IDK Flashcards
TYPES OF RETINAL HAEMORRHAGES AND LAYER OF RETINA AFFECTED
Flame haemorrhages - NFL
Dot and blot haemorrhages - inner and outer plexiform layers.
Hard exudates and CMO (epinephrine, latanoprost and nicotinic acid are recognized causes) - outer plexiform layer.
% of pt w/ acute symptomatic PVD w/ vitreous haemorrhage that have a retinal tear?
75%
Haemorrhage or vitreous cells (tobacco dust) are highly suggestive of retinal breaks.
Most common cause of hyper acute purulent conjunctivitis
B - what culture medium to grow it
C- complications
Neisseria gonorrhoea - use Chocolate agar/Thaymer Martin
If untreated-> corneal ulceration, perforation and endophthalmitis as N.g can progress through intact corneal epithelium
Retinal capillary endothelial cells are surrounded by what 3 things:
Thick basal lamina
Pericytes
Astrocyte foot processes
Coat’s disease
Retinal telangiectasia
EXUDATIVE RETINAL DETACHMENT W/ ASSOC VASCULAR ABNORMALITIES
Not hereditary and not assoc w/ systemic vascular abnormalities
Men predominantly affected.
Children predominantly effected
Where are the axons of cells in the retinal layer
Horizontal cells - inner nuclear layer.
Amacrine cells and bipolar cells - inner plexiform layer
Ganglion cells - nerve fibre layer of the retina
CHECK
TROCHLEAR N
nucleus - anterior part of the periaqueductal grey matter in the inferior colliculus
supplies only somatic efferent innervation to the superior oblique
emerges from the posterior aspect of the brain stem, just inferior to the inferior colliculus
The trochlear nerve is unusual in that it decussates before leaving the brainstem
CULTURE MEDIUMS
Thaymer-Martin =
MacConkey =
Blood agar =
Chocolate agar =
Cooked meat broth =
Thioglycate agar =
Lowstein-Jensen =
McCoy =
Non-nutrient agar w/ E.coli =
Sabouraud agar =
Thaymer-Martin = Gram neg cocci e.g. Neisseria
MacConkey = Lactose fermenting gram negative
Blood agar = MOST But Haemophilus, Neisseria, Moraxella
Chocolate agar = MOST incl (Con) Haemophilus, Neisseria, Moraxella
Cooked meat broth = Anaerobes, fastidious organisms
Thioglycate agar = Aerobes on surface, anaerobes inside
Lowstein-Jensen = Mycobacteria TB
McCoy = Obligate intracellular bacteria
Non-nutrient agar w/ E.coli = Acanthomoeba
Sabouraud agar = Fungi
DEFINE
Pharmacokinetics
Pharmacodynamics
Pharmacokinetics = drug absorption, distribution, elimination
Pharmacodynamics = biochemical and physiological effect of drug and their mechanisms of action at organ/subcellular/macrocellular level.
Sclera vs Cornea
- Water content
- CT arrangement
- 68% in sclera
75-80% in cornea - Sclera
- dense irregular CT - type 1 collagen
- Less proteoglycans and glycosaminoglycans in its matrix than cornea
Cornea
- regular CT arrangement - type 1 (also 4,5,7)
- More proteoglycans and glycosaminoglycans in its matrix
Ficks law
Rate of diffusion
MOA OF ANTIFUNGALS
ECHINOCANDIN E.G. MICAFUNGIN
- interferes w/ glucan synthesis, which is an essential component of fungal cell walls
POLYENE E.G. AMPHOTERICIN, NYSTATIN, PIMARICIN
- interact w. sterols in fungal cell membrane to form channels causing leakage
AZOLE E.G. FLUCONOZOLE, KETOCONAZOLE, ITRACONOZOLE
- inhibits p450 dependent enzymes involved in biosynthesis of ergosterol, required for fungal cell membrane structure and function
GRISAN E.G. GRISEOFLUVIN
- binds to tubular, preventing microtubule assembly
GLUTARAMIDE E.G. CYCLOHEXIMIDE
- inhibits protein synthesis at ribosomal level
ANTIMETABOLITES E.G. 5-FLUROCYTOSINE
- inhibits both DNA/RNA synthesis via intracytoplasmic conversion of 5-fluorocytosine to 5-flurouracil
ROD/CONE TO GANGLION CELL RATIO
Cone:GC in fovea is 1:1
—> mainly parvocellular pathway to lamellae 3-6 in LGN
Rod:GC in periphery is 10,000:1
——>mainly magnocellular pathway to lamella 1 and 2 in LGN
STANDARD ERROR
STANDARD ERROR OF MEAN = S.D/sqrt of n
standard error of the mean is a measure of this scatter, i.e. how accurate is the sample mean as an estimate of the true population mean.
Blood supply of LGN
DUAL supply
1. ANTERIOR CHOROIDAL ARTERY (branch of ICA)
2. LATERAL POSTERIOR CHOROIDAL ARTERY (branch of post. CEREBRAL artery)
EPINEPHRINE causes
- cortisol release
- anxiety and sweating
- glycogenolysis and glycolysis
- reduced appetite
- lowering of IOP
lattice CORNEAL DYSTROPHY
AD
Corneal stromal dystophy
- fine criss-crossing lines in stroma
Microscopy - amyloid deposition (also present in Avellino dystrophy)
Test with congo red - green birefringence
EMBRYOLOGICAL ORIGIN OF OCULAR TISSUE
SURFACE ECTODERM
- LENS
- LACRIMAL GLAND AND NASOLACRIMAL SYSTEM
- EPITHELIUM OF CORNEA
- EPITHELIUM OF CONJUNCTIVA
- MEIOBIAN GLANDS
NEUROECTODERM
- RETINA
- OPTIC NERVE
- SPHINCTER PUPILLAE AND DILATOR PUPILLAE
- EPITHELIUM OF IRIS
- EPITHELIUM OF CILIARY BODY
MESODERM
- EOM
- BLOOD VESSEL ENDOTHELIUM AND IN SCLERA AND CHOROID
- SUSPENSORY FIBRES
- ANGLE OUTFLOW APPARATUS
NEURAL CREST
- IRIS STROMA
- CORNEAL STROMA AND ENDOTHELIUM
- TM and SCHLEMM’S CANAL
- CILIARY MUSCLE
- CONNECTIVE TISSUE
- BONY STRUCTURE OF ORBIT
CAVERNOUS SINUS
Location in relation to other structures
Either side of sella turcica
Lateral and superior to sphenoid sinus
Immediately posterior to optic chiasm
CAVERNOUS SINUS
receives blood from which veins
Facial veins (via sup and inferior ophthalmic veins)
Sphenoid veins
Middle cerebral veins
CAVERNOUS SINUS
Empties into..
