C38311: Primary open-angle glaucoma - part 2

Closing Date: 13/11/2014

Ocular disease Ocular examination Options

Part 1 of this article reprised the relationship between structural and functional outcomes in primary open-angle glaucoma. It then discussed the interpretation of the optic nerve head features and of the thicknesses of the retinal nerve fibre layer and of the macular ganglion cell/ inner plexiform layer complex, respectively, derived by optical coherence tomography (OCT). In the final part of this article, the interpretation of the visual field printout will be discussed, and an insight will be given into the utility of combined structural and functional probability analyses in the diagnosis and management of primary open-angle glaucoma.

Interpretation of the visual field printout

The components of the printout are illustrated for the Humphrey Field Analyzer (HFA) in Figure 8 but are applicable to most types of perimeter.

Figure 8: Single field printout of the visual field recorded with the SITA Fast algorithm and Program 24-2 of the Humphrey Field Analyzer (HFA) for the left eye of a patient with a nuclear cataract and glaucoma. Note the difference in the appearance of the Total and Pattern Deviation probability maps illustrating the effect of the cataract

Figure 8: Single field printout of the visual field recorded with the SITA Fast algorithm and Program 24-2 of the Humphrey Field Analyzer (HFA) for the left eye of a patient with a nuclear cataract and glaucoma. Note the difference in the appearance of the Total and Pattern Deviation probability maps illustrating the effect of the cataract

What was done?

This question refers to the stimulus program (the array of stimulus locations to be examined), eg Program 24-2; to the stimulus size (the default is usually Goldmann size III which subtends an angle of 0.431° at the eye); to the threshold algorithm (the sequence of stimulus luminances by which an estimate of threshold is obtained), eg SITA Fast; and to other details such as the refractive correction used (1). The background luminance for most perimeters is generally not changeable and, as was stated in Part 1 of this article, is normally 10cdm-2 (31.5asb).

Are the results Accurate/ Adequate?

This question refers to the number of incorrect responses to each of the two sets of reliability parameters, the false-positive and the false-negative catch trials, and to the number of fixation losses detected by the Heijl-Krakau blind spot technique (2).

The false-positive catch trials are generated by the perimeter occasionally purporting to present a stimulus. If the patient apparently ‘sees’ the stimulus, a false-positive response is recorded. A rate of false-positive responses of >20 per cent of the total number of apparent presentations indicates an unreliable test result due to a ‘trigger-happy’ or ‘jumping the gun’ patient. With the SITA algorithms of the HFA, a false-positive response is deemed to have occurred if the patient responds either within a designated period, based upon the their own response times for ‘true’ responses, from the appearance of the stimulus, or after a fixed time following disappearance of the stimulus, or both.15 With this latter approach, which supersedes the earlier method and slightly shortens the duration of the examination, false-positive responses of >15 per cent can be considered to constitute an unreliable result.

The false-negative catch trials are generated by the presentation of a stimulus at a given location which is brighter than the sensitivity recorded earlier in the examination. If the patient fails to see the stimulus, a false-negative response is recorded. An incorrect response rate of >33 per cent of the total number of false-negative catch trial presentations has traditionally been used to indicate an unreliable test result. However, an ‘unacceptably’ high proportion of false-negative responses occurring progressively towards the end of the examination indicates a fatigue effect. Equally so, an ‘unacceptably’ high proportion of false-negative responses can be physiologically associated with moderate to severe damage to the visual field and arises from the inherent increased variability associated with the reduced sensitivity at the given stimulus location.16

