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Basic Research
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GLAUCOMA |
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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.
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Glaucoma Diagnostic
Technologies |
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Robert
D. Fechtner, MD |
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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. |
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Clinical Pharmacology
Research |
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Robert
D. Fechtner, MD; Paul J.
Lama, MD |
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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. |
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Phase 3 and Phase
4 Drug Studies |
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Robert
D. Fechtner, MD |
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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. |
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New Technologies |
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Robert
D. Fechtner, MD |
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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. |
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Subconjunctival Mitomycin
C: A Toxicity Study |
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Paul J. Lama,
MD; Brenda Pagán-Durán,
MD |
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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. |
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