Inferior petrosal sinus -> Internal jugular vein
Superior petrosal sinus ->Sigmoid sinus -> IJV
Most common cause of CL associated corneal ulcers
Pseudomonas
sensitive to aminoglycoside (neomycin, gentamicin) and quinolone (ciprofloxacin) antibiotics.
MITOSIS
INTERPHASE - chromosomes prepare to divide
PROPHASE - chromosomes condense
METAPHASE - chromosomes line up on equator of cell
ANAPHASE - chromosomes begin to seperate
TELOPHASE - chromosomes have segregated to the poles and the nuclear membranes reform
SYMPATHETIC OPHTHALMITIS
B/l granulomatous pan-uveitis - can occur after traumatic injury to 1 eye, where uveal tissue is incarcerated in sclera
Dalen - Fuch’s nodules are an accumulation of macrophages in the RPE
Condition can lead to exudative retinal detachment secondary to severe inflammation, with consequent hypotony and phthisis bulbi.
Oxybuprocaine
Local anaesthetic - toxic if used systemically
Bacteriostatic so proxymethocaine preferred for corneal scrapes
Tetracaine has longer anaesthetic effect that oxybuprocaine
Muscles of facial expression
The muscles of facial expression are innervated by the facial nerve and include:
procerus
frontalis
corrugator supercilii
orbicularis oculi
zygomaticus major and minor
levator labii
nasalis
depressor supercilii
occipitofrontalis
buccinator
THYROID HORMONES
Peptides
T3>T4
99% bound to thyroxine binding globulin
Thyroxine sensitises myocardium to NA
HYPERSENSITIVITY REACTIONS W/ EXAMPLES
ACID
T1 - ALLERGIC
IgE mediated - quick onset after exposure
E.g. bee sting, latex, drug allergy
T2 - CYTOTOXIC/ANTIBODY-MEDIATED
E.g Haemolytic reactions, Good pasture syndrome, Hyperacute graft rejection, blood transfusion reaction
T3 - IMMUNE COMPLEX/IGG/IGM MEDIATED
Immune complex deposition
E.g Hypersensitivity pneumonitis, SLE, PAN, RA, glomerulonephritis
T4 - DELAYED/CELL-MEDIATED
E.g. chronic graft reactions, contact dermatitis.
HORNER’S SYNDROME
Miosis - reacts normally to light
Partial ptosis - disappears w/ topical phenylephrine
Conjunctival injection
Updrawing of lower eyelid which looks like enophthalmos
Decreased sweating of face
DOWN’S SCREENING TEST
At 12wks, together the
Nuchal scan (Thickened)
bHCG (Elevated)
PAP (Reduced)
identifies those at high risk of a Down syndrome pregnancy in greater than 80% of cases.
Primary metabolic substrate of the cornea is
Glucose
synaptic terminals of the cones/rods
cones - pedicles
rod - spherules
CHOROID LAYER comprising large arteries and veins
Haller’s layer comprises large arteries and veins.
Sattler’s layer, which lies above Haller’s layer, is composed of arterioles and venules which supply the choriocapillaris directly above.
Above layers are not fenestrated unlike the capillaries in the choriocapillaris which lie above both layers -> Fluoroscein leakage is seen in the choriocapillaris.
Clinical and anatomic terms for the regions of the fundus:
CLINICAL
posterior pole -> macular lutea ->fovea centralis
ANATOMICAL
area centralis -> fovea -> foveola
posterior pole: area centralis
(the area between the vascular arcades)
macula lutea: fovea
(1.5 mm diameter area, yellow from xanthophyll)
fovea centralis: foveola
(0.35mm central depression with thickened margins)
MOA of botox
Botox binds irreversibly
to presynaptic receptors on the nerve terminal of the neuromuscular junction,
inhibiting the release of acetylcholine following an action potential.
Dimensions of CORNEA
Form ant 1/6th of eyeball
LENGTH
10.6mm vertically
11.7mm horizontally (10mm at birth)
Post diameter circular 11.7mm
THICKNESS
Centre is thinnest 0.5-0.6mm
Peripherally 0.7mm
RAD OF CURVATURE
Ant surface - 7.7mm
Post surface - 6.9mm
More curved in vertical than horizontal plane (regular astigmatism)
n=1.37
LAYERS OF CORNEA
FRONT TO BACK
EPITHELIUM
BOWMAN’S LAYER
SUBSTANTIA PROPRIA
DESCEMET’S MEMBRANE
ENDOTHELIUM
Diploë
Diploë is the name of the spongy bone that separates tables of compact bone.
WALLS OF ORBIT
MEDIAL (post to anterior)
- Body of sphenoid
- Ethmoid
- Lacrimal
- Maxilla
FLOOR
- Maxilla
- Palantine
- Zygoma
LATERAL WALL
- Zygoma
- Great wing of sphenoid
ROOF
- Frontal
-Lesser wing of sphenoid
MEIOBIAN GLAND
tarsal glands embedded in the tarsal plates.
openings, 20–25 in each lid
posterior to both the lash line and the grey line
modified sebaceous glands - oily substance forms outer layer of the precorneal tear film
Meibomian gland dysfunction/posterior blepharitis
Anterior blepharitis involves crusting/debris and inflammation around the lash line, and the two often coexist.
A chalazion is a lipogranulomatous inflammatory cyst resulting from a blocked Meibomian gland.
