Dealing with Glaucoma: Small Animal and Equine Approaches

Vet Times The website for the veterinary profession https://www.vettimes.co.uk

DEALING WITH GLAUCOMA: SMALL ANIMAL AND EQUINE APPROACHES

Author : Claudia Hartley

Categories : Vets

Date : November 15, 2010

Claudia Hartley examines the clinical signs, management techniques and surgical options for this condition, and compares diagnostic implements

GLAUCOMA can be most simply defined as a rise of intraocular pressure (IOP), ultimately causing both pain and blindness.

In our domestic species, to a large extent this is true. Predictably, however, this is an oversimplification, and glaucoma is better described as a group of diseases characterised by an optic neuropathy, with the principal risk factor being an elevated IOP.

Humans can suffer the same pathological changes associated with increased IOP (changes in the retina and optic nerve) at normal intraocular pressures – so-called normotensive glaucoma – hence the more complicated definition. This has not yet been described in dogs, cats or horses.

Primary glaucoma is associated with no antecedent ocular disease process and is hereditary. It is invariably bilateral, although one eye is usually affected first. Two broad forms exist – the first associated with goniodysgenesis (an abnormal drainage angle), and open-angle glaucoma. While primary glaucoma (Figure 1) is perhaps the more common glaucoma type encountered in dogs, secondary glaucoma (Figure 2) is more common in cats and horses (where primary glaucoma is relatively rare). Dogs can also suffer from secondary glaucoma – the most common precipitating conditions include uveitis (intraocular inflammation), lens luxation, intraocular neoplasia and previous intraocular surgery (via uveitis).

1 / 6 Open-angle glaucoma is relatively rare in canine patients, but it has been reported in Norwegian elkhounds, miniature and toy poodles, and beagles. Beagles, in particular, have been extensively studied, largely as a model for human disease.

Goniodysgenesis has been reported in basset hounds, bouvier des Flandres, great Danes, Samoyeds, Siberian huskies, English and American cocker spaniels, English and Welsh springer spaniels, Dandie Dinmont terriers and Welsh terriers, among others (see Table 1).

Pigmentary glaucoma (Figure 3) has largely been reported in cairn terriers, but also in two golden retrievers, and is accompanied by pigment deposition in the iris base throughout the trabecular meshwork and within the sclera. This pigment can be readily identified within the sclera as large, coalescing, black plaques of pigment. Histopathological studies of pigmentary glaucoma are conflicting, but it is generally accepted to be melanin deposition within tissues, scavenged by macrophages (becoming melanophages), rather than deposition of melanocytes.

Aqueous humour is produced by the non-pigmented ciliary epithelium covering the processes of the ciliary body. It is produced by three main mechanisms: diffusion (osmotic gradients), ultrafiltration (hydrostatic gradients) and active secretion. Active secretion of sodium ions into the aqueous by the nonpigmented ciliary epithelium (via Na+K+ATPase pumps) results in osmotic water movement into the posterior chamber. This active secretion is believed to be responsible for 80 to 90 per cent of aqueous production.

Carbonic anhydrase is responsible for catalysing the reaction of H2O + CO2 ? H+ + HCO3-. Bicarbonate (HCO3-) is required for transport with the sodium ions, and inhibition of carbonic anhydrase and reduction of bicarbonate production – and, therefore, sodium ion transport – results in reduced aqueous production.

Aqueous humour flows through the posterior chamber (between the iris and the lens) and through the pupil to the anterior chamber. Aqueous outflow occurs through the iridocorneal angle, past the pectinate ligament and into the ciliary cleft via the corneoscleral trabecular meshwork. From here, aqueous fluid drains to the angular aqueous plexus, and then to the scleral venous circulation (conventional outflow).

Unconventional outflow is achieved via the iris base, uveoscleral trabecular meshwork and into the suprachoroidal space. In dogs, the conventional outflow accounts for 85 per cent of aqueous outflow, and the remaining unconventional outflow is approximately 15 per cent of total outflow – although this drops to three per cent in glaucomatous dogs. In cats, 97 per cent of outflow is via the conventional pathway (three per cent unconventional). In horses, the aqueous outflow facility is approximately three times that of dogs, with a greater reliance on uveoscleral outflow than in other species.