Fixation loss catch trials are generated by the presentation of a stimulus into the physiological blind spot. If a patient responds to the stimulus, a fixation loss is recorded. If the incorrect responses are >20 per cent or >30 per cent (depending upon the authority) of the total number of stimulus presentations within the blind spot, the test results are deemed to be unreliable. With the HFA, approximately 5 per cent of the total number of stimulus presentations are presented within the blind spot. An alternative approach to the Heijl-Krakau technique is to utilise gaze tracking (available on the HFA 740i and above) whereby an infra-red source is imaged on the pupil centre. The distance between the pupil centre and the first Purkinje image is tracked throughout the examination. An eye movement results in a greater distance between the pupil centre and the Purkinje image. The outcome is displayed two dimensionally (amplitude of movement against time to occurrence) on the monitor of the perimeter in near real

time and on the printout. An upward deflection represents an eye movement and a downward deflection a loss of the infrared image through lid closure, pre-corneal tear film disruption etc (Figure 9). However, it should be noted that the amplitude of the upward deflection is truncated at 10° ie an eye movement of 10° is indistinguishable from that of, say, 20°.

Figure 9: Printout of the results of the gaze tracker from a patient with ‘good’ fixation (Top) and from a patient exhibiting major difficulties in sustaining fixation (Bottom)

Figure 9: Printout of the results of the gaze tracker from a patient with ‘good’ fixation (Top) and from a patient exhibiting major difficulties in sustaining fixation (Bottom)

If the responses to any one type of catch trial fall outside the normal limits, an ‘xx’ is printed alongside the given result.

The test duration is given in minutes and seconds. A prolonged test duration suggests that the patient may have had difficulty in understanding the requirements of the examination and/ or sustaining concentration.

Is the field Normal?

If a Defect is present, what type of defect is it?

The type of defect is then Evaluated to confirm whether it is compatible with the signs and symptoms of the patient.

The correct answer to each of these questions depends upon a number of factors including an expert understanding of the various statistical procedures for the representation of the visual field; upon a sound knowledge of the physiological variability associated with the estimate of the threshold, both in the normal and in the diseased eye; and upon feedback from the perimetrist on the performance of the patient during the examination.

The various methods of representing sensitivity are outlined below.

Numeric display – absolute values of sensitivity

The numeric values of sensitivity are displayed in the numeric display (3). The blind spot, indicated by a triangle, is situated at approximately 15° eccentricity in the temporal field.

Grey scale

The grey scale (4) provides a graphical representation of the differential light sensitivity value at each stimulus location, and interpolates for the value of sensitivity between locations. In the case of the HFA, the system uses 10 shades of grey to represent the complete range of sensitivity values, with eight of the 10 shades each representing an interval of 5dB. A value of 0dB is represented by black and a value of =41dB by white. The grey scale is not corrected for the decline in sensitivity with increase in eccentricity, which is more pronounced superiorly, and, therefore, the normal grey scale is usually lighter centrally than peripherally and usually darker superiorly than inferiorly. It is also not corrected for the decline in sensitivity with increase in age, which is greater peripherally than centrally, and, therefore, in the case of the normal visual field, the grey scale appears darker as the age of the patient increases, particularly at the edges.

Total Deviation plot

The numerical values (5) represent the difference in dBs between the measured value of sensitivity at each stimulus location and the age-corrected normal value of sensitivity contained within the database of the perimeter. In the case of the HFA, a negative sign indicates that the measured value of sensitivity is lower (ie worse) than the expected age-corrected normal value.

Pattern Deviation plot

The numerical values (6) represent the difference in dBs between the measured value of sensitivity at each stimulus location and the age-corrected normal value of sensitivity contained within the database of the perimeter, after having corrected for (ie removing) any overall differences in the height of the visual field from that of the normal (that arising, for example, either from a cataract, a small pupil, a ‘significant’ corneal opacity or an incorrect refractive correction). The correction in the height of the visual field is known as the General Height Adjustment. In the case of the HFA, the magnitude is defined as the value of the seventh most positive or least negative difference between the measured sensitivity and the age-corrected normal value of sensitivity across the 51 Total Deviation values corresponding to the Program 24-2 format (the sensitivity derived at the 52nd location, 9° immediately below the blind spot, is omitted). Although not displayed on the printout, the General Height Adjustment

can be estimated by comparing the difference between the Total and Pattern Deviation values at any given location (the difference, itself, may vary by 1dB between locations due to the mathematical rounding of the measured and age-corrected normal thresholds to integer values displayed on the printout).