INNERVATION OF LACRIMAL GLAND
Parasympathetic supply
lacrimatory nucleus OF FACIAL CN7
-> nervus intermedius
-> pterygopalatine ganglion
-> via the maxillary nerve to its zygomatic and zygomaticotemporal branches
->via the lacrimal nerve to the gland.
Sympathetic supply,
superior cervical ganglion
->nerve plexus surrounding ICA
-> deep petrosal nerve to its zygomatic and zygomaticotemporal branches
->via the lacrimal nerve to the gland.
Sensory supply
- From lacrimal nerve, which is a branch of the trigeminal nerve (V1).
FORAMEN SPINOSUM
Connects middle cranial fossa with inferotemporal fossa
Transmits
-meningeal n of mandibular n
middle meningeal artery and vein
EOM VS SKELETAL MUSCLES
Thin, delicate CT including epimysium sheath
Loosely packed muscle fibres
Larger fibres in centre, small in periphery
Long muscle spindles 1mm in length
More vascular
BRANCHES OF FACIAL CN7 N
Two Zebras Bit My Coccyx
-Temporal
-Zygomatic
-Buccal
-Mandibular
-Cervical
Lens Capsule Dimensions
posterior pole 2–3 μm
anterior pole 9–14 μm
peri-zonular region the capsule is 17–28 μm
site of attachment of the vitreous base?
Peripheral retina and pars plana
PARS PLICATA and PARS PLANA
pars plicata forms the anterior portion and is contiguous to the posterior surface of the iris. It represents approximately one quarter of the whole CB.
The pars plana, the posterior portion of the CB, is contiguous to the choroid at the ora serrata
LAYERS OF CHOROID
Outer to inner
VESSEL LAYER
-loose CT w/ melanocytes
- embedded w/ large-medium vessels (branches of short posterior ciliary arteries)
CAPILLARY LAYER
- wide-bore capillaries w/ sac like dilatations
- again supported by CT and melanocytes
- lined by continuous layer of fenestrated endothelial cells
- capillary density and bore greatest at macula
BRUSCH’S MEMBRANE
2-4micrometers thick
1. BM of choriocapillaris
2. Outer collagenous layer
3. Elastin layer
4. Inner collagenous layer
5. BM of RPE
CILIARY BODY
AP length temporal (5.6-6.3mm) >nasal (4.6-5.2mm)
Blood supply - via the
- anterior ciliary arteries
- long posterior ciliary arteries
The ciliary body stroma lies between the ciliary muscle and the ciliary epithelium.
Layers of ciliary body muscles
outer longitudinal layer - attaches to the scleral spur
middle radial layer - continuous w/ corneoscleral meshwork
third (innermost) - composed of circular fibres
CONTRACTION OF CILIARY MUSCLES ESP 1 AND 3 -> used in convergence, accomodation
IRIS BLOOD SUPPLY
Iris capillaries are non-fenestrated - tight junctions and pericytes contribute to the blood ocular barrier.
Most of the anastomoses between the major and minor arterial circles run through the IRIS STOMA in a radial manner. (Anterior border layer - significant vascularisation here suggests ischaemic insult.)
The MAJOR arterial circle of the iris receives blood from
- anterior ciliary arteries (which travel anteriorly with the extraocular muscles before piercing the sclera)
- long posterior ciliary arteries (which pierce the sclera near the optic nerve and run anteriorly between the sclera and choroid to the ciliary body).
The MINOR arterial circle of the iris is at the level of the collarette
LYMPHATIC DRAINAGE
Right lymphatic duct (empties into right subclavian vein) - drains right head, neck, arm
Thoracic duct (empties into left into left subclavian vein) - drains rest of body
GCA - what part of artery affected
Internal elastic lamina (part of intima) is fragmented in giant cell arteritis.
Compared to plasma, aqueous contains:
- Higher levels of
- lactate
- ascorbate;
- Similar concentrations of
- Na
- K
- Mg
- Lower levels
- bicarbonate;
- glucose
- calcium (about half that of plasma),
- much lower levels of albumin.
COLLAGEN SYNTHESIS
Stage of collagen synthesis
Transcription
DNA → RNA
TRANSLATION
RNA → peptide formation
The basic amino acid sequence is repeating triplets
(Glycine-X-Y )n
where X is often proline, Y is often hydroxyproline Polypeptides (primary structure) twist into a left-handed helix (secondary structure; ≠ α-helix)
POST-TRANSLATIONAL MODIFICATION (ENDOPLASMIC RETICULUM)
- Vitamin C-dependent HYDROXYLATION of the Y-position amino acid
- GLYCOSYLATION
- TRIPLE HELIX FORMATION (tertiary structure) linked by covalent S–S bonds
EXCRETION FROM CELL
Cleavage of terminal peptide chains, making it insoluble
(EXTRACELLULAR MODIFICATION)
Lysine oxidation
Formation of crosslinks
matrix metalloproteinases (MMPs)
zinc and calcium-dependent endopeptidases
act as an enzyme cascade to degrade extracellular matrix.
required for normal tissue growth (make room)
regulated by Endogenous inhibitors called TIMPs are present in normal tissues
released mainly by neutrophils in acute inflammation
___
MMPs in the cornea,
- maintenance of normal framework (principally MMP-2)
- remodelling following injury: MMPs:
- MMP-1 (a collagenase),
- MMP-2 (a gelatinase)
- MMP-3 (a stromelysin),
all produced primarily by the stroma, along with MMP-9 (a gelatinase) produced primarily by the epithelium.
MMP-9 is involved in corneal epithelial remodelling.
LENS PROTEIN
Cytoplasmic interdigitations between lens fibres contain channels formed by MIP26 (aquaporin-0)
FIBROBLAST growth factor stimulates the differentiation of lens epithelial cells into lens fibres
genes encoding α-crystallin are found on chromosomes 21 and 11
Glycosaminoglycans
- composed of long chains of repeating disaccharides
-relatively inflexible molecules
-strongly hydrophilic - form a gel resistant to compression
-high negative charge
corneal endothelial cell pump
moves sodium and bicarbonate from the stroma to the aqueous by active transport.
mediated by a sodium/potassium-dependent ATPase and a bicarbonate-dependent ATPase,
facilitated by co-transporters.
