June 2009

Ophthalmology

Anne Gemensky Metzler, DVM, MS, DACVO
Ohio State University


Management of Canine Corneal Diseases

CORNEAL PATHOPHYSIOLOGY

A. Transparent, non-vascular and colorless anterior portion of the fibrous tunic
  1. Composed of dense connective tissue arranged in a regular lamellar pattern.

  2. Normal corneal thickness in dogs is approximately 0.5 to 0.6 mm and thickness increases with age and weight of the animal.

  3. Transparency maintained by the following mechanisms:
    1. Regular lamellar pattern
    2. Physiological pump of the posterior endothelium corneal dehydration (deturgescence)
    3. Non-keratinized anterior surface epithelium
    4. Small diameter of the collagen fibrils
    5. The cornea is the most powerful refractive surface of the eye and will bend light in order to focus the object being in the visual field onto the retina.

  4. Corneal function: most powerful refractive surface of the eye and bends light in order to focus the image onto the retina.
B. Four Corneal Layers: multilayered anterior epithelium, stroma, Descemet's membrane, endothelium.
  1. Epithelium consists of basal cells that lie on a thin basement membrane, two to three layers of polyhedral or wing cells and two to three layers of nonkeratinized squamous epithelial cells that are continuous with the conjunctival epithelium.

  2. Stroma (substantia propria) forms the bulk of the cornea (90%)
    1. Extracellular matrix and parallel lamellar arrangement of collagen fibrils separated by less than a wavelength of light.
    2. Keratocytes interwoven between the collagen fibrils and extracellular matrix.
      1. Possess cellular extensions that help to maintain the integrity of the stromal lamellae.
      2. After deep corneal injury, keratocytes differentiate into fibroblasts and contribute to scar formation.

  3. Descemet's membrane - located on the posterior surface of the cornea, is an acellular basement membrane that functions as a protective boundary within the cornea and thickens as it is produced throughout life by the corneal endothelium.

  4. Corneal endothelium is a monolayer of flattened polygonal cells lining the posterior aspect of the cornea.
    1. Metabolic (sodium-potassium-ATPase) pumps function to maintain a state of deturgescence in the corneal stroma to maintain the optical clarity.
    2. In the adult, the endothelium rarely undergoes mitosis and there is an age-dependent loss of endothelial cells. Cells enlarge and spread to compensate for loss of neighboring cells.
C. Corneal response to injury and disease
  1. Corneal ulceration usually occurs secondary to trauma and will result in edema.

  2. Focal edema is usually due to an epithelial defect and diffuse edema is usually due to an endothelial defect.

  3. Vascularization is a nonspecific change and the cornea will vascularize at the depth of the lesion.
    1. Superficial vascularization = branching vessels that cross the limbus
    2. Deep vessels = straight brush border appearance and do not cross the limbus
    3. Vascularization begins two to four days after an insult or injury and then continues at a maximum of one millimeter per day thereafter.

  4. Pigmentation is a nonspecific change that is due to chronic irritation, but can be a result of specific diseases such as chronic superificial keratitis (pannus).

  5. Scarring and granulation tissue are due to injuries that penetrate the stroma.
D. Response of neighboring structures to corneal disease
  1. The axonal and oculopupillary reflexes result in conjunctival hyperemia, miosis (pupil constriction), ciliary muscle spasm (seen as blepharospasm and photophobia), increased protein levels in the aqueous humor(aqueous flare).

  2. Topical atropine alleviates some of the discomfort by paralyzing the iris and ciliary body muscles.
E. Normal corneal wound healing
  1. With superficial epithelial defects, basal cells migrate to cover the defect within one hour of the injury, and within 24 to 48 hours mitosis begins to replenish cell loss.

  2. Uncomplicated corneal ulcers will heal within 5 to 7 days unless the underlying etiology persists, the ulcer is infected or it has a basement membrane defect (indolent ulcer).

  3. Stromal wound healing is slower and involves epithelial sliding and stromal replacement. Initially there is edema at the site of epithelial loss until the defect has re-epithelialized. Fibroblast proliferation provides structural support for the stromal defect.

  4. Defects resulting from full thickness ulcers or lacerations are sealed initially with fibrin from blood-aqueous-barrier breakdown. The surrounding epithelium begins to replicate. Then, neutrophils infiltrate the wound. Keratocytes are converted to fibroblasts that produce collagen and invade the fibrin plug in three to six days. Collagen and glycosaminoglycan synthesis and collagenase simultanenously remodel the cornea. Lost stromal lamellae are replaced by fibrous scar tissue that may not be transparent.

  5. Corneal strength is not regained for months-years following stromal injury.

  6. Corneal endothelial loss is restored by hypertrophy (increase in cell size) of the endothelial cells to retain their barrier effect. These cells are slowly lost with age and they do not undergo mitosis in the adult animal. If a significant number of endothelial cells are lost, diffuse corneal edema will develop.

  7. Corneal opacity in response to disease or injury can be classified based on color.
    1. White opacities include edema, cellular infiltrate, calcium and lipid infiltrates and scars.
    2. Brown opacities include pigmentation (all species) and sequestrum formation (cats only).
    3. Red opacities include vascularization and intrastromal hemorrhage.
F. Diagnosis and Treatment of Ulcerative Corneal Disease
  1. Causes of corneal ulceration:
    1. Dogs, corneal ulcers are usually the result of trauma, keratoconjunctivitis sicca (KCS aka. "Dry Eye"), corneal degeneration, bullous keratopathy secondary to endothelial dystrophy or degeneration or indolent ulcers.
    2. Cats, they are usually caused by feline Herpesvirus-1 (FHV) infection.

  2. Four types/degrees of ulcerative keratitis in small animals: superficial, midstromal, deep (descemetocele), and melting corneal ulcers. Indolent ulcers are a type of superficial ulcer.

  3. Diagnosis:
    1. Initial evaluation requires determining the extent of corneal involvement and then performing the appropriate diagnostics and therapy.
    2. Schirmer tear test should be performed to rule out KCS in all cases of non-traumatic/non-perforated corneal ulceration.
      1. Normal values: ?15 mm/minute
      2. Greater than normal STT values are expected in cases of corneal ulceration/ocular pain due to increased reflex tearing; therefore, a normal STT in an eye with an ulcer may indicate KCS.
    3. Corneal culture and susceptibility is indicated in all cases where corneal infection is suspected based on clinical appearance and/or chronicity and in all cases of stromal involvement.
      1. Corneal culture may not be feasible due to risk of perforation in ulcers with greater than mid-stromal involvement or descemetoceles.
      2. Corneal culture may not be feasible due to risk of wound leakage in perforated corneal ulcers.
      3. Culture is best performed using a moistened culturette and before application of topical anesthetics to increase yield and viability of organisms.
    4. Fluorescein stain to determine the size of the ulcer or if the epithelium is intact.
      1. Best done before application of topical anesthetic
      2. Helpful to diagnose a descemetocele (see below).
    5. Corneal cytology is indicated in all cases where corneal infection is suspected based on clinical appearance and/or chronicity and in all cases of stromal involvement.
      1. May be performed after application of topical anesthetic.

  4. Superficial corneal ulcers are caused by trauma to the epithelium due to injury, pre-existing eyelash disorders (distichiasis or ectopic cilia), lagophthalmos, KCS and trichiasis.
    1. Superficial ulcers are painful and clinical signs include blepharospasm, epiphora, and pawing at the eye.
    2. Clinical appearance: break in epithelium only, fluorescein positive, focal corneal edema, no divot or defect in corneal stroma.
      1. Infected superficial ulcer: same as above except increased pain, evidence of anterior uveitis, and white-yellow cellular infiltrate
    3. They generally heal within 72 hours unless the underlying etiology is not removed, the ulcer has become infected, or it is indolent.
    4. Therapy for uncomplicated corneal ulcers is broad-spectrum topical antibiotic solution or ointment (triple antibiotic QID) and topical atropine (SID to BID).
    5. Topical corticosteroids are always contraindicated with corneal ulcers!!

  5. Indolent/refractory ulcers (a.k.a. Boxer ulcer, recurrent erosion) are a specific type of superficial corneal ulcer that result from failure of the epithelium to adhere to the underlying basement membrane.
    1. The Boxer breed is predisposed as are middle aged to older dogs of any breed.
    2. Routine corneal ulcer therapy alone is not sufficient for these ulcers; they require debridement of the ulcer's redundant epithelial edges and a multiple grid keratotomy (MGK).
      1. Debridement and MGK Procedure: Quiet room, good animal restraint, topical anesthetic, dry cotton-tipped swabs to debride epithelium, 25-gauge needle using beveled edge held at a 30 degree angle to the cornea to create the grid lines completely covering the ulcer and extending a small distance into the normal surrounding epithelium.
      2. Warn owner that dog's eye will be much more uncomfortable for 24-48 hours after the debriement/MGK procedure due to irritation of superficial corneal nerve endings.
      3. Dogs with secondary entropion or severe blepharospasm will benefit from a temporary contact lens (do not leave in without cleaning for greater than 5 days).
      4. Topical antibiotic (Terramycin® ointment or triple antibiotic solution) q 8 hours and atropine (q 24-72 hours) are used to prevent secondary bacterial infection and control pain, respectively.
        1. Use of tetracyclines topically and/or orally has been associated with increased rate of healing of indolent/refractory ulcers in-vitro and in retrospective evaluation in-vivo
    3. Recheck ulcer every 5-7 days until healed. ? 90% are healed within 10-14 days.
    4. Don't repeat debridement and MGK for at least 2 weeks.
    5. Topical corticosteroids are always contraindicated with corneal ulcers!!

