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# Corneal Anatomy

# 3 General Layers

  1. The outside layer is non-keratinized squamous epithelium, which is 5–7 layers. Epithelial turnover is every 7 days. The epithelium has a basement membrane that is basically insignificant clinically and histologically in veterinary medicine. This epithelial layer accounts for ~5% of the cornea’s thickness and is divided into 3 layers:

    1. Basal cells — deepest layer, single cell thickness, attached to basement membrane via hemidesmosomes. Only epithelial layer to undergo mitosis.

    2. Wing cells — middle transitional layer between basal cells and squamous cells. It is 2–3 cells thick in dogs.

    3. Squamous cells — anterior layer, 2–3 cells thick in dog, microplicae and microvilli on surface help stabilize tear film, tight junctions between squamous cells limit permeability.

  2. The stroma makes up 90% of the corneal thickness. It is primarily collagen and GAGs and has low cellularity. The collagen in lamellae span the corneal diameter. The stroma can take months to rebuild when damaged. The collagen is formed from keratocytes (modified fibroblasts).

  3. The endothelium and its basement membrane (Descemet’s membrane) make up the inside layer. Proliferative potential is very low. The endothelium is a single layer of hexagonal cells that are important in maintaining state of relative dehydration of cornea via active pumps.

# Thickness

  • The cornea is 0.5–0.6 mm thick in the dog and cat and about 1 mm in horses.
  • With corneal edema, the thickness of the cornea can substantially increase in the area of edema.

# Limbus

  • The area where the edge of the cornea meets the conjunctiva and sclera. When blood vessels invade the cornea, they begin from the limbus.
  • A good area to closely examine for early corneal change

# Corneal innervation

  • Sensation is via the ophthalmic division of the trigeminal nerve.
  • Superficial injury is often more painful than deep as the pain receptors are superficial.
  • Brachycephalics have fewer nerve branches than dolichocephalics and mesocephalics.
  • Interestingly, this sensory innervation also provides factors necessary for corneal health (e.g., a neuropeptide called Substance P), and poor or disrupted innervation can lead to a syndrome called neurotrophic keratitis.

# Corneal Physiology

# Functions of the Cornea

  • Supports intraocular contents
  • Transmits light
  • Refracts light (40–42 diopters)

# Corneal nutrition

Being avascular, corneal nutrition comes from two major sources:

  • Aqueous humor
  • Tears (major source of oxygen)

# Mechanisms to maintain clarity

  • Avascularity — instead of using vasculature for its metabolic needs, the cornea uses aqueous humor and tears.
  • Non-pigmented-non-keratinized epithelium
  • Highly organized arrangement of small diameter collagen fibrils — these fibrils extend the entire diameter of the cornea. This arrangement allows 99% of the light to pass through the cornea without scatter.
  • Relative dehydration
    • The normal cornea is relatively dehydrated, containing about 70% water by weight (compared to 95+% for most tissues).
    • This dehydration is an active process, as the cornea is bathed by fluid on both sides eager to enter — aqueous humor on the inside; tears on the outside.
    • In a normal cornea the endothelial cells constantly pump aqueous humor (via the Na-K-ATPase pump) that has imbibed into the deeper stroma back into the anterior chamber while the epithelial barriers keep tears out.
  • Tear film: Prevents keratinization and washes away resident and transient bacteria so their numbers stay in check.

# Response to disease

  • Edema

    • White/blue opacity of the cornea; when dense can have a cobblestone appearance
    • Occurs with damage to endothelium or loss of epithelium – glaucoma, ulceration, anterior uveitis, endothelial dystrophy, lensl uxation.
    • With corneal ulceration, the corneal edema is present because the missing epithelium cannot keep tears out, so they enter the stroma in the area of the ulcer causing a mild, faint, and focal edema.
    • Whenever you see dense, widespread corneal edema, it is usually due to endothelial disease.

  • Cellular infiltration

    • Denser white or yellow appearance to the cornea, irregular
    • Occurs with immune mediated disease (pannus), neoplasia, or with infected corneal ulcers.

