Sclera, Episclera, Limbus, Conjunctiva Flashcards

1
Q

Which two structures make up the dense fibrous outer tunic of the eye?

A

Cornea and sclera

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2
Q

How is the cornea different from the sclera?

A

Interference theory - cornea needs to be clear to allow light to pass through

Cornea = multiple parallel layers (lamellae) of collagen fibres arranged in a regular lattice equidistantly apart from one another. This allows for transparency.

Sclera = interwoven collagen fibrils without this precise arrangement making it appear more white and dense.

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3
Q

Which embryological structure are the corneal epithelium, limbus and conjunctival epithelium derived from?

A

Surface ectoderm

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4
Q

Which embryological structure does the limbus stroma originate from?

A

Neural crest cells

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5
Q

What are the layers of the sclera?

A

Innermost layer = lamina fusca (elastic fibres) - separated from choroid by potential space (suprachoroidal space - involved in uveoscleral AH outflow), fine branching collagen fibres connect lamina fusca with choroid and long ciliary nerves/posterior arteries course within this space.

Middle layer = sclera proper (white fibrous layer, stroma, avascular)
Outer layer = loose connetive tissue (episclera) - external boundary of the sclera.

Outer layer = Episclera (thin collagenous and vascular layer)
Thickens anteriorally where it binds with Tenon’s capsule and the subconjunctival connective tissue towards the limbus.

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6
Q

Why does the sclera need to be rigid?

A

Provide resistance to IOP and maintain spherical shape of the globe along with the cornea.

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7
Q

What channels are found within the sclera?

A

Contains smal channels to accomodate the long and short ciliary nerves, long posterior ciliary arteries, vortex veins and anterior ciliary vessels.

While sclera generally a tough barrier it is through these channels that disease processes can enter/leave the globe.

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8
Q

What is the lamina cribrosa?

A

Sieve like opening of the sclera in the region of the exit of the optic nerve.

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9
Q

What is the intrascleral plexus?

A

Located in anterior portion of the scleral stroma
Interconnecting veins that receives aqueous humour from angular aqueous plexus.
Draining venous blood mixes with draining aqueous into the anterior ciliary vein or posterior vortex vein.

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10
Q

How is aqueous usually circulated in dogs/cats?

A

Majority = conventional route (97% in cats, 85% in dogs)
AH passes through pupil into anterior chamber there enters the corneoscleral trabecular meshwork in the iridocorneal drainage angle through to the venous angular aqueous plexus and ultimately systemic venous circulation through plexus of small veins in the sclera - scleral venous plexus.

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11
Q

What other alternate pathways are there of aqueous circulation?

A

Posteriorly into vitreous
Anteriorally within the iris stroma or across the cornea
Uveoscleral route (3% ouflow in cat, 15% in dogs) - unconventional route

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12
Q

Describe the uveoscleral route for AH flow.

A

Aqueous in the iris root passes through ciliary body and choroid via supraciliary and suprachoroidal spaces. From there passes through sclera and episcleral tissues into the orbit.

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13
Q

List the main differences between the sclera and cornea.

A

Opaque (due to arrangement of collagen)
Contains some blood vessels(whilst cornea avascular)
Rigid

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14
Q

Where is the sclera widest?

A

Widest near insertions of the EOM and at the intrascleral plexus

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15
Q

Where is the sclera thinnest/thickest?

A

Near equator and posterior to EOM insertions = thinnest
Limbus and lamina cribosa = thickest

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16
Q

What is the innervation to the sclera?

A

Ciliary nerves - arise from branching of the trigeminal (ophthalmic branch)

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17
Q

What is the blood supply to the sclera?

A

Branches of anterior ciliary arteries anterior to insertions of recti muscles form dense episcleral plexus - a rich blood supply existing beneath the conjunctiva

Posterior sclera - small branches from long and short ciliary arteries.

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18
Q

What tissues are neighbouring tissues to the episclera?

A

Cornea, conjunctiva and choroid - any inflammatory process within these tissues can affect and vice versa and inflammation within the episclera/sclera can affect those tissues.

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19
Q

Are the episcleral vessels located above or below the conjunctival vessels?

A

Episcleral vessels = below conjunctival
Important when differentiating hyperaemia.

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20
Q

Describe the conjunctiva.

A

Thin vascular mucous membrane lining the inner surface of the eyelids, inner and outer TEL and the anterior sclera.
Reflected at ventral and dorsal fornices - conjunctival sacs.

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21
Q

How can the conjunctiva be further divided into sections?

A

Palpebral conjunctiva = lines upper/lower eyelids
Bulbar conjunctiva = anterior aspect of globe and connects it close to the corneoscleral limbus (can be pigmented or non pigmented

Conjunctiva of leading edge of TEL tends to be pigmented.

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22
Q

Where is the conjunctiva most tightly adhered

A

Eyelid margins, leading edge of the third eyelid and at the limbus.

Otherwise elastic tissue to allow for ocular motility.

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23
Q

How is the conjunctiva prevented from dessication? What types of epithelium are there?

A

Tear film will coat the conjunctival epithelium - prevents dessication and provides nourishment.
Stratified squamous (non keratinised) &
stratified columnar

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24
Q

Which type of epithelium of the conjunctiva contain goblet cells - what do they produce?

A

Columnar epithelium
Goblet cells - produce mucin for trilaminar tear film

Abnormalities of conjunctiva may therefore lead to lack of mucin within tear film, decreased resistance to infectious agents and restriction of ocular motility.

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25
Q

Which species has the highest goblet cell density?

A

Cats - more numerous in palpebral zones and on anterior surface of TEL.

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26
Q

What is the blood supply to the conjunctiva?

A

Extensive network (vascular tissue)
Branches of dorsal and ventral palpebral and malar arteries
Terminal branches of the ciliary arteries

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27
Q

What is the innervation to the conjunctiva?

A

Branches of long ciliary, zygomaticotempora, intratrochlear and frontal nerves.

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28
Q

List the main functions of the conjunctiva.

A

Allow for ocular motility (mobile tissue generally)
Anatomical ocular barrier
Lining for the surrounding ocular structures - eyelids, TEL and anterior sclera.
Goblet cells - mucin of tear film (inner layer of tear film)
Immune defence - lymphoid tissue

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29
Q

What is the CALT?