  6. Superficial ulcers in cats - See Feline Ophthalmology

  7. Midstromal corneal ulcers are usually infected, painful, and have associated uveitis.
    1. Clinical appearance: visible divot or defect in stroma, usually more pronounced and extensive corneal edema, fluorescein-positive, white-yellow cellular infiltrate may be visible, anterior uveitis (miosis, refractory to pharmacologic mydriasis, aqueous flare)
    2. These ulcers should be evaluated by a culture/sensitivity and cytology performed.
      1. Diff-Quik to screen for neutrophils, rods and/or cocci bacteria
      2. If organisms found on cytology, culture and susceptibility should be submitted
      3. If cytology is negative for PMNs and organisms and no corneal cellular infiltrate is observed, culture is optional.
    3. Ulcer must be monitored closely for progression to deeper ulcers or perforation - Hospitalize patient or recheck at least every 24-48 hours!
    4. Initial topical antibiotic therapy should include triple antibiotic solution or ointment every 2 to 4 hours for 24 hours then q 4-6 hours until healed.
    5. If this fails to stop progression, then change to a stronger antibiotic such as topical fluoroquinolone such as ciprofloxacin (Ciloxan®, Alcon) every 4-6 hours.
    6. Topical atropine (q 24-72 hours) should be used to relieve pain
    7. Tear replacement therapy if needed (TID to QID).
    8. Most infected ulcers are caused either by opportunistic gram-positive organisms or Pseudomonas species.
    9. The fluoroquinolones (see Summary Canine Ulcer Treatment) have excellent efficacy against Pseudomonas spp. as well as good gram-positive spectrums and are superior to gentamicin and tobramycin.
      1. Gentamicin has poor efficacy again gram-positive flora and is only ~85% effective again Pseuodomas aeruginosa; therefore, it is a poor choice for treatment of most corneal ulcers.
    10. Surgical management is indicated for ulcers that have progressed beyond the mid-stroma! Surgery commonly involves debridement of affected stroma and placement of a conjunctival pedicle graft.

  8. A descemetocele is the deepest type of corneal ulcer and perforation is imminent.
    1. Clinical appearance: Exposed Descemet's membrane does not retain fluorescein and since it is basement membrane, it does not absorb fluid like the stroma and remains clear relative to the adjacent edematous stroma. There is always a visible divot around the descemetocele.
      1. Clinical hint: Descemet's membrane rarely bulges forward. Most often, observed bulging of the cornea is due to keratomalacia, edema or fibrin clot/uveal prolapse after corneal perforation.
    2. Deep ulcers, descemetoceles and perforated corneal ulcers are ophthalmic emergencies that require immediate surgical intervention.
    3. Conjunctival pedicle flaps with or without a tectonic (support) graft or corneoconjunctival transposition are the treatments of choice depending on the case.
    4. Antibiotic therapy:
      1. Triple antibiotic solution is used first, if this is not effective as evidenced by progression of the ulcer or by cytology results, then changing to a fluoroquinolone solution is indicated until culture results are available.
      2. Systemic antibiotics are indicated when a perforated corneal ulcer is present.
      3. Topical atropine therapy is indicated for cycloplegia and ciliary spasm.
      4. Ophthalmic solutions should be used in cases of perforation or impending perforation because ointments are extremely irritating to the intraocular structures.
      5. Third eyelid flaps are contraindicated for this or any other ocular disease in dogs and cats.

  9. Melting corneal ulcers are rapidly progressive ulcers caused by enzymatic degradation of the stroma, usually due to bacterial infection with Pseudomonas aeruginosa or beta-hemolytic Streptococcus species or excessive collagenase activity induced by neutrophilic infiltrate.
    1. Clinical appearance: Severe corneal edema, variable degrees of ocular pain, pronounced swelling and malacia of the cornea resulting in a drooping or bulging appearance. Melting may commonly manifest in dogs as "drilled out" defects in the stroma rather than stromal swelling and bulging. Cellular infiltrate may or may not be apparent. Usually considerable anterior uveitis (aqueous flare, miosis, hypopyon).
    2. Medical therapy includes topical antibiotic therapy as described above, and topical atropine.
    3. Topical anticollagenolytic agents can be used (tetracycline family member topically or orally). The tetracycline family has been shown to chelate zinc and calcium and stabilizes collagenolytic activity.
      1. When treating with both a tetracycline (bacteriostatic) and a bacteriocidal topical antibiotic, administration should be separated by 1-2 hours.
    4. Surgery is often indicated and includes debridement of affected stroma and placement of a conjunctival pedicle graft. This condition is also an ophthalmic emergency.

  10. Corneal perforation occurs after full-thickness progression of an ulcer through descemet's membrane and the endothelium or corneal laceration.
    1. Clinical appearance: Deep corneal defect surrounding a protruding area of clotted fibrin/aqueous (usually tan-yellow +/- blood) or uveal tissue (tan to brown or black +/- hemorrhage) plugging the defect.
      1. May visualize leakage of aqueous humor and/or blood through the defect.
      2. The anterior chamber usually appears shallow or collapsed.
      3. Dyscoria may be observed if the defect is plugged by an iris prolapse and the chamber is reformed.
      4. Siedel test: fluorescein dye is applied to the corneal surface. Dye penetrates into the anterior chamber making the aqueous green or clear aqueous leaking from the defect can be seen flowing in the green tear film.
    2. Prognostic factors to consider before determining treatment:
      1. Size of ulcer
        1. Better prognosis with smaller defect to repair
      2. Health of surrounding cornea
        1. Need some healthy surrounding corneal tissue to suture corneal and/or conjunctival graft
      3. Size of uveal prolapse
        1. Smaller more acute prolapse generally has better prognosis than larger more chronic prolapse
      4. Anterior chamber
        1. Formed, deeper AC indicates that the defect is not leaking and generally has a better prognosis
        2. Hyphema, when extensive, indicates significant intraocular injury and therefore has a poorer prognosis
        3. Fibrin in the AC is a normal response to trauma, leaking and helps to plug the defect. Extensive fibrin formation may be associated with a worse prognosis due to sequelae of synechia, cataract, etc.
        4. Hypopyon suggests corneal +/- intraocular infection and may indicate a poorer prognosis.
        5. When opacity of the anterior chamber such as blood, fibrin precludes examination of the lens and fundus, ocular ultrasonography is indicated.
      5. Lens involvement
        1. Surface visible, no evidence of capsule laceration or cataract - better prognosis
        2. Surface not visible due to fibrin, blood - risk of capsule laceration
        3. Lens capsule laceration/rupture - lens extraction is required to prevent cataract, severe lens-induced uveitis and secondary glaucoma
      6. Posterior segment health/prognosis for vision
        1. Menace, dazzle (light perception) and pupillary light reflexes should always be evaluated.
          1. Absent menace may be due to pupil occlusion or opacity of the ocular media
          2. Absent direct and consensual PLR and dazzle reflex indicates severe damage to the retina +/- optic nerve; therefore prognosis is poor
          3. Presence of PLR and dazzle indicates at least 2-5% of the retina is functioning but is non-specific in predicting long-term quality of vision
        2. Ocular ultrasonography - indicated when opacity of the ocular media precludes examination of the fundus
          1. Vitreal hemorrhage and/or retinal detachment - poor prognosis
      7. Patient/client factors - age/health of patient, financial ability of client, etc.
    3. Treatment:
      1. Emergency referral for surgical therapy is recommended
      2. Recommend placing an Elizabethan collar to prevent further ocular trauma
      3. Ophthalmic solutions should be used in cases of perforation because ointments are extremely irritating to the intraocular structures.
      4. Systemic antibiotics and non-steroidal anti-inflammatories are indicated
      5. Surgical options include corneoconjunctival transposition, corneal transplantation and conjunctival pedical grafting
      6. For cases with a poor prognosis for vision or globe salvage, enucleation must be considered.
G. Treatment of Nonulcerative Corneal Disease
  1. Chronic Superficial Keratitis (a.k.a. Pannus) is a progressive immune-mediated disease with lymphocytic-plasmacytic cellular infiltrate, pigmentation and vascularization.
    1. German shepherd dogs and Greyhounds are predisposed but any dog can be affected.
    2. Pannus begins at the temporal or inferotemperal limbus and progresses centrally.
    3. If not treated appropriately, it can infiltrate the entire cornea.
    4. In some dogs the third eyelid can also be involved (called "plasmoma").
    5. The clinical signs, signalment and cytology specimens that yield lymphocytes and plasma cells will confirm the diagnosis.
    6. Therapy:
      1. Topical corticosteroids initially three to four times daily (0.1% dexamethasone or 1% prednisolone acetate) then weaned over 4-8 weeks to treatment q 48 hours, then eventually discontinued.
      2. Maintained with topical 0.2% cyclosporine (Optimmune®, Schering Plough), 2% cyclosporine compounded in oil or 0.02% tacrolimus compounded in solution or ointment twice daily.
      3. Consider canine sunglasses, Doggles®, to reduce UV light exposure to the cornea (www.doggles.com)
      4. Rarely, topical medication is not effective and subconjunctival corticosteroids, oral corticosteroids (prednisone at the anti-inflammatory dose) or beta irradiation (i.e. strontium 90) may be necessary.
    7. Pannus is more difficult to treat in dogs living at higher altitudes due to increased UV light exposure.
    8. Disease is not curable but can be adequately controlled.

  2. Eosinophilic keratitis is unique to the cat and horse - See Feline Ophthalmology.
CANINE ULCER MANAGEMENT SUMMARY

Diagnostics:
  1. Preliminary examination
    1. Determine depth of ulcer: epithelial, stromal, desmetocele or rupture/full-thickness
    2. Evaluate for signs of infection: yellow-white cellular infiltrate, excessive pain, uveitis (miotic pupil), stromal loss or malacia (melting), active corneal vessels
    3. Rule out conjunctival foreign body or other predisposing causes of mechanical trauma (distichia, ectopic cilia, entropion, etc.)

  2. Culture and susceptibility for aerobic bacteria (moisten sterile swab w/ sterile saline first to improve yield of organisms or break vial at bottom of prepared culturette w/ Stewart's transport medium).

  3. Schirmer tear test to rule out keratoconjunctivitis sicca
    1. Normal ? 15 mm/minute
    2. In the presence of an ulcer/ocular pain, reflex tearing should result in an increased STT in a normal eye.

  4. Fluorescein stain
    1. To determine size of the ulcer or if the epithelium is intact
    2. Also useful to diagnose a desmetocele-Descemet's membrane is basement membrane and does not stain while corneal stroma does. Descemet's membrane is clear and does not imbibe the stain while exposed stroma is cloudy/edematous and stains green.

  5. Topical anesthetic then cytology to look for bacteria and fungi (Diff-Quik)
Antibacterials:
  1. Triple antibiotic ophthalmic ointment or solution - Sig: 1/8" q 4-6 hours
    Cost $15-25
    **Broad-spectrum - good 1st choice for infected ulcer or prophylactic therapy

  2. Ciprofloxacin ophthalmic oint or soln. (Ciloxan) - Sig: 1/8" (or 1 drop) q 4-6 hours
    Cost $50-55 per 5 ml; $45-50 per 5 gm tube ointment
    **Penetrates intact epithelium therefore used to treat stromal abscesses

  3. Ofloxacin ophthalmic soln. (Ocuflox) - Sig: 1 drop q 4-6 hours
    Cost $50-60 per 5 ml
    **Penetrates intact epithelium and reaches therapeutic levels in aqueous humor better than Ciloxan

  4. Levofloxacin soln. (Quixin) - Sig: 1 drop q 6 hours
    Cost $60
    **Penetrates corneal epithelium 6X better than Ciloxan
Anticollagenases:
  1. Autogenous serum - Sig: 0.1 ml q 4 hours (discard after 48 hours)
    **For melting ulcers if not treated surgically

  2. Oxytetracycline oint (Terramycin) - Sig: 1/8" q 6-8 hours
    **For melting ulcers (has anti-collagenase and immune modulating properties)
    **Separate use of this Abx (bacteriostatic) from use of other bacteriocidal Abx by at least 1-2 hours

  3. Doxycycline - Sig: 5 mg/kg PO BID
Anti-inflammatories

1) Carprofen (Rimadyl) - Sig: 2 mg/kg orally q 12-24 hours

2) Diclofenac sodium (Voltaren) - Sig: 1 drop q 6-8 hours

Mydriatic:

1) Atropine 1% solution or ointment
Sig: 1/8" or 1 drop q 8-12 hours initially or as needed to keep pupil dilated.
**Not recommended to use more frequently than q 8 hours
**If uveitis is well controlled, pupil may stay dilated 48 hours or more from a single application.

Candidates for Surgical Therapy:
  • Depth of ulcer near or greater than 50% stromal depth
  • Desmetoceles
  • Perforated ulcers
  • Melting ulcers
  • Corneal lacerations
  • Stromal abscesses, especially in axial cornea, no vessels approaching and/or if refractory to therapy


    Diagnosis and Treatment of Cataracts

    Cataracts

    A. Any opacity of the lens without regard to etiology

    B. Causes of cataracts in dogs:
    1. Inherited is the most common cause
    2. Diabetes mellitus - as glucose levels increase in the eye with diabetes, hexokinase becomes saturated, glucose accumulates in the lens and begins to be metabolized by the sorbitol pathway, sorbitol and fructose accumulate within the lens cells resulting in a hypertonic state which causes water to accumulate, the lens fibers continue to swell and rupture forming vacuoles in the lens cortices and eventually the entire lens becomes opaque.
    3. Nutritional disorders
      1. arginine or other amino acid deficiencies
      2. Xylose excess: rats
      3. Galactosemia: kangaroos, wallabies fed cow's milk
    4. Progressive Retinal Atrophy (PRA) - dialdehyde toxins are released from the degenerating retina causing subcapsular and cortical lens opacities
    5. Electrolyte/mineral imbalances: hypocalcemia
    6. Trauma
    7. Inflammation (uveitis) = especially cats and horses
    8. Electric cord shock
    9. Irradiation (radiation therapy for cancer)
    10. Toxins or drugs - corticosteroids in humans, disophenol (DNP), naphthalene in dogs, hygromycin in sows; DMSO: transient
    11. Senility - may refer to time of onset and etiology (not nuclear sclerosis)
    12. Persistent vascular remnants
    C. Classification of cataracts
    1. By age of onset (does not imply etiology)
      1. congenital: present at birth
      2. juvenile: few months to 6 years
      3. senile: dog >6 years
    2. By location (determined by slit lamp)
      1. capsular
      2. subcapsular (anterior, posterior, equatorial)
      3. cortical
      4. nuclear
      5. axial
      6. polar
    3. By degree of maturation
      1. Incipient (less than 10% of tapetal reflection obstructed)
      2. Early Immature (10 to 50% of tapetal reflection/fundic view obstructed) - refer at this stage to increase success of the surgery
      3. Late Immature (51 to 99% of tapetal reflection/fundic view obstructed)
      4. Mature (100% of tapetal reflection/fundic view obstructed)
      5. Hypermature (cortical lens material may undergo liquefaction and part of the tapetal reflex may be seen; the lens capsule may be wrinkled with multifocal dense white plaques, the anterior chamber depth may be increased, may see signs of lens-induced uveitis)
    D. Tendency to progress
    1. nuclear: usually static
    2. cortical: variable, often progressive
      1. anterior cortical - more likely progressive
      2. posterior cortical
        1. axial, well-demarcated - unlikely to progress
        2. peripheral/vacuoles - likely to progress
      3. equatorial: often progressive
    E. Sequelae to cataracts
    1. These dogs should not be used in a breeding program
      1. If selling animal, the buyer must be told!
    2. The dog may lose vision (depends on liklihood of progression)
    3. Chronic or hypermature cataracts will develop lens-induced uveitis, may develop secondary glaucoma and/or retinal detachment
    4. Diabetic cataracts may result in severe lens-induced uveitis
    5. Diabetic cataracts that progress rapidly may result in spontaneous rupture of the lens capsule due to massive lens fiber swelling.
    F. Treatment of cataracts
    1. Rule out diabetes mellitus
    2. There is no medical therapy for cataracts!
      a. N-acetyl-cysteine products do not work!!!
    3. Surgery is the treatment of choice
    4. Surgical success rates: best outcome (>90% success) if the cataract is immature-mature, success decreases to <85% if cataract is hypermature
    G. Surgical techniques:
    1. Phacoemulsification
      1. Ultrasonic fragmentation of the lens
      2. Intraocular lens prosthesis placement
        1. Silicone foldable IOL with squared edges
          1. Best inhibition of lens epithelial cell migration and capsule fibrosis
          2. Larger surface area therefore less likely to decenter
          3. Decreased corneal incision length from approx 8 mm to approx 4 Martin
            1. Less astigmatism & shorter closure time
      3. Two-handed technique - using a second instrument to shorten surgical time in hard lenses or improve stability of subluxated lenses
      4. Capsule tension ring
        1. PMMA ring designed to keep capsule taut to decrease capsule scarring
        2. Also useful for improving stability of subluxated lenses
      5. If the cataractous lens is subluxated, phacoemulsification can sometimes still be done, but intracapsular extraction (ICCE) may be required.
      6. If the cataractous lens is luxated, it will require intracapsular extraction (ICCE) and a sulcus-fixated intraocular lens prosthesis can be sutured into the posterior chamber (behind the iris) - see Lens Luxations below.
      7. There is no laser treatment for cataracts!!!! ND:YAG laser is used often in human patients for secondary cataracts (we call this posterior capsular opacification, PCO)
    Lens Subluxations and Luxations

