Ординатура / Офтальмология / Английские материалы / Clinical Ophthalmology A Systematic Approach 7th Edition_Kanski, Bowling_2011

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Fig. 10.29 Humphrey perimetry

Testing patterns

Most important defects in glaucoma occur within the central 30° radius of field, so this is the area most commonly tested.

•The pattern of the points analyzed in a particular test is located at the top left on a standard HFA printout; 24–2 is an example in widespread routine use in which ‘24’ denotes the extent, in degrees, to which the field is tested on the temporal side (tested to 30° on the nasal side in the 24–2). The number after the dash (–2 or sometimes –1) describes the pattern of the points tested.

•The –2 strategy involves a grid of test points spaced 6° apart, offset from the vertical and horizontal meridia whereas the –1 includes points along the vertical and horizontal meridia.

•In another common glaucoma pattern, 30–2, the area tested extends to 30° temporally as well as nasally.

•Other examples include 10–2 and FF-120; 10–2 is used to assess an area of central radius 10° – as defects here may threaten central vision careful monitoring is commonly required. FF (‘full field’) – 120 (120°) is used to assess neurological defects. The HFA can also be used to perform binocular field testing (e.g. Esterman strategy) to assess statutory driving entitlement.

Testing strategies

1Suprathreshold strategies are rapid (6 minutes per eye) qualitative programs. An 88-point screening test using a three-zone strategy may be used initially as it is fast and less demanding than full threshold formats. An absolute defect is indicated with a black square and a relative defect with a cross.

2Full-threshold strategy is now seldom used, mainly because of its long duration, frequently 15–20 minutes/eye including setup, making it difficult for patients to maintain concentration. Initially four points are tested to determine threshold levels which are then used to predict the levels for neighbouring points and so on until the entire field has been tested. Multiple additional threshold checks are performed.

3SITA (Swedish Interactive Thresholding Algorithm) uses an extensive database of normal and typically glaucomatous fields to estimate threshold values, and takes the patient's ongoing responses into account to arrive at adjusted estimates throughout the test, based on probability levels. It stops testing a given location when the margin of error is acceptable, and uses response time rather than false positive catch trials to estimate the false positive rate (there is a strong correlation between the two). The stimulus presentation rate is speeded up in fast responders. Standard and faster versions are available; SITA-Fast uses similar methods to SITA-Standard and is preferred by some practitioners, but may be less repeatable and slightly less sensitive.

Displays

1The numerical display (numerical grid) is located to the left of the grey scale and to the right of the reliability indices. It gives the measured or estimated (depending on strategy) threshold in dB at each point. In a full-threshold strategy, where the threshold is rechecked either as routine or because of an unexpected (>5 dB) result, the second result is shown in brackets next to the first.

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2The grey scale represents the adjacent numerical display in graphical form and is the simplest display to interpret: decreasing sensitivity is represented by darker tones. Each change in grey scale tone is equivalent to a 5 dB change in sensitivity at that location.

3Total deviation display (Fig. 10.30 left) represents the difference between the test-derived threshold at each point and the normal sensitivity at that point in the general population, correcting for age. Negative values indicate lower than normal sensitivity, positive values higher than normal.

4Pattern deviation (Fig. 10.30 right) is derived from the total deviation values adjusted for any generalized decrease in sensitivity in the overall field which might be caused by other factors such as lens opacities or miosis. It therefore demonstrates localized defects such as occur in glaucoma.

5Probability displays are located below the numerical total and pattern deviation displays (Fig. 10.30 bottom). These constitute a graphical representation of the percentage (<5% to <0.5%) of the normal population in whom the measured defect at each point would be expected. Darker symbols represent a greater likelihood that a defect is significant.

Fig. 10.30 Total deviation, pattern deviation and probability indices

Reliability indices

Reliability indices reflect the extent to which the patient's results are reliable and should be analyzed first. If grossly unreliable, further analysis of a visual field printout is of little value. In patients who consistently fail to achieve good reliability indices it may be useful to switch to a suprathreshold strategy or kinetic perimetry.

1Fixation losses indicate steadiness of gaze during the test. They are detected in older HFA versions by presenting stimuli to the blind spot; if the patient responds, a fixation loss is recorded. The fewer the number of losses the more reliable is the test. A ‘gaze monitor’ is used on newer HFAs. A high fixation loss score may occur if the instrument has incorrectly plotted the blind spot.

2False positives are detected when a stimulus is accompanied by a sound. If the sound alone is presented and the patient still responds, a false positive is recorded. False positive responses do not increase in damaged visual fields. With a high false positive score the grey scale printout appears abnormally pale (Fig. 10.31). Fixation losses are also frequently high and the glaucoma hemifield test shows abnormally high sensitivity. In SITA testing, false positives are estimated based on the response time, which correlates well with the false positive rate.

3False negatives are detected by presenting a stimulus much (9 dB) brighter than threshold at a location where the threshold has already been determined. If the patient fails to respond a false negative is recorded. A high false negative score indicates inattention or tiredness. It may also be due to short-term fluctuation associated with glaucoma, and may be an indicator of disease severity rather than patient unreliability. The grey scale printout in individuals with high false negative responses tends to have a clover-leaf shape (Fig. 10.32).

4Interpretation. It is important to note that there is relatively little research evidence in this area, with limited absolutes in branding a field as clearly reliable or unreliable. With SITA strategies, false negatives or false positives over about 15% should probably be regarded as highly significant, and with full-threshold strategies, fixation losses over 20% and false positives or negatives over 33%.

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1Physiological principles. Ganglion (M) cells with relatively large diameter axons comprise 25% of the ganglion cell population. They are particularly susceptible to glaucomatous damage and appear to be preferentially lost in early glaucoma. A loss of a small number of these cells has a considerable effect on visual function. Psychophysical tests have been devised to target visual function provided by these magnocellular pathways in the detection of early glaucoma.

2Frequency-doubling illusion is produced when a low spatial frequency sinusoidal grating (less than one cycle per degree) undergoes high temporal frequency counter phase flicker (>15 Hz). The rapid alternation in which the light bars become dark and vice versa produces the illusion of the grating having doubled its frequency.

3The perimeter is a tabletop instrument (Fig. 10.33 bottom) which can be used under normal room lighting and requires no patching, since the viewing canopy automatically covers the eye not being tested. The device requires minimal training and is relatively portable.

4Stimuli are presented in 17 or 19 sectors in the central 20° or 30° depending on the program used, screening or full threshold.

5Testing time is short with full threshold programs taking about 5 minutes per eye and screening procedures between 45 and 90 seconds per eye. Because of this most patients prefer the FDT test to conventional perimetry.

6Results are displayed and printed together with reliability indices, probabilities, mean deviation and pattern standard deviation (Fig. 10.33 top). FDT has high sensitivity both in screening to differentiate healthy individuals from those with glaucoma and for quantifying glaucomatous damage. The results are minimally affected by refractive error of up to 6 D and not at all by pupil size. The device has an age-adjusted normative database, as well as a statistical analysis package for immediate evaluation of results.

7The Humphrey Matrix is a more recently introduced FDT perimeter which allows extended testing of considerably larger areas of field than the basic screening version. It is thus proposed as being at least comparable to the HFA for refined diagnosis and monitoring.

Fig. 10.33 Frequency-double perimeter and display

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Ocular hypertension

Definition

In the general population the mean IOP is 16 mmHg; two standard deviations on either side of this gives a ‘normal’ IOP range 11–21 mmHg. The distribution is Gaussian with the curve skewed to the right (Fig. 10.34).

•In the elderly the mean IOP is higher, particularly in women, and the standard deviation greater than in younger individuals. This means that ‘normal’ IOP in elderly women may range up to 24 mmHg and not 21 mmHg.

•It is estimated that 4–7% of the population over the age of 40 years have IOPs >21 mmHg without detectable glaucomatous damage: ‘ocular hypertension’ (OHT).

•An absence of angle-closure is implicit, and there should be no detectable cause of secondary glaucoma, though sometimes the term OHT is used to describe raised IOP in these contexts.

Fig. 10.34 Distribution of intraocular pressure in the general population

Risk factors for developing glaucoma

The Ocular Hypertension Treatment Study (OHTS) was a multicentre longitudinal trial. In addition to looking at the effect of treatment in ocular hypertensives (IOP <32 mmHg), invaluable landmark information was gained about the effect of a range of putative risks for conversion from OHT to glaucoma; the percentage of OHT patients likely to develop glaucoma taking key factors into account is set out in Tables 10.3 and 10.4 (median follow-up was 72 months). Additional considerations are discussed below. Limitations included the possibility that early glaucomatous damage was already present in some of the patients classified as having OHT. The fact that some percentages appear anomalous may be due to the relatively low numbers in different subcategories.

Table 10.3 -- Risk of developing glaucoma according to IOP (intraocular pressure) and CCT (central corneal thickness)

Table 10.4 -- Risk of developing glaucoma according to vertical C/D ratio and CCT

CCT ≤555 µmCCT >555 to ≤588 µmCCT >588 µm

The following factors were significant on multivariate analysis:

1 Intraocular pressure. The risk increases with increasing IOP.

2 Age. Older age is associated with greater risk.

3Central corneal thickness (CCT). The risk is greater in eyes with low CCT and lower in eyes with higher CCT. This is probably due

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to resultant underand over-estimation of IOP although it has been proposed that associated structural factors, perhaps at the lamina cribrosa, might also be important.

4Cup–disc (C/D) ratio. The greater the C/D ratio the higher the risk. This may be because an optic nerve head with a large cup is structurally more vulnerable, or it may be that early damage is already present.

5Pattern standard deviation (PSD). A greater PSD result represented a significant risk. It is possible that this signified early glaucomatous field change.

The following factors were significant on univariate analysis only; they were not significant in isolation but were over-ridden when the factors considered above were taken into account.

1 African-American race was associated with a higher glaucoma risk. 2 Gender. Males were more likely to convert.

3 Heart disease was found to be significant.

Factors examined in the OHTS but not found to be significant are listed below.

1Myopia, although it is suspected that myopic discs are more susceptible to glaucomatous damage at a lower IOP than emmetropic discs.

2 Diabetes. An apparent protective effect of diabetes was initially found, but later analysis with refreshed data did not confirm this.

3Family history of glaucoma was not found to be a risk factor for conversion.

4Other factors which were not examined in the OHTS but may be important include retinal nerve fibre defects (though the presence of these may be taken to indicate pre-perimetric glaucoma – see below) and specific peripapillary atrophic changes.

Pre-perimetric glaucoma

This concept refers to glaucomatous damage, usually manifested by a suspicious optic disc and/or the presence of retinal nerve fibre layer defects, in which no visual field abnormality has developed. The field testing modality for this purpose is usually taken as standard achromatic automated perimetry.

Management

In the OHTS, untreated patients with ocular hypertension had a 9.5% cumulative risk of developing POAG after 5 years; treatment (which aimed to reduce IOP by 20% or more and to reach 24 mmHg or less) reduced this to 4.4%. Hence, when deciding on whether to start treatment it is important to take into account that it will be necessary to treat a large number of patients in order to prevent the development of glaucoma in a single individual.

•Age, and so life expectancy, is a key point to consider. In general, only those at higher risk should be treated, although patient preference may be a decisive factor.

•Most practitioners would treat every patient with an IOP of 30 mmHg or more. The decision to treat in patients with varying risk profiles is commonly less than straightforward, and has to be made on an individual basis.

•Various guidelines exist, but there is a high level of disagreement even between glaucoma specialists. Careful monitoring is a reasonable alternative in many circumstances.

•OHT almost certainly increases the risk of retinal venous occlusion, an additional point to take into account when considering whether to start treatment.

•Drug choice is the same as for POAG, although a less aggressive pressure-lowering approach is frequently taken.

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Primary open-angle glaucoma

Introduction

Definition

Primary open-angle glaucoma (POAG), also referred to as chronic simple glaucoma, is a generally bilateral disease of adult onset characterized by:

•An IOP >21 mmHg at some stage.

•Glaucomatous optic nerve damage.

•An open anterior chamber angle.

•Characteristic visual field loss as damage progresses.

•Absence of signs of secondary glaucoma or a non-glaucomatous cause for the optic neuropathy.

POAG is the most prevalent type of glaucoma in individuals of European and African ethnic origin. It affects both sexes equally.

Risk factors

1 IOP. The higher the IOP, the greater the likelihood of glaucoma.

2Age. It is more common in older individuals.

3Race. It is significantly (perhaps four times) more common, develops at an earlier age, and may be more difficult to control in black individuals than in whites.

4Family history of POAG. First-degree relatives of patients with POAG are at increased risk. An approximate risk to siblings is four times and to offspring twice the normal population risk.

5Diabetes mellitus. Many studies suggest a correlation between diabetes and POAG.

6Myopia is associated with an increased incidence of POAG and myopic eyes may be more susceptible to glaucomatous damage.

7Vascular disease. A range of systemic conditions linked to vascular compromise may be associated, though clear-cut relationships have proved difficult to demonstrate consistently. Systemic hypertension, cardiovascular disease, diabetes and vasospastic conditions such as migraine have all been implicated. Poor ocular perfusion may be a risk factor for glaucoma progression.

Genetics

Mutations at 15 loci in the human genome have so far been identified as associated with POAG and are designated primary open angle glaucoma-1A (GLC1A) to GLC1O. Four susceptible genes have been identified: the MYOC gene (chromosome 1q21-q31), coding for the glycoprotein myocilin that is found in the trabecular meshwork and other ocular tissues, the OPTN gene on chromosome 10p, which codes for optineurin, the WDR36 gene on chromosome 5q22, and the NTF4 gene on chromosome 19q13.3. Among them MYOC is the most frequently mutated gene in POAG: a study of unrelated POAG patients found myocilin mutations in at least 4% of the adults. A number of different mutations have been described in the MYOC gene, though the normal function of myocilin and its role in causing glaucoma is as yet undetermined. If a single family member develops glaucoma prior to age 35 years, the chances that the genetic defect is a mutation is the myocilin gene may be as high as 33%.

Steroid responsiveness

A proportion of the population develops an elevation in IOP in response to a course of topical steroid; more potent steroids have a greater propensity to elevate IOP, as does greater frequency of instillation. This tendency is more marked in patients with POAG and their close relatives. Intraand periocular steroid administration, including periocular application of steroid skin cream and nasal administration, are also prone to elevate IOP. Systemic steroids are much less prone to cause elevation of IOP, but substantial, probably dose-dependent, rises can occur and some authorities have advocated screening for all patients on systemic steroids, perhaps those on dexamethasone in particular. The precise mechanism of the ‘steroid response’ is uncertain, but it may be mediated by an increase in trabecular meshwork cell myocilin production.

Pathogenesis of glaucomatous optic neuropathy

Retinal ganglion cell death in glaucoma occurs predominantly through apoptosis (programmed cell death) rather than necrosis. The preterminal event is calcium ion influx into the cell body and an increase in intracellular nitric oxide; glutamine metabolism is intrinsically involved. After initial injury, a cascade of events results in astrocyte and glial cell proliferation, and alterations in the extracellular matrix of the lamina cribrosa, with subsequent optic nerve head remodelling. Multiple factors are likely to be involved, but the mechanisms remain relatively speculative: the process of glaucomatous damage and the relationship with IOP and other potential influences is still poorly understood. One or both of the following mechanisms may be involved:

1Direct mechanical damage to retinal nerve fibres at the optic nerve head, perhaps as they pass through the lamina cribrosa.

2Ischaemic damage, possibly due partly to compression of blood vessels supplying the optic nerve head.

Insults via both mechanisms might lead to reduction in axoplasmic flow, interference with the delivery of nutrients or removal of metabolic products, deprivation of neuronal growth factors, oxidative injury and the initiation of immune-mediated damage.

Screening

Universal population screening for glaucoma has not been demonstrated to be cost-effective, and current practice restricts screening to high-

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risk groups, such as older individuals, those with a history of POAG in a close family member over the age of 40, and people of black ethnicity. In these groups, screening tends to be performed sporadically via routes such as commercial sight tests, which may lead to the relative exclusion of underprivileged economic groups. Population screening with tonometry alone is unsatisfactory, since it will label as normal a significant number of cases with other features of POAG such as cupping and visual field loss. Even with the added criterion of a vertical cup–disc ratio of >0.4, only a proportion of potential POAG patients will be identified. It is therefore prudent for routine screening eye examinations to include visual field examination as well as tonometry and ophthalmoscopy.

Diagnosis

History

1Visual symptoms will usually be absent, unless damage is advanced. Sometimes symptomatic central field defects may occur at an early stage, in the presence of a relatively normal peripheral field.

2Previous ophthalmic history. Specific enquiry should be made about:

•Refractive status as myopia carries an increased risk of POAG, and hypermetropia of primary angle-closure glaucoma (PACG).

•Causes of secondary glaucoma such as ocular trauma or inflammation; previous eye surgery, including refractive surgery may affect IOP reading.

3Family history

•POAG or related conditions such as OHT.

•Other ocular disease in family members.

4Past medical history. Asking specifically about the following may be indicated.

•Asthma, heart failure or block, peripheral vascular disease: contraindications to the use of betablockers.

•Head injury, intracranial pathology including stroke that may cause optic atrophy or visual field defects.

•Vasospasm: migraine and Raynaud phenomenon.

•Diabetes, systemic hypertension and cardiovascular disease may increase the risk of POAG.

5Current medication

•Steroids including skin cream and inhalants.

•Oral beta-blockers may lower IOP.

6 Social history including smoking and alcohol intake, especially if toxic/nutritional optic neuropathy is suspected.

7Allergies especially to any drugs likely to be used in glaucoma treatment, particularly sulfonamides.

Examination

1Visual acuity is likely to be normal except in advanced glaucoma.

2Pupils. Exclude a relative afferent pupillary defect (RAPD); if absent then subsequently develops this constitutes an indicator of substantial progression.

3 Colour vision assessment such as Ishihara chart testing if there is any suggestion of an optic neuropathy other than glaucoma. 4 Slit-lamp examination. Exclude features of secondary glaucomas such as pigmentary and pseudoexfoliative.

5 Tonometry, prior to pachymetry, noting the time of day.

6Pachymetry for CCT.

7Gonioscopy.

8Optic disc examination should always be performed with the pupils dilated, provided gonioscopy does not show critically narrow angles. Red-free light can be used to detect RNFL defects.

9 Perimetry should usually be performed prior to clinical examination.

10 Optic disc or peripapillary RNFL imaging as described above.

Visual field defects

1The earliest changes suggestive of glaucoma consist of increased variability of responses in areas that subsequently develop defects. Alternatively there may be slight asymmetry between the two eyes.

2Paracentral, small, relatively steep depressions (Fig. 10.35A and B) constitute approximately 70% of all early glaucomatous field defects. Since the defects respect the distribution of the retinal nerve fibre layer they terminate at the horizontal midline; defects above and below the horizontal therefore are not aligned with each other. Central/paracentral scotomata may be most appropriately monitored using the 10–2 Humphrey perimetry pattern.

3Nasal (Rønne) step represents a difference in sensitivity above and below the horizontal midline in the nasal field. It is a common finding usually associated with other defects (Fig. 10.36A and B). A temporal wedge is less common but has similar implications.

4Arcuate-shaped defects develop as a result of coalescence of paracentral scotomas. They typically develop between 10° and 20° of fixation in areas that constitute downward or, more commonly, upward extensions from the blind spot around fixation (Bjerrum area). With time, they tend to elongate circumferentially along the distribution of arcuate nerve fibres (Seidel scotoma) and may eventually connect with the blind spot (arcuate scotoma) reaching to within 5° of fixation nasally (Fig. 10.37A and B).

5 Enlargement of scotomas due to damage to adjacent fibres. 6 Deepening of scotomas and development of fresh defects.

7A ring scotoma develops when arcuate defects in upper and lower halves of the visual field join. Misalignment between the two often preserves the nasal step (Fig. 10.38A and B).

8End-stage changes are characterized by a small island of central vision typically accompanied by a temporal island. The temporal

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island is usually extinguished before the central.

Fig. 10.35 Mild damage. (A) Minimal cupping; (B) small paracentral scotoma

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Fig. 10.36 Moderate damage. (A) Moderate cupping; (B) arcuate scotoma and a nasal step

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