The Fundus Flashcards
What are the 3 main layers which make up the fundus?
- Sclera (fibrous tunic - part of the uvea)
- Choroid with choroidal vasculature and pigmentation and the tapetum lucidum
- Retina with retinal pigment epithelium and translucent neurosensory layer and retinal vasculature.
What is the role of the sclera in the fundus?
Outmost layer of the fundus = provides structural support and protection to the inner eye components.
What is the role of the choroid in the fundus?
Choroid lies beneath the sclera - highly vascularised and responsible for supplying oxygen and nutrients to outer layers of the retina.
Also acts as a cooling system dissipating heat produced by light absorption.
What is the role of the tapetum lucidum?
Tapetum lucidium = present within the choroid
Enhances night vision by reflecting light back through the retina that has already passed through the retina once.
What is the innermost layer of the fundus and how is it divided?
Innermost = retina
Split into retinal pigment epithelium and neurosensory cells (including photoreceptors) - capture and process visual information before sending it to the brain via the optic nerve.
Describe the embryology of the retina - where is it derived from? When does the RPE and Neurosensory Retina develop?
Retina derives from posterior portion of optic cup
Differentiates from 2 layers of neuroectoderm origin
Outer layer = retinal pigment epithelium (fully developed day 25 gestation)
Inner layer = neurosensory retina (fully developed day 33)
Sub retinal space between these 2 layers is a potential gap and represents the location of most types of retinal detachment.
Where do the sclera, choroid and tapetum originate from embryologically?
Which structures are fully differentiated at birth and which continue to develop after birth?
Arise from neural crest mesenchyme which forms 2 layers.
Outer layer = sclera
Inner layer = choroid and tapetum
Sclera and choroid fully differentiated at birth
Tapetum continues to develop until about 4 months post partum
What is required to differentiate normally in order for the sclera and choroid to develop normally? What can we see if this doesn’t happen?
Retinal Pigment Epithelium need to differentiate correctly in order for choroid and sclera to form correctly.
If does not occur than can see uveoscleral colobomas with primary RPE abnormalities.
What are the 3 types of vitreous and what are their different roles?
Primary vitreous = contains hyaloid vasculature to nourish the embryonic lens. Hyaloid system should regress during last stages of development and before birth - condenses into Cloquet’s canal (clear narrow central zone) with closure of the foetal fissure.
Secondary vitreous = main portion of adult vitreous, develops with closure of the foetal fissure. Main composition - water, collagen, hyaluronic acid produced by peripheral hyalocytes.
Tertiary vitreous = contributes to development of the lens zonules at lens equator.
Describe the development of the optic nerve embryologically.
- Early embryogenesis retinal ganglion cells extend their axons towards the optic stalk gradually forming the optic nerve which exits the eye via the optic disc.
- A glial sheath forms around the hyaloid artery and as it regresses glial cells migrate into optic nerve
- Optic nerve reaches the brain on day 32
- Myelination begins at the chiasm, progresses to the eye and reaches the optic disc after birth
- Postnatally the optic nerve continues to mature and refine its connections with the brains visual centres to optimise visual function.
When does full fundic development occur?
Full fundic development does not occur until 8-10 weeks of age post natally.
Hence when eyelids open for first time the ophthalmoscopic appearance shows a lilac-blue colour throghout indicating the presence of an immature fundus that has not yet differentiated into tapetal and non tapetal zones.
How does the choroid receive its blood supply?
Short posterior ciliary arteries that enter the globe in the vicinity of the optic nerve
What type of animals may have visible choroidal vasculature as a normal variation and why?
Subalbionotic animals with blue eyes (dilution of ocular pigmentation) - no tapetum and no pigment in the RPE
Choroid visible as intricate meshwork of vessels radiating outwards from optic nerve head.
If no choroidal pigmentation either can see against the white of the sclera.
Describe the shape and appearance of the tapetum. Why is it visible normally and what is its function?
Part of the choroid
Roughly semicircular in shape
Variations in colour
Visible due to absence of melanin within the retinal pigment epithelium
Main function = reflect light that has already passed through the retina, restimulating photoreceptors and enhancing dim light vision.
