Clinical Research

 

Basic Research

 
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  GLAUCOMA  
     
 

The Glaucoma Diagnostic Laboratory, under the direction of Dr. Robert D. Fechtner, is investigating new therapies for treating ocular disease. This center provides patients and physicians with the latest imaging and laser technologies, including ultrasound biomicroscopy (UBM), confocal scanning topography (Heidelberg Retina Tomograph and Topographic Scanning System [TopSS]), scanning laser polarimetry (GDx), a simultaneous stereo camera, and various psychophysical tools. As new technologies continue to emerge, the laboratory will play an even greater role by providing a research environment conducive to the development and testing of novel strategies for the early diagnosis of glaucoma as well as for monitoring disease progression. The laboratory houses a research facility for basic science/clinical research and offers programs for physician/patient education. Two funded projects are active in the laboratory. The Heidelberg Retina Tomograph is being used for the HRT ancillary study of the Memantine Neuroprotection Study. This multicenter ancillary study will explore the ability of computer-assisted technology to detect glaucomatous progression in patients with established disease. Dr. Fechtner’s research team has evaluated the prototype scanning laser polarimeter and is collecting data for a population-based normative data. The goal of this research will be to provide quality medical care through the application of the latest clinical findings.

 
     
  Glaucoma Diagnostic Technologies  
  Robert D. Fechtner, MD  
  The Glaucoma Diagnostic Laboratory at NJMS is now fully functional and incorporates the most advanced imaging technologies to study eye structures relevant to glaucoma. Recent efforts have focused on the use of scanning laser polarimetry to understand the corneaÕs effect on retinal measurements. Dr. Fechtner and collaborators are evaluating the first prototypes and incorporating individualized hardware and software strategies to improve the technologyÕs sensitivity and specificity. This will allow the technology to be used more reliably in a greater proportion of patients. Initial data collection for a normative database is completed. Dr. Fechtner is also studying metabolic imaging and the Glaucoma Division, in collaboration with the New Jersey Institute of Technology, is developing new technologies under a grant from the National Medical Testbed. One study uses spectroscopy to evaluate the oxygenation of small areas of retina. Previous efforts have focused on medium to large vessels. Dr. FechtnerÕs group is attempting to extract data from studies on small vessels, and a prototype is being constructed. This group is also studying how to use the optical properties of the aqueous humor as an indicator of blood glucose levels for the noninvasive monitoring of these levels for diabetic patients. Other studies focus on functional testing. The visual functional testing capabilities of the Glaucoma Division now include dedicated instruments for achromatic automated perimetry, short-wavelength perimetry, and frequency doubling testing. These technologies are being used in clinical trials including the Memantine Neuroprotection Study.  
     
  Clinical Pharmacology Research  
  Robert D. Fechtner, MD;  Paul J. Lama, MD  
  Medication is the initial therapy for elevated intraocular pressure (IOP). Ophthalmic beta-blockers represent the most common medications used to lower IOP. However, beta-blockers can have systemic adverse effects. Drs. Fechtner and Lama have now completed both arms of a prospective study of the incidence of contraindications to beta-blocker use in the general clinic population and in the glaucoma clinic population at NJMS. These results were presented at ARVO. Dr. Lama has authored a review of this topic, which was accepted for publication in the American Journal of Ophthalmology. A standard way to initiate therapy for glaucoma is to medicate one eye and compare the change in pressure between the treated and untreated eye. In collaboration with The University of Arkansas, this group has completed a retrospective study of the predictive value of the one-eye trial. Results were presented at ARVO. We have also successfully submitted a proposal to the Ocular Hypertension Treatment Study to analyze a similar data set collected prospectively. These analyses may help guide the search for the appropriate medical therapy for glaucoma.  
     
  Phase 3 and Phase 4 Drug Studies  
  Robert D. Fechtner, MD  
  An international phase 3 study of an NMDA antagonist, memantine, has been initiated by Allergan, Inc. NJMS is now an active study site (and the only site in New Jersey) and is one of the recruiting sites with the highest success rate for screening. Patient recruitment is underway and several 1-year visits have been completed. Dr. Fechtner is participating in this important study, the first which seeks to find a medical therapy for glaucoma by using a parameter other than eye pressure. This landmark study may change the way glaucoma is treated in the future.  
     
  New Technologies  
  Robert D. Fechtner, MD  
  A collaborative team, who seeks to explore opportunities for the development of new technologies in ophthalmology, has been assembled in conjunction with the New Jersey Institute of Technology. Core members of the team are Gordon Thomas, PhD, distinguished professor of physics at NJIT, Richard Greene, MD, PhD, director of NJITÕs Center for Appropriate Technology in Health, and Robert Fechtner, MD. Areas of interest include self-tonometry, new approaches for administering topical medications, retinal oximetry, and non-invasive glucose monitoring. This group has successfully obtained extramural support. The first completed project was the first independent laboratory and clinical evaluation of a self-tonometry system. Results were presented at ARVO and have been submitted for publication.  
     
  Subconjunctival Mitomycin C: A Toxicity Study  
  Paul J. Lama, MD; Brenda Pagán-Durán, MD  
  Drs. Lama and Pagan-Duran have been studying the effects of subconjunctival mitomycin C in a laboratory model. Mitomycin C (MMC) is a potent antifibrotic agent used intraoperatively to improve the success rate of glaucoma filtering surgery. However, the current mode of application of MMC produces variable tissue absorption. Thus, titration for efficacy and control for complications remain a challenge. The purpose of this project is to determine whether subconjunctival injection of fixed doses of MMC can be done safely using a laboratory model. The first part of the study will establish a threshold level of toxicity. MMC was injected subconjunctivally at the 12-o’clock position in a laboratory model. An observation period of 4 weeks followed injection. Slit-lamp examination (SLE), tonometry, dilated fundus examination (DFE), pachymetry, specular microscopy, electroretinography, and fluorescein angiography were performed pre-injection and post-injection at days 7 and 28. SLE, tonometry, and DFE were repeated also at 24 hours and 14 days post-injection. All ocular findings were recorded and signs of overt toxicity monitored. High doses were noted to cause scleral thinning and, therefore, were considered toxic. A threshold dose for overt toxicity was determined. A dose/response curve is being generated to establish a range of doses that can produce the desired ocular effects without toxicity. A subconjunctival injection of MMC vehicle was administered as a control. After the clinical phase, 30 samples were examined histologically. Cell culture will also be performed to determine fibroblast growth inhibition at different doses and times from injection. Administration of a fixed dose of MMC via subconjunctival injection may provide a simple and safe route of delivery. Studying the clinical and histologic effects will enable us to determine the most efficacious dosages with the fewest complications related to toxicity.