Potassium and chloride move to the aqueous predominantly by passive diffusion.
PERICYTE COVERAGE
frequency of 1:1 pericytes to endothelial cells
meticulous metabolic demands of the retina and the requirement to maintain the blood–retinal barrier.
Conversely choroid — less dense coverage of pericytes, facilitating exchange of metabolites.
ROLE OF PERICYTES
contractile cells embedded in the BM of vessels
regulatory functions
- communicating w/ endothelial cells
by paracrine signalling and direct contact.
-maintaining the blood–brain barrier - regulate permeability.
?role in controlling cerebral blood flow.
VEGF
Aflibercept - decoy VEGF receptor molecule
Bevacizumab VEGF mab
Ranubizumab VEGF man-fragment
VEGF synthesis is upregulated by
TNFα, TNF-β, IL-1α, IL-6, prostaglandin
E2, epidermal growth factor, fibroblast growth factor, insulin-like growth factor-1, keratinocyte growth factor and platelet-derived growth factor.
All three identified VEGF receptors act via intracellular tyrosine kinase activity.
ROLE - promote the division and survival of vascular endothelial cells, VEGF promotes vascular dilatation and permeability to macromolecules. It also has functions in regulating gene expression, cell migration and nitric oxide production.
CONE/ROD PHAGOCYTOSIS
About 10% of the rod outer segment is phagocytosed daily, and it takes 9–10 days for the renewal cycle to be complete.
Melatonin is synthesized by photoreceptors in conditions of darkness and suppresses dopamine production. Conversely, local dopamine production increases during conditions of light and suppresses melatonin production. These mechanisms are involved in modulating the circadian rhythm of photoreceptor renewal, with rod disc shedding and phagocytosis occurring at first light.
Cone outer segments are predominantly shed at the onset of darkness.
Rod discs are phagocytosed in groups of approximately 200. It is hard to measure cone segment phagocytosis experimentally.
STRUCTURE OF MRNA
introns are removed before it leaves the nucleus as mature mRNA
a poly-adenine tail provides stability to mature mRNA leaving the nucleus and helps to prevent degradation before translation
a cap of ATP/GTP is added to the 5’ end which facilitates binding to the ribosome
the start codon is AUG which codes for methionine
it is synthesised from a single strand of DNA by RNA polymerase II enzyme
The inner capillary plexus of the retina is contained in the
ganglion cell layer.
Collagen type that forms an integral part of hemidesmosomes and the anchoring fibril architecture of the corneal epithelium to the Bowman’s.
TYPE VII 7
SIGMOID SINUS
continuation of the transverse sinus
ends below the jugular foramen.
groove of the sigmoid sinus is on the mastoid process of the temporal bone; and runs along the border of the temporal and occipital bones.
receives blood from the cavernous sinus via the superior and inferior petrosal sinuses
close proximity to the mastoid air cells, infection in this region can cause thrombosis.
Compared to plasma, CSF has:
Increased
-pH
-Chloride
- magnesium
Lower everything but
- (low o2 as low pH)
- (almost absent protein)
- (glucose is 2/3rd that of blood)
Main GAG or corneal stroma
keratan sulphate (most common) and dermatan sulphate
Staph aureus:
- grows well on blood agar
- main commensal of the outer eye
- aerobic
- non-motile
- it is a Gram positive bacteria
- it can produce exotoxins
Rx for corneal ulcer caused by filamentous fungi
Topical natamycin
Causative organisms include
Fusarium,
Aspergillus
Penicillium
Cyclosphosphamide MOA, SEs
alkylating agent - interferes with DNA replication by forming intrastrand and interstrand DNA cross-links.
SE: most commonly bone-marrow suppression, particularly granulopoiesis and lymphopoiesis, which is almost universal.
Haemorrhagic cystitis is also common, occurring in up to 10% of patients. Other side-effects include bladder cancer, hepatic toxicity, amenorrhoea and azoospermia (usually reversible).
Yoked muscles ??
Yoked muscles receive equal and simultaneous innervation in accordance with the Hering ‘s law. The right inferior rectus is yolked with the left superior oblique (as the eyes look right and downwards). Other options supplied are true.
The Purkinje effect
The Purkinje effect describes the shift in spectral sensitivity from 555nm (yellow) to 505nm (blue-green) with dark adaptation as rod function overtakes cone function. This results in an enhanced sensitivity to short (blue-green) wavelengths at dusk.
Reis–Buckler Corneal dystrophy
-aD
-characterised by granular deposits in the epithelial basement membrane.
-stain with Masson’s trichrome.
-manifests clinically as recurrent corneal erosion and corneal opacification which may require corneal grafting.
NB: All corneal dystrophy is autosomal dominant apart from Macular Corneal Dystrophy (aR).
Gene Therapy
-aims to treat a genetic condition by replacing the abnormal gene with a healthy one or by manipulating its expression.
Viral vectors include adenoviruses, retroviruses, adeno-associated viruses and herpes simplex viruses.
Non-viral vectors include liposomes and naked DNA in the form of plasmids.
Ribozymes (RNA that catalyses reactions) are also a tool in gene therapy but they are not vectors: they are used to cut mRNA of the target gene to block transcription.
Antigen presenting cells:
Antigen presenting cells (APCs) include:
monocytes,
macrophages,
dendritic cells,
some B cells,
activated endothelial cells.
They constitutively express MHC class II molecules.
APCs do not include T cells; the main function of APCs is to allow T cells to recognise antigens.
Minimum sterilisation times for dry and moist heat
Moist Heat Temperature (oC)
121–124 - 15mins
126–129 - 10mins
134–138 - 5mins
Dry Heat Temperature (oC)
160 - 180mins
170 - 60mins
180 - 30mins
BOTOX
Botulinum toxin A is a protein
of Clostridium botulinum - gram +ve
internalised by cholinergic nerve terminals and inhibits the exocytosis of acetylcholine.