  • Fibrosis/Scar formation

    • Also a white opacity (may be hard to distinguish from edema) of the cornea
    • Caused by abnormal arrangement of collagen fibers, often decreases with time, topical corticosteroids may lead to faster scar resolution.
    • Recall that one reasons for corneal clarity is regular periodicity of the stromal collagen fibers. When collagen is secreted in the repair of a corneal stromal defect, the new collagen is laid down haphazardly and does not attain this regular periodicity. The result is an opacity.

  • Pigmentation/Melanosis

    • Can occur with any chronic irritation and be associated with active or inactive disease.
    • May improve with medications (steroids, tacrolimus) but denser forms rarely return to full clarity.

  • Vascularization

    • An early marker of corneal disease, all vascularization begins at the limbus and takes approximately 1 week to get started.
    • After beginning, they typically grow 1-2 mm per day.
    • Presence of vascularization indicates active chronic disease. When the cornea is injured or inflamed, the metabolic needs change. The cornea then recruits vessels from an arcade of limbal vessels to meet these changing metabolic needs.
    • Superficial vessels develop in response to superficial keratitis, and deeper vessels develop in response to either deep corneal disease or intraocular diseases such as uveitis and glaucoma.
    • Superficial vessels are usually solitary vessels that branch dichotomously and often extend far into the cornea.
    • Deep vessels form more of a “brush border,” with multiple short straight vessels densely packed together; these vessels usually don’t make it to the center of the cornea.
    • As the keratitis resolves, the cornea’s need for a blood supply diminishes. The endothelial channel that had formed within the cornea then collapses, but the “track” that it laid down remains, and appears as a translucent line within the cornea. These are referred to as ghost vessels.

      Guaging chronicity of corneal disease

      Given there’s a specific time frame for vessel ingrowth — it’s therefore possible to guage the chronicity of corneal disease if vessels are noted — 7 days + 1 day/mm of vessels.

      This estimation doesn’t work for more chronic corneal disease or for periodic disease as the architecture (ghost vessels) can re-fill with blood — but their presence indicates recent re-activation or continuation of a chronic problem.

  • Secondary uveitis

    • Results from an axonal nerve reflex in the trigeminal nerve and is referred to as axon reflex uveitis.
    • The axon reflex mechanism causes signs of anterior uveitis including: protein and cellular leakage from uveal blood vessels (aqueous flare), ciliary spasm (resulting in pain) and pupillary miosis.
    • Topical treatment for secondary uveitis (e.g. topical steroids or NSAIDs) should not be done in cases of corneal ulceration as their use may slow or complicate re-epithelialization. Topical atropine for discomfort or dilation can be used or systemic anti-inflammatories if the uveitis is significant.

# Mechanisms of corneal healing

  • Epithelial defects (e.g. superficial ulcers)

    • When corneal epithelial cells sense a loss of “contact inhibition,” the basal epithelial cells will slide across the bare corneal stroma.
    • Fibronectin is laid down on the stromal surface, and fibronectin receptors on the basal aspect of the basal epithelial cells attach to these receptors, then “ratchet” across the stroma using actin and myosin filaments.
    • Once the stroma is covered, the epithelial cells undergo mitosis to thicken back to the normal 7-8 cell thickness.
    • An entire cornea can reepithelialize in 4-7 days — the presence of an ulcer for longer than a week requires re-evaluation for a persistent underlying cause.

  • Stromal defects/ulcers

    • Avascular healing:
      • Neutrophils come in via chemotaxis. The local keratocytes die.
      • Surrounding keratocytes “transform” into fibrocytes, migrate, synthesize collagen and mucopolysaccharides.
      • Matrix metalloproteinase (MMP) enzymes produced by both the cornea and the invading PMNs degrade necrotic tissue in a relatively controlled fashion.
      • The epithelium migrates to cover the defect.
      • Maximum wound strength is achieved in 6–12 months.
    • Vascular healing:
      • Cellular infiltrate is greater. Vessels invade the stroma and granulation tissue is created.
      • The scar is denser than with avascular healing. Eventually the vessels collapse and become ghost vessels.

# Corneal Ulceration

A lesion of the cornea that is a result of the loss of corneal epithelium +/- stroma.

