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early POAG diagnosis. At present, the optic head morphological and morphometric analysis is considered to give important clues to the early diagnosis of the disease and the follow-up of its progression. In fact, the ganglion cells death, which is responsible for the functional damage, directly affects both the optical head morphology and the RNFL thickness, thus anticipating the clinical and VF damage.

The examination of the optic nerve head and the papillary area should be simple, quick, objective, accurate, and reproducible. Recently, the new lasers based on polarimetric technique (GDx) and on confocal tomography (Heidelberg retinal tomograph, HRT) have allowed the objective and reproducible morphological and morphometric evaluation of both optic nerve head and RNFL.

The GDx scanning laser polarimeter

The GDx (Laser Diagnostic Technologies, Inc., San Diego, CA), performing a scanning laser polarimetry study of the retina, is a noninvasive diagnostic technique used to estimate the RNFL thickness using a polarized laser beam with a wavelength of 780 nm (Hollo et al., 1997; Weinreb et al., 1998; Yamada et al., 2000).

The linear birefringence property of RNFL is determined by the presence of the microtubules with a parallel disposition within the nervous fiber, inducing a variation of polarization of the light beam, which passes through them. These polarization changes, called retardation, are linearly related to the histological characteristic of the analyzed structure and can be registered by a polarization detector, giving an evaluation of the RNFL thickness.

The polarization detector measures the retardation of the light coming from the analyzed retinal point. The thickness of RNFL, obtained through an algorithm, is shown by means of color representations, in an image of 256 256 pixels that is acquired and stored in the computer memory.

The image acquisition is possible also with a miotic pupil, unless the pupillary diameter is not

lower than 2 mm, although a regular pupillary diameter is essential to perform the examination correctly (Weinreb et al., 1995).

Since other birefringent ocular tissues, such as the cornea, may interfere with the results of the test, a corneal compensator was added to allow the evaluation of the variation in birefringence due to the corneal interference, which is peculiar for each patient (Greenfield et al., 2000; Weinreb et al., 2002a). This latest version of the RNFL analyzed is named GDx-VCC (variable corneal compensator), which compensates the individual corneal birefringence hence allowing a good correction of the corneal polarization effect. In this way, a more reliable evaluation of the RNFL thickness can be achieved (Weinreb et al., 2002b; Tannenbaum et al., 2004).

Before performing the test, it is necessary to insert patients’ personal and clinical data, such as date of birth, gender, ethnicity, associated systemic disease, and spherical equivalent. Each eye will be examined on its own. The test progression is as follows.

A first scansion, called corneal compensation, is carried out on the macular region where the birefringence is assent. This measure is used to obtain the compensation of the corneal birefringence; the examiner must check the exact positioning of the ellipse corresponding to the macular region, which will appear homogeneously colored in blue (Fig. 1).

Once the corneal birefringence compensation has been carried out, the ‘‘acquisition’’ phase will take place. In this phase, it will be possible to get

Fig. 1. Image of the macular region evenly stained in blue due to the absence of the birefringence.

compensated images of the RNFL. The compensation check is carried out only once, at the first test, and the value obtained is stored in a database to be used in future examinations. It is possible that a new measurement of corneal compensation is required in case of overcoming cataract or refractive surgery. In this phase, an ellipse delimiting the optic nerve head will be shown. This ellipse can be modified in order to compensate the presence of optic nerve anomalies, such as peripapillary atrophy and scleral crescent.

During the acquisition phase, two concentric circles will be shown around the papilla. The area of calculation is included between the two circles. Three images will be automatically acquired. The final image is obtained from a mean of these three images. This image is divided into four segments centered on the optic nerve head: superior and inferior 1201 wide, nasal 701 wide, and temporal 501 wide. In this way are identified the areas from where the data are obtained and showed in the graphic representation called TSINT (temporal, superior, nasal, inferior, temporal). The measures obtained in the different areas will contribute to obtain the so-called nerve fiber index (NFI), which is supposed to reflect the probability that the patient has a glaucomatous damage on a scale from 0 to 100, where values above 40 are considered abnormal.

The area where the calculation is performed is automatically determined and is set on a minimal dimension. It extends only for 35 pixels with an inner diameter of 27 pixels and 8 pixels width (Fig. 2).

In the emmetropic eye, it is possible to have the dimensions expressed in millimeters, as they are measured on the retina: outer ray 1.628 mm and inner ray 1.256 mm. The values expressed in pixels are worked out so that 256 values, uniformly distributed along the circular area, are obtained.

Three areas of different dimensions are available for the calculation of the parameters: small, medium, and large. In Table 1 are summarized the dimensions of each variable.

In general, it is advisable to use a small calculation area because it allows better quality and more reliable results.

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Fig. 2. Calculation area.

Table 1. Parameters of three area used for calculation

In case of patients with peripapillary atrophy, myopic crescent, or other optic nerve head morphological anomalies, it is better to use larger areas because with the small one the data collected could be unreliable.

Performing the measurements, the computer calculates the light retardation from all the areas considered. The data obtained from each patient are compared with the database obtained in normal subjects of the same age. In this way are evaluated 13 indexes, which include several measurements obtained in the peripapillary region.

The results are represented in a printout (Fig. 3), where data and images, obtained for each eye, are presented separately according to two types of analysis, namely, nerve fiber analysis (NFA) and serial analysis.

Nerve fiber analysis

The NFA includes fundus images, RFNL thickness map, TSINT parameters, NFI, TSINT graphic, and deviation from reference map.

The central TSNIT graphic shows data from both eyes in order to facilitate the evaluation of the

interocular symmetry, which is only shown in this graph.

Color image: Color has been artificially added to this image of the optic nerve head and the peripapillary retina in order to assist their

observation and to allow the evaluation of the quality of the scan performed (Fig. 4).

Thickness (polarization) map: This map gives a color-coded image of the measured points to indicate RNFL thickness. Bright colors (red and yellow) are associated with thicker areas, signifying healthy RNFL. Dark colors are associated with thinner areas, indicating less healthy RNFL. In the scheme from normal subjects, light yellow and red colors are allocated in the superior and inferior sectors, while green and blue colors are located in nasal and temporal sectors, respectively (Fig. 5).

Standard deviation map: This is a superpixel map showing different colors with respect to the probability to deviation from normal values of reference (Fig. 6).

TSNIT (double hump) graph: In TSNIT

graph are shown the normal values (shaded area) and patient values (dark line) relative to the RNFL thickness on the data obtained in the calculation area. Looking at the TSNIT graph, from left to right, are shown the thickness values of the temporal, superior, nasal, inferior, and temporal again. In normal condition, the RNFL profile shows a double hump aspect with higher thickness in the superior and inferior sectors and lower values in nasal and temporal sectors (Fig. 7).

TSNIT symmetry graph: This is a confrontation of the TSINT graphs from both eyes of the patient. In this graph, it is possible to evaluate if there are differences in the RNFL

Fig. 4. Color image of the optic nerve head and the peripapillary area.

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Fig. 5. Thickness polarization map.

Fig. 6. Standard deviation map.

Fig. 7. TSNIT double hump graph.

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thickness and TSNIT form and position between the two eyes.

Deviation from normal map: In this map, the RNFL thickness of the patients is compared with normative database. Small colored squares indicate the percentage of deviation from normal value in a certain evaluated point. The area from where the squares are evaluated is shown on black and white image of the ocular fundus for reference. A color legend defines the statistical significance of the devia-

tion from normal values with a significance comprised between pW5% and po0.5%.

TSNIT parameters: The data from the calculation area of the patients are matched with those from a normative database. The parameters are encoded according to different colors to indicate the deviation from normal values and can help in distinguishing between glaucomatous and normal subjects. However, these parameters should be considered together with other clinical data of the patients.

In the TSNIT table are considered the following parameters:

1.TSNIT average: It indicates the mean thickness values in the calculation area.

2.Superior average: It indicates the mean thickness of the pixels in the superior 1201.

3.Inferior average: It indicates the mean thickness of the pixels in the inferior 1201.

4.TSNIT standard deviation.

5.Inter-eye symmetry: It shows the correlation of the TSNIT data for corresponding points of both eyes. If the ratio is close to 1, the RNFL will be symmetric in both eyes.

Nerve fiber indicator: It is an indicator of the probable presence of the POAG. The GDxVCC system has an algorithm aimed to optimize the confrontation between normal and abnormal RNFL; to obtain this algorithm, images from glaucomatous and normal eyes were used.

The NFI is shown in a numeric format from 0 to 100. The higher the number, the higher is the probability that the patient is affected by glaucoma. This index is not related to the gravity or the progression of POAG.

Although there may be some exceptions, it is possible to use the following scale as a guideline for NFI evaluation:

o30, low probability of POAG 30–50, suspect of POAG

W50, high probability of POAG

The NFI depends on the good positioning of the circle, which must be centered on the optic nerve head; a modification of the circle position can interfere with the NFI value obtained.

Symmetry: This is the mean ratio between the mean of the 210 thickest measurements from the superior and inferior sectors. The closer the ratio to 1, the higher the RNFL symmetry in these sectors.

Superior ratio: This is the mean ratio between the mean of the 210 thickest measures from the superior and temporal sectors.

Inferior ratio: This is the mean ratio between the mean of the 210 thickest measures from the inferior and temporal sectors.

Superior/nasal: This is the mean ratio between the mean of the 210 thickest measures from the superior and nasal sectors.

Max modulation: It gives an indication of the differences existing between the thickest and the thinnest areas of the RNFL. The higher this number, the higher the difference between thick and thin RNFL areas. In normal eyes, where the inferior and superior RNFL thickness is higher than that of nasal and temporal, the number obtained is generally higher than 1.

Superior maximum: This is the mean of the 210 thickest measurements of the superior sector.

Inferior maximum: This is the mean of the 210 thickest measurements of the inferior sector.

Ellipse modulation: Similar to the max modulation parameters, it indicates the difference existing between the thickest and thinnest areas of RNFL. These parameters used only the points along the ellipse circumscribing the optic nerve.