Lens & Vitreous Flashcards
Describe how the lens forms embryologically.
1.Result of development of optic vesicle (outbudding of neuroectoderm) as the prosencephalon makes contact with and induces thickening of the surface ectoderm.
- Surface ectoderm develops into lens placode which then invaginates.
This invaginated surface ectoderm separates from the surface ectoderm to form the lens placode made of a hollow monolayer of cells. - Posterior cells elongate to form the primary lens fibres - obliterates the cavity and forms the lens vesicle.
- Anterior cells remain as anterior lens epithelium - anterior epithelial cells form secondary lens fibres throughout the lifetime of the animal. They also divide at the lens equator and extend anteriorally to posteriorally to form the lens cortex.
- Anterior lens capsule continues to thicken over time as it is an active basement membrane.
- The posterior capsule is a non active basement membrane and in the absence of disease remains the same thickness.
Describe the embryology of the vitreous.
Which type of vitreous remains after development?
Primary vitreous contains - hyaloid artery, mesenchymal cells, fibrillar material and macrophages.
Secondary vitreous - cellular and fibrillar material and expands further as primative hyalocytes start to function.
Tertiary vitreous - collagen fibres forming precursors to lens zonules
Primary vitreous and hyaloid artery regress leaving Cloquet’s canal - main bulk of vitreous = secondary vitreous
How does the developing lens get its blood supply? When does this usually regress?
What can be seen with incomplete regression?
Developing lens is supplied by the tunica vasculosa lentis from the hyaloid artery posteriorly and from the pupillary membrane anteriorly.
Usually regressed by 14 days post partum in the dog.
Failure/incomplete regression = persistent pupillary membranes, persistent hyaloid artery, persistent tunica vasculosa lentis or persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous.
How is the lens supported and suspended within the eye?
What structure does the lens lend support to?
Zonules - originating from ciliary body and insert in a criss-cross pattern on the lens capsule - anterior and posterior to the equator.
Further support from attachments to the anterior vitreous through the hyaloideocapsular ligament.
Anteriorly lens supports the iris which takes on its convenx contour as it crosses the lens surface.
Why does the lens have such excellent transparency?
1.Parallel orientation of adjacent fibres
2. Minimal nucleated cells (lens fibre cells lose their nuclei - proteins in lens are post-translational and there is no turnover of proteins within lens)
3. Interdigitation of cell membranes with one another.
4. Lacks blood supply/vasculature after development
Which structure in the eye is the largest avascular but mainly cellular tissue in the body?
The Lens!
Describe how the fibres within the lens are arranged.
Elongated fibres
Anterior to posterior orientation
High levels of soluble proteins (crystallins)
Meet at anterior and posterior poles along suture lines
How do the suture lines in the canine and feline lens appear anteriorly and posteriorly.
Anterior = Y shape
Posterior = inverted Y shape
What is the thickness of the lens capsule - is it thicker anteriorly or posteriorly and why? How does this thickness change with time?
Describe it’s structure.
Lens = contained within the lens capsule, basement membrane derived from anterior and posterior epithelium.
Acellular structure - transparency
Allows diffusion of nutrient and waste across it but is impervious to cellular migration.
Thickest anteriorly = 20mm at birth
Equator = 8-12mm
Posterior - 2-4mm
Anterior lens capsule thickness increases with time - 5-8mm per year - epithelial cells remain present at anterior lens capsule, active basement membane
Posterior lens capsule = epithelial cells only present during early lens development and then regress so posterior lens capsule does not thicken with age.
What is the prime refractive interface of the eye? What are the functions of the lens?
Cornea = prime refractive interface of eye NOT lens
Lens does however have higher refractive index than aqueous or vitreous so does play a role in the focusing of light upon the retina.
As ciliary muscles relax and contract (decreasing and increasing the tension on the zonules) there is some limited change in lens curvature allowing alteration in focal length to allow objects at different distances to focus upon the retina - this process is known as accommodation (not as important in domestic species as in humans!)
What is the volume of vitreous in the dog. Where does it attach and what is it’s composition?
Dogs = 1.7ml vitreous
Attachments = Vitreous base at ora ciliaris, edge of optic nerve, hyaloideocapsular ligament to lens.