In cases of corneal ulceration, you need to assess the ulcer for 4 things:

  1. Etiology of the ulcer — THE SINGLE MOST IMPORTANT PART OF THE EVALUATION! If there is a removable etiology and you don’t resolve it, the ulcer will not heal!

  2. Depth of the ulcer — Is it superficial, into the stroma, down to Descemet’s membrane, or completely perforated?

  3. Presence of either of 2 “complicating factors”: infection or matrix metalloproteinases.

  4. Rate of progression (i.e., is it deepening, and, if so, how quickly?) – Often can’t determine this at the first evaluation, other than to say if MMP activity is present. If there is MMP activity the ulcer will progress (i.e., deepen) very quickly without intervention.

Associated clinical signs:

  • Blepharospasm — squinting. Pain from corneal ulcers has 2 sources.

    1. The first is the corneal itself – the cornea is richly innervated by sensory fibers of the ophthalmic branch of the trigeminal nerve.

    2. The second is the ciliary body. The axons of the ophthalmic branch of the trigeminal nerve send branches off into uveal tissue, where release of neurotransmitters (primarily a neuropeptide called “substance P”) causes, among other things, ciliary body spasm.

      Ciliary spasm is very painful (ciliary spasm also occurs when you go from a darkened room into bright light). This phenomenon of corneal injury causing ciliary spasm via ophthalmic branch axons is termed “axon reflex.”

  • Epiphora — excessive tearing. Tears are produced by the main lacrimal gland and gland of the third eyelid, and drained by the nasolacrimal duct. Epiphora can be caused by overproduction in response to painful stimuli (such as that seen with a corneal ulcer) or by diminished drainage.

# Diagnostics:

  • Fluorescein stain:
    • The diagnostic modality of choice — fluorescein is a hydrophilic water soluble dye taken up by the stroma.
    • The corneal epithelium & Descemet’s membrane are lipophilic and hydrophobic thus preventing transcellular passage of fluorescein) and contains very robust interepithelial tight junctions (preventing paracellular passage of fluorescein).
    • Fluorescein applied to the cornea will simply run off the surface and not adhere. When the epithelium is denuded, the underlying hydrophilic stroma is exposed. The ulcer will appear green which is accentuated with a cobalt blue filter.
    • When using the strip, moisten the end and either drip the solution on the cornea or touch the wet tip to the conjunctiva and rinse with saline.

# Causes of corneal ulcers

  1. Trauma

  2. Eyelash abnormalities — distichia, ectopica cilia

  3. Eyelid abnormalities — entropion, eyelid tumors

  4. Foreign bodies

  5. Dry eye

  6. Indolent ulcers

  7. Trauma

    • History of exposure to other pets, flora, alkali, shampoo, mace, shape of ulcer.
    • Treatment
      • Prevent infection: Use a broad spectrum antibiotic such as triple antibiotic TID-QID
      • Treat pain due to ciliary spasm: Use atropine to effect usually BID-QID

  8. Eyelash abnormalities

    • Distichia:

      • Cilia originating from near the tarsal gland, emanating from tarsal gland opening on eyelid margin.
      • These do not always cause an ulcer but may prevent one from healing.
      • Some distichia are present without causing disease. Especially common in cockers, dachshunds and poodles.
      • Treatment
        • Freeze with a double freeze thaw cycle with liquid nitrogen or nitrous oxide.
        • Other less recommended therapies are electroepilation and excision. -
        • The distichia can be pulled as a temporary solution to help determine significance. More may grow or the treated ones may come back.
        • All distichia do not need need to be treated as many are asymptomatic.

    • Ectopic cilia:

      • Cilia originating from tarsal gland that emanates from the palpebral conjunctiva.
      • May not occur until middle age.
      • These can be difficult to see → with magnification look about 4 mm in from eyelid margin. They are usually at 12 o’clock on the upper lid and may be camouflaged by pigment.
      • Treatment
        • Excise cilia en bloc from conjunctiva. Warn owners that more may grow. Look closely for more ectopic cilia when the animal is anesthetized.

    • Entropion:

      • Turning in of eyelid margin that results in hairs rubbing the cornea.

      • Entropion can be conformational, spastic, involutional, or cicatricial; this must be determined during the examination.