Toxocariasis
nematodal infection
typically affects children.
posterior uveitis
part of the differential diagnosis of leukocoria.
Both toxocara and toxoplasma can be transmitted to humans via ingestion of animal faeces. Toxocara canis ova are shed in dog faeces; Toxocara cati ova and Toxoplasma gondii cysts are shed in cat faeces.
Both toxocara and toxoplasma cause white chorioretinal lesions and, in some cases, vitritis.
Infection may be asymptomatic.
Haemophilus influenzae
aerobic, Gram-negative bacillus
The descriptor coccobacillus is often applied, as the rods are very small and can give the appearance of cocci.
Haemophilus influenzae is best cultured on chocolate agar with added X and V factors.
common cause of respiratory tract infections and sinusitis, the latter becoming orbital cellulitis if spread through the orbital wall occurs.
encapsulated serotypes being more virulent and invasive.
IOL placement moved anteriorly
Adjust by -1D
(if 17.5-28)
If >28D, -1.5
If <17.5D –0.5
If IOL< 9.5 dioptres - keep same
Uveal tract melanomas - percent of locations
8% iris,
12% ciliary body
80% choroid
Retinal detachment causes
Accumulation of sub retinal fluid in all types
RHEGMATOGENOUS
Most common
Liquefaction of vitreous, vitreous traction, retinal tear/break
COMMON CAISES
- PVD causing retinal tear or hole
- Dehiscence of the anterior retina at the ora serrata causing retinal dialysis (usually due to trauma)
EXUDATIVE/SEROUS
Compromised outer blood-retinal barrier
COMMON CAUSES
- Vascular e.g ARMD
- Inflammatory e.g posterior scleritis
- Neoplastic e.g. choroidal melanoma
TRACTIONAL
Contracting proliferative retinal membranes, abnormal vitreoretinal adhesions
COMMON CAUSES
- Proliferative DM retinopathy
- Proliferative viteoretinopathy
- ROP
Proliferative vitreoretinopathy
- common cause of failure following retinal detachment surgery
- more common with
-large breaks,
-multiple operations
-duration of retinal detachment.
-may also occur in untreated retinal detachment.
Following the break in the retina, RPE cells migrate into the subretinal space and vitreous.
The blood–retinal barrier is broken and inflammatory cells are recruited.
Fibrosis and collagen production occur, contributing to the formation of retinal membranes.
Contraction of these can lead to retinal detachment and, if untreated, ocular hypotony (not raised intraocular pressure) and ultimately phthisis bulbi.
Phases of healing of a full-thickness corneal laceration
MINS
- Retraction of Descemet’s and stromal collagen
- Fibrin plug formation
- Stromal oedema
- Invasion of leukocytes from aqueous and limbal vessels
HOURS
- Transformation of leukocytes and of stromal keratocytes into fibroblasts
- Collagen formation
- Start of epithelial regeneration
DAYS
- Endothelial sliding, filling in gaps in endothelium and Descemet’s
WEEKS
- Replacement of stroma and Bowman’s layer with scar tissue
Ciclosporin
DRUG CLASS
MOA
OTHER EXAMPLE W/IN CLASS
SEs
calcineurin inhibitor
inhibits transcription of IL2 and other cytokines
TACROLIMUS, CICLOSPORIN
SEs:
nephrotoxicity
tremor
hirsutism
gingival hypertrophy
HORNERS TESTS
effects of
COCAINE 4%
HYDROXYAMPHETAMINE 1%
APRACLONIDINE 0.5%/1%
PHENYLEPHRINE 1%
COCAINE
Fails to dilate pupil as NA reuptake inhibitor but no NA released
HYDROXYAPHETAMINE
ONLY fails to dilate in 3RD ORDER LESIONS as causes release of NA
APRACLONIDINE (ALPHA 2 AGONIST W/ WEAK ALPHA1 ACTIVITY)
Denervation hypersensitivity to apraclonidine occurs due to up regulation of iris alpha-1 after a few days
Pupil dilates in all cases
PHENYLEPHRINE (A1 AGONIST) - SAME AS APRACLONIDINE
BRIMONIDINE
α2 adrenoreceptor agonist
lowers aqueous production
AND
increases uveoscleral outflow.
α2 agonists such as brimonidine carry more risk of allergy (approximately 10%).
However, they are considered safer than the others in pregnancy,
and
not contraindicated in asthma (unlike BBs).
MOA OF THROMBOXANE A2
Vasoconstriction
Platelet aggregation
EICOSANOIDS
Eicosanoids are an important group of signalling molecules and inflammatory mediators that include prostaglandins and thromboxanes (together termed prostanoids), and leukotrienes. They can be generated as required in response to stimuli. The inflammatory response always involves prostanoid generation.
The precise stimuli vary depending on cell type and include cell damage, thrombin (platelets), complement-derived C5a (neutrophils) and bradykinin (fibroblasts). They are derived from arachidonic acid, which is liberated from cell membrane phospholipids in a rate-limiting step catalysed primarily by phospholipase A2.The enzymes cyclooxygenase (COX-1 and COX-2 isoforms) and lipoxygenase then catalyse the production of different eicosanoids from free arachidonic acid.
Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce inflammation by inhibiting cyclooxygenase and therefore the biosynthesis of prostaglandins, but subsequently have no effect on their actions on target tissue. Prostaglandins exert their effects by acting on G-protein coupled receptors.
Thromboxane A2 is an eicosanoid which causes vasoconstriction and platelet aggregation.
HISTAMINE EFFECTS
H1
Intracellular
- phospholipase C activation
- increase Ca2+
Extracellular
- increased vasc permeability
- vasodilation
- CNS depressant
H2
Intracellular
-Activation of adenylate cyclase
- increase in cAMP
Extracellular
- Increase gastric acid production
- Increase cardiac stroke volume
__
3 histamine receptors - g-protein coupled.
WHAT IS CHROMATICITY
nature of the reflected light determines the object’s colour.