Herbivores = fibrous tapetum
Carnivores = cellular tapetum
(Humans and other diurnal animals lack tapetum resulting in fundus that varies from red to orange to grey depending on amount of choroidal pigmentation)
How is the retinal pigment epithelium visualised on fundoscopy?
Can be visualised in the non tapetal fundus and is usually brown to black depending on the concentration of melanin granules in the cells.
Is still present across the whole fundus as part of the retina but lacks pigment in the tapetal section of the fundus usually.
How can disease affect the apperance of the RPE on fundoscopy?
Disease - can alter degree of pigmentation within theRPE
Inflammation, infection, degenerative processes within retina can all affect degree of pigmentation.
Hyperpigmentation - can be see in the tapetal fundus e.g chorioretinal scar (often encircled by tapetal hyperreflectivity due to thinning of the neurosensory retina)
Depigmentation - e.g RPE atrophy with retinal degeneration - depigmented or pale areas within the non tapetal fundus giving a mottled appearance.
What is the function of the RPE?
Outermost layer (facing choroid)
RPE supports retinal function by recycling used photopigment, storing Vitamin A for photopigment synthesis, renewing outer segments of photoreceptors and acting as part of the blood-retina barrier for ocular immune defence.
Why can we not directly visualise the neurosensory retina on fundoscopy? How can we detect changes to this layer instead?
Cannot directly visualise as translucent.
Instead as it lies over the tapetum it reduced the reflectivity of the tapetum and makes the non tapetal areas slightly greyer than frank brown/black.
Thinning of the retina (often associated with retinal degeneration) = increased reflectivity of the tapetum (hyperreflectivity)
Thickening - (cellular infiltration/subretinal space fluid accumulation) leads to hyporeflectivity
What are the 10 layers that make up the retina from outermost (facing choroid) to innermost (facing vitreous).
- Retinal Pigment Epithelium (RPE)
- Photoreceptor layer - inner and outer segments of rods and cones and where vision initiation occurs. Photoreceptors absorb light photons through photopigment, triggers complex biochemical cascade that generates neuronal signal - process if called phototransduction.
- External limiting membrane - separates photorecptor layer from their nuclei
- Outer nuclear layer - contains nuceli of rods and cones
- Outer Plexiform layer - synaptic layer - axonal extensions of photoreceptors form synaptic expansions. Synapse with bipolar, horizontal and adjacent photoreceptors cells. Plays a role in early visual signal processing.
- Inner nuclear layer - contains nuclei of bipolar, horizontal and Mullers and amacrine cells.
Bipolar cells = synapse with photoreceptors - relaying visual signal to internal retina and retinal ganglion cells
Horizontal and amacrine cells - modulate neuronal activity in the outer and inner retina
Muller cells - span entire retina providing structural support and other physiological functions. - Inner plexiform layer - second synaptic layer - synapses between bipolar, amacrine and retinal ganglion cell dendrites enabling complex processing of the visual signal
- Ganglion cell layer = cell bodies of retinal ganglion cells (axons for the optic nevrve)
- Optic nerve fibre layer - retinal ganglion cell axons converging on the optic disc to form the optic nerve transmitting visual signals to the brain
- Internal limiting membrane - Innermost retinal layer adjacent to the vitreous, basement membrane to which the inner ends of Mullers cells are attached.
Why is the retina arranged in what seems a counterintuitive fashion with the RPE and photoreceptors being in outermost and the retinal ganglion cells the innermost?
This arrangement is most likely due to the high metabolic demands of the photoreceptors meaning they need close proximity to their blood supply the choroid.
What is the dual blood supply of the retina?
Photoreceptors supplied by the choroid
Inner retina supplied by the retinal vessels
Which types of animal have the following types of fundus?
Merangiotic
Pauangiotic
Holangiotic
Anangiotic
Merangiotic = rabbit (horizontal retinal vasculature)
Pauangiotic = horse (30-60 short retinal vessels surrounding the optic nerve)
Holangiotic = dogs and cats
Anangiotic = birds
Describe the retinal vasculature anatomy in the cat.