        • Conformational is due to a disproportionate size of orbit and globe position. Seen most commonly in Shar peis, rottweilers, Chows, bulldogs. These do not correct with topical anesthesia.
        • Spastic entropion occurs secondary to ocular pain such as that from an ulcer. The pain causes the dog to retract the globe thereby allowing the eyelids to roll in. This does correct with topical anesthesia.
        • Cicatricial entropion occurs when chronically spastic tissue scars rolled in or secondary to scar formation from trauma.
        • Involutional is an acquired conformational entropion that occurs secondary to loss of orbital tissue.

      • Puppy entropion occurs in Shar Pei puppies. This is not treated surgically; rather 2-3 temporary tacking vertical mattress sutures are placed to roll out the lid.

        • Use 4-0 or 5-0 vicryl and let it fall out on its own. If you can get these sutures to stay in for 2-3 weeks, the lids will often remain in a more normal position meaning that permanent (i.e., Hotz-Celsus) correction won’t be needed.
        • A pragmatic problem to appreciate in these cases is that due to the abnormal subdermal tissue in Shar Peis the sutures often tear out before they’ve been in long enough (often in a few days). The only recommendation if this happens is to replace them…​just be sure to warn your owners that it could happen when you put in the first set of sutures so they’re not surprised!

      • Ophthalmic examination including STT and fluorescein must be done. The eyes must be examined with and without topical anesthetic.

      • Treatment of Entropion

        • Conformational, involutional, or cicatricial:
          • Modified Holz Celsus. This procedure can be applied to any area of the eyelid - lateral, middle, upper, lower, complete. Treat any secondary ulcers medically or surgically as indicated. When suturing the crescent we use 5-0 or 6-0 vicryl as the tags are soft if they contact the cornea.
        • Spastic entropion:
          • Treat the primary cause, +/- tacking , contact lens, third eyelid flaps.
        • Collagen injection:
          • A newer technique is to inject collagen into the eyelid - this is handy for short-term cases of entropion such as puppy entropion or for cases where the animal is too infirm to undergo general anesthesia.
          • The injection will last approximately 1 year before it is naturally dissolved with the body’s collagenases

  9. Eyelid mass: Tumors and infections of the eyelid margin can rub the cornea leading to ulceration (rarely) or can result in trauma that prevents ulcerations from healing.

    • Treatment:
      • Debulking alone often leads to recurrence of the mass within a year or less
      • Can perform surgical removal (wedge-resection) or debulking with cryotherapy
      • See eyelid section for more detail

  10. Foreign body: May present as a bump on the cornea if the foreign body is embedded, or it may become lodged behind the third eyelid or within the conjunctival tissue.

    • Treatment
      • Usually can remove the foreign body with just topical anesthesia and very fine forceps. Also hydropulsion can work well (snap off the needle from a 25 ga or smaller needle and then flush vigorously). Occasionally will need to cut over the foreign body to retrieve it.

  11. Keratoconjunctivitis sicca: A disease resulting in keratitis and conjunctivitis caused by a lack of aqueous tear production.

    • Diagnostics
      • Schirmer tear test, often have large amounts of mucopurulent exudate
    • Treatment
      • Lacrimomimetics (cyclosporine, tacrolimus) with artificial tears
      • Some of the immunomodulatory agents (e.g. cyclosporine/tacrolimus) might reduce the immune response which could complicate healing if infection is present.
      • See KCS section for more detail

  12. Indolent ulcers – see below

# Superficial Ulcers

  • A relatively flat corneal surface will be seen and the ulcer may not be visible without fluorescein stain.
  • Signs are blepharospasm, epiphora, discharge, evidence of pain, and conjunctival hyperemia.
  • After any predisposing factors are eliminated, these ulcers are generally treated with triple antibiotic and atropine.

# Stromal ulcers

  • Any ulcer that invades the stroma results in a divot that makes the corneal surface uneven.
  • Simply an ulcer that’s extended beyond the epithelium into the stroma.
  • Can extend into the superficial stroma, mid-stroma, or deep stroma.
  • Dog may or may not be in extreme pain. Some are infected and have a gelatinous appearance (MMPs) and are rapidly progressing; others are a continuation of the inciting cause.
  • Treatment of this ulcer is dependent on infection, “melting” and predisposing cause.