‘Colour’ = chromaticity
Depends on:
* Hue
* Saturation
* Luminance
Hue is not independent of luminance (which in this context could also be referred to as luminosity or brightness): with increasing brightness, eventually all hues appear yellow-white (the Bezold–Brücke effect), whilst with very low luminosity all hues appear achromatic.
The perceived colours of objects around us are a product of both the light source and the surface properties of the objects, which determine the composition of the reflected light.
The maximal spectral sensitivity of green cones is 535–550 nm.
LIGHT/DARK ADAPTATION
Dark adaptation is the process by which the retina increases in sensitivity to light in response to decreasing background illumination.
The dark adaptation curve plots the light intensity required to perceive a spot of light versus time. It is bipartite, with an initial rapid (5–10 minutes) increase in cone sensitivity and then a slower period (15–30 minutes) where rods reach their maximum sensitivity. Thus dark adaptation is complete in 30 minutes in normal subjects.
Fully dark adapted rods allow perception of a spot of light at least 100 times dimmer than cones.
Light adaptation occurs more rapidly than dark adaptation.
AQUEOUS HUMOUR PRODUCTION
INHIBITED BY ONCOTIC PRESSURE
Oncotic pressure is generated by plasma proteins and works against aqueous humour production. Recall that the aqueous is virtually free of protein in the healthy state.
PRODUCTION MAINTAINED BY
- active secretion in the double- layered ciliary epithelium,
- passive diffusion of ions down their concentration and charge gradients and
- ultrafiltration of water and solutes secondary to the CAPILLARY HYDROSTATIC PRESSURE.
Of these processes active secretion is thought to account for 80–90% of aqueous humour production.
Regarding hearing
Regarding hearing
Depolarisation of the hair cell in the cochlea occurs due to the influx of
POTASSIUM
Higher frequencies are detected by hair cells near the base of the cochlea
Sound is audible to humans between 20 and 20,000 Hz
Sound is converted by the organ of Corti into action potentials in the auditory nerves
Mechanism of OPTICAL COHERENCE TOMOGRAPHY
A broadband, low coherence light source is directed at the desired target
A beam splitter is used to simultaneously direct the same light source at
a reference mirror
The reflected light from both the desired target and the reference mirror are directed onto a detector, and the interference pattern is analysed using low coherence interferometry to construct an image of the desired target.
Lacrimal gland - how many ducts
12 excretory ducts.
orbital portion of the gland contains fine interlobular ducts that unite to form 3-5 main excretory ducts,
joining 5-7 ducts in palpebral portion
RETINITIS PIGMENTOSUM
can be caused by a host of mutations, some of which code for rhodopsin.
peripheral retinal atrophy with streaks of pigmentation (bone-spicule appearance—> fine and course strands of pigmentation)
microscopy reveals evidence of retinal vessel attenuation and hyalinization.
it causes night blindness
it can lead to tunnel vision
individuals are typically affected in early adult life
Shifting the hemoglobin-oxygen dissociation curve to the right
increases the release of O2 to the tissues. This shift occurs in
acidosis,
raised temperature
increased 2,3 DPG.
The volume of the eye is
6.5ml.
Where do junctional scotoma and binasal defects lie?
What causes them
Junctional scotoma
Anterior to chiasm at the junction of the optic nerve
Sphenoid meningioma
Binasal
Lateral to chiasm
Dilatation of 3rd ventricle in hydrocephalus
Superior bitemporal
Inferior to chiasm
Pituitary adenoma
Inferior bitemporal
Superior to chiasm
Craniopharyngioma; suprasellar or olfactory groove meningioma
Name
Location
of
Lacrimal Accessory Glands
Krause -> around the conjunctival fornix.
Wolfring -> at the border of the tarsal plate.
Branches of EXTERNAL CAROTID ARTERY
Some Anatomists Like Freaking Out Poor Medical Students:
S – superior thyroid artery
A – ascending pharyngeal artery
L – lingual artery
F – facial artery
O – occipital artery
P – posterior auricular artery
M – maxillary artery
S – superficial temporal artery
The most vulnerable sites to globe rupture are:
*at or just posterior to the insertion of the rectus muscles;
* At the corneoscleral junction (limbus);
* At the site of previous surgical incisions.
ie. Where the sclera is thinnest. Ie usually anterior to the equator
Globe ruptures occur more often in the left eye, as a significant proportion are due to assault by a right-handed assailant.
Volumes of chambers
Anterior chamber = 250micro litres
Posterior chamber = 60 micro litres
Vitreous body = 4ml
Intraocular volume = 6.5ml
Enzyme-linked immunosorbent assay (ELISA)
plate-based assay
both qualitative and quantitative
used to detect
- antigen
- antibody
- peptides,
- proteins
- hormones.
HIV
It is highly sensitive and specific, although it may not detect a mutated antigen.
Unlike radioimmunoassay, ELISA does not require the use of radioisotopes. Instead the antibodies (or antigens) are labelled with an enzyme (such as horseradish peroxidase) which induces a colour change in a substrate when present.
major neurotransmitter at the synapse between photoreceptors and
bipolar cells
GLUTAMATE
VISUAL CYCLE
The human visual cycle involves phototransduction and the subsequent regeneration of visual pigment. 11-cis retinal (a chromophore) is covalently bound to opsins via a lysine residue on one of the transmembrane domains. Upon photon absorption, it undergoes photoisomerisation from 11-cis retinal to all-trans retinal, triggering the phototransduction cascade. All-trans retinal is converted to all-trans retinol in the photoreceptor outer segment before being transported to the retinal pigment epithelial cells, where it is reconstituted into the 11-cis retinal isoform (an isoform of vitamin A derived from carotenoids).
actin
Actin is an important component of the cytoskeleton. It is a protein in the form of a microfilament, 7 nm in diameter, and can exist in monomeric and polymeric forms. Unlike microtubules, which are larger and rigid, actin is flexible.
As well as providing structural support, actin is involved in cell motility, cell division, cell–cell interactions, contractility and the interaction of transmembrane and cytoplasmic proteins.
