The glaucomatous optic nerve staging system with confocal tomography

History of optic nerve examination

Since the first images of the fundus were obtained with an ophthalmoscope, created by Helmholtz1 145 years ago, examination methods have continued to improve. First, examination with direct ophthalmoscopy was used, followed by examination with binocular indirect ophthalmoscopy, optic disc drawings, optic disc stereophotographs, planimetry, Takamoto and Schwartz’s stereophotogrammetry, neuroretinal rim measurements, Airaksinen and Tuulonen’s evaluation of the retinal nerve fiber layer, optic disc pallor measurements, angiofluoresceinography of the optic disc, image analyzer (Rodenstock Optic Nerve Head Analyzer, Topcon Analyzer), laser scanning ophthalmoscopy, and Lotmar and Goldmann’s stereochronoscopy. All these methods are extensively explained in the worthwhile book The Optic Nerve in Glaucoma, by Rohit Varma and George Spaeth.2

Of these methods, we still use retinofluoresceinography, because of its particular usefulness. We no longer use stereoscopic photographs of the optic nerve in adults, due to the significant interobserver variation in interpretation of the results, as reported in the literature.3-5 But stereoscopic photographs are useful for optic nerve examinations in children under two years of age because, due to their flat corneas, with confocal tomography we have so far failed to obtain good images. In Boston, we learned about Schwartz and Takamoto’s stereophotogrammetry,6 a very reliable method, the results of which are consistent with those obtained with the Heidelberg Retina Tomograph (HRT). However, it is a time-consuming method. We later performed neuroretinal rim measurements using Airaksinen et al.’s method,7 which we could put into practice

thanks to Dannheim and Airaksinen’s personal communications. This turned out to be the most useful method. We also tried Lotmar and Goldmann’s optic disc stereochronoscopy.8 All these methods require pupil dilation.

For the above-mentioned methods, and particularly for measuring optic disc parameters (area, cup area, neuroretinal rim), the formula introduced by Littman in 1982 for the first time allowed us to obtain the dimensions (length, surface) of any observable object in the fundus (exudates, tumors, foreign bodies, optic discs, vessels, etc.). Images of these elements can be observed with considerable magnification produced by the ocular system.

This morphometric magnification was corrected in order to find real values with the Littman formula.9 Littman was an engineer who worked for Zeiss and whom we had the chance of meeting in Buenos Aires. Since 1982, thanks to his formula, we have been able to obtain real measurements, in mm or mm², of a body or structure on the retina. For this formula, corneal curvature, which is measured with an ophthalmometer, axial length, which is measured by echometry, and refraction, are very important. Corneal thickness, its posterior curvature, lens face curvatures, depth of the anterior chamber, and lens thickness, are not required. This is because, even if they varied, their influence on the measurement would be minimal. This formula does not apply to aphakia, pseudophakia, and refraction changes due to opacity of the lens.

Finally, in 1990, the HRT was introduced by Heidelberg Engineering (Burk et al.10, etc.), and it was with this device that we started our extensive research in 1991, ten years ago, with more than 7300 patients having been examined to date.

In this chapter, we will deal with what we be-

lieve is a very important topic, the HRT parameters used for optic nerve staging in glaucoma, as well as the follow-up of optic nerve damage.11

The tomographic classification is mainly based on the volumes of the said structures, and only secondarily on surfaces and other parameters. This is due to the possibility of stereometric and tridimensional analyses.

The advantage provided by volume measurements over area measurements, is that the former are raised to the third power, while the latter are only raised to the second power (whenever change occurs, no matter how slight, there is a greater variation if the value is raised to the cube than if it is raised to the square).

Parameters used for glaucoma staging

As already stated, the main parameter used for the classification was volume, followed by area, thickness, and slope. The volumes taken into consideration are neuroretinal rim volume, and cup volume. The most important is, in fact, neuroretinal rim volume, but cup volume is also taken into account since a decrease in neuroretinal rim volume produces an increase of cup volume; this is a causeeffect relationship. The same occurs with area, the cup area (red) increases as the rim area (green and blue) decreases.

The most important parameters used for the classification are listed in Table 1 and are illustrated in Figure 1, where the parameters belonging to the optic disc are separated from those that are analyzed in the contour line graph. These latter parameters are: mean retinal nerve fiber layer (RNFL) thickness, height variation of the contour line, and area enclosed by the contour line and the reference plane in the contour line height variation diagram (RNFL cross-sectional area). As we all know, the

Table 1. Parameters used for classification

Rim volume

Cup volume

Rim area

Cup area

Cup shape measure

Mean RNFL thickness

Height variation of contour line

Area between curve and plane

reference plane, far from being just another parameter, is the limit on which most parameters strictly depend, and with which they have a close relationship. Due to this, its position must always be verified and, when performing a longitudinal study, it must be checked to see that it always remains at the same level.

