AVAILABLE TECHNOLOGIES
There are several technologies that quantitatively assess the ocular structure for the purposes of glaucoma detection and management. Confocal scanning laser ophthalmoscopy can evaluate the optic nerve head, and the commercially available device is the Heidelberg Retina Tomograph (HRT; Heidelberg Engineering GmbH, Dossenheim, Germany). Optical Coherence Tomography (OCT) can also be used for the objective quantitative assessment of the optic nerve structure, and the commercially available device is the Stratus OCT (Carl Zeiss Meditec Inc., Dublin, CA).
Physicians can measure the retinal nerve fiber layer with either scanning laser polarimetry or OCT. The commercially available scanning laser polarimeter is the GDx VCC (Laser Diagnostic Technologies, San Diego, CA). Finally, physicians can assess glaucoma patients' macular thickness with either OCT or the Retinal Thickness Analyzer (RTA; Talia Technologies Ltd., Neve Ilan, Israel).
DETECTING GLAUCOMA WITH IMAGING TECHNOLOGIES
The Optic Nerve
Confocal scanning laser ophthalmoscopy with the HRT takes a series of optical sections at various depths within the optic nerve tissue. The device acquires and then reconstructs between 16 and 64 planes. Next, the HRT determines the topography of the optic nerve head and retina. After the user draws a contour line defining the optic disc margin, an automated algorithm determines a variety of optic nerve head parameters. Many of these parameters are based on a reference plane that is defined as 50 µm posterior to the mean retinal height along 6º of the temporal inferior sector. Structures above the reference plane and within the contour line are considered to be rim, and those below the reference plane are designated as cup. OCT uses near infrared light at 820 nm and measures the flight time of that light in a Michaelson-type interferometer. The use of low coherence light permits high-resolution imaging by limiting the width of the signal envelope. Resolutions are on the order of 8 to 10 µm with the Stratus OCT device.
Birefringence
Scanning laser polarimetry uses polarized light to determine the amount of birefringence in the eye. The retinal nerve fiber layer is birefringent, as are the cornea and crystalline lens. The older version of the technology, the GDx (Laser Diagnostic Technologies), had a fixed corneal compensator to allow for anterior segment birefringence. The compensator assumed that the anterior segment birefringence had an orientation of 15º nasally downward and an amplitude of 60 nm. Unfortunately, there is a wide distribution of orientations and amplitudes of corneal birefringence in the population, so there was inaccurate anterior segment birefringence compensation in a significant number of cases.1 This suboptimal anterior segment compensation led to falsely positive or falsely negative results with regard to nerve fiber layer (NFL) thickness.
A clinical means to determine whether adequate anterior segment birefringence compensation has occurred is to scan the macula with the GDx. If little or no macular birefringence can be seen, and if the residual macular birefringence has an even pattern, the clinician may assume that there is relatively good anterior segment birefringence compensation, because there is little actual retinal nerve fiber layer in the macula. By contrast, if the clinician observes a prominent hourglass pattern in the patient's macula, the anterior segment birefringence compensation is probably inadequate, and scans of the peripapillary retinal nerve fiber layer should not be used.1
The modified GDx device is based on the macular scanning principle. The GDx VCC compensates for anterior segment birefringence by neutralizing the macular birefringence signal. Measurements of retinal nerve fiber layer thickness with the GDx VCC correspond much more closely to measurements with other technologies than do measurements with the fixed corneal compensator.2-4
Comparative Findings
Several studies3-6 have compared the various imaging technologies. Most have found that the devices discriminate well between normal and glaucomatous eyes. Since the GDx VCC is so new, there are limited data on disease discrimination with this device.3,4
DETECTING PROGRESSION
As stated earlier, a critical aspect of imaging technology is its ability to detect disease progression. Unfortunately, because studies of glaucomatous progression take so long to accomplish, there is little information in the literature regarding the ability of these technologies to detect disease progression. Probably the best article on the subject used the HRT to detect disease progression in a group of patients with glaucoma.7 In this study, the investigators showed that (1) the HRT detected optic nerve head changes more frequently than visual field changes occurred and (2) most individuals with visual field changes had optic nerve head changes, but fewer than half of those with optic nerve changes experienced visual field changes.
Interestingly, another study used OCT to longitudinally measure peripapillary NFL thickness.8 The researchers saw progression with OCT more often than on visual fields, and nearly all individuals with visual field progression also demonstrated progression by OCT.
The reason for the disconnection between structural and functional measures of glaucoma may be related to the fact that 30% to 40% of retinal ganglion cells must be lost before standard functional measures such as visual fields can detect damage. By contrast, structural loss seems to follow a more linear pattern of decay and may show damage much earlier in the disease process.
MACULAR THICKNESS AND GLAUCOMA
It is intriguing that glaucomatous damage may be detected in the macula. Ran Zeimer, PhD, of The Wilmer Eye Institute at Johns Hopkins University in Baltimore first proposed this idea, which was considered heretical when first voiced. Dr. Zeimer suggested that, because (1) retinal ganglion cells are specifically lost in glaucoma, (2) the macula is the region of the retina where the ganglion cell layer is more than one cell thick, (3) 50% of retinal ganglion cells in the eye reside in the macula, and (4) a ganglion cell body is 15 µm or more in size, whereas its axon is only 1 to 2 µm in diameter, detecting glaucomatous damage should be much easier through the evaluation of macular thickness than through the evaluation of peripapillary NFL thickness.9
In fact, glaucomatous damage does correspond well with macular thickness. In two published studies,10,11 however, OCT showed that peripapillary NFL thickness had a stronger association with disease status than did macular thickness. This finding may be due either to the fact that circumpapillary scans measure the representation of the entire macula and not just the macular 50% of the retinal ganglion cells, or to differential rates of decay of the ganglion cells and their axons.
CONCLUSIONS
Physicians may use a variety of technologies to assess the retinal and optic nerve head structure of glaucoma suspects and patients. Improvements in resolution may lead to the increased reproducibility, sensitivity, and specificity of results. Imaging may be useful, not only for clinical patient care, but also for outcome evaluation in studies, of medications, and of other interventions. The ultimate goal is to develop imaging technologies that enable the earliest possible detection of disease and its progression so that physicians may prevent vision loss.
Supported in part by NIH R01-EY13178-4, RO1-EY11289-16, and P30-EY13078; by a grant from the Massachusetts Lions Eye Research Fund Inc.; and by Research to Prevent Blindness in New York.
Joel S. Schuman, MD, is Professor and Vice Chair at the New England Eye Center, Tufts–New England Medical Center, Tufts University School of Medicine in Boston. Dr. Schuman has received research funds from Carl Zeiss Meditec Inc., Laser Diagnostic Technologies, and Talia Technologies Ltd. He is an inventor of OCT. Dr. Schuman may be reached at (617) 636-7950; jschuman@tufts-nemc.org.
1. Weinreb RN, Bowd C, Greenfield DS, Zangwill LM. Measurement of the magnitude and axis of corneal polarization with scanning laser polarimetry. Arch Ophthalmol. 2002;120:7:901-906.
2. Greenfield DS, Knighton RW, Feuer WJ, et al. Correction for corneal polarization axis improves the discriminating power of scanning laser polarimetry. Am J Ophthalmol. 2002;134:27-33.
3. Bagga H, Greenfield DS, Feuer W, Knighton RW. Scanning laser polarimetry with variable corneal compensation and optical coherence tomography in normal and glaucomatous eyes. Am J Ophthalmol. 2003;135:521-529.
4. Weinreb RN, Bowd C, Zangwill LM. Glaucoma detection using scanning laser polarimetry with variable corneal polarization compensation. Arch Ophthalmol. 2003;121:218-224.
5. Bowd C, Zangwill LM, Berry CC, et al. Detecting early glaucoma by assessment of retinal nerve fiber layer thickness and visual function. Invest Ophthalmol. 2001;42:1993-2003.
6. Schuman JS, Wollstein G, Farra T, et al. Comparison of optic nerve head measurements obtained by optical coherence tomography and confocal scanning laser ophthalmoscopy. Am J Ophthalmol. 2003;135:504-512.
7. Chauhan BC, McCormick TA, Nicolela MT, LeBlanc RP. Optic disc and visual field changes in a prospective longitudinal study of patients with glaucoma: comparison of scanning laser tomography with conventional perimetry and optic disc photography. Arch Ophthalmol. 2001;119:1492-1499.
8. Wollstein G, Schuman JS, Price LL, et al. Evaluating Longitudinal Retinal Nerve Fiber Layer (RNFL) Thickness Changes with Optical Coherence Tomography (OCT). Paper presented at: Annual meeting of the American Academy of Ophthalmology; October 21, 2002; Orlando, FL.
9. Zeimer R, Asrani S, Zou S, et al. Quantitative detection of glaucomatous damage at the posterior pole by retinal thickness mapping. A pilot study. Ophthalmology. 1998;105:224-231.
10. Guedes V, Schuman JS, Hertzmark E, et al. Optical coherence tomography measurement of macular and nerve fiber layer thickness in normal and glaucomatous human eyes. Ophthalmology. 2003;110:177-189.
11. Greenfield DS, Bagga H, Knighton RW. Macular thickness changes in glaucomatous optic neuropathy detected using optical coherence tomography. Arch Ophthalmol. 2003,121:41-46.