A

Conjunctival associated lymphoid tissue in the stroma of conjunctiva (lamina propria)

Organised lymphoid tissue in the superficial stroma - diffuse layer + lymphoid follicles

Deeper - lymphatic vessels, nerves and blood vessels

Key role in protecting ocular surface by initiating and regulating immune responses.
Must also tolerate diverse conjunctival flora on ocular surface
Protects against infectious agents - defensive role of conjunctiva.

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30
Q

How does mucin produced by the goblet cells also contribute to immune defence of the eye?

A

Mucin - innermost layer of tear film
Coats ocular surface combining with the glycocalyx of the cornea
Traps and immobilises debris and microbes so they can be evacuated from the tear film.
Binds antimicrobial peptides and proteins - lysozyme and IgA.

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31
Q

What is tenon’s capsule?

A

Tenon’s capsule = fascial sheath
Thin membrane enveloping eye and separating it from the orbital fat
Tenon’s capsule blends with the episclera just behind corneoscleral junction and fuses with bulbar conjunctiva
Capsule fuses with and extends to the sheath of the optic nerve and the sclera around entrance of optic nerve.

Separates conjunctiva from episclera - should not include in conjunctival pedicle grafts as increases risk of graft contracture/failure.

Sub Tenons injections - technique for regionala anaesthesia - extraocular muscle akinesis and mydriasis

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32
Q

What is the limbus?

A

Transitional zone between the cornea and sclera
Usually clearly defined as narrow (1mm) pigmented region encircling the cornea periphery.

Junction of the conjunctival and scleral epithelia and corneal and scleral stroma.
Where conjunctiva, tenons capsule and episclera meet.

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33
Q

What type of cells are found at the limbus and why are they important?

A

Limbus = contains pluripotent limbal epithelium stem cells
Essential for the health and maintenance of corneal surface both under normal and wound healing conditions.

Acheive via amplification, proliferation and differentiation into corneal epithelium

Also act as a physiological barrier to the ingress of conjunctival cells across the cornea.

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34
Q

What can dysfunction/destruction to the limbal stem cells lead to?

A

Dysfunction (e.g in some cases of multiple ocular defects) or destruction (chemical, thermal, inflammatory)

= Can lead to conjunctivalisation of the cornea
May have issues with corneal wound healing/persistent corneal ulceration

Herpes-virus in cats = common cause of limbal stem cell damage.

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35
Q

How is the limbus associated with the drainage angle?

A

Outermost aspect of the drainage angle - termination of descemet’s membrane
Limbal border zone internally between corneal endothelium and anterior trabeculum also contains specialised cells that can be activated to migrate and repopulate the trabecular meshwork after trabecular injury.

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36
Q

What steps should be performed initially in the investigation of scleral, episcleral, limbal and conjunctival disease.

A

Hx - trauma, duration, change in appearance etc

Clinical exam - assess for trauma, neoplasia, signs of systemic disease

Routine ophthalmic examination

Remember only most anterior aspects of sclera/episclera may be examined and that these tissues lie beneath a translucent bulbar conjunctiva.

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37
Q

Compare conjunctival vessels to episcleral vessels

A

Position - conjunctival = superficial, episcleral = deep
Width - conjunctival = narrow/fine, episcleral = wider and larger
Colour - conjunctival = pink/red, episcleral = deep red
Pattern - conjunctival = form loops, more tortuous can be seen to cross limbus if extend onto adjacent cornea. Episcleral = enter sclera and disappear from view just before limbus - straight vessels
Movement = conjunctival = freely mobile , episcleral = fixed to globe
Individual vessels - conjunctival = not distinct, episcleral = distinct
Location = conjunctival = palpebral, bulbar, nictitans, episcleral = overlying sclera
Response to topical 0.25% phenylephrine = conjunctival = blanch rapidly, episcleral = blanch much more slowly
IOP = conjunctival alone (expected to be norma), episceral (glaucoma, uveitis or normal - episcleritis)
Pupil size = conjunctival - expected to be normal, episcleral (mydriasis = glaucoma, miotic = uveitis, normal = episcleritis)
Significance = conjunctival = surface disease or corneal disease, episcleral = deep intraocular disease (episcleritis, scleritis, uveitis, glaucoma, orbital disease)

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38
Q

When during fundic examination may you be able to visualise the underlying sclera (lamina fusca layer)?

A

Subalbinotic animals - lack of pigment in the retina and choroid - leads to transparency and visualisation of the white lamina fusca of the sclera with retinal and choroidal vessels superimposed on top.

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39
Q

Which conditions can we see an increased scleral show with?

A

Macropalpebral fissure (often brachys)
Exophthalmos e.g extraocular polymyositis
Proptosis
Hydrothalmos/buphthalmos due to chronic glaucoma
Strabismus
Microphthalmos/microcornea
Phthisis bulbi

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40
Q

How can the colour of the conjunctiva and sclera be altered in some disease states?

A

Conjunctivitis/episcleritis = red
Jaundice = yellow
Pigment accumulation (particularly melanocytic tumour or ocular melanosis = dark.
Anaemia = white

Thinning may also see homogenous dark - iris visible under lamina fusca

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41
Q

When may thickening/thinning of the conjunctiva/episclera occur?

A

Thickening - inflammatory disease and neoplasis
Thinning - glaucoma/staphyloma (stretching)

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42
Q

What do conjunctival follicles indicate and which age/species are the often common in?

A

Conjunctival follicles = chronic antigenic stimulation
Common in young dogs

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43
Q

When is subconjunctival haemorrhage most commonly seen?

A

Trauma
Other differentials = coagulopathy (e.g thrombocytopaenia) /vasculitis

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44
Q

What is chemosis?

A

Conjunctival oedema - sign rather than a condition
Caused by any stimulus that results in acute inflammation - trauma, toxin, acute allergic conjunctivitits, infectious agent
Can preclude eyelid closure and risk desiccation of the cornea.

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45
Q

What techniques are there for investigating conjunctival/episcleral disease?

A

Cytology
Microbial culture/sensitivity
Biopsy for histopathology (biopsy of the sclera or episclera can be performed as diagnostic procedure but may also be used to debulk/remove lesion)
(Needle biopsies of firm nodules less likely to yield diagnostic result unless lymphoma or infectious agent suspected).

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46
Q

How can conjunctival biopsy be performed?

A

Can be performed under local topical anaesthesia /sedated
Conjunctival sac cleaned with dilute 1:50 povidone iodine then topical anaesthetic (0.5% proxymetacaine) applied to area of anticipated biopsy site with cotton tipped applicator for 10 seconds - maximally effective after 1 minute and max effect 25 mins

Conjunctival biopsy - fine toothed forceps (Bishop Harman) used to raise affected conjunctiva then sectioned with tenotomy scissors.

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47
Q

How is episcleral/scleral biopsy performed?

A

Should be done under minimum of sedation + topical but GA generally advisable.
Prep with povidone iodine 1:50
Overlying conjunctiva resected from lesion
Sharp corneal scissors or No 64 Beaver blade used to remove representative sample
Sample placed in 10% formalin
Conjunctival defect should not need suturing unless >1cm squared
Gentle pressure applied to site and bleeding should stop within 2-3 minutes. If not adrenaline (ephinephrine can be applied to area at dilution of 1:10,000 to provide vasoconstriction.
Broad spectrum topical AB used for 3-5 days pending lab results.

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48
Q

What may cause an out of focus area on fundic examination?

A

Coloboma (congenital absence of normal ocular tissue) - sclera, retina, optic nerve
Scleral ectasia (thinning) - congenital, acquired with buphthalmos associated with glaucoma or due to medication (repeated triamcinolone injections)

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49
Q

When is ocular ultrasound useful in scleral disease?

A

If suspect scleral rupture - focal irregular contour with decreased echogenicity of the sclera in conjunction with intraocular haemorrhage is suggestive.

Most common site of rupture = posterior pole of sclera or adjacent to optic nerve head

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50
Q

What is the average thickness of the sclera?

A

Approx 0.7mm at limbus
0.24mm at equator
0.45 near optic nerve

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51
Q

What is a dermoid? Where is most common site in dogs?

A

Congenital choristoma (normal skin in an abnormal area) - usually cornea, conjunctiva or eyelids.
Full differentiated and non neoplastic but in inappropriate place.
Temporal limbus most common site extending onto cornea in dogs but can occur anywhere.

Young dogs- had since birth!

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52
Q

What clinical signs are associated with dermoids?

A

Ocular discharge (epiphora or mucopurulent discharge), conjunctival and corneal irritation, potentially corneal ulcerations

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53
Q

Which breeds are predisposed to dermoids?

A

French Bulldogs, Dachshund, Dalmatian, Shih Tzu, Dobermann, GSD, St Bernards

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54
Q

How would you treat a dermoid?

A

Needs to be surgically removed (usually once >6 months of age)
Lateral canthotomy - aid exposure of globe

Dermoids typically involve corneal stroma and superficial conjunctiva - superficial keratectomy/conjunctivectomy usually curative.
Generally does not require grafting after removal but may do in some instance and should be prepared for that possibility.
Surgical conjunctival defects <1cm heal by itself, larger defects - suture with 6/0 vicryl
Temporary tarsorrhaphy may be performed - >25% corneal surface removed often sensible
Curative surgery unless resection incomplete.

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55
Q

What is a staphyloma? Where do they occur most commonly?

A

Thinned bulging sclera with a lining of uveal tract - congenital
Occur most commonly in posterior pole and optic nerve usually also involved or at equator of globe.

May be a feature of Collie-Eye Anomaly or Ehlers-Danlos syndrome or part of multiple ocular abnormalities that occur with Merle Ocular Dysgenesis.

Can occur anteriorally and manifests as anteriorly protruding dark blue (due to uvea) mass with cystic appearance.

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56
Q

How can you distinguish a staphyloma from uveal melanoma?

A

Gentle palpation - softness of the mass
+/- ocular ultrasound

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57
Q

What treatments are there for staphylomas?

A

Posterior staphyloma - no treatment indicated
Anterior staphyloma (focal) - repaired with autografting procedure using scleral autograft or xenograft/other suitable tissue.
Specialist procedure

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58
Q

What is the prognosis for eyes with staphylomas?

A

Extensive staphyloma = usually blind
In these cases may consider enucleation, especially if the protrusion is preventing blinking.

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59
Q

What is a sclerocornea?

A

Congenital non progressive condition - corneoscleral limbus indistinct as there is an extension of the sclera into the peripheral cornea.
Thought to be due to disturbance of mesenchymal and surface ectodermal growth at the rim of optic cup.

May be seen with other congenital ocular defects and associated with Ehlers-Danlos syndrome.

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60
Q

What type of disorder is seen most commonly with the conjunctiva/episclera?

A

Inflammatory conditions = most common
Majority thought to be immune mediated!

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61
Q

Which breeds are most commonly affected by episcleritis?

A

American Cocker Spaniel, Shetland Sheepdog, Collies breeds
Lurchers
Airedales
English Springer
BUT any breed can be affected!

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62
Q

What are the 2 forms of canine episcleritis? What type of disease is it and why do we think this?

A

Diffuse and nodular
Primary inflammatory condition - immune mediated (based on response to immunosuppressives and histopathology - inflammatory reaction dominated by histiocytes, lymphocytes and/or plasma cells)

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63
Q

What types of infection/disease may episcleritis sometimes follow on from?

A

Ehrlichia, Ochocerca, Toxoplasma.
Occasionally related to ocular trauma or extension of opthalmitis.

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64
Q

How is diffuse episcleritis characterised?

A

Diffuse = generalised or regional episcleral vascular injection with thickening of surrounding episclera
Often accompanied by mild corneal oedema and peripheral neovascularisation adjacent to area.

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65
Q

How is nodular (granulomatous) episcleritis usually characterised?

A

Describes several disease processes - nodular fasculitis, fibrous histiocytoma, proliferative conjunctivitis, pseudotumour limbal granuloma and collie granuloma.

Unilateral or bilateral thickened area - most often temporal limbus
Hyperaemia of the episclera over top
Adjacent tissues often also inflamed and may be seen with conjunctivitis, keratitis, scleritis, blepharitis and chorioretinitis.

66
Q

What type of infiltrate can we often see in the cornea adjacent to an area of nodular episcleritis.

A

Can result in lipid infiltration into cornea (lipid keratopathy) with chronicity.

67
Q

What are the main differential diagnoses for nodular episcleritis?

A

Lymphoma, squamous cell carcinoma, amelanotic limbal melanoma
(In some cases biopsy indicated)

68
Q

What is the treatment for episcleritis?

A

Topical corticosteroids - 1% Prednisolone acetate or 0.1% dexamethasone - preferred 1st line tx
Initially recommended 3-4x daily then gradually reduced - in some cases can be withdrawn although less frequent maintainance dose may be required to prevent relapse.

