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NEW TECHNOLOGY How the Techno-Revolution Here's a peak at how biomedical engineering will
improve your diagnostic and therapeutic capabilities. by Charles M. Wormington, O.D., Ph.D., Philadelphia One reward of optometric practice is that we're witnesses to the advance of biomedical technology.
New diagnostic devices, medicines, laser procedures and surgeries transform patient care from one year to the next. This pace will accelerate in the next decade as new modes of diagnosis and treatment emerge from the research labs.
Among the most dramatic strides will be gene-based approaches to disease detection and management. The genomics revolution will make a tremendous impact on optometry and all fields of health care (see, Nerve Fiber Layer Assessment • Retinal laser polarimetry.
The GDx Nerve Fiber Analyzer from Laser Diagnostic Technologies uses a scanning unit to move a diode laser beam up and down on the retina. The beam passes twice through the nerve fiber layer. Beam measurement after these passes yields the thickness of the NFL in tiny increments. The device then presents the results numerically and graphically. The measurement takes less than a second, and pupil dilation isn't necessary. We can use the device to detect early-stage glaucoma as well as other optic neuropathies.
• Optical coherence tomography. The Optical Coherence Tomography Scanner from Humphrey Instruments also uses a diode light source to provide a cross-sectional image of the NFL. It can penetrate mild-to-moderate
cataracts, but a cloudy vitreous or dense cataracts will impede its use. OCT's clinical applications extend from the retina to the anterior segment. It can measure the NFL and help detect and monitor glaucoma. You can
use it to detect and follow macular edema, holes and degenerations. It's helpful in diagnosing other retinal and choroidal diseases, detachments, inflammations and tumors. Potential applications include using the scanner to measure
corneal thickness; gauge the corneal ablation depth in refractive surgeries; measure the angle, anterior chamber depth and iris thickness; calculate IOL power; and evaluate cataracts. • Laser biomicroscopy.
This diagnostic tool is now available in the Retinal Thickness Analyzer and Laser Slit from Talia Technology. This laser slit lamp projects a narrow beam from a green helium-neon laser to image the fundus, perform retinal scans and generate thickness maps. Using this optic section of the retina helps in the early diagnosis of aging changes, glaucoma, macular edema, epiretinal membranes, macular holes and cysts, and RPE detachments.
New Automated Perimetry • SITA.
The Swedish Interactive Thresholding Algorithm is a new program for the Humphrey Field Analyzer II that was first released in 1997. An updated version was unveiled last year. The SITA Standard 24-2 threshold test is the full version that's comparable to Humphrey's standard algorithm. It's twice as fast as the standard program, and it's more accurate and consistent. The old test takes about 12 minutes, the new test about half that.
SITA Fast is similar to Humphrey's FastPac but twice as fast (three vs. seven minutes). Its accuracy and reproducibility match those of FastPac. But use this only as a screening or practice threshold test. Given its
limitations, you should never use it to follow a glaucoma patient. Results vary too much within the test itself and from one test to the next to make it useful for serial visual fields in glaucoma. Instead, the SITA Standard
program can be used to follow glaucoma patients. Unlike the old Humphrey thresholding programs, the SITA program weighs all factors as the test goes along to estimate the threshold at each point in real-time. Factors
that affect the stimuli presentation include the normal age-corrected threshold value, the patterns of loss typical of the disease, the patient's previous responses, the normal frequency-of-seeing curve, the estimated
frequency-of-seeing curve based on location, and false answer rates. The program measures the patient's reaction time and adjusts stimuli presentations accordingly. The new algorithm computes when to stop at each test
location. It spends more time at sites where the result is unsure and less time where the results are consistent. When the patient completes the test, the program re-estimates the results from each location. • SWAP.
Short-Wavelength Automated Perimetry, or blue-on-yellow perimetry, detects and monitors early glaucomatous damage in patients with ocular hypertension or nascent glaucoma. Blue-on-yellow perimetry employs a two-color increment
threshold paradigm to isolate and assess the sensitivity of the short-wavelength-sensitive (i.e., blue) cones and ganglion cell system. Blue-on-yellow deficits in glaucoma suspects predict the onset and location of visual field
loss which shows up later with standard white-on-white automated perimetry. In one longitudinal study of 76 ocular hypertensive eyes with normal white-on-white automated perimetry results, nine eyes had abnormal
blue-on-yellow results.1 Five years later, five of the nine eyes with abnormal blue-on-yellow results developed glaucomatous visual field loss on standard white-on-white automated perimetry. None of the 67 eyes that had been normal
with blue-on-yellow perimetry had abnormal white-on-white perimetry results. Blue-on-yellow deficits can precede white-on-white field loss by at least three to four years.1,2 Blue-on-yellow perimetry is most useful for
detecting early glaucomatous loss in patients with ocular hypertension and for monitoring those with early field loss. Once significant glaucomatous damage occurs, little or no blue-on-yellow sensitivity remains throughout the
central visual field. Blue-on-yellow perimetry may assist in assessing damage in diabetic retinopathy and certain neuro-ophthalmic deficits more readily than standard automated visual field testing. It's especially
useful for optic neuritis and multiple sclerosis. Cataract Surgery, PDT • Laser Lens Lysis from IOLAB (Nd:YAG laser). Meanwhile, researchers have taken photodynamic therapy (PDT) beyond oncology to potential ocular applications. They've used photosensitizer molecules to ablate tumors
through selective uptake by tumor cells. Subsequent exposure to focused visible laser radiation leads to cell death. Hyperproliferative cells take up the photosensitizers more than the normal resting cells. Neovascular endothelial
cells also have an accelerated uptake. This selectivity suggests that PDT might be useful in other diseases involving either hyperplasia or neovascularization. Potential ocular uses include ocular tumors, ARMD,
corneal disease, diabetic retinopathy and glaucoma. Clinical trials have been run to treat wet ARMD with a diode laser and verteporfin, a second-generation photosensitizer.3,4 This therapy is under review by the Food and Drug
Administration and may be approved for use in early 2000. Looking to the Future • Diagnosis.
Very soon we'll be diagnosing diseases before symptoms ever appear by identifying predictable genetic markers. And, we'll have the tools in our offices to provide reliable diagnoses. Already we've identified genetic markers for HIV, reducing dramatically the time it takes to diagnose HIV infection.
• Treatment. Within 10 years you'll have microchip technology that will allow you to identify which pathogen is causing a disease and to select the most specific treatment for that pathogen.
Dr. Wormington, an associate professor at the Pennsylvania College of Optometry, lectures and writes frequently on new technologies with ocular applications. He is currently
working on a book on ophthalmic lasers . 1. Johnson CA, Adams AJ, Casson EJ, Brandt JD. Blue-on-yellow perimetry can predict the development of glaucomatous visual field loss. Arch Ophthalmol 1993;111:645-50. |
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From glaucoma to ARMD,
nearly every ocular disease has a genetic component. That's precisely why genomics and molecular biology are already changing the way we diagnose and treat diseases. And, gene-based approaches figure to play a prominent role in
disease prevention. The genome revolution will equip us with clinical tools once unimaginable. With advances in molecular biology comes an exotic new vocabulary once confined to the research journals. Terms such as exons,
introns, recombinant DNA, PCR, and Northern analysis have become the common currency of today's clinical research journals and ophthalmic literature. Recall that the human genome consists of all the DNA in every human cell. The
course of genetic information flows from DNA to RNA to protein. It's a two-stage process that involves: 1) transcription, the use of the genetic code in DNA to make messenger RNA; and 2) translation, in which the information
encoded in mRNA is used to make proteins. This is the playing field on which molecular biologists aim to conquer once-invincible diseases. Human Genome Project • Map the human genome.
Through linkage studies the researchers have determined the order of DNA markers. This information enables us to locate disease genes through family-based genetic linkage studies. This part of the project is essentially done, a map of 30,000 human genes having been released.
• Sequence all human DNA.
This involves specifying the sequence of the nucleotide bases—adenine, cytosine, guanine and thymine—in the DNA. The exact sequence of these bases encodes the genetic information. A complete and highly accurate human genome sequence is scheduled for completion by the end of 2003.
• Explore ethical, legal and social issues.
Key issues include fairness and confidentiality in how genetic information gets used, as well as the psychological impact and stigmatization of an individual's genetic differences. Reproductive issues and testing for specific conditions for which there's a family history pose dilemmas, too. The clinical issues include educating providers and patients. Testing standards and quality-control measures for testing procedures also merit discussion. Product commercialization is another concern.
• Develop comparative genomics. This
involves mapping and sequencing the genomes of various model organisms like the bacterium E. coli and the mouse. This will help to develop the essential technology and to aid understanding of the meaning of the human genome sequence.
• Advance functional genomics.
This deals with the interpretation of the functions of the various human genes. Knowing the sequence of a particular gene is only the first phase of understanding; knowing what that gene does is the next stage of understanding. Determining the protein that is coded for by the gene can then lead to knowledge of the function of that protein and hence of that gene.
Gene Chips • A p53 tumor suppressor gene chip to detect mutations in a gene that's mutated in more than 50 percent of all human cancers. Ocular Applications Our understanding of the genetic basis of glaucoma, for example, has
advanced rapidly. We know that mutations in the myocilin gene at the GLC1A locus on chromosome 1 occur in some patients with juvenile- and adult-onset POAG. Researchers have reported five other genetic sites for POAG. Isolating the
genes and characterizing the culpable gene products will offer insight into retinal and optic nerve susceptibility factors in glaucoma. This will lead us to redirect our treatment efforts from the trabecular meshwork to the retinal
and nerve tissues ultimately responsible for visual loss. It's already possible to diagnose presymptomatic at-risk individuals. One large group of at-risk patients has undergone such testing.1 Identifying additional
glaucoma genes and devising cost- and time-efficient mutation screening strategies may enable a broader screening. Antisense Drugs Antisense drugs are complementary strands of small portions of messenger RNA. These oligonucleotide drugs bind to a specific sequence of nucleotides in their mRNA target, inhibiting the production of the
disease-causing protein. The cell's enzymes mark the bound mRNA for rapid breakdown. The antisense oligonucleotide can then seek out and disable another identical mRNA strand. Potential applications include:
• Regulation of gene expression in retinal neovascularization, CMV retinitis, cancer, Alzheimer's disease, several viral diseases and inflammatory diseases. 1. Mackey DA, Craig JE, McNaught AI, et al. Predictive DNA testing for glaucoma with the GLC1A gene: experience with a large Australian family (abstract). Invest Ophthalmol Vis Sci 1998;39:S31. |
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