3 major pairs of cilioretinal arteries and veins
Originate around the periphery of the optic disc
Arcing around the area centralis they create a seemingly vessel free zone although a capillary network does still exist.
Describe the retinal vasculature anatomy in the dog.
20 cilioretinal arterioles radiating from the optic disc along with 3-4 major veins
Partial venous circle present on the optic disc (unlike cats)
Area centralis appears free of vasculature
Retinal vessels more tortuous than in other species.
What are the 4 portions of the optic nerve (CN II) and what does the optic nerve consist of?
Intraocular
Intraorbital
Intracanicular
Intracranial
Optic nerve consists of ganglion cells axons surrounded by myelin.
What type of flow is important for optic nerve function and at what pressure if this flow interrupted?
Axoplasmatic flow = important for optic nerve function and metabolism but pressure sensitive
> 50mmHG = no flow
What is the optic nerve head (also known as optic disc/optic papilla)? Where is it located on the fundus?
Location where retinal ganglion cells turn approximately 90 degrees to exit the eye as the optic nerve.
Located ventrolateral to posterior pole of eye and remains fixed due to the underlying optic foramen.
What things can affect the visibility and appearance of the optic nerve head as normal variations?
Presence of myelin and degree of myelination
(cats = occurs posterior to the disc making it appear round and dark whereas dogs = myelination typically begins at the disc leading to variations in size, shape and colour based on the myelination extent)
Visibility may vary based on tapetal and non tapetal regions, appearing in either the tapetal fundus, non tapetal fundus or at their junction.
What is the physiologic cup or pit on the optic nerve head?
Centre of the disc may show a dark spot
Represents the origin of the embryonic hyaloid vasculature
Particularly prominent in myelinated optic nerve heads
Rarely some residual hyaloid tissue may remain and extend short way into the vitreous (Bergmeister’s papilla)
What is the role of the vitreous and what is it composed of?
Complex gel
Mainly water (99%)
Collagen fibres that form structural framework~
Hyaluronic acid - cells hyalocytes
Mucopolysaccharides
Role = maintain ocular shape and volume
Keep structures such as lens and retina in proper positions
Small role in nutrition for the posterior lens and retina
Refractive index similar to lens does not contribute significantly to light refraction (but must remain transparent to allow light to pass through)
Storage site for retinal metabolites and waste products - e.g glycogen, potassium, free radicals and lactate.
Define the following:
Scotopic vision
Mesopic vision
Photopic vision
How can this relate to ERG?
Scotopic vision (very low light intensities) - only rods are active
Mesopic vision (medium light intensities) - both rods and cones active
Photopic vision (bright light intensities) - rods are oversaturated and only cones continue to function
In ERG the function of the rod and cone photoreceptors can be distinguished using different light intensities during retinal stimulation.
What determines the richness of colour vision?
Determined by photopigment classes in the CONE retinal photoreceptors.
Classified by the wavelength at which the OPSIN molecule in the cone photoreceptors has its peak absorption.
How does the colour vision of the following species vary?
Humans & Primates
Dogs & Cats
Horse
Reptiles & Avians
Humans & Primate = trichromatic vision
Possess blue, red and green OPSIN
Dogs & Cats dichromatic (deuteranope) - blue opsin and red opsin
Horse dichromatic (protanope) = blue opsin & green opsin
Reptile, fish, avians - tetrachromatic (additional opsin molecule with peak absorbance in UV range)
What is visual acuity and how is it provided?
What is the area centralis/visual streak? What do birds have instead?
Visual acuity = high resolution vision and visual discrimination
Cones > Rods
Cones and their retinal ganglion cells have high density in the central retina - this is known as the area centralis/visual steak
(although in dogs/cats and horses rods still outnumber cones accounting for lower visual resolution and greater light sensitivity)
Birds = fovea instead, only populated by cones and provides high visual acuity and colour perception.
Why does the tapetum lead to a reduction in visual acuity?
Enhances vision in low light settings but decreases visual acuity through light scatter.
Which photorecptor type is primarily responsible for detection of motion?
Rods = motion
Rod rich retina in most domestic mammals - motion detecting ability especially in low light is well developed.