PHARYNGEAL ARCHES
1
Muscles of mastication (masseter, pterygoids, temporalis);
mylohyoid;
tensor tympani;
tensor veli palatini;
anterior belly of digastric
2
Muscles of facial expression (surrounding the eye these include orbicularis oculi; corrugator supercilii; depressor supercilii; procerus and occipitofrontalis);
stylohyoid;
stapedius;
posterior belly of digastric
3
Stylopharyngeus
4
Pharyngeal constrictors,
levator veli palatini,
cricothyroid
5
Intrinsic muscles of the larynx except cricothyroid
SINUSES PRESENT @
The sphenoid sinus normally develops two to three years after birth and reaches
its adult size around age 14. The ethmoid and maxillary sinuses are usually present at birth, while the frontal sinuses, although occasionally present at birth, usually appear at around two years after birth. They continue to develop well into and even following puberty. The maxillary sinuses are the first sinuses to appear (usually at 3–4 months’ gestation) and are also the largest paranasal sinuses.
HYALOID ARTERY
The hyaloid vasculature develops between the 3rd and 8th week along with the primary vitreous.
From 18 weeks, the hyaloid vessels, the tunica vasculosa lentis and the primary vitreous begin to atrophy. As they regress, Cloquet’s canal is formed.
Blood flow in the hyaloid artery stops at around 30 weeks, and by this point it has ceased to be visible on ultrasound.
By 34–35 weeks it has lost its connection to the optic nerve and has essentially disappeared, though fragments can take longer to resorb entirely.
CORNEAL DYSTROPHY INHERITENCE
Macular dystrophy - aR disorder.
Granular, lattice and Reis– Buckler dystrophies are all aD, resulting from mutations in the TGF-β-induced gene on chromosome 5q31 (as are Avellino dystrophy and Thiel–Behnke dystrophy).
ANIRIDIA
b/l disease
congenital - mutation at PAX6 on chromosome 11
a DOMINANT
Ocular features include nystagmus, cataracts and foveal/optic nerve hypoplasia, with later complications including keratopathy and glaucoma.
The commonest variant (approximately 70% of aniridia cases) is inherited in an autosomal dominant pattern, with no systemic associations.
Of the smaller number of non-familial (sporadic) cases, 30%–50% are associated with nephroblastoma (Wilm’s tumour) due to deletion of the WT1 locus adjacent to PAX-6. Genitourinary malformations and mental retardation may also occur; this is sometimes referred to as WAGR syndrome (Wilm’s tumour–Aniridia–Genital anomalies–Retardation).
A rare form of aniridia is Gillespie syndrome, which is usually autosomal recessive and associated with cerebellar ataxia.
HARDY WEINBERG EQUILIBRIUM
The Hardy–Weinberg equilibrium describes the constancy of gene frequencies in a population from one generation to the next. For a gene with two alleles, it is expressed as:
p2 + 2pq + q2 = 1
where p and q are the frequencies of the two alleles of a gene (i.e. p + q = 1).
It only applies in randomly-breeding populations, in the absence of mutation, genetic drift and natural selection.
VON HIPPEL LINDAU
autosomal DOMINANT cancer syndrome
mutation in the VHL gene on chromosome 3.
Retinal angiomata (also known as capillary haemangiomata) are the cardinal ocular feature. These are visible on dilated fundoscopy, progressing from a small dot to a vascular mass. These can be treated with laser or cryotherapy and can cause retinal detachment.
Cerebellar haemangioblastoma is also a cardinal feature of VHL but not an ocular one.
Other non-ocular features include renal cell carcinomas and phaeochromocytomas.
Chromosomes
Metacentric
Submetacentric
Acrocentric
Holocentric
Telocentric
COMPLEMENT
account for 15% of serum proteins
form an important immunological effector mechanism.
most complement is produced by the liver, extrahepatic synthesis occurs in mononuclear phagocytes. The complement system functions as an enzyme cascade or series of zymogens.
The classical cascade is triggered by antibody–antigen binding, and by acute phase proteins such as CRP.
The alternative pathway is initiated by binding of C3b to factorB on the surface of an organism or foreign material.
There are several regulatory mechanisms preventing inappropriate complement activity, including factor H and factor I (but not factor B), C1 inhibitor and sialic acid.
COAGULASE PROMOSTES BACTERIAL SPREAD
Coagulase indirectly promotes the conversion of fibrinogen to fibrin, which coats the surface of the bacterium and helps to isolate it from host defence mechanisms, including phagocytosis.
The following promote bacterial spread.
Streptokinase activates fibrinolysin and dissolves fibrin clots;
hyaluronidase breaks down the extracellular matrix constituent hyaluronate;
collagenase dismantles collagen.
RISK REDUCTIONS
The relative risk reduction (RRR) = (5/10) x 100 = 50%
The absolute risk reduction (ARR) = 10% - 5% = 5%
INCLUSION BODIES
Owl’s eye inclusion = CMV
Cowdry type A inclusion bodies are nuclear = HSV, VZV
Inclusion bodies can be detected on light microscopy in haematoxylin and eosin (H&E) stained preparations, and may be present in the cytoplasm (predominantly RNA viruses), the nucleus (generally DNA viruses) or both (as in cytomegalovirus).
PRISMS
Porro prisms
-deviated 180degrees AND inverted
-not transposed
DOVE
- inverted
- not deviated or transposed
Wollaston prisms
- split an incident beam of light into two polarised emergent beams at a fixed angle without dispersion.
Fresnel prisms
- series of parallel small prisms of equal refracting angle which cause an equivalent prismatic effect to a single large prism of the same angle.
MAGNIFICATION OF LENSES
60 = 1.15
66 = 1.00
78 = 0.93
90 = 0.76
REFRACTIVE INDICES
Air = 1
Aqueous/Vitreous humour/Water = 1.33
Cornea = 1.37
Lens = 1.38-1.41
Crown glass = 1.52
Hruby Lens
planoconcave lens
used with the concave surface towards the patient.
It has a power of –58.6 D
forms a virtual, erect
and diminished retinal image that lies within the eye of the patient but within the focal range of the slit lamp (usually in the pupillary plane when the lens is positioned close to the patient’s eye).
