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Glaucoma

 

Glaucoma is progressive damage to the optic nerve due to high intraocular pressure (pressure within the eye).  Damage to the optic nerve results in a gradual loss of field of vision.  Untreated, tunnel vision occurs followed by total blindness.  In dogs, glaucoma is a painful and blinding disease associated with high intraocular pressure.  In dogs, glaucoma treatment is usually unsuccessful and most affected dogs require removal of their eyes to relieve the pain.

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The eye is continually generating fluid, so without proper drainage, the fluid builds up and creates pressure on the eye structures.  The back of the eye, where the optic nerve enters is the easiest place for the fluid to bulge out, but this pinches the optic nerve, reducing transmission of signal to the brain.

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Intraocular pressure becomes elevated when the natural fluid in the eye, (called the aqueous humor), is unable to drain normally.  The abnormal drainage can be due to disturbances in the drainage structure, (called the trabecular meshwork), which results in open angle glaucoma.  It can also be due to physical obstruction at the front, (anterior chamber), of the eye, which is called angle closure glaucoma.

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Types of Glaucoma

 

It will be important to identify the specific types of glaucoma that arise in the Entlebucher population, along with any noticeable symptoms and practical treatments.

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Primary – Glaucoma is termed primary when the cause is considered to be inherited.  It is thought to affect over 40 breeds of dogs worldwide.  In the AKC, glaucoma is ranked as the 37th disease out of a list of 300 different diseases of concern.

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Treatment – The only treatment is aimed at reducing the pressure inside the eye to alleviate the constriction of the optic nerve.  Eye drops to reduce pressure may prevent further damage to the nerve or at least slow down the progression of blindness.

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Canine glaucoma refers to a group of disorders of the dog’s eye.  Although many therapies transfer easily between humans and dogs, glaucoma treatment does not fall into this group.  Glaucoma related blindness is generally considered preventable or controllable in humans whereas in dogs, this is not true.  The eyes are typically enucleated (removed) to manage the pain of uncontrolled high ocular pressures in dogs.

Anatomy of the Normal Eye

 

Normal vision occurs when light enters the eye, passing through the clear cornea, then through the hole in the iris we call the pupil, and through the lens (marked in red).  The lens focusses the light onto the retina (the screen in the movie theatre).  The retina has receptors called rods and cones which capture the light patterns and convey the image to the brain through the optic nerve.  In the brain, the image is reassembled and occurs as instantaneous vision.

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The most common genetic eye diseases are summarized below, indicating the part of the eye that is affected by the disease.

 

PRA – degeneration (wrinkling) of the retinal screen

Cataracts – clouding of the lens (coloured red)

Glaucoma- abnormal drainage of fluids, high pressure damages optic nerve

Collie Eye Anomaly - impaired nutrition of the choroid behind the retina

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Anatomy of the Eye in Glaucoma

 

In order to understand glaucoma, it is important to refresh your knowledge of the anatomy of the eye.  In the diagram above, focus on finding the aqueous humour, the trabecular network and the optic nerve.  Glaucoma is caused by a lack of drainage of normal fluid from the back of the eye to the front.  The fluid in the eye is called the aqueous humour.  The drainage network of the eye is called the trabecular network and the optic nerve is how signals from the eye are transmitted to the brain.  Notice that at the back of the eye, around the optic nerve, there is an opening.  This is where excess fluid in the eye bulges into the nerve space, constricting the optic nerve and thereby causing glaucoma blindness 

 

Open angle glaucoma – This condition is not common in Entlebuchers

Primary open angle glaucoma (POAG) results as a dysfunction or obstruction of the drainage mechanism of the eye.  The trabecular meshwork which normally allows eye fluid to drain freely can be thought of as a sieve.  Over time, with age, the sieve may not work as well, (dysfunction) slowing the passage of fluid.  Blunt force trauma to the eye or the use of steroids are also factors potentially increasing pressure.  Alternately, drainage in the eye can be impeded by obstruction of the drainage mechanism, which can be thought of as material accumulating in the sieve, clogging the network and reducing drainage.  Obstructions can be blood cells, pigment or inflammatory cells. 

 

Dog breeds known to be affected by POAG include the Beagle, the Norwegian Elkhoun and the Peitit Basset Griffon Vendeen. 

 

Treatment of open angle glaucoma is targeted at reducing the intraocular pressure.  Eye drops, laser or surgery may improve the function of the sieve.  Removal of steroids will help the pressure come down.  Anti-inflammatory eye drops may be used if inflammation is the cause.

 

 

Closed angle glaucoma – This condition is the common  type of glaucoma in Entlebuchers.

Primary angle closure glaucoma (PCAG) is the most common form of primary glaucoma in dogs and has been shown to be significantly associated with pectinate ligament dysplasia (PLD), an abnormal iridocorneal angle that has been shown to be highly hereditary.  PLD is often used interchangeable with the term goniodysgnesis.  The pectinate ligaments are slender, widely separated fibers of connective tissue that cross the iridocorneal angle. 