Oral corticosteroids indicated for cases that do not respond to topicals alone.

Subconjunctival/intralesional corticosteroids in some cases.

Azathioprine alone or in conjunction with corticosteroids 2mg.kg q 24hrs for 1 week then reduced to 1mg/kdf q24hrs for 2 weeks then 1mg/kg 1-2x weekly once clinical signs resolved. Potential toxic effects - myelosuppression, hepatotoxicosis and GI upset. Bloods before and during tx.

Ciclosporin 5mg/kg q24hrs for 30 days (with/without oral steroids), Dose then reduced to 2.5mg/kg q 24hrs or 5mg/kg EOD

Tetracycline together with niacinamide (form of VitB3) orally TID at 250mg/drug <10kg, 500mg/drug >10kg

Surgical excision with lamellar keratectomy
Debulking/cryosurgery
Beta radiation therapy also been used

If infectious agent is identified or suspected then appropriate tx of those diseases should be started e.g toxoplasmosis, ehrilichia, leishmania etc

69
Q

What type of disorder is scleritis? How is it classified?

A

Uncommon
Primary immune mediated disorder - idiopathic

Classified as necrotising vs non necrotising based on the presence or absence of collagen necrosis of scleral biopsy.

70
Q

How does non necrotising scleritis appear?
What breeds may be predisposed?

A

Non necrotising = less severe
Regional or diffuse thickening of the sclera with hyperaemia of the overlying conjunctiva/episclera.

Ocular pain, epiphora, and involvement of intraocular tissues. Severe/chronic = involvement of choroid resulting in retinal detachment or chorioretinal degeneration with vitreal exudate.

Springer/Cocker Spaniels predisposed.

71
Q

How does necrotising scleritis appear?

A

Aggressive, severe and painful
Affects chorioid, retina and episclera also

72
Q

How would you confirm scleritis and the type?

A

Scleral biopsy - specialist procedure due to risk of globe perforation

Biopsy - dense accumulation of plasma cells and lymphocytes within sclera.

73
Q

How can scleritis be managed?

A

Lifelong immunosuppression - systemically via oral corticosteroids +/- azathioprine

Overall prognosis = guarded and prognosis for retention of vision or the globe is poor.
Systemic immune mediated disorder may be present concurrently.

Non necrotising may respond to systemic NSAIDs

Topical NSAID/steroids may increase comfort and treat uveitis but will be unable to treat the scleritis

74
Q

What other ocular abnormalities would we expect to see with scleral rupture?

A

Scleral rupture = high amount of force

Lens luxation, hyphaema, retinal detachment, lens capsule rupture, vitreal haemorrhage, protrusion of uveal tract through injury, corneal rupture.

75
Q

How can scleral rupture be detected?

A

Visually = if at limbus or if globe proptosed

Detected on ultrasound

76
Q

What clinical signs would increase suspicion for a scleral rupture?

A

360 degree subconjunctival haemorrhage
Hyphaema
Eyelid and conjunctival swelling

77
Q

What locations are the most common points for scleral rupture?

A

Deforming blow results in scleral rupture at points of weakness = Equator, posterior pole and adjacent to optic nerve, occasionally limbus.

78
Q

How can the globe be assessed following trauma?

A

Facilitated by topical anaesthesia
+ve menace = good prognostic sign
+ve dazzle = indicates still some retinal/optic nerve function
PLR presence does not confirm vision but is positive prognostic indicator -ve does not necessarily imply blindness.

79
Q

How may a simple scleral wound near the limbus be treated? What about more extensive injuries?

A

May be suitable for direct surgical closure
More extensive - phacoemulsification/scleral grafting
Many cases = enucleation if severe trauma with poor prognosis for vision/comfort.

80
Q

What is the difference between a penetrating and perforating injury.

A

Penetrating = single wound e.g dental elevator
Perforating = entry and exit wound e.g gunshot

81
Q

What can penetrating/perforating injuries of the sclera lead to?

A

Secondary complications - endophthalmitis, lens capsule damage/rupture, retinal detachment

Possible phthisis bulbi/blindness/enopthalmitis - usually poor prognosis and require enucleation.

82
Q

How may scleral injuries sometimes be approached?

A

Suture of the sclera but may also require lens removal, vitrectomy and scleral grafting - specialist procedure if attempt to try and salvage eye.

83
Q

How does glaucoma affect the sclera?

A

Episcleral congestion - normal flow of blood through ciliary body to vortex veins impeded by raised IOP

Hydrophthalmos/Buphthalmos - prolonged raised IOP causes sclera and cornea to stretch and globe enlarged. Scleral ectasia - aquired thinnning of sclera due to dilatation. Sclera appears slightly blue and underlying uvea visible. Increase in globe size occurs more readily in younger animals as sclera more elastic.

Optic nerve cupping - distortion of lamina cribosa also compressed posteriorly by increased IOP
Affects axoplasmic flow, reducing blood supply to optic nerve head and leads to optic nerve axonal death and blindeness. Axon death + physical stretching + compression and alteration of tissue in lamina cribosa = appearance of optic nerve cupping.

84
Q

Why is scleral neoplasia often more common at the limbus?

A

Area of high mitotic activity and superiotemporal aspect of limbus = exposed to ultraviolet light.

85
Q

What are the most common types of neoplasia to affect the sclera?

A

Melanoma, haemangioma, haemangiosarcoma, lymphoma, squamous cell carcinoma

Primary neoplasia uncommon but intraocular/orbital tumours may invade optic nerve and scleral vasculature.

86
Q

What is the typical appearance of limbal melanomas in dogs?

What breeds are over-represented?

A

Focally pigmented elevated mass at the limbus
May be hyperaemia of overlying conjunctiva as well as infiltraton/opacification of adjacent cornea.

GSD, Golden Retriever and Labrador Retriever
Genetic predispositon demonstrated in latter 2 breeds
Neoplasm of the pigmented melanocytes at the limbus.

87
Q

Are limbal melanomas in dogs typically benign or malignant?
How might they be removed?

A

Generally benign with low metastatic potential but can become quite large and in younger dogs may grow rapidly.

Full thickness surgical resection or debulking usually with adjunctive tx e.g cryotherapy.
Defect repaired with corneoscleral allograft, nictitans cartilage, sheet of porcine small intestinal submucosa or conjunctival advancement flap.

Alternative tx Photocoagulation either with a diode or neodynium aluminium garnet laser.

Prognosis = good.

88
Q

What should limbal melanoma be distinguished from?

A

Differentiate from intraocular melanoma which can penetrate sclera
Orbital exenteration required for these cases to contain spread of tumour.
Can be challenging to differentiate.

Limbal = slow growing, discrete and typically do not penetrae sclera/invade adjacent iris/ciliary body.

Malignant ocular melanomas = grow rapidly, larger/less well defined and invade uvea/sclera
May present with glaucoma and systemic signs if already metastasis.

Ocular ultrasonography/gonioscopy can help differentiate if diagnosis unclear.

89
Q

What is ocular melanosis in dogs also known as and which breed is it most commonly seen in?

A

Ocular melanosis = pigmentary glaucoma

Cairn Terriers - autosomal dominant mode of inheritance

Bilateral condition but not symmetrical.

Other breeds e.g Labrador and Boxer may also be affected by abnormal pigment deposition and glaucoma.

90
Q

Describe the main findings with ocular melanosis in the dog (Cairn Terrier)

A

Bilateral but not symmetrical
Proliferation and migration of pigmented cells - melanocytes and melanophages

Early stages iris periphery = thickened
As disease progresses iris becomes darker and pigment exfoliates into anterior chamber
Multifocal dark patches of pigmentation become evident on anterior sclera and progressively enlarge

Gonioscopy - angle = dark due to presence of pigment and cleft narrow due to swollen iris periphery

91
Q

Why does glaucoma develop with ocular melanosis in the dog?

A

Occlusion of drainage angle with melanocytes and melanophages - obstruction of AH outflow and also narrowing of drainage angle due to thickened iris root.

92
Q

What is the prognosis for ocular melanosis?

A

Poor prognosis for ocular melanosis
Responds poorly to medication
Carbonic anhydrase inhibitors may slow down progression of glaucoma

Advanced stages= enucleation

93
Q
A
94
Q
A
94
Q
A
95
Q

List some congenital conditions of the conjunctiva

A

Conjunctival cysts
Conjunctival dermoids

95
Q

What clinical signs are associated with conjunctivitis in dogs?

A

Conjunctival hyperaemia
Ocular discharge
Chemosis
Conjunctival thickening/ulceration
Subconjunctival haemorrhage
Follicle formation

96
Q

How can canine conjunctivitis be classified?

A

Duration - acute, chronic, recurrent
Appearance - mucoid, mucopurulent, purulent, follicular, haemorrhagic
Cause - infectious, traumatic, secondary to keratitis, tear film abnormalities, trichiasis, uveitis, glaucoma, orbital disease

97
Q

What are the most common causes of conjunctivitis in dogs compared to cats?

A

Dogs = tear film or adnexal abnormalties

Cats = infectious agents

98
Q

List the possible aetiologies of canine conjunctivitis.

A

Bacterial - gram +ve cocci (not common)
Viral - canine distemper
Parasitic - thelazia spp in certain countries
Mycotic - blastomycosi
Neonatal - accumulation of exudates behind closed eyelids, usually with bacterial or viral component
Immune mediated - allergic (atopic dogs), plasma cell conjunctivitis (pannus), follicular conjunctivitis (chronic conjunctivitis, usually young dogs), systemic immune mediated diseases (blepharoconjunctivitis e.g pemphigus complex)

Iatrogenic - owners cleansing eyes with inappropriate cleaner

Secondary to adnexal disease - trichiasis (entropion, distichiasis, ectropion, ectopic cilia, hairy caruncles)

Secondary to tear film abnormalities - KCS, qualitative tear film issues

Secondary to trauma/environmental irritants - foreign body, dust, chemicals, eye medications

Neoplasia - e.g inflamed in region of eyelid mass

Secondary to other ocular disease - due to communication between episcleral and conjunctival vessels, conjunctival vessels secondarily congested when episcleral congested (vice versa not true!)

99
Q

How can cell type (e.g from conjunctival biopsy) help determine aetiology of conjunctivitis?

A

Neutrophils - predominate in acute conjunctivitis
Eosinophils - immune mediated/allergic
Lymphocytes/plasma cells = chronic/immune mediated

Can also look for changes in goblet cell density and epithelial changes on biopsy.

100
Q

How do ocular tear film abnormalities lead to conjunctivitis?

A

Conjunctiva inextricably linked with precorneal tear film
Goblet cell deficiency e.g KCS reduces mucin component of tear film = reduced adherence of tear film to ocular surface (measure with TFBUT)

Reduction in aqueous component = epithelial hyperplasia and keratinisation (tear film keeps hydrated)
Chronic inflammation of ocular surface = increased surface friction
Dehydration and malnutrition of corneal and conjunctival epithelium - secondary consequence = corneal ulcerations which have poor healing and are more prone to infection.

101
Q

How is conjunctival hyperaemia caused?

A

Redness or injection of conjunctival blood vessels

Release of inflammatory mediators (conjunctivitis)
Compromised venous drainage (orbital disease, cherry eye, uveitis)
Congestion due to glaucoma - engorgement of episcleral vessels due to reduced flow from ciliary body to vortex veins, increased flow forwards to episcleral veins and secondary conjunctival engorgement.
Compression of jugular veins = e.g tight collar

102
Q

What is chemosis?

A

Chemosis = oedema of the conjunctiva
Response to allergy, toxin or trauma, foreign bodies
Occurs due to loose arrangement of conjunctival stroma
Can be dramatic and prevent eyelid closure and lead to desiccation of conjunctival epithelium.

103
Q

What may cause conjunctival thickening?

A

Chronic oedema
Chronic infiltration
Neoplasia

104
Q

What is follicular conjunctivitis associated with?

A

Chronic inflammation - usually younger, large breed dogs with poor adnexal conformation.
Semitransparent nodules primarily on bulbar side of third eyelid

Tx options - correct conformation surgically if factor, topical tears, topical steroids

105
Q

What would be the approach to allergic conjunctivitis?

A

Acute allergic conjunctivitis e.g drug, insect sting - dramatic chemosis and blepharoedema, usually bilateral, histamine and IgE release.

Tx - systemic corticosteroids and antihistamine +/- topical steroid

Chronic allergic conjunctivitis:

Conjunctival hyperaemia and epiphora, may be pawing/rubbing eyes and mild discomfort.
Response to allergens, pollens, moulds, dust mites

Avoid allergen/topical steroids/topical mast cell stabilisers/systemic antihistamines/hyposensitisation

106
Q

What is a plasmoma?

A

Lymphoplasmacytic inflammation with similar pathogenesis to CSK (chronic superficial keratitis)
Patchy depigmentation and thickening of the third eyelids with mucoid discharge
May also have keratitis or occur in isolation

Treated with topical ciclosporin or steroids.

107
Q

How is bacterial conjunctivitis usually addressed?

A

Commensal bacteria reside in conjunctiva
Bacterial conjunctivitis = secondary to eyelid abnormalities or tear film abnormalities generally.

Mostly gram +ve = staphlylococcus
Pending culture results = broad spectrum topical treatment typically used.

108
Q

What happens with ophthalmia neonatorum?

A

Occurs in puppies and kittens
Form of conjunctivitis in neonatal period
Usually due to delayed/incomplete opening of eyelids (ankyloblepharon)
Staphylococcal infection may result in keratoconjunctivitis - intrauterine infection or infection during birth
Bead of purulent material at medial canthus and bulging eyelids
Eyelids need to be opened carefully - endophthalmitis can occur otherwise
Bathe with warm water, use closed forceps to gradually prize open.

109
Q

Apart from conjunctivitis what other abnormalities may be seen with canine distemper?

A

Conjunctivitis along with KCS, chorioretinitis and optic neuritis
Rhinitis and trachobronchitis - tonsilitis, pyrexia etc
Direct immunofluorescence/PCR tests avaliable

110
Q

How is Thelazia callipaeda treated ?

A

Parasite that can cause conjunctivitis
Not endemic to UK - Mainland Europe
Vector = Phortica (fruit fly)
Clinical presentation - worms visible in eye, epiphora, conjunctivitis, occasionally corneal ulceration

Treatment = manual removal, flushing, imidacloprid and moxidectin (advocate), milbemycin and praziquantelt (Milbemax)

111
Q

Which adnexal abnormalities can lead to conjunctivitis?

A

Diamond eye - combination of entropion/ectropion (St Bernard, Basset, Great Dane) + often macropalpebral fissure

Brachycephalic breeds - macropalpebral fissue + medial entropion of lower lids and lagophthalmos

Facial droop - animals with heavy folds of skin on forehead that cause entropion of upper eyelids (St Bernard, Chow Chow, Shar Pei, Bassett, Mastiff)

Entropion

Distichiasis - Bulldogs, Poodle, Shetland Sheepdog

Facial conformation should be assessed prior to any sedatives or topical anaesthetics
Conjunctivitis is resolved when the adnexal abnormality is rectified.

112
Q

What is ligneous conjunctivitis and which breeds/sex is it seen in?

How is it treated?

A

Rare - female Dobermann’s and occasionally Golden Retrievers

Bilateral chronic condition
Ulcerative conjunctivitis with membranous thickening of the palpebral and TEL conjunctiva
Plasminogen deficiency thought to be present

Diagnosis = conjunctival biopsy
Histopath = amorphous eosinophilic hyaline material observed
Upper respiratory and urinary tracts may also be affected

Treatment = topical ciclosporin but systemic immunosuppressants may also be required.
Recurrence is common
Euthanasia or death may result if systemic effects.

113
Q

What are the differentials for subconjunctival haemorrhage?

A

Trauma
Coagulopathies - angiostronglosis, Von Willebrand factor deficiency, thrombocytopaenia etc
Vasculitis

Haemorrhage as a result of trauma typically self resolves within 7-10 days
Work up if no indication of trauma/suspicion of coagulopathy.

114
Q

How would you investigate conjunctivitis?

A

Hx - duration, concurrent signs, type of discharge, in contact animals, unilateral or bilateral, vaccination/worming status, on any medications currently

General PE if indicated

Ophthalmic exam - adenxal conformation, palpebral reflex, globe retropulsion, health of globe, presence of conjunctival foreign bodies, tear film quatity and quality, nasolacrimal drainage, tonometry

Diagnosis - observation of cause, C+S/PCR, conjunctival cytology, conjunctival biopsy, response to treatment

115
Q

What are the main treatment approaches to conjunctivitis?

A

Manage the primary condition e.g KCS/adenxal conformation
Keep eyes clean - cooled boiled water

Topical medications - artificial tears, broad spectrum antibiotics, steroids (not 1st line in cats!), NSAID’s, antivirals

Systemic if necessary (blepharitis, dermatitis, otitis) - steroids if immune mediated, anti-histamines (allergy), antibiotics if infectious.

Surgical tx if necessary e.g correction of entropion, flushing tear ducts, removing masses, removing foreign bodies

116
Q

What types of primary conjunctival neoplasia are seen?

A

Overall not common in conjunctiva - very amenable to biopsy
Primary masses mostly benign but some types can be malignant.

Haemangioma/haemangiosarcoma
Melanoma
Mast cell tumour
Squamous cell carcinoma
Papilloma
Fibroma
Fibrosarcoma
Adenoma/adenocarcinoma

117
Q

What types of secondary conjunctival neoplasia are there?

A

Lymphoma
Systemic histiocytosis
Transmissable Veneral Tumour

118
Q

Which breeds of cat are most prone to dermoids?

A

Burmese and Birman - typically situated at lateral canthus or at lateral limbus and involve conjunctiva and cornea.

119
Q

Which congenital abnormality of the sclera can also be seen in cats?

A

Congenital staphyloma
Thinned stretched sclera with a lining of uveal tract
(Can also get staphylomas secondary to raised IOP or trauma)

Can repair with fascial graft

Associated with posterior segment coloboma e.g affecting optic nerve head and peripapillary retina and choroid or alternatively iris coloboma.

120
Q

What is feline post traumatic sarcoma?

A

Uncommon but highly metastatic tumour
Arises from globe several years later - associated with ocular injury especially if damage to the lens was sustained.
Poor prognosis with rapid metastasis to CNS

121
Q

Why are cats prone to dental associated injuries to the globe?

A

Caudal maxillary tooth roots close proximity to orbit
Penetration most commonly occurs ventrally at 6 o clock position along same trajectory
May also get injuries associated with infraorbital nerve block.

Posterior lens capsule often penetrated as well as the globe.

Ocular signs usually occur within days of dental procedure but can develop weeks later.

Chronic uveitis and intraocular infection (endophthalmitis) and it sequelae are painful conditions with poor prognosis
Most commonly results in enucleation - secondary glaucoma.