Deposition material and location in
Fleischer rings
Kayser Fleischer rings
Fleischer rings = iron deposition in the basal epithelial layers at the base of the cone
Kayser–Fleischer rings = copper deposition in Descemet’s membrane caused by Wilson’s disease and certain other hepatobiliary pathologies
Malignant vs Benign
mesenchymal cells
Malignant tumours originating from have the suffix -SARCOMA, whereas benign mesenchymal tumours have the suffix -oma (compare liposarcoma: malignant with lipoma: benign).
Similarly malignant tumours originating from
the epithelial cells of surface tissues are denoted CARCINOMA (e.g. squamous cell carcinoma) and benign tumours are denoted papillomas (e.g. basal cell papilloma).
Glandular epithelial cell tumours are called ADENOCARCINOMA if malignant and adenoma if benign.
Tumours derived from neuroectodermal cells are generally malignant, with the notable exceptions of neurofibromas, ganglioneuromas and some meningiomas.
POOR PROGNOSTIC FACTORS IN
CHOROIDAL MELANOMAS
Epitheliod cells
Monosomy 3
Partial duplication of 8q
Old
Large tumour size
Extrascleral extension
Following separation of the neurosensory retina from the retinal pigment epithelium…..
- Degeneration of photoreceptors
- Proliferation and migration of the retinal pigment epithelium
- Subretinal recruitment of macrophage
Corneal graft rejection
RISK FACTORS
type IV hypersensitivity reaction.
Risk factors include:
* Young age
* Repeat grafts
* Large grafts
* Preoperative stromal vascularisation
* Loose or broken sutures
* Active inflammation
Muscarinic anatogonist
Examples
EFFECTS
Atropine, cyclopentolate and ipratropium
SE: dry mouth, tachycardia, palpitations, and urinary retention.
The first two agents are common topical mydriatics and cycloplegics, whereas ipratropium is used as an inhaled bronchodilator.
//Pyridostigmine is an inhibitor of acetylcholinesterase, used in the treatment of myasthenia gravis. It enhances rather than blocks acetylcholine activity at parasympathetic synapses.
AQUEOUS FLOW
CONVENTIONAL - via TM (pressure dependent)
* trabecular meshwork to Schlemm’s canal;
* Schlemm’s canal to collector channels and aqueous veins of Ascher;
* collector channels and aqueous veins of Ascher to venous plexuses and conjunctival veins)
e.g muscarinic agonist pilocarpine causes miosis and ciliary body contraction to open TM channels
UNCONVENTIONAL - uveo-scleral flow
e.g prostaglandin analogue e.g lantoprost
BBlocker/Carbonic anhydrase inhibitors (e.g. dorzolamide)
- reduce aqueous production
AAgonist (e.g. brimonidine) - reduce aqueous production and increase aqueous outflow
Drusen LOCATED WHERE
Drusen is situated between the basement membrane of the RPE and the Bruch’s membrane.
The parasympathetic nerves travel along the
inferior division of the oculomotor (third) nerve
—> nerve supplying the inferior oblique muscle
ciliary ganglion;
short ciliary nerve to innervate the sphincter pupillae.
Squamous cell carcinoma consists of squamous cells with prominent nuclei and abundant eosiophilic cytoplasm.
BCC exhibits the pathognomonic palisading of cells at the periphery of the tumour.
NF Type 1 and 2
Autosomal DOMINANT
NF Type 1 occurs from a mutation in the NF-1 gene on chromosome 17. It is characterised by:
cafe-au-lait spots
Lisch nodules
goniodysgenesis
retinal hamartomas
optic nerve glioma
phaeochromocytoma (nf1 and vhl)
NOTE: B/L acoustic neuroma is associated with NF Type 2 but can also occur in NF1
________
NF2 - chromosome 22
nearly all patients with NF2 will develop b/l acoustic neuromas before 30
meningioma
EOG
The EOG is an indirect measure of the standing potential of the eye. It depends on a normal retinal pigment epithelium. It requires co-operation of the patient who moves the eyes back and forth over a specific distance. The light response is higher than dark response. The result is given as a ratio between light to dark response. The normal ratio is more than 180%.
Luminous flux is the total light (or perceived light power) emitted from a source. It is measured in lumen (lm).
Luminous intensity is the light emitted per unit solid angle; it is measured in candelas.
Illumination/illuminance is a measure of the amount of light arriving at a surface. It is measured in lux, which measures luminous flux per unit area.
Luminance is a measure of the amount of light emitted, reflected, or transmitted from a surface; luminance is measured in lamberts.
Stickler’s syndrome
most common inherited cause of retinal detachment,
most common cause of rhegmatogenous retinal detachment in childhood.
AMINOGLYCOSIDES
e.g. GENTAMYCIN
NEOMYCIN
STREPTOMYCIN
they are not as effective against systemic infection if given orally
bind 30s subunit on ribosomes -> inhibits protein synthesis
they act on messenger RNA
they are NOT effective against streptococci or anaerobes as
they require aerobic transport mechanisms to enter the bacterial wall
what is the power of the study
(1 - beta) is also called the power of a study.
It is the probability of not accepting (i.e. rejecting) the null hypothesis when the alternative hypothesis is true.
Put another way, it is the probability that if there is indeed a difference, that this difference will be found statistically.
The circle of least confusion in Sturm’s conoid coincides with the focal point of the spherical equivalent of the toric lens.
A patient with a history of keratoconus presents with a 1-day history of painful reduction in vision as shown in the image above. What is the initial treatment of choice?
This patient has hydrops caused by a rupture of Descemet’s membrane with resultant corneal oedema and opacification. The initial therapy includes topical steroids, cycloplegics, and hypertonic saline drops. Once the condition has settled, scarring may occur and corneal transplantation may then be considered. Corneal transplantation should not be considered in the acute stage while the eye is inflamed.
120 million rods
6 million cones in the retina.
The chorda tympani is a branch of the nervus intermedius which in turn is a sensory component of the facial nerve. It contains: the parasympