Lacrimal System Flashcards
How can the lacrimal system be divided?
Lacrimal secretory system - lacrimal gland, nictitans gland, meibomian glands, conjunctiva/cornea (production of pre-ocular tear film)
Lacrimal excretory system - lacrimal punctae, canaliculi, lacrimal sac, nasolacrimal duct and nasal punctae. (drainage of tears from ocular surface)
Where do the orbital lacrimal gland, third eyelid gland, conjunctival goblet cells and meibomian glands originate from embryologically?
Surface ectoderm
Which species may the Haderian gland be found in and what is it?
Rabbits and rodent = accessory lacrimal gland
Why are tears essential?
Maintain ocular surface health:
Lubricate ocular surface
Flush away debris - allowing for atraumatic eyelid closure
Nutrition to the avascular cornea
Protective anti-microbial proteins (lactoferrins)
Help with refraction - clear vision
What is the trilaminar tear film composed of?
Lipid, aqueous and mucin
More recent studies show each layer is more intricately mingled
How thick is the tear film appoximately?
7-10 um (possibly slightly thicker)
What portion makes up the majority of the tear film?
Majority aqueous
How does the tear film usually adhere to the cornea?
Corneal epithelial cells have microplicae and microvili which increase surface area of tear binding.
Glycocalyx expressed by the corneal epithelium interact with mucins and promote retention of the tears (wettability)
How are the layers of the tear film arranged?
Mucin - adherence to cornea
Aqueous - middle, largest portion (antimicrobial proteins within this layer)
Lipid - outside, reduces evaporation and contributes to stability of tear film.
Which cells produce mucin?
Goblet cells (holocrine) of the conjunctiva, particularly concentrated in lower conjunctival sac - medial/ventral.
Found less commonly in the bulbar conjunctiva.
How can mucins be further classified?
Membrane bound or secretory
Membrane bound mucins = found on edge of micropilae of surface corneal epithelial cells foriming a dense glycocalyx at epithelial-tear film interface.
Prevents pathogen penetrance and enhances aqueous coherence.
Secretory mucins = help remove debris, hold fluid in place and bind defence molecules.
Where is the aqueous layer produced and how much is produced there in terms of %?
Lacrimal gland = 70% aqueous tear film
Nictitans/TEL gland = 30% aqueous tear film
Bulk of tear film = aqueous
What is aqueous tear film composed of?
Water, electrolytes, glucose, urea, surface-active polymers, glycoproteins, tear proteins
Tear proteins = secretory IgA, IgG, IgM, albumin, lysozyme, lactoferrin, lipocalin, epidermal growth factor, transforming growth factor, interleukins
Where is the lipid of the tear film produced?
Meibomian glands (modified sebaceous glands)
Produce lipid (meibum)
Stabilises tear film and reduces evaporation
Where are the meibomian glands located and how many are there per eyelid?
What type of gland are they?
Located within tarsal plate of the eyelids
20-40 per eyelid
Holocrine
Lipid meibum transported through a ductule to the orifice at the eyelid margin.
Openings on the eyelid margin form a line often referred to as the grey line.
What do the lipids in the meibum consist of?
Wax monoesters, sterol esters, triglycerides, free sterols, free fatty acids, polar lipids
How are tears distributed across the corneal surface?
Distributed by blinking and third eyelid excursions
Corneal drying prevented by ongoing tear production and blinking
What is the innervation to the lacrimal and third eyelid glands?
Parasympathetic (most important) + small amount sympathetic
Originate PSM nucleus of facial nerve in brainstem- facial nerve to petrous temporal bone to internal acoustic meatus and facial canal then to greater petrosal nerve and deep petrosal nerve to nerve of pterygoid canal synapsing at pterygopalatine ganglion (in the orbit)
Post ganglionic PSM fibres run with zygomatic nerve of trigeminal, branches off and becomes lacrimal nerve
Why anatomical factors can affect the distribution of the tear film?
Brachycephalics - lagophthalmos (incomplete blink) - central drying
Imability to blink - e.g facial nerve paralysis
TEL - abnormal shape/function
Eyelids - entropion, trichiasis, ectropion (more evaporation)
How do we measure tear production?
Schirmer Tear Test
Test strip placed lower eyelid - 1 minute
Measurement of length of wetting
What does STT-1 measure? What is the normal value.
Volume of tear lake and both basal and reflex tear production (stimulated by the strip against the conjunctiva/cornea)
Normal value = 15mm wetting/min
Values <10mm wetting/min diagnostic for KCS with consistent clinical signs
Readings between 10-15 = equivocal - repeat again periodically in these cases. ?treat if consistent clinical signs.
What does STT-2 measure?
Local anaesthetic e.g proxymetacaine already applied followed by gentle drying of lower conjunctival sac.
Only measures basal tear production (reflex abolished by local)
Readings approx half of those with STT-1
Which breeds are predisposed to KCS and should have STT performed periodically?
WHWT, Cavaliers, English/American Cocker Spaniels, English Bulldog, English Bull Terrier, Pekingese, Pug, Shih Tzu, Lhasa Apso, Samoyed, Blood hounds
When is it contraindicated/not appropriate to perform the STT?
Desmetocoele (restraint/disturbance to eye) risks rupture
Which endocrine disease have had an association with KCS also reported?
Hypothyroidism
Diabetes
Hyperadrenocorticism
How can we measure the qualitative tear film?
Tear film break up time or Rose Bengal staining
Fluorescein applied followed by enforced blinks to distribute fluorescein evenly
Eyelids then held open and corneal surface observed for signs of break up
Tests ocular mucin component (corneal wettability) and lipid layer (tear film stability and reduction of evaporation)
Normal TFBUT = 15-25 seconds
Less than this suggest tear film quality issue
Rose Bengal = stain uptake not seen in healthy corneas but present when mucus layer of tear film absent
(can be irritant on application so excess should be flushed with saline to avoid discomfort)
What is keratoconjunctivitis sicca?
Reduction in tear film production
How can we specifically test lipid production from the meibomian glands?
Meibometry - application of test strip against eyelid margin followed by placement of strip into meibometer - numerical reading of lipid level on strip.
Currently experimental only in veterinary species but done in humans
List the possible causes of KCS.
Immune mediated (majority of cases)
Congential alacrima
Congenital KCS (in conjunction with ichthysiform dermatosis on Cavaliers)
Neurogenic KCS
Secondary to metabolic diseases - hypothyroidism, diabetes, HAC
Drug induced KCS
Trauma/inflammation to lacrimal gland, orbit or innervation
Infectious - canine distemper
Chronic blepharoconjunctitis
Iatrogenic KCS (removal of TEL gland)
What are the clinical signs of KCS?
Tacky mucopurulent ocular discharge - adhered to cornea in strings
Recurrent conjunctivitis +/- corneal ulceration (if present slow to heal)
Conjunctival thickening
Corneal vascularisation (due to lack of nutrition from tear film)
Corneal pigmentation
Corneal fibrosis
Corneal keratinisation
Severe cases = blindness (pigmentation/fibrosis severe)
Non specific signs so often missed/underdiagnosed.
What type of infiltrate is seen in dogs with immunogenic KCS?
Lympho-plasmacytic infiltrate associated with acinar fibrosis and atrophy - suggests immunological basis for disease
How would you treat immunogenic KCS?
Topical ciclosporin 0.2% (optimmune) - mainstay of therapy, licensed for this indication
Lifelong treatment to suppress immune mediated attack and allow lacrimal recovery.
Treatment started earlier = more effective as less lacrimal tissue permanently damaged
Lag phase - 2-4 weeks but up to 8 weeks before improvement in tear film seen during which false tear products should be applied.
Once lacrimal tissue recovers false tears can often be withdrawn.
Ineffective: - Both off licence
Stronger concentration - 1-2% in corn oil and applied BID (can be irritant topically so some dogs will not tolerate)
Tacrolimus (0.03%) - occasional ocular irritation
(Associated with skin cancer in humans - make aware, lymphoma incidence in mice)
What type of drug are ciclosporine and tacrolimus?
Calcineurin inhibitors
Activation of T cell receptor = rise in intracellular calcium which via calmodulin activates calcineurin. Calcineurin = regulates activation and subsequent nuclear translocation of nuclear factor of activated T cells (NF-AT) which increases activity of genes coding for IL-2 and related cytokines.
Calcineurin inhibitors prevent T cell production of specific inflammatory cytokines thereby reducing immune mediated inflammation (T cell lymphocyte mediated disease) within lacrimal gland.
Suppresses lacrimal acinar and conjunctival cell apoptosis, thereby restoring more normal tear film production (quantitatively and qualitatively)
How else might ciclosporine improve tear film quality not just quantity?
Improves conjunctival mucin secretion by stimulating goblet cells - may contribute to therapeutic effect on KCS
Direct lacrimal stimulant effect also reported and mediated by increased neurotransmitter release
When might topical antibiotics be required for KCS patients?
More prone to secondary bacterial infections/conjunctivitis
May be required until tear film returned to normal.
Normal flora of conjunctiva disrupted with KCS - bacterial culture/sensitivity may be indicated.
Why can we see neurogenic KCS?
Due to way lacrimal gland innervated
Lacrimal gland = parasympathetic innervation mainly (small amount sympathetic)
Originate from parasympathetic nucleus of facial nerve within brainstem, run with facial nerve via petrous temporal bone, internal acoustic meatus and facial canal. Then join greater petrosal nerve and deep petrosal nerve (sympathetic) to form the nerve of pterygoid canal. Fibres synapse at pterygopalatine fossa in pterygopalpatine ganglion.
Post ganglionic fibres then join the zygomatic nerve (branch of trigeminal) and finally branch off as the lacrimal nerve to reach lacrimal gland.
Due to intimate contact with peripheral vestibular system and middle ear disease processes such as otitis can affect facial nerve function and therefore tear production.
Why may we see Horner’s syndrome with neurogenic KCS?
Can sometimes see Horners + KCS
Sympathetic innervation also passes in close contact to structures of inner/middle ear - disease of these structures may see Horner’s + KCS
How do patients with neurogenic KCS present?
Ipsilateral dry eye + nose (xeromycteria)
Innervation to lateral nasal gland (parasympathetic control via facial nerve) shares the same pre-ganglionic fibres proximal to the pterygopalatine fossa.
Occurs if lesion proximal to pterygopalatine fossa.
What STT reading do patients with neurogenic KCS usually have?
<5mm/wetting (often 0)
Whilst other eye often normal.
How may you work up a case of neurogenic KCS further?
Neurological examination - involvement of other cranial nerves
PE including aural examination
Diagnostic imaging if suspicious of underlying cause - (CT bony structures e.g tympanic bullae, or MRI)
What causes of neurogenic KCS are there?
Idiopathic (majority of cases)
Middle ear disease - otitis interna/media
Skull trauma
Facial nerve damage/lesion (neoplasia)
How would you treat neurogenic KCS?
Treat underlying cause if detected
(Otitis media - prolonged course antibiotic 6-8 weeks)
(Inflammation petrous temporal bone - NSAIDS)
Trauma - facial nerve damage may/may not resolve with time
Frequent application of topical tear film replacement (may need hourly to begin with!)
DO NOT RESPOND TO CICLOSPORIN/TACROLIMUS
PILOCARPINE = given orally as very irritant when applied topically and not well tolerated.
Due to denervation hypersensitivity using pilocarpine works as PARASYMPATHOMIMETIC
Oral = 1 drop 2% pilocarpine per 10kg 2-3x daily
Dose increased by 1 drop increments at each dosing until signs of systemic toxicity (hypersalivation, vomiting, diarrhoea, cardiac arrhythmia) then dose lowered to previous highest dose tolerated.
Topical pilocarpine = 0.1-0.25% in saline - may cause blepharospasm, miosis and conjunctival hyperaemia
Which drugs may induce KCS?
Pre-anaeshetic and anaesthetic agents - reduce tears for 24hrs at least (associated with duration, >2hrs = longer)
Anti-cholinergics - atropine
(Ocular lubrication for all anaesthetised patients and continued in at risk breeds e.g brachys for at least 48hrs)
Atropine (used for uveitis management) - can be prolonged
Important to measure tear production before application - may exacerbate disease e.g if ulcer due to KCS
Systemic sulphomaides (sulfasalazine, trimethoprim-sulphonamide, sulfadiazine) - acute onset KCS. T cell mediated response to proteins haptenated by oxidative sulfonamide metabolites may be responsible. Prolonged systemic use = permanent severe KCS following complete atrophy of the glands.
Etodolac (NSAID)