 

Development of these ligaments was thought to be complete at 8 weeks and a single gonioscopy prior to breeding was sufficient to identify the problem.  It is now known that goniodysgenesis can progress over time, so regular testing by gonioscopy is advised.  Although PLD and glaucoma are commonly seen together, not all dogs with PLD go on to develop glaucoma, implying that other risk factors are also involved. 

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The onset of closed angle glaucoma is characterized by very rapid increase in intraocular pressure, within a few hours, which is extremely painful and often leads to sudden and irreversible blindness

 

Breeds known to be at risk include the Siberian Husky, the Flatcoated Retriever, the Basset Hound, the English and Welsh Springer spaniels, the American Cocker spaniel and the Spanish Water dog.  Incidence in the Entlebucher Mountain Dog has increased in recent years. 

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Primary closed angle glaucoma is a structural problem of the eye, where the iris becomes pressed up against the cornea and obstructs access to the trabecular meshwork, resulting in accumulating fluid and pressure in the eye.  There are four known reasons for this to occur.  Pupil block occurs when the fluid cannot move through the pupil from the back of the eye to the front.  Fluid builds up in the back, pinching the optic nerve.  Plateau iris occurs when the ciliary body is enlarged or rotates forward, pushing the peripheral iris forward.  Lens-related angle closure results when an increase in lens size pushes the entire iris forward.  Posterior segment-related angle closure occurs when a mass, (tumor, cyst or bleeding) at the back of the eye pushes the lens and the iris forward. 

 

No matter the cause, the treatment aims to lower intra-ocular pressure by physically re-opening the closed angle.  In humans, laser iridotomy creates an opening in the border of the iris which allows fluid to move through the eye.  Other treatments include laser iridoplasty, cataract surgery, vitrectomy and glaucoma surgery.

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Acute angle closure glaucoma or acute primary angle closure occurs when he drainage angles at the front of the eye become completely occluded and fluid is unable to drain out of the eye.  Pressure elevates to extreme levels, causing headache, eye pain, nausea and blurred vision in humans.  This is an ophthalmic emergency.  Left untreated, the optic nerve will be irreversibly damaged and cause glaucoma blindness. 

 

Symptoms of acute angle closure are a red eye, a pupil that does not react to light and a cloudy cornea.  If treated early enough, it can often be improved within a few hours in humans, using eye drops, tablets, injection in the vein, indentation, laser iridotomy and/or laser iridoplasty.

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Risk factors for glaucoma in humans include age (over 40), race (African ancestry), family history (close relative), myopia (short sightedness) and diabetes.  In Entlebuchers, the cause, risk factors and early symptoms are not well understood.  Especially in the case of acute angle closure, it is difficult to recognize the dog’s symptoms quickly enough to achieve successful treatment.

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Glaucoma Angles

 

In the illustration above, the different structures involved in glaucoma are marked.  Open angle glaucoma is related to the drainage system of the eyeAngle closure glaucoma is a function of the shape and location of different eye structures.  Notice how either type of glaucoma cause accumulation of fluid and increased pressure within the eye, which in turn constricts the optic nerve and impedes transmission of signal to the brain.

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Heritability

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We do not currently understand very well how glaucoma arises nor how it is inherited by offspring.  Because Entlebuchers are such a rare breed, (with a very small population), there is very little data and no studies specific to our breed. 

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Pectinate ligament dysplasia is a known risk marker for developing glaucoma in other breeds in Europe.  Two dogs with ‘terrible angles’ are more likely to have offspring with ‘bad angles’.  Most dogs with affected angles don’t get glaucoma but dogs that get glaucoma usually have ‘bad angles’.

DNA & Genetic Testing

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To date, only four mutations have been identified as responsible for primary glaucoma in dogs.  All are autosmomal recessive forms of POAG.  Two mutations lie in a gene called ADAMTS10 and cause POAG in Beagles and Norwegian Elkhounds respectively.  Two more mutations lie in the closely related gene called ADAMTS17 and have been identified as the cause of POAG in the Petit Basset Griffon Vendeen and Basset Hound respectively.

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PCAG is believed to be genetically complex in comparison to POAG in most breeds.  Currently there are no DNA tests available to identify dogs at risk.  James Oliver, a veterinary opthamologist in the UK has undertaken a study with the aim to identify genetic risk factors for PCAG in multiple breeds.  Gonioscopy data and DNA samples have been collected on over 1400 dogs worldwide.  As the genetic cause of POAG may vary from breed to breed, it is important to begin collecting similar data for Entlebuchers.