Composition - 99% water (H20), collagen and hyaluronic acid, very small amount of glycoprotein (cartilage matrix)
Hyalocytes in periphery thought to produce hyaluronic acid.
How does the mature lens recieve nutrients and oxygen + remove waste?
What are the consequences if there is disruption to this system?
Lacks blood supply = transparency
Aqueous humour and to lesser extend vitreous humour deliver nutrients and remove waste.
Any disruption to normal aqueous or vitreous humour constituents and physiology may induce a change in health of the lens epithelial cells.
Any change in lens hydration, protein levels and structure, cell membrane permeability or cell metabolism can lead to precipitation of crystallins or disruption of the lens fibres in relation to one another = opacification and cataract formation.
Why do lens fibres lack the capacity for repair?
Lens fibres = lost nuclei and organelles to achieve transparency = limited ability to repair.
Protective mechanisms to counter this = high levels of anti-oxidants and UV filtering
Damage = likely to be irreversible once has lead to cataract formation.
Draw a diagram of the structure of the lens.
Diagram should include:
Anterior capsule with monolayer of epithelial cells (no cells on posterior surface)
Subcapsule
Cortex
Nucleus of lens
Equator (at periphery)
Label anterior and posterior surfaces.
What mechanisms are in place within the lens to prevent cataract formation (aggregation of crystallin proteins) via oxidation.
Alpha crystallin = major protein in the lens
No new turnover of proteins in the lens - post translational
Dual action - primary structural protein but also acts as chaperone molecule - prevents oxidative damage of molecules and even reverse protein misfolding.
Dietary anti-oxidants also have key role in preventing lens protein photo-oxidation - plant antioxidants ascorbate, tocophenol, carotenoids and flavonoids
Vital lens molecule glutathione.
Glutathione = oxidation transfer system between proteins at risk and the anti-oxidants there to save them. Glutathionine peroxidase required to keep in reduced state - produced by anterior lens epithelial cells.
This enzyme needs to be able to move through the lens so depends on lens still being in relatively fluid crystal state. (Age related cataracts - enzyme activity reduces through the very photo-oxidation was meant to prevent, increased density and aggregation of proteins slows down glutathione movement through lens)
Is the dazzle reflex usually intact with a opacity in the visual axis e.g cataract?
Yes dazzle usually intact - subcortical reflex (does not tell you about vision)
Unlikely to affect dazzle as light will usually pass through an opacity but in a very diffuse manner.
Lack of dazzle indicates issue within neurosensory retina, optic nerve, facial nucleus or facial nerve.
Do animals with cataracts usually have an intact PLR?
Yes generally will still have intact PLR - subcortical reflex (does not assess vision)
PLR sometimes slower but should be present
Absent PLR= pathology with neurosensory retina, optic nerve or oculomotor nucleus and nerve.
What components make up the visual axis? How does this differ from the visual field?
Visual Axis:
Air
Tear Film
Cornea
Aqueous Humour
Lens
Vitreous Humour
Neurosensory Retina
Visual axis = anything light has to pass through to reach the retina
Visual field = area visible from an eye
In an eye with no opacities of the visual axis the visual field is formed by the position of the globe within the orbit, the orbital rim, the eyelids, size of the cornea and pupil and size of the neurosensory retina.
Assessment of relevance of any opacities should be made in light of their effect on the visual field.
Small corneal opacity will have less effect than opacity of the same size on the lens.
How should we examine and assess the lens?
How can parallax help us determine the location of an opacity?
Dilation of pupil - 1% tropicamide and wait 30 mins (unless suspicion of glaucoma or lens instability)
Distant direct ophthalmoscopy - tapetal reflection able to identify and opacities within the visual axis - appear as dark shadows against the tapetal reflection.
Location can be obtained using PARALLAX - observer moves to right any opacities anterior to centre of the lens move to the left whilst opacities that are posterior to the lens appear to move to the right with the observer. (Converse is true if the eye moves and observer stays still)
Opacity at centre of lens (nucleus) appears stationary as either the observer or eye moves.