Occurs more commonly in cats as thinner alveolar bone between orbit and tooth roots compared to dogs.

122
Q

How does iris tissue protruding through a limbal or scleral laceration appear?

A

Prolapsed iris tissue = usually covered by thin layer of tan coloured clotted aqueous humour

Dyscoria (abnormal pupil shape) due to incarceration of this iris tissue - often more obvious when testing the PLR

123
Q

What are the most common tumours of the feline episclera/sclera/limbus?

A

Epibulbar (limbal) melanoma (less frequent than in dogs, occasionally metastasise) - regular monitoring recommended, increasing in size then treat with beta radiation, surgical exicsion + cyrotherapy or diode laser photocoagulation.

2nd most common tumour in this area = lymphoma.

124
Q

What type of conjunctivitis is most common in the cat? What other causes are there?

A

Infectious = no 1 cause

125
Q

List the types of conjunctivitis seen in cats.

A

Viral - FHV-1, calicivirus
Bacterial - Chlamydophila felis, Mycoplasma felis, neonatal
Immune mediated - eosinophilic keratoconjunctivitis/conjunctivitis, systemic immune mediated disease e.g associated with pemphigus
Parasitic - thelazia nematodes
Adnexal disease - entropion (distichiasis/ectopic cilia rare), ectropion (eyelid mass/old injury)
Tear film defieciency - KCS rare in cats
Neoplasia - squamous cell carcinoma/lymphoma
Trauma
Environmental irritants
Foreign bodies
Secondary to other ocular disease - keratitis, uveitis, glaucoma, orbital disease, Horner’s

126
Q

Discuss Feline Herpes-virus 1 - which cells does it invade?

A

FHV-1 widespread
75-97% cats seropositive for virus
FHV-1 invades and replicates in the epithelia of the conjunctiva and respiratory tract with more limited replication in corneal epithelium.
FHV-1 can cause both primary and secondary conjuncitivitis/keratitis.
Predisposes to secondary bacterial infection which can also worsen the signs.

127
Q

What are the clinical signs of feline herpesvirus?

A

Young kittens = “cat flu” - ocular and respiratory signs
Ocular signs -serous to mucopurulent discharge, conjunctival hyperaemia and chemosis and in some cases corneal ulceration and symblepharon formation

128
Q

What type of corneal ulcers can be seen with FHV-1 infection? Which stain is superior for detection?

A

Dendritic (branching) ulcers - consider pathognomonic for FHV-1
Rose Bengal stain = superior for diagnosing as basement membrane of epithelium often remains intact.

Dendritic ulcers can progress and coalesce resulting in broader geographic ulcers.

129
Q

What happens in cats with FHV-1 after acute infection?

A

80% of cats become latent carriers with the virus dormant in the trigeminal ganglia

Periodic reactivation of the virus occurs with stress related events (rehoming, labour, corticosteroid treatment) - recrudescence of disease.

Clinical signs with recrudescence often milder - conjunctival hyperaemia and swelling, dendritic or geographic corneal ulceration.

130
Q

Which ocular diseases may also be associated with FHV-1 infection?

A

Corneal sequestrum
Chronic stromal keratitis
Eosinophilic/proliferative keratitis
Uveitis and dermatitis

131
Q

How is FHV-1 diagnosed?

A

Often based on clinical suspicion (classical ocular and systemic signs)

PCR - but unable to distinguish wild type vs vaccine strains

132
Q

What options are there for the treatment of FHV-1 cats?

A

Uncomplicated viral infection = self limiting within 10-14 days
Initial approach = nursing care, stress free environment, control any secondary bacterial infection with topical antibiotics.

Corneal ulceration - topical broad spectrum antibiotics e.g chloramphenicol/fusidic acid
(Geographic ulcers with epithelial under running may also benefit from gentle cotton bud epithelial debridement)

Antivirals - use usually reserved for chronic ongoing cases/dendritic ulcers/active upper respiratory disease. Need to be applied 5-6x daily to be effective.

133
Q

Make a list of antivirals in order of descending in vitro efficacy. (Most effective to least effective)

A

Triflurothymidine
Ganciclovir
Idoxuridine
Ciclofovir
Penciclovir
Aciclovir

134
Q

What do antivirals do?

A

Reduce viral load and shedding improving clinical signs.

135
Q

Which systemic antiviral may be used in some cases of FHV-1 infection?

A

Systemic famciclovir (pro drug to penciclovir)
Administered orally 90mg/kg TID
Option for cats who won’t tolerate 5-6x daily application of topical antivirals but efficacy debated.
Expensive +++

136
Q

What other drugs may be given for FHV-1 infection - discuss efficacy.

A

Interferon - limited evidence for use

Lysine - competes with arginine and reduces viral replication rate in vitro. Given orally and is safe to use in cats - 500mg bolus twice daily with aim to reduce viral shedding but not evidence of efficacy currently - mainly anecdotal.
Act of administering may increase stress - increased risk of FHV-1 flare ups!

137
Q

What are the typical clinical signs of calicivirus?

A

FCV = common upper respiratory pathogen
Typical systemic signs = fever, rhinitis, oral mucosal ulceration and chronic stomatitis.
Originally thought just mild conjunctivitis but recent studies suggest can be primary ocular pathogen.
10% of affected cats - mild to moderate conjunctivitis along with conjunctival epithelial ulceration

138
Q

How is calicivirus typically diagnosed?

A

Clinical signs

Virus isolation or PCR to diagnose

139
Q

Why can calicivirus not be treated with antivirals as with FHV-1 infection?
What type of treatment should always be considered with calicivirus?

A

RNA virus rather than DNA virus
Antivirals for FHV-1 target viral DNA synthesis.

Topical broad spectrum antibiotics - reduce complications associated with secondary bacterial infection

140
Q

What are the clinical signs of chlamydial infection in cats?

A

Often young cats
Blepharospasm, serous ocular discharge, conjunctival hyperaemia and pronounced chemosis
Initially unilateral then with time bilateral
Over time initial serous discharge becomes mucopurulent and conjunctiva may become thickened.

Chronic cases = conjunctival hyperaemia with follicle formation and hyperplasia
Left untreated can develop chronic carrier state

141
Q

How is Chlamydia diagnosed?

A

Clinical signs/presentation
PCR testing for the organism

142
Q

How is Chlamydial infection treated?