What methods are there for assessment of the fundus and how should fundic assessment ideally be performed?
Examine fundus after dilation so can visualise peripheral fundus (unless glaucoma/lens instability prevents) - topical 1% tropicamide
Methods to examine the fundus:
Indirect ophthalmoscopy - monocular (20D and 30D lens) and binocular techniques (head mounted)
Inverted and reversed virtual image, wide field view of fundus - identify lesions
Distant direct ophthalmoscopy - tapetal reflection assessment
Close direct ophthalmoscopy - magnified view of area of fundus ‘zoom in’ on areas on interest identified with the indirect method. Upright image with 15-17x magnification,
Compare and contrast direct and indirect ophthalmoscopy methods of visualising the fundus.
Indirect = broad field of view, reduced magnification (better for overall assessment of the fundus, maintain greater working distance from patient - good if temperament not very amenable!)
Binocular indirect has benefit of stereopsis - 3D perception of depth in the observed structures
Disadvantage = image INVERTED AND REVERSED (upside down and backwards) and virtual.
Close direct = examine areas in greater magnification 15-17x, ‘zoom in’ on areas identified on indirect exam, true image
Both techniques complement each other and should be performed together when examining the fundus.
What is electroretinography (ERG)? What is it used for?
ERG = technique that measures small electrical potentials generated in the retina when it is stimulated by light.
Potentials known as ‘waves’ are recorded using a corneal electrode and amplification and recording systems.
ERG = assessment of retinal function
Indications for use:
Retinal function in cataract patients prior to surgery
Differentiate causes of sudden blindness where retinal lesions are not visible (SARDS, early retinal degeneration/PRA, optic neuritis without papillitis, CNS disease)
What do the ERG responses vary based on? How do we utilise this to look at the rods/cones.
ERG responses will vary based on factors such as:
Dark adaptation & Light stimulus characteristics
Use these responses to isolate rods/cones
Dark adapted conditions - dim light stimulus primarily elicits response driven by rods
Light adapted conditions - response mainly driven by the cones
Pure cone driven response to flickering light stimuli at 30Hz or higher
What equipment is required to perform an ECG?
Sedated patient
Recording system
Amplification
Electrodes - jet corneal contact lens, subdermal reference and earthing electrode)
Flash photo stimulator
Farraday cage - prevent intereference
What waveforms do we typically see with a normal ERG?
What does a flat line on an ERG indicate?
A wave = photoreceptor response
B wave = bipolar cells
C wave = retinal pigment epithelium
Flatline on an ERG = peripheral blindness
What factors may influence the ERG readings?
Differences in anaesthetic protocol
Temperature
Oxygenation
Farraday cage use = less interference from other electrical equipment
Species
Breed
Age
Try to standardise protocols for ERG’s as much as possible to help with interpretation.
What modality can we use to evaluate the fundus when ophthalmoscopy is not possible (e.g due to mature cataracts, hyphaema, severe corneal oedema etc)
Ocular ultrasound
Pathology can see affecting fundus:
Persistent embryological structures in vitreous
Intraocular neoplasia
Retinal detachments (highly reflective, continuous linear structure with attachments at optic disc posteriorly and ora ciliaris anteriorly resembling wings of a seagull)
What modality would we want to use to examine the optic nerve itself?
MRI
(Ultrasound can be used but difficult and much less sensitive)
What is the chromatic pupillary light reflex and what do we use it for?
Red/blue chromatic pupillary light reflex - used to distinguish between outer and inner retina as well as optic nerve disease in canine patients.
Evaluates PLR in response to red or blue light.
Red light = stimulates both rods and cones due to its high intensity
Blue light = activate melanopsin in specific ganglion cells as well as rods and cones
Blue light can therefore trigger PLR response independently of the photoreceptors.
Photoreceptor degeneration - red PLR absent but blue PLR intact due to intact retinal ganglion cells
SARDS = most common indication
With SARDS blue PLR remains intact whilst red PLR absent (photoreceptor loss)
Optic neuritis = both PLR reflexes lost
75% sensitivity and 100% specificity in detecting retinal degeneration and detachment - swift, easy and accurate diagnostic tool for canine patients with retinal and optic nerve disease.