Concept and limits of normality

The concept of normality is based on the fact that all the optic disc parameters are normal. Nevertheless, in clinical practice, sometimes, for one reason or another, the fact that one or two parameters are not within the limits of normality or normal range does not indicate pathology. The concept and limit of normality are outlined in Figure 2.

The limits of normality were obtained in a study of 108 normal volunteers.12 Table 2 lists the most important limits, for example, for neuroretinal rim volume, the normal inferior limit (3.20 mm3) and not the normal superior limit, is given, since this is mainly used to differentiate a large neuroretinal rim from an optic disc edema.

In some patients, a neuroretinal rim smaller than 320 µm3 may be found during the first tomography, which makes it fall within the classification of borderline. Nevertheless, it must be taken into account

Fig. 2.

Table 2. Limits of normality

that the evolution of these patients sometimes does not involve optic nerve damage, but remains stable for years, which indicates a physiological or normal decrease of the neuroretinal rim in this group of patients.

Evolution phases

Glaucomatous optic disc evolution was classified into the following groups:

normal borderline phase 1 phase 2 phase 3 phase 4

With the exception of borderline optic discs, the remaining phases are separated from one another by more than two standard deviations, rendering separation into the various groups more significant. Only parameters meeting this requirement are mentioned, since most of those remaining have no significant differences between the various evolution phases.

Normal optic discs (Table 3) are characterized by a just visible Elschnig’s ring, except in the temporal area. Both poles have important fiber bundles, which correlate with the two camel humps displayed by the contour line diagram (Fig. 3).

Table 4. Borderline optic discs

Normal visual field

In borderline optic discs (Table 4), neuroretinal rim volume is normal on measuring the entire disc, but if we analyze the rim volume by octants and quadrants, there is a decreased value in one of these sectors. The decrease of neuroretinal rim volume in this phase does not affect the whole optic disc. It corresponds with Burk’s pseudonormal optic discs, in which the humps remain unchanged and there is slight neuroretinal rim loss. With the exception of cup increase, no parameters are altered (this is seen less frequently) (Fig. 4).

Phase 1 optic discs (Table 5) are characterized by a generalized decrease in retinal thickness that can be seen in the contour line diagram as an approximation between the contour line proper and the reference plane. At the same time, a decrease in the height of the camel humps, which correlates with the loss of fiber bundles (see tridimensional presentation), and with the fact that Elschnig’s ring is more visible than before, can be seen (Fig. 5).

Phase 2 optic discs (Table 6) already have a loss

Table 5. Phase 1

Normal visual field

of up to 50% of their total retinal nerve fibers. The disappearance of both humps, which correlates with a huge cup increase that invades the superior and inferior poles, can be seen. The mean RNFL thickness, preventing the contour line from approaching the reference plane, remains unchanged (Fig. 6).

Phase 3 optic discs (Table 7) are characterized by a huge decrease in mean RNFL thickness, which causes the contour line to approach towards the reference plane (when localized defects occur, the contour line reaches the reference plane in the damaged areas). The summation image allows the bottom of the cup and Elschnig’s ring clearly to be seen in their full extent. The cup surface covers

Table 6. Phase 2

Beginnings of visual field defects

Table 7. Phase 3

Visual field defects

Table 8. Phase 4

Visual field in stage 3 (terminal)

almost the entire optic disc surface. The neuroretinal rim persists like a thin halo around it (Fig. 7).

Phase 4 optic discs (Table 8) are characterized by a final decrease in retinal thickness, where the contour line is parallel to the reference plane and, in the places where there is no neuroretinal rim left, the contour line height variation diagram is below the reference plane. This fact correlates with the appearance of white areas in analysis of the surfaces and with the presence of absolute visual field defects (Fig. 8).

All six phases are summarized in Figure 9. In normal optic discs, as well as in borderline discs, Elschnig’s ring can only be seen in the temporal sector, whereas in all other phases, it can be seen almost to its full extent, due to fiber atrophy. The bottom of the cup can be more clearly seen from phase 2 onwards. When the brightness of the retina is observed in each section, it can be seen that this decreases steadily from normality to phase 4. Cup shape measures change rapidly. In phase 2, the cup slope is almost perpendicular, while in phases 3

and 4, bayonet-shaped vessels are revealed. The small vessels become more and more evident and their contours are more visible as they become more definite (this is due to atrophy of the retinal nerve fibers). Nevertheless, at first sight, the condition of the optic disc in phase 4 may seem better than in phase 3. Also, the time elapsing between normal and borderline optic discs, or between borderline and phase 1 optic discs may seem the same. This is easily solved with stereometric analysis of the surfaces.