Total and Pattern Deviation probability analysis plots

The Total Deviation and the Pattern Deviation values at each stimulus location are expressed in terms of the statistical probability (7 and 8, respectively) of the given deviation lying within the range encountered in the age-corrected normal population. The shade of the pixel representing the given statistical probability darkens as the likelihood decreases of the deviation being encountered within the normal range (expressed as a p value). This is the most useful part of the report: the statistical procedure permits the identification of overall (Total Deviation) and localised (Pattern Deviation) abnormalities of the visual field, respectively.

The presence and significance level of a given individual pixel on the Pattern Deviation probability plot should be viewed in conjunction with the others in terms of their spatial relationship and diagnostic position, ie a nasal step, an arcuate defect, an homonymous quadrantanopia etc.

The grey scale is of little clinical value in the evaluation of early visual field loss since it can appear normal in the presence of an obvious defect by Pattern Deviation probability analysis (Figure 10).

Figure 10: Single field printout of the visual field recorded with the SITA Standard algorithm and Program 24-2 of the HFA for the right eye of a patient with glaucoma. The paracentral/early arcuate defect present in the Pattern Deviation probability map is not evident in the grey scale or in the output of the Glaucoma Hemifield Test. Age-corrected suprathreshold perimetry with the HFA, at least, would not detect the presence of the field loss

Figure 10: Single field printout of the visual field recorded with the SITA Standard algorithm and Program 24-2 of the HFA for the right eye of a patient with glaucoma. The paracentral/early arcuate defect present in the Pattern Deviation probability map is not evident in the grey scale or in the output of the Glaucoma Hemifield Test. Age-corrected suprathreshold perimetry with the HFA, at least, would not detect the presence of the field loss

In cases of severe loss, the General Height Adjustment cannot be calculated with any certainty and, therefore, with the HFA, the Pattern Deviation map is not displayed on the printout. In such instances, the grey scale is more useful.

Glaucoma Hemifield Test

The Glaucoma Hemifield Test (9) provides a linguistic description of the appearance of the visual field, based upon a comparison of the number and severity of the Pattern Deviation probability symbols between the superior (top) and inferior (bottom) halves of the field. The test is applicable only to the results of patients with suspected or manifest glaucoma. It is totally unsuitable for the evaluation of patients with homonymous quadrantanopia or hemianopia etc.

The visual field indices

The three visual field indices (10), Mean Deviation (MD), Pattern Standard Deviation (PSD) and Visual Field Index (VFI) each provide a quantitative summary measure of a given aspect of the visual field. If the magnitude of the MD or PSD falls outside the normal range, the appropriate statistical probability value is indicated next to the particular index. The values, themselves, of the indices are of little diagnostic use but are more useful for the assessment of progressive disease.

Mean Deviation (MD)

The Mean Deviation indicates the average overall difference in the height of the patient’s visual field from that of the age-corrected normal field. The index is weighted such that the sensitivity recorded in the more central locations exerts a greater influence than that recorded at the more peripheral locations. It becomes more negative as the overall field worsens. However, it is adversely influenced by such factors as cataract and inappropriately corrected refractive error.

Pattern Standard Deviation (PSD)

The Pattern Standard Deviation indicates the difference in the shape of the patient’s visual field from that of the age-corrected normal field, ie the extent of the localised, or focal, abnormality. In advanced field loss, the magnitude of the PSD is no longer representative of the damage (ie as the field loss becomes more widespread, the amount of pure localised loss becomes less).

Visual Field Index (VFI)

The Visual Field Index is relatively resistant to the effects of cataract. It approaches (but cannot be greater than) 100 per cent in normal fields and is 0 per cent in perimetrically blind patients, ie those who are unable to see the size III stimulus at maximum luminance at any location. The index is weighted to reflect the greater importance of the paracentral regions of the field. It is essentially a staging index, ie an index to document the time course of progressive loss, but can be useful for indicating to the patient the severity of their field loss.

Case number 3

The patient in Figure 8 has primary open-angle glaucoma in the left eye, together with a nuclear sclerotic cataract. He was examined with the SITA Fast algorithm and program 24-2 using a +8.00DS trial lens which incorporated the appropriate correction for the viewing distance of the perimeter bowl (1). The response to each of the three types of catch trials (2) indicates that a reliable response was obtained. The values of sensitivity in the numerical display indicate severe loss in the superior hemifield, which is absolute to the Goldmann size III stimulus at each of nine locations superior nasally (indicated by <0). The grey scale (4) reflects the severity of the loss in the superior field. The Total Deviation values (5), but more particularly the Total Deviation probability levels (6) illustrate the superior hemifield loss but also suggest that all but one of the stimulus locations in the inferior field exhibit a sensitivity which lies outside the age corrected normal range at a value of p=0.05. This latter abnormality is not readily visible in the grey scaling of the inferior field. The General Height, estimated from the difference between the Total (5) and the Pattern Deviation values (7) is approximately -4dB, ie there is an overall reduction in the height of the visual field from the age-corrected normal height. This reduction is mostly, if not all, attributable to the nuclear sclerosis (it is hotly debated as to whether glaucoma produces generalised/ diffuse loss in addition to focal loss). Adjusting for the reduction in height, ie by adding approximately 4dB to each of the Total Deviation values removes the adverse influence of the cataract and highlights the glaucomatous loss as evidenced by the Pattern Deviation values (7) and by the Pattern Deviation probability map (8). In this instance, the appearance of the Pattern Deviation probability map is compatible with that of the grey scale. The outcome of the Glaucoma Hemifield Test (9) confirms the impact of the severe superior altitudinal defect, as do the Visual Field Index, the Mean Deviation and the Pattern Standard Deviation (10).

Examples of various types of glaucomatous visual field loss are given in Figure 11.

Figure 11: The grey scale, numeric values of sensitivity, and the Total and Pattern Deviation probability maps for four different cases of glaucomatous field loss. The steep sided and absolute paracentral defect illustrated in the top case is frequently associated with normal tension glaucoma

Figure 11: The grey scale, numeric values of sensitivity, and the Total and Pattern Deviation probability maps for four different cases of glaucomatous field loss. The steep sided and absolute paracentral defect illustrated in the top case is frequently associated with normal tension glaucoma

Combined structure and function probability evaluation

The need to assess, concomitantly, both structure and function in glaucoma underlines the importance of the simultaneous evaluation of the outcomes from OCT and from perimetry and such an approach is very topical.17-18 One example of software which enables the simultaneous evaluation of the outcomes from the Cirrus HD-OCT with that of the HFA is Forum Glaucoma Workplace.

The inverted en-face topographical distribution of the retinal nerve fibre layer thickness, represented in probability levels, overlaying the Pattern Deviation probability levels of Program 24-2, is shown in the centre of Figure 12 for a patient with glaucoma.

Figure 12: Forum Glaucoma Workplace combined 24-2/30-2 and RNFL Report for a patient with glaucoma exhibiting a superior arcuate defect in each eye. Note the strong association between the retinal nerve fibre layer thickness probability levels and the Pattern Deviation probability levels

Figure 12: Forum Glaucoma Workplace combined 24-2/30-2 and RNFL Report for a patient with glaucoma exhibiting a superior arcuate defect in each eye. Note the strong association between the retinal nerve fibre layer thickness probability levels and the Pattern Deviation probability levels

The superior arcuate defect in each eye by Pattern Deviation probability analysis is clearly associated with an attenuated retinal nerve fibre thickness.

The same type of plot is shown in Figure 13 for a patient with glaucoma, which is more advanced in the left eye. The optic nerve head parameters in the right eye each exhibit borderline abnormality (p<0.05); however, functional abnormality appears before structural abnormality of the peripapillary retinal nerve fibre layer thickness.