# Descemetocele

  • A very deep ulcer that extends all the way through the stroma to Descemet’s membrane.
  • Characteristically the walls of the descemetocoele take up stain and the floor of the ulcer does not.
  • Surgery should be done as perforation is a big risk

# Perforation/Iris Prolapse

  • Occurs with trauma or worsening of a deep ulcer to the point of a hole developing in the cornea.
  • Within minutes of perforation, the hole hopefully becomes plugged with fibrin or iris.
  • Fluorescein stain may show aqueous leakage. Look for collapsed anterior chamber, fibrin plug, miotic pupil, hypopyon. These should always be cultured!

# Facet

  • A “divot” in the corneal stroma that has an intact overlying epithelium.
  • It takes some time for the keratocytes to secrete enough collagen to completely fill the stomal defect.
  • If re- epithelialization occurs prior to complete filling, then a facet will be present.
  • On occasion, especially in older dogs, the defect may never completely fill in, leaving a chronic facet. This is almost never a problem…it’s only a concern if the facet is so deep that the cornea is significantly thinned and weakened.

# Melting ulcers (Collagenolytic)

  • Etiology: Melting ulcers are stromal ulcers complicated by the release of proteases and collagenases called matrix metalloproteinases (MMPs) that cause rapid progressive stromal dissolution.
  • Matrix metalloproteinases are a family of enzymes that have proteolytic activity.
  • There are over a dozen different MMPs, most of which are known by numbers – MMP1, MMP2, etc. Collagenase is also an MMP.
  • Several MMPs have been shown to be associated with rapid degradation of the corneal stroma in some cases of corneal ulceration.
  • If MMP activity is present in a case of corneal ulceration, the stroma will rapidly degrade, and appear soft and malacic.
  • Melting portions of the cornea that takes up stain is grayish and generally extends beyond (in front of the surrounding epithelium) because it is so edematous. If it sloughs it may leave a descemetocele.

# Where do MMPs come from?

  1. The cornea itself. MMPs are normally present in the cornea and serve the function of cleaning up necrotic debris in cases of stromal ulceration. Occasionally these enzymes go beserk for no apparent reason and don’t stop when they’re done cleaning…they continue right on through normal, healthy corneal stroma. This overactive expression of corneal MMPs seems more common in eyes of brachycephalics. We do know that one cause of stimulation of otherwise latent MMPs is administration of topical corticosteroids. This is but one reason that steroids are STRICTLY CONTRAINDICATED in cases of corneal ulceration.

  2. Invading leukocytes, especially PMNs. PMNs are a double-edged sword in cases of corneal ulceration. They are necessary to keep infection at bay, but they also liberate large quantities of proteolytic enzymes, including MMPs. This would make you think that steroid administration might be helpful, in that they do inhibit influx of PMNs – but this potential positive benefit is far outweighed by the fact that they will activate latent MMPs as mentioned above, and also make the cornea more susceptible to infection.

  3. Microorganisms. A large variety of bacterial and fungal organisms are capable of secreting MMPs. Enzymatic digestion of the cornea is favorable to their survival. As for bacteria Pseudomonas and β hemolytic Streptococcus are the best MMP secretors. For this reason, all melting ulcers should be scraped for cytology and samples submitted for bacterial culture and sensitivity. Fungal ulcers are rare in small animals.

# Deep ulcers

Stromal ulcers, descemetoceles, perforations and melting ulcers

# Etiologies for ulcers with stromal loss

  1. Bacterial infection
  2. Fungal infection
  3. Uncomplicated ulcer gone bad
  4. Bacterial infection: Most are infected with Pseudomonas, staphylococcus or streptococcus. Must scrape for cytology and culture.
  5. Fungal infection: Rare in small animals. May appear brown in color. Identify based on cytology and culture. Treat with antifungals.
  6. Chronic unrelenting irritation: Any deep ulcer requires a complete ophthalmic exam, cytology, culture & sensitivity.

# General therapy of deep ulcers

Prognosis is dependent upon history, duration, presence of infection.