Aqueous production and outflow should equal each other to maintain a constant IOP.

2 / 6 Overproduction of aqueous has not been demonstrated; it is generally accepted that a lack of drainage is responsible for rises in IOP. In humans, many surgical treatments are directed toward increasing aqueous outflow, as this is the primary abnormality.

The classic presentation of acute glaucoma is a blind, red and painful eye, with a fixed, dilated pupil and diffuse corneal oedema. Unfortunately, not all cases are textbook presentations – for example, some cases will have a mid-sized pupil, and corneal oedema can be mild or absent. Clinical signs may be related to the extent and duration of IOP elevation, and are often asymmetrical between two eyes in the same dog.

Primary open-angle glaucoma can present more insidiously, with periods of mild corneal oedema and variable episcleral congestion. Owners may not present the dog for examination until the disease is relatively advanced. Cases with goniodysgenesis and a narrow or closed drainage angle can present with sudden and catastrophic increases in IOP. The trigger for this sudden increase is unclear, but the ciliary cleft appears to acutely collapse.

Tonometry

Diagnosis of increased IOP is achieved by tonometry. The Schiotz tonometer (Figure 4), an indentation tonometer, is reliable in experienced hands, although it requires thorough cleaning after each use to ensure accurate results. The Schiotz must also be placed on a horizontal corneal surface, meaning the dog must be held with its nose in the air to achieve the correct angle. The IOP is calculated by measuring the pressure (by means of a weighted plunger) required to indent the cornea and by following conversion tables.

More expensive to purchase, but, I believe, much easier to use, is the applanation tonometer, Tono- pen (Tono-pen Vet or Tono-pen XL).

This tonometer (Figure 5) measures the pressure required to applanate (flatten) a prescribed area of cornea, and is displayed as a reading in mmHg. Repeated measurements are averaged and the error factor between these displayed; readings of greater than five per cent should be disregarded. Like the Schiotz, topical local anaesthesia is required. However, the Tonopen can be used after recent intraocular surgery, which is not recommended with the Schiotz tonometer.

A rebound tonometer, such as the TonoVet (Figures 6a and 6b), can be used without topical local anaesthesia, and measures the deceleration of a small linear probe fired against the cornea, thereby estimating IOP. The instrument must be used perpendicular to the corneal surface, which is not usually difficult to achieve in dogs or cats. Some evidence suggests that, in cats, the TonoVet is more accurate, although a rough conversion formula is available for the Tonopen to achieve an estimate of the equivalent TonoVet reading.

Anecdotally, some veterinary ophthalmologists have also reported less iatrogenic corneal

3 / 6 ulceration with the TonoVet in cats.

Gonioscopy

Gonioscopy is examination of the iridocorneal angle (Figures 7a and 7b) using a gonioscopy lens to visualise it.

In dogs, the curvature of the cornea is such that this angle cannot be inspected directly. The angle is assessed for width of the opening, as well as appearance of the pectinate ligaments. The opening to the ciliary cleft is described as either open, narrow or closed. The ciliary cleft behind the angle cannot be directly visualised, although highresolution ultrasound (20mHz) can allow assessment of a crosssection of the trabecular meshwork within the cleft. Ultrasound biomicroscopy (50mHz) requires general anaesthesia, and is generally reserved for experimental studies. However, it provides outstanding resolution of the ciliary cleft.

Medical treatment

Medical treatment of primary glaucoma is aimed at reducing aqueous production.

The three main groups of topical anti-glaucoma agents are carbonic anhydrase inhibitors, beta blockers and prostaglandin analogues. Prostaglandin analogues are the most potent, and are described as increasing uveoscleral outflow. They cause a tight miosis, which in rare cases can be so severe as to affect vision. They should be used twice daily in canine patients (once daily in humans). Prostaglandins are not effective in cats that lack the appropriate receptor for the IOPreducing action (although miosis may still occur), and are not recommended in horses where their effect is limited and they may potentiate underlying uveitis (the most common precipitating factor for glaucoma in horses).