What two methods do we have for screening for inherited eye disease?
DNA testing
Eye examinations
The two should be used complementarily
Describe how eye examinations for inherited diseases are performed.
Eye examination scheme - BVA, performed by ophthalmologists selected to be on their panel
Used to detect clinical signs of neonatal/congenital hereditary eye disease
Litters of puppies and breeding dogs should be examined under the scheme (ideally annually)
Final examination when the dog is 8yrs also recommended to ensure late onset inherited diseases are recorded accurately.
Eye examination = identification of phenotype (physical presence of disease)
Eyes examined thoroughly with slit lamp, indirect and direct ophthalmoscopy and additional gonioscopy in some breeds affecting by pectinate ligament abnormality/goniodysgenesis.
How can DNA testing be used for screening for inherited eye disease. What are the 2 types of test and what are the advantages of using DNA tests.
DNA screening - identification of genotype
Simple = often cheek swab
2 types = mutation detection tests and linkage tests
Mutation - precisely identify specific mutated gene causing the disease, categorising animals as genetically clear, carriers or affected for recessively inherited conditions.
Linkage - only identify approximate location of the mutation, not the actual mutation itself making them less accurate than mutation tests.
Advantages = can be conducted on animals of any age (before breeding and sexual maturity - some diseases do not present clinically until much later in animals life when has already been bred from), detect carriers who are not clinically affected but in breeding could lead to affected individuals in recessive conditions.
Identification of actual mutation - 100% accurate with no subjectivity (linkage tests do carry margin of error)
Disadvantage - need to know the specific mutation for the disease in order to perform DNA testing
Compare and contrast the use of DNA testing vs Eye Examination for screening for inherited eye disease.
Genetic DNA testing = 100% accurate (excluding sampling/lab error), only tests for a single specific gene mutation, identifies carriers for recessive diseases, identifies genetically clear animals for breeding, identifies animals before onset of clinical signs of eye disease (several inherited eye diseases do not present until later in life when animal has already been bred from) - GENOTYPE
Need to know specific gene mutation for this to be used however - many inherited eye diseases unknown gene for inheritance.
Eye examination = more subjective interpretation, screens for wide range of both inherited and non inherited ocular disease, unable to identify carriers, cannot distinguish unaffected from carrier animals and those animal affected with late onset disease prior to breeding, unable to identify affected animals until ocular clinical signs become apparent. - PHENOTYPE
Describe PHPV/PHTVL (persistent hyperplastic primary vitreous)
Which breeds are predisposed.
Congenital inherited condition
During embryonic development lens receives nutrients from hyaloid artery which reaches the posterior lens around day 25 of gestation.
Tunica vasculosa lentis also develops around this time.
Day 45 vascular supply should start to regress as well as the primary vitreous and this process should be fully completed by 2-4 weeks post birth.
In some cases there is persistence of these vessels and this leads to formation of fibrovascular plaques on the posterior lens capsule.
Plaques = yellow/white densities, pigment foci and visible blood vessels
Often associated with lens colobomas, persistent capsulopupillary vessels, posterior lenticonus, intralenticular and retrolental haemorrhage, secondary cataracts and persistence of hyaloid artery.
Breeds predisposed = Dobermann, Staffordshire Bull Terrier
Inheritence complex - suspect autosomal dominant with incomplete penetrance
Specific genes not identified.
Grading scheme depending on severity of lesion.
High grades may affect vision.
What is retinal dysplasia?
Term that encompasses various congenital and neonatal conditions where the retina has abnormally differentiated during embryonic development.
Genetic (majority) vs external factors (e.g radiation, infectious agents e.g canine herpes virus)
What mode of inheritance causes the majority of retinal dysplasias?
Most cases of inherited retinal dysplasia caused by autosomal recessive gene defects.
What are the 2 main appearances of retinal dysplasias? How do they affect vision
Multifocal retinal dysplasia vs Total retinal dysplasia
Multifocal = vision normal in many dogs
Total = blindness