Just because opacities appear to move does not immediately mean within lens (just within visual axis as they could also be in the cornea, anterior chamber or vitreous)
Close Direct ophthalmoscopy - examine lens with more magnification than naked eye
+12 = anterior lens capsule
+8 = posterior lens capsule (after adjustment for observers vision - refractive error)
Slit lamp biomicroscopy - allows observer to see magnified binocular image of lens.
Obliquely directed slit beam allows identification of location of lesions with more accuracy than any other technique as well as allowing assessment of the position of the lens within the eye.
Great for depth assessment of cataracts.
When is ultrasound useful when dealing with lens opacities?
What abnormalities of the lens can be identified on ultrasound?
Useful when there is opacification or any abnormality of structures anterior to the lens or opacification of the lens itself
Central anterior and posterior capsules readily viewed as hyperechoic lines because these acoustic interfaces lie perpendicular to the ultrasound beam.
Abnormalities = cataracts, lens capsule rupture, lens luxation/subluxation, persistent tunica vasculosa lentis/hyaloid artery, lentiglobus or lenticonus and posterior synechiae.
Why can microphthalmia occur? What other abnormalities is it associated with?
Microphthalmia = due to failure to develop full sized lens placode and poor presentation of the optic vesicle.
Can also be due to reduced intraocular pressure due to failure of optic fissure to close on schedule.
Abnormalities that may be seen with microphthalmia include - microphakia, cataracts, anterior segment dysgenesis,
What is a lens coloboma - why can they occur?
Lens coloboma = absence of part of lens
Occurs due to lack of development of zonules in region apposing affected area (not a true coloboma - lack of zonules = poor lens growth adjacent the area of zonule deficiency)
What is a persistent pupillary membrane and how may they present on the lens? What would be a differential for them on the lens?
Failure of the pupillary membranes during development to regress
In some cases of PPM the membrane remains attached to the lens capsule leading to focal opacification of the capsule and occasionally the subcapsular region.
DDx - posterior synechiae - differentiate as PPM’s originate from iris collarette rather than pupil margin.
Another type of mesenchymal remnant can be seen in the form of pigment spots on anterior lens capsule (English Cockers over-represented) - not associated with cataract formation, one or both eyes can be affected.
DDx for this pathology would be iris rests (deposits on lens capsule resulting from prior adhesion of the darkly pigmented surface of the posterior iris) - generally mesenchymal remnants lighter, flat in profile and axial.
What breed is predisposed to congenital cataracts and how do they present?
Miniature Schnauzers
Autosomal recessive inherited condition
Bilateral and usually symmetrical and primarily involve lens nucleus although can extend into the cortex.
May be associated with posterior lenticonus and/or microphakia.
How else may congenital cataracts occur if not inherited like in the Miniature Schnauzer?
What other abnormalities can congenital cataracts be associated with? And what is MOD and which breeds predisposed to this?
Congenital cataracts = present at birth
Other forms of congenital but non inherited cataract are recognised sporadically and thought to result due to in utero insults.
Other ocular abnormalities associated with them include - microphakia, PPM’s, persistent hyperplastic tunica vasculosa, persistent hyperplastic primary vitreous, retinal dysplasia, microphthalmia, oscillating type of nystagmus.
Above abnormalities may all be included in suspected hereditary complex of multiple ocular defects (MOD)
Breed predisposed to MOD - Cavaliers, Golden Retriever, Cocker Spaniel, Old English Sheepdog, West Highland White Terrier.
What is persistent hyperplastic primary vitreous/persistent hyperplastic tunica vasculosa?
PHPV & PHTVL - usually see both together. Can occasionally get PHTVL by itself but uncommon - fine filamentous web or punctate/pigmented opacities on posterior lens capsule. May be unilateral or bilateral.
Aetiology - Hyaloid system and tunica vasculosa lentis become hyperplastic during early embryological development and continue to proliferate following birth. (Dysplasia rather than failure of regression)
Degree of visual impairment depends on degree of proliferation of the hyaloid system and presence of complications e.g cataract formation and haemorrhage.
Clinical lesions vary:
Fine pigment spots on posterior lens capsule
Fibrovascular plaques involving posterior lens capsule
Accompanied by - lentigoblus, lenticonus or coloboma, cataracts, intralenticular haemorrhage, persistent hyaloid artery, persistent pupillary membranes and capsulo-pupillary vessels (pigmented strands or patent vessels originating from retrolental plaque and insert on anterior surface of the lens)
How is PHTVL/PHPV graded and which breeds are predisposed?
