Page of

Glaucoma 

Glaucoma
Chapter:
Glaucoma
Source:
Training in Ophthalmology (2 ed.)
Author(s):

Andrew Tatham

and Peng Tee Khaw

DOI:
10.1093/med/9780199672516.003.0008

Basic sciences

Clinical assessment

Clinical knowledge

Practical skill

Surgical skills

8.1 Optic nerve head anatomy

The optic nerve head, or optic disc, is the region where retinal ganglion cell (RGC) axons exit the eye through the scleral canal. The optic nerve head represents a weak spot in the corneo-scleral envelope and it is therefore subject to intraocular pressure (IOP)-induced stress and strain. The optic nerve head is believed to be the major site of RGC axon damage in glaucoma.

The mean optic disc area is 2.2 ± 0.5 mm2 (measured from Elschnigs rim at the margin of the scleral canal); however, disc size varies considerably between individuals. Hypermetropic eyes, with shorter axial lengths, tend to have small ‘crowded’ discs, whereas myopic eyes tend to have larger discs. The optic disc also tends to be larger in black populations. Optic disc size should be measured if glaucoma is suspected, as it can influence interpretation of measures such as cup/disc ratio (see Section 8.4).

Zones of the optic nerve head

The OHN represents the intraocular portion of the optic nerve. It consists of four zones determined by the relationship of the nerve and lamina cribrosa (see Figure 8.1):

Fig 8.1 Anatomy of the optic nerve head

Fig 8.1
Anatomy of the optic nerve head

Zone 1: Retinal nerve fibre layer

The retinal nerve fibre layer (RNFL) consists of approximately 1.2 million unmyelinated RGC axons. This point is important, as unmyelinated axons have a much higher energy requirement than do myelinated axons, a fact which may be highly relevant in the pathogenesis of glaucomatous neuroaxonal damage. The axons follow a precise pattern as they course towards the scleral canal. Fibres arising from between the disc and fovea pass directly to the optic nerve head as the papillomacular bundle. Fibres from the nasal, superior, and inferior retina also take a direct route to the optic nerve head. Fibres from the areas temporal to the fovea follow arcuate paths around the papillomacular bundle to enter the optic nerve head at its upper and lower margins.

Zone 2: Prelaminar zone

In the prelaminar zone, RGC axons turn from the retinal plane by 90° to form the optic nerve. Spatial order continues with axons from RGCs in the central retina located near the centre of the nerve, and axons from RGCs in the peripheral retina located in the periphery of the optic nerve. The major supporting cell of the optic nerve head is the astrocyte glial cell. Astrocytes processes are widespread and are in close proximity to the nerve fibres, separating bundles of the fibres. The astrocytes have giant mitochondria, an observation that suggests they supply large amounts of energy to the axons and also provide ‘waste disposal’ functions.

Zone 3: Lamina zone

The lamina cribrosa is a continuation of the inner sclera. It consists of approximately ten perforated connective tissue beams. Together, the beams form a mesh-like structure spanning the scleral canal. The lamina provides structural and functional support for axons passing through the scleral canal, and a passageway for retinal blood vessels. The lamina is a site of biomechanical weakness in the eye and therefore a location of stress and strain. The lamina is considered the principal site of nerve fibre damage in glaucoma. The dura mater of the optic nerve also begins in this zone as a continuation of the outer sclera.

Zone 4: Post (or retro) lamina zone

This portion of the optic nerve head marks the beginning of myelination of the RGC axons.

Using the slit lamp, it is possible to assess the RNFL, the prelaminar zone, and the anterior lamina cribrosa.

Zones of the optic nerve head on slit lamp examination

Neuroretinal rim

The optic disc can be divided into the neuroretinal rim and the cup. The neuroretinal rim is the tissue between the outer edge of the cup and disc margin. It is composed of neuroglia, astrocytes, and RGC axons that will eventually pass through the lamina cribrosa. A plentiful blood supply and the presence of axoplasm give the healthy rim an orange-red appearance. The neuroretinal rim has a characteristic configuration obeying the ISNT rule: the inferior rim is thickest, followed by the superior rim, the nasal rim, and then the temporal rim. If this rule is not obeyed, a pathological condition such as glaucoma is a possibility.

Optic cup

The optic cup is a three-dimensional depression, either round or ovoid, in the centre of the optic disc. The cup represents an absence of axons and partial exposure of the lamina; it therefore appears slightly pale. Pallor of the cup should not be confused with pallor of the neuroretinal rim, as the latter indicates a non-glaucomatous process. The limit of the cup can be determined as the first discernible change in surface contour as the nerve fibres course posteriorly. Within a population, the number of axons in the optic nerve head is relatively constant but the scleral canal (and therefore the size of the disc) varies in size depending on factors such as the size of the globe. As the RGC axons occupy a similar volume, the size of a normal optic cup can vary considerably.

Retinal blood vessels

The central retinal artery, a branch of the ophthalmic artery, tends to be nasal to the central retinal vein. Both vessels enter/exit the optic disc centrally then course nasally, following the edge of the cup. Cilioretinal arteries occur in about 25% of the population, most arising from the temporal rim.

Blood supply

The main arterial supply of the optic nerve head is via the posterior ciliary arteries derived from the ophthalmic artery. Fifteen to twenty short posterior ciliary arteries pierce the sclera close to the optic nerve, forming an incomplete anastomosis within the sclera around the optic nerve (the circle of Zinn–Haller). One or two long posterior ciliary arteries pierce the sclera further away. Small end arterial branches leave the circle of Zinn–Haller to feed the optic nerve head via capillaries within the lamina cribrosa beams. There is no direct blood supply to RGC axons in the laminar region; instead, nutrients arrive by diffusion from laminar capillaries. Venous drainage is via the central retinal vein and also by drainage into the peripapillary choroid.

8.2 Aqueous fluid dynamics

Aqueous humour is a transparent, colourless fluid continually produced by the ciliary body. Aqueous is similar to plasma but has lower levels of glucose and protein (assuming an intact blood–aqueous barrier) and higher levels of ascorbate and lactate than plasma does. Aqueous humour provides structural and nutritional support to the avascular cornea and lens and also removes metabolic waste products. Production and outflow of aqueous humour must be balanced to maintain a steady-state IOP. Aqueous humour dynamics describe the balance of aqueous humour production and outflow through the trabecular meshwork (TM) and uveoscleral pathways.

Aqueous production

Aqueous humour is produced by the ciliary body, a triangularly shaped structure attached to the sclera at the scleral spur. Approximately 70 ciliary processes are located on the inner, anterior surface of the ciliary body at the pars plicata. The epithelium of each process has two neuroepithelial layers:

  1. 1. An inner, non-pigmented epithelium in contact with the posterior chamber (this layer represents a continuation of the retina)

  2. 2. An outer, pigmented epithelium in contact with the stroma of the ciliary process (this layer represents a continuation of the retinal pigment epithelium)

Tight junctions between the non-pigmented cells form the blood–aqueous barrier. Each process has a central arteriole ending in a rich, highly fenestrated capillary network.

Aqueous humour is formed via a combination of active secretion (70%–80%), ultrafiltration (20%), and diffusion (10%) as follows:

  1. 1. Plasma from the fenestrated capillaries in the ciliary processes moves down a hydrostatic pressure gradient into the ciliary process stroma (ultrafiltration).

  2. 2. Plasma-derived ions are taken up across the basolateral surface of the outer pigmented epithelium and move to the non-pigmented cells via gap junctions. They are then transported into the intercellular clefts between the non-pigmented cells (active secretion). Carbonic anhydrase mediates the transport of bicarbonate, which in turn affects sodium ions.

  3. 3. Active transport produces an osmotic gradient across the ciliary epithelium. Water follows ions into the intercellular spaces, allowing diffusion into the posterior chamber (diffusion). Aquaporin water channels aid the transport of fluid.

After secretion into the posterior chamber, aqueous passes around the lens equator and flows through the pupil into the anterior chamber, where it circulates because of convection currents derived from the temperature difference between the cornea and iris (see Figure 8.2). Some of the aqueous flows directly towards the cornea and then flows downwards in the anterior chamber. In pigmentary dispersion, the pigment granules therefore deposit on the central and inferior cornea.

Fig 8.2 Diagram of aqueous fluid dynamics showing normal flow from the ciliary body through from the posterior chamber to the anterior chamber and then the angle

Fig 8.2
Diagram of aqueous fluid dynamics showing normal flow from the ciliary body through from the posterior chamber to the anterior chamber and then the angle

Ultrafiltration and diffusion are passive processes and depend on capillary hydrostatic pressure, oncotic pressure, and IOP. Active secretion does not depend on IOP but instead relies on enzyme systems including the Na+/K+-ATPase pump, ion transport by symports and antiports, calcium- and voltage-gated channels, and carbonic anhydrase. Active secretion is reduced by inhibitors of metabolism, e.g. hypoxia and hypothermia.

Rate of aqueous flow

Aqueous flow has a circadian rhythm, being higher during the morning than at night. Daytime aqueous humour turnover is estimated to be 1.0% to 1.5% of the anterior chamber volume per minute (approximately 2.9 μ‎l/min in a healthy young adult). The anterior chamber has an average volume of 0.25 ml. Turnover declines by about 2.4% every 10 years.

Aqueous outflow

Conventional (trabecular) route

This passive, pressure-sensitive route represents the primary means of outflow. Aqueous passes first through the TM and then into Schlemms canal. The TM is a sieve-like structure at the anterior chamber angle made up of three anatomically distinct portions: the uveal meshwork (innermost), the corneo-scleral meshwork, and the juxtacanalicular or endothelial meshwork (outermost). Transport into Schlemms canal is by transcellular channels in the form of ‘giant vacuoles’ of fluid crossing the inner wall. The outer wall of the canal contains the openings of collector channels, which leave at oblique angles to connect either directly or indirectly with episcleral veins. The TM accounts for 75% of resistance to outflow, with 25% occurring beyond Schlemms canal. The major site of resistance within the TM is believed to be the juxtacanalicular TM.

Alternative (uveoscleral) route

The remaining aqueous outflow occurs across the iris root and the face of the ciliary body, passing between the muscle fibres into the supraciliary and suprachoroidal spaces, where it is drained by the choroidal circulation. This route is not pressure dependent and in young individuals can account for 40% to 50% of outflow. The proportion of aqueous outflow via each route differs by age and disease. Patients with primary open-angle glaucoma have increased resistance to flow through the TM.

IOP

The relationships between IOP, aqueous production (flow), and aqueous outflow is described by the modified Goldmann equation:

where F is the rate of aqueous flow (in healthy young eyes, approximately 2.9 μ‎l/min, decreasing by 2.4% per decade, lower during sleep than during waking hours), C is facility of outflow (in healthy eyes, between 0.1 and 0.4 μ‎l/min/mmHg); Po is IOP, Pe is the episcleral venous pressure (in healthy eyes, between 8 and 10 mmHg) and U is uveoscleral outflow. Episcleral venous pressure is subject to circadian variation and also varies with posture (higher when supine than when standing up).

8.3 Glaucoma pathogenesis

Glaucoma is defined as ‘a disease of the optic nerve with characteristic changes in the optic nerve head, and typical defects in the visual field, with or without raised intraocular pressure’ (UK National Institute of Clinical Excellence (NICE) guidelines). In other words, glaucoma is an optic neuropathy. Patients are not required to have raised IOP to be diagnosed with glaucoma; however, IOP is usually the only modifiable risk factor. Glaucoma may be primary or secondary and associated with an open or closed angle.

The pathogenesis of glaucomatous optic neuropathy is complex and not fully understood but glaucoma is likely to be due to damage to RGC axons at the level of the lamina cribrosa. Integrity of the RGC axon is essential for survival of the cell. If the axon is damaged, disruption of retrograde transport of neurotrophins from the lateral geniculate nucleus and superior colliculus to the cell body, and anterograde transfer of cellular organelles may lead to RGC apoptosis.

A direct mechanical theory and a vascular or ischaemic theory have been proposed as potential causes for axon damage. A recent energy theory proposes astrocyte axon dissociation as the primary mechanism of axon damage. A combination of factors is likely to be responsible.

IOP-related stress and strain

Mechanical displacement of the lamina cribrosa due to pathological levels of IOP may directly damage RGC axons passing through its mesh-like pores. Indirect damage may also occur because of the effects of IOP on glial support cells, including disassociation from axons, and RGC blood and nutrient supply.

Normal IOP may be defined by range within a population; however, whether an IOP is normal for a particular patient is another matter. Two eyes exposed to the same IOP may respond in different ways; that is, some optic nerves are sensitive to relatively low pressures whereas others are resilient to relatively high pressures.

Corneal thickness, hysteresis, hydration, and curvature can affect IOP measurements. IOP is also affected by breath holding, eyelid squeezing, strenuous wind instrument playing, and wearing a tight necktie (all lead to an increase in IOP).

Impaired blood flow and nutrient diffusion

An insufficient blood supply may contribute to glaucomatous retinal ganglion cell damage by reducing oxygen and nutrient delivery to the RGCs, supporting cells, and optic nerve head connective tissues. Impaired blood flow may also increase the susceptibility of the RGC axons to mechanical damage and explain why glaucomatous damage occurs in some eyes at relatively low levels of IOP.

Ocular perfusion pressure

  • The Barbados Eye Study showed a link between glaucoma and low ocular perfusion pressure (OPP).

  • A mean OPP <40 mmHg was associated with a 2.6 relative risk of glaucoma.

  • Low OPP can be due to high IOP or low systemic BP, where mean BP = diastolic BP + 1/3(systolic BPdiastolic BP)L

Low systemic BP

  • Low systemic BP has been associated with an increased risk of glaucoma progression.

  • Progression of primary open-angle glaucoma and normal tension glaucoma has also been associated with nocturnal BP dipping.

  • Dipping is classified as a 10%–20% reduction in mean BP between waking and sleeping; extreme dipping occurs if there is a >20% reduction.

  • Glaucoma has also been associated with systemic vascular disorders such as hypertension and cardiovascular disease.

Vasospasm

  • Vasospastic conditions such as migraine and Raynauds syndrome are associated with glaucoma, possibly because of impaired autoregulation of the blood supply.

  • The Collaborative Normal Tension Glaucoma Study found a significant association between the rate of glaucoma progression and migraines in normal tension glaucoma.

Autoimmune and inflammatory factors

  • Cytokines released by injured RGCs or glial cells may contribute to the death of adjacent cells.

8.4 Optic nerve head assessment in glaucoma

Glaucoma is a specific form of optic neuropathy, and recognition of optic nerve head changes typical of glaucoma is key to diagnosing glaucoma. Raised IOP is of importance but primarily for stratifying risk and does not need to be present to diagnose glaucoma.

Optic nerve and/or RNFL changes are often the first signs of glaucoma. Abnormalities can be difficult to detect but are best seen stereoscopically; therefore, the pupil should be dilated. Use the slit lamp and indirect fundus lenses (e.g. 78 dioptres (D)). Detailed disc drawings should be taken and, at baseline, optic disc imaging is essential. Further images should be taken if any change is noted. Increasingly, optic nerve and RNFL imaging techniques are also used to provide quantitative measurements.

Scheme for optic nerve head examination

It is important to have a system for optic nerve head examination, to ensure signs are not missed. Specifically search for each feature.

Size

Measure the size of the optic disc as the vertical diameter from scleral rim to scleral rim. The normal disc is vertically oval.

Optic discs vary in size, with an average vertical diameter of 1.8 mm. Discs can be categorized as:

  • Small: <1.5 mm

  • Medium: 1.5–2.0 mm

  • Large: >2.0 mm

The size of the normal optic cup depends on the size of the optic disc. Small cups can be glaucomatous in eyes with small discs. The disc diameter can be measured by projecting a narrow, bright beam from the slit lamp, and the height of the beam can adjusted to measure the vertical dimension of the disc as the slit overlies it. A correction factor must be applied depending on the power of the fundus lens used:

  • A 60 D lens has a correction factor of 1.0×

  • A 78 D lens has a correction factor of 1.1×

  • A 90 D lens has a correction factor of 1.3×

Neuroretinal rim

The edge of the neuroretinal rim can be detected as the first contour change at the surface of the optic disc. This contour change corresponds to the first bend in the retinal vessels as they dip into the cup, not to the extent of pallor. Glaucoma is characterized by progressive loss of the neuroretinal rim; this loss is generally greater at the inferior and superior poles than elsewhere. Loss may be diffuse (see Figure 8.3) or localized (see Figure 8.4).

Fig 8.3 Colour fundus photograph showing diffuse thinning of the neuroretinal rim and significant glaucomatous cupping

Fig 8.3
Colour fundus photograph showing diffuse thinning of the neuroretinal rim and significant glaucomatous cupping

Fig 8.4 Colour fundus photograph showing a focal notch of the inferior neuroretinal rim

Fig 8.4
Colour fundus photograph showing a focal notch of the inferior neuroretinal rim

The Werner–Jones ISNT rule determines the normal rim configuration (see Section 8.1). If this rule is not followed, the disc is likely to be glaucomatous, unless there are other abnormal features of the disc that would explain deviation (e.g. tilting).

Tilting of the optic disc produces a gently sloping rim in one sector, and a narrow, sharply defined rim in the opposite sector (see Figure 8.5). A normal optic nerve has a 15° tilt of the inferior pole towards the fovea. If the nerve is very tilted, it may be difficult to assess the neuroretinal rim accurately. Assess the colour of the rim, as pallor increases the likelihood of a non-glaucomatous process.

Fig 8.5 Colour fundus photograph showing a tilted optic nerve head

Fig 8.5
Colour fundus photograph showing a tilted optic nerve head

RNFL

Loss of nerve fibres may initially be detectable as defects in the RNFL. Like rim loss, RNFL loss may be diffuse or localized (see Figure 8.6). The healthy RNFL glistens and has fine striations visible. Localized defects appear as slits or wedge-shaped defects in the usual uniformly reflective sheen of the RNFL. The defects follow the pattern of retinal striations (i.e. they are arcuate) and are best seen at the transition point between normal and abnormal areas within two disc diameters of the disc, under red-free (green) illumination.

Fig 8.6 Colour fundus photograph showing a retinal nerve fibre layer defect as a dark band extending from the optic disc supero-temporally

Fig 8.6
Colour fundus photograph showing a retinal nerve fibre layer defect as a dark band extending from the optic disc supero-temporally

Diffuse defects can be harder to visualize but may be appreciated owing to a difference in the brightness of the RNFL on comparing the two eyes, or on comparing superior and inferior peripapillary RNFLs in the same eye. Vessels running within the RNFL will also become more visible with diffuse thinning.

Peripapillary atrophy

Chorioretinal atrophy surrounding the optic nerve head consists of two zones: an inner beta zone (i.e. beside the optic disc), and an outer alpha zone (i.e. away from optic disc). Alpha-zone atrophy is due to variable irregular hyper- and hypopigmentation of the retinal pigment epithelium (RPE) and is common in normal eyes. Beta-zone atrophy is more important and is correlated with neuroretinal rim loss; it enlarges as glaucoma progresses. In beta atrophy, there is visibility of the sclera and choroidal vessels because of atrophy occurring in the RPE and the choriocapillaris (see Figure 8.7).

Fig 8.7 Colour fundus photograph showing peripapillary atrophy around a glaucomatous optic disc

Fig 8.7
Colour fundus photograph showing peripapillary atrophy around a glaucomatous optic disc

RNFL haemorrhages

Optic disc or RNFL haemorrhages are found in 4%–7% of glaucomatous eyes, most frequently in areas of focal neuroretinal rim loss. They are common in normal tension glaucoma. Haemorrhages can be located either on the optic disc itself, where they appear blot-like, as small splinter haemorrhages, or in the immediate peripapillary area, with a flame-shaped configuration due to their location within the RNFL (see Figure 8.8).

Fig 8.8 Colour fundus photograph showing an optic disc haemorrhage at the superior pole of the disc

Fig 8.8
Colour fundus photograph showing an optic disc haemorrhage at the superior pole of the disc

Haemorrhages may be difficult to see and are best detected after dilatation. Under red-free light, the haemorrhage appears dark. Haemorrhages are most common in the infero- or supero-temporal regions and take 6 weeks to 9 months to clear.

The presence of an optic disc haemorrhage indicates likely glaucoma progression. The site of a haemorrhage should be documented, as it can represent a marker for future focal disc damage and visual field loss.

Other features

Vertical cup/disc ratio

Enlargement of the vertical cup/disc ratio (CDR) is secondary to the loss of RGCs leading to a thinning of the neuroretinal rim. A problem with CDR is that it is highly variable, with a normal range of 0 to 0.85; however, a CDR >0.65 is found in less than 5% of the normal Caucasian population. Whether a CDR is normal depends on the size of the optic disc. Asymmetry between the CDR of fellow eyes usually does not exceed 0.2 (assuming equal refractive status).

Notching

An increase in cup size may occur by concentric enlargement or focal loss of the neuroretinal rim. Focal loss can cause a notch. Notching occurs most frequently inferiorly. A notch may indicate an area of the disc in which circulation has been compromised.

Saucerization

Saucerization is a gentle concavity extending over most of the disc diameter, resulting in indiscernible cup edges.

Pallor

Pallor should be not be confused with cupping. Pallor within the cup and of the rim may indicate a non-glaucomatous cause for the optic neuropathy.

Laminar dot sign

Loss of neuroretinal tissue may expose the underlying pores of the lamina cribrosa.

Nasalization

The central retinal vessels emerge in the centre of the optic disc and initially course nasally. If the nasal rim becomes eroded, the vessels will follow the erosion and become displaced nasally (nasalization).

Bayoneting

In a healthy disc, vessels pass over the sloping rim of the cup to reach the retina. This creates a mild kink or change in direction of the vessel. With loss of the neuroretinal rim, a vessel may pass into a recess below the rim before climbing on to its surface. This creates a double angulation (a z-shaped bend) which looks like a bayonet.

8.5 Glaucoma imaging devices

Optic nerve imaging is useful for the diagnosis of glaucoma and detection of progression.

Optic disc stereophotographs

Stereoscopic photography provides high-resolution images of the optic disc and peripapillary retina, creating a permanent record for comparative purposes. A dilated pupil and clear media are required for quality photographs. The evaluation of glaucomatous progression will be subjective, with both inter- and intra-observer variability, even when the images are viewed by highly trained glaucoma experts. RNFL defects are sometimes more easily detected on photographs than by fundus examination.

Confocal scanning laser ophthalmoscopy

The Heidelberg retinal tomograph (HRT; developed by Heidelberg Engineering) provides quantitative data regarding the topography of the optic nerve head and the peripapillary retina. HRT uses a diode laser with a 670 nm light source to scan the optic nerve head and peripapillary retina. Following the scan, the operator is required to manually draw an outline around the disc. A reference plane is then created 50 μ‎m deep with respect to the temporal edge of the disc. Everything within the disc outline and deeper than the reference plane is considered to be the cup. Everything above the reference plane is considered to be neuroretinal rim. Distances of structures from the reference plane are analysed by computer software to produce three-dimensional reconstructions of the disc and retina.

Moorfield’s regression analysis

HRT provides information regarding neuroretinal rim area, disc area, and cup size. An assessment is made as to whether sectors of the disc are abnormal, and a probability map is generated. The Moorfields regression analysis (MRA) compares the global and sectorial rim areas, adjusted for age and disc size, to a database of normal eyes. Sectors are then classified as normal, borderline, or abnormal (see Figure 8.9).

Fig 8.9 Heidelberg retinal tomograph report for both eyes of a subject with glaucoma
The Moorfields regression analysis results are outside normal limits

Fig 8.9
Heidelberg retinal tomograph report for both eyes of a subject with glaucoma

The Moorfields regression analysis results are outside normal limits

Glaucoma probability score

The glaucoma probability score (GPS) is another automated algorithm that generates a probability score of having glaucoma. The GPS uses information regarding horizontal and vertical RNFL curvature, cup size and depth, and neuroretinal rim steepness. An advantage of the GPS is that it does not need the manually drawn disc margin contour line. The values in the MRA and GPS results are displayed as red crosses when outside normal limits, yellow exclamation points when borderline, and green ticks when within normal limits.

Loss of neuroretinal rim area on HRT has been associated with glaucoma progression. HRT 2, Version 3, includes software that allows longitudinal analysis (topographic change analysis). This version also includes an enlarged race-specific normative database.

Disadvantages

Variation occurs because of the need to manually draw the reference outline around the optic disc. Thickness measurements depend on the position of the reference plane along the z-axis.

Scanning laser polarimetry

The GDx (developed by Carl Zeiss Meditec, Inc.) is a confocal scanning laser polarimeter used to assess the thickness of the peripapillary RNFL. It uses a polarized infrared (780 nm) light source.

RGC axons have birefringent properties because of their arrangement in parallel bundles. When a birefringent tissue reflects polarized light, the light undergoes a phase shift corresponding to the thickness of tissue through which it has passed. The GDx quantifies RNFL thickness by measuring the phase shift (or retardation) of reflected light and then using that value to estimate RNFL thickness. Compensation for other birefringent ocular structures such as the cornea and lens is made. The GDxVCC (for variable corneal compensation) takes account of corneal birefringence. GDxECC (for enhanced corneal compensation) is more advanced than the other two polarimeters and eliminates other artefacts.

The data provided include a TSNIT (thickness in temporal, superior, nasal, inferior, and temporal quadrants) graph, which in normal eyes has a double hump (greater thickness in superior and inferior sectors). The RNFL thickness is classified as being within normal limits, borderline, or outside normal limits. A guided progression analysis is available for comparing serial GDx images. GDxVCC is repeatable to within 4 μ‎m.

Disadvantages

Data from different generations of GDx are not interchangeable. Opacities in the media can create abnormal retardation patterns.

Optical coherence tomography

Optical coherence tomography (OCT) uses low-coherence (near-infrared) interferometry to measure light backscattered from the retinal layers. Light scattered from different layers has different frequencies. The principle is similar to ultrasonography except that light is used rather than sound. Many single A-scans are acquired to provide a cross-sectional image of the retina, from which tissue thickness layers can be measured. The RNFL has particularly high reflectance because of its parallel nerve fibre bundles.

The original form of OCT was time domain OCT (TD-OCT). TD-OCT detects the echo time delay between the sample and a moving reference arm. A new version of OCT, spectral domain OCT (SD-OCT) has a stationary reference arm and collects backscattered light of different frequencies (due to different layers) simultaneously. This method reduces the acquisition time, which leads to fewer movement artefacts and allows resampling, to ensure precise placement of the scan. SD-OCT provides more A-scans and has a better axial resolution (3–6 μ‎m) than TD-OCT does.

Peripapillary RNFL thickness is assessed using a single circular scan that is centred on the optic nerve head and has a diameter of approximately 3.4 mm. The circle scan is unwound and a linear result presented. The optic nerve head itself can be assessed using multiple radial linear scans to provide data on cupping and neuroretinal rim. SD-OCT is able to generate a RNFL thickness map, and thickness values can be averaged for different sectors or globally (see Figure 8.10). Global measurements are more reproducible.

Fig 8.10 Example of an optical coherence tomography report in a patient with advanced glaucoma in both eyes

Fig 8.10
Example of an optical coherence tomography report in a patient with advanced glaucoma in both eyes

The higher resolution of SD-OCT also allows imaging of the ganglion cell complex (GCC) in the inner retina in the macular region. RGC loss is a key pathological feature of glaucoma, so imaging of the GCC is of great interest for the future. Other recent developments include enhanced depth imaging OCT, which allows examination of deeper structures in the optic nerve head, such as the lamina cribrosa.

Disadvantages

One disadvantages of OCT is that it may be less able to detect change in patients with advanced glaucoma, compared to functional tests. Also, OCT is not able to detect disc haemorrhages, so it should not replace clinical examination.

Imaging the angle

Imaging of the anterior chamber drainage angle can be useful in assessing patients with suspected angle closure. It is particularly useful for determining the mechanism of angle closure. At present, the role of imaging is to supplement, not replace, gonioscopy. The drainage angle may be imaged using anterior segment OCT or ultrasound biomicroscopy (UBM).

Anterior segment OCT

Anterior segment OCT uses the scleral spur as the reference point (see Figure 8.11). Look for apposition anterior to the scleral spur to diagnose angle closure. This method has good sensitivity but poor specificity for detecting angle closure, as compared to gonioscopy.

Fig 8.11 Example of anterior segment optical coherence tomography in an eye with an open angle

Fig 8.11
Example of anterior segment optical coherence tomography in an eye with an open angle

Advantages

  • Non-contact procedure (can be done immediately after surgery)

  • Can be done in darkness, avoiding light-induced pupil constriction

  • Can use quantitative tools to assess the angle

Disadvantages

  • Cross-sectional rather than 360° view

  • Not able to assess pigmentation or angle vessels

  • Poor view of structures behind the iris, such as the ciliary body

UBM

UBM is similar to conventional ultrasound imaging. An eyecup holding a coupling medium is used and the patient must be in a supine position.

Advantages

  • Good view of structures behind the iris, such as the ciliary body

  • Not limited to optically transparent tissues (can be done in eyes with opaque corneas)

Disadvantages

  • Direct contact procedure

8.6 Tonometry and pachymetry

Tonometry

Tonometry is the clinical measurement of IOP. Tonometers measure IOP indirectly through the cornea and rely on the principle that, the higher the pressure in a sphere, the greater the force required to indent it. Tonometry may be by contact or non-contact (using a jet of air).

Goldmann applanation tonometry

Goldmann applanation tonometry (GAT) is the current gold standard of tonometry, although its accuracy is affected by corneal properties.

Imbert–Fick principle

GAT is based on the Imbert–Fick principle, which states that the pressure of a sphere equals the force of flattening (F) divided by the surface area of flattening (A), or P = F/A.

The Imbert–Fick principle assumes that the sphere has a constant radius of curvature, is dry, infinitely thin, and that aqueous humour does not move during testing. These assumptions are untrue of the globe. Goldmann took into account tear-film capillary action, which draws the tonometer towards the cornea, and the elastic repulsive force of the cornea. He calculated that, when applanation occurred over a circular area with a diameter of 3.06 mm, these two forces would cancel each other.

GAT consists of a prismatic doubling device in the centre of a cone-shaped, 3.06 mm plastic head (the biprism head). The head is mounted on a metal rod attached to a coiled spring. The spring may be adjusted to change the forwards force of the head. The tonometer is mounted on a slit lamp and aligned so the examiner looks down the barrel of the tip using one eye. Oblique illumination with a cobalt-blue light is used. Fluorescein and topical anaesthesia are instilled. When the biprism head comes into contact with the cornea, two yellow-green semicircles are seen in the image of the tear-film meniscus. The dial, and thus the forwards force in the head, is adjusted until the inner margins of the semicircles just touch, so that the applanation area becomes 3.06 mm in diameter. The semicircles oscillate with each ocular pulse, so the reading is taken when the inner borders meet at the midpoint of the movement. The grams of force applied (as read from the dial) are multiplied by ten to give a reading in millimetres of mercury.

Compensation for corneal astigmatism of more than 3 D is achieved by placing the flattest corneal meridian at 45° to the axis of the biprism head (align the red mark on the prism holder with axis of the minus cylinder). In high or irregular astigmatism, take the average of two measurements: one when the biprism is horizontal, and another with it vertical.

Sources of error with GAT

  • Overestimates of true IOP:

    • Examiner pressing on globe whilst holding lids

    • Wide meniscus (excessive fluorescein or tears)

    • Unequal semicircles due to misalignment

    • Against-the-rule astigmatism

    • Thick or rigid cornea (including corneal scar)

    • Patient squeezing (apprehension or blepharospasm)

    • Valsalva manoeuvre (breath holding)

    • Restrictive clothing around neck (tie, shirt collar)

    • Eccentric gaze (accentuated in restrictive orbital disease)

  • Underestimates of true IOP:

    • Thin meniscus (too little fluorescein or poor tear film)

    • Thin cornea (including previous corneal refractive surgery)

    • Corneal oedema (easier to indent)

    • Ocular ‘massage’ (gonioscopy or repeated measurements)

    • With-the-rule astigmatism

    • Poor or infrequent calibration of instrument

    • Inter-observer variability

Other problems with GAT

  • Infection risk: need strict adherence to hygiene and sterilization protocols

  • Use disposable prisms in known infection (particularly prion protein diseases).

  • Corneal abrasion: possible with inappropriate or repeated measures

Non-contact tonometry

Non-contact tonometry uses the same principles as GAT, but a puff of air is used to flatten the cornea. The force of airflow required to flatten is proportional to IOP. There is no requirement for topical anaesthesia. This technique is less accurate with high IOPs than with low or normal IOPs.

Perkins tonometry

Perkins tonometry is similar to GAT but uses a handheld battery-powered device. The technique is more difficult than GAT is and therefore less accurate; however, it can be used in a vertical or a supine position, so is useful for bed-bound patients and those unable to position on the slit lamp; 59% of readings are within 2 mmHg of GAT. Tonometer heads of different weight (e.g. disposable heads) may be inaccurate.

The Tono-Pen

The Tono-Pen is a battery-powered device held like a pen. A microprocessor within the device is connected to a strain-gauge transducer that measures the force of the central plate, which is 1.02 mm in diameter, as the plate applanates the corneal surface. The tip is covered with a disposable latex sleeve to prevent infection. Several measurements are taken and averaged to provide a digital readout. The Tono-Pen is useful for eyes with distorted or oedematous corneas but tends to overestimate at low IOPs and underestimate at high IOPs; 48% of readings are within 2 mmHg of GAT.

The iCare rebound tonometer

The iCare tonometer is a handheld device with a trigger and a thin, disposable, stainless steel probe with a length of 50 mm. The device is held 4 to 8 mm from the cornea; the probe, repelled by a magnet, bounces off the cornea. The deceleration of the probe is used to calculate the IOP. A series of measurements can be taken rapidly. This tonometer does not require anaesthesia and is particularly useful when GAT may not be possible, such as in young children and in patients who cannot hold their eyelids open for Goldmann tonometry, including some patients with dementia. It is also useful in eyes with an irregular corneal surface; 52% of measurements are within 2 mmHg of GAT.

Factors such as corneal hysteresis (a measurement of the dynamic properties of the cornea) play a role in IOP measurement accuracy. New devices such as dynamic contour tonometry and the ocular response analyser are thought to offer more accurate measures of IOP, independent of corneal thickness.

Dynamic contour tonometry

Dynamic contour tonometry uses a slit-lamp-mounted contact tonometer designed to compensate for the effects of the cornea on tonometry (see Figure 8.12): The effects of the cornea are reduced, as the tonometer head is contour matched to the cornea. IOP is recorded using a miniature pressure sensor; 100 IOP readings are taken every second over a 5–8-second period. The ocular pulse amplitude is also measured; 49% of measurements are within 2 mmHg of GAT. DCT tends to give higher readings than GAT does at low IOPs.

Fig 8.12 The dynamic contour tonometer, mounted to the slit lamp

Fig 8.12
The dynamic contour tonometer, mounted to the slit lamp

Ocular response analyser

The ocular response analyser is a non-contact air impulse tonometer. It provides two applanation pressures with each measurement. An air impulse causes the cornea to move in until applanation. The cornea then becomes slightly concave, before moving outward, where there is a second applanation. The difference between the inward and outward applanation pressure depends on the viscoelastic properties of the cornea (corneal hysteresis). A corneal compensated IOP measurement is thus provided which is thought to be less influenced by corneal properties than ones provided by GAT; 46% of measurements are repeatable within 2 mmHg of GAT.

Pachymetry

Pachymetry is used to measure central corneal thickness (CCT). ‘The measurement of CCT aids in the interpretation of IOP measurement results and the stratification of patient risk for glaucoma’ (American Academy of Ophthalmologists’ Glaucoma Guidelines, 2005). The mean CCT is 550 μ‎m, whereas the peripheral cornea can be up to 1 mm thick.

The Ocular Hypertension Treatment Study showed CCT to be a powerful predictor for the development of glaucoma (eyes with CCT <555 μ‎m were at three times greater risk of developing glaucoma than those with a CCT >588 μ‎m). Part of this finding is attributed to the inaccuracies induced in IOP measurement because of varying CCT. IOP tends to be underestimated in eyes with thin corneas because of increased deformability, whereas IOP is overestimated in eyes with thick corneas. In addition, a thin cornea may reflect a thin eye and weak optic nerve head tissues.

Pachymetry can be performed using ultrasonic or optical techniques. Although there are slight differences between the two methods of measurement, for the purposes of clinical practice, they are equally efficacious.

The most user-friendly and thus most commonly used method is that of ultrasound. This method has a range of 280–1000 μ‎m, and a clinical accuracy of ±5 μ‎m. Ultrasound energy is emitted from the probe tip, and some of the energy is reflected back towards the probe in the form of an echo at the first tissue interface it reaches (i.e. endothelium to aqueous humour). Measurement data are then calculated on the time it takes for the echo to travel back to the probe.

Method

  • The eye is anaesthetized with drop of local anaesthetic.

  • The patient is asked to look straight ahead.

  • The probe is touched lightly against the central cornea, ensuring perpendicular alignment throughout testing (see Figure 8.13).

Fig 8.13 Use of a pachymeter
The eye is anaesthetized and the probe placed onto the central cornea

Fig 8.13
Use of a pachymeter

The eye is anaesthetized and the probe placed onto the central cornea

Several measurements are taken to provide an average. The accuracy of ultrasonic pachymetry is dependent upon the perpendicularity of the probe to the cornea, whilst the reproducibility relies on probe placement at the exact corneal centre.

8.7 Gonioscopy

Examination of the anterior chamber or the iridocorneal angle is essential in all patients with suspected glaucoma. It allows one to differentiate between open- and closed-angle glaucomas and to identify pathological changes. The drainage angle cannot be visualized directly because of the internal reflection of light by the peripheral cornea. Gonioscopy is a technique that allows visualization of the angle by replacing the tear-film–air interface with a tear-film–goniolens interface.

Limbal chamber depth

Before gonioscopy, assess limbal chamber depth (LCD), as follows:

  • Using the slit lamp, offset the illumination column from the axis of the microscope by 60°.

  • Direct the brightest, narrowest beam of vertical light at the limbal cornea, at the most peripheral part that permits a clear view of the peripheral iris.

  • The resulting slit image of the cornea is used as a reference for the anterior chamber depth (represented by the optically empty gap between the posterior corneal surface and the iris).

  • LCD is expressed as a percentage or fraction of the thickness of the cornea (Van Hericks grade).

Van Hericks grades

  • Grade 1: LCD < ¼ corneal thickness

  • Grade 2: LCD = ¼ corneal thickness (see Figure 8.14)

  • Grade 3: LCD = ¼ to ½ corneal thickness

  • Grade 4: LCD ≥ the full thickness of the peripheral cornea (see Figure 8.15)

Fig 8.14 Assessment of limbal chamber depth
The clear gap behind the cornea is approximately one-quarter the width of the cornea (Van Hericks Grade 2), indicating a potentially occludable angle

Fig 8.14
Assessment of limbal chamber depth

The clear gap behind the cornea is approximately one-quarter the width of the cornea (Van Hericks Grade 2), indicating a potentially occludable angle

Fig 8.15 Assessment of limbal chamber depth
The clear gap behind the cornea is almost the width of the clear cornea (Van Hericks Grade 4)

Fig 8.15
Assessment of limbal chamber depth

The clear gap behind the cornea is almost the width of the clear cornea (Van Hericks Grade 4)

There is good correlation between LCD and angle grading by gonioscopy; however, LCD is not a substitute for gonioscopy. LCD ≤ 25% has a sensitivity of >95% and a specificity of 66% for detecting gonioscopically occludable angles.

Direct gonioscopy

Direct goniolenses or gonioprisms are used to allow direct visualization of the angle. There are several types (e.g. Koeppe (360°), Barkan (120°), and Swan–Jacob lenses) and their main use is in the direct visualization of the angle in the operating room for surgical procedures (e.g. goniotomy, or synechiolysis). The technique requires high magnification with illuminated loupes, a portable slit lamp or operating microscope, and the patient to be lying supine. A four-mirror direct gonioscope (Khaw) can also be used for standard slit lamp examination and for laser treatment of the angle.

Indirect gonioscopy

Indirect goniolenses or goniomirrors are used to provide a mirror image of the opposite angle and are used in conjunction with a slit lamp. There are two main types: Goldmann lenses and Zeiss lenses (see Figure 8.16).

Fig 8.16 Examples of two gonioscopy lenses

Fig 8.16
Examples of two gonioscopy lenses

Goldmann lenses

  • Single- or double-mirror lens with a contact-surface diameter of 12 mm (greater than the surface area of the cornea)

  • The concave surface of the lens is steeper than that of the cornea, so a coupling agent is required to bridge the gap (this agent may cause temporary blurring of vision afterwards).

  • Provides excellent view of angle structures and stabilizes the globe

  • If an iris convexity obscures the view, one can still see ‘over the hill’ if the patient looks in the direction of the mirror. Take care not to indent the cornea, as this will result in iatrogenic opening of the angle.

Method

  • Instil topical anaesthetic (e.g. benoxinate).

  • Ensure lens is disinfected with appropriate solution.

  • Instil coupling agent (e.g. Viscotears or methylcellulose) in lens concavity.

  • Needs to be performed in a dark room, as light causes pupillary constriction and may lead to a falsely open angle. Also avoid shining the slit lamp beam across the pupil.

  • Hold down lower lid and ask patient to look up.

  • Insert lens, with the mirror at the 12 o’clock position and ask the patient to look straight ahead.

  • Use a 2 mm slit beam, with the axis perpendicular to the mirror.

  • Rotate lens clockwise until all quadrants are viewed.

Zeiss lenses

  • Four-mirror lens on a handle, with a contact-surface diameter of 9 mm (less than the corneal diameter)

  • The curvature of the lens is flatter than the cornea is, so no coupling agent is required.

  • Can be used for indentation gonioscopy; axial pressure on the central cornea by lens will cause flattening of the anterior chamber and force aqueous humour into the angle, thus opening it if possible (allowing distinction between appositional and synaechial closure and identification of plateau)

  • Entire circumference of angle visualized with minimal rotation

Method

  • As for ‘Zeiss lenses’, but tear film is adequate as a coupling agent, and the lens is placed directly on the centre of the cornea (see Figure 8.17)

  • Minimal or no rotation is required.

  • It is important not to press too firmly until indentation is desired, as pressing too firmly will artificially open the angle. The aim is to hold the lens in gentle apposition with the cornea so that the contact meniscus is occasionally lost. If corneal tension lines are seen, too much force is being applied. Indentation is achieved by anterior–posterior force.

Fig 8.17 Gonioscopy using a Zeiss-type lens

Fig 8.17
Gonioscopy using a Zeiss-type lens

Identification of angle structures

The key to gonioscopy is the corneal wedge (see Figure 8.18). The wedge is an image created by a thin slit lamp beam, offset at 15°–45°, and viewed through the goniolens. The beam creates two reflections forming a wedge shape. The apex of the corneal wedge is used to locate Schwalbes line as the location where the two reflections meet. Identification of the corneal wedge helps avoid mistaking secondary pigmented lines for the TM. There are four main structures to examine, which can be remembered via the mnemonic ‘S-T-S-C’:

Fig 8.18 The corneal wedge light reflex in an eye with a heavily pigmented angle

Fig 8.18
The corneal wedge light reflex in an eye with a heavily pigmented angle

S: Schwalbes line

  • Schwalbes line is the most anterior angle structure and represents the peripheral termination of Descemets membrane and the anterior limit of the TM.

  • Circumferential whitish, glistening ridge, occasionally pigmented

T: Trabecular Meshwork

  • Extends from Schwalbes line to the scleral spur with a ‘ground glass’ appearance. The anterior portion of the TM is non-pigmented.

  • The pigmented posterior functional portion adjacent to scleral spur is grey-blue. Pigmentation increases with age and is most marked inferiorly.

  • Increased pigmentation may be evident in pigment dispersion syndrome or pseudoexfoliation.

S: Scleral spur

  • Narrow whitish band posterior to the trabeculum

  • Represents the most anterior projection of the sclera and is the site of attachment of the ciliary body longitudinal muscle

C: Ciliary body

  • Brown-grey circumferential band

  • The root of the iris inserts into the anterior portion of the ciliary body.

  • The width of the ciliary body varies depending on iris insertion: it is narrow in hyperopes and wide in myopes.

Other structures

Schlemms canal

  • Occasionally seen as a slightly darker line deep with respect to the posterior trabeculum

  • Blood seen in canal, with raised episcleral venous pressure (compression by Goldmann goniolens or pathological process)

Iris processes

  • Small extensions of the iris inserting at level of the scleral spur

  • Present in one-third of normal eyes; does not draw the iris up in the way that peripheral anterior synechiae (PAS) do

Blood vessels

  • Form a radial pattern at the base of the angle recess and, as a general rule, do not cross the scleral spur

  • Pathological vessels follow a random pattern, beginning as fine lacy fronds, and are later accompanied by a fibrous ‘scaffold’.

Angle grading

Spaeth grading system

In this system, three features are assessed:

  • Iris insertion: the system for grading iris insertion can be remembered via the mnemonic ‘ABCDE’ (an insertion anterior to a C grade is pathological):

    • A: Anterior to Schwalbes line

    • B: Behind Schwalbes line

    • C: sCleral spur visible

    • D: Deep; ciliary body visible

    • E: Extremely deep (>1 mm of the ciliary body visible)

  • Anterior chamber angle

    • Estimate the angle width in degrees between two tangents; one drawn from the pigmented TM along the posterior surface of cornea, and another from the pigmented TM along the peripheral iris.

    • If the pigmented TM is not visible, the angle is 0°.

  • Curvature of the iris; assessed as follows:

    • b: Bowing anteriorly

    • p: Plateau configuration (sudden steep rise after insertion before the iris flattens)

    • f: Flat

    • c: Concave posterior bowing

    • The features can be combined and abbreviated, e.g. D30p for a deep, 30° angle with a plateau configuration.

Shaffer grading system

The angle is graded 0–4 according to the most posterior angle structure visualized (see Table 8.1). The amount of trabecular pigmentation should also be noted. An occludable angle is defined as an angle in which there are two or more quadrants (≥180°) of iridotrabecular contact (ITC). Indentation gonioscopy should be used to determine whether angle closure is due to apposition or PAS.

Table 8.1 The Shaffer grading system

Grade

Angle size

Angle structure seen

Angle description

4

35–45°

Ciliary body

Wide open

3

20–35°

Scleral spur

Open

2

20°

Posterior pigmented TM

Moderately narrow

1

10°

Schwalbe’s line

Very narrow

0

No structures visible

Closed

TM, trabecular meshwork.

Reprinted from American Journal of Ophthalmology, 68, 4, Van Herick et al., ‘Estimation of Width of Angle of Anterior Chamber Incidence and Significance of the Narrow Angle’, pp. 626–629. Copyright (1969) with permission from Elsevier

8.8 Perimetry I

Perimetry is a psychophysical test to evaluate a patient’s visual field. This test is an essential part of glaucoma management, as loss of visual function reduces quality of life. Glaucomatous RGC damage leads to specific patterns of field loss. Visual field defects may occur before detectable structural defects or vice versa. Serial field tests should be used to assess for progression. Perimetry is also valuable in the identification and monitoring of certain neurological diseases.

The visual field is described as ‘an island of vision surrounded by a sea of darkness’. This island is depicted as a hill with maximum height at fixation, owing to the high density of photoreceptors at the fovea. Visual acuity decreases towards the periphery in a steep fashion nasally and more gradually temporally. There is a ‘blind spot’ 10°–20° temporal to fixation; this spot corresponds to the optic nerve head. The normal visual field extends 60° superiorly, 60° nasally, 80° inferiorly, and 90° temporally.

An overall reduction in field sensitivity (e.g. cataract) will flatten the hill. A localized defect is known as a scotoma, which can be ‘absolute’ (total loss of vision) or ‘relative’ (area of partial visual loss with reduced sensitivity).

Kinetic perimetry

Kinetic perimetry can be performed by simple confrontation, a tangent (Bjerrum) screen, Lister perimeter, or Goldmann perimeter. It provides a two-dimensional measure of the boundary of the hill of vision. A stimulus of fixed size and intensity is steadily moved from a non-seeing to a seeing area of the field along set meridians at 15° intervals. The points at which the stimulus is perceived are plotted on a chart and joined by a line to form isoptres. Using stimuli of different intensities will provide a contour map of the visual field.

Goldmann perimeter

The Goldmann perimeter is the most commonly used kinetic perimeter. It is useful for patients unable to perform reliable automated perimetry, for low visual acuity, and if a neurological defect is suspected. The patient sits one side of the bowl and presses a button when a stimulus is seen; the examiner sits at the other side to present targets and record responses.

  • Roman numerals 0–V represent increasing target size.

  • Arabic numerals 1–4 represent increasing light intensity.

  • Lowercase letters represent the use of filters (a = darkest; e = brightest).

Advantages

The test can be carried out at any speed. The examiner can assess patient responses and adapt to them.

Disadvantages

Small scotomas may be missed between isoptres. Results depend on the skill of the examiner. No statistical analysis is made. This test is not suitable for the detection of early glaucomatous defects.

Static perimetry

Automated static perimetry uses a machine with preset programs, for example Henson, Octopus, and Humphrey perimeters. It provides a three-dimensional measure of the vertical boundaries of the visual field. The size and location of the target are constant but a varying luminance of the target is used to determine ‘threshold’ retinal sensitivity at different locations of the field.

Standard automated perimetry (SAP) is static computerized threshold perimetry with a white-on-white stimulus. The Humphrey perimeter is the most frequently used analyser in the United Kingdom. It consists of a hemispherical bowl onto which the target is projected. The patient presses a button when the target is seen. A background luminance of 31.5 apostilb (asb) is used. The examiner can choose testing strategies, including suprathreshold and full-threshold tests.

Suprathreshold testing

Suprathreshold testing is mainly used for screening. Points of light at luminance levels 2–6 dB above the expected normal threshold values are presented at various locations in the visual field. Missed targets will reflect areas of decreased sensitivity that can be further analysed if required. The Humphrey analyser can be used to perform 120-point screening, in which a positive test is defined by a total of 17 missed points, or 8 missed points in any one quadrant.

Threshold testing

Threshold testing is used for more detailed assessment. Threshold luminance values are plotted and compared with age-matched normal values. The Humphrey analyser increases the intensity of its stimulus in 4 dB steps until a threshold is crossed. The threshold is then rechecked by decreasing the intensity by 2 dB steps. Testing may be of the central 10°, 24°, or 30°.

Full-threshold 30–2

  • Tests 76 points (6° apart) in the central 30° of the field

  • Long and laborious test

Full-threshold 24–2

  • Tests 54 points (6° apart) in the central 24° of the field

  • Cuts test time by one-fifth

  • Gold standard for monitoring glaucoma

Full-threshold 10–2

  • Tests 68 points (2° apart) in the central 10° of the field

  • Used in advanced glaucoma where fixation is threatened

The Swedish Interactive Thresholding Algorithm (SITA) Standard or the SITA Fast programs have generally replaced full-threshold testing.

SITA Standard

  • Uses computerized algorithms based upon a normative database

  • Utilizes threshold values of adjacent points to determine starting points, thus saving time by asking fewer ‘questions’

SITA Fast

  • Same method as the SITA Standard but less scrutiny at each point

  • Faster but less reliable than the standard test

All automated test procedures have a significant learning curve that should be taken into account. Often three to four consecutive tests are required before reliable fields are obtained.

Esterman visual field testing

An Esterman chart/program using static perimetry is part of the UK’s DVLA visual standards for driving. The Group 1 (ordinary licence) standard specifies a field of at least 120° on the horizontal; the field is measured using a white target equivalent to the Goldmann III4e setting. In addition, there should be no significant defect in the binocular field which encroaches within 20° of fixation above or below the meridian. Acceptable central loss includes scattered single missed points or a single cluster of up to three contiguous points. Those who have been driving with static defects and non-progressive eye conditions for many years can be considered on an individual basis. The Group 2 (vocational licence) standard requires a ‘normal binocular visual field’ with no provision for exceptional cases.

Humphrey analyser displays

Numerical

  • Gives a threshold (in decibels) for each point

  • Figures in parentheses for the same point are checked a second time.

Greyscale

  • Decreasing sensitivity represented by darker tones

  • Useful for examining the gross shape of the field defect

Total deviation

  • Represents the deviation of a patient’s result from age-matched controls

  • Upper numerical and lower greyscale displays

Pattern deviation

  • Total deviation adjusted for generalized depression in the overall field

  • Can correct for diffuse loss such as that induced by the presence of cataract

  • Upper numerical and lower greyscale displays

Probability values

  • Probability values (represented as p) indicate the significance of defects.

  • Refers to the probability that the sensitivity is normal

  • Shown as <5%, <2%, <1%, and <0.5%

Humphrey analyser reliability indices

Fixation losses

  • Stimuli are presented within the blind spot.

  • If the losses are seen by the patient, he/she is clearly not fixating correctly.

  • If losses exceed 20%–30%, reliability should be questioned.

False positives

  • ‘Trigger-happy’ patients who press the button with no stimulus present

  • Greyscale printout is abnormally pale

  • Should be <10% for a reliable test

False negatives

  • Test points of known sensitivity are rechecked with a brighter stimulus.

  • If not seen by patient, may be due to inattention or fatigue

  • A greyscale printout with a high number of false negatives has a cloverleaf pattern.

  • Should be <20% for a reliable test

Global indices

Mean deviation

  • Mean elevation or depression of the field compared with age-corrected normal

  • May be due to overall defect or localized loss

Visual field index

  • Similar to the mean deviation but expressed as a percentage and centrally weighted

  • The visual field index (VFI) takes into account cataract.

Glaucoma hemifield test

  • Assesses asymmetry between the top and bottom halves of the field (one hemifield tends to be damaged first in glaucoma)

  • The results are graded as being outside normal limits, borderline, or within normal limits.

Other indices include the pattern standard deviation, which is a measure of focal loss or variability within the field compared to an age-corrected normal, and short-term fluctuation, which is a test of intra-test consistency where ten preselected points are tested twice.

Sources of error in perimetry

Poor reliability or performance by patient

  • Check reliability indices.

Incorrect date of birth

  • Threshold testing takes patient age into account.

Miosis

  • Apparent loss of peripheral field: dilate if <3 mm

Media opacities

  • Overall depression of whole field: corrected by pattern standard deviation plot

Uncorrected refractive error

  • Overall depression, particularly central sensitivity

  • Error greater than 1 D cylinder uncorrected may cause peripheral scotoma.

  • Testing should be performed with near-vision correction after the age of 40 or in aphakes/pseudophakes.

Spectacles

  • Can cause rim artefacts (concentric scotoma)

Ptosis/blepharochalasis

  • Superior field defects (tape lids up during test)

Facial anatomy

  • A large nose or protruding supraorbital margins may cause pseudodefects.

Visual field practicalities

  • Watch for a ‘learning effect’.

  • A visual field defect should only be considered real after repeat testing.

  • Disc features should match the visual field defects.

  • Other causes of visual field defects should be ruled out, e.g. chorioretinal lesions and tilted discs.

8.9 Perimetry II

Other perimetry devices

Short-wavelength automated perimetry

Short-wavelength automated perimetry (SWAP) was developed with the hope that field defects might be detected earlier than with SAP (e.g. the Humphrey visual field test), but this expectation has not been confirmed. SWAP uses static threshold testing with a large blue stimulus against a bright yellow background. The theory is that the blue visual pathways are preferentially damaged in glaucoma. Blue pathways also have less redundancy than other pathways and thus any glaucomatous loss of blue-pathway nerve fibres manifests as a visual field defect early in the condition. SWAP is sensitive but is less specific than SAP. SWAP has greater short-term and long-term fluctuation than SAP does, making detection of progression difficult. SWAP also takes longer and is affected more significantly by media opacities, compared to SAP.

Frequency-doubling perimetry

Frequency-doubling technology measures the function of the magnocellular pathway, which includes a subset of RGCs (parasol RGCs, which have large dendritic trees and cell bodies) that detect motion and which are lost early in glaucoma. Testing is performed by rapid reversal of a grating of low spatial frequency (narrow black and white bars) at a high temporal frequency (25 flickers per second) to create a doubling-frequency illusion. The contrast of the stimulus is varied during the test, and the patient presses a button when the flickering stimulus is detected. The perimeter is a compact and portable unit, screening takes less than 1 minute per eye, and the technique has good sensitivity and specificity.

Glaucoma field defects

Diagnostic criteria for glaucomatous visual field defects (European Glaucoma Society Guidelines)

In the absence of retinal or neurological disease affecting the visual field, visual field loss is considered significant when:

  1. 1. An abnormal glaucoma hemifield test is confirmed on two consecutive tests.

  2. 2. Three abnormal points are confirmed on two consecutive tests, with p <5% probability of being normal, with point one having p <1%, and all being not contiguous with the blind spot.

  3. 3. Corrected pattern standard deviation is less than 5% if the visual field is otherwise normal, as confirmed on two consecutive tests.

Any defect or suspected defect must be confirmed by repeated testing.

Typical glaucomatous field defects

Arcuate defect

Axons from ganglion cells temporal to the optic nerve follow an arcuate course. Damage to these axons results in an arcuate field defect (see Figure 8.19). Axons in the superior and inferior retina are separated by the horizontal raphe, a line intersecting the fovea and optic nerve. Ganglion cells superior to the raphe arc superiorly and those inferior to it arc inferiorly.

Fig 8.19 A Humphrey visual field (24–2) printout showing a typical inferior arcuate visual field defect

Fig 8.19
A Humphrey visual field (24–2) printout showing a typical inferior arcuate visual field defect

Nasal step

A nasal step is a nasal defect due to a peripheral temporal lesion that respects the horizontal midline, again because of the horizontal raphe (see Figure 8.20). Nasal step may be superior or inferior.

Fig 8.20 A Humphrey visual field (24–2) printout showing a typical nasal step visual field defect

Fig 8.20
A Humphrey visual field (24–2) printout showing a typical nasal step visual field defect

Temporal wedge defect

Axons from ganglion cells in the nasal fundus travel directly to the optic. Damage to this axon group produces a wedge-type visual field defect.

Paracentral defect

Although paracentral defects may appear small, they are serious and vision-threatening due to their proximity to fixation (see Figure 8.21). Most commonly found supero-nasally, they tend to respect the horizontal raphe. Superior and inferior defects may thus not be aligned. Paracentral defects can coalesce to form arcuate defects.

Fig 8.21 A Humphrey visual field (24–2) printout showing a dense paracentral scotoma

Fig 8.21
A Humphrey visual field (24–2) printout showing a dense paracentral scotoma

As glaucoma progresses, multiple defects can present which enlarge and deepen with time. End-stage defects are characterized by a small remaining island of central vision with an accompanying isolated patch of temporal field. Typically central vision is preserved until late (see Figure 8.22); however, paracentral defects can develop early in disease, particularly in normal tension glaucoma.

Fig 8.22 A Humphrey visual field (24–2) printout showing end-stage glaucoma
Such patients should be assessed using a 10–2 program

Fig 8.22
A Humphrey visual field (24–2) printout showing end-stage glaucoma

Such patients should be assessed using a 10–2 program

Glaucoma severity staging

Visual fields are often used to stage glaucoma. A classification based on that of Hodapp is:

  • Early glaucoma: mean deviation <−6 dB and no points in the central 5°, with <15 dB sensitivity

  • Moderate glaucoma: mean deviation < −12 dB, with no point in the central 5° with 0 dB sensitivity and only one hemifield with a sensitivity <15 dB within the central 5°

  • Severe glaucoma: mean deviation worse than that for moderate glaucoma

Detecting progression

Progression can be examined via event-based analysis (determines whether a specific visual field has changed from a previous visual field by an amount greater than that expected owing to test–test variability) or a trend-based analysis (determines the rate of change).

A simple global trend analysis might consist of plotting the mean deviation or VFI value of an eye over time. This analysis can help predict whether progression is likely to lead to loss of vision during a patient’s life (see Figure 8.23).

Fig 8.23 An example of trend analysis of the visual field index over time (left), and an example of event analysis using the Glaucoma Progression Analysis program (right)

Fig 8.23
An example of trend analysis of the visual field index over time (left), and an example of event analysis using the Glaucoma Progression Analysis program (right)

The Glaucoma Progression Analysis program compares pattern deviation values to determine if progression has occurred (see Figure 8.23). At least three SAP tests are needed. In the graphical output, a square means the point has not worsened, an open triangle indicates the point has worsened on one visit, a half-filled triangle indicates that the point has worsened on two consecutive visits, and a filled triangle indicates that the point has worsened on three consecutive visits.

The Progressor program performs a trend-based analysis using linear regression of the threshold values from each test point. Results are presented for each test location by a series of bars representing different SAP test dates (see Figure 8.24). A short bar indicates a near-normal sensitivity, and a long bar indicates an abnormally low sensitivity. The significance of change is colour coded, with hot colours (white, red) indicating significant change, and grey meaning no change.

Fig 8.24 Example of progression in a right eye
The Progressor software shows hot colours in the progressing points

Fig 8.24
Example of progression in a right eye

The Progressor software shows hot colours in the progressing points

8.10 Ocular hypertension

Ocular hypertension (OHT) is a condition characterized by consistently raised IOP and with anatomically open angles in which the optic nerve and visual field show no signs of glaucomatous damage.

Prevalence

Population studies show that IOP has a normal distribution with the curve skewed to the right, as there are more normal people with an IOP above the mean pressure of 16 mmHg than there are with an IOP below it. The statistical definition of the upper limit for ‘normal’ IOP is 21 mmHg, which is two standard deviations above the mean value. An IOP >21 mmHg is used as the cut-off for the definition of OHT: 4%–10% of the population over 40 years of age will have an IOP >21 mmHg but no detectable signs of glaucoma.

Risk factors

  • Increased age

  • Female

  • Ethnic origin: those of black African or Afro-Caribbean origin are more at risk than those of other ethnic origins are

  • Systemic hypertension

  • Corticosteroid use: oral or inhaled

  • Diabetes mellitus

  • Positive family history of glaucoma

Clinical evaluation

History

  • Asymptomatic

  • Family history of glaucoma

Examination

  • Applanation tonometry

  • Gonioscopy

  • Pachymetry

  • Stereoscopic slit lamp optic disc evaluation

  • Visual field assessment

  • Baseline optic disc imaging

Management

OHT treatment is indicated only in those individuals recognized to be at increased risk of conversion to open-angle glaucoma. The Ocular Hypertension Treatment Study trial from 2002 provides useful information regarding risk. This study was a multicentre randomized controlled trial in which patients with OHT were assigned to either observation or topical medications (IOP needed to be lowered 20% from baseline). The probability of developing glaucoma over 5 years was halved by treatment, from 9.5% in the observed group to 4.4% in the treated group. The conclusion was that treatment should be considered for individuals with OHT who are at moderate-to-high risk.

The challenge is to assess the risk of glaucomatous damage for a particular individual, at a particular IOP, and in a particular eye.

Risk factors for conversion to glaucoma

Ocular risk factors

  • High presenting IOP

  • Large vertical CDR

  • CDR asymmetry >0.2

  • Disc haemorrhage

  • RNFL defect

  • Thin central corneal thickness: in the Ocular Hypertension Treatment Study, those with a CCT <555 μ‎m were three times more likely to develop glaucoma than those with thicker corneas

Systemic risk factors

  • Age

  • Family history

  • Black African or Afro-Caribbean origin

The UK NICE guidance on OHT recommends:

  • Start treatment when IOP is >32 mmHg, no matter the CCT.

  • If the CCT is >590 μ‎m, treat only if the IOP is >32 mmHg.

  • If the CCT is 555–90 μ‎m, treat if the IOP is >25 mmHg, but only until the age of 60.

  • If the CCT is <555 μ‎m, there should be a low threshold for treatment in patients younger than 60; for patients over 60, the threshold should be slightly higher than that for patients under 60.