# Medical treatment alone

  1. Topical antibiotics q2h based on cytology and culture (usually ciprofloxacin, ofloxacin, or tobramycin with compounded cefazolin)
  2. Serum q2h if melting or infected
  3. Atropine to effect. Usually required QID in the beginning until the pupil opens
  4. E-collar

# Surgical treatment

  1. Conjunctival graft (this is a must for descemetoceles or iris prolapse)
  • A conjunctival pedicle graft is a surgical procedure in which a strip of bulbar conjunctiva is sutured over the corneal ulcer.
  • This gives the compromised cornea some structural support making it less likely to perforate and transposed conjunctiva will also have some fibroblasts on it, which will further serve to strengthen the wound.
  • Second and probably most importantly, it provides a constant blood supply to the ulcer. The blood supply is important because serum contains a couple of compounds that inhibit MMP activity: α2-macroglobulin and α1-antitrypsin.
  • Commercially available collagen sheets are available to place between the ulcer and the graft. Two such products are: BioSys™, which is made from porcine small intestinal submucosa, and A-Cell™, which is made from urinary bladder.
  1. Enucleation – when all else fails and there is no hope for vision.

# Indolent ulcers

  • Also known as Spontaneous Chronic Corneal Epithelial Defect – SCCED
  • A chronic SUPERFICIAL non-healing ulcer with loose edge of epithelium.
  • The general pathology appears to be due to lack of functional hemidesmosomes. There have been several hypotheses regarding why this occurs, including (i) a primary corneal dystrophy; (ii) overactive levels of protease in the tear film which degrade the fibronectin network onto which the basal epithelial cells migrate; and (iii) the presence of an acellular zone in the anterior stroma that prevents attachment of an overlying epithelium.
  • There may, in fact, be more than one pathophysiology, with indolent ulceration being a “final common pathway.”
  • These are seen especially in boxers and old Golden Retrievers.
  • Fluorescein stain may migrate under the loose edge. There is no sign of infection such as a stromal cellular infiltrate or deepening of the ulcer.

# Treatment

  • Debride with dry cotton swab after applying topical anesthetic AND
  • Grid keratotomy or punctate keratotomy
    • A 22 – 25 ga. needle is used to make cross-hatches over the ulcer bed.
    • These “scratches” should be into the superficial stroma, but no deeper.
    • They should begin about 1 mm in normal epithelium, extend across the ulcer bed, and continue into normal epithelium on the other side for about 1 mm.
    • The scratches should be about 1 mm apart.
    • Be certain to do this sterilely.
    • It is not know why this procedure facilitates the “next wave” of epithelium to adhere, but it might be due to disruption of a putative anterior stromal acellular zone. An alternative, but essentially identical, procedure is multiple punctate keratotomy or diamond burr.
  • Antibiotics — topical ophthalmic oxytetracycline may help by stimulating transforming growth factor β thereby enhancing epithelial migration.

# Additional therapies

  • Serum - has not been shown to improve outcomes in indolent ulcers
  • Adequan™ is a polysulfated glycosaminoglycan (PSGAG) labeled for intraarticular use in the horse or intramuscular use in the dog in the treatment of arthritis.
    • PSGAGs are protease inhibitors. As it has been shown that at least some indolent ulcers are due to an overactive tear film protease system that then degrades the fibronectin network on which the basal epithelial cells try to migrate, PSGAGs may reduce these proteases and allow the fibronectin to form.
    • We suggest the equine product, which comes in 2 ml syringes and needs to be diluted 1:1 with artificial tears to prepare eye drops.
  • Topical morphine sulfate eye drops. A therapy for alleviating the pain associated with disruption of corneal nerve endings. The solution is made from 1% IV morphine, and is given TID. This therapy has been shown to NOT interfere with corneal wound healing.
  • Cyanoacrylate — 19 of 20 healed. Can be tricky to apply and can be irritating.
  • +/- E-collar
  • Contact lens — protects any newly formed epithelium from being wiped away by the action of the eyelids. Used only rarely because of the poor retention rate.
  • Other alternatives include a lamellar keratectomy or a conjunctival pedicle graft…these are usually reserved these therapies for indolent ulcers that haven’t healed after 6-8 weeks of appropriate therapy.
  • Typically recheck these in a week or 2 and utilize various therapies. These may take weeks to heal, may recur in same eye or occur in the other eye.