Figure 10 shows the six phases together in the ‘measure’ menu, with the color-coded analysis of the surfaces. In normal optic discs, the cup is surrounded by a large neuroretinal rim and not centered in the optic disc. This occurs in normal conditions due to the huge infiltration of fibers at the superior and inferior poles. In borderline optic discs, it is possible to see how the surface of the cup increases at the expense of decrease of the rim area. Simultaneously, the cup becomes central and its area invades the tilted neuroretinal rim area, thus reducing its separation from the flat neuroretinal

Fig. 8

Fig. 9.

rim. In phase 1 optic discs, the cup continues to increase and gets closer to the flat neuroretinal rim, leaving a thin separation covered by the tilted neuroretinal rim. The total surface of the neuroretinal rim decreases markedly. In Phase 2 optic discs, the cup increases considerably and starts to become

slightly eccentric, and the tilted rim disappears completely in these regions. Consequently, the cup surface borders the flat rim surface. This fact can sometimes cause localized defects and, together with the diffuse atrophy of the rest of the retina, it correlates with the onset of the visual field defects

Fig. 10.

in this phase. In Phase 3 optic discs, the cup surface almost covers the complete optic disc region. The tilted rim has almost completely disappeared. Only a thin flat rim margin separates the cup from the external optic disc margin. This small volume of neuroretinal rim keeps the visual function at the same level; this is correlated with the rapid visual field loss produced when the remaining neuroretinal rim is damaged. In phase 4 optic discs, the cup occupies almost all the optic disc surface and, in some sectors, where the neuroretinal rim has been completely destroyed, the cup touches the external optic disc margin, making the total absence of the neuroretinal rim evident in that sector. White regions can occur in phase 4, which are due to the fact that the retinal surface is below the level of the reference plane in the most badly damaged sectors. These lesions produce absolute optic disc defects that have a bad prognosis.

The role of confocal tomography (Heidelberg Retina Tomograph)

Classification of clinical cases

Case 1

A 64-year-old male (left eye). Best-corrected visual acuity: sph: -1; cyl: -0.25 in 0°. Diagnosis: openangle glaucoma (eight years earlier). The diurnal pressure curves performed during those eight years revealed an intraocular pressure (IOP) of 33 mmHg at the 7 a.m. measurement, while at 9 a.m., and at

1, 3, 6, 9 and 12 p.m., all the readings were below 19 mmHg. Medical therapy succeeded in lowering the morning peak to 24-28 mmHg. The visual field was normal according to computerized perimetry, and HRT revealed a phase 1 optic nerve head (ONH) (Figs. 11 and 12).

Case 2

A 72-year-old male. Diagnosis: chronic narrowangle glaucoma. Under hypotensive therapy for 15 years. IOP without medication: 31 mmHg; and with medical therapy: 24 mmHg. Peripheral iridectomy with a YAG laser was performed, later supplemented by argon-laser trabeculoplasty, which regulated the IOP to: mean: 17 mmHg; variability: 1.5, according to the diurnal pressure curve. HRT revealed a phase 2 ONH (left eye) associated with a borderline visual field (Figs. 13 and 14).

Case 3

A 57-year-old female (left eye). Diagnosis: openangle glaucoma and myopia. Visual acuity: 10/20 with sph: -5.00. The diurnal pressure curve showed a mean of 23 mmHg and a variability of 1.6. Computerized perimetry revealed a stage 3 visual field, with an MD of 18.9 and a CLV of 96.4. HRT revealed a left phase 3 ONH (Figs. 15 and 16).

Case 4

A 65-year-old female. Diagnosis: open-angle glaucoma (20 years earlier). Trabeculoplasty performed five years earlier. IOP monitoring was performed by another ophthalmologist by means of single-spot

Fig. 15.

Fig. 16.

checks and not by diurnal pressure curves, with readings of 25 mmHg being taken. Current bestcorrected visual acuity: 18/20 (with sph: 0.75). Computerized perimetry revealed a stage 3 visual field, with an MD of 23.2, and a CLV of 60.5. HRT showed a phase 4 ONH (Figs. 17 and 18).

Follow-up of optic nerve damage

One of the more interesting applications of HRT is the follow-up of optic nerve damage.