Ultimately the decision to treat is an individual one for the clinician and patient, and the above is only a guide. The decision to treat must take into account the risk/benefit ratio of treatment and weigh the side effects of medication and the individual’s life expectancy with the probability of functional visual loss. An IOP of >32 mmHg may be treated in an effort to reduce the risk of central retinal vein occlusion, especially in a patient with other cardiovascular risk factors predisposing to central retinal vein occlusion (CRVO) or in whom CRVO has already occurred in the fellow eye.

Treatment is usually with topical ocular hypertensives such as prostaglandin analogues or beta blockers. The aim is to lower the IOP to a safe level for the individual patient; one would expect at least a 20% reduction.

Follow-up

After the initial visit, if medication has been commenced, a 1–4 month review is recommended to assess the response to treatment. Depending on the risk factors present, follow-up is then normally performed every 6–12 months. After several visits, a patient with mild OHT but with no signs of conversion to glaucoma may be able to be discharged to the community for optometric follow-up on a 1–2 yearly basis. Increasingly, low-risk patients are managed in shared care with optometrists, either in hospital or in the community.

Prognosis

Although the Ocular Hypertension Treatment Study found that 9.5% of untreated individuals with OHT and an IOP of 24 mmHg or more convert to glaucoma over a 5-year period, the individual risk of conversion depends on the presence or absence of the risk factors (see ‘Risk factors for conversion to glaucoma’).

8.11 Primary open-angle glaucoma

Primary open-angle glaucoma is a progressive, chronic optic neuropathy with characteristic structural changes to the optic nerve head and RNFL. Patients develop reproducible visual field defects, which are often, but not always, consistent with the extent of RNFL damage. Typical visual field defects include a nasal step or an arcuate or paracentral defect. Gonioscopy shows a macroscopically normal and open drainage angle and there is no identifiable secondary cause.

Elevated IOP is not included in the definition of primary open-angle glaucoma as the disease may occur when the IOP is within the normal population-based range (see Section 8.14). The susceptibility of the optic nerve to damage varies among patients and at different stages of disease.

Eyes may be labelled ‘glaucoma suspect’ if they have optic disc appearances suspicious of glaucoma but without evidence of progressive changes, and normal visual fields.

Prevalence

Primary open-angle glaucoma is the most prevalent of all the glaucomas and is the third leading cause of blindness worldwide. It occurs in approximately 2% of the population over the age of 40, increasing with age to over 4% of those over 80. The incidence is similar in males and females.

Clinical evaluation

History

  • Asymptomatic until there is significant loss of the visual field, especially as early visual field loss tends to involve the nasal field, which overlaps with the fellow eye

  • Damage results in negative scotomas.

  • The patient may have difficulty in moving from bright to dark rooms and in judging steps and kerbs. Inability to deal with contrast, particularly rapidly changing contrast, may become a major issue.

Risk factors for the development of primary open-angle glaucoma

  • Factors increasing risk of conversion of OHT to glaucoma (see Section 8.10)

  • Positive family history in a first-degree relative: risk is doubled for a parent but quadrupled for a sibling

  • Myopia

  • Diabetes mellitus

  • Risk rises continuously with increasing IOP

  • Also enquire about other risk factors such as systemic hypotension, anaemia, and vasospastic disorders (migraine, Raynauds syndrome).

The inheritance of primary open-angle glaucoma is multifactorial. Relatives of patients with primary open-angle glaucoma have a 22% risk of developing glaucoma, compared to 2%–3% of controls. The myocillin gene on Chromosome 1q was the first gene associated with glaucoma. Myocillin, which is also known as the TM-inducible glucocorticoid response (TIGR) protein, is found in the TM but its role is unknown. The presence of mutated myocillin may increase the vulnerability of the TM to cellular insults. The discovered genes predisposing to glaucoma only account for about 5% of cases of primary open-angle glaucoma.

Risk factors for blindness in primary open-angle glaucoma

  • Advanced disease at presentation

  • Suboptimal IOP control

  • Black African or Afro-Caribbean race

  • Low socio-economic status

Examination

  • Visual acuity

  • GAT: reveals a raised IOP, usually in the region of 24–32 mmHg. There may be fluctuations in IOP (90% of patients have diurnal variations up to 5 mmHg).

  • CCT

  • Gonioscopy: open angle with normal appearance is a key feature in making the diagnosis

  • Blood pressure

  • Stereoscopic dilated optic disc examination

  • SAP

Screening

Screening should be routinely performed for patients over the age of 40 who have first-degree relatives with primary open-angle glaucoma. Free eye tests on the UK National Health Service are available for this group and for all individuals over 60. If IOP is normal, screening should occur every 2 years until age 50, then annually thereafter. Screening should begin earlier if a family member developed glaucoma at a young age.

Management

The aim of treatment in primary open-angle glaucoma is to preserve visual function. This aim is achieved by controlling the IOP whilst minimizing any adverse effects of treatment. It is important to realize that primary open-angle glaucoma cannot be cured but that control of IOP can slow progression. Large randomized control trials have shown the benefit of lowering IOP; some of these are summarized in Section 8.27.

In most cases, medical treatment is used as the first resort and will often involve a prostaglandin analogue. Additional medications may be added if needed. Surgery may be considered as a first-line treatment if advanced damage is present at presentation. Laser treatment (e.g. selective laser trabeculoplasty (SLT)) may also be considered as a first-line option, particularly in those with early disease, ocular surface disease, or in those who find instilling eye drops difficult. Specific pharmacological and surgical management options are discussed in later chapters.

Target IOP

It is useful to set a target pressure when initiating treatment. The target IOP should be individualized and based on factors such as the IOP at presentation and the IOP at which documented damage has occurred. Patients with a low baseline IOP are likely to need a low target IOP; however, the target depends on the risk of sight loss. Factors such as age, family history, the severity of glaucoma, the rate of progression, and the status of the fellow eye are important when deciding a target IOP. Ensure the patient is at the centre of decisions regarding treatment. The target IOP level should be re-evaluated at each visit in light of the visual field and optic disc.

Follow-up

After a decision to treat, reassessment of IOP should be performed within 6 weeks and any side effects evaluated. If IOP reduction is satisfactory, this interval may be extended to 3 to 6 months, depending on disease severity.

8.12 Primary angle closure

The defining feature of angle closure is contact between the iris and posterior pigmented TM, or ITC. ITC causes damage to the TM, resulting in PAS and increased IOP with resultant damage to RGCs and glaucoma. ITC may be due to the iris being pushed forwards, as in cases of pupil block, or being pulled back towards the TM, for example by inflammatory PAS. Secondary causes of angle closure are discussed in Section 8.13.

Pathophysiology

A physiological situation of relative pupillary block occurs in all eyes, owing to contact between the posterior iris at the pupil margin and the anterior lens surface (see Figure 8.25). The result is resistance to aqueous flow from the posterior chamber to the anterior chamber. The pressure differential causes the peripheral iris to bow forwards (iris bombé). If the angle is predisposed, ITC may occur and aqueous outflow become blocked.

Fig 8.25 Diagram of the mechanism of pupil block

Fig 8.25
Diagram of the mechanism of pupil block

Some eyes are anatomically predisposed to angle closure because of (i) the relative anterior location of the iris lens diaphragm, (ii) a shallow anterior chamber, and (iii) a narrow chamber angle. Irido-lenticular contact is at its maximum with a mid-dilated pupil; therefore, dim lighting and mydriatics may provoke angle closure.

PAC may also occur without pupil block because of angle crowding and the occlusion of the drainage angle by thick iris folds, or as a manifestation of the plateau iris configuration. In plateau iris configuration, the central anterior chamber depth is normal and the iris plane is flat, until a steep insertion into the ciliary body at the periphery.

Classification of PAC

Previous nomenclature regarding angle closure has been confusing. The following staging is now used:

  1. 1. Primary angle closure suspect (PACS)

    • PACS is defined as the presence of two or more quadrants of ITC (≥180°).

    • The IOP is normal and there is no evidence of PAS or glaucomatous optic neuropathy.

    • Eyes with PACS are at risk of primary angle-closure glaucoma (PACG) or an acute attack of angle closure.

    • About one in four eyes with PACS develop either an elevation in IOP or PAS within 5 years.

  2. 2. Primary angle closure (PAC)

    • In primary angle closure, ITC is present but there are also features indicating that obstruction of the TM by the peripheral iris has occurred, namely, PAS and/or raised IOP.

    • There is no evidence of glaucomatous optic neuropathy.

    • An eye with primary angle closure has a 1 in 3 chance of progressing to PACG within 5 years.

  3. 3. PACG

    • PACG is defined as the presence of both ITC and glaucomatous optic neuropathy.

In these definitions, ITC should not be secondary to other ocular pathologies causing PAS, for example uveitis, trauma, or neovascularization.

Prevalence

The prevalence of primary open-angle glaucoma in European populations has recently been estimated as 0.4%. Three-quarters of those affected are female. There is a much higher prevalence of primary open-angle glaucoma in Inuit and Chinese populations than in other populations. The worldwide prevalence of primary open-angle glaucoma is estimated at 0.7% in those aged over 40 years. Primary open-angle glaucoma is a more blinding disease than primary open-angle glaucoma is.

Clinical evaluation

History

Symptoms associated with PAC and raised IOP, for example pain, redness, blurring, and haloes, may be present; however, these symptoms have poor sensitivity and specificity, and most patients with PAC are asymptomatic.

Assess the following risk factors:

  • Increased age

  • Female gender

  • Inuit and/or Far-Eastern descent: PAC is rare in black populations

  • Positive family history

  • Use of topical or systemic medications associated with angle closure, e.g. nebulized bronchodilators, muscle relaxants, and other sympathomimetic or anticholinergic drugs

Examination

  • Visual acuity

  • Assess refractive status: hypermetropia is a risk factor

  • GAT

  • CCT

  • Gonioscopy

  • Shallow anterior chamber: assess LCD and central anterior chamber depth

  • Narrow drainage angle: perform gonioscopy of both eyes

  • Short axial length: nanophthalmic eyes are at particular risk; therefore, if the axial length is less than 21 mm, also assess scleral thickness

  • A dilated exam is not advisable in eyes with PAC until treatment has been performed.

Differential diagnosis

  • Neovascular glaucoma

  • Inflammatory glaucoma

  • Lens-induced angle closure

  • Uveal effusion, e.g. with systemic medication (topiramate, sulphonamides), scleritis, pan-retinal photocoagulation (PRP)

  • Aqueous misdirection

  • Secondary causes of pupil block, e.g. silicone oil, anterior chamber intraocular lens (AC-IOL)

  • Axenfeld–Reiger syndrome (see Section 8.22)

  • Iridocorneal endothelial syndrome

Management

It is recommended that PACS should be treated, usually with laser peripheral iridotomy (Laser PI). A Laser PI allows aqueous humour to bypass the pupil block, thus reducing iris bombé and contact between the iris and the TM. Patients with primary angle closure or PACG can also be treated initially by Laser PI; however, lens extraction may also be a good option.

If ITC is still present following Laser PI, options include long-term pilocarpine (although this is not well tolerated and should only be continued if it successfully opens the angle), argon Laser PI (ALPI), or lens extraction. If IOP remains high, glaucoma surgery such as trabeculectomy may be needed. Glaucoma surgery should be avoided in eyes with very small axial lengths because of the high risk of complications, particularly aqueous misdirection. Laser treatment for primary angle closure is discussed in Section 8.25.

Acute angle closure

Acute angle closure (see Figure 8.26) is one of the few ophthalmic emergencies, because, if left untreated, it can result in irreversible visual loss.

Fig 8.26 Colour anterior segment photograph showing the eye of a patient in acute angle-closure glaucoma
There is ciliary injection, the pupil is mid-dilated, and the cornea is slightly oedematous

Fig 8.26
Colour anterior segment photograph showing the eye of a patient in acute angle-closure glaucoma

There is ciliary injection, the pupil is mid-dilated, and the cornea is slightly oedematous

Clinical evaluation

History

  • Consider the risk factors listed under primary angle closure.

  • May be asymptomatic but often patients have ocular pain, red eye, and tearing

  • Haloes around lights

  • Reduced vision

  • Nausea and vomiting

  • Headache

  • Previous intermittent episodes of blurred vision and ocular pain

Examination

  • Ciliary injection

  • Corneal oedema (fine ground glass) and epithelial bullae

  • Shallow anterior chamber: assess LCD

  • Aqueous flare with and without cells

  • Stromal iris atrophy with a spiral-like configuration

  • Fixed/sluggish mid-dilated pupil; vertically oval

  • IOP greater than 40 mmHg; can be up to 100 mmHg

  • Closed angle on gonioscopy

  • Glaucomflecken: small grey-white anterior subcapsular opacities; indicate previous episodes of markedly raised IOP

  • Optic disc oedema and hyperaemia

  • Gonioscopic examination of the fellow eye is essential to look for an occludable angle.

Differential diagnosis

  • Primary open-angle glaucoma with unusually high IOP

  • Uveitic glaucoma

  • Neovascular glaucoma

  • Malignant glaucoma

  • Pigment dispersion syndrome/glaucoma

  • Anterior chamber angle tumour or mass

  • Other causes of ocular pain (migraine, cluster headache)

Management

Initial

The aims of treatment are to break the pupil block, lower IOP, and control inflammation. It is usually possible to lower IOP via medications. Aqueous suppressants, including acetazolamide, topical beta blockers, and topical alpha agonists, should be given immediately.

  • Acetazolamide 500 mg intravenously

  • Timolol eye drops, 0.25% or 0.5%

  • Iopidine eye drops, 1%

  • Dexamethasone eye drops, 1%

  • Pilocarpine eye drops, 2% or 4%, to both eyes; may not be effective in high IOP because of iris ischaemia; avoid intensive pilocarpine

  • Have the patient lie in a supine position.

  • Analgesics and anti-emetics, if needed

After 1 hour

  • Recheck IOP; if IOP has fallen and corneal clarity permits, perform Laser PI.

If IOP still high, consider:

  • Corneal indentation

  • ALPI: can be performed more easily through an oedematous cornea than Laser PI

  • Mannitol 20% (1–2 g/kg) intravenously over 45 minutes

  • Oral glycerol 50% (1.0–1.5 g/kg) in lemon juice

  • Be cautious if using mannitol/glycerol in elderly patients with cardiovascular and/or renal disease.

After a further 1 hour

If IOP is not reduced by the above measures, options might include surgical iridectomy or use of a cyclodiode laser with the eventual aim being to remove the crystalline lens. If there is an adequate corneal view, consider Laser PI. Glycerine can be used to clear the cornea. Laser PI is indicated in the fellow eye, as more than 50% of patients will develop symptoms in the second eye if it is left untreated.

Follow-up

Patients should not be discharged following acute angle closure until they have a patent Laser PI. Following laser iridotomy to both eyes, if the IOP is controlled, then patients can be discharged but should continue to use pilocarpine eye drops, 2% (or 4% if the iris is dark), four times a day and topical steroid such as dexamethasone eye drops, 0.1%, every two hours to the affected eye and four times a day to the fellow eye. Once patency of the Laser PI is confirmed, the pilocarpine can be stopped and gonioscopy repeated to ensure the angle remains open.

Persistent angle closure may be due to PAS, a plateau iris configuration, or a phacomorphic component. In such cases, glaucoma drainage surgery, ALPI, or cataract extraction may be considered. The urgency of the procedure will depend on whether the IOP can be controlled medically. If the pressure is controlled medically, it is better to defer surgery until inflammation has resolved.

Prognosis

Prognosis depends on the duration and severity of the attack. Prompt IOP lowering is essential to prevent irreversible optic nerve damage. There may also be permanent TM damage because of inflammation, appositional angle closure, and PAS causing the IOP to increase over time. Occasionally, the IOP will spike because of the recovery of temporary ciliary body shutdown, which resulted from ischaemia induced by the high IOP.

8.13 Secondary angle closure

The management of eyes with secondary angle closure is often different to those with primary angle closure. A warning sign that there may be a secondary cause is a difference in anterior chamber depth between eyes.

Angle closure can be due to four mechanisms, although there is often a combination involved:

  1. 1. Pupil block (80%)

    • Discussed in Section 8.12; however, in secondary angle closure, it may be due to secondary causes such as anterior lens dislocation, posterior synechiae, vitreous, silicone oil, or an AC-IOL

  2. 2. Obstruction at the level of the iris or ciliary body (10%)

    • This condition may occur because of a thick iris, an anterior iris insertion, or an anteriorly located ciliary body; an example is plateau iris.

  3. 3. Obstruction at the level of the lens (8%)

    • The lens plays a role in most types of angle closure; however, angle closure can be primarily ‘phacomorphic’. In these cases, the lens is usually hypermature or may be subluxed.

  4. 4. Posterior pushing mechanism (2%)

    • Due to forwards movement of the iris lens diaphragm, secondary to an abnormality behind the lens

    • Causes include cilio-choroidal effusion and aqueous misdirection. Posterior pushing mechanisms usually cause shallowing of the central as well as the peripheral anterior chamber (i.e. there is not iris bombé).

This section discusses Mechanisms 2–4.

Obstruction at the level of the iris or ciliary body

Angle closure at the level of the iris may be secondary to the proliferation of abnormal tissue in the angle, for example due to neovascularization or iridocorneal endothelial syndrome. These are anterior pulling mechanisms. Angle closure at the level of the iris may also occur due to an abnormal iris configuration.

Plateau iris configuration

  • Defined as a narrow or closed angle on gonioscopy, with a flat iris plane and a deep central anterior chamber

  • Indentation gonioscopy shows the double hump sign: the peripheral hump is due to an anteriorly positioned ciliary body, which keeps the peripheral iris close to the TM, and the central hump is due to the iris resting on the lens surface.

  • Other features are a thick iris, anterior iris insertion, and prominent last iris roll.

  • Another possible cause is the presence of iridociliary cysts, which may be seen on UBM.

Plateau iris syndrome

  • Diagnosed when an Laser PI has failed to reverse appositional angle closure in an eye with a plateau iris configuration

  • More common in women than in men and tends to present at a younger age than primary angle closure does

  • Accounts for 50% of patients who have angle closure with a patent Laser PI

  • Recurrent or prolonged apposition leads to PAS and irreversible angle closure.

Eyes with plateau iris configuration should be treated with Laser PI, as there may be an element of pupil block. If plateau iris syndrome follows, treatment may be with ALPI or long-term pilocarpine.

Obstruction at the level of the lens

Increased lens thickness and anterior positioning of the lens contribute to primary angle closure; however, secondary angle closure, in which the lens is the primary cause, is usually due to factors such as lens subluxation (e.g. Marfan syndrome, trauma) or a very large (and usually white) cataract.

Posterior pushing mechanism

Causes include:

  1. 1. Aqueous misdirection

  2. 2. Choroidal effusion

    • A choroidal effusion is due to an accumulation of fluid in the suprachoroidal space.

    • May be due to inflammation (scleritis, uveitis), increased choroidal venous pressure (nanophthalmos, scleral buckling, PRP), tumours, or drugs (topiramate)

8.14 Normal tension glaucoma

Normal tension glaucoma is a form of open-angle glaucoma characterized by a peak IOP that is consistently within the statistically normal range, that is, there is glaucomatous optic neuropathy with an IOP of less than 21 mmHg, in the absence of a secondary cause. Normal tension glaucoma should be considered a diagnosis of exclusion.

Pathogenesis

Although IOP remains a significant factor, non-pressure-dependent processes are likely to be important. For example, there is evidence that systemic vascular dysregulation and localized vasospasm are risk factors. Such evidence suggests that impaired blood flow to the optic nerve may contribute to glaucomatous damage.

Prevalence

Although once thought to be uncommon, up to one-third of patients with open-angle glaucoma can be classified as having normal tension glaucoma (Beaver Dam Study). It is more common in the elderly than in other age groups, but up to 30% of patients are under 50 years. The overall prevalence of normal tension glaucoma in the general population is estimated at 0.15%; however, NTG accounts for 90% of glaucoma in the Japanese population.

General risk factors for normal tension glaucoma

  • IOP: the optic nerve is susceptible to damage at relatively low levels of IOP

  • Thin CCT

  • Increased age

  • Female gender (2 : 1)

  • Race: Japanese

  • Positive family history

  • Diabetes mellitus

  • Myopia

Risk factors for reduced blood flow to the optic nerve head

  • Vasospasm: history of migraine or Raynauds phenomenon

  • Hypercoagulability

  • Nocturnal hypotension

  • Autoimmune disorders

  • Sleep apnoea

Clinical evaluation

History

  • Need to specifically enquire about risk factors for reduced blood flow

Examination

  • As for OHT/primary open-angle glaucoma

  • Phasing (diurnal IOP curve) to elucidate any IOP spikes. Office-hour phasing may still miss a nocturnal peak in IOP.

Specific clinical features for normal tension glaucoma

  • Visual field defects are often more localized, deeper, steeper, and closer to fixation than those in primary open-angle glaucoma.

  • The amount of visual field loss may be greater than expected on optic disc appearance.