Bilateral inherited trait reported in the Dobermann, Staffordshire Bull Terrier, Miniature Schnauzer but can also be seen sporadically in other breeds and can be seen unilaterally.
Graded 1 to 6 depending on severity.
Grade 1 = minor posterior capsular cataract and retrolental dots
Grade 2= more intense central posterior capsular cataract with yellow/brown retrolental fibrous tissue and pigment dots. PPM also often seen.
Grade 3 = persistent tunica vasculosa lentis - hyaloid system visible with retrolental meshwork and abnormalities as for grade 2
Grade 4 = lenticonus and abnormalities as for grade 3
Grade 5 = combination of grade 3 and 4 abnormalities
Grade 6 = combination of former grades associated with lens coloboma, microphakia and accumulations of blood and pigment.
How can PHPV/PHTVL be prevented/when is treatment indicated?
Selective breeding to prevent as inherited condition in certain breeds (e.g excluding grade 2-6 from breeding programmes)
Can progress in some breeds (Dobermann) and lead to progressive cataracts and blindness - less likely to do this in the SBT.
When vision severely impaired but morphology and function of retina ok then phacoemulsification with posterior capsulectomy and anterior vitrectomy can be considered - however risks associated with vitrectomy mean much less success than with uncomplicated cataract surgery + potential for haemorrhage from persistent hyaloid artery.
Describe a persistent hyaloid artery - why do they occur? What differential would you consider?
Occurs due to failure of the hyaloid vascular system to regress normally.
Relatively uncommon and sporadic.
Clinical signs vary in accordance with the part of the hyaloid artery structure that has remained.
Most common = small vascular remnant on the posterior lens capsule but the opacity is rarely progressive.
Remnant does not usually carry blood but a persistent hyaloid artery may remain in rare cases and be patent - haemorrhage from this vessel into the lens or vitreous may occur.
Differential = PHPV/PHTVL
What is aphakia/microphakia?
Aphakia = complete absence of the lens
Microphakia = small lens (may be a feature of multiple congenital ocular abnormalities or as part of the PHVTL/PHPV complex
Lens appears small within the pupil and may have an aphakic cresent similar to that seen with lens subluxation - however there is little evidence of lens instabilty and the zonules appear normal in numbers but stretched to cover the extra distance between the lens and ciliary body.
What is Peter’s Anomaly and anterior segment dysgenesis?
Incomplete separation of the lens placode from the surface ectoderm may leave the lens confluent with the cornea.
Cornea and lens are usually opacified at this location.
Extremely rare for this condition to occur
List the congenital conditions that can occur with the lens and vitreous?
Congenital cataracts (inherited vs MOD vs in utero insult)
Microphakia/Aphakia
Lenticonus/Lentiglobus
Lens Coloboma
Persistent pupillary membrane
Peter’s Anomaly
Persistent hyaloid artery
Persistent tunica vasculosa lentis/persistent hyperplastic primary vitreous
What is the definition of a cataract?
Cataract = any opacity of the lens or its capsule
What are the 4 criteria that are usually used to classify cataracts?
Age of onset - congenital, juvenile, senile
Aetiology - Primary (e.g hereditary or senile cataracts) vs Secondary (other intraocular disease, electrocution, radiation, trauma, metabolic disease etc)
Extent - Incipient vs Immature vs Mature vs Hypermature
Position - Capsular, Subscapsular, Nuclear, Cortical, (within or outside the visual axis)
Classification important for looking at potential for progression.
Why are cataracts important to classify and examine?
Can be sight threatening, painful and sometimes indicator of other disease.
What is the difference between a congenital, juvenile and senile cataract?
Congenital = cataract at birth
Juvenile = develops early on in animals life
Senile = first seen in middle aged to older animals (no defined cut off between juvenile and senile)
What are hereditary cataracts?
Cataracts where there is genetic basis - clinical features and morphological changes vary breed to breed.
Which gene has a mutation that can cause hereditary cataracts and which breeds does this mutation affect?