There are three periods of evolution in glaucoma: the hypertensive period, when there is neither optic nerve damage nor visual field defects, but with ocular hypertension as the only sign; the preperimetric period is characterized by the presence of either borderline, or phases 1 or 2 optic nerve damage, with the visual field still appearing normal. In the perimetric or final period, the optic nerve falls into either phase 2, 3, or 4, and the visual field is either borderline or belongs to stage 1, 2, or 3.

We have designed our own medical records which include a chart on the first page, where the

corresponding phase, stage, and, finally, period of each case can be ticked. Once the evolution stage of the patient has been determined, if duly recorded on the chart (one for each eye) with the dates of the examinations at the beginning of the patient’s record, the ophthalmologist is spared valuable time when the patient comes back for a follow-up, since he can identify the patient’s stage of evolution at a glance, and there is no need to check the entire records and confocal tomography and visual field examination printouts (Fig. 19).

It should be stressed here that IOP should not be measured in single spot-checks, but rather by means of diurnal pressure curves, with the first measurement being made at 6 a.m. with the patient still in bed, using applanation tonometry.

The following clinical histories are examples of this routine procedure, by which the evolution period of the disease is identified according to whether ocular hypertension has been controlled or not, thus enabling us to prescribe adequate medical therapy, change the current therapy, or suggest surgery.

Case 1

Record No. 6369, JD, a 56-year-old male

The patient presented for consultation in 1997, when he was in the hypertensive evolution period of glaucoma with normal optic nerve and visual field. He was diagnosed with chronic narrow-angle glaucoma. In 1998, he underwent laser iridectomy for narrow-angle, which regulated his IOP. His follow-up consultations were carried out abroad, where he was diagnosed as having low-tension glaucoma. However, when he returned home in 1999, HRT was performed and visual field examinations and the diurnal pressure curve revealed severely pathological IOP values at 6 a.m. (Figs. 20 and 21).

Case 2

Record No. 5001, LDC, a 68-year-old female

At her first consultation in 1993, the patient’s right eye was in the perimetric evolution period, with the optic nerve in phase 2 and the visual field in stage 2. Visual acuity was 0.4 in OD and 0.8 in OS. The patient was diagnosed as having chronic narrowangle glaucoma. The first surgical procedure was performed in June 1993, and the IOP was successfully regulated according to the diurnal pressure curves. In 1998, the IOP became higher, with peaks of 26 mmHg detected in 2000 in the right eye, and the diurnal pressure curve was seriously pathological (mean: 22.86 and SD: 95), but normal in the fellow eye. Evolution of the condition of the optic nerve and visual field progressed because the patient failed to comply with her medical therapy for a year, when the IOP started to rise (Figs. 22 and 23).

Case 3

Record No. 4457, DOJC, a 29-year-old male

At his first consultation in 1991, the patient was diagnosed with pigmentary glaucoma in the hypertensive period (with normal visual field and optic nerve). However, IOP readings were elevated, with single spot-checks reaching as high as 24-26 mmHg, resulting in pathological diurnal pressure curves. Medical therapy was initiated and he is still being followed up, in particular by IOP monitoring by several diurnal pressure curves (Figs. 24 and 25).

Some of the considerations to be taken into account with regard to diagnosis and follow-up are:

In the vast majority of cases, there is consistency between the time elapsed with untreated ocular hypertension, the evolution phase of optic nerve damage, and the evolution stage of the visual field defect. Here, we will mainly deal with the correlation between the two latter parameters: optic nerve and visual field. It is during phase 2 in the evolution of optic nerve damage that the visual field typically starts to deteriorate. Whenever there is no correlation between the optic nerve and visual field condition, i.e., when the optic nerve is in either phase 3 or phase 4 while the visual field is normal or slightly abnormal, either of the following situations should be suspected: firstly, the presence of a scotoma that goes undetected by the visual field, in which case the number of stimuli examined is not enough. Another program with a greater number of stimuli – such as a macular program – should therefore be used, and, if a scotoma is detected, there is a correlation; otherwise, a disease other than glaucoma should be considered.

Secondly, a normal optic nerve may be associ-

Fig. 21. c. IOP values according to the diurnal pressure curve. During the day, and particularly at 9 a.m., noon, and 3 and 6 a.m., the IOP values are normal, while at 6 a.m., with the patient still in bed, they are 28 mmHg in OD and 26 in OS. Adequate medical therapy is prescribed, which, if refractory, will lead to surgery.

ated with an evident visual field defect. In this case, another disease still to be identified should be suspected. However, a few cases may be diagnosed as ‘vasospastic low-tension glaucoma’, since a visual field defect can be accompanied by a normal optic nerve.