    A. Etiology (all involve degeneration or damage to the ciliary zonules)
    1. Primary/inherited - most terrier breeds
    2. Secondary to glaucoma (buphthalmia causes the zonules to break)
    3. Secondary to chronic uveitis (especially in cats)
    4. Associated with hypermature cataracts
    5. Trauma (uncommon)
    B. Clinical Signs
    1. Aphakic crescent (a portion of the pupil is devoid of the lens)
    2. Iridodonesis and phacodonesis (quivering of the iris and lens, respectively)
    3. Deep anterior chamber if lens is posteriorly displaced
    4. Shallow anterior chamber if lens is anteriorly displaced
    5. Blepharospasm, corneal edema and increased intraocular pressure especially if anterior lens luxation; usually acute
    6. Complications of lens luxation: corneal endothelial damage (corneal edema, usually focal ventral paraxial), glaucoma, anterior uveitis
    C. Treatment of lens luxation
    1. Surgical intervention: intracapsular lens extraction (ICLE)
      1. This is a surgical emergency if the lens is anteriorly luxated
      2. Even a posterior luxation may require removal because leaving the loose lens will predispose the eye to chronic uveitis, glaucoma and retinal detachment
      3. Prognosis is dependent on the cause, duration of the luxation and extent of secondary damage and presence of secondary glaucoma.
    2. Medical management with miotic agent
      1. Latanoprost (Xalatan) or travaprost (Travatan) q 12 hours
      2. Induces extreme miosis to keep lens posterior
      3. Antiglaucoma: increases uveoscleral aqueous outflow to lower IOP
      4. May be useful for contralateral subluxated eye after unilateral luxation
    3. No clinical study has been performed to date comparing the long-term retention of vision and maintenace of IOP after ICLE vs. latanoprost or travaprost
    4. Current treatment of luxation or subluxation is ICLE + endolaser of ciliary processes
    Nuclear Sclerosis

    A. Aging change due to compression of nucleus by cortical fibers

    B. Age of onset:
    1. dog: 6 years
    2. cat: 7-9 years
    3. horse: 15 years
    C. Diagnosis is made by dilating the pupil and seeing the fundic reflex

    D. Treatment of nuclear sclerosis: none

    E. If cloudiness progresses to the point where the dog is blind and the fundic reflex is not visualized, then senile cataract has developed and may require surgical treatment.

    Lens-induced uveitis

    A. Immune-mediated intraocular inflammation caused by liquefaction and leakage of lens proteins from the lens capsule
    1. Most commonly occurs with rapid cataract progression, especially in diabetic dogs and young dogs.
    2. Cataracts do not need to be mature/hypermature in order to see uveitis.
    B. Clinical signs: photophobia, blepharospasm, hyperemia, miosis, resistence of the pupil to dilate with tropicamide or atropine, aqueous flare, corneal edema

    C. Treatment:
    1. Atropine 1% ophthalmic solution or ointment
      1. Contraindicated if intraocular pressure is elevated!!
      2. Use topically q 12-72 hours
      3. Stabilizes blood aqueous barrier, eliminates photophobia, prevents posterior synechia and seclusion of the pupil
    2. Prednisolone acetate 1% (Econopred Plus or Pred Forte or generic)
      1. Contraindicated with presence of corneal ulceration!!
      2. Use topically 2-4 times daily initially then gradually wean to once daily or every other day.
      3. May cause insulin resistance in diabetic dogs at high dosages
    3. Diclofenac 0.1% (Voltaren)
      1. Non-steroidal anti-inflammatory
      2. Not as potent as topical prednisolone
      3. Use topically 2-4 times daily initially then wean to once daily
      4. Does not affect insulin requirement of diabetic; therefore a good maintenance drug after uveitis is well-controlled
    4. Carprofen (Rimadyl)
      1. Non-steroidal anti-inflammatory
      2. Works well in conjunction with topical medications
      3. 0.5 mg/kg PO q 12-24 hours
    5. Refer ASAP for evaluation of cataracts for surgery.

    Diagnosis and Treatment of Canine Glaucoma

    Causes of Canine Glaucoma
    1. Breed predisposition:
      1. Over 40 breeds that can develop inherited primary glaucoma.
      2. Inherited or breed-related glaucomas are the most common causes seen in practice.
      3. Primary glaucoma is rare in non-purebred dogs.

    2. Three types of primary glaucoma in dogs:
      1. Narrow/closed angle, open angle, and pectinate ligament dysplasia.
      2. Gonioscopy, examination of the iridocorneal angle, can be used to determine the type of glaucoma present.

    3. Narrow/closed angle glaucoma
      1. Most frequent cause of primary glaucoma in the United States
      2. American Cocker Spaniel is the most common breed

    4. Open angle glaucoma
      1. Most common in the Beagle
      2. Most common cause of glaucoma in humans.

    5. Pectinate ligament dysplasia
      1. Abnormal development of the pectinate ligaments with persistent sheets of mesodermal tissue with flow holes for aqueous humor exit.
      2. Arctic circle breeds and Basset hounds are the most common breeds affected.

    6. Causes of secondary glaucoma:
      1. Anterior lens luxation
        1. Inherited in most Terriers breeds
      2. Anterior uveitis
      3. Retinal detachment
      4. Intraocular neoplasia
    **The goal of the practitioner is to determine whether the patient has glaucoma, if it is primary or secondary and if it is acute or chronic. Once this is established, then a treatment plan can be initiated.

    Clinical Signs and Treatment

    A. Acute Congestive Glaucoma
    • Best to assume it is an acute episode and treat it aggressively.
    • True ophthalmologic emergency
      • A few hours can make the difference between maintaining or losing potential for vision.
    • Clinical signs:
      • IOP greater than 40 mmHg
      • Corneal edema
      • Episcleral injection
      • Mid-sized or mydriatic (dilated) pupil
        • Sluggish or absent pupillary light reflex (PLR)
      • Ocular pain (epiphora, elevated third eyelid, and blepharospasm)
      • Diminished or complete loss of vision.
    • Treatment
      • Should be initiated immediately!
      • Standard initial therapy for rapid IOP lowering includes one of the following three options:
        • Latanoprost 0.005% (Xalatan)
          • 1 drop initially, then every 8-12 hours
          • Prostaglandin analog
            • Causes intense miosis (pinpoint pupil)
          • Increases unconvential (uveoscleral) aqueous outflow
          • Rapidly lowers IOP in most cases
            • May decrease IOP to normal within 20 mintues.
            • Peak effect may take 1-3 hours.
          • Contraindicated with primary uveitis and anterior lens luxation
          • Expensive but most effective glaucoma treatment
          • *Can be used in place of mannitol initially
          • *If no response within 20-30 minutues, can also administer an osmotic diuretic
        • Intravenous mannitol, 20% or 25%
          • Osmotic diuretic - large sugar molecules pull water from vitreous into vessels
          • *Contraindicated in congestive heart failure!
          • Dose: 0.5 to 2 gram/kg given IV over 15 to 20 minutes
            • 5cc/lb of 20% mannitol, 4cc/lb of 25% mannitol
          • *Best to give an anti-inflammatory dose of a corticosteroid before the mannitol to prevent reperfusion injury of the retina
            • eg. SoluDelta Cortef 15 mg/kg IV over 5 min.
          • Withhold water for 2-4 hours after administration
        • Oral glycerine
          • Osmotic diuretic - can be used instead of mannitol
          • May induce vomiting
            • Can give metaclopramide prior to glycerine to prevent
          • Contraindicated with congestive heart failure and diabetes mellitus
          • Dose: 0.5-1.5 gm/kg PO (2/3 ml/lb)
          • Withhold water for 2-4 hours after administration
          • Inexpensive, long shelf life.
    • Additional initial therapy can include one or more of the following:
      • Oral carbonic anhydrase inhibitors (CAI)
        • Methazolamide (Neptazane)
        • Dichlorphenamide (Daranide)
        • 2-5 mg/kg PO q 8-12 hours (start with q 12 hours)
      • Topical carbonic anhydrase inhibitors
        • 2% dorzolamide/Trusopt - 1 drop q 8 hours
        • 1% brinzolamide/Azopt - 1 drop q 8 hours
      • Combination drug - 2%dorzolamide/0.5% timolol (Cosopt)
        • 1 drop q 8-12 hours
    • Ongoing maintenance treatment:
      • Once the IOP decreases consistently below 20 mmHg for a 12-24 hour period, then medical management is continued until laser surgery is necessary.
      • If the IOP does not drop significantly or below 25-30 mmHg, then laser surgery is immediately indicated.
      • Maintenance medical management
        • Carbonic anhydrase inhibitors
          • Oral CAIs (methazolamide, dichlorphenamide)
            • 2-5 mg/kg q 8-12 hours (start with q 12 hours)
          • Topical CAIs (dorzolamide, brinzolamide)
            • One drop q 8 hours
          • Latanoprost 0.005% (Xalatan) -
            • 1 drop q 8-12 hours (start with q 12 hours)
            • Xalatan should be used if the CAIs do not control IOP adequately.
          • Pilocarpine 2% - (1 drop q 8-12 hours)
            • Parasympathomimetic
            • Increases aqueous outflow by ciliary muscle contraction, opens trabecular meshwork
            • Less effective but less expensive than latanoprost
            • Typically not effective if IOP > 35
            • Induces transient uveitis and possible blepharospasm due to ciliary muscle spasm
          • Beta-blockers (Timolol or Betaxolol)
            • One drop q 12 hours
            • Have poor IOP lowering effect; therefore only suitable in combination with other drugs or for prophylactic therapy (see below)
        • Often a combination of these medications is necessary to adequately control IOP for a period of time.
        • IOP should be monitored weekly or every 2 weeks for the first month to ensure that this therapy is adequate, then q 1-3 months.
        • If IOP does not stay within the "safe range" (below 20 mmHg), then laser surgery is indicated.
    • Surgical management for sighted eyes
      • Laser cyclophotocoagulation
        • Diode laser is used most commonly by veterinary ophthalmologists for management of glaucoma.
        • Selectively destroys pigmented cells in the ciliary body (site of aqueous humor production) leading to decreased IOP by decreased production of aqueous humor.
        • Transscleral - non-invasive
          • Moderate cost
        • Endolaser - can directly visualize and treat ciliary processes
          • Usually requires that cataract surgery be performed at the same time to prevent cataract formation associated with the procedure.
          • Expensive
      • Cryocycloablation
        • Destroys the ciliary body by freezing
        • Less commonly used
          • Induces more inflammation than the diode laser and can cause cataracts and retinal detachment.
      • Gonioimplants
        • Shunts placed into the anterior chamber to allow exit for aqueous humor usually into the sub-conjunctival space.
        • These are expensive to install and do not function effectively long-term due to excessive fibrin production in the aqueous humor of canine patients.
    • Prophylactic therapy for contralateral eye:
      • If glaucoma is suspected to be primary based on signalment, then use a topical medication in contralateral eye as a prophylactic measure.
        • Dorzolamide, brinzolamide or timolol q 12 hours
      • Prophylactic treatment will blunt IOP increases, make the owner look at the eye twice daily and has been shown to significantly prolong vision in the contralateral eye.
    B. Early Noncongestive Glaucoma
    • Clinical signs
      • May be subtle or nonexistent.
      • Pupil may be slightly mydriatic
      • Variable episcleral congestion
      • Corneal edema may be mild and transient (if present)
      • Fundus appears normal
      • IOP will range between 25 and 35 mmHg.
      • These dogs will usually have a sudden marked elevation in IOP within weeks.
    • Therapy for this early stage of glaucoma can include one or more of the following medications:
      • Trusopt or Azopt (1 drop q 8 hours)
      • Neptazane or Daranide (2-5 mg/kg q 8-12 hours)
      • Xalatan (1 drop q 8-12 hours)
      • Pilocarpine 2% - (1 drop q 8-12 hours)
        • Less effective but less expensive than latanoprost
        • Induces transient uveitis and possible blepharospasm due to ciliary muscle spasm
    • Recheck the IOP in 30-60 minutes to ensure that the medications are decreasing the IOP, then in 3-5 days.
    • Recheck the IOP every 2-3 months thereafter.
    • Prophylactic therapy for contralateral eye
      • If glaucoma is suspected to be primary based on signalment, then use a topical medication in contralateral eye as a prophylactic measure.
        • Dorzolamide, brinzolamide or timolol q 12 hours
        • Prophylactic treatment will blunt IOP increases, make the owner look at the eye twice daily and has been shown to significantly prolong vision in the contralateral eye.
      • If the IOP begins to rise despite medications, then adding another medication is indicated.
      • The client should be informed of the likely need for referral and laser cycloablation.
      • If IOP?20, laser surgery should be considered.
    C. End-Stage Glaucoma
    • Clinical signs:
      • Buphthalmia
      • Haab's stria (breaks in Descemet's membrane)
      • Blindness
      • Variable IOP (usually between 5 and 50 mmHg)
      • Severe optic nerve cupping and diffuse retinal degeneration.
      • The lens may be subluxated or luxated and cataractous.
      • Chronic exposure keratitis (vascularization and pigmentation)
      • Vision loss is irreversible
      • Surgical options
        • Enucleation
        • Evisceration with intrascleral prosthesis
        • Laser cycloablation to make the patient comfortable.
        • Intravitreal injection with gentamicin
          • For animals that are unable to withstand extended anesthetic event
          • Financial constraints
          • Disadvantages:
            • Inability to predict the eventual size of the globe
            • May need to be repeated
            • Risk of injecting the lens and causing uveitis
            • If there is any potential for vision, it will irreversibly destroy the intraocular structures.
    D. Causes and Treatment of Secondary Glaucoma
    • Clinical management of secondary glaucoma requires diagnosis of the underlying cause and treatment of the specific problem. If there are residual secondary changes (such as peripheral anterior or posterior synechia) then this may require medical or surgical management of glaucoma as described above.
    • If the glaucoma is due to uveitis, latanoprost/Xalatan and pilocarpine should be avoided as these drugs can potentiate inflammation and cause increased risk of posterior synechia due to the miosis induced by the drugs.