  • Localized (slit or wedge) defects of RNFL

  • Increased propensity for optic disc haemorrhages

  • Acquired optic disc pits

  • Peripapillary atrophy more common

Further investigations (as appropriate)

  • Blood pressure, blood glucose level, serum autoantibodies, erythrocyte sedimentation rate, C-reactive protein test

  • 24-hour BP monitoring

  • OPP

  • Laboratory testing for infectious or inflammatory conditions

Neuroimaging if compressive disease suspected because of the following features:

  • Age less than 50 years

  • Poor visual acuity

  • Pallor of neuroretinal rim

  • Discrepancy between disc cupping and visual field loss

  • Visual field loss that respects the vertical midline

Differential diagnosis

  • Primary open-angle glaucoma with diurnal fluctuations

  • Intermittent angle closure

  • Hereditary optic neuropathy

  • Compressive lesions of anterior visual pathway

  • Acquired optic neuropathies (ischaemic, toxic, drug-induced, or nutritional optic neuropathy)

  • Systemic disorders (syphilis, tuberculosis, sarcoidosis, and multiple sclerosis)

  • Hypoperfusion (including history of large-volume blood loss)

  • Optic disc anomalies (drusen, large pits, colobomas)

Management

Despite the IOP being statistically within the normal range, reduction of IOP reduces the risk of progression. The Collaborative Normal Tension Glaucoma Study showed that lowering IOP by 30% significantly reduced the rate of progression (12% of treated vs 34% of untreated progressed at 7 years). Although many untreated eyes showed no progression, there was a significant minority that had rapid loss of vision.

Medical

  • Prostaglandin analogues (greater IOP-lowering effect at night)

  • Alpha 2 agonists (may have additional neuroprotective effects)

  • Carbonic anhydrase inhibitors (may increase ocular blood flow)

  • Beta blockers (if needed, consider once a day morning use only, because of possible adverse effects on BP and on optic nerve head perfusion)

  • Trial of supramaximal medical therapy and effect on progression of field loss may help to establish optimal management.

Improve optic nerve head blood flow

There may be some specific circumstances where a ‘blood flow risk factor’ can be addressed in collaboration with the patients GP or physician. First, treat any underlying medical conditions.

  • Prevent nocturnal hypotension: Patients with normal tension glaucoma may have a low night-time BP. In patients who show progression despite a low IOP, consider 24-hour ambulatory BP monitoring to look for a nocturnal dip (>20% decreased from baseline is considered to be a large dip). Nocturnal dipping may have a reversible cause (e.g. use of an oral hypotensive drug, particularly at night).

  • If the patient has migraines or peripheral vasospasm (Raynauds disease), consider calcium channel blockers (may decrease vasospasm and increase capillary dilatation).

  • Consider gingko biloba (but not if patient has a bleeding tendency or is on clopidogrel or warfarin). Should be stopped before surgery.

Surgical

  • Laser trabeculoplasty (less likely to achieve a low enough IOP in normal tension glaucoma than in primary open-angle glaucoma)

  • Trabeculectomy, probably combined with antimetabolite and adjustable releasable sutures to achieve low range pressures (there may be a very small ‘target pressure’ window)

Follow-up

  • As for primary open-angle glaucoma

8.15 Steroid-induced glaucoma

Raised IOP and eventually glaucoma may occur following corticosteroid administration in so-called steroid responders. Steroid-induced glaucoma is most common with the use of topical steroids such as dexamethasone or prednisolone but can also occur with oral, intravenous, or inhaled steroids and with the use of over-the-counter steroid creams for conditions such as eczema (especially if used on the face). Ask every patient with suspected glaucoma about current and past steroid use.

With the increasing use of periocular and intravitreal steroids, steroid-induced glaucoma will probably increase. A DRCR.net study of intravitreal triamcinolone for diabetic macular oedema found that 20% of eyes treated with 1 mg triamcinolone had significant elevation of IOP, and 6% of eyes needed IOP-lowering medication at 2 years.

Pathophysiology

The condition is not completely understood, but steroids are known to have several effects on the TM, all of which contribute to an increased outflow resistance and hence increased IOP. Changes to the TM include an increase in glycosaminoglycans, decreased membrane permeability, reduced breakdown of extracellular and intracellular structural proteins, and reduced local phagocytic activity by cells that filter and clean debris from the aqueous humour. These effects usually take about 2–4 weeks to manifest, but sometimes the IOP rise is acute.

Several genes are responsible for TM changes; however, the most extensively studied is MYOC, which encodes the protein myocillin (also known as TIGR). This protein is induced in human cultured TM cells after they have been exposed to dexamethasone for 2–3 weeks, a timescale which appears to fit with that for steroid-induced IOP elevation.

Risk factors

  • Past or current steroid use of any type: e.g. for asthma, skin disorders, allergies, autoimmune disease, uveitis

  • Endogenous elevation of steroid (Cushings syndrome)

  • Primary open-angle glaucoma or pigmentary glaucoma

  • Family history of glaucoma

  • Age over 40

  • Diabetes mellitus

  • High myopia

  • Connective tissue disease

Prevalence of steroid response

Armaly et al. examined the IOP response to a 4-week course of topical dexamethasone. They reported three groups with steroid-induced raised IOP:

  • Five per cent of the population showed a high response, with an IOP increase >15 mmHg.

  • One-third of the population showed a moderate response, with an IOP increase of 6 to 15 mmHg.

  • Two-thirds of the population are non-responders.

A response was more likely in primary open-angle glaucoma patients, with more than 90% showing a moderate or high response.

Clinical evaluation

History

  • Use of topical, intraocular, periocular, inhaled, nasal, oral, intravenous, or dermatological steroid

  • Presence of known risk factors

Examination

  • Usually unremarkable; chronicity tends to prevent corneal oedema

  • Stopping steroids may confirm the diagnosis

Management

  • A baseline measurement of IOP should be taken prior to starting steroid therapy.

  • Discontinue steroids if IOP rises.

  • Use ocular steroids that are weaker or less pressure-inducing than the one(s) currently used by the patient, e.g. fluorometholone (FML™), rimexolone (Vexol™), or loteprednol (LotemaxTM).

  • IOP-lowering therapy as for primary open-angle glaucoma

  • If induced by a depot steroid, surgical removal may be indicated.

Follow-up

  • Careful monitoring of patients at risk is required because of the insidious nature of this condition.

  • Topical therapy: measure IOP a few weeks after start of therapy then at regular intervals

  • Intravitreal injections: patients must be monitored for up to a year after injection

  • Patients on long-term systemic steroids should visit their own optometrist for regular IOP checks.

Prognosis

IOP usually returns to normal within 1 to 4 weeks of cessation of treatment; however, in about 3% of cases, IOP remains elevated.

8.16 Traumatic glaucoma

Blunt ocular trauma results in ocular indentation and a sudden expansion of tissues in the opposite plane. As the vitreous offers some resistance, most of the transmitted force is directed laterally along the iris towards the TM, the ciliary body, and the zonules. This force can tear these tissues in addition to tearing the associated blood vessels and thus causing a hyphaema.

Penetrating trauma may lead to direct damage to any of the ocular structures. Secondary open- or closed-angle glaucoma may occur via a variety of mechanisms and may develop years after the injury.

Pathophysiology

Early-onset traumatic raised IOP

One-third of eyes with hyphaema develop raised IOP. The presence of a hyphaema and low IOP should alert to the presence of a ruptured globe. IOP may be raised because of:

  • TM obstruction with fresh red blood cells and fibrin

  • Pupillary block due to blood clot

  • Haemolytic glaucoma (due to breakdown products)

  • Steroid-induced glaucoma due to treatment

Late traumatic glaucoma

  • Ghost cell glaucoma: Ghost cells are rigid, haemolysed erythrocytes that may block the TM; typically results in elevation of IOP 1 to 3 months after a vitreous haemorrhage. Ghost cells are khaki or tan coloured.

  • Haemolytic glaucoma: occurs when red blood cells and macrophages block the TM

  • Haemosiderotic glaucoma: very rare glaucoma due to intraocular haemorrhage with iron deposition in the TM; may occur years after the injury

  • PAS formation

  • Posterior synechiae formation with iris bombé

  • Angle recession: a tear in the ciliary body between longitudinal and circular muscle layers; an indicator of direct TM damage, not the direct cause of the raised IOP

Prevalence of raised IOP following trauma

The larger the hyphaema, the more likely the IOP to be raised; however, there are exceptions, and patients with sickle cell may have a small hyphaema but high IOP. Rebleeding increases the risk. Coles et al. found raised IOP in the following groups:

  • In 13.5% of those with a hyphaema that was up to half the size of the anterior chamber

  • In 27% of those with a hyphaema that was greater than half of the size of the anterior chamber

  • In 52% of those with total hyphaema

Risk factors for raised IOP following trauma

  • Young age

  • Male gender (3 : 1)

  • Black populations and Hispanics (related to the presence of sickle cell disease or trait):

    • Rigid cells more easily trapped in TM

    • Vascular occlusion and optic nerve damage at lower IOP

  • Predisposition to primary open-angle glaucoma

  • Antiplatelet or anticoagulant drugs (including alcohol)

  • Large initial hyphaema

  • Eight-ball hyphaema: total black hyphaema clot; black colour related to the ischaemic environment in the anterior chamber

  • Delayed presentation

  • Rebleed

Clinical evaluation

History

  • Details of injury (exact time, type of injury)

  • Family history of a bleeding disorder or sickle cell disease

  • Drug history (aspirin, NSAIDs, anticoagulants, alcohol)

  • Previous history of trauma (chronic glaucoma)

  • May be asymptomatic or have decreased vision, photophobia, pain, nausea, or vomiting

Examination

  • Subconjunctival haemorrhage

  • Hyphaema (or microhyphaema)

  • Anterior chamber may be deeper than that in the fellow eye

  • Iris sphincter tear or iridodialysis

  • Gonioscopy:

  • Lens subluxation, cataract, or phacodonesis

  • Vitreous haemorrhage

  • Choroidal rupture

  • Retinal dialysis or detachment; commotio retinae

Investigations

  • B-scan ultrasonography (if no view of posterior pole)

  • CT scan (if suspect orbital fracture or intraorbital foreign body)

  • Haemoglobin electrophoresis (if suspected sickle cell disease)

Management of traumatic hyphaema

Complications of hyphaema include PAS and corneal blooding staining. Risk factors for corneal bloodstaining are high IOP, a large hyphaema, prolonged clot duration, rebleeding, and corneal endothelial cell dysfunction. An early sign is a straw-yellow discolouration of the corneal stroma. Patients with sickle cell disease or trait have a higher incidence of rebleeding and raised IOP. Sickled erythrocytes are less able to pass through the TM. Avoid drugs that promote acidosis and sickling (acetazolamide, mannitol), and consider surgical evacuation at an early stage.

General

  • Protective eye shield

  • Bed rest

  • Elevation of head

  • Anti-emetics

  • Systemic BP control

  • Avoid antiplatelet and anticoagulant drugs

Medical

  • Topical cycloplegic and corticosteroid

  • The use of cycloplegic agents is controversial; movement of the iris may theoretically predispose to dislodgement of the clot and a rebleed.

  • Consider using an antifibrinolytic drug in high-risk patients.

  • Topical aqueous suppressants

  • Systemic carbonic anhydrase inhibitors and hyperosmotics (contraindicated in sickle cell)

  • Avoid miotics.

Surgical

  • Anterior chamber washout may be required if IOP is uncontrolled.

  • Anterior vitrectomy

  • Trabeculectomy with antimetabolites

  • Surgery indicated with healthy optic nerve if:

    • IOP >60 mmHg for 2 days (to prevent optic atrophy)

    • IOP >35 mmHg for 5 days (to prevent corneal blood staining)

    • Sickle cell patients if IOP >24 mmHg for 24 hours

    • Hyphaema fails to resolve to <50% of the anterior chamber by Day 8 (to prevent PAS)

The aim of surgery is to reduce the risk of irreversible corneal bloodstaining. Earlier intervention is advised if the optic nerve is compromised or there is endothelial dysfunction.

Follow-up

  • Daily monitoring is necessary until the hyphaema clears (rebleed risk highest at 2–5 days after injury).

  • Perform gonioscopy 4–6 weeks after injury to look for angle recession.

  • Glaucoma may develop weeks to years after the event; therefore, inform patients of glaucoma risk and ensure annual IOP checks with a local optometrist. If there is a large degree of angle recession, close follow-up may be appropriate.

Prognosis

  • The prognosis is highly dependent upon the degree of initial damage and the amount of disruption to the TM.

  • Rebleeds tend to result in more IOP-related problems than the initial bleed does.

  • In high-risk patients with markedly uncontrolled IOP, the visual prognosis may be guarded.

Management of angle-recession glaucoma

Angle recession occurs when a cleft forms between the circular and longitudinal muscles of the ciliary body. It is visible as an irregular widening of the ciliary body band on gonioscopy (see Section 8.7; compare the two eyes).

Angle recession is common after a hyphaema; however, only 6% to 7% of eyes with angle recession eventually develop glaucoma. The greater the circumference recessed, the greater the risk of glaucoma. Eyes with less than 180° of recession are unlikely to develop glaucoma. Patients that develop angle-recession glaucoma have a high incidence of primary open-angle glaucoma in the contralateral eye.

Treatment

  • Aqueous suppressants

  • Hyperosmotics

  • Trabeculectomy (increased rate of failure compared to primary open-angle glaucoma)

  • Argon laser trabeculoplasty (ALT) has limited success and may exacerbate angle damage.

Management of cyclodialysis cleft

A cyclodialysis cleft is a focal detachment of the ciliary body from its insertion at the scleral spur. The cleft creates an abnormal pathway for aqueous humour to drain into the suprachoroidal space, thus resulting in low IOP. A cyclodialysis cleft appears as a deep angle recess with a gap between the sclera and ciliary body but, because of very low IOP, it may be difficult to detect on gonioscopy. Anterior segment OCT or UBM may be useful.

Treatment

  • Initially, conservative treatment should be tried.

  • Atropine 1% three times a day (allows the ciliary muscle to relax and come into contact with the sclera)

  • Avoiding topical steroids may facilitate this process.

  • Closure may take 6 to 8 weeks.

  • Cryotherapy (often successful in small clefts that have not closed with atropine)

  • Surgical closure (direct cyclopexy (surgical fixation) may be needed for moderate to large clefts).

Follow-up

  • Following successful closure, there may be a very high spike in IOP, requiring treatment with aqueous suppressants and hyperosmotics.

8.17 Inflammatory glaucomas

Inflammation within the anterior segment and which is caused by uveitic conditions can result in raised IOP (secondary OHT). If raised IOP causes glaucomatous optic nerve damage or visual field defects, it is known as inflammatory or uveitic glaucoma.

Pathophysiology

Ocular inflammation causes breakdown of the blood–aqueous barrier, resulting in the liberation of protein and inflammatory cells into the aqueous. Inflammatory glaucoma may occur with an open or closed angle and be secondary to a systemic or ocular uveitic condition. Patients may also develop glaucoma secondary to steroid use for treating ocular inflammation.

Secondary open-angle glaucoma

May be caused by:

  • Obstruction of the TM by cellular debris, protein, or macrophages

  • Trabeculitis: inflammation and oedema of the TM, leading to a reduction in intertrabecular pores, or the formation of precipitates which reduce aqueous outflow

  • Prostaglandins: released in the inflammatory process; may contribute to raised IOP by compromising the blood–aqueous barrier)

Secondary angle-closure glaucoma

With pupil block

  • Anterior segment inflammation may result in the formation of 360° posterior synechiae causing iris bombé.

  • Pupil block may lead to shallowing of the anterior chamber, to appositional angle closure, and to the development of permanent PAS.

Without pupil block

  • In chronic anterior uveitis, contraction of inflammatory debris within the angle can pull peripheral iris over the trabeculum, causing gradual but progressive angle closure.

  • Angle neovascularization from ischaemic processes may also result in the formation of PAS.

  • Ciliary body swelling due to intraocular inflammation may result in the forwards rotation of the ciliary body, also causing angle closure.

Prevalence

Ten per cent of uveitics have chronically elevated IOP with many having wide and episodic fluctuations. There may be long periods where the pressure is normal and therefore patients may progress with apparently normal IOP.

Risk factors

  • Pre-existing primary open-angle glaucoma

  • Being post surgery

  • Being post trauma

  • Drugs (1% of patients on prostaglandin analogues develop uveitis)

  • Rigid AC- IOL (uveitis-glaucoma-hyphaema syndrome)

  • Presence of uveitic conditions associated with secondary glaucoma:

    • Juvenile rheumatoid arthritis

    • Ankylosing spondylitis

    • Reiters syndrome

    • Psoriatic arthritis

    • Herpetic uveitis: herpes simplex virus (HSV), varicella-zoster virus, rubella, mumps

    • Lens-induced uveitis: phacoanaphylactic, phacolytic, lens particle

    • Sarcoidosis

    • Vogt–Koyanagi–Harada syndrome

    • Behçets disease

    • Sympathetic ophthalmia

    • Syphilis

    • Tuberculosis

Clinical evaluation

History

  • Symptoms of acute uveitis

  • Previous history of uveitic episodes

  • Systemic history of associated disorder

Examination

  • Signs of acute or chronic uveitis or of a previous uveitic episode

  • The signs present will depend on the primary cause of the uveitis.

  • Gonioscopy is most important, as it will elucidate the primary mechanism and thus the treatment.

Investigations

  • Basic uveitic screen, including bloods and chest X-ray

  • Additional tests as appropriate for the suspected uveitic process

Management

For all mechanisms, find and treat any cause for the uveitis.

Control intraocular inflammation

  • Topical, periocular, or sub-Tenons corticosteroid

  • Oral corticosteroid: up to 1 mg/kg per day, depending on severity

  • Steroid-sparing agents: ciclosporin, methotrexate, azathioprine, mycophenolate

  • Prevent and break synechiae, and relieve ciliary and iris sphincter spasm (regular cycloplegics).

Reduction of IOP

  • Aqueous suppressants: beta blockers, alpha agonists, topical carbonic anhydrase inhibitors

  • Systemic carbonic anhydrase inhibitors: acetazolamide

  • Hyperosmotic agents: mannitol, glycerol

  • Avoid prostaglandins because of the risk of inducing cystoid macular oedema.

For secondary angle closure with pupil block

  • Laser iridotomy is less likely to be effective in uveitis than in other conditions, because of the presence of inflammatory membrane behind the pupil; thus surgical iridectomy may be a better option.

For secondary angle closure without pupil block

  • Trabeculectomy (with adjunctive antimetabolites)

  • Glaucoma drainage devices

  • Avoid cyclodestructive procedures.

Follow-up

It is extremely important to monitor patients closely as there may be permanent compromise of aqueous outflow. IOP may increase after inflammation has resolved, owing to the recovery of ciliary body shutdown.

Prognosis

The prognosis depends on the extent of permanent damage to the drainage mechanism and the recurrent nature of the uveitic condition. The prognosis is worse than for primary open-angle glaucoma (higher pressures, more likely to need surgery than in primary open-angle glaucoma).

Specific inflammatory glaucoma syndromes

Posner–Schlossman syndrome

Also known as glaucomatocyclitic crisis, Posner–Schlossman syndrome is a condition in which there are recurrent episodes of unilateral mild anterior uveitis associated with marked elevation of IOP (40–80 mmHg) thought to be due to a trabeculitis. Patients tend to be asymptomatic. There is only mild inflammation visible in the anterior chamber.

Fuchs heterochromic iridocyclitis

Also known as Fuchs uveitis syndrome, Fuchs heterochromic iridocyclitis is a low-grade, chronic, anterior uveitis associated with secondary cataract and glaucoma. It is almost always unilateral. The classic presentation is of stellate keratic precipitates scattered throughout the endothelium. The iris may be hypochromic (see Figure 8.27). Posterior synechiae are not a feature. Initially, the rise in IOP is intermittent before becoming chronic. Approximately 30% of cases develop glaucoma. The condition may have an infective cause (rubella, cytomegalovirus).

Fig 8.27 Colour anterior segment photographs of both eyes of the same patient, showing marked heterochromia

Fig 8.27
Colour anterior segment photographs of both eyes of the same patient, showing marked heterochromia

8.18 Pseudoexfoliative glaucoma

Pseudoexfoliation syndrome (PXF) is a systemic condition thought to be a generalized basement membrane disorder, which results in white powdery deposits within the anterior segment of the eye, with weakness of the zonules. PXF material impairs aqueous outflow, resulting in raised IOP and secondary open-angle glaucoma.

Pathophysiology

PXF material is composed of filamentous proteoglycosaminoglycans, which aggregate to form granular, electron-dense grey/white fibrillar deposits. It is thought to occur because of abnormal extracellular matrix material metabolism. PXF is associated with mutations in the LOXL1 gene, which encodes a protein involved in elastin cross-linking.

PXF material is believed to be produced by the lens epithelium, iris pigmented epithelium, and non-pigmented epithelium of the ciliary body. It is visible on the iris, the lens, the ciliary body, the TM, the anterior vitreous face, the corneal endothelium, and the conjunctiva and has been found in the endothelial cells of blood vessels within the eye and orbit. PXF material has also been identified in the skin, the myocardium, the lung, the liver, the gall bladder, the kidney, and the cerebral meninges; this observation suggests that PXF is an ocular manifestation of a systemic disorder.

Increased IOP is due to ‘clogging’ of the TM both by PXF material and by pigment released from the iris as a result of pathological friction against the rough deposits on the anterior lens capsule. In addition, trabecular endothelial dysfunction occurs, increasing outflow resistance in the TM and raising IOP. PXF differs from true exfoliation syndrome, which is often observed in glass-blowers and where schisis of the anterior lens capsule occurs.

Prevalence

  • The prevalence of PXF varies by country. It is typically thought of as having a Scandinavian genetic origin (Iceland and Norway have 20%–25% prevalence), but it also occurs in populations as diverse as Japanese and Aboriginal Australians.

  • Prevalence increases with age.

  • The Framingham Eye Study found that:

    • The prevalence of PXF was 0.6% of people aged 52–64 years.

    • The prevalence of PXF was 5% of people aged 75–85 years.

  • The risk of glaucoma is five times greater in PXF patients than in the normal population (Blue Mountains Eye Study).

  • Overall, approximately 25% of open-angle glaucoma worldwide is pseudoexfoliation related.

Risk factors

  • Age

  • Female gender (3 : 2) for PXF (males = females for pseudoexfoliative glaucoma)

  • Race (Scandinavian)

Clinical evaluation

History

  • Rarely symptomatic

  • May have foreign body sensation (possibly because of subclinical involvement of conjunctiva)

  • History of complicated cataract surgery

Examination

  • Signs may be unilateral or bilateral with asymmetry.

  • Deposition of pseudoexfoliation flakes or of pigment within the anterior segment

  • IOP spikes may occur following pharmacological mydriasis.

  • Patchy increase in trabecular pigmentation

  • Sampaolesi’s line may be present (see Figure 8.18).

  • Peripupillary iris transillumination defects

  • Depigmented (moth-eaten) pupillary ruff (see Figure 8.28)

  • Classic concentric (bullseye) deposition on anterior lens capsule (see Figure 8.29): (i) a central translucent zone, (ii) a clear zone (pseudoexfoliation rubbed off by pupil movement), and (iii) a peripheral granular zone

  • Nuclear sclerotic cataract, lens subluxation, phacodonesis

Fig 8.28 Colour anterior segment photograph showing fine pseudoexfoliative material at the pupil margin

Fig 8.28
Colour anterior segment photograph showing fine pseudoexfoliative material at the pupil margin

Fig 8.29 Colour anterior segment photograph showing the pseudoexfoliative material on the anterior surface of the lens

Fig 8.29
Colour anterior segment photograph showing the pseudoexfoliative material on the anterior surface of the lens

Management

Medical therapy is as for primary open-angle glaucoma, although pseudoexfoliative glaucoma is more resistant than primary open-angle glaucoma. Laser trabeculoplasty may be more effective in pseudoexfoliative glaucoma than in primary open-angle glaucoma because of the presence of trabecular hyperpigmentation, which results in an increased uptake of laser energy. Trabeculectomy in pseudoexfoliative glaucoma has the same success rate as in primary open-angle glaucoma. However, PXF causes challenges for cataract surgery, including small pupils, zonular instability, an increased risk of vitreous loss, and post-operative IOP elevation.

Follow-up

Pseudoexfoliative glaucoma tends to progress more rapidly than primary open-angle glaucoma does, so needs watching closely. Patients with PXF but not glaucoma should have at least annual glaucoma screening.

Prognosis

Pseudoexfoliative glaucoma has a poorer prognosis than primary open-angle glaucoma does because of the high IOP present at the time of diagnosis, significant diurnal IOP fluctuation, and often a rapid progression of glaucomatous damage.

8.19 Pigmentary glaucoma

Pigment dispersion syndrome (PDS) is a bilateral condition characterized by dislodgement of pigment from the posterior iris pigment epithelium, resulting in mid-peripheral transillumination defects. The pigment particles are carried by aqueous convection currents and deposited on structures throughout the anterior segment. Obstruction of the TM by pigment can result in increased IOP (pigmentary OHT) and a secondary open-angle glaucoma known as pigmentary glaucoma.

Pathophysiology

PDS may be inherited as an autosomal dominant trait with variable penetrance. The anterior chamber is deep, and the iris appears to bow posteriorly in a concave configuration. Posterior bowing is due to reverse pupil block caused by a relative increase in pressure in the anterior chamber. There is friction between the posterior pigment layer of the iris and the underlying lens zonules. The friction causes pigment release into the anterior chamber; the released pigment leads to obstruction of the intertrabecular spaces, reduced aqueous outflow facility, and permanent damage to the TM via damage to phagocytic trabeculocytes though pigment overload, denudation, collapse, and sclerosis. Exercise, mydriasis, and accommodation can increase posterior iris concavity, leading to additional irido-zonular contact and pigment dispersion. In some patients, strenuous exercise leads to a ‘pigment storm’ and high IOP spikes.

Prevalence

Prevalence of PDS is approximately 2.5%. Estimates for conversion to pigmentary glaucoma are 5.0%–10.0% at 5 years, 15.0% at 15 years, and 35.0% at 35 years. Pigmentary glaucoma accounts for 1.0%–1.5% of all glaucoma. Risk factors for conversion include male gender, myopia, the presence of a Krukenberg spindle, and, most importantly, a high initial IOP.

Risk factors

  • Age 20–45 years; later in females

  • Male gender: PDS affects men and women equally but men are more likely to develop pigmentary glaucoma

  • Race: Caucasian

  • Myopia

Clinical evaluation

History

  • Usually asymptomatic

  • May have blurred vision, haloes, or headache during ‘pigment storm’, e.g. after exercise

Examination

  • Krukenberg spindle: vertical deposition of pigment on and within the corneal endothelial cells

  • Endotheliopathy: endothelial cells in PDS show pleomorphism and polymegathism

  • Deep anterior chamber

  • Pigment showers: small pigment specks floating within the anterior chamber

  • Iris transillumination defects: mid-peripheral radial spokes, present in 86% of cases, retroilluminate (see Figure 8.30)

  • Pigment on anterior surface of iris (preferentially within furrows), possibly causing heterochromia

  • Pigment on anterior and posterior lens surfaces

  • Glaucomatous optic atrophy

  • Lattice degeneration: present in up to one-third of cases; also higher incidence of retinal detachment than in the general population.

Fig 8.30 Colour anterior segment photograph showing typical slit-like iris transillumination defects
The patient has also had a trabeculectomy and has a superior peripheral iridectomy

Fig 8.30
Colour anterior segment photograph showing typical slit-like iris transillumination defects

The patient has also had a trabeculectomy and has a superior peripheral iridectomy

Gonioscopy

  • Wide-open angle

  • Concavity of iris near insertion; backwards bowing of the iris

  • Diffuse trabecular hyperpigmentation; the degree of pigmentation correlates with severity

  • A pigmented Schwalbes line creates a dark line that is similar to Sampaolesi’s line in PXF.

Differential diagnosis

  • Primary open-angle glaucoma with hyperpigmented trabeculum

  • Pseudoexfoliative glaucoma

  • Pseudophakic pigmentary glaucoma: rubbing of haptics/optics against the posterior iris

  • Uveitis

  • Melanoma

  • Iris and ciliary body cysts

  • Trauma

Management

  • Medical therapy as for primary open-angle glaucoma

  • Pilocarpine should be considered, as it can increase aqueous outflow, reverse posterior iris bowing, and prevent pupil dilation; however, it is poorly tolerated.

  • Trabeculectomy: success rate similar to primary open-angle glaucoma

  • Prophylactic Laser PI can theoretically be used to relieve reverse pupil block in PDS but the long-term benefits in the prevention of glaucoma are not proven and the treatment is controversial. Laser PI is only likely to succeed in the active stages of the disease and in the presence of observable posterior iris bowing. Laser treatment also carries the risk of further TM damage due to pigment release.

Follow-up

Patients with PDS and a normal IOP with no signs of glaucoma need regular IOP checks only, which can be done by their own optometrist; otherwise, follow-up is as for primary open-angle glaucoma.

Prognosis

Long-term prognosis is good. Pigment dispersion tends to decrease with age because of miosis and gradual lens enlargement, which increases relative pupil block, thus lifting the peripheral iris away from the zonules.

8.20 Neovascular glaucoma

Neovascularization of the iris (NVI, or rubeosis iridis) can be initiated by any process causing widespread posterior segment hypoxia with subsequent raised levels of vascular endothelial growth factor (VEGF). If neovascularization of the angle occurs and treatment is not initiated in the early stages, synechial angle closure and glaucoma will result.

Pathophysiology

In an attempt to revascularize, the ischaemic retina produces vasoproliferative factors (e.g. VEGF), which diffuse throughout the eye, including into the anterior segment. Vasoproliferative factors stimulate angiogenesis. Neovascularization usually starts with endothelial budding from capillaries at the pupil margin (although it can also start within the angle). The new vessels then grow in an irregular pattern over the surface of the iris towards the angle (see Figure 8.31).

Fig 8.31 Neovascularization of the iris

Fig 8.31
Neovascularization of the iris

Neovascular tissue invading the angle (see Figure 8.32) arborizes with proliferating connective tissue from myofibroblasts to form a fibrovascular membrane. This membrane may block the TM, thus causing a rise in IOP. The condition is reversible initially; however, if untreated, the myofibroblasts, which have smooth muscle characteristics, will contract and pull peripheral iris over the TM in a zip-like manner, resulting in PAS.

Fig 8.32 Gonioscopic view of new vessels within the angle

Fig 8.32
Gonioscopic view of new vessels within the angle

Prevalence

  • Ischaemic CRVO: 16%–60% of patients develop neovascular glaucoma (depending on the extent of capillary non-perfusion).

  • Proliferative diabetic retinopathy: approximately 20% of type 1 diabetes mellitus patients with proliferative diabetic retinopathy eventually develop neovascular glaucoma.

  • CRAO: approximately 18%

Risk factors

  • Ischaemic CRVO (most common cause of unilateral neovascular glaucoma):

    • Age

    • Systemic hypertension

    • OHT/primary open-angle glaucoma

    • Hypercoagulable state

    • Vasculitis

    • Drugs: diuretics

    • Retrobulbar external compression: e.g. from thyroid eye disease, orbital tumour

  • Diabetes mellitus: the most common cause of bilateral neovascular glaucoma

  • Ocular ischaemic syndrome; e.g. from carotid artery disease

  • BRVO

  • CRAO/BRAO

  • Chronic retinal detachment

  • Sickle cell retinopathy

  • Ocular neoplasm

  • Chronic uveitis

  • Endophthalmitis

  • Sympathetic ophthalmia

  • Radiation retinopathy

Clinical evaluation

History

  • Asymptomatic in early stages

  • Ocular pain or photophobia

  • Red eye

  • Reduced vision

Examination

  • Congestion of globe

  • Corneal oedema

  • Raised IOP

  • Aqueous flare

  • Possible hyphaema

  • Rubeosis iridis: check the angle gonioscopically prior to dilation

  • Synechial angle closure

  • Distorted pupil with ectropion uveae

Differential diagnosis

  • Angle-closure glaucoma

  • Post-vitrectomy inflammation

  • Uveitis: radial engorged vessels

  • Intraocular tumours

Management

  • Prevention is the best treatment.

  • PRP: should be done as soon as neovascularization is detected, not deferred to a routine laser list

  • Intravitreal anti-VEGF agents: in conjunction with PRP may prevent glaucoma occurring in eyes with NVI; not effective alone at controlling IOP once PAS and neovascular glaucoma are established; also show promise as an adjunct to glaucoma surgery because of their effects on wound healing

  • Aqueous suppressants

  • Atropine eye drops, 1%, twice a day: increases uveoscleral outflow

  • Topical corticosteroid: controls congestion and inflammation

  • Trabeculectomy: with antimetabolites combined with an intravitreal anti-VEGF drug; guarded prognosis

  • Glaucoma drainage device

  • Cyclodestructive procedure: cyclodiode laser

  • Enucleation

Follow-up

  • Close follow-up is crucial, as neovascular glaucoma can be reversible in early stages.

  • Fill-in PRP is applied as required.

  • An ischaemic CRVO can cause neovascular glaucoma within 3 months (so-called 90-day glaucoma) or up to 2 years later.

Prognosis

  • Excellent if condition is fully treated in early stages

  • Extremely poor once synechial angle closure has occurred

8.21 Aqueous misdirection

Aqueous misdirection (malignant glaucoma), also known as ciliary block glaucoma, is a type of secondary angle-closure glaucoma. Aqueous misdirection usually follows penetrating surgery in eyes that are anatomically predisposed, particularly eyes with a short axial length.

Pathophysiology

Ocular surgery causes a not fully understood initiating event (postulated to be sudden anterior chamber decompression) that changes the direction of aqueous humour flow. UBM has shown the ciliary body to be anteriorly rotated so that it causes the ciliary processes and lens equator to come into contact (see Figure 8.33). The anterior vitreous face may also contact the iris and ciliary processes. There may be an underlying shallow peripheral ciliochoroidal effusion.

Fig 8.33 Diagram showing the proposed mechanism of malignant glaucoma

Fig 8.33
Diagram showing the proposed mechanism of malignant glaucoma

These changes may prevent the aqueous humour from flowing forwards through the pupil into the anterior chamber. Instead, the aqueous humour may flow into the vitreous, leading to an increase in vitreous volume, increased posterior segment pressure, forwards displacement of the lens–iris diaphragm, and shallowing of the anterior chamber. In contrast to the case with pupil block, there is shallowing both centrally and peripherally.

Aqueous misdirection may present days, months, or years after surgery. IOP may be normal or high and may be associated with secondary angle closure. Aqueous misdirection has been reported after trabeculectomy, cataract surgery, laser iridotomy, laser suture lysis, scleral buckling, and anterior segment laser procedures; it has also been reported to occur spontaneously.

Differential diagnosis

  • Choroidal effusions: B-scan ultrasonography should be performed

  • Suprachoroidal haemorrhage: may be associated with sudden pain

  • Pupil block: anterior chamber remains deep centrally

  • Overfiltration and wound leak : anterior chamber may be shallow but the IOP will be low

Risk factors

  • Choroidal effusions

  • Filtration surgery: particularly for PACG

  • Cataract surgery

  • Nd:YAG capsulotomy or laser iridotomy

  • Nanophthalmos: small globe with normal lens size

  • Increased age or cataract: increased lens size

  • Trauma or pseudoexfoliation: decreased anterior–posterior lens position due to weak or ruptured zonules

  • Inflammation or vascular engorgement: swelling of the ciliary body

  • Chronic miotic use

Clinical evaluation

History

  • Recent eye surgery: can be up to months post-operatively

  • Blurred vision

  • Usually no pain

Examination

  • Shallow anterior chamber: central and peripheral

  • No iris bombé

  • High IOP, or relative increase after glaucoma surgery

  • Corneal oedema, if the IOP is high or there is lens–endothelial contact

Investigations

  • UBM

Management

Medical (50% respond)

  • Topical cycloplegics/mydriatics (atropine 1% four times a day): paralyses the ciliary muscles, tightens the zonules, and helps pull the lens posteriorly

  • Topical aqueous suppressants: reduce the amount of aqueous humour entering the vitreous

  • Oral or systemic hyperosmotic agents

  • Topical corticosteroids

  • Discontinue miotics

Surgical

  • Cyclodiode laser: 10–15 shots at 1500 mW for 1500 milliseconds in 1 quadrant

  • Decompartmentalize the eye: aim to create communication between the anterior and posterior segments to allow the free movement of aqueous humour

  • Pseudophakic eye:

    • Nd:YAG laser to the peripheral anterior hyaloid face through a pre-existing peripheral iridectomy

    • Surgical decompartmentalization with pars plana vitrectomy and removal of anterior hyaloid as far peripherally as possible

  • Phakic eye:

    • Surgical decompartmentalization with a lens extraction–posterior capsulectomy–vitrectomy procedure

8.22 Iridocorneal endothelial syndrome and iridocorneal dysgenesis

Iridocorneal endothelial syndrome

Iridocorneal endothelial syndrome is an acquired condition consisting of three separate entities with overlapping features:

  1. 1. Essential iris atrophy

  2. 2. Chandlers syndrome

  3. 3. Cogan–Reese syndrome

These entities have in common an abnormal corneal endothelial cell layer, which forms a membrane over the angle structures and iris, initially causing secondary open-angle glaucoma but eventually leading to angle closure because of iridocorneal adhesions and contraction of the membrane.

Pathophysiology

Endothelial cells in iridocorneal endothelial syndrome have been found to be morphologically similar to epithelial cells; this observation suggests that the cells are derived from an embryological ectopia or a metaplastic process. HSV has been implicated in the aetiology of this condition, as HSV DNA has been found in a large number of iridocorneal endothelial syndrome corneal specimens by PCR; however, a definite link has not been proven. The pathological membrane complex migrates over the drainage angle, causing obstruction and secondary angle closure with formation of PAS. Tractional forces may cause distortion of the iris in opposing quadrants. Corneal opacity/oedema is also a feature because of increased IOP and reduced endothelial cell count.

Prevalence

  • Rare, but exact incidence is not known

  • Approximately 50% of iridocorneal endothelial syndrome patients develop glaucoma.

  • Patients with the Cogan–Reece variant are at greatest risk of developing raised IOP.

Risk factors

  • Age: 20–50 years

  • Sex: female

  • History of HSV

  • Race: Caucasian

Clinical evaluation

History

  • Asymptomatic in early stages; often an incidental finding

  • Later on:

    • Decreased vision

    • Ocular pain

    • Red eye

    • Iris abnormalities

Examination

The three entities are based on signs present in early stages of the disease. During the later stages, they can be indistinguishable. Signs are always unilateral. There are no non-ocular features. Corneal specular microscopy is useful and shows pleomorphic endothelial cells with intracellular dark spots.

  • Common signs:

    • Asymptomatic in early stages; often an incidental finding

    • Corectopia: distortion of pupil (see Figure 8.34)

    • Pseudopolycoria: ‘extra’ pupils

    • Iris atrophy: moth-eaten iris; of varying severity

    • ‘Hammered silver’ appearance to endothelium

    • Broad-based PAS

Fig 8.34 Mild corectopia in iridocorneal endothelial syndrome

Fig 8.34
Mild corectopia in iridocorneal endothelial syndrome

Chandlers syndrome (most common)

  • Characterized by severe corneal changes, blurred vision, and haloes

  • Normal or mild iris changes; no iris holes

Progressive iris atrophy

  • Characterized by severe iris changes, corectopia, pseudopolycoria, atrophy, and ectropion uveae

Cogan–Reese (iris naevus) syndrome

  • Characterized by the presence of pigmented nodules in the iris stroma

  • A sheet of membrane-like material covers the iris; naevi form where the iris tissue protrudes through.

  • The iris has a flattened appearance.

Management

  • Topical therapy is often ineffective

  • Hypertonic saline for corneal oedema

  • Trabeculectomy plus antimetabolites: the filtration site should be in an area free of membrane; there is a high failure rate, owing to membrane growing over the sclerostomy, and high post-operative inflammation

  • Glaucoma drainage devices (also high failure rate)

  • Cyclodestructive therapy

  • Penetrating keratoplasty for corneal changes

  • Laser trabeculoplasty is not recommended, as it increases the formation of PAS.

Follow-up

  • To assess corneal clarity and development of glaucoma

Prognosis

  • Poor, owing to resistance to therapy

Axenfeld–Riegers syndrome

Pathophysiology

  • Represents a spectrum of anterior segment maldevelopment with or without iris and systemic abnormalities

  • Unlike iridocorneal endothelial syndrome, Axenfeld–Riegers syndrome is present at birth (see also Section 9.26).

  • Axenfeld anomaly: a prominent anteriorly displaced Schwalbes line (posterior embryotoxon) is present with associated iridocorneal adhesions. The posterior embryotoxon appears as a white line in the peripheral cornea (partial or 360°) visible on slit lamp examination in most, or by gonioscopy. NB: Posterior embryotoxon is seen in 15% of normal eyes and is not associated with glaucoma if present in isolation.

  • Reiger anomaly: Axenfeld anomaly plus iris changes (see Chapter 9, Figure 9.36)

  • Reiger syndrome: Reiger anomaly with non-ocular features

  • Genetics: typically autosomal dominant, with associated mutations described in the PITX2 gene (Chromosome 4q25), the FOXC1 gene (Chromosome 6p25), and on Chromosome 13q

Clinical features

Corneal

  • The hallmark is a posterior embryotoxon.

  • The central cornea is typically normal.

Angle abnormalities

  • Iris processes/bands/sheets extend across the angle to the TM or even up to the posterior embryotoxon.

  • High insertion of the iris can obscure the scleral spur.

Iris abnormalities

  • May be absent

  • Include iris hypoplasia with easily visible iris sphincter, corectopia (displaced pupil), and polycoria (iris holes)

Glaucoma

  • There is a 50% risk of raised IOP; glaucoma usually develops in the second or third decade (very rarely in infancy).

  • Patients with high iris insertion are more prone to developing glaucoma.

Non-ocular features

  • Facial: maxillary hypoplasia, broad nasal bridge, telecanthus, prominent lower lip, micro/hypodontia

  • CNS: mental retardation, empty sella syndrome

  • Genital: hypospadias

  • Endocrine: growth hormone deficiency

Treatment

  • Consider physician referral.

  • Angle surgery in children can be considered.

  • Treat glaucoma as in primary open-angle glaucoma: medically initially then surgery (trabeculectomy/glaucoma drainage devices).

  • Laser trabeculoplasty is not possible/is contraindicated, owing to angle abnormalities.

8.23 Ocular hypotensive agents I

Ocular hypotensive agents lower IOP by increasing aqueous humour outflow (e.g. prostaglandin analogues) and/or suppressing aqueous humour production (e.g. carbonic anhydrase inhibitors).

Prostaglandin analogues

Mechanism of action

Agonists of prostaglandin F2 alpha increase outflow mainly through the uveoscleral pathway. This effect is thought to be due to the activation of matrix metalloproteinases and consequent increase in the turnover of the extracellular matrix. IOP reduction in an excess of 30% is often achieved.

Side effects

Local

  • Stinging

  • Tearing

  • Hyperaemia

  • Darkening of the iris

  • Thicker and longer lashes

  • Cystoid macular oedema

  • Anterior uveitis

Systemic

  • Upper respiratory tract infection

  • Backache

  • Chest pain

  • Myalgia

  • Exacerbation of angina, and new shortness of breath

Contraindications

  • Pregnancy

  • Inflammatory conditions, including post-surgical (aphakic and pseudophakic with posterior capsule breaks at greatest risk)

Preparations

  • Latanoprost (Xalatan): available as 0.005%

  • Travoprost (Travatan): available as 0.004%

  • Bimatoprost (Lumigan): available as 0.03% and 0.01%

  • Tafluprost (Saflutan): available as 0.0015% (preservative free)

  • Generally used as a first-line therapy, owing to proven efficacy and tolerability

  • All have a duration of action of 24 hours.

  • All have once-daily night-time dosing.

Beta blockers

Mechanism of action

Beta adrenergic antagonists block the beta receptors of the ciliary body, thus decreasing aqueous humour production. They can be non-selective, acting on both beta 1 receptors and beta 2 receptors, or cardioselective and thus more potent at beta 1 receptors. Beta blockers are less effective at reducing the nocturnal diurnal IOP peak than other agents are.

Side effects

  • Most occur within the first week.

Local

  • Stinging

  • Dry eye

  • Hyperaemia

Systemic

  • Bradycardia or heart block

  • Bronchospasm

  • Fatigue

  • Mood change

  • Impotence

Contraindications

  • Asthma, chronic obstructive pulmonary disease, bradycardia (resting heart rate of less than 60 bpm), heart block, congestive cardiac failure

  • Patients already on systemic beta blockade or calcium channel blockers should be monitored for potential additive toxicity.

Preparations

Timolol maleate (Timoptol)

  • Non-selective

  • The majority of patients achieve 20% IOP reduction but 10% of the population are unresponsive.

  • Effectiveness can diminish in the first 2 weeks (short-term escape).

  • Further diminishing efficacy may occur within 3 months (long-term drift).

  • Onset of action within 30 minutes; peak at 2 hours.

  • Available as 0.25% and 0.5% (similar efficacy; therefore, 0.25% should be first choice)

  • Twice-daily dosing

Timolol LA (0.25% or 0.5%)

  • Long-acting variant

  • Changes from liquid to gel-like state when instilled

  • Once-daily dosing

  • Transient blurring for up to 5 minutes often occurs

Levobunolol (Betagan; 0.25% or 0.5%)

  • Non-selective

  • Onset of action within 1 hour; peak at 2–6 hours

Betaxolol (Betoptic; 0.5%)

  • Selective beta 1 blocker

  • Use with great care in patients with respiratory conditions.

  • Cardiac patients still contraindicated.

  • Onset of action within 30 minutes; peak at 2 hours; duration up to 12 hours

  • Twice-daily dosing

Alpha agonists

Mechanism of action

Alpha 2 adrenergic agonists act on alpha receptors in the ciliary body to inhibit aqueous secretion.

Side effects

Local

  • Irritation

  • Allergy

  • Dry eye

Systemic

  • Dry mouth

  • Hypotension

  • Sedation

Contraindications

  • Monoamine oxidase inhibitor use

  • Brimonidine is contraindicated in children less than 7, as it crosses the blood–brain barrier and causes respiratory depression.

Preparations

Brimonidine (Alphagan; 0.2%)

  • Also increases uveoscleral outflow

  • Animal studies suggest that there may be neuroprotective properties.

  • Peak effect at 2 hours; duration of action, 12 hours

  • Twice-daily dosing

  • Allergy occurs frequently with long-term therapy, presenting sometimes months later.

Apraclonidine (Iopidine)

  • Onset of action within 1 hour; duration of at least 2 hours

  • Available as 0.5% (27% IOP reduction) or 1% (37% IOP reduction)

  • Causes allergic conjunctivitis in 9% within 3 months and in 50% after long-term treatment

  • Exhibits tachyphylaxis (decreased therapeutic response following initial doses)

  • Its main use is for the prevention of IOP spikes in the short term, e.g. after anterior segment laser and in angle-closure glaucoma patients.

  • Also plays a role in those already on maximal medical therapy who are unsuitable for surgery

Cholinergic agents

Mechanism of action

Cholinergics act on muscarinic receptors of the ciliary muscle, causing the ciliary muscle to contract and move anteriorly. The anterior tendons of the ciliary muscle insert into the TM; therefore, contraction causes the TM to spread, Schlemms canal to dilate, and outflow resistance to decrease.

Side effects

Local

  • Brow ache

  • Accommodative spasm

  • Variable myopia

  • Retinal tear/detachment

  • Decreased peripheral and night vision

Systemic

  • Gastrointestinal upset

  • Abdominal cramping

  • Salivation

  • Potential heart block

Contraindications

  • Peripheral retinal pathology

  • Central media opacity

  • Young age: increased myopic effect

  • Uveitic patients

  • Less effective in patients with damaged TMs

  • Chronic use can result in permanent miosis: problems with dilated fundoscopy.

Preparations

Pilocarpine

  • Onset of action within 20 minutes; peak at 2 hours; duration up to 6 hours

  • Available as 0.5%, 1%, 2%, 3%, and 4%

  • Administered four times a day; short duration of action

  • Dosage increased in stepwise increments

  • Maximum concentrations usually 2% for light irises, 4% for brown/dark irises

Topical carbonic anhydrase inhibitors

Mechanism of action

  • Inhibition of the enzyme carbonic anhydrase decreases aqueous humour production in the ciliary body.

  • Achieves a 20% reduction in IOP

Side effects

Local

  • Mild hyperaemia

  • Stinging

  • Bitter taste

Systemic

  • Diuresis

  • Fatigue

  • Gastrointestinal upset

  • Stevens–Johnson syndrome

  • Aplastic anaemia

Contraindications

  • Sulphonamide sensitivity

  • Use with caution in corneal decompensation (carbonic anhydrase is an important enzyme in the corneal endothelial pump).

Preparations

Dorzolamide (Trusopt)

  • Available as 2%

  • Dose three times a day alone, or twice a day with concurrent beta blocker use.

Brinzolamide (Azopt)

  • Available as 1%

  • Twice-daily dosing

  • The suspension form allows the drug to be buffered at physiological pH (so that it is therefore more comfortable and with fewer allergic reactions, compared to other preparations).

8.24 Ocular hypotensive agents II

Systemic carbonic anhydrase inhibitors

Mechanism of action

  • As for topical treatment

  • Oral or intravenous administration will also cause dehydration of the vitreous.

Side effects

  • As for topical carbonic anhydrase inhibitors

  • Additional systemic concerns: hypokalaemia, renal stones, paraesthesia (tingling of hands and feet), nausea, cramps, malaise, depression, impotence

Contraindications

  • Sulphonamide sensitivity

  • Hyponatraemia

  • Hypokalaemia

  • Renal stones

  • Use of thiazide diuretics or digitalis

  • Pregnancy

Preparations

Acetazolamide (Diamox)

  • IOP reduction up to 35%

  • Available as 125 mg or 250 mg tablets or 250 mg slow-release capsules orally, or as 500 mg vials for use intravenously

  • Dosing four times a day for tablets, twice a day for slow-release capsules, or stat dosing as required for intravenous use

  • Maximum dosage: 1000 mg in 24 hours

Hyperosmotic agents

Mechanism of action

  • Dehydrates the vitreous and reduces intraocular volume by increasing plasma osmolality, thereby drawing fluid into the intravascular space

Side effects

  • Diuresis, cardiac failure, urinary retention (in men), backache, headache, myocardial infarction, confusion

  • Also vomiting, when glycerine is used

Contraindications

  • Congestive cardiac failure, pre-existing dehydration

  • Also watch for diabetic ketoacidosis with glycerine (broken down to glucose).

  • Caution in elderly patients and those with renal disease

  • Only used when rapid reduction is required when IOP is dangerously high

Preparations

Glycerine

  • Oral agent in 50% solution

  • Needs rapid ingestion to maximally change osmolality

  • Serve mixed with orange juice or over ice to reduce vomiting

Mannitol

  • Drug of choice, as no penetration into vitreous cavity

  • Dosage 1–2 g/kg of 20% solution given intravenously over 45 minutes

Fixed dose combinations

The fact that only two drops of the fixed dose combinations need to be used decreases the preservative load and may improve compliance. A disadvantage is that all the fixed dose combinations include beta blockers, which may be contraindicated; also, the fixed dose combinations contain the highest available concentration of the drugs (e.g. timolol 0.5%). These agents should not be used as first-line therapy and should only be utilized when the efficacy and tolerability of the individual components have been established.

Preparations

Cosopt

  • A combination of 0.5% timolol and 2% dorzolamide

  • Twice-daily dosing

Combigan

  • A combination of 0.5% timolol and 0.2% brimonidine

  • Twice-daily dosing

Xalacom/DuoTrav/GanFort

  • A combination of 0.5% timolol and Xalatan/Travatan/Lumigan, respectively

  • Once-daily dosing

Use of ocular hypotensive agents during pregnancy and lactation

Discuss plans for management of glaucoma during pregnancy in all women of childbearing age. The risks of medication to the foetus must be balanced against the risk of visual loss to the mother. Ideally, all glaucoma medications should be avoided, particularly prior to conception and during the first trimester. IOP tends to decrease during pregnancy.

The FDA categorizes medication safety during pregnancy into Categories A to D:

  • Category A: Safety established using human studies

    • No glaucoma medications are in this category

  • Category B: Presumed safe based on animal studies

    • Brimonidine (although it does cross the placenta and may cause respiratory depression; contraindicated in children <7 years old)

  • Category C: Uncertain safety. No human studies but animal studies show adverse effect.

    • Beta blockers: fetal bradycardia

    • Carbonic anhydrase inhibitors: reports of forelimb deformities with oral use in animals

    • Prostaglandin analogues: risk of premature labour

  • Category D: Unsafe

If medications cannot be stopped, beta blockers are probably the best option in early pregnancy but consider stopping prior to birth. Advice should be given on punctal occlusion and consider using the once-daily gel form. Prostaglandin analogues should be avoided at all stages.

Beta blockers are not recommended during lactation, but topical carbonic anhydrase inhibitors and prostaglandin analogues are reasonable options.

Consult the latest safety information before prescribing in pregnancy.

8.25 Laser therapy for glaucoma

Argon Laser Trabeculoplasty (ALT)

ALT involves the application of discrete laser burns to the TM (see Figure 8.35). The Glaucoma Laser Trial (1990) found ALT to be as effective as timolol for the initial treatment of glaucoma; however, as patients in that trial had used ALT in one eye and timolol in the other, a drug crossover effect could have biased results. The effectiveness of ALT also decreases with time. In eyes with initial success (at least a 20% reduction in IOP), approximately 19% fail after 1 year and an additional 10% fail each year thereafter, reaching a 65% failure rate at 5 years. With the introduction of better medications, ALT is not a first-line treatment.

Fig 8.35 Technique of ALT
The laser is aimed at the junction of pigmented and non-pigmented TM. (1) The appearance of evenly spaced, round spots of blanching with clear edges with or without a small bubble is the ideal reaction. (2) Production of an oval spot means the aiming beam is not perpendicular to the TM and thus requires refocusing

Fig 8.35
Technique of ALT

The laser is aimed at the junction of pigmented and non-pigmented TM. (1) The appearance of evenly spaced, round spots of blanching with clear edges with or without a small bubble is the ideal reaction. (2) Production of an oval spot means the aiming beam is not perpendicular to the TM and thus requires refocusing

Mode of action

There are two main theories concerning the mode of action of ALT:

  1. 1. Mechanical theory: coagulative damage to the TM causes collagen shrinkage and scarring, thus exerting traction on the adjacent TM and opening intertrabecular spaces.

  2. 2. Cellular theory: migration of macrophages into the TM occurs in response to coagulative damage. Macrophages phagocytose any debris present, thus improving aqueous outflow.

Indications

  • Primary open-angle glaucoma, pigmentary glaucoma, and pseudoexfoliative glaucoma

  • Ineffective in paediatric glaucoma and secondary glaucoma

  • Not suitable if angle abnormalities are present

Laser settings

  • Use a 50 μ‎m spot with a 0.1-second duration at 300–850 mW.

  • Start with low power setting and increase if reaction is inadequate; less power is required if the pigment is heavy than if otherwise.

Method

  • Follow laser safety protocols.

  • Gain patient consent (including advising on failure and complications).

  • Instil topical anaesthetic and apraclonidine 1% (to prevent IOP spike).

  • Insert Latina goniolens at the 12 o’clock position (as the inferior angle is easiest to visualize).

  • Identify the anterior border of the pigmented TM as the site to treat.

  • Focus the aiming beam perpendicular to the TM (round spot with a clear edge).

  • Look for blanching or small bubbles whilst treating.

  • Place 50 equally spaced shots over 180° (or entire circumference with 100 burns).

  • Instil additional apraclonidine 1%.

Post-procedure guidelines

  • Check for IOP spike after 1 hour.

  • Prescribe topical steroid four times a day for 1 week and continue usual glaucoma medication.

  • Arrange follow-up in 4–6 weeks.

  • If IOP reduction is inadequate after 180° treatment, consider ALT for the remaining superior 180°.

  • Do not treat the same area twice.

Complications

  • PAS: if burns applied too posteriorly or energy too high

  • Bleeding: if blood vessels inadvertently treated (apply pressure with goniolens)

  • IOP spike

  • Anterior uveitis

Selective Laser Trabeculoplasty (SLT)

SLT is a newer procedure, which is employed in a similar manner as ALT but uses a Q-switched, frequency-doubled Nd:YAG laser with a frequency of 532 nm (see Figure 8.36). Pulse duration of 3 nanoseconds is used (ALT is 0.1 seconds). The energy used in SLT is several thousand times lower than that used in ALT.

Fig 8.36 Selective laser trabeculoplasty machine

Fig 8.36
Selective laser trabeculoplasty machine

In theory, SLT selectively targets pigmented TM cells and spares adjacent tissue from collateral thermal damage. The exact mechanism of action is unknown but it appears to be cellular rather than mechanical.

Indications

  • Indications are similar to those for ALT.

Laser settings

  • Fixed spot size, 3-nanosecond duration; start at 0.4 mJ (high pigment) to 0.8 mJ (low pigment)

  • Adjust according to response.

Method

  • Follow laser safety protocols.

  • Gain patient consent (including advising on failure and complications).

  • Instil topical anaesthetic and apraclonidine 1% (to prevent IOP spike).

  • Insert Latina goniolens (or equivalent with zero magnification).

  • Start with low power setting and increase if reaction is inadequate.

  • Look for fine champagne bubbles; reduce energy level to 0.1 mJ below bubble formation threshold.

  • Treat 180° or 360° with 50 or 100 shots, respectively.

  • Instil additional apraclonidine 1%.

Post-procedure guidelines

  • Topical NSAIDs (not steroids) four times a day for 4 days post-treatment

  • Arrange follow-up in 2–6 weeks.

Success is more likely with 360° of treatment (approximately 80% of cases achieve a 20% reduction in IOP, and 60% achieve a 30% reduction in IOP when SLT is used as the initial treatment). A response may take 4 to 6 weeks to be maximal. As with ALT, the effects of SLT wear off over time; however, unlike ALT, SLT can be repeated. If there has been no IOP-lowering effect with the first treatment, retreatment is not recommended.

Complications

  • Rare; but anterior chamber inflammation and IOP spike may occur

Cyclodiode laser

Cyclodestructive procedures lower IOP by destroying part of the ciliary body, thus reducing aqueous inflow. The most common method at present employs a trans-scleral diode laser (a cyclodiode laser). Endoscopic cyclophotocoagulation is also available in some centres.

The success rate of cyclodiode laser treatment depends on the type of glaucoma treated. Often the procedure needs to be repeated.

Indications

  • Uncontrolled end-stage secondary glaucoma, e.g. for pain relief

  • Patients with multiple previous failed glaucoma procedures

  • Primary procedure in certain eyes where surgery is inappropriate

  • To reduce IOP; as a temporizing measure before undertaking surgery

Laser settings

  • Typical settings for the laser are 1500 milliseconds at 1500 mW.

  • If popping occurs, reduce the power with or without increasing the duration.

  • The number of burns given can be varied depending on the eye but 30 are typical.

Method

  • Follow laser safety protocols.

  • Gain patient consent (including advising on failure/retreatment and complications).

  • Administer sub-Tenons or peribulbar anaesthetic (diode laser treatment is painful).

  • Patient lies flat and an eyelid speculum is inserted.

  • Use transillumination to confirm the location of the ciliary body.

  • The ciliary body appears as a dark area 0.5–2.0 mm from the limbus.

  • Eyes that have undergone multiple previous surgeries may have abnormally placed ciliary bodies or even areas where the ciliary body is absent.

  • Place the diode probe against the globe with the heel at the anterior margin of the ciliary body (see Figure 8.37).

  • Apply burns circumferentially, avoiding 3 and 9 o’clock (positions of posterior ciliary nerves), areas of subconjunctival haemorrhage (will reduce laser penetration), and areas of scleral thinning (risk of perforation).

  • Treat 270°, sparing one quadrant.

Fig 8.37 The technique of cyclodiode laser
The probe is placed vertically on the anaesthetized eye with the base of the probe against the limbus

Fig 8.37
The technique of cyclodiode laser

The probe is placed vertically on the anaesthetized eye with the base of the probe against the limbus

Post-procedure guidelines

  • Prescribe topical steroid (e.g. dexamethasone 0.1%) 6–8 times per day for 1 week.

  • Continue all usual glaucoma medication; arrange follow-up in 1–2 weeks.

Complications

  • Conjunctival burns

  • Iris burns (if too anterior)

  • Localized scleral thinning

  • Corneal decompensation

  • Anterior uveitis

  • Bleeding (hyphaema or vitreous haemorrhage)

  • Hypotony (including phthisis bulbi)

  • Aqueous misdirection/malignant glaucoma

  • Cataract

  • Retinal or choroidal detachment

  • Sympathetic ophthalmitis

Peripheral iridotomy (PI)

Laser PI involves creating a conduit for the flow of aqueous humour via a laser-induced puncture through the peripheral iris (see Figure 8.38). This procedure allows for the free passage of aqueous humour between the posterior and anterior chambers. The position of the iridotomy should be within the superior iris, covered by the upper lid to minimize risk of monocular diplopia and glare, and as peripheral as possible to prevent damage to the lens. Three-quarters of cases of appositional angle closure are reversed following Laser PI.

Fig 8.38 Iris transillumination defects seen after laser peripheral iridotomies
Only one Laser PI is necessary and, if placed under the upper lid, it should be as peripheral and as close to 12 o’clock as possible. Laser PIs are now also done at 3 o’clock and at 9 o’clock to avoid a meniscus effect diverting light to the 12 o’clock peripheral iridotomy and thus causing visual disturbance; one randomized trial has suggested that the incidence of visual disturbance is reduced with fully interpalpebral iridotomies

Fig 8.38
Iris transillumination defects seen after laser peripheral iridotomies

Only one Laser PI is necessary and, if placed under the upper lid, it should be as peripheral and as close to 12 o’clock as possible. Laser PIs are now also done at 3 o’clock and at 9 o’clock to avoid a meniscus effect diverting light to the 12 o’clock peripheral iridotomy and thus causing visual disturbance; one randomized trial has suggested that the incidence of visual disturbance is reduced with fully interpalpebral iridotomies

Indications

  • PACS, primary angle closure, primary angle glaucoma

  • Secondary angle closure where pupil block is a component

Laser settings

  • Use the lowest energy possible to achieve a patent Laser PI.

  • Typically use single 0.8 to 1.5 mJ shots and expect to use a total energy of up to 50 mJ.

  • Thin blue irises need a lower power setting than thick brown irises do; the latter should have argon laser pretreatment.

Method

  • Follow laser safety protocols.

  • Gain patient consent (including advising on risks).

  • Gonioscopy should have been performed before the procedure, and the findings documented.

  • If the patient is taking warfarin, check recent international normalized ratio.

  • Instil pilocarpine 2% at least 30 minutes before treatment (miosis will ‘unfold’ peripheral iris).

  • Instil apraclonidine (iopidine) 1% (to prevent IOP spike).

  • Instil topical anaesthetic.

  • Insert contact lens, such as an Abraham iridotomy lens.

  • Position the Laser PI between 11 and 1 o’clock but never at the level of the lid margin.

  • Look for iris crypts or thin areas that will be easier to penetrate.

  • A ‘pigment gush’ indicates successful penetration.

  • If there is bleeding (occurs in 50% of cases), gentle pressure on the iridotomy lens should stop it.

  • Instil additional apraclonidine 1% at the end of the procedure.

Post-procedure guidelines

  • Prescribe topical steroid (e.g. dexamethasone 0.1%) hourly for 24 hours (day only) and then four times a day for 1 week. The aim is to limit any inflammatory response, which could increase PAS if the angle remains narrow.

  • Check IOP after 1 hour.

  • Arrange follow-up for 1 week to check IOP and assess patency of peripheral iridotomy.

  • Gonioscopy should be repeated to detect any deepening in the angle and to exclude residual narrowing due to phacomorphic or plateau iris components.

Complications

  • One in four risk of a short-term change in vision; vision change usually will resolve by 6 weeks.

  • Glare: most likely if Laser PI positioned at the level of the lid margin, owing to the prismatic effect of the marginal tear strip

  • Bright horizontal line (marginal tear strip) or dark vertical lines (lashes)

  • Transient pressure rise: tends to occur within 1 hour; more common if high pretreatment IOP or PAS

  • Anterior chamber inflammation

  • Corneal burns: increased risk with shallow anterior chamber

  • Lens opacities: can occur at treatment site but tend to be localized and non-progressive; lens rupture has been reported

  • Macular damage: theoretical risk if beam is aimed perpendicularly

  • Visual loss (1 in 7000)

Argon laser pretreatment

  • Use the Wise or Abraham contact lens and treat in two phases:

    1. 1. Low power: 80–130 mW, 0.05 seconds, 50 μ‎m; make a rosette pattern of soft pitting in the iris using 15–20 shots

    2. 2. High power: 700–750 mW, 0.1 second, 50 μ‎m; apply 10–20 shots until the radial muscle fibres are visible

  • Complete the iridotomy using the Nd:YAG laser as for PI.

Argon laser peripheral iridoplasty (ALPI)

In ALPI, the argon laser is used to shrink the peripheral iris and draw it away from the TM. ALPI is useful for the treatment of plateau iris syndrome and primary angle closure (acute or chronic). It is successful in about 50% of cases. ALPI is not appropriate for most patients with PAS and may worsen them.

  • Prepare the patient using the same steps as for iridotomy.

  • Use a 500 μ‎m spot, 0.5–0.7 seconds; start with low power (100 mW) and increase (up to 180–300 mW).

  • Apply 15–20 shots around the peripheral circumference of the iris.

  • Avoid the cornea.

  • Look for a gentle contraction of the iris stroma.

  • Post-operative treatment is the same as for Laser PI but continue pilocarpine for at least 1 week to prevent PAS developing. ALPI can be used in the acute setting for primary angle closure but must be followed by Laser PI.

Complications

  • Transient pressure rise

  • Ache

  • Reduced vision

  • Dilated pupil, unresponsive to light causing glare; can be avoided with appropriate spacing of the burns

  • Corneal burns

Argon laser suture lysis

Following trabeculectomy, an argon laser may be used to lyse fixed nylon sutures in the scleral flap. Laser treatment can be performed through the tip of a glass rod or by using a Blumenthal laser lens. When a suture is lysed, there is likely to be increased flow under the scleral flap into the subconjunctival space and the sub-Tenons space (the bleb). Whether or not laser suture lysis is necessary depends on the surgical technique and wound healing. Sutures may be obscured by subconjunctival haemorrhage or a thick Tenons capsule.

8.26 Glaucoma surgery

Glaucoma surgery may be indicated when IOP is not satisfactorily controlled with medication, when medication is contraindicated, or when compliance is poor. Surgery may also be offered as initial treatment in patients who present with advanced disease.

The main surgical options are trabeculectomy, or insertion of a glaucoma drainage device (tube). There are also a growing number of alternative procedures, including non-penetrating surgery. The type of surgery selected should be tailored to suit the individual, as each has its own specific risk–benefit profile. This section focuses on adult glaucoma surgery.

Trabeculectomy

The aim of trabeculectomy is to create a fistula that is guarded by a superficial scleral flap. The fistula allows aqueous humour to flow from the anterior chamber to the sub-Tenons space, forming a ‘bleb’ of fluid that is then absorbed into the episcleral vessels (see Figure 8.39). A challenge of trabeculectomy is managing wound healing. Fibrosis and scarring can lead to closure of the fistula and surgical failure; therefore, intra- and post-operative anti-fibrotics such as mitomycin C and 5-fluorouracil can be used to prevent fibrosis and are increasingly used in all patients; however, they are associated with complications, including corneal epithelial defects, post-operative wound leaks, and cystic thin-walled blebs that predispose to chronic hypotony, late-onset bleb leak, and endophthalmitis.

Fig 8.39 Example of trabeculectomy with mitomycin C
Placement of mitomycin C polyvinyl alcohol sponges under the Tenons capsule

Fig 8.39
Example of trabeculectomy with mitomycin C

Placement of mitomycin C polyvinyl alcohol sponges under the Tenons capsule

The problems associated with anti-fibrotics can be largely avoided by adopting a meticulous surgical technique. Using modern techniques such as ‘The Moorfields Safer Surgery System’ trabeculectomy with adjunctive anti-fibrotics can achieve success rates of 80%–90% in primary open-angle glaucoma.

Method

  1. 1. Place a 7–0 silk traction suture into the superior cornea.

  2. 2. Create a fornix-based conjunctival flap.

  3. 3. Clear episcleral tissue and wet-field cauterize the proposed flap area.

  4. 4. Create a rectangular scleral flap that is two-thirds of the scleral thickness. Ensure the flap is wider than it is long to encourage posterior drainage (see Figure 8.40).

  5. 5. Dissect the scleral flap forwards until clear cornea is reached.

  6. 6. Pre-place at least two 10–0 nylon sutures in the scleral flap (to enable quick closure).

  7. 7. Perform a temporal paracentesis. Consider placement of an anterior chamber maintainer.

  8. 8. Make an incision into the anterior chamber.

  9. 9. Complete the sclerostomy posteriorly using a punch (Kelly or Khaw punch).

  10. 10. Perform peripheral iridectomy (see Figure 8.41).

  11. 11. Ensure adequate flow.

  12. 12. Tie the scleral flap sutures (fixed, releasable, or adjustable sutures; see Figure 8.42).

  13. 13. Aim for no flow after sutures are secured (see Figure 8.43).

  14. 14. Close the conjunctiva so that it is ‘watertight’, with 10–0 nylon.

  15. 15. Inject steroid/antibiotic subconjunctivally.

Fig 8.40 Creation of a scleral flap

Fig 8.40
Creation of a scleral flap

Fig 8.41 Peripheral iridectomy (following sclerostomy)

Fig 8.41
Peripheral iridectomy (following sclerostomy)

Fig 8.42 Three releasable sutures

Fig 8.42
Three releasable sutures

Fig 8.43 End of surgery with releasable sutures visible through conjunctiva

Fig 8.43
End of surgery with releasable sutures visible through conjunctiva

Augmented trabeculectomy

Treatment with mitomycin C or 5-fluorouracil can take place before or after creation of the scleral flap but must occur before the anterior chamber is entered. A typical treatment is mitomycin C 0.2 mg/ml for 3 minutes, applied using polyvinyl alcohol sponges placed under the conjunctival/Tenons flap (with or without a scleral flap; see Figure 8.44). We use 3 minutes, as tissue absorption plateaus after this time. Great care should be taken to avoid contact with the cornea or with the conjunctival wound edge. The area is then thoroughly irrigated with balanced salt solution before completion of the trabeculectomy.

Fig 8.44 Slit lamp examination of trabeculectomy bleb

Fig 8.44
Slit lamp examination of trabeculectomy bleb

  • Note that 5-fluorouracil (50 mg/ml) inhibits DNA synthesis.

  • Mitomycin C (0.2–0.5 mg/ml) alkylates DNA.

  • Anti-fibrotic use can be titrated to the risk of scarring.

Risk factors for scarring

  • Neovascular glaucoma

  • Previous failed trabeculectomy

  • Secondary glaucoma (e.g. inflammatory, post-traumatic, or iridocorneal endothelial syndrome)

  • Prolonged use of antiglaucoma medication (particularly adrenergic drugs)

  • Previous conjunctival or cataract surgery

  • African ancestry

  • Age less than 40 years

Post-operative care

  • Topical steroid every 2 hours for 2–4 weeks, then four times a day for a further 2 months

  • Topical antibiotic four times a day for 1 month

  • Follow-up at 1 day and then weekly for the first month

Frequent follow-up is needed to allow manipulation of the bleb. For example, if the IOP is too high, the eye may be massaged and sutures loosened, removed, or lysed with a laser. 5-Fluorouracil and steroids can be injected adjacent to the bleb to modify the healing response. A sudden drop in IOP during surgery should be avoided; it is preferable to have a high IOP in the first days after surgery and then to gradually lower the pressure through bleb manipulation.

Early post-operative complications

Shallow anterior chamber

  • Causes

    • Wound leak: low IOP, Seidel positive, peripheral iridectomy patent, bleb poor/flat

    • Ciliary body shutdown: low IOP, Seidel negative, peripheral iridectomy patent, bleb poor/flat

    • Overfiltration: low IOP, Seidel negative, peripheral iridectomy patent, bleb good/large

    • Pupil block: high IOP, Seidel negative, peripheral iridectomy non-patent, bleb flat, iris bombé

    • Aqueous misdirection: high IOP, Seidel negative, peripheral iridectomy patent, bleb flat, shallow central anterior chamber

    • Suprachoroidal haemorrhage: variable IOP, Seidel negative, peripheral iridotomy patent, bleb variable, pain

Specific treatment depends on cause but if the anterior chamber is flat, there is a risk of corneal decompensation due to lenticulo-corneal touch. In such cases, the anterior chamber needs to be reformed urgently using balanced salt solution, a viscoelastic, or gas.

Low IOP (hypotony)

  • Causes:

    • Wound leak

    • Ciliary body shutdown

    • Overfiltration

  • Consequences:

    • Shallowing of the anterior chamber

    • Choroidal detachment

    • Hypotonous maculopathy

    • Corneal oedema

    • Suprachoroidal haemorrhage

  • Management:

    • Taper or stop topical steroids.

    • Cycloplegics to reduce shallowing of anterior chamber

    • May need reformation of the anterior chamber or revision of the trabeculectomy

    • Large choroidal effusions (especially if ‘kissing’) may need drainage.

Wound leak

  • Consider bandage contact lens.

  • Taper or stop steroids.

  • May require suturing

Overfiltration

  • Topical atropine to prevent shallowing of anterior chamber

  • Aqueous suppressants to assist spontaneous healing of fistula by temporarily reducing aqueous flow through it.

  • Autologous blood injection into bleb

  • Bleb revision, with resuturing of the sclera flap

Suprachoroidal haemorrhage

  • Very rare with the precautions of ‘safer surgery’

  • Increased risk if poorly controlled BP, anticoagulant use

  • Drainage may be necessary.

Filtration failure

  • The bleb may be flat, e.g. because of obstruction of the sclerostomy or scleral flap, or because of subconjunctival fibrosis.

  • A specific cause of failure is an encapsulated bleb (Tenons cyst), which is a firm, dome-shaped cavity made of hypertrophied Tenons capsule with engorged surface vessels. It tends to develop 2–8 weeks post-operatively and may or may not result in raised IOP.

  • Management.

    • Bleb manipulation: removal of releasable sutures, loosening of adjustable sutures, or laser suture lysis of fixed sutures

    • Needling, with or without 5-fluorouracil and steroids. Local anaesthetic injected beforehand will reduce intra- and post-procedure pain and may also reduce scarring

Visual loss

  • May be due to ‘wipe-out’ of visual field, suprachoroidal haemorrhage, or hypotonous maculopathy

Late post-operative complications

Filtration failure

  • Rate of failure is 10% in 1 year, and 25% in 5 years.

  • May be treated with needling and 5-fluorouracil, e.g. if subconjunctival fibrosis (‘ring of steel’)

  • Repeat surgery in the form of mitomycin C trabeculectomy or placement of a glaucoma drainage device may be required.

Blebitis

In contrast to bleb-related endophthalmitis, blebitis is an isolated bleb infection. It may be due to direct spread through a leaking bleb or transconjunctival migration of bacteria. Streptococcal species are the most common pathogens found in this condition.

  • Causes

    • Thin-walled, avascular, cystic blebs

    • Inferior bleb location

    • Bleb leak

    • Blepharitis

    • Contact lens use

    • Ocular trauma

    • Advanced age

    • Immunosuppression

  • Symptoms

    • Red, uncomfortable eye

    • Discharge

    • Tends to have a prodrome of a few days

  • Signs

    • ‘Milky’ bleb; if the anterior chamber has more than 1+ anterior chamber cells, treat as endophthalmitis

  • Management

    • Admit.

    • Conjunctival swab

    • Topical ofloxacin/cefuroxime hourly day and night

    • Oral moxifloxacin 400 mg in the morning for 10 days; Augmentin 625 mg three times a day

    • Review within 4 hours to check progression.

    • Start Pred Forte 1% four times a day 24–48 hours later if improving.

Bleb-related endophthalmitis

  • Risk factors:

    • As for blebitis

  • Symptoms:

    • Red, painful eye with reduced vision; usually sudden onset

  • Signs:

    • ‘Milky’ bleb

    • Anterior uveitis

    • May have hypopyon, vitritis

  • Management:

    • As for blebitis but also requires urgent vitreous tap and intravitreal vancomycin 2 mg and amikacin 0.4 mg (or ceftazidime 2 mg)

    • Intravitreal dexamethasone 0.4 mg is also given.

    • Any risk factors for infection can be treated later.

Leaking bleb

  • A key concern is the development of endophthalmitis.

  • Bleb revision may be required (e.g. conjunctival advancement, free patch autograft, or sclera allograft patching).

Visual loss

  • Often due to surgically induced cataract; cataract surgery increases the risk of bleb failure

  • If cataract surgery is performed, use topical steroids every 2 hours and consider subconjunctival 5-fluorouracil post-operatively.

Bleb dysesthesia

  • Ten per cent risk; may require bleb revision

Glaucoma drainage devices

Glaucoma drainage devices (GDDs) consist of a silicone tube attached to an endplate secured to the equatorial episclera. The tube is inserted into the anterior chamber to create a direct communication between the chamber and the sub-Tenons space (see Figure 8.45). The endplate acts as a surface for bleb formation. IOP reduction is by passive, pressure-dependent outflow of aqueous humour. Some devices also have regulatory valves. GDDs include Molteno tubes, Baerveldt tubes, and Ahmed valves. GDDs are increasingly used once medication or trabeculectomy has failed. The Tube versus Trabeculectomy Study also suggested that GDDs be used more frequently in patients who have had previous conjunctival surgery, including cataract surgery.

Fig 8.45 The tip of a Baerveldt tube visible in anterior chamber with a Supramid suture visible inside

Fig 8.45
The tip of a Baerveldt tube visible in anterior chamber with a Supramid suture visible inside

GDDs can be classified into those with resistance (Ahmed valves) and those without resistance (Molteno tubes and Baerveldt tubes). Surgery using tubes with no resistance will result in hypotony in the early post-operative period unless the tube is ligated (with nylon or Vicryl) or blocked with an internal stenting suture (using Supramid). The aim of tube ligation is to prevent excess flow until healing offers some resistance to flow at the endplate. The ligature may dissolve or be removed, depending on the material used.

The Ahmed valve is a unidirectional, pressure-sensitive valve designed to open when the IOP is 8 mmHg; however, there is a wide variation in the true opening pressure.

A reduction in IOP can generally be obtained through the use of endplates with a large surface area. The Baerveldt tube has a surface area of 250 mm2 or 350 mm2, the Molteno tube has a surface area of 135 mm2, and the Ahmed valve has a surface area of 185 mm2.

Indications

  • Uncontrolled glaucoma despite previous surgery

  • Secondary glaucoma where trabeculectomy is likely to fail, e.g. neovascular and post-traumatic, iridocorneal endothelial syndrome

  • Presence of conjunctival scarring

  • Contact lens wearer who needs glaucoma surgery

Complications

  • Over-drainage

  • Malposition: endothelial or lenticular touch

  • Erosion/exposure of tube: occurs in 2% of cases

  • Failure of drainage: blocked tube or encapsulation of bleb over footplate

  • Diplopia: occurs in 5% of cases

Non-penetrating surgery

Non-penetrating surgery is a term used to describe a group of surgeries in which the rate of aqueous drainage is controlled by the TM and Descemets membrane rather than tension in the scleral flap. It is more technically challenging than penetrating surgery. Non-penetrating surgery minimizes the risks associated with penetration into the eye, but the reduction in IOP is less.

Non-penetrating surgery is not appropriate in some glaucoma types (e.g. neovascular glaucoma). A narrow drainage angle is a relative contraindication. It may be a good option in eyes that do not need a low target pressure or in patients with mild glaucoma.

Deep sclerectomy

  • Two scleral flaps are fashioned and the deep flap excised to leave a thin membrane consisting of TM/Descemets membrane (Descemets window).

  • The window allows the diffusion of aqueous humour from the anterior chamber into the subconjunctival space and can result in a shallow filtration bleb.

  • Inadvertent perforation of Descemets window requires conversion to a trabeculectomy.

  • Goniopuncture using an Nd:YAG laser can be used to convert a deep sclerectomy to a penetrating procedure (needed in 50% of cases).

Viscocanalostomy

  • As for a deep sclerectomy but, in addition, Schlemms canal is dilated with high-density viscoelastic, and the superficial scleral flap is sutured tightly to minimize bleb formation.

  • Canaloplasty is a similar procedure but involves 360°Cannulation of Schlemms canal with a microcatheter. A suture can be threaded into Schlemms canal to permanently distend that structure.

Other surgical procedures for glaucoma

Peripheral iridectomy

  • To relieve pupil block, when Laser PI is not possible

Goniotomy

  • Indicated for primary congenital glaucoma, to open the abnormal angle (see Chapter 9, Section 9.26)

Trabeculotomy

  • Indicated for congenital glaucoma, to open Schlemms canal directly to the anterior chamber (see Chapter 9, Section 9.26)

Other devices

  • Several new surgical devices for glaucoma have been launched recently, including those working by increasing meshwork, such as via Schlemm canal flow (iStent, Hydrus, Trabectome), micro shunts draining to the subconjunctival space (Ex-PRESS, Xen, and Inn Focus microtube implants) and suprachoroidal space implants (Cypass, Istent supra). Further studies are currently underway to determine their long-term efficacy.

8.27 Glaucoma clinical trials

Treatment versus no treatment

Collaborative Normal Tension Glaucoma Study

  • Compared treatment vs no treatment in normal tension glaucoma

  • The treatment goal was a 30% reduction in IOP through the use of medications, ALT, or trabeculectomy.

  • Showed that 12% of treated versus 35% of controls progressed (optic disc or visual field) after 5 years

  • Surgically treated eyes were more likely than eyes that were not surgically treated to develop cataracts.

  • Showed that, as a group, patients with normal tension glaucoma benefit from IOP reduction

  • The effect of CCT was not examined.

Early Manifest Glaucoma Treatment Study

  • Compared treatment vs no treatment in early to moderate glaucoma

  • Recruitment through population screening

  • Treatment with ALT and betaxolol

  • Showed that a 25% reduction in IOP reduced risk of progression by 50%

  • Risk of progression decreased 10% for each 1 mmHg reduction in IOP.

Ocular Hypertension Treatment Study

  • Compared treatment vs no treatment in OHT

  • Patients had IOPs between 21 and 32 mmHg.

  • Treatment to lower IOP by at least 20% was associated with a 50% reduction in risk of glaucoma (4.4% of treated vs 9% of controls at 60 months).

  • Both the optic disc and the visual field need to be monitored, as conversion occurred almost equally frequently by visual field defect alone or disc changes alone.

  • Not every patient with OHT needs treatment; patients with OHT should be risk stratified.

  • Thin CCT, increased age, high IOP, and a large vertical cup : disc ratio were risk factors for conversion.

Comparison of treatments

Collaborative Initial Glaucoma Treatment Study

  • Compared medical treatment and trabeculectomy in newly diagnosed glaucoma

  • Surgery reduced IOP more than medications did (40% vs 31%, respectively).

  • There was no difference in progression between the groups.

Advanced Glaucoma Intervention Study

  • Compared two treatment protocols involving ALT and trabeculectomy in uncontrolled glaucoma

  • Showed that low IOP and low IOP fluctuation are associated with reduced progression, with a likely dose–response relationship

  • Eyes with an average IOP >17.5 mmHg progressed more than eyes with an average IOP <14 mmHg did.

Fluorouracil Filtering Surgery Study

  • Compared trabeculectomy alone to trabeculectomy with 5-fluorouracil, in eyes with previous cataract surgery or failed filtering surgery

  • 5-Fluorouracil was given via post-operative injections (twice a day for 1 week, then once a day for 1 week).

  • The 1-year failure rates were 28% with 5-fluorouracil vs 50% without (the difference was sustained at 5 years).

Tube versus Trabeculectomy Study

  • Compared mitomycin C trabeculectomy to GDD surgery (350 mm2 Baerveldt tube)

  • Included eyes with previous cataract extraction with or without unsuccessful trabeculectomy

  • At 5 years, there was equally good IOP reduction in each group (64% in both groups had an IOP of 14 mmHg or less).

  • Neither glaucoma operation was superior to the other; the results support the use of tube surgery in eyes other than just those with refractory glaucoma.

Ahmed Baerveldt Comparison Study

  • Compared Ahmed valves and Baerveldt tubes in patients with inadequately controlled glaucoma on maximal medial therapy

  • Included primary glaucomas with previous intraocular surgery, and secondary glaucomas known to have a high failure rate with trabeculectomy

  • One-year results showed that IOP reduction was greater with the Baerveldt tube than with the Ahmed valve.

  • Both GDDs had a similar safety profile but the Baerveldt group needed more post-operative interventions.

The Effectiveness of Early Lens Extraction for theTreatment of PACG Study

  • Ongoing study comparing early lens extraction to laser iridotomy for the treatment of PACG.

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