Uveal Tract & Glaucoma Flashcards
What are the 3 layers of the uveal tract?
Iris, Ciliary Body, Choroid
Which structures make up the anterior uvea?
Iris + Ciliary Body
What structure is also known as the posterior uvea?
Choroid
What are the functions of the 3 structures of the uvea?
Iris = regulation of light entering the eye (sphincter and dilator musculature)
Ciliary body = production of aqueous humour to maintain IOP, facilitates lens accommodation and aqueous humour drainage through the iridocorneal angle.
Choroid = thin vascular tunic lining the inner aspect of the globe, rich blood supply - ensures optimal nutrition and oxygenation to the outer retina.
Immunosensitive making it a common site for inflammatory response in the eye.
Describe the embryological steps that occur to form the uveal tract.
Day 19 post fertilisation
1. Optic cup invaginates creating bilayered medullary epithelium
2. Innermost (vitreal side) differentiates into the inner pigmented epithelium of the iris and non pigmented ciliary body and neurosensory retina
3. Outermost (scleral side) - outer pigment epithelium of iris (dilator and sphincter muscles), pigmented epithelium of ciliary body and the retinal pigment epithelium (RPE)
4. Closure of optic cup occurs via fusion of optic fissure allowing IOP to be established (optic fissure lies in 6 o clock positon - failure of fissure to close = colobomas affecting iris, choroid and optic nerve)
What is the difference between a typical coloboma and an atypical coloboma?
Typical coloboma = failure of optic fissure to close during development at 6 o clock position
Atypical coloboma = occur away from 6 o clock position and occur through different mechanism.
Which uveal structures develop from the neural ectoderm?
Posterior iris epithelium
Bilayered ciliary epithelium
Which uveal structures develop from the neural crest?
Stroma of iris, ciliary body and choroid
Ciliary muscles
Which uveal structure develops from the mesoderm?
Vascular endothelium
How can developmental abnormalities of the uvea be divided?
Incomplete development - e.g colobomas
Maldevelopment - e.g anterior segment dysgenesis
Incomplete regression - e.g persistent pupillary membranes
What is Collie Eye Anomaly typically associated with? What do the DNA tests for this condition check for and why is litter screening still important for these at risk breeds.
Choroidal hypoplasia (always bilateral)
Coloboma of optic nerve (can be unilateral)
DNA test = only detects choroidal hypoplasia - can be negative and still have coloboma of optic nerve
Litter screening 6-7 weeks old
(later than this can appear to ‘go normal’ = choroidal hypoplasia harder to see as tapetal reflection develops at 11-12 weeks.
A lot of dogs do not have both coloboma and choroidal hypoplasia
Mild = no visual deficit
Coloboma = risk of retinal detachment/glaucoma
What types of persistent pupillary membranes can be seen and how are they differentiated from anterior synechiae?
Iris to Iris
Iris to lens
Iris to cornea
Remnants = speckles
PPM’s always originate from iris collarette
How is the iris divided in terms of anatomy?
Peripheral ciliary zone
Central pupillary zone
Iris collarette = transition between the two zones and the origin of pupillary membrane remnants.
How does the peripheral iris attach to the sclera?
Peripheral iris attaches to sclera at region of limbus via pectinate fibres comprising the pectinate ligament.
(Important in glaucoma = pectinate ligament issues = goniodysgenesis)
What makes up the majority of the iris and how does this differ between the anterior and posterior iris?
Why is this anatomy clinically important?
Majority of iris = stroma, no epithelium to its surface
Modified stromal border forms anterior aspect.
Clinically important - pre-iridial fibrovascular proliferation (PIFM) formation and chronic intraocular disease (described clinically as rubeosis iridis)
New vessels and fibroblasts of fibrovascular membrane do not have to penetrate an epithelium as would be required at other intraocular sites of fibrovascular proliferation.