    • Anterior Lens Luxation
      • Clinical signs - see lens lecture notes
      • Mechanisms of IOP increase:
        • Pupillary block by lens
        • Anterior displacement of the the iris causing the ICA to close
        • Vitreous herniation anteriorly blocking the drainage angle or pupil.
        • Mechanical damage by subluxated lens bumping on iris causes low-grade inflammation and formation of pre-iridal fibrovascular membrane (PIFM)
      • Treatment:
        • If IOP > 35 mmHg, treat as above for acute congestive glaucoma
        • If IOP < 35 mmHg, treat as above for non-congestive glaucoma
        • Refer for immediate surgery to preserve vision.
          • Assess menace, dazzle and pupillary light reflexes first to determine if the eye has potential for vision
            • Positive response = potential for sight
            • Negative response = guarded prognosis for vision
          • If IOP > 40 mmHg, need to re-assess the reflexes after IOP is lowered as all reflexes are usually lost at this IOP level, but may return when IOP is lowered.
          • If globe is buphthalmic and/or optic nerve is cupped, then prognosis for vision is poor. Most of these globes are enucleated or receive and intrascleral prosthesis.
        • Even if the IOP is not elevated, an anterior lens luxation should be referred immediately for lensectomy surgery +/-placement of a sutured intraocular lens implant +/- endolaser are indicated to maintain vision.
          • Prognosis is better if IOP is <25 mmHg

    • Anterior Uveitis
      • Definition: inflammation of the iris and ciliary body.
      • Clinical signs and treatment - see uvea lecture notes
      • Diagnosis:
        • Thorough ophthalmic and physical examination
        • Labwork to rule out or identify systemic disease
        • Measurement of the IOP
          • In cases of uncomplicated anterior uveitis, the IOP will be lower than the fellow unaffected eye
          • If the IOP is higher than the fellow unaffected eye, then treatment for secondary glaucoma as well as uveitis is important.
      • Treatment of uveitis and glaucoma:
        • Medical management of anterior uveitis should be started immediately to prevent secondary glaucoma from occurring.
        • Prednisolone acetate 1% (1 drop q 6 hours)
        • Atropine 1% (1 drop q 12-48 hours)
          • Should not be used if IOP is elevated > 20 mmHg!
        • Oral anti-inflammatory medications
          • May be necessary for severe uveitis
          • Prednisone 0.5-1 mg/kg/day, then tapered
          • Carprofen, meloxicam, etc.
        • Appropriate bloodwork (CBC, serum chemistry panel, urinalysis and serology) is indicated prior to beginning systemic medications.
        • If the IOP is elevated (> 20 mmHg or compared to the contralateral unaffected eye):
          • Topical and/or oral anti-glaucoma therapy indicated
          • Discontinue topical atropine.
          • Xalatan and pilocarpine are contraindicated in cases of primary uveitis and secondary glaucoma because can promote further inflammation.

    • Retinal Detachment
      • Retinal detachment causes release of vascular endothelial growth factor (VEGF).
      • VEGF induces growth of a fibrovascular membrane on the surface of the iris (Pre-Iridal Fibrovascular Membrane - PIFM) and this can cover the iridocorneal angle causing impedence to aqueous humor outflow.
      • Treatment of retinal detachment will depend on the underlying cause (e.g. systemic hypertension, inflammatory or neoplastic cellular infiltrate, etc.).
      • Treatment of the secondary glaucoma can include medical therapy and laser surgery. Enucleation or evisceration are indicated if vision loss is irreversible and may provide a diagnosis.

    • Intraocular or Extraocular Neoplasia
      • Intraocular tumors (melanoma, adenoma/ adenocarcinoma of the anterior uvea, and lymphoma) can infiltrate the iridocorneal angle, cause anterior uveitis or induce preiridal fibrovascular membranes causing secondary glaucoma.
      • Enucleation is recommended if uveitis or glaucoma results or for malignant primary or secondary tumors.


    Diagnosis and Treatment of Uveal Disease

    Introduction
    • "The eye is the window to the soul."
    • Many systemic diseases have ophthalmic components (eg. uveitis)
    • Ophthalmic disease may be the only evidence of systemic infection
    • Clinical signs are often non-specific
    Uveal Anatomy
    • Uvea = pigmented vascular tunic
    • Anterior uvea
      • Iris
      • Ciliary body
        • Pars plicata - ciliary processes
        • Pars plana
    • Posterior uvea
      • Choroid
    • Blood vessels
    • Nerves
    • Muscle
    • Pigmented and non-pigmented epithelium
    • Connective tissue stroma
    Functions of the Uvea
    • Ciliary processes produce aqueous humor
    • Provides blood supply to iris and retina
    • Immune/inflammatory responses
    • Pupillary sphincter aids in accommodation
    • Ciliary body muscle aids in accommodation and aqueous outflow
    Uveal Physiology (Aqueous)
    • Aqueous humor produced by the non-pigmented epithelium of the ciliary processes
    • Aqueous flows through pupil and flows out through iridocorneal angle
    • Aqueous humor provides nutrition for the lens and removes waste products
    • In a normal non-inflamed eye, aqueous is clear like water
    Uveitis
    • Inflammation of part or all of the uveal tract
    Clinical Signs:
    • Blepharospasm, photophobia
    • Miosis
    • Conjunctival/scleral hyperemia
    • Aqueous flare
    • Inflammatory cells on corneal endothelium (keratic precipitates)
    • Inflammatory cells in vitreous or choroids
    • Decreased intraocular pressure
    • Decreaed vision
    Anterior uveal signs of inflammation
    • Iridal infitrates & neovascularization
    • Hyphema
    • Aqueous flare
    • Lipid flare
    • Hypopyon
    • Fibrin in AC
    Signs of Chronic Uveitis
    • Posterior synechia
    • Pigment on the anterior lens capsule
    • Cataract
    • Lens subluxation/luxation
    • Rubeosis iridis - neovascularization of the iris
    • Secondary glaucoma
    Choroidal Disease
    • Inflammation retinal inflammation
    • Exudate retinal detachment
    • Hemorrhage retinal detachment
    • Serous effusion retinal detachment
    Optic nerve disease
    • Papillitis (ex. Cryptococcosis, GME)
    Miscellaneous Conditions of the Uvea
    • Persistant pupillary membranes
    • Heterochromia irides
    • Uveal cysts
    Uveitis-Etiology
    • Trauma
    • Systemic infectious disease
      • Bacterial, viral, fungal, protozoal, rikettsial
    • Neoplasia
      • Primary or secondary (metastatic)
    • Immune-mediated disease
      • Equine recurrent uveitis, VKH-like disease
    Uveitis-Diagnosis
    • Thorough physical exam imperative!!
    • CBC + platelet count, chemistry panel, UA
    • +/- Specific serology for infectious diseases
    • +/- Thoracic radiographs
    • +/- Bone Marrow Aspirates, etc.
    Bacterial diseases
    • Leptospirosis
    • Brucellosis
    • Septicemia (esp. foals)
    • Lyme's disease
    Rickettsial diseases
    • Ehrlichia canis
    • Rickettsia ricketsii
    • Ehrlichia platys
    • Vasculitis + thrombocytopenia anterior uveitis, intraocular hemorrhage +/- retinal detachment
    Viral Diseases
    • Canine distemper virus (CDV)
    • Infectious canine hepatitis (CAV)
    • Feline herpesvirus
    • Panleukopenia
    • FELV/FIV/FIP
    Algae
    • Protothecosis
    • Collies
    • Bloody diarrhea
    • Exudative retinal detachments
    • Vitreoretinal hemorrhages
    • Anterior uveitis
    Protozoal diseases
    • Leishmaniasis - rare in USA; blepharitis > uveitis
    • Toxoplasmosis
      • Cats > dogs; wallaby, kangaroo
      • Granulomatous anterior uveitis, retinochoroiditis, optic neuritis, myositis of extraocular muscles
    Systemic mycoses
    • Cryptococcosis
    • Blastomycosis
    • Histoplasmosis
    • Coccidiomycosis
    • Aspergillosis
    • Candidiasis
    • **Hallmark is chorioretinitis>>anterior uveitis
    Cardiovascular diseases
    • Systemic hypertension
      • Hypertensive retinopathy, hyphema
    Neoplastic diseases
    • Lymphosarcoma = most common!!!
      • Most common signs in dog = hyphema, anterior uveitis, iridal thickening
      • Poorer Px for treatment response if ocular involvement
    • Primary or metastatic ocular tumors
    Canine Iris Melanoma
    • Hereditary in labrador and golden retrievers
    • Most common primary uveal tumor in dogs and cats
    • Usually focal mass
    • Benign (<5% metastasize)
    • Locally invasive with 2° uveitis/glaucoma
    • Tx: Laser ablation
    Canine Ciliary Body/Choroidal Melanoma
    • Low metastatic potential
    • Cannot treat locally with laser
    • Enucleation may be required
    • Extraocular extension may occur
    Canine Ciliary Body Adenoma/Adenocarcinoma
    • Second most common primary uveal tumor in dogs
    • Usually benign behavior
    • Low metastatic potential
    • Enucleate if causing uveitis and/or glaucoma
    • Some are surgically resectable
    Feline Iridal Melanosis
    • Benign iris hyperpigmentation
    • Must differentiate from iris melanoma
    • Flat, golden brown pigment
    • No dyscoria
    • Middle aged-older cat
    • Monitor carefully in young cat for any evidence of neoplastic transformation
    Feline Diffuse Anterior Uveal Melanoma
    • Malignant?65%
    • Mature cat
    • Invasion of iris stroma dyscoria
    • Young cat: recommend enucleation
    • Old cat: metastases are unlikely/slow to cause death
    Immune-mediated Uveitis
    • Uveodermatologic syndrome/VKH-like disease:
    • Equine Recurrent Uveitis
    • Lens-induced uveitis
    • Diagnosis of exclusion
    Lens-induced uveitis (LIU)
    • Phacolytic uveitis:
      • Deviation of the normal low level of T-cell mediated tolerance to lens proteins (crystallin) and other lens components
    • Phacoclastic uveitis:
      • Severe uveitis in response to massive exposure to lens proteins
      • May lead to secondary glaucoma
    • Clinical signs:
      • Acute LIU: Miosis, hypotony, scleral injection, resistance of pupil to dilation, +/- aqueous flare, +/- keratic precipitates
      • Chronic LIU: Iris hyperpigmentation, posterior synechia, pigment on anterior lens capsule, +/- aqueous flare, +/- keratic precipitates
    • Treatment of Lens-induced Uveitis
      • Atropine 1% - q 12-24 hours
      • Prednisolone acetate 1% - q 6-8 hours
      • Non-steroidal anti-inflammatory drugs
        • Diclofenac 0.1% (Voltaren) - q 6 hours
        • Flubriprofen 0.3% (Ocufen) - q 6-8 hours
        • Nepafenac 0.1% (Nevanac) - q 8-12 hours
        • Carprofen - 2 mg/kg PO q 12-24 hours
        • Eliminate the cause - cataract surgery!
    Feline Uveitis Treatment
    • Atropine ointment SID or PRN
      • Solution makes cats salivate profusely!!
    • Topical corticosteroids T-QID
      • Dexamethasone or prednisolone acetate
      • Caution: may exacerbate or induce FHV-1 flare-up
      • Consider topical or systemic interferon-alpha to prevent FHV-1 recrudescence
    Uveodermatologic syndrome/VKH-like disease
    • Akita predisposed
    • Immune-mediated attack of uveal and dermal pigment
    • Panuveitis
    • Depigmentation of the mucocutaneous junctions (eyelid, nose, lips)
    • Depigmentation of the iris, choroid and retinal pigmented epithelium
    • Dx: biopsy of nasal planum
    • Tx: Prednisone orally @ immunosuppressive dose 1-3 mg/kg/day
    • Azathioprine
    Other Causes of Uveitis:
    • Parasitic (heartworm disease)
    • Ophthalmomyiasis (cuterebra, etc.)

    Feline Ophthalmology

    Unique Anatomy
    • Elliptical pupil
    • Nasal and temporal ciliary nerves innervate pupillary sphincter
    • Prominent major arterial circle
    • Deep anterior chamber
    • Pectinate ligaments visible without gonioscopy
    Fundus
    • Small, round, gray optic nerve head
    • Unmyelinated, therefore slightly depressed
    • No vascular anastomosis over the nerve head
    • Very large yellow tapetum surrounds optic nerve head
    • 3-4 main arteriolar/venule branches
    Normal values
    • Schirmer Tear Tests - Mean = 17 mm +/- 6 mm (range=11-23mm)
      • However, sympathetic tone can completely shut down tear production resulting in 0 mm wetting
    • Intraocular Pressure (IOP) = 15-20 mmHg
      • IOP may transiently increase after instillation of atropine or tropicamide
    • Palpebral fissure length - 28 mm
    Diseases
    • Congenital defects
    • Adnexal and Orbital Diseases
    • Corneal Diseases
    • Uveitis
    • Cataract
    • Glaucoma
    • Retinal Diseases
    • Neoplasia
    Congenital Defects
      Eyelid agenesis
      • Absence of eyelid margin, usually affecting the dorsolateral eyelid margin
      • Associated with PPM's and intraocular coloboma of iris and optic nerve in Snow Leopards and some domestic cats
      • Results in trichiasis and exposure keratitis
      Treatment:
      • Medical management with topical lubricants
      • Cryosurgery to remove trichiasis hairs
      • Eyelid reconstruction
        • Various techniques reported such as rotational pedicle flap

      Corneal/conjunctival dermoid
      • Fleshy mass with hair/hair follicles on corneal &/or conjunctival surface

      Congenital Cataract and Microphakia
      • Usually nuclear cataract that becomes compressed and less significant to vision with age and therefore don't often require surgery
      • Dilemma=formation of neural pathways from retina to brain during development
        • May preclude functional vision if opacity persists long enough to prevent this development\

      Persistant Pupillary Membranes
      • Iris to iris - not clinically significant
      • Iris to lens or iris to cornea may cause corneal or lens opacity and some vision impairment

      Retinal Dysplasia
      • Vermiform or linear retinal folds
      • Causes:
        • Developmental anomaly
        • Heredity
        • In-utero panleukopenia infection
      • Not typically significant to vision
      • Non-progressive
    Adnexal Diseases
      Entropion
      • Medial entropion - common conformational abnormality in brachycephalics
        • Spastic entropion - seen in intact males and cats w/ FHV-1 related keratoconjunctivitis
      • Tx: modified Hotz Celcus +/- very conservative lateral canthoplasty (don't want to shorten lids much as the palpebral fissure length is already small relative to globe size)

      Blepharitis
      • Demodex (rare)
      • Scabies (Notoedres cati) - very pruitic and contagious
      • Myiasis (Cuterebra sp.)
      • Dermatophytosis (M. canis>M. gypseum & T. mentagrophytes)
        • Zoonotic potential!!
        • Tx: topical miconazole, clotrimazole or thiabendazole or systemic griseofulvin or ketoconazole
        • **Must avoid contact of topical preparations with the cornea & conjunctiva
      • Eosinophilic granuloma complex
        • Dx: eosinophils on cytology or biopsy
        • Tx: systemic corticosteroid
        • Px: excellent response to treatment
      • Feline herpesvirus
        • Blepharitis + multifocal/diffuse dermatologic disease
          • Alopecia, lichenification, crusting
        • Tx: Interferon-alpha 2a or 2b - 30-1000 IU PO SID x 7 days on, 7 days off, lysine 500-1000 mg PO SID or divided BID, +/- systemic antibiotics for secondary bacterial infection

      Prolapsed gland of the nictitans
      • Burmese, Persian breeds
      • May have later onset than dogs (reported up to 6 years of age at onset).
      • Clinical appearance and treatment is the same as for dogs (pocket imbrication technique).