# Corneal laceration

Lacerations are caused by trauma. Depth determines treatment regimen.

  • If less than ½ thickness can treat medically, if <2/3 thickness needs primary closure.

  • If the lens has been perforated, the lens or globe may need to be removed.

# Treatment

  • Medical treatment: treat as if corneal ulcer. Watch for signs of infection
  • Surgical treatment: close primarily with sutures

# Pigmentary Keratitis

  • Non-specific changes that develop with long standing trauma/ irritation to the cornea.
  • Manifests as corneal vascularization, corneal pigmentation, corneal scarring

# Etiologies

  • Keratoconjunctivitis sicca
  • Trichiasis/Aberrant dermis
  • Nasal fold trichiasis
  • Pagoda
  • Lid/Ectropion
  • Lagophthalmia
  • Entropion

# Pannus (or chronic superficial keratitis)

  • An often bilateral immune mediated vascularized, pigmented lesion of the cornea.
  • Begins as a red vascularized conjunctival lesion that initially invades the temporal or inferior temporal limbus.
  • Vascularization and pigmentation then invades the central cornea.
  • Eventually it is a fleshy lesion that may involve the entire cornea, causing blindness.
  • The etiology is probably multifactorial, incorporating immune-mediated, genetic, and UV radiation. German shepherds are predisposed although it can occur in any breed.

# Diagnostics

  • Appearance, signalment. Cytology will reveal lymphocytes and plasma cells.

# Treatment

  • This disease is usually controllable but not curable.
  • Begin treatment with topical dexamethasone or prednisone TID to QID then taper down to a controlling dose.
  • It may take 3-4 weeks to get response. Cyclosporine or tacrolimus can also be used especially for maintenance. Very rarely can a pannus dog go off therapy completely.
  • Most of these dogs can go down to once daily or once every other day dex or CsA or tacrolimus to stay in remission. The vascularization is used to monitor whether the lesion is quiescent or active.
  • Radiation can be used in severe cases.

# Differentiation of Whitish Corneal Lesions

# Scars

Result from abnormal alignment of corneal stromal lamella or thickening or hyperkeratosis of the corneal epithelium. Usually occur 2° to ulceration or other chronic disease.

Appearance:

  • Grey irregular opacity +/- vessels and pigment

Diagnostics:

  • Fluorescein negative, white or pigmented opacity

# Corneal dystrophy (lipid dystrophy)

A primary, axially located, bilateral, inherited disorder of the cornea that is not accompanied by corneal inflammation or systemic disease. Typically this results from deposition of lipid in the cornea.

Etiology:

  • Inherited condition in which the corneal metabolism is not normal.
  • Inheritance has been proven in many breeds. Some of the breeds that it is most frequently seen in are the Shetland sheepdog, beagle, husky.
  • This disease is bilateral and symmetrical.

Appearance:

  • Bilateral usually oval white/grey glittery refractile opacity on the cornea with no vessels

Treatment:

  • Usually none needed, if becomes severe, anecdotally a low fat diet might help if the dog is on a high fat diet and some have reported a response to cyclosporine A.
  • Additionally, rule out Cushing’s or hypothyroidism.

# Corneal degeneration

  • Deposition of lipid and/or calcium secondary to some other ocular disease. Usually surface disease like ulceration.

# Lipid keratopathy

Appears as a white grey glittery appearance +/- vessels and pigmentation. Seems very common in the German shepherd.

Treatment:

  • Usually none needed, if becomes severe, anecdotally a low fat diet might help if the dog is on a high fat diet and some have reported a response to cyclosporine A.
  • Additionally, rule out Cushing’s or hypothyroidism.

# Calcific keratopathy

A disorder of the cornea that is characterized by deposition of mineral (usually calcium) in the cornea. Corneal calcification generally appears as short spicules of a whitish, chalky looking material in the superficial corneal stroma. May be primary disease in geriatric dogs.

Treatment:

  • If becomes severe, try treatment with topical EDTA in artificial tears to chelate the calcium as it can lead to descemetocele formation.