 

Glossary of Terms

 

Cataract – is very complex genetically and is not known to be related to glaucoma.
Research into glaucoma, will also provide more data and knowledge about cataracts and other genetically controlled eye disease, just by collecting the gonioscopy and tonometry data.

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Gonioscopy – must be performed BEFORE dilation of the eyes or during dilation.  A special contact lens is placed on the front surface of the eye after the eye has been numbed with anesthetic eye drops.  This goniolens may have a mirror which allows the opthamologist to see the drainage angles of the eye directly.  Some pressure may be applied to the eye and it is usually performed in the dark, when the pupil is naturally dilated.  In the dark, the pupil is dilated to its fullest and the drainage angles are at their narrowest.  The gonioscopy measures the angle in the eye where the iris (coloured part of the eye) meets the cornea.  If the back of the trabecular meshwork is the last visible layer, the angle is described as narrow.  If only the front of the trabecular meshwork is visible, the angle is generally 10 degrees or less and likely to close.

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Goniolens – a variety of lenses can be used to conduct a gonioscopy.  For research purposes, it is important to note the type of lens on the gonio report.  Direct lenses allow the opthamologist to see the angles directly, while indirect lenses include a mirror.

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The direct lens provides an excellent view but requires costly equipment, the dog lying on its back, and is time consuming.  It tends to show the angles more open because of the supine position.  It has the advantage of being able to view both eyes for comparison.  Some direct lens are Koeppe (prototype diagnostic lens), Richardson Shaffer (for infants), Layden (for premature infants), Hoskins Barkan (prototype surgical and diagnostic lens), Thorpe (operating room lens) and Swan Jacob (surgical lens for children).

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The indirect lens is more convenient to use, has controlled illumination and allows manipulation but the two eyes cannot be compared at the same time.  It also requires cooperation of the patient.  Indirect lenses include the Goldmann Single Mirror (62’ angle), Goldmann Three Mirror (59’ angle), Zeiss Four Mirror (45’ angle, requires a holder), Posner Four Mirror (modified Zeiss with handle), Sussmann Four Mirror (hand held Zeiss type), Thorpe Four Mirror (62’ angle, requires fluid bridge) and Ritch Trabeculoplasty Lens (50’ and 62’ angles).

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Tonometry  - the measurement of intraocular pressure both pre and post dilation is an important part of glaucoma detection.  The eye is numbed using drops, then the opthamologist applies a small amount of pressure to the eye using a tonometer or a warm puff of air.  Normal pressures range from 12 to 22 mmHg but this is unique to each person.  Glaucoma is generally diagnosed above 20 mmHg.  In acute angle closure glaucoma, pressures above 40 mmHg are not unusual.

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Testing – Gonioscopy and tonometry are the only tools currently available to help breeders reduce the incidence of this disease.  Regular gonioscopiy exams are advised as the eyes are now known to change over time and dogs can progress from clear exams to acute disease in a short period of time.  Dr. McLellan has advised that testing by IOP, gonioscopy and DP should be conducted every 2 years as results can change dramatically over the life of the dog.  Establishing a solid base line is critical to early diagnosis and potential treatment options.

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High resolution ultrasound of the eye may be helpful in identifying glaucoma but ophthalmologists are not all able to access the technology.  The test is not yet accepted as predictive of future eye health concerns.  Gonioscopy is the most widely used tool for diagnosing angle closure, providing a 360 degree assessment of the angle width, observation of pigmentation of the trabecular meshwork, neovascularization or recession of the angle.  These measures all help to diagnose both the problem and its cause.

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Gonioscopy unfortunately also has limitations.  It requires anesthetic and is a subjective technique.  It requires contact of the lens with the eye which can artificially widen the angle.  It also must be performed prior to dilation or immediately as the pupil is dilating, which requires more time at the clinic.  Analysis of the gonioscopy results can be misinterpreted by practitioners less familiar with the technique.  It is therefore best conducted by an ophthalmologist specializing in its use.

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There are many other tests which can be used to assess the eye angles including at least for humans, the scanning peripheral depth analyzer, the Pentacam, Ultrasound Biomicroscopy (UBM) and anterior segment OCT.  Of these, the OCT is the most often utilized, being easy to administer, comfortable for the patient and providing quantitative results.  Unfortunately OCT alone is not sufficient to decide on appropriate treatment but may be able to detect the likelihood of future angle closure even better than gonioscopy alone.  OCT is best used as an adjunct test to provide a different measure of the angles than a gonioscopy. 

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There is currently no standard grading scheme for the results of gonioscopies for glaucoma but a ‘bad angle’ is predictive of the risk of developing the disease.  Gonioscopy is used to diagnose a number of different problems with the eye.  Grading systems have been developed focused on these different problems. 

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Analysis of the gonioscopy results is best performed by comparison to previous results by the same ophthalmologist, well-practiced in the test.  As a subjective test, results may not translate perfectly from one practitioner to another.

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