Glaucoma – Feline

Synonyms:
Closed-angle glaucoma
Goniodysgenesis
Melanocytic glaucoma
Narrow-angle glaucoma
Ocular hypertension
Open-angle glaucoma
Pigmentary glaucoma
Primary glaucoma
Secondary glaucoma

Disease Description:
Definition
Glaucoma refers to elevated intraocular pressure (IOP) that is either sustained or fluctuating. It can ultimately result in death of retinal ganglion cells. Glaucoma encompasses a broad category of diseases but is commonly referred to in the singular tense. Although normotensive glaucoma has been identified in people, it has not been documented in the cat or dog.

Pathophysiology
Glaucoma is one of the most damaging of all ocular diseases. Glaucoma initially induces microscopic damage that can lead to macroscopic changes as the disease progresses. Glaucoma is ultimately a neurodegenerative disease. Because retinal neuronal cells affected by elevated IOP are responsible for relaying visual signals, glaucoma often results in blindness. Glaucoma also has deleterious effects on other ocular structures including sclera, cornea, iridocorneal angle, iris, lens, vitreous, and optic nerve.

Classifications
Primary Glaucoma
Primary glaucoma is inherited, breed-related glaucoma. It typically affects purebred dogs, and is rare in cats. Primary glaucoma develops from anatomic malformation of the iridocorneal drainage angle (e.g. narrow angle glaucoma, goniodysgenesis), or from accumulation of abnormal glycosaminoglycans in the trabecular meshwork that results in resistance to aqueous humor outflow (i.e. primary open angle glaucoma, POAG).¹ Breeds with narrow or closed-angle glaucoma also typically have developmental goniodysgenesis. Anatomic conditions responsible for primary glaucoma are bilateral, although onset of glaucoma is almost always unilateral and asynchronous. If one eye is diagnosed with primary glaucoma, the contralateral eye is at risk for developing the disease. Because cats typically have insidious glaucoma with subtle signs, cats with primary glaucoma may present with bilateral disease because the initial eye affected was not perceived to have problems by the owner.

Secondary Glaucoma
Secondary glaucoma is caused by an underlying ocular or systemic disease that results in abnormal aqueous humor drainage from the eye. Potential causes include anterior lens luxation, uveitis, hyphema, pupillary block (e.g. posterior synechiae with iris bombe, lens luxation, vitreous herniation), intraocular neoplasia, pigmentary uveitis, and intraocular surgery. Aqueous outflow obstruction may also occur with pre-iridal fibrovascular membrane formation, peripheral anterior synechia, and cellular infiltration of the iridocorneal angle. Secondary glaucoma is often unilateral, although bilateral glaucoma may occur if the underlying disease afflicts both eyes. In cats, secondary glaucoma due to anterior uveitis is the most common cause of glaucoma and far more common that primary or genetic glaucoma.^2-6 Anterior uveitis in cats may also cause synechia, pupillary block and anterior lens luxation, which can also all contributed to development of glaucoma.

Disease Description in This Species:
Etiology
Unlike dogs, genetic causes of primary glaucoma have not been identified in cats. However, a mutation in LTBP2 has been shown to cause congenital glaucoma in domestic cats.⁷ Otherwise, genetic testing has not been be utilized in this species. This is also likely related to the decreased incidence of primary glaucoma in cats compared to dogs.

Diagnosis
Physical Examination Findings/History: Because glaucoma may arise secondary to uveitis associated with infectious and systemic diseases, as well as metastatic intraocular neoplasia, systemic abnormalities are possible. Complete physical examination is indicated to identify the presence of systemic disease and its contribution to development of glaucoma. In many cases, however, glaucoma is primarily an ocular condition and identified on ophthalmic examination.

Secondary glaucoma is far more common than primary or breed-related glaucoma in cats. Glaucoma typically occurs after chronic intraocular disease, usually related to anterior uveitis. There are many causes of anterior uveitis in cats with infectious and idiopathic disease being the most common.² Intraocular neoplasia may also occur, causing glaucoma early or late in the disease process. A thorough physical examination along with systemic labwork with or without infectious disease testing is indicated for cats with glaucoma[RD1] .^3-6  

Ophthalmic Examination Findings: Changes associated with glaucoma vary depending on the stage of disease. Findings associated with acute glaucoma may include blepharospasm, conjunctival hyperemia, episcleral injection, ciliary flush (perilimbal corneal vascularization), diffuse corneal edema, mydriasis, vision loss, and optic nerve and peripapillary retinal edema. With chronicity, additional findings may include buphthalmos, corneal Haab’s striae, lens subluxation, cataract, optic nerve cupping and atrophy, and retinal degeneration. Some eyes have more subtle abnormalities (i.e. “silent glaucoma”).  This type of glaucoma is more common in cats.  Unlike dogs, cats often have more insidious signs of glaucoma including buphthalmos, mydriasis, corneal edema and lens subluxation. Cats rarely experience clinical signs of acute glaucoma like blepharospasm, third eyelid elevation, ciliary flush or episcleral injection. Tonometry is helpful in cats suspected to be affected with intraocular pressure elevations or in cases of intraocular disease. Care should be utilized when obtaining intraocular pressure evaluation in cats because body position, eyelid manipulation and jugular compression can artifactually elevated pressure readings.⁸ Thorough ophthalmic examination is indicated to search for potential causes of glaucoma and assess the opposite eye. Referral for gonioscopy, slit lamp biomicroscopy, and indirect ophthalmoscopy should be considered. Congenital glaucoma in cats is associated with increased corneal diameter and decreased corneal sensitivity.⁹

Tonometry: Diagnosis of glaucoma relies on measurement of IOP via tonometry. IOP can be reliably measured by indentation (e.g. Schiotz tonometer), applanation (e.g. TonoPen), and rebound tonometry (e.g. TonoVet). Schiotz tonometry is technically challenging and has been largely replaced by rebound or applanation tonometry because the latter are now readily available. Digital estimation of IOP (i.e. pressing on the globe with one or more fingers) is unreliable. Topical ophthalmic anesthetic is applied prior to indentation or applanation tonometry but is not needed for rebound tonometry. Because normal IOP can vary between individuals, IOP differences between the two eyes are as important as absolute IOP values. Always perform tonometry on both eyes. Normal IOP in the dog generally ranges from 10-20 mmHg but can be as high as 20-24 mmHg with rebound tonometry. IOPs >25 mmHg or a significant disparity in IOP (i.e. >7-8 mmHg) between eyes is considered abnormal. It is important to note that a single measurement of IOP may not accurately reflect aqueous humor dynamics because IOP may vary widely during the day, and from one day to the next. Animals with glaucoma have sustained elevation of IOP.

IOP can be falsely elevated with patient excitement, fear, or stress; excessive physical restraint (especially pressure applied to the head and neck);⁴ marked blepharospasm with globe retraction; and application of digital pressure to the eye while holding the eyelids open. If IOP results are unexpected or do not match the clinical signs, repeated measurements can be performed in a darkened, quiet environment using different restraint techniques. Note that almost all sedatives alter IOP, although these alterations are not typically clinically relevant.¹⁰ Topical steroid and non-steroidal anti-inflammatory therapy in cats can also raise IOP.¹¹

Gonioscopy: Gonioscopy is visualization of the iridocorneal angle through a specialized corneal contact lens (Figure 1). The iridocorneal angle of the dog is not readily visible because of its steep corneal curvature; angle of light refraction by the cornea; prominent limbus; and shallowness of the anterior chamber. Iridocorneal angle of the cat can be visualized with indirect ophthalmoscopy and magnification because the of the deeper anterior chamber. Determining morphology of the iridocorneal angle is useful in distinguishing primary from secondary glaucoma.

Goniodysgenesis: Most glaucoma in dogs arises from goniodysgenesis, or abnormal formation of the iridocorneal drainage angle inside the eye. On gonioscopy, instead of individual pectinate ligaments separated by obvious flow-through openings, large sheets of tissue are separated by irregularly-spaced holes (Figure 3). This type of glaucoma may also occur in the cat, although this is rare.^3-5

Open Angle: POAG in dogs is characterized by a morphologically-normal iridocorneal angle (Figure 2), and development of glaucoma earlier in life than with PACG. Despite its normal appearance, immunohistochemical and microscopic abnormalities of the angle are present. POAG is the least common form of primary glaucoma in clinical practice but has been demonstrated in several dog breeds. POAG may occur in cats and has been clinically reported in the literature;¹ however, this is poorly understood.

Genetic Testing: DNA tests for inherited glaucoma have been reported in dogs, but is not currently available for cats. This is likely due, in part, to the paucity of pure-bred cats and rare incidence of the disease in this species.

Other Tests: If glaucoma is secondary and may be caused by a systemic illness that has induced intraocular disease, then a thorough medical workup is indicated. Although biochemical markers have been found in some human forms of glaucoma, no clinically-applicable markers have been identified in affected dogs and cats.¹⁰

Prevalence and Signalment
Primary glaucoma is rare in cats, but has been identified in Burmese and European Short-haired cats. A LTBP2 mutation has also been identified as a cause of congenital glaucoma in domestic cats.⁷

Most cases of glaucoma are secondary in cats, with secondary glaucoma typically caused by uveitis.^3-6

Clinical Signs
Signs of acute glaucoma may include blepharospasm, episcleral injection, ocular discharge, diffuse corneal edema, and mydriasis. With unilateral disease, vision loss may not be detected by the owner.  Because glaucoma is thought to cause headache-like pain, some cats may show subtle behavioral signs, such as lethargy, somnolence, and decreased activity. Perilimbal corneal vascularization, aqueous flare, iris discoloration, and dyscoria may be present with underlying intraocular inflammation. Feline glaucoma is often less clinically apparent than canine glaucoma. There may be more subtle signs present in cats, thus pressure evaluation and client education is important regarding the discomfort associated with glaucoma. Many clients do not perceive that the patient is in pain, but behavioral changes are noted once the pressure is alleviated.

Signs of chronic glaucoma may also include buphthalmos, corneal Haab’s striae, lens subluxation, cataract, retinal and optic nerve atrophy. In general, presence of buphthalmos (i.e. corneal diameter between 9 and 3 o’clock larger than the opposite eye) is an indication glaucoma has been present for some time and the eye is permanently blind. Interestingly, IOP may improve in buphthalmic eyes during end-stage glaucoma as the ciliary body dies and the globe becomes stretched (Figure 12); however, during this process, the patient is painful due to prolonged elevated intraocular pressure. Other ophthalmic and systemic signs may be present if glaucoma is secondary.

• Etiology:
• Cataract, intumescent
• Congenital anomalies
• Genetic, hereditary
• Hyphema
• Intraocular neoplasia
• Lens instability
• Lens luxation (anterior)
• Ocular melanosis
• Pupillary block
• Surgery
• Trauma
• Uveitis

Breed / Species Predilection:

• European shorthair¹²
• Siamese¹³
• Burmese¹⁴
• Russian blue¹⁵

Sex Predilection:
None

Age Predilection:
None

Clinical Findings:

• AFEBRILE
• Anisocoria, pupils unequal
• Aphakic crescent
• Behavior abnormal, behavioral change
• Blepharospasm, eye pain
• Blindness acute, sudden
• BLINDNESS OR OTHER VISUAL DEFICIT
• Blindness partial, visual deficit
• Buphthalmos
• Conjunctival congestion, hyperemia
• CONJUNCTIVITIS
• Corneal mass
• Corneal opacity
• Corneal ulcer, keratitis
• Corneal vascularization
• Depression, lethargy
• Dyscoria
• Edema conjunctiva, chemosis
• Edema corneal
• EDEMA, SWELLING
• Epiphora, lacrimation increased
• Episcleral injection/congestion
• Glaucoma
• HYPERPIGMENTATION
• Hypopyon
• Iridodonesis
• Iris bombe
• Iris color variation
• Iris pigmentation abnormal
• Lagophthalmos
• Lens luxation, subluxation
• MASS
• Menace response absent or decreased
• Miosis
• MYDRIASIS
• OCULAR DISCHARGE
• Ocular discharge mucoid
• Ocular discharge serous
• PAIN
• PHOTOPHOBIA
• Pupillary light reflex absent
• Pupillary light reflex decreased
• Sleep inappropriate or abnormal
• Synechia, anterior
• Third eyelid inflammation
• Third eyelid, nictitating membrane prolapsed
• UVEITIS
• Uveitis, anterior

Diagnostic Procedures:		Diagnostic Results:
Gonioscopy		Mesodermal goniodysgenesis
		Narrow, closed iridocorneal angle in eye
		Open iridocorneal angle in eye
Ocular examination		Anterior chamber deep
		Anterior chamber shallow
		Aqueous flare
		Cataract, lens opacity
		Hyphema, blood anterior chamber eye
		Intraocular pressure increased on tonometry
		Iridocyclitis, iris/ciliary body inflamed
		Lens in posterior chamber
		Leukocoria, leukokoria
		Optic disc atrophied
		Optic disc cupping
		Peripapillary tapetal hyperreflectivity
		Retinal blood vessels tortuous
		Retinal degeneration
		Retinal vascularity decreased
		Tapetal reflectivity increased

Treatment / Management:
Glaucoma is often an aggressive, progressive disease. In cats, because glaucoma is typically secondary, identification of underlying disease processes is important. Referral to a veterinary ophthalmologist may be indicated. In addition, labwork including CBC, full chemistry, thyroid testing and FeLV/FIV should be considered with the practitioner to screen for systemic disease. Unfortunately, pain associated with onset of glaucoma may be overlooked because blepharospasm and photophobia do not always occur. Hence, glaucoma can be advanced before it is diagnosed. Treatment of glaucoma can be subdivided in cats into therapy of medical management for chronic glaucoma; surgical therapy for sighted eyes and surgical therapy of chronic, unremitting glaucoma in blind eyes. Potentially visual eyes with secondary glaucoma (e.g. uveitis, anterior lens luxation, neoplasia) are usually treated with surgery or other interventions because medical therapy alone is often unsuccessful.

SPECIFIC THERAPY
Acute and Chronic Glaucoma Therapy
Acute glaucoma is rare in cats. This may be due to lack of clinical identification since glaucoma in cats is more subtle clinically than in dogs. More likely; however, acute glaucoma is rare because the underlying causes of glaucoma in cats cause an insidious, slowly progressive glaucoma. By the time glaucoma is recognized, there is typically chronic ocular disease present.^2-6

In cases of elevated pressure in cats, identification and treatment of underlying diseases is crucial. Often, the underlying disease must be treated concurrently with glaucoma. If the ophthalmic disease is advanced and the pressure is elevated, referral should be considered. In cases of chronic or severe uveitis and secondary glaucoma unresponsive to medical therapy, enucleation may be the only viable option for comfort.

Maintenance Medical Therapy
Various anti-glaucoma medications are available, most of which are topical formulations. Choice of medication is somewhat dependent on the type of glaucoma; whether the eye is visual or has a good prognosis for vision with IOP control; client goals; and concurrent systemic or ocular conditions. Medical therapy may be the primary method of treating many forms of secondary glaucoma. For eyes with primary glaucoma, medical therapy with carbonic anhydrase inhibitors is the treatment of choice in cats.^16-19

Carbonic Anhydrase Inhibitors (CAIs): Topical CAIs include dorzolamide 2% and brinzolamide 1%. Dorzolamide is also available as a combined product with timolol maleate 0.5%. Topical CAIs are administered q 8-12 hrs. Dorzolamide (because of its lower pH) and other topical CAIs may be irritating. In rare instances, topical CAIs can cause an immune-mediated reaction that leads to severe keratitis that does not improve with topical steroids, and only resolves with discontinuance of the CAI.²¹ CAIs may also cause local allergic reactions, especially with long-term use. These reactions often manifest as chronic conjunctivitis with conjunctival thickening, blepharitis, mucopurulent discharge, and corneal vascularization. In mild cases, such reactions often diminish with administration of topical corticosteroids. In more severe cases, the CAI must be discontinued because of ongoing periocular inflammation. Some treated eyes tolerate a different CAI with a different vehicle.

Brinzolamide is available as a subconjunctival implant; however, studies evaluating its long-term efficacy are lacking. Further research is needed to determine if it is an effective treatment option in cats that do not tolerate topical therapy. The author has utilized this for cats and has had success in treating primary and secondary glaucoma in cats. This is promising in this species because, over time, cats tend not to tolerate long term topical therapy. Either behaviorally, they no longer allow it or physiologically, they react to topical medication long term. Topical medication reactions are more common in cats than in dogs. Additionally, hypokalemia has been reported in cats with topical CAI administration.²⁰

Methazolamide (2-4 mg/kg PO q 8-12 hrs) is available in tablet form. Because systemic CAIs may cause vomiting, diarrhea, lethargy, metabolic acidosis with Kussmaul respiration, and hypokalemia, they have largely been replaced by topical CAIs. This medication has not been used in cats for treatment of glaucoma in the literature. Due to risk of systemic side effects, oral CAI’s should be avoided in cats.

Prostaglandin Analogues: Prostaglandin analogues are thought to be ineffective in cats due to lack of receptors in the uvea for these medications.²¹ This has been questioned some in the literature,²² but largely these medications are not utilized in cats. In addition, this class of medication upregulates inflammation and because most causes of glaucoma in cats is due to chronic uveitis, prostaglandin analogues are typically not helpful in treatment of feline glaucoma.

Other Therapies: Because cats are more sensitive to topical medication, other therapies such as demecarium bromide and pilocarpine should not be administered to cats. In addition, they have limited efficacy for feline glaucoma due to the nature of this condition in cats and high prevalence of underlying ophthalmic disease as the cause of secondary glaucoma in this species.

Surgical Therapy of Sighted Eyes
Surgical therapy is rarely utilized in cats. Surgical treatment for aqueous misdirection syndrome is a possible exception as this has been shown to be effective at controlling intraocular pressure due to the nature of the disease.²³ Use of laser therapy has not been studied in cats, likely due to the paucity of primary glaucoma in this species. In addition, laser therapy or cryotherapy causes damage to the ciliary body and may indirectly damage the lens. Lens damage in cats has been shown to be a risk factor for intraocular traumatic lens-induced sarcoma formation. One case report exists describing the successful use of an Ahmed valve for primary glaucoma in a young Russian blue;¹⁵ however, this is not commonly performed in cats. Further research is needed to determine if valve placement is a viable option for glaucoma treatment in cats.

Lensectomy: Removal of the lens is the preferred treatment for anterior lens luxations resulting in glaucoma. However, in cats, referral to determine candidacy for the surgery is indicated because anterior lens luxation and glaucoma in cats is typically due to underlying ophthalmic disease.

Surgical Therapy of Blind Eyes
Salvage procedures are often considered for irreversibly blind eyes, especially when IOP becomes refractory to the above treatments.

Enucleation: Enucleation, with or without intraorbital prosthesis, is a good option for alleviating pain associated with glaucoma (i.e. IOP >50 mmHg) refractory to all initiated treatments. Enucleation may also be considered for blind eyes with glaucoma that is poorly controlled on medical therapy (i.e. IOP >30 mmHg), or when medical therapy becomes too expensive or overwhelming for the owner. Certain causes of glaucoma (e.g. intraocular neoplasia) are also indications for enucleation.

Evisceration/Prosthesis: Evisceration and insertion of an intrascleral prosthesis is a cosmetic procedure that can be considered for eyes blind with primary glaucoma. It is not commonly performed in cats due to the appearance of a black or “ghost” eye. However, for bilateral disease, it may be an option or in cases in which clients do not wish to have the eye enucleated.²⁴ This procedure should not be performed in eyes with intraocular masses since intraocular tumors in cats can be metastatic.

Gentamicin and Cidofovir Ciliary Ablation: Intravitreal gentamicin or cidofovir injections should not be performed in cats due to the risk of traumatic lens-induced sarcoma formation. This is a metastatic tumor and has been linked to trauma and these injections in cats.²⁵

SUPPORTIVE THERAPY
Treatment of underlying conditions causing secondary glaucoma (e.g. uveitis) is indicated. For uveitis, topical and oral or injectable anti-inflammatory therapy may be indicated. Analgesics may also be helpful but oral analgesics do not alleviate pain associated with severe glaucoma, if IOP is not reduced. Medications that may increase IOP, such as mydriatics (e.g. atropine, cyclopentolate, tropicamide) and nonsteroidal anti-inflammatory drugs (can decrease aqueous outflow) are avoided in most eyes with glaucoma.

MONITORING
It appears that cats are more resistant to optic nerve damage and vision loss with elevated intraocular pressure than dogs. However, over time, glaucoma causes permanent damage to the retina and optic nerve and can be blinding in cats. It is important to note that glaucoma is painful and even if a patient is not exhibiting signs of “pain,” this type of pain causes headache-like pain. Often, the client does not perceive that the cat is in pain until the glaucoma is treated or the eye is removed. The goal is to return IOP to normal (i.e. <25 mmHg, ideally 10-15 mmHg). Sustained IOPs >30 mmHg indicate the need for more aggressive therapy. If medical therapy fails, referral should be considered. For blind painful eyes with sustained glaucoma, enucleation is the treatment of choice for cats.

PROGNOSIS
Prognosis for primary glaucoma is guarded over time. Prognosis for secondary glaucoma is dependent upon the underlying cause and whether it can be treated effectively.

Preventive Measures:
Screening Tests
Genetic Test: A mutation in LTBP2 has been shown to cause congenital glaucoma in domestic cats. Otherwise, genetic testing has not been be utilized in this species. This is also likely related to the decreased incidence of primary glaucoma in cats compared to dogs.

Gonioscopy: This modality may be utilized in cats, but is not routinely performed as a screening measure due to the low prevalence of primary glaucoma.

IOP Measurement: Intermittent monitoring of IOP is not utilized in normal cats. If uveitis is present or intraocular pathology, IOP monitoring should be performed periodically (q2-6mo depending on the severity of disease). This is especially because glaucoma in cats is not as clinically apparent to the owner or clinician compared to dogs.