# Corneal edema

Greyness to the cornea occurring 2° to excessive fluid between the corneal lamellae. Caused by glaucoma, ulceration, anterior uveitis, endothelial dystrophy, or lens luxation. Normally edema is prevented by the endothelial Na-K-ATPase pumps and the corneal epithelium acting as a physical barrier to the entrance of tears into the stroma.

  • Endothelial dystrophy

    • A progressive dysfunction of the endothelial cells
    • Boston Terriers, Chihuahuas and Dachshunds
    • Typically develops in middle aged and older dogs
    • Primary clinical sign is an axial or temporal focus of corneal edema that usually progresses to involve the entire cornea.
    • Topical hyperosmotic (5%) sodium chloride ointment may draw the corneal edema fluid into the tear film, but this ointment generally can’t keep pace with the entry of fluid into the cornea so it is minimally effective.
    • If the edema becomes bad enough, it will result in the formation of actual “blisters” within the cornea called corneal bullae (and hence goes by the name “bullous keratopathy”). These bullae can rupture, causing a superficial ulcer that is very difficult to get to heal.

  • Endothelial degeneration

    • Being a very wimpy cell type, anything that traumatizes, touches or in any way negatively affects the endothelium can cause endothelial dysfunction.
    • Even aging can lead to edema because all mammals are born with a certain complement of endothelial cells, and they begin dropping out early in life. Being post-mitotic, they cannot replace themselves (at least in most species). In some individuals, the degree of endothelial cell loss is sufficient to result in edema in old age.

Treatment

  • If the edema becomes severe, corneal bulla may form. Then use 5% NaCI ophthalmic ointment QID. The NaCl will not take the edema away; it will just reduce it to the point that bulla no longer form.

# Corneal stria

White/grey linear streaks in the deep cornea that occur due to breaks in Descemet’s membrane secondary to glaucoma.

# Corneal Masses

Etiologies:

  • Corneal neoplasia
  • Limbal melanoma
  • Dermoid
  • Epithelial inclusion cyst
  • Granulation tissue

  1. Corneal neoplasia: Squamous cell carcinoma is most common but extremely rare in dogs and cats.

    • Diagnostics:
      • Histopath of biopsy specimen, cytology may be suggestive of neoplasia but is rarely diagnostic.
    • Treatment:
      • Keratectomy +/- Strontium irradiation

  2. Limbal melanoma: A darkly pigmented infiltrative benign tumor at the limbus.

    • Usually located at the dorsal limbus and are slightly elevated.
    • More common in large breed dogs especially German Shepherds and labs.
    • These tumors tend to be more invasive and grow more rapidly in younger dogs. In older dogs the tumors are more static. While these tumors are benign by definition, they can be locally invasive.
    • Treatment:
      • If it is an old dog and the mass is not progressing, it can be watched.
      • Current therapy is diode laser therapy or cryotherapy → the diode preferentially photoablates darkly pigmented tissues and is an easy, effective, and minimally invasive therapy. Also a full thickness scleral graft can be done.

  3. Dermoid: A congenital brown to pink mass on cornea with hair growing from it. Congenital but may not cause a problem until the dog is 6 months to a year of age.

    • Treatment:
      • Keratectomy, usually dermoids are very superficial

  4. Epithelial inclusion cyst: A raised cystic structure lined by nonkeratinized squamous epithelium. Usually caused by trauma.

    • Treatment:
      • Keratectomy is curative

  5. Granulation tissue: Pink fleshy mass occurring with chronic injury such as entropion. Treat inciting cause. Topical steroids may be used in select cases to hasten resolution.

  6. Nodular granulomatous episclerokeratitis (NGE): An idiopathic inflammatory lump at the limbus made up of fibroblasts, lymphocytes, and macrophages, with occasional neutrophils and plasma cells.

    • Has gone by many other names in the past (nodular fasciitis, fibrous histiocytoma, collie pseudotumor), but these are probably slightly different variations of the same syndrome.

    • Has a breed predisposition for Collies and Shelties, but can be seen in any breed.

    • Treatment:

      • Generally responds to a variety of immunosuppressive strategies, including topical corticosteroids, oral azothioprine and β-irradiation. Also can be treated with surgical excision, and even subtotal resection is often curative.
Last Updated: 9/21/2021, 6:52:46 PM

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