Heat Shock Factor 4
Boston Terrier (also suffers from secondary type of hereditary cataract as well), French Bulldog, Staffordshire Bull Terrier
Autosomal recessive - early onset and progressive cataracts - posterior suture lines
Base pair deletion for HSF4 in the Australian Shepherd - dominant with incomplete penetrance hereditary cataracts - posterior cortical or subcapsular.
What type of cataract is seen in working breeds? List the breeds affected. What is it’s mode of inheritance?
Belgian Shepherd, Golden Retriever, Labrador Retriever, Irish Setter, Giant Schnauzer, Large Munsterlander, Leonburger, Chesapeake Bay Retriever, Siberian Husky.
Triangular or propellar shaped posterior polar subscapsular with occasional progression to extensive and generalised cortical cataract
(Progression of disease more likely in the Husky - other breed seldom progresses to have significant effect on vision)
Unknown mode of inheritance
Describe senile cataracts.
Age of onset not well defined but do show typical changes in middle aged to older dogs.
Type of primary cataract aetiology.
Generally nuclear - opacification of nucleus alongside nuclear sclerosis and/or wedge shaped or diffuse cortical cataract formation in early stages.
Slowly progressive type of cataract - vision loss after months to years
What disease are the majority of metabolic cataracts associated with in dogs?
How do cataracts occur with this disease?
Diabetes mellitus
Main pathway for glucose metabolism in lens = anaerobic glycolysis, rate of which is determined by enzyme hexokinase. Once the glucose levels become too high relative to the levels of hexokinase an alternative pathway of glucose metabolism is invoked using the enzyme ALDOSE REDUCTASE.
Glucose metabolised by aldose reductase and produces SORBITOL
Increases the OSMOTIC POTENTIAL of the lens attracting in water and causing COAGULATION OF LENS PROTEINS.
Typically lenses of diabetic patients develop water clefts due to the increase in lens volume INTUMESCENCE that occurs as fluid enters the lens capsule.
Where does water clefting typically occur in the lens of a diabetic patient and why?
Clefting (entrance of water into lens and increase in lens volume) tends to occur along suture lines of the lens because these are the weakest point of the lens.
What can be used to reduce or delay the onset of cataract formation in diabetic patients?
Does this work to reduce already formed cataracts?
Alpha Lipoic Acid - aldose reductase inhibitor
Once cataract has formed however cannot be reduced medically.
What other metabolic disease apart from diabetes mellitus can lead to cataract formation?
Hypocalcaemia
What other ocular consequences can be seen secondary to diabetic cataracts?
Phacolytic and Phacoclastic uveitis - risk of then developing secondary glaucoma.
Why do you not see diabetic cataracts very commonly in cats?
Cats - by age of 5 diminished amount of aldose reductase therefore less use of this alternative glucose pathways to convert glucose to sorbitol.
How can nutritional cataracts occur? Where do they typically present in the lens?
Perinuclear cataracts
Reported in puppies fed on certain types of milk replacer
May be partially reversible cataracts.
Diets deficient in certain proteins and vitamins may also lead to some cataract formation.
How can traumatic cataracts occur? What are the two types of trauma and are there any other consequences for the lens?
How should the lens be assessed after truama?
Blunt trauma - vibration injury to the lens material or lens instability due to damage to the lens zonules. In very severe blunt trauma, compressive forces can lead to rupture of the globe leading to expulsion of the entire lens.
Penetrating trauma - claws, thorns, teeth, foreign bodies etc.
Teeth - tend to have compressive force as well and so injury that occurs to the lens is more severe and vision threatening.
Thorns/claws may appear to only cause minor injuries to the outer structures of the eye but can have devastating impact on lens.
All animals presenting with corneal injuries should have the lens also assessed in case the lens capsule has been compromised.
Pupil dilation essential to assess lens properly after injury (so long as no lens instability noted) as the insult may have occurred at the periphery of the lens even with central corneal injuries.
What is the difference between a penetrating and non penetrating lens injury?
Penetrating corneal injury may cause either penetrating or non penetrating lens injury.
Penetrating = rupture of lens capsule
Non penetrating = lens capsule remains intact but there may be focal or complete cataract development due to disruption of the anterior lens capsule epithelial cells.