PIFM’s = major cause of reduced AH drainage and secondary glaucoma in dogs/cats
Posterior aspect lined by pigmented bi-layered epithelium that is continuous with pigmented/non pigmented bi-layered epithelium of ciliary body.
Where does the dilator muscle of the iris originate?
Dilator = anterior epithelial layer of bilayered posterior epithelium of iris
Is actually a myoepithelium and acts as the dilator.
Where does the sphincter muscle of the iris originate? How does the arrangement of this muscle vary between dogs and cats?
Stroma close to the pupillary margin - smooth muscle fibres of iris sphincter.
Dogs = circular arrangement
Cats = longitudinal arrangement
How is blood supplied to the iris and how is blood drained from iris?
Blood supply = long posterior ciliary arteries which lead to major arterial circle (3 and 9 o clock positions)
Drainage = anterior choroidal circulation
How are the iris sphincter and dilator muscles innervated?
Sympathetic = pupillary dilation via iris dilator muscle (first, second and third order neurons)
Parasympathetic = pupillary constriction via iris sphincter muscle (oculomotor - CN III)
Describe the anatomy of the ciliary body.
Continuation of posterior aspect of iris
Triangular shape in cross section
Smooth muscle (parasympathetically controlled), connective tissue, blood vessels and nerves
Also makes up uveal part of iridocorneal drainage angle in the form of the uveal trabecular meshwork posterior to the pectinate ligament within the ciliary cleft.
Inner aspect (vitreal side) - lined by inner non pigmented and outer pigmented epithelium
Inner surface divided into pars plicata anteriorally, pars plana posteriorally
What is found on the pars plicata of the ciliary body?
Heavily folded surface - ciliary proccesses
Flatten out posteriorly at junction with pars plana.
Lens zonular fibres originate from tips and valleys of the ciliary processes and insert adjacent to lens equator therefore suspending the lens caudal to the iris and pupil.
Describe the blood supply to the ciliary body.
Supply = major arterial circle of the iris
Drainage = anterior choroidal vessels to the vortex veins
What are the 3 processes which are required for the production of aqueous humour in the ciliary body? Where do they take place?
- Diffusion
- Ultrafiltration
- Active secretion
Take place at the level of the non pigmented epithelium
What is the main conventional outflow drainage path for aqueous humour?
Conventional outflow = via iridocorneal angle and uveal trabecular meshwork
What percentage of aqueous humour outflow is via the non conventional (uveoscleral route) in dogs and cats?
Dogs - 15%
Cats - 3%
How may contraction of the smooth musculature of the ciliary body lead to increased AH outflow via the conventional pathway?
Contraction - provides accommodation by moving lens forwards and increasing lens curvature
(This is very limited in dogs and cats however)
How is the choroid subdivided into layers? List them in order from outside to inside.
- Suprachoroideae
- Large vessel layer
- Medium vessel layer
- Choriocapillaris
- Bruch’s membrane
Where does the choroid extend to and from and what is it sandwiched between?
From ora ciliaris retinae to optic nerve head
Sandwiched between retinal pigmented epithelium (inner) and sclera (outer)
How is blood supplied to and from the choroid?
Short and long posterior ciliary arteries
Venous drainage = via vortex veins
What is the aim of the blood-ocular barrier?
Ensure retinal nutrition whilst minimising entry of substances into the eye which may interfere with transparency of the ocular media.
Contributes to ocular immune privilege
How is the blood-ocular barrier subdivided?
Blood - aqueous barrier
Blood - retinal barrier
What comprises the blood-aqueous barrier?
Tight junctions in non pigmented ciliary body epithelium + pigmented posterior iris epithelium and non fenestrated blood vessels of the iris.
Due to high surface area of ciliary processes the non pigmented epithelium of the ciliary body plays a major role in this barrier.
What comprises the blood-retinal barrier? What can be used to test the integrity of this barrier?
Tight junctions in the retinal pigment epithelium
Fluorescein angiography can be used to test integrity.
What other elements are there to immune privilege of the eye?
- Blood-ocular barrier - subdivided into blood-aqueous and blood-retinal barriers
- Aqueous humour composition - ascorbic acid and other antioxidants
- Anterior chamber associated immune deviation (ACAID) - spleen associated, antigen detected in eye - activated antigen presenting cells migrate to marginal zone of spleen. Production of antigen specific T regulatory lymphocytes that return to eye and reduce delayed type hypersensitivity.
- Lack of intrinsic lymphatic system
What occurs when ocular immune privilege systems fail or become overwhelmed?
UVEITIS!
Ocular immune privilege systems overwhelmed or fail = breakdown of blood-ocular barrier and clinical signs of uveitis
What are the 3 basic events that comprise inflammation of the uvea?
- Increased blood supply
- Augmented vascular permeability
- White blood cell migration
What the developmental abnormalities of anterior uveal tissue seen in dogs?
Heterochorma iridis
Subalbinism
Merle ocular dysgenesis
Persistent Pupillary Membranes
Aniridia/iris hypoplasia/coloboma
Anterior segment dysgenesis
What acquired conditions can be seen in the anterior uveal tissue of dogs?
Iris atrophy
Iris melanosis
Iridociliary cysts
Uveitis
Intraocular haemorrhage
Ocular melanosis
Neoplasia
What is heterochroma iridis?
Normal variation whereby there are different colours within the same iris or two irides.
May occur as manifestation of colour dilution in some breeds e.g Husky or may be associated with colour dilution genes such as Merle and be accompanied by multiple ocular defects (Merle ocular dysgenesis)
Distinguish from acquired colour changes due to uveitis or neoplasia.
What is subalbinism?
Another variation of normal - dilution of ocular pigmentation
Blue iris and red fundus reflex
Non pigmented fundus with visualisation of the choroidal vessels
Separate to complete albinism which is not reported in dogs and cats which the eye lacks all pigment.
Describe Merle Ocular Dysgenesis. Which breeds are predisposed?
Breeds = Australian Shepherd, Great Dane, Old English Sheepdog, Rough and Smooth Collies
Multiple ocular abnormalities associated with the Merle gene
Individuals carrying two copies of the dominant gene (homozygotes) = most severe ocular abnormalities and an excessively white coat.
Uveal abnormalities - heterochromia iridis, iris hypoplasia, PPM’s, corectopia (non central pupil), dyscoria (misshapen pupil), black rimmed pupil (from prominent iridial pigmented epithelium), iris coloboma, choroidal coloboma, choroidal hypoplasia, equatorial staphyloma (protrusion of uvea through scleral defect)
Non uveal abnormalities - microphthalmos, cataract, scleral ectasia (scleral defect), retinal dysplasia and retinal detachment.
Varying degrees of deafness also associated with this condition.
What is aniridia/iris hypoplasia/iris coloboma?
Aniridia = born without an iris (very rare)
Hypoplasia - can be partial (focal thinning of iris) or total (full thickness coloboma)
Typical iris coloboma = 6 o clock position
Atypical = positioned elsewhere
What does pseudopolycoria describe?
Term used where appears there are additional pupils due to iris coloboma (full thickness)
What may occur is cases of iris coloboma where this extends to the ciliary body?
Adjacent lens periphery is abnormally shaped due to lack of zonular fibres - incorrectly referred to as lens coloboma.
What is the role of the pupillary membranes during ocular development. How do PPM’s occur and present?
Anterior tunica vasculosa lentis and pupillary membrane provide nutrition to the developing lens and anterior chamber in utero.
Should start to regress pre-partum and have fully regressed by 6 weeks post partum.
Incomplete regression = persistent pupillary membrane
Typical PPM’s = strands of iris tissue ORIGINATING FROM IRIS COLLARETTE can insert on:
Iris
Lens
Corneal endothelium
(Free floating PPM’s can also occur)
Clinically insignificant - remnants, iris to iris and free floating
Iris to cornea - focal corneal oedema (progressive = topical hyperosmotic ointments may be beneficial)
Iris to lens - cataract
What is anterior segment dysgenesis?
Malformation of the anterior segment and usually associated with microphthalmos
Faulty separation = corneal, iris, lens and iridocorneal drainage angle abnormalities e.g iris sheet of tissue adherent to cornea, shallow anterior chamber, cornea to lens contact, lens malformations, cataract and glaucoma.
What is Peter’s Anomaly?
Iris to Cornea PPM is present in combination with defect in posterior corneal stroma, descemet’s membrane and endothelium
Which main differentials should be considered when you observe iris to cornea PPM’s, Peter’s Anomaly or anterior segment dysgenesis?
Which differential should you consider for iris to iris PPM?
Which differential should you consider for PPM remnants?
How can you differentiate these conditions?
Iris to cornea PPM ddx =Previous penetrating corneal trauma.
Anterior synchiae associated with prior corneal trauma - span pupil margin towards a full thickness corneal scar (dyscoria)
Iris to lens PPM = ddx posterior synechiae
Posterior synechiae originate on pupillary margin/posterior iris surface only
PPM remnants = ddx iris rest
Iris rest (post inflammation) = peripheral and always black in colour
PPM remnant = light brown and central position
What is iris atrophy? How does it appear and which reflex may be affected.
Most commonly result of aging in dogs
Thinning of the iris - often diffuse but can be localised
Any breed can be affected
Pupils may appear dyscoric, dilated and have reduced PLR’s.
Photophobia can present in severe cases.
Can occur asymmetrically resulting in anisocoria.
Secondary iris atrophy can occur following trauma, chronic uveitis or glaucoma.
What is iris melanosis - what differentials would you consider?
Iris melanosis = focal iridial hyperpigmentation that is of no clinical significance
Flat and not raised lesions
Do not progress or change over time.
Main ddx - anterior uveal melanoma and ocular melanosis
What are iridociliary cysts and where do they originate from? What treatment options are there?
Can be congenital or acquired
Arise from posterior pigmented epithelium of iris or from inner non pigmented ciliary body epithelium
Generally benign
Occasionally can interfere with AH outflow or adhere to lens/cornea causing opacification.
If causing obsruction/opacification tx = deflation of cysts via FNA or irrigation/aspiration or laser ablation
(specialist)
How can you differentiate an iridociliary cyst from an iridociliary tumour?
Transillumination is required
Bright light source will transilluminate cysts with the aid of the tapetal reflex.
Transparent = cyst
Opaque = mass
Define anterior vs posterior uveitis vs panuveitis.
Uveitis = inflammation of the uveal tissue
Anterior uveitis = inflammation of the iris/ciliary body
Posterior uveitis = inflammation of the choroid
Panuveitis = inflammation of all 3 portions of the uvea
What are the clinical signs seen with uveitis. Divide them into specific to uveitis and non specific to uveitis.
Specific:
Photophobia
Aqueous flare (pathognomonic for uveitis) ‘Tyndall effect’
Anterior chamber cells
Anterior chamber fibrin (often cats)
Keratic precipitates
Hyphaema (other ddx - coagulopathies, systemic hypertension, trauma, A.vasorum)
Hypopyon
Iris swelling
Rubeosis iridis
Iris nodules (other ddx iris neoplasia)
Miosis (other ddx - Horners)
Reduced IOP
Non specific:
Corneal oedema
Blepharospasm
Epiphora
Conjunctival and episceral hyperaemia
Chemosis
Ciliary flush
Pain
Decreased vision
List the possible sequelae to uveitis.
Persistent corneal oedema +/- bullous keratopathy
Posterior synechiae (iris to lens)
Dyscoria/restricted pupil movement
Peripheral anterior synechiae
Pigment on anterior lens capsule
Pre-iridial fibrovascular membranes (PIFMS)
Ectropion uveae - PIFM contract and pull pupil outwards
Iris bombe - synechiae all way around, trapped fluid from ciliary body - bulging of iris forwards and secondary glaucoma
Glaucoma
Iris atrophy
Iris cyst formation
Cataracts
Lens luxations - breakdown of zonules
Vitreal degeneration
Retinal detachment
Phthisis bulbi - end stage eye, often glaucoma before, ciliary body stops producing AH and eye shrinks
Blindness
List the possible causes of uveitis in dogs.
- Traumatic - blunt vs penetrating
- Immune mediated - cataract (phacolytic), lens capsule rupture (phacoclastic), uveodermatological syndrome
- Metabolic - hyperlipidaemia
- Infectious
- Viral = Canine adenovirus ‘blue eye’
- Rickettsial = Ehrlichia canis, Rickettsia rickettsii
- Bacterial = bacteraemia (pyometra), Borrelia burgdorfei (Lyme’s disease), Brucella canis, Leptospira
- Protazoal - Toxoplasma, Neospora, Leishmania
- Fungal - Cryptococcus, Aspergillus, Blastomyces, Coccidiodes, Histoplasma
- Parasitic - ocular larval migrans (toxocara), ocular filariasisis (angiostrongylus vasorum), ophthalmyaiasis interna (Diptera spp), Onchocerca spp
- Algal - Prototheca spp - Neoplastic
Primary intraocular - melanoma, iridociliary adenoma/adenocarcinoma
Multicentric - lymphoma, histiocytic neoplasia
Metastatic
Paraneoplastic- hyperviscosity syndrome - Miscellaneous
Idiopathic
Breed Related = Golden Retriever Pigmentary uveitis
Ulcerative keratitis (any cause)
Drug induced (Prostaglandin analogues)
Describe the typical steps in work up of a canine case of uveitis.
- Clinical history - known trauma, travel hx, concurrent diseases, neutering status, general health, parasite control.
- Complete PE to assess patient systemically - e.g evidence of pyrexia, neoplasia (generalised lymphadenopathy), pyometra (discharge) etc
- Complete ophthalmic examination
- Initial work up:
Haematology/biochem/urinalysis +/- culture if in house analysis suggestive of UTI
Infectious disease screening - Ehrlichia/Borrelia PCR testing, +- Leishmania PCR if travel hx, serology for Toxoplasma/Neospora)
If history/PE suspicious for concurrent systemic disease may also perform
- Diagnostic imaging - chest radiography/CT
Abdominal ultrasound
+/- FNA of any abnormal tissues or biopsy
Systemic blood pressure measurement (in cases of intraocular haemorrhage)
Faecal analysis - specifically looking for angiostrongylus vasorum (direct examination)
Aqueocentesis and cytology and not without risk - exception being where strong evidence of lymphoma
Diagnostic enucleation and histopath - reserved for irreversibly blind and painful eyes.
When is further more widespread investigation warranted in cases of uveitis?
Bilateral uveitis - especially if presenting with acute, synmmetrical onset of disease
Abnormal PE suggestive of systemic disease
Posterior uveitis
Hyphaema
Severe uveitis - especially before considering immunosuppressives
In the UK are dogs or cats more likely to have infectious causes of uveitis?
Cats = mostly infectious
Infectious causes less common in dogs by comparison.
What are the two types of trauma? How does their prognosis compare and how can they present?
- Blunt trauma = poor prognosis generally for both vision and comfortable eye.
Globe rupture possible - usually equator or posterior pole
Signs of rupture = globe collapse, very low IOP, chemosis, hyphaema and subconjunctival haemorrhage. Ocular ultrasound can help confirm and may also reveal retinal detachment, cyclodialysis (separation of iris and ciliary body from sclera), lens luxation, hyperechoic opacities in posterior segment and ill defined scleral borders.
Absence of dazzle = poor prognostic indicator
Enucleation often tx of choice in severely traumatised, blind eyes.