A

Should be treated systemically as can become established in and genitourinary tracts

Doxycycline = recommended tx.
10mg/kg orally SID for 3-6 weeks
(Oral doxycycline always with food swallow/water - associated with stricture/oesophagitis in cats)

Topical tx - cleansing ocular surfaces
Broad spectrum antibiotic that has antichlamydial efficacy e.g tetracycline if avaliable.

143
Q

What type of disease is mycoplasma associated with? How is it treated?

A

Clinical significance controversial
Conjunctivitis (more significant role when conjunctivitis already present)
Clinical signs - unilateral conjunctivitis with conjunctival hyperaemia and serous/purulent ocular discharge that typically becomes bilateral after a few days

Disease thought to be self limiting to 30 days
Treatment = same as chlamydial conjunctivitis (doxycycline) and typically responds well to therapy.

144
Q

What is symblepharon? What is is often a sequelae to?

A

Adhesion of the bulbar, palpebral or third eyelid conjunctiva to other regions of ocular surface e.g cornea or to itself

Sequelae to FHV-1 infection or chemical injury

145
Q

How may symblepharon affect the eye?

A

Adhesion = reduced mobility, reduced vision (obscuring cornea), reduced tear production and distribution
Fusion over lacrimal puncta = chronic epiphora
Fixed protrusion of TEL if adhesions from TEL conjunctiva
Most severe form entire cornea conjunctivalised and blind

146
Q

Why is surgical management of symblepharon so challenging?

A

Adhesions often reform following removal
Due to limbal stem cells (essential for normal corneal epithelial health) being destroyed - permanent change
FHV-1 infection - cytolysis of limbal stem cells
Damage to limbal area during chemical injury

Poor epithelial regeneration capacity so removal of the conjunctiva adhered to the corneal surface is rapidly followed by reconjunctivalisation.

147
Q

Discuss how you might attempt to surgically approach symblepharon (usually cases where blind and trying to restore vision or cases with extremely limited motility)

A

Aim = increase mobility/vision
Many cases comfortable and should be left alone
Recurrence common due to chronic FHV-1 infection and due to permanent destruction of limbal stem cell population

Fibrous adhesion resection if conjunctiva to another epithelial surface
Soft contact lens/confomer to help keep separated
Superficial keratectomy over limbus if adhered to cornea, conjunctiva sutured to edge of limbus OR conjunctiva sutured back with fonix based conjunctival flap (Arlt or Lembert suture) - also post op contact lens/temporary tarsorrhaphy
Topical AB’s until no fluorescein uptake then course of steroids but beware FHV-1 recrudescence.

148
Q

Does keratoconjunctivitis sicca (KCS) occur in cats?

A

Yes but rare compared to dogs
Conjunctivitis/purulent to mucopurulent discharge often presenting sign so do perform STT in cases of conjunctivitis

149
Q

Describe lipogranulomatous conjunctivitis in cats.

A

Often older cats - inflammatory condition
Meibomian glands affected in one or both eyes (principally upper eyelids)
Regional, non ulcerated cream coloured nodules visible beneath palpebral conjunctiva
Histo = lipid free lakes surrounded by regions of granulomatous inflammation
Any breed - higher incidence in Persians
Solar radiation suspected to play a role (animals with little periocular pigmentation)
Occasionally have concurrent eyelid neoplasia.

150
Q

What treatment options are there for lipogranulomatous conjunctivitis in cats?

A

Monitor +/- lubrication

If irritation surgical treatment - curettage of the glands through conjunctival surface
Multiple glands close to one another strip of conjunctiva and underlying lipogranulomas may be resected and defect allowed to heal via secondary intention.

151
Q

Describe eosinophilic conjunctivitis in cats.

A

Less common than eosinophilic keratitis
Middle aged to older cats
One or both eyes
Thickening, depigmentation and erosions of lid margin with belpharospasm, swelling and redness of conjunctiva and third eyelid

?possible associated with FHV-1

152
Q

How can we diagnose eosinophilic conjunctivitis in cats.

A

Clinical appearance
Cytology of conjunctival scrapings
Biopsy for histopath

Inflammatory cells - predominately neutrophils + mast cells and eosinophils with rare lymphocytes/plasma cells

153
Q

How can we treat eosinophilic conjunctivitis?

A

Anti-inflammatory therapy (e.g corticosteroids 0.1% dexamethasone phosphate or 1% prednisolone acetate) or immunosuppressant therapy (0.02% ciclosporin ointment)

154
Q

How does feline ocular mycobacteriosis typically present (feline TB)?
How is it diagnosed?

A

Typically nodular skin disease but affects eye in 6.6% cases
Affect any structure of eye including conjunctiva and sclera but uveitis is most common ocular manifestation.

Diagnosis = challenging, histopath - Ziehl Neilson staining (findings of granulomatous to pyogranulomatous inflammation with acid fast organisms)
Typing = myobacterial culture, PCR with further sequencing or interferon gamma release assay required.

Treatment = triple antibiotic protocol for several months

155
Q

What types of neoplasia are seen within the conjunctiva of cats?

A

Squamous cell carcinoma
Melanoma
Haemangioma/haemangiosarcoma
Mucoepidermoid carcinoma
Fibrosarcoma
Mast cell tumours
Lymphoma

156
Q

Discuss SCC in the conjunctiva of cats.

A

Not usually just conjunctiva alone (eyelids/globe)
Lack of pigment + UV radiation thought to predispose
Surface cytology/biopsy to help differentiate from inflammatory process e.g lipogranulomatous conjunctivitis, eosinophilic conjunctivitis
Locally invasive
Surgical excision/debulking with adjunctive treatment
e.g cyrotherapy, hyperthermia, immunotherapy, radiation, photodynamic therapy

Prognosis = guarded unless complete excision with good margins achieved

157
Q

Discuss melanoma within the conjunctiva of cats.

A

Uncommon
Bulbar conjunctivitis usually
Can be amelanotic
Locally aggressive and may metastasise
Exenteration often treatment of choice

158
Q

Discuss haemangiosarcoma of the conjunctiva of cats.

A

Uncommon
High UV light exposure/age = predisposing factors
Superficial red/brown nodule
Early complete resection = curative
Recurrence possible

159
Q

Discuss mast cell tumours of conjunctiva of cats.

A

More common for them to affect eyelids
Variable appearance - diffuse to nodular
Most often histologically benign
Complete surgical excision usually curative

160
Q

Discuss conjunctival lymphoma in cats.

A

Uncommon in just conjunctiva but has been reported
Secondary neoplasia - typically extension from other locations