About ten years ago glaucoma was screened mainly by measurement of pressure in the eye which, when high, justified a clinical examination of the optic nerve and the performance of an automatic visual field test. First developments resulted in no further use being made of traditional Goldman kinetic perimetry due to the fact that it had difficulty in detecting the first small deficits. It was replaced by Humphrey or Octopus static perimetry. In cases where the visual field was normal and the optic nerve seemed to have an acceptable appearance, isolated hypertension was suspected and the decision as to whether to treat it depended on the individual doctor.

Currently a much more rigorous approach is possible thanks to new screening techniques, involving both the visual field and the optic nerve.

Systematic measurement: evaluation of the thickness of the cornea

In the presence of any kind of ocular hypertension, it is essential to measure the thickness of the cornea by pachymetry. The average measurement is 550 μm. When the cornea exceeds 600 μm, pressure is over-estimated. When, on the contrary, it is lower than 500 μm, it is under-estimated. There is no chart available to correct ocular pressure easily depending on the thickness of the cornea, because other confounding factors also play a role here, such as corneal rigidity. Nevertheless, measurement of the thickness of the cornea is now seen as essential.

New visual field tests: Matrix and Blue-Yellow

"Traditional" perimetry using white spots on a white background explores certain types of ganglion cells which are damaged in glaucoma. However, these cells (type β, representing 80% of ganglion cells in the eye) are not the first to be affected at the onset of glaucoma. This is why this type of perimetry only shows damage when 20 to 30% of the optic fibres have been destroyed.

Optic fibres damaged earliest in glaucoma are α type cells, representing 10% of ganglion cells. They correspond histologically to the so-called "magnocelluar" route because they have large diameter axons. This route specialises in transmission of the information linked to movement and flickering. These cells are explored using perimetry by frequency doubling, known as FDT (Frequency Doubling Technology). In practice, this is an examination that is very easy to perform but one which requires new equipment. Instead of seeing a luminous spot, the patient detects the appearance of oscillating vertical bars. Using this technique it is possible to detect the infra-clinical lesions that occur about 5 years before more severe damage (Fig. 1).

Fig. 1: Reading from a visual field test of the right eye by FDTMatrix. Patient with hypertension without any damage to the visual field for white. On the reading, damage is shown in the form of an inferior nasal projection. This is early glaucoma.

Another approach consists of using blue stimuli on a yellow background, performing blue-yellow perimetry or, more exactly, at short wavelength.

Within just ten years these vision exploration techniques have become regular practice. In the presence of isolated hypertension and a normal visual field for white, a FDT-Matrix test is recommended, i.e. blue-yellow perimetry, particularly in young patients.

Considerable progress: imaging of optical fibres and of the papilla

Over the past five years approximately, various different technologies have been developed to quantify the thickness of optical fibres. Alongside this, other machines can also be used to evaluate the optic nerve by measuring its various elements (volume or surface area of the excavation, surface area of the neuroretinal ring, …). Initial versions of these devices were unable to obtain results that could be easily reproduced. Today they can be used in general practice. Three devices are currently available, the OCT, the GDx and the HRT.

OCT or optical coherence tomography

Optical coherence tomography is a noninvasive, non-contact ocular imaging technique which is used to measure structures and distances in vivo with resolution of approximately 10 μm. It is similar to "B mode" ultra-sound imaging and uses a light beam of wavelength 820 nm. OCT can be used to evaluate the parameters of both the papilla and the layer of para-papillary optical fibres. There are several versions, the most recent of which is the OCT spectralis. Use of OCT in various ophthalmological pathologies, macular in particular, is justification for its widespread diffusion. It is therefore the most frequently used to evaluate glaucoma disease too. Graphic representation is done both of the papilla and the optical fibres. In terms of the papilla it would appear difficult to discover which is the most useful parameter (surface or volume of the excavation). It is easier to analyse the layer of optical fibres. The most frequently used representation in glaucoma is the one where measurement of the thickness of optical fibres appears. The readings for each eye and in each quadrant are indicated in black. They are considered normal if the line is located in the green zone, worth monitoring if in the yellow zone and truly abnormal if they are in the red zone. On the lower section of the reading, for each region studied, a colour code (green, yellow or red) indicates the degree of abnormality (Fig. 2).

Fig. 2: OCT Spectralis. Abnormal results. The layer of optical fibres for each eye is presented in the middle of the diagram, in black for each eye (right eye on the left and left eye on the right). There is the beginning of damage to the layer of optical fibres located in the red section of the probabilities diagram for the left eye.

GDx, or "Glaucoma Diagnostic Technology"

GDx performs polarimetry by confocal laser scanning (wavelength 780 nm) and is used to measure peripapillary optical fibres. The measurement principle is based on the birefringence properties of ganglion cell axons. The microtubules along the length of these axons lead to a change in direction of the polarised light, with a delay in reflection of the latter. The more optical fibres there are, the longer this delay in reflection will be. The examination is performed without dilatation and without optical correction. It lasts only a few seconds per eye.

The results for both eyes are expressed on a single sheet with the column on the left corresponding to the right eye and the one of the right to the left eye. The central section contains a summary of the values for both eyes. Numerous parameters are proposed, the most important being the thickness of the optical fibres in the various regions around the papilla. Insofar as there are more optical fibres in the superior and inferior regions than in the nasal and temporal regions, normal values (in pale green or pale pink) trace a sinusoid. Readings for the patient tested appear in dark green or red (Fig. 3).

Fig. 3: Altered GDx values. Initial damage appears here with the GDx in the form of a deficit of a beam of inferior fibres on the right, an initial form of this damage also exists on the left.

This representation is interesting, particularly because it underlines a major variation from normal values. This is logical since the number of optical fibres varies in the population from 800,000 to 1.2 million per eye. This is in fact a major limitation in statistical evaluation of results.

HRT or Heidelberg Retina Tomograph

The Heidelberg Retina Tomograph (HRT) is a confocal laser scanning tomograph. The light source is a 670nm wavelength laser that produces three series of horizontal and vertical cross-sections of the optic nerve in 32 successive planes in around 2 seconds. Using these images the papilla is reconstituted, along with the parapapillary region. However, the operator has to determine manually, using the computer mouse, the contour line of the optical disc. This is a critical stage since errors regarding this localisation lead to differences in the assessment of all the parameters. However, this stage only has to be gone through once when the first measurement is taken. The machine thus evaluates lots of stereoscopic parameters, in terms of surfaces (Cup-Disc ratio, surface of the retinal ring) or of excavation volume. Software specifically designed for screening and tracking glaucoma is integrated into the latest versions of HRT. This is "Moorfields" regression analysis. The HRT therefore concentrates on analysis of the papilla and it also partially evaluates the layer of optical fibres.

The new HRT version III offers representation on a single page of results for both eyes, with the right eye on the left and the left eye on the right. In the upper section an image of the fundus of the eye is given, on which is superimposed the position at depth of the papillary structures, in red below a reference view (this is therefore excavation), in blue the slope of the latter and in green the more superficial areas, that is to say the neuroretinal ring. The intermediate diagram shows the papilla divided into 6 zones to which are allocated damage probabilities (green: normal, yellow: worth monitoring, red: abnormal). Finally, in the lower section is a diagram of the measurement of optical fibres with the physiological aspect in double (Fig. 4).

Fig. 4: Abnormal HRT results. In the upper section are shown parameters relating to the optic nerve and in the lower section (RNFL) the Retinal Nerve Fiber Layer corresponds to the optical fibres. A small green mark at each level indicates that results are normal. A yellow exclamation mark corresponds to values worth monitoring. Red crosses indicate that there is a deficit in these areas.

Clinical contribution made by these new technologies

Optic nerve head analysers have existed for years, but they were not used because they were not very reliable. The new versions of the 3 existing machines are much more efficient, but remain limited particularly in certain situations where they would be very useful, specifically when the peripapillary region is not normal. This is the case, for example with strong myopia or papillary dysversion. Each technology is benefiting from new improvements, particularly tracking programmes which detect any deterioration in glaucoma damage. Currently however, careful analysis by stereoscopic ophthalmoscopy – with assessment of the depth of the excavation – remains nevertheless of capital importance. In case of disagreement between the results, it is better to rely on clinical examination.

It would be tempting to replace perimetric examinations, which are sometimes difficult to perform, by a more objective evaluation of the situation thanks to analysers of the optical fibres or of the optic nerve. However, the variability of results with current versions of these machines does not enable us to be satisfied with these examinations alone for monitoring patients with ocular hypertension.

Conclusion

In 10 years, glaucoma evaluation has changed completely. New early diagnosis methods and methods for monitoring evolution of the disease have come on the market, both in terms of the visual field and of structure analysis. This enables a more rigorous approach to the management of patient treatment because it is now possible to detect appearance or deterioration of the disease and to manage it better.

References