Finally, it should be borne in mind that the data supplied by the HRT are valuable for discs with an area within the normal range. However, they are not accurate in the case of small discs or megalopapillas.

Vihanninjoki et al. have recently published a study on this,13 stating that the most important parameters for diagnosis and follow-up are, firstly, the cup-shape measure and, thereafter, mean RNFL

thickness and neuroretinal rim. They also supplemented the examination of their cases with blueyellow visual fields, and concluded that the four above-mentioned parameters are the most important for differentiating normal cases from glaucomatous ones.

Blue-yellow visual field examinations are only useful when they are corrected according to the autofluorescence (transmission properties) of the lens, which changes with age. The only difficulty in this regard is that the device for measuring autofluorescence is very expensive.

Conclusions

Optic nerve evaluation with confocal tomography permits the diagnosis of glaucomatous optic disc neuropathy in its early stages of evolution, when ophthalmoscopy is not yet able to detect any changes.

Moreover, optic disc measurement is just as important as IOP and visual field measurement, since it is possible to stage the disease in each individual case using these three techniques. It is very difficult to differentiate between glaucoma in the hypertensive period and preperimetric glaucoma without the aid of confocal tomography. Furthermore, if it is difficult to stage a patient with optic disc biomicroscopy, it will be even more difficult to determine whether glaucomatous optic disc neuropathy has progressed in any way.

In our opinion, optic nerve confocal tomography is a vital tool in the evaluation of glaucomatous patients, their accurate early diagnosis, staging, and follow-up, as well as for judging the efficacy of their medical and/or surgical treatment.

Fig. 23. Preand postoperative optic nerve condition in 1993 and follow-up confocal tomography examinations performed in 1996 and 1999, showing the marked changes in the neuroretinal rim from the postoperative examination to the one performed in 1999. The visual field shows consistent clear variations in the MD, which increases from 8.9 to 9.9, as well as in the CLV, which changes from 70.1 to 51.1.

tomography confocal with system staging nerve optic glaucomatous The

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References

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2.Varma R, Spaeth G: The Optic Nerve in Glaucoma. Philadelphia, PA: JB Lippincott Co 1993

3.Leydhecker W, Krieglstein GK, Colloni EV: Observer variation in applanation tonometry and estimation of the cup disc ratio. In: Krieglstein GK, Leydhecker W (eds) Glaucoma Update: International Glaucoma Symposium, Nara, Japan, 1978, pp 101-117. Berlin/Heidelberg/New York: Springer Verlag 1979

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5.Varma R, Steinmann WC, Scott IU: Expert agreement in evaluating the optic disc for glaucoma. Ophthalmology 99:215-221, 1992

6.Takamoto T, Schwartz B: Photogrammetric measurements of the optic disc in glaucoma. Int Arch Photogrammetry 23(B5):732, 1980

7.Airaksinen PJ, Drance SM, Douglas GR, Schulzer M: Neuroretinal rim areas and visual field indices in glaucoma. Am J Ophthalmol 99:107, 1985

8.Goldmann H, Lotmar W: Rapid detection of changes in the optic disc: esterochronoscopy. Graefe’s Arch Clin Exp Ophthalmol 202:87-90, 1977

9.Littman H: Zur Bestimmung der wahren Grobe eines Objektes auf dem Hintergrund des lebenden Auges. Klin Mbl Augenheilk 180:286, 1982

10.Burk R, Konig J, Rohrschneider K, Noack H, Volcker HE, Zinser G: Analysis of three-dimensional optic disk topography by laser scanning tomography: parameter definition and evaluation of parameter inter-dependence. In: Nasemann J, Burk ROW (eds) Scanning Laser Ophthalmoscopy and Tomography, pp 161-176. Munich: Quintessenz 1990

11.Sampaolesi R, Sampaolesi JR: Confocal Tomography of the Retina and the Optic Nerve Head. Heidelberg: CityDruck 1999

12.Sampaolesi JR, Sampaolesi R: Lecture: Study of normality in the optic nerve head with HRT, presented at Curso y Simposio Argentino de Glaucoma, July 1995, Buenos Aires, Argentina

13.Vihanninjoki K, Teesalu P, Burk ROW, Läärä E, Tuulonen A, Airaksinen PJ: Search for an optimal combination of structural and functional parameters for the diagnosis of glaucoma: multivariate analysis of confocal scanning laser tomograph, blue-on-yellow visual field and retinal nerve fiber layer data. Graefe’s Arch Clin Exp Ophthalmol 238:477-481, 2000