- Penetrating trauma
All should be treated with topical and systemic AB’s - endophthalmitis = possible sequelae
Uncomplicated punctures - small punctures will self seal and require symptomatic medical therapy in form of topical antibiotics, mydriatics and anti-inflammatories + systemic antibiotics and anti-inflammatories.
Careful assessment of lens capsule integrity important following mydriasis.
Penetrating trauma with lens injury - phacoclastic uveitis complicatiom. >2mm injuries = early lens removal via phacoemulsification
Small capsular tears <2mm may self seal and can oftne resolve following prompt medical tx.
Lens involved = risk of septic implantation syndrome - impregnation of bacteria into lens which then acts as growth medium - endophthalmitis
Can have delayed onset for septic implantation syndrome = 10 days to 1 year reported.
Cats = also risk of post traumatic sarcoma development following lens injury and ocular trauma.
Penetrating wounds with iris prolapse
Larger perforations iris may be pushed forwards into defect and may temporarily seal
Acute cases <24hrs - reposition iris and globe repair should be performed
Chronic wounds = increased risk of infection and suppurative endophthalmitis
Ocular foreign bodies
DO not grasp with forceps - can push further into cornea/anterior chamber
Perpendicular removal with foreign body spuds/needles
Iatrogenic globe perforation - maxillary tooth removal, often associated with retinal detachment and endophthalmitis. Poor prognosis.
What is septic implantation syndrome?
Bacteria implanted directly into lens during full thickness corneal perforation (often cat claw injuries)
May initially respond well to medical therapy however following period of latency (often months) a severe secondary endophthalmitis develops and the globe then requires enucleation.
What are the 2 main types of lens induced uveitis? Why do they occur?
Likely that in the normal lens small amounts of lens protein (which is weakly antigenic) escape and induce T cell tolerance. This tolerance is overwhelmed when the immune system exposure to crystallins is increased by cataract formation, lens trauma or lens capsular rupture leading to uveitis.
- Phacolytic uveitis = lens capsule intact
All stages of canine cataract = some form of subclinical uveitis
Rapidly progressive cataracts e.g diabetic cataracts often display severe secondary uveitis and prompt medical tx (topical and systemic anti-inflammatories) + phacoemulsification is vital
Failure to do so = lens capsular rupture, retinal detachment and secondary glaucoma preventing from being candidate for cataract surgery. - Phacoclastic uvieits = ruptured lens capsule
Either due to trauma or spontaneous rupture (rapidly progressive cataract)
Large amounts of lens capsule material overwhelms T cell tolerance leading to severe uveitis.
Early referral for phacoemulsification is essential in cases of lens capsule rupture.
Describe uveodermatological syndrome - how is it treated and which breeds are predisposed?
Immune mediated condition - destruction of melanocytes in eyes and skin
Vision and globe threatening
Akitas, Huskies and other larger breeds predisposed
Ocular signs = severe panuveitis, retinal detachment, glaucoma
Skin and hair depigmentation around face and genitals but can be more diffuse.
Crusting around mucocutaneous junctions
Diagnosis - signalment, clinical signs, skin biopsy (histopath = granulomatous inflammation around pigmented cells)
Tx = aggressive immunosuppressives
Oral prednisolone + azathioprine or ciclosporin
Topical tx - frequent corticosteroids +/- anti glaucoma treatment
Prognosis for vision/globe = poor
Often develop secondary refractory glaucoma
Lifelong treatment always required.
How may hyperlipidaemia lead to uveitis in dogs? Which breed is predisposed? What can be seen as a rare complication?
Lipid influx into anterior chamber - lipid-laden AH when there is a breakdown of the blood-aqueous barrier (anterior uveitis) and concurrent hyperlipidemia.
Systemic work up required to identify and treat cause of hyperlipidaemia.
Minature Schnauzers = occurs more commonly alongside idiopathic uveitis
Rare complication of hyperlipidaemia = intraocular tumour - Xanthogranulomas (Miniature Schnauzers that suffered from diabetes and hyperlipidemia)