Carbonic anhydrase inhibitors reduce aqueous production by limiting the production of bicarbonate ions and, therefore, the associated active secretion of sodium ions, with incumbent water movement into the posterior chamber. Beta blockers reduce aqueous production by blocking beta receptors on the ciliary epithelium, inducing a decrease in cyclic adenosine monophosphate (cAMP) levels and a subsequent reduction in secretory function.

Osmotic diuretics can be used in emergency situations; however, these should be used with caution in animals with preexisting systemic disease. As they expand, circulating volume and causing diuresis, concurrent cardiac or renal failure is a contraindication of the use of osmotic agents, such as mannitol.

Glycerol can be used orally as an osmotic agent, but is associated with nausea and vomiting in some animals, and is again contraindicated in cardiac or renal failure, as well as diabetes mellitus as glycerol is metabolised to glucose.

4 / 6 In secondary glaucoma, the primary disease should be addressed, where possible. Anterior lens luxation and a pupillary block of aqueous flow, may be addressed surgically by intracapsular lens extraction. Where glaucoma is secondary to uveitis, uveitis treatment is important. It is interesting and frustrating to note that prostaglandin analogue action may be blunted by the concurrent use of topical steroids. In horses and cats, where secondary glaucoma is the more common type, addressing the uveitis responsible may be sufficient to reduce IOP.

Neuroprotection is in its infancy in dogs, but is an area of much research in human patients. Increases in IOP are associated with retinal ganglion cell death and a subsequent release of the excitotoxic neurotransmitter, glutamate. Glutamate causes intracellular calcium accumulation and cell death of neighbouring cells.

Cell death causes further release of glutamate, accounting for the deterioration of vision noted by many owners, despite IOP control.

Calcium channel blockers (such as amlodipine) have been proposed as potential neuroprotective agents, although scientific evidence is lacking in dogs.

Surgical treatment

Surgical treatment for glaucoma is generally considered the mainstay of treatment, as medical treatment is destined to fail once outflow becomes zero.

Unfortunately, no surgical treatment is strikingly successful as yet. Increasing aqueous outflow in dogs using gonioimplants (Figure 8) has varying success rates due to the ultimate fibrosis of the drainage bleb. In humans, this is less of a problem, and trabeculectomy and drainage implants are largely successful. Early failure due to fibrin accumulation within the drainage tube can be alleviated with intracameral injections of tissue plasminogen activator (a fibrinolytic agent).

Laser destruction of the ciliary body epithelium to reduce aqueous production had been undertaken transclerally (transscleral cyclophotocoagulation), with limited success.

The advent of endoscopic cyclophotocoagulation (ECP; Figures 9a and 9b) has brought increased success rates, with American colleagues reporting success in 85 per cent of cases (unpublished). ECP is now available in the UK at five clinics, and although results have been encouraging in some cases, it appears that the UK success rates are substantially below those in the USA for reasons that remain unclear.

Cryodestruction of the ciliary body is reserved for blind eyes, as postoperative IOP spikes are likely to be blinding. Cyclocryotherapy is less frequently used, as it is associated with postoperative pain and IOP spikes, which is difficult to justify for cosmetic reasons.

5 / 6 Enucleation (Figure 10) is the kindest option for most cases that are both blind and in pain. Evisceration and intrascleral prosthesis placement can be used to provide a more cosmetic globe, although the advantage for the animal is questionable.

Intravitreal gentamicin can be used to chemically ablate the ciliary body epithelium to maintain a cosmetic globe, but cannot be used in a visual eye (retinotoxicity). Again, this is largely for the benefit of the owner – the exception being where a surgical operation cannot be considered for other medical reasons.

• Visit www.vetsonline.com for previously published articles on ophthalmology.

6 / 6