Figure 13: Forum Glaucoma Workplace combined 24-2/30-2 and RNFL report for a patient with glaucoma exhibiting arcuate defects in both hemifields of the left eye and a paracentral visual field defect in the right eye. Note the strong association between the retinal nerve fibre layer thickness probability levels and the Pattern Deviation probability levels in the left eye. The visual field loss in the right eye is present with a seemingly normal retinal nerve fibre layer

Figure 13: Forum Glaucoma Workplace combined 24-2/30-2 and RNFL report for a patient with glaucoma exhibiting arcuate defects in both hemifields of the left eye and a paracentral visual field defect in the right eye. Note the strong association between the retinal nerve fibre layer thickness probability levels and the Pattern Deviation probability levels in the left eye. The visual field loss in the right eye is present with a seemingly normal retinal nerve fibre layer

Similarly, the topographical distribution of the macular ganglion cell/ inner plexiform layer complex thickness, as a probability level, overlaying the pattern deviation probability levels of Program 10-2 (which thresholds 68 locations with a 2° separation out to 9° eccentricity) for another patient with glaucoma is shown in the centre of Figure 14.

Figure 14: Forum Glaucoma Workplace combined Program 10-2 and macular ganglion cell/inner plexiform layer thickness report for a patient with glaucoma. Note the strong association  between the structural and functional outcomes

Figure 14: Forum Glaucoma Workplace combined Program 10-2 and macular ganglion cell/inner plexiform layer thickness report for a patient with glaucoma. Note the strong association between the structural and functional outcomes

Forum Glaucoma Workplace is an advanced glaucoma management tool, and is an optional module for Forum; a Zeiss data management system. Forum is able to store dicom files from Zeiss and other manufacturers’ diagnostic instruments.

Forum Glaucoma Workplace also brings an added dimension to the detection and management of glaucoma. The interactive software enables the practitioner to interrogate the various datasets in order to optimise the clinical decision making at any given visit. An example of such utility is the Guided Progression Analysis (Figures 15 and 16) which is separately applicable to the outcomes of OCT and of perimetry.

Figure 15: Forum Glaucoma Workplace Guided Progression Analysis in the left eye for a glaucoma suspect illustrating the en-face RNFL Thickness and RNFL Deviation maps and the slopes of the average, superior, and inferior RNFL thicknesses, derived from the 200x200 optic disc cube, over the follow-up period

Figure 15: Forum Glaucoma Workplace Guided Progression Analysis in the left eye for a glaucoma suspect illustrating the en-face RNFL Thickness and RNFL Deviation maps and the slopes of the average, superior, and inferior RNFL thicknesses, derived from the 200x200 optic disc cube, over the follow-up period

The software evaluates the given outcome over the follow-up period and references it to the initial/ base line examinations. The baseline can be changed at the intervention of the examiner, for example, to assess the outcome of any change in therapy (Figure 16).

Figure 16: Forum Glaucoma Workplace Guided Progression Analysis for the visual field in the left eye of a patient with glaucoma. Top left: the visual field at the initial two examinations. Bottom left and bottom right: the final visual field of the series recorded approximately eight years after the first examination. Middle left: The marked progressive loss as evidenced by the decline in the VFI over time. Top right: The visual field at the two immediate examinations following change in therapy. Middle right: the arrest of the progression in the visual field is clearly evidenced by the outcome of the VFI referenced to the new baseline at the time of the change in therapy

Figure 16: Forum Glaucoma Workplace Guided Progression Analysis for the visual field in the left eye of a patient with glaucoma. Top left: the visual field at the initial two examinations. Bottom left and bottom right: the final visual field of the series recorded approximately eight years after the first examination. Middle left: The marked progressive loss as evidenced by the decline in the VFI over time. Top right: The visual field at the two immediate examinations following change in therapy. Middle right: the arrest of the progression in the visual field is clearly evidenced by the outcome of the VFI referenced to the new baseline at the time of the change in therapy

Anterior chamber angle assessment

In addition to the optic nerve head and posterior pole applications of OCT, most OCT instruments also enable a viewing of the anterior chamber angle (Figure 17).

Figure 17: The Cirrus HD-OCT 500 image of the anterior chamber of a patient with a narrow angle

Figure 17: The Cirrus HD-OCT 500 image of the anterior chamber of a patient with a narrow angle

Summary

The advantage of a combined evaluation of structural and functional outcomes, defined in terms of probability evaluation, in the diagnosis and management of glaucoma is clear. The ability to interrogate accompanying software to enhance the decision making process is also apparent.

It is surely inevitable that high resolution imaging techniques will eventually replace the traditional ophthalmoscopic techniques in the assessment of glaucoma, at least. It is also likely that imaging of the anterior chamber angle will also supersede that of gonioscopy.

Model answers

(The correct answer is in bold text)

1 Above what percentage of false positive results would be considered unreliable when using SITA algorithms?

A 5

B 10

C 15

D 20

2 What percentage stimuli are presented to the blind spot in the Heijl-Krakau technique when using the HFA?

A 5

B 10

C 15

D 20

3 Which of the following is most likely to impact upon the Pattern Deviation plot but not the Total Deviation plot

A Cataract

B Chorioretinitis scar in paracentral area

C Uncorrected refractive error

D Corneal dystrophy

4 Which of the following values for the Mean Deviation (MD) is most likely to represent the worst visual field?

A Zero

B A negative value

C A positive value

D MD does not indicate worsening field

5 Which of the following as a single value gives some indication of progression of loss over time?

A Mena deviation

B Glaucoma Hemifield Test

C Pattern Standard Deviation

D Visual Field Index

6 Which of the following is unlikely to be found in a patient with established glaucomatous field loss?

A Nasal step

B Steep-sided paracentral defect

C Visual Field Index approaching 100

D Reduced retinal nerve fibre layer thickness

References    

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2 Weinreb RN, Aung T; Medeiros FA. The pathophysiology and treatment of glaucoma: A review. Journal of the American Medical Association, 2014;311:1901-1911.

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4 Miglior S, Zeyen T, Pfeiffer N, et al. Results of the European Glaucoma Prevention Study. Ophthalmology, 2005;112:366-375.

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12 Quigley HA, Dunkelberger GR, Green WR. Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. American Journal of Ophthalmology, 1989 15;107:453-464.

13 Harwerth RS, Wheat JL, Fredette MJ, Anderson DR. Linking structure and function in glaucoma. Progress in Retina and Eye Research, 2010; 29:249-271.

14 Medeiros FA , Zangwill LM, Anderson DR, et al. Estimating the rate of retinal ganglion cell loss in glaucoma. American Journal of Ophthalmology, 2012; 154: 814-824.

15 Olsson J, Bengtsson B, Heijl A, Rootzen H. An improved method to estimate frequency of false positive answers in computerized perimetry. Acta Ophthalmologica Scandanavica, 1997;75:181-183.

16 Bengtsson B, Heijl A. False-negative responses in glaucoma perimetry: indicators of patient performance or test reliability? Invest Ophthalmolology and Visual Science, 2000; 41:2201-2004.

17 Bizios D, Heijl A, Bengtsson B. Integration and fusion of standard automated perimetry and optical coherence tomography data for improved automated glaucoma diagnostics. BMC Ophthalmology, 2011;11:20.

18 Raza AS1, Zhang X, De Moraes CG, et al. Improving glaucoma detection using spatially correspondent clusters of damage and by combining standard automated perimetry and optical coherence tomography. IInvest Ophthalmolology and Visual Science, 2014;55: 612-224.

Professor John Wild is Professor of Clinical Vision Sciences at Cardiff University and Honorary Research Fellow at the University Hospital of Wales