hardship in a society with limited public transportation. Maintaining financial self-sufficiency is impossible when the patient can no longer read bills or write checks. Finally, the most basic forms of enjoyment, such as reading, watching television, or seeing the faces of grandchildren are stolen from the patient. The frail independence of elderly people is thus all but destroyed, and with bleak expectations for the remaining years of life, the patient often sinks into deepening depression.

Diabetic retinopathy can affect people of all ages, but it is the leading cause of blindness in the young and middle aged. These working people often must surrender their independence to family members or to dwindling social programs. Unable to draw up and self-administer insulin, partially blind patients can sometimes not meet their own basic health care needs. With decades of life expectancy and a progressively deteriorating illness, their future will include loss of wages and of the ability to provide for their families and their retirement.

Retinopathy of prematurity, another retinal blood vessel disease, is the leading cause of blindness in children. It affects infants who were lucky enough to survive their very premature birth only to start life with the handicap of partial or total blindness.

In the United States and the rest of the industrialized world, the advent of laser surgery some two decades ago has reduced the incidence of blindness from these kinds of retinal diseases. However, laser treatments are of limited effectiveness not only because of disease recurrence and progression, but because they are, by their nature, destructive to the retina they attempt to preserve

A Pharmacological Revolution in Retina

Great successes in molecular biology and genetic engineering over the last decades have recently resulted in new classes of "smart" medications that target the pathways which lead to blindness in retinal diseases. Instead of cauterizing large amounts of retinal tissue with therapeutic lasers, we now have the ability to modulate the chemical pathways of blood vessel growth and function. An excellent illustration of the amazing complexity of these new medications is the story of rhuFab.

For decades, scientists correctly suspected that chemical messengers -- molecules produced by injured ocular tissues -- are released into the eye cavity. These then promote the growth of new abnormal blood vessels into the eye. Additionally, they cause the normal vessels to behave abnormally and leak serum into the retina. Any one of these pathological reactions impairs vision. In 1989, a scientist working for Genentech purified and cloned this molecule, called Vascular Endothelial Growth Factor (VEGF). This discovery allowed the development of strategies to inhibit the effect of VEGF (pronounced Vej-ef) in the eye. RhuFab is one of the most promising of several molecules that block VEGF.

The process of producing RhuFab begins by injecting cloned human VEGF into a mouse. The mouse immune system recognizes this human molecule as foreign and develops an antibody to fight it. This results in mouse anti-human VEGF antibodies. This mouse antibody is cloned and split. The part of the molecule that makes this antibody mouse-specific is cleaved and replaced by its human counterpart. The mouse anti human VEGF antibody is thus humanized. This allows the antibody to be used inside a human without triggering an immune response against it. The humanized mouse anti-human VEGF antibody is then cleaved again to make it small enough to penetrate across the human retina. The medication is further enhanced before injection into the human eye to block the growth of new blood vessels and the leakage that accompanies them. It is worthy to note that the same types of medications are not only useful in ophthalmology, but have a major impact in the treatment of cancer. Cancerous tumors need new blood vessels to supply them with nutrients, and they produce the same VEGF mediator to induce the growth of their own blood supply. Blocking VEGF in a tumor can stop its growth. In fact, the parent compound of rhuFab, has recently been approved as a cancer drug under the name Avastin.

From the Lab to the Pharmacy the FDA pathway and Clinical Trials

Prospective new drugs face a daunting challenge in their path from promising molecules in the laboratory to FDA approved drugs. Most of them never make it. For the ones that make it out of the lab and through clinical animal trials, a series of extensive human studies are necessary. These clinical trials in humans are structured in three or even four phases, spanning many years of testing, and involving hundreds or thousands of patients in many simultaneous clinical sites. In Phase I, safety is the primary concern. A small number of patients are enrolled under extraordinarily strict FDA supervision to ensure the safety profile of a potential new medication for a one-year period. A Phase II trial follows which continues to evaluate safety in a larger number of patients, but is mostly concerned with efficacy. If a prospective new medication passes both safety and efficacy in phase I and II multi center trials, a much larger Phase III trial is started. In Phase III, hundreds to thousands of patients are enrolled for a minimum of two years in many clinical research centers, sometimes in several countries. A Phase III trial provides an opportunity for infrequent, unexpected adverse effects to be identified in the larger patient population, and it generates statistically significant data on both safety and efficacy. Once the data is collected and analyzed, the FDA can decide if the new drug is acceptable, needs additional testing, or should be rejected.

Numerous biotechnology laboratories are producing competing potential drugs. In order to ensure reliability of data and the elimination of any potential bias, these drugs are studied in all phases under exceedingly detailed, standardized study protocols. For example, in a normal clinical situation, the simple act of checking vision, or visual acuity may last a few minutes. The same procedure in a study protocol will take about an hour with a specially trained and certified technician. Since the visual acuity is the endpoint in all ophthalmology studies, it is of paramount importance that this variable is measured in the most precise, consistent and reproducible way. The same meticulous attention to detail and documentation applies to every step in the trial. All documentation is reviewed periodically by visiting study monitors, and all imaging studies are sent to a centralized reading center to ensure that treatment decisions are not subject to bias by the local investigators. A variety of laboratory data, such as blood tests and electrocardiograms, are obtained to monitor patient safety. At each site, a dedicated study coordinator has the responsibility of running the study according to protocol. A single, on-site principal investigator (PI) supervises the coordinator, the sub-investigators and all the study personnel. The PI alone is responsible to the FDA and the study sponsor for every aspect of the study conducted at the institution. The stakes are very high. For a biotech drug company, failure may lead to catastrophic financial losses. For patients it may lead to additional years of blindness without a cure.

The Retina Consultants Research Activities

The pharmacological revolution in retina therapy promises to enormously impact the fight against blindness, and The Retina Consultants of the Lions Eye Institute have taken a major role, participating in numerous trials to date. They are the only group of retinal specialists in the Capital District Area, and they formed the Retina Division in the Department of Ophthalmology of Albany Medical Center. In addition to taking care of numerous patients from upstate NY, VT and western MA, they are conducting multiple simultaneous clinical trials in addition to independent research. Dr. Paul Beer, who is the head and founder of the Retina Consultants, is a clinical professor of Ophthalmology at Albany Medical College and the former Director of the Retina Division in the Department of Ophthalmology. He has been a PI or co-investigator for nearly 30 research protocols throughout his 16 years in practice, and his independent research has led to landmark publications in the field of intraocular injectable steroids. He has been a study design committee member on a National Eye Institute sponsored study for diabetic macular edema which started July 2004, and is the recipient of the Merit Award from the American Society of Retinal Specialists. Furthermore, under Dr. Beer's supervision, the Albany Medical College ophthalmology residents performing research in retina have received the Robert D. Reinecke annual research award for the last four years. Every member of Dr. Beer's team at the Lions Eye Institute is certified and participates in multiple FDA-supervised clinical trials.

Dr. Beer has formed the Retina Research Foundation Inc., a not-for-profit corporation (501(c) (3) status pending), with the primary purpose of building and supporting a dedicated retina research facility in the new Lions Eye Institute building which opened in November 2005. In addition to supporting the Retina Research Center, the Retina Research Foundation, Inc. is broadly positioned to support research in ophthalmology, patient advocacy, and educational initiatives for international physicians here or abroad.