      Corneal and Conjunctival Diseases
      • Feline eosinophilic keratoconjunctivitis
      • Feline infectious keratoconjunctivitis
      • Corneal sequestrum
      • Bullous keratopathy

      Feline Eosinophilic Keratoconjunctivitis
      • Clinical signs:
        • Conjunctival hyperemia with thickening and a cobble-stoned appearance
        • Corneal vascularization extending from the limbus and pink-white stromal infiltrate
        • White caseous surface exudate
        • Usually mild to no pain/blepharospasm
        • Diagnosis: Cytology from conjunctival scrape reveals eosinophils and /or mast cells
      • Treatment:
        1. Topical corticosteroids (careful, because commonly seen associated with FHV-1)
          1. 3-4 times daily initially, then wean over several weeks
          2. May try to discontinue after 4-6 weeks
          3. Consider treating with L-lysine or interferon to reduce risk of FHV-1 recrudescence.
        2. Megesterol acetate - 2.5-5 mg/cat PO SID x 5 days, then 2.5 mg PO q 48 hours x 5 days, then continue to wean. Can often wean down to 1.25-2.5 mg once weekly and can sometimes wean off completely without recurrence.
          1. Side effects: diabetes mellitus, pyometra, weight gain, mammary gland hyperplasia, neoplasia, behavioral changes. Side effects are rare at the low dosage used.

      Feline Infectious Conjunctivitis
      • 4 common infectious etiologies:
        1. Herpesvirus
        2. Chlamydia
        3. Mycoplasma
        4. Calicivirus

    1. Feline Herpesvirus-1 Keratoconjunctivitis
    • Also known as feline rhinotracheitis
    • Most common cause of ocular disease in cats
    • Over 85% of cats harbor the virus and half of these will manifest with conjunctivitis or keratoconjunctivitis.
    • Superficial corneal ulcers in cats are almost always due to persistent FHV infection.
    • Conjunctival clinical signs (may have one or more of the following):
      • Conjunctival hyperemia, chemosis
      • Epiphora
      • Classic "herpes discharge" = red-brown
      • Blepharospasm
      • *Conjunctivitis is much more common than keratitis
    • Corneal clinical signs:
      • Early corneal manifestation: punctate to linear or dendritic ulcers
      • Later, these may coalesce and form larger geographic ulcers
      • Diagnosis:
        • Fluorescein staining
        • Rose Bengal staining: a vital stain; therefore, stains devitalized epithelial cells before they have sloughed and created an ulcer. However, this stain can be toxic to epithelial cells, especially in high concentration; therefore, is rarely used.
        • Culture and susceptibility to rule out secondary infection if cornea is ulcerated with stromal loss and/or cellular infiltrate
        • Corneal/conjunctival cytology
          • Rule out bacterial infection & eosinophilic keratoconjunctivitis
          • Dx: intranuclear inclusion bodies
          • Can do IFA for Chlamydia or FHV-1 if done before fluorescein is applied
        • Nested PCR - expensive and false positives and false negatives occur
        • Virus Isolation
      • Treatment:
      • *Minimize stress in cat's environment!!!
      • *L-Lysine 500-750 mg PO daily in canned food
        • *Veterinary product now available in palatable flavored powder or paste (Viralys )
      • *Interferon alpha 2a or 2b
        • -30-100 IU PO daily
          • -Can alternate 7 days on therapy with 7 days off therapy
        • -30-1000 IU/ml topical solution: start at 3-4 times daily and wean to lowest possible dose without recurrence of clinical signs
      • *Topical antivirals should be reserved for cases with corneal ulceration!!
        • Not needed for conjunctivitis unless very severe
        • Irritating and expensive!
        • Idoxuridine and vidarabine are least irritating
          • Can obtain from most compounding pharmacies
          • Use ointment form 3-4 times daily until ulcer healed
        • *Systemic antivirals
          • -Famcyclovir
            • -Anecdotal dose: 1/4 of a 125mg tablet orally q 12 hours x 8-10 days
              • No known systemic side effects at this dose
              • Published experimental dose of 90mg/kg q 8 hours is not cost-effective
            • Minimum age to treat 4-5 weeks
            • Most effective for acute disease
            • Treatment course may be repeated if needed
            • Can use 1/8 tablet orally q 12 hours in kittens
        • *Biannual intranasal/topical ocular FHV-1 vaccine
          • Provides local IgA immunity to reduce number and severity of flare-ups
        • *Topical Oxytetracycline (Terramycin®) ou qid for 3 weeks may be used if cornea is ulcerated to prevent secondary infections while the disease runs its course.
      • Prognosis:
        • Infection is usually self-limiting and resolves in approximately 21 days
        • Guarded-herpes is forever!!
          • Must inform clients that the disease may be controllable, but is not curable due to latency of virus in trigeminal ganglion.
      • Sequelae:
        • Punctate, linear or diffuse corneal scarring
        • Symblepharon: adhesions of conjunctival to corneal or conjunctival surfaces due to ulceration of the epithelium
        • Corneal sequestration and/or mineralization
        • Nasolacrimal obstruction due to conjunctival scarring
        • Keratoconjunctivitis sicca

    2. Chlamydial conjunctivitis
    • Clinical signs: begins unilateral, may spread to other eye in 3-7 days unless treated. Chemosis, hyperemia, mucopurulent discharge (pseudomembrane)
    • Diagnosis: cytology (intracytoplasmic inclusion bodies between days 7and 14 of infection, PMN's); IFA on conjunctival scrapings (do not stain before collecting specimen).
    • Treatment:
      • Oxytetracycline (Terramycin®) or chloramphenicol ointment qid for 3 weeks
      • Oral doxycycline 5 mg/kg PO for 3 weeks - clears carriers
    • Prognosis: good - usually responds well to treatment
    • Zoonotic: causes conjunctivitis in humans ("pinkeye" in children); therefore, advise clients to wash hands after handling and treating affected cats.

    3. Calicivirus
    • Clinical signs:
      • Mild to moderate conjunctivitis
      • Oral mucosal ulcers, 7-10 days duration
    • Treatment: Supportive. Usually recover without sequela

    4. Mycoplasma conjunctivitis
    • Clinical signs:
      • Usually unilateral, but may spread
      • Mild hyperemia, pseudodiphtheritic membrane can be peeled off
      • Serous to mucopurulent discharge
    • Diagnosis: by signs and cytology (coccoid clusters on epithelial cell wall)
    • Treatment: Oxytetracycline or chloramphenicol topically or doxycycline PO

    5. Corneal Sequestrum:
    • Definition:
      • A desiccated and necrotic region of corneal stroma undermined by inflammatory cells
      • Has a characteristic
    • Clinical signs:
      • *Blepharospasm, epiphora
      • *Light brown-yellow to dark black discoloration of usually the axial corneal stroma
      • *Corneal vessels may extend to the sequestrum and can result in extrusion or sloughing of the plaque
      • *May or may not have associated corneal ulceration
    • Causes:
      • Brachycephalic conformation with lower medial entropion and increased corneal exposure and desiccation
      • FHV-1
      • Any chronic corneal irritant
    • Treatment:
      • Surgical excision (keratectomy +/- conjunctival pedicle graft) provides the most rapid healing
      • Topical antibiotics if ulcerated
      • Topical lubricants improve comfort and may help prevent recurrence
        • Genteal
        • Celluvisc
      • Topical interferon??
        • Some ophthalmologists use; no scientific reports
    • Prognosis:
      • Fair to good with surgery
      • Can recur, but conjunctival grafting and addressing the primary cause may reduce risk of recurrence

    6. Bullous Keratopathy
    • Clinical signs:
      • Rare condition unique to cats
      • Acute onset of a focal severe swelling of the corneal stroma
    • Cause: unknown
    • Treatment: Third eyelid flap to apply pressure to the swollen stroma.

    7. Uveitis
    • Clinical signs:
      • Epiphora, aqueous flare, miosis, conjunctival hyperemia/chemosis, corneal edema, keratic precipitates, iridal neovascularization ("rubeosis irides"), iridal nodules, inflammatory cells in the vitreous ("hyalites")
      Causes:
      • Always suspect systemic disease!!! 38-70% are diagnosed with systemic disease!
      • FELV, FIV, Toxoplasmosis, FIP, FHV-1, systemic mycosis, bartonellosis
      • Idiopathic/immune-mediated
      • Young cats & kittens can have recurrent mild-moderate episodes of uveitis
        • No cause determined-viral??
        • Resolve quickly with topical anti-inflammatory treatment
      • Diagnosis:
        • Thorough physical exam is imperative!
        • Start with CBC, Profile, UA and choose additional diagnostics based on signalment, history and PE and bloodwork + risk of exposure to infectious diseases.
          • FELV/FIV
          • Toxoplasma gondii IgG/IgM
          • Bartonella spp. Western blot testing
      • Treatment:
        • Topical anti-inflammatories
          1. Diclofenac 0.1% (Voltaren) - 3-4 times daily, then wean
          2. 1% prednisolone acetate (Econopred or Pred Forte) - 3-4 times daily, then wean
            1. Caution-watch for FHV-1 flare-up
        • Atropine 1% ophthalmic ointment!!
          • *Don't use atropine solution in cats-the bitter taste makes them salivate profusely!!
        • For Bartonellosis:
          • Azithromycin 10 mg/kg PO SID x 3 weeks = first choice
          • Doxycycline 10 mg/kg PO BID x 3 weeks for refractory cases
        • Sequela:
          • Posterior synechia and lens capsule pigment deposits
          • Cataract
          • Lens luxation
          • Secondary glaucoma
          • Retinal degeneration
          • Blindness
        • Prognosis:
          • Guarded, depends on the etiology

    8. Cataracts
    • Congenital cataracts
      • Nuclear-usually get smaller with age and usually don't require surgery
    • Hereditary cataracts - very uncommon in cats
    • Most cataracts in cats are secondary to uveitis!!!

    9. Glaucoma
    • Primary glaucoma is rare and is often congenital or neonatal
      • Siamese
    • Secondary glaucoma
      • Causes:
        • Most glaucoma in cats is secondary to uveitis!!!
        • Aqueous misdirection syndrome
          • Not well understood
          • Shallow anterior chamber secondary to anterior displacement of lens
          • Treatment is carbonic anhydrase inhibitors +- lens removal and vitrectomy
        • Uveal cysts
          • Large cysts behind iris result in compromise of iridocorneal angle
          • Treatment: laser photoablation of cysts is curative
        • Intraocular neoplasia
      • Treatment:
        • Dorzolamide 2% ophthalmic solution (Trusopt) - 1 drop q 8 hours
        • Timolol 0.5% ophthalmic solution (Timolol) - 1 drop q 8-12 hours
        • Dorzolamide+timolol (Cosopt) - 1 drop q 8 hours
        • Ciliary body cyclophotocoagulation
      • Prognosis:
        • Poor, especially when secondary to uveitis

    10. Retinal Diseases
    • Taurine Deficiency
    • Fluoroquinolone Associated Retinal Toxicity
    • Progressive Retinal Atrophy
      • Abyssinians
    • Hypertensive Retinopathy

    11. Taurine Deficiency/Feline Central Retinal Degeneration (FCRD)
    • Clinical signs:
      • Initially tapetal hyperreflectivity due to retinal thinning in area centralis
      • Progresses to linear region of hyperreflectivity along the tapetal-non tapetal junction
      • Late stage is diffuse hyperreflectivity
    • Cause:
      • Dietary deficiency - 500-750 ppm is recommended requirement to prevent retinal disease
        • Associated with feeding dog food or home-made diets
      • Deficiency of taurine uptake
    • Treatment:
      • Taurine supplementation or correct diet
    • Prognosis: Guarded-the retinal degeneration is permanent, but appropriate dietary change or supplementation may prevent progression

    12. Fluoroquinolone Associated Retinal Toxicity
    • Reported in clinical patients after enrofloxacin use only
    • Experimentally induced with high doses of other fluoroquinolones
    • Clinical signs:
      • Affects 1 in 122, 414 cats (0.0008% incidence)
      • Acute onset partial vision impairment or blindness following systemic treatment with enrofloxacin
      • Fixed dilated pupils
      • Ophthalmoscopic evidence of retinal thinning (tapetal hyperreflectivity, vascular attenuation) apparent within several days to weeks
      • Electroretinogram testing: extinguished response confirmed extensive outer retinal disease
    • Cause:
      • Idiosyncratic reaction
      • In 16/17 cats, the total daily dosage exceeded 5 mg/kg
      • One blind 15-year-old cat received only 4.6 mg/kg
      • Age may be a predisposing factor as older cats (>12 year) developed blindness at a lower dose than younger (<9 years).
    • Treatment: None
    • Prognosis: Grave-blindness is usually irreversible

    13. Progressive Retinal Atrophy
    • Hereditary retinal degeneration in Abyssinian & Siamese cats
    • Clinical signs: mydriasis, nystagmus, vision impairment progressing to blindness; tapetal hyperreflectivity and vessel attenuation
    • Abyssinians:
    • Early onset = rod cone dysplasia
      • Onset at 4 weeks and may be blind by 1 year
    • Later onset = rod cone degeneration
      • Onset at 1.5-2 years of age with progression to blindness over 2 - 4 years

    14. Hypertensive Retinopathy
    • Signalment: usually cats > 10 years of age
    • Cause:
      • Systemic hypertension (usually systolic blood pressure (BP) > 160 mmHg)
        • Chronic renal failure - up to 65% of cats with CRF had hypertensive retinopathy in one report
        • Hyperthyroidism
        • Idiopathic
    • Clinical signs:
      • Dilated pupils, sluggish to absent PLR, blindness
      • Hyphema
      • Early fundic changes: Multifocal well-demarcated foci of inner retinal and sub-retinal edema
      • Later fundic changes: Focal bullous lesions coalesce and progressive to complete bullous retinal detachment with retinal, sub-retinal and vitreal hemorrhage
      Treatment:
      • *Amlodipine 0.625 mg/cat PO q 24 hours lowers BP from 198 to 155 mmHg in one report
        • In another report, treatment lowered BP in 31 of 32 cats and resulted in improved vision in 18 of 26 cats
      • *Furosemide decreases ability of RPE to remove subretinal fluid by 84%; therefore is contraindicated in treatment of retinal detachment!!
    • Prognosis:
      • Depends on chronicity and extent of the detachment
      • With rapid diagnosis and treatment, bullous detachments have 50% or more chance of reattaching and regaining vision

    15. Neoplasia
    • Uveal melanoma
      • Signalment: Any mature cat
      • Clinical signs:
        • Progressive pigmentation of the iris over months to years
        • Changes in pupil shape or motility suggest invasion of iris stroma
        • Glaucoma secondary to infiltration of iridocorneal angle
        • Iris nevus or freckly could be a pre-neoplastic change, especially in younger cat
      • Behavior:
        • Metastatic rate may be up to 63%
        • Metastasis may occur up to 1 to 3 years after enucleation
        • Have much greater concern with metastasis in younger cat than aged cats
        • Ophthalmologists and pathologists disagree on behavior
          • In one recent study (Dubielzig et al, 1997), cats with tumor confined to iris and cats with moderate spread (diffuse iridal involvement and spread to iridocorneal angle had survival times similar to cats in the control group.
          • Cats with advanced melanoma (aggressive iridal infiltration & iris posterior pigmented epithelium and ciliary body) had shorter survival times than control cats and the cause of death usually suggested metastatic disease.
      • Treatment:
        • *Diagram or photograph and monitor all iris pigmentation
        • *Monitor for raised, velvety appearance, dyscoria, decreased PLR, uveitis, extension to iridocorneal angle, rapid progression or obvious mass
        • *Consider enucleation earlier in younger cat if these changes are noted
        • *A 15 year old cat with mild changes is unlikely to die of metastatic disease; therefore these can be safely monitored.

    • Squamous cell carcinoma
      • Signalment: older white-faced cats, especially those living at high altitudes
      • Clinical signs:
        • Slightly raised or ulcerated lesion at or adjacent to eyelid margin
      • Treatment:
        • Wide surgical excision + blepharoplasty
        • Cryosurgery
        • Radiation (teletherapy or brachytherapy)
        • Hyperthermia
      • Prognosis:
        • Depends on histologic grade of tumor
          • Well-differentiated tumors treated early=good prognosis for cure
          • Extensive or poorly differentiated tumors=guarded prognosis for cure

    • Trauma-associated sarcoma
      • Signalment: 7-15 year old cats
      • Clinical signs:
        • Chronic uveitis
        • Glaucoma
        • Intraocular hemorrhage
        • Visible intraocular mass
      • Cause:
        • Trauma to lens
          • Trauma may precede the tumor by average of 5 years
        • Chronic uveitis
        • Intraocular surgery
        • Intravitreal gentocin injection for glaucoma
      • Treatment:
        • Early enucleation with orbital exenteration
      • Prognosis:
        • Grave-despite early intervention, most cats die due to extension of tumor along optic nerve to brain or regional lymph node and distant metastasis within several months.

    • Other adnexal tumors in cats: basal cell carcinoma, mast cell tumor, fibrosarcoma

    Additional suggested readings:
    1. Glaze, MB and Gelatt KN. Feline Ophthalmology. In: Gelatt's Veterinary Ophthalmology. Philadelphia: Lippincott, Wilkins and Williams, 1999: 997-1052.
    2. Wiebe V and Hamilton P. Fluoroquinolone-induced retinal degeneration in cats. J Am Vet Med Assoc 2002; 221 (11): 1568-1571.

    • © 2009 - Anne Gemensky Metzler, DVM, MS, DACVO - All rights reserved