Evaluation of medications that lower intraocular pressure, increase fluid outflow, and that strengthen the eye against the effects of high pressure (neuroprotective agents).
Two radically new medications are currently being tested. The first of these destabilizes the nanofiber skeletons of the cells of the trabecular meshwork, allowing them to lose their connections with each other and transiently round up, an action which may allow debris trapped in the meshwork and clogging it to be released. The second drug is injected under the conjunctiva near the cornea in a slowly biodegradable matrix, which may provide long-standing pressure reduction, up to 3-6 months, as an alternative to eye drops.
We have investigated the success of the titanium-sapphire laser in the treatment of open-angle glaucoma. This laser has just received FDA approval.
Current studies involve the development of new glaucoma drainage implants, and a new operation (canaloplasty) to widen Schlemm's canal (the final portion of the drainage pathway in the eye.
The gold shunt is an implanted in such a way as to drain fluid from the anterior chamber to behind the iris, thus avoiding the bleb associated with trabeculectomy. In the next stage of these investigations, awaiting FDA approval, tiny "chads" in the front portion of the shunts will be lasered to create tiny openings in order to increase the ability of the shunts to drain fluid.
Canaloplasty is another new operation designed to attempt to avoid formation of a bleb by threading a suture around the 360 degrees of Schlemm's canal and tightening it, thus widening the canal and permitting more efficient drainage of aqueous humor.
Studies are also underway evaluating the Trabectome, an instrument designed to peel away the trabecular meshwork and expose Schlemm's canal directly to the fluid in the anterior chamber in order to bypass the blocked meshwork and allow aqueous humor to enter Schlemm's canal directly.
Ologen, a microtechnology-based, biodegradable membrane, developed in Taiwan to create a safer, effective, less complication-prone filtering bleb than currently obtained with the commonly used antiscarring drugs, 5-FU and mitomycin C, has just been approved by the FDA and will be undergoing both a comparative prospective protocol and investigations into new uses during glaucoma surgery.
Research on Exfoliation Syndrome
Exfoliation syndrome (XFS) is the most common identifiable cause of open-angle glaucoma worldwide, comprising the majority of glaucoma in some countries. Its widespread distribution, its frequency, and its potential association with other diseases is only beginning to be realized. At the cellular and biochemical levels, XFS is a distinct entity, with a unique mechanism of development that is still being elucidated. People with XFS have 6-8 times the chance of developing glaucoma as those without it. XFS is characterized by the production and progressive accumulation of a fibrillar extracellular material in many ocular tissues. XFS is also a cause of cataracts and operation on cataracts in XFS is accompanied by a greater rate of complications. An increasing number of associations with specific systemic disorders is being reported, including transient ischemic attacks, hypertension, angina, myocardial infarction, stroke, asymptomatic myocardial dysfunction, Alzheimer's disease, and hearing loss. This disorder was the subject of the 2009 Optic Nerve Rescue and Restoration Think Tank, bringing together scientists from many fields from around the world, to devise new approaaches into investigation and treatment. We have earmarked this as the first major glaucoma to be potentially reversible and even curable.
In collaboration with Professor Jorge Ghiso at New York University, investigations into the molecular composition of exfoliation material were published in 2007. This study used mass spectroscopy to reveal a number of different proteins present in the material, including complement C1q, a molecule associated with chronic inflammatory disease, suggesting that XFS should be included in this category. The discovery of the genetic mutations involved in XFS were also described in Iceland in 2007 and confirmed in a publication involving patients at NYEE. The gene is involved in the synthesis and maintenance of elastic tissue throughout the body, offering a suggestion as to the connection between XFS and the various vascular diseases with which it has been recently associated. These include myocardial ischemia, cerebrovascular insufficiency, and arterial dysfunction. Atomic force microscopy and tissue culture are new approaches currently being used to determine the nature of the material and to produce it in quantities sufficient to analyze biochemically.
Other investigations involve testing exfoliation suspects for the gene and testing children of patients with XFS for the genetic mutations to determine their future susceptibility.
Multifocal visual-evoked potentials as a potential avenue for objective assessment of visual function and to enhance our understanding of glaucoma pathophysiology and the relationships between structural and functional injury in glaucoma. Extensive research into this new tool has been ongoing for several years in collaboration with Professor Donald Hood, PhD, Departments of Psychology and Ophthalmology, Columbia University.
Also known as fundus perimetry, microperimetry is a new technique which allows for exact topographic correlation between portions of the central retina and their light sensitivity. The principle rests on the possibility to see —in real time— the retina under examination by infrared light and to project a defined light stimulus over an individual, selected location. Microperimetry allows quantification of retinal threshold in the macular area. Sequential examinations allow evaluation of the natural history of disease, and monitoring of the effect of therapeutic intervention. We are using this tool to image in fine detail early glaucomatous visual field defects in the central fixation area, especially common in normal-tension glaucoma, and to monitor both their progression and the response to treatment. Our recent studies support its use to detect early central visual field loss before conventional perimetry. It also shows good correlation and better repeatability when compared with other devices that evaluate the central retina and its function.
Retinal Functional Imaging
This new device is the only commercially available technology that provides real-time calculation of the velocity of the retinal blood flow. By using a sequence of high-quality photographs of the retina and its vessels, the device measures the velocity of each red cell and based on the caliper of the vessels one can estimate the blood supply at each retinal region, such as the macular or parapapillary retina. This is particularly useful to understand the role of blood flow and new modalities of treatment (independent of the IOP) that could potentially prevent glaucomatous visual loss.
Glaucoma genetics research
Glaucoma genetics research involves normal-tension glaucoma, primary open angle glaucoma, exfoliation syndrome, pigmentary glaucoma and congenital glaucoma. A major breakthrough in 2007 was the discovery of the mutations causing exfoliation syndrome and exfoliative glaucoma. Not everyone with these mutations develops exfoliation syndrome. We are now engaged in a search for modifier genes which determine whether or not someone with these mutations will develop exfoliation sydrome or exfoliative glaucoma. We are investigating the presence of modifier genes in various glaucomas and correlating these with the age of onset and severity of the glaucoma.
The Ocular Imaging Center is among the best equipped in the world. We have made great strides in the development of new diagnostic modalities. Virtually all early research related to ultrasound biomicroscopy (UBM) was first performed at NYEE. These studies have allowed us to accumulate a huge amount of data that may be helpful to better understand the diseases of the anterior segment of the eye, such as angle closure glaucoma. Research instrumentation includes confocal scanning laser polarimetry, confocal scanning laser ophthalmoscopy, optical coherence tomography, and multifocal visual evoked potentials. Ocular imaging includes: ultrasound biomicroscopy (UBM), time-domain and Fourier-domain optical coherence tomography (OCT), scanning laser polarimetry (GDx Access), retinal thickness analyzer (RTA) and Heidelberg retinal tomography (HRT). Confocal scanning microscopy provides high resolution in vivo imaging of anterior segment structures, being capable of detecting signs of early disease not seen during slit-lamp examination. Recently, we have been using three different types of Fourier-Domain OCT (FD-OCT), which provide 3-dimensional images of the anterior and posterior segments of the eye. It allows, for example, obtaining real-time, high-resolution images (up to 3 microns) of the optic nerve, retinal nerve fiber layer and retina. These are the main sites of glaucomatous injury and therefore also allow early detection of the disease before the patient presents any symptoms, Moreover, because of its ultra-high speed of image acquisition this technology allows better repeatability of measurements being able to detect change (worsening) more accurately, if it occurs. The Shelley and Steven Einhorn Clinical Research Center at NYEE will be one of the most advanced such facilities in the world, with numerous imaging devices both currently used and in development, for study of every structure of the eye.