Figure 1. The HRT II.
Elliot M. Kirstein, O.D., F.A.A.O.
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For decades, precise observation and documentation of the optic nerve head has been essential for the diagnosis and management of glaucoma. In previous generations, physicians depended on ophthalmoscopic observations, colored drawings, and clinical notes to determine whether the nerve had been damaged by glaucoma.
Fundus photography provided a great leap forward in optic nerve head documentation and this was soon followed by stereophotography, which allowed nerve head contours to be visualized. Although photography allowed doctors to discard their colored drawing pencils, photography still does not provide enough precise information to detect subtle nerve head changes associated with disease progression.
The development of laser imaging techniques has allowed another advance to be made in the ability of eye care specialists to image and quantify optic nerve head contours. The Heidelberg Retinal Tomograph II (HRT II) uses confocal scanning laser ophthalmoscopy (CSLO) to produce pseudo-three-dimensional images of the nerve head. It also produces a set of precise numerical measurements that can be used to document nerve head status and changes.(18, 22, 23, 25, 27, 28, 31, 32, 35, 37, 40, 41)
This course focuses on the role of the HRT II in the diagnosis and management of glaucoma. It includes a description of HRT II technology along with clinical applications and case reports demonstrating its use.
HOW THE TEST IS ADMINISTERED
The HRT II has chin and forehead rests and an eyepiece into which the patient looks. Initial preparation requires the examiner to adjust the focus of the eyepiece to the patient's prescription. Patients with cylinder requirements over 1.00 D can either wear their own eyeglasses during testing or HRT cylinder lenses can be used to provide proper focus and an acceptable image.
Figure 1. The HRT II.
The device is then adjusted so that the light beam enters the patient's pupil while she/he looks into the HRT II eyepiece and observes a glimmering red square. Next, depending on which eye is being tested, the patient shifts his/her gaze to a green fixation target located to the left or right of the square. (A secondary external fixation light is also available for use.) When the patient's alignment is satisfactory, the Acquisition Button is pressed and HRT II begins automatic processing. From this point forward, all the patient has to do is maintain fixation on the green spot and the HRT II automatically gathers information about the shape and contours of the optic disc. Data acquisition and analysis takes between one and two minutes depending on cup depth and can easily be performed by a trained technician.
A key to clinical application and reliability of the HRT II is its relative ease of use. Excellent image quality can be achieved through a non-dilated pupil (but dilation is sometimes helpful). (42) Acceptable data can also be acquired through a patient's contact lens, moderately compromised media, or a wide range of spectacle prescriptions. However, significantly compromised media, e.g., cataracts, can reduce the ability of the HRT II to acquire usable data.
HOW THE HRT II WORKS
The HRT II acquires its data by use of a confocal scanning laser ophthalmoscope. This technique uses a 670-nm diode laser sharply focused at different depths within the eye to scan a series of 15 by15 degree areas.
To understand how the CSLO forms an image, consider a laser system precisely focused at a certain depth within the eye just above the optic nerve head (i.e., just slightly out in the viterous from the nerve). The laser beam is scanned back and forth point by point across a 15 by 15 degree area centered on the nerve head. Within this area, the HRT II records data from 147,456 separate points (AKA, pixels).
A simplistic (and not totally accurate) way to think of how the HRT II records its images is to assume that if the beam strikes any tissue that is in focus in the plane of its scan, the location the tissue and the depth of the scan plane are recorded by the HRT II computer.
Fig. 2. Optical Pathway in a Confocal Microscope System. (http://www.is.kochi-u.ac.jp/Bio/instrumentrs/clsm.html)
The focal plane for the laser is then lowered in small increments toward the back of the eye and another scan is made. Again, any tissue locations that are in focus in the plane of the scan will be recorded by the computer.
The process of advancing the focal plane of the laser and scanning is continued until the deepest part of the optic cup is reached. Depending on cup depth, the HRT II laser will be focused at between 16 and 64 different planes.
After the first set of scans is complete, the HRT II makes two additional full sets of scans to improve accuracy and reduce the effects of any head or eye movements.
After completing the 3 sets of scans, data are combined to produce a pseudo-three-dimensional image of the nerve head. The HRT II computer also provides numerical values for various aspects of nerve head topography.
Numerical values calculated by the HRT II include disc, cup, and rim volumes and areas; cup to disc ratio; mean cup depth; cup-shape measure; difference in height of the nerve fiber layer tissues (height variation contour) at various points around the disc; and overall mean retinal nerve fiber layer thickness.(8, 14, 19)
Fig. 3. Information from147,456 pixels is recorded for each plane at which the laser is focused.
Figs. 4 and 5. Data from three complete sets of scans, each consisting of pixels from between 16 and 64 planes, are used to create a pseudo-three-dimensional image.
Image quality is statistically graded by the HRT II so that clinicians can delete images that fall below acceptable criteria. Each image is accompanied by a "topography standard deviation (TSD)" value. TSD values under 10 represent excellent reliability, values of 10 to 20 are very good, 20 to 30 are good, 30 to 40 are acceptable, and those over 40 are considered unreliable for baseline or follow up analyses.
Fig. 6. Standard Deviation Guidelines
UNDERSTANDING HRT II DATA AND CLINICAL APPLICATIONS
After the baseline images are captured by the HRT II, the next step for the doctor or technician is to manually define the optic disc margin. This critical step is accomplished by plotting a series of dots around the margin of the disc on the reflectance image provided by the computer. The disc margin is defined as the inner edge of the scleral (Elschnig's) ring.
Sometimes the borders of the disc are difficult to define and it becomes necessary to study the reflectance, topographical, and pseudo-three-dimensional images to reasonably define the margin. If the doctor is not satisfied with the margin definition, it can be edited and redefined at the time during the baseline visit or at any future patient visit.(10, 38)
When the disc margin of the baseline data is redefined, all other data will be corrected and compared to the new definition. This makes it impossible to have different and inconsistent margins defined at separate patient visits.
Fig. 7. At the time of the initial examination, the examiner places a ring of points around the optic nerve head border. For precise comparison, these reference points are maintained at future visits. If the examiner chooses to adjust the points, the HRT II automatically adjusts them for the entire series of examinations.
Although the HRT II generates a long list of stereometric disc parameters, the rim area, rim volume, cup shape measure, height variation contour, and mean retinal thickness seem to be the most useful in making a baseline evaluation and for tracking glaucoma progression.
Fig. 8. Normal values
The Table in Figure 8 shows values for normals, along with corresponding values from early, moderate, and advanced glaucoma patients. The Table is a numeric representation derived from a normative study, which was compiled at Heidelberu University in Germany under the direction of Reinhard Burk. The parameters mentioned above are highlighted in gray on the Table.(16, 17, 40) (For those unfamiliar with the statistical term "regression analysis," just substitute the word "prediction" for regression and the meaning becomes clearer. Certain values and combinations of values have been found to predict the status of a patient's glaucoma.)
Moorfields' Regression Analysis makes comparisons between neuroretinal rim area, disc area, and a normative database to make an initial analysis and classification. (The statistical term "normative" simply implies that comparison data were averaged from a large number of normal patients who did not have glaucoma.)
In addition to the numeric tables, the Moorfields regression analysis provides a graphical analysis of optic nerve and rim area topography by dividing the nerve into six sectors and reporting the status of each sector. A check mark means "within normal limits," an exclamation mark means "borderline," and an X suggests that the topography is "outside normal limits."
The following images show HRT II analyses with numeric values and graphic analyses for a patient with all six optic nerve sectors "within normal limits," followed by "borderline," and "outside normal limits" examples. The colored bar graphs on the numeric reports indicate the amount of tissue within each sector: green indicates "within normal limits" and red means "outside of norms." There is an additional bar, which represents a global calculation for rim tissue topography across all 6 areas.
Figs. 9 and 10. HRT II analysis showing numeric values and graphic analysis with all six optic nerve sectors "within normal limits," followed by individual results which are "borderline" and "outside normal limits." The colored bar graphs on the numeric reports depict the amount of tissue within each sector, which is within (green) or outside of (red) normal limits. There is an additional bar, which represents a global calculation.
Figs. 11 and 12. A "borderline" optic nerve with retinal surface height display. When a particular optic nerve image is presented, the doctor may view the topographic profile of a nerve head in the horizontal or vertical meridian. The classic double hump, which we expect to see in the profile of a normal nerve, can easily be observed and compared in either meridian.
Figs. 13 and 14. Classification "outside of normal limits" showing thin nerve fiber thickness at 5:00 in the upper Figure and two area of "outside of normal limits" in the lower Figure.
CASE EXAMPLE #1 - DISPARITY IN DISC DIAMETER
In this 60 year-old Caucasian male patient, threshold visual fields were entirely normal. Applanation tensions were OD 16 mm and OS 15 mm. Acuities were 20/20 in each eye, pachymetric measurements were OD 545 microns and OS 550 microns, indicating reliable Goldmann applanation findings. There was no family history of glaucoma noted.
Gonioscopy showed Grade 3 open angles with normal pigment in each eye. Pulsatile ocular blood flow (POBF), measured with the Paradigm Dicon ocular blood flow analyzer, was normal as well. A POBF value of 17 microlitres/second in each eye implies robust ocular perfusion with symmetry and low risk for glaucoma.(21, 24)
Fig. 15. The pair of images above is from an individual with an obvious and significant disparity in disc diameter
In this individual, the disc area of the left eye (2.47 square mm) is greater than the disc area of the right eye (1.53 square mm). In addition to the area measurement of the discs provided by the HRT II, a measurement of rim areas are also generated. In the left eye, the rim area is 1.39 square mm and the rim area in the right eye it is 1.12 square mm. The paradox in this case is that the right eye might have more chance of being glaucomatous than the left eye because it has the smaller rim area.
Without the physical measurements of the nerve and rim areas provided by the HRT II, this patient might have been incorrectly diagnosed with normal tension glaucoma of the left eye. Based on the HRT II information, the diagnosis of optic disc size disparity without glaucoma was made. Rather than treating the patient, he was asked to return in six months for comparison to baseline findings.(31-33)
CASE EXAMPLE #2 - SMALL SYMMETRIC NERVES
Patients with small discs can be deceptive. The ophthalmoscopic view of this patient is one of apparently healthy nerves with healthy margins. Although the patient's high Goldmann pressures, low pachymetric measurements, and repeatable field loss cause great concern, knowing the disc size and rim area helps tell the rest of the story.
Fig. 16. The HRT II report above is from a glaucomatous patient with small discs (about 1.6 square millimeters). Having low rim area (0.92 square millimeters) and thin inferior margins, this individual has a repeatable superior nasal field defect in each eye and a history of untreated pressures in the low 30's. Pachymetry readings were thin at 505 microns OD and 512 microns OS, indicating some underestimation of actual intraocular pressures.
A small nerve can have advanced disease and still appear to be healthy. The HRT II disc area measurement of 1.6 square millimeters indicates that this nerve is unusually small. The rim area is only 0.92 square mm, which is less than would be expected for a disc this small. Thus this patient has glaucoma, which explains the repeatable field loss associated with chronically high IOPs. (21)
CASE EXAMPLE #3 - NORMAL TENSION GLAUCOMA
This patient has a superior nasal threshold field defect which in now within 5 degrees of fixation. The HRT II Moorfields' analysis clearly demonstrates the loss of inferior rim tissue, which corresponds to his superiornasal visual field defect. Fortunately, he has responded well to his therapy (qhs travaprost), which dropped his IOPs from 17mm Hg OD and 18 mm Hg OS to 12mm Hg in each eye. Pachymetry results were average at 545 microns OD and 555 microns OS. This indicates that his Goldmann measurements were valid.
Fig. 17. The HRT II report above is from a patient with profound normal tension glaucoma. The two X's at the inferior margin of the disc imply that the retinal nerve fiber thickness in the inferior margin is statistically outside of normal limits.
This patient will return for follow up in 3 months and will repeat HRT II and threshold visual fields at least every six months to check for progression and to help monitor the efficacy of treatment.
ANALYSIS OF PROGRESSION
Excellent glaucoma management requires careful consideration of all risk factors, followed by sequential comparison to baseline findings, and re-evaluation of additional risk factors as they evolve.
In early glaucoma, structural changes can occur within the nerve and can precede visual field defects by months or years. Documentation of disc rim tissue loss is a key in confirming glaucomatous progression. The HRT II provides an objective method for detecting and monitoring very subtle and early glaucomatous nerve head changes.
Data from follow-up exams are automatically adjusted by the HRT II to compensate for eye movements, rotation, tilt, magnification changes, and other artifacts. Then they are objectively compared on a pixel by pixel basis to data from the baseline exam. When complete data from at least three examinations are available, the HRT II will mark areas of significant change on its reports. This analysis does not require that a contour line be drawn on the image.
The HRT II progression analysis is conducted by the Change Probability Program in which a new image is mathematically compared to the previous images. Areas of significant change in depression are marked in red on the image and areas with significant increases in elevation are marked in green. Although the doctor might elect to view and compare changes in raw data form, the progression analysis software provides a pictorial format for assessing those changes.
Fig. 18. A follow up report showing significant nerve fiber loss (red highlighted area indicates significantly increased depression/loss).
Fig. 19. A series of images showing no significant progression.
Fig. 20. A series of images showing significant nerve fiber loss at 5:00.
With any new clinical technology, eye care providers must consider how to add the information that it provides into the existing body of information that has previously been used to make management and treatment decisions. HRT II optic nerve head analysis can help to manage glaucoma patients in several ways.
One area of importance is the ability of the HRT II to provide a detailed initial description and baseline measurements of nerve head features. Although the traditional cup/disc ratio and description of the rim tissue have been gold standards for defining the physical attributes of the nerve, the HRT II provides a litany of additional data that give a far more complete picture of nerve head architecture. It is now possible to specify with mathematical precision disc size, rim area, cup slope, and nerve fiber layer thickness.
The HRT II also allows visualization of the nerve head with salient clinical features marked at various locations within it. It has been well established, for example, that a cup/disc ratio of 0.65 has entirely different implications in a 1.5 mm diameter nerve as compared with a nerve head twice as wide. Although the 0.65 cup/disc ratio in a larger nerve may be physiologic, that same cup/disc ratio in a smaller nerve may be profoundly glaucomatous.
THE FUTURE
Use of confocal techniques to assess optic nerve head architecture is a relatively new concept, and the HRT II is a relatively new instrument. In the future, it is anticipated that the normative database used by the HRT II will be expanded to include many more subjects, including those of different races and ages. It is also expected that as clinicians gain more familiarity and experience with the HRT II, additional information on normal test-retest fluctuations and on the magnitude of changes in the various nerve head parameters that warrant concern will be developed.(42-44)
It is also probable that use of the HRT II to assess elevation changes in the macular or peripheral retinal regions will be more fully developed. These capabilities will make the device useful for assessing conditions beyond glaucoma and will help to justify the purchase of a CSLO instrument.
SUMMARY
In day-to-day management of glaucoma, vision care specialists are commonly presented with inconclusive data such as unreliable fields and/or borderline intraocular pressures upon which to base treatment decisions. The progression analysis tools provided by the HRT II can help to resolve uncertainty regarding the management of these patients.
In the diagnosis and management of early glaucoma, nerves with irrefutable glaucomatous cupping are seldom seen. The ability to document subtle nerve abnormalities and changes is necessary to validate treatment decisions. When concise documentation of baseline abnormalities and changes in optic nerve head features are considered in conjunction with other glaucoma risk factors and clinical findings, better management decisions for glaucoma patients will result.
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Contact the Author:
Elliot M. Kirstein, O.D., F.A.A.O.
11304 Montgomery Road
Cincinnati, Ohio 45249-2313
drkirstein@drkirstein.com
Dr. Kirstein is the director of an optometric group practice in Cincinnati, Ohio, specializing in glaucoma and primary eye care. He has lectured for Interzeag (Haag-Streit), and, for the past five years, he has worked as a consultant and lecturer for Ocular Blood Flow Labs of the U.K. and Paradigm Dicon Medical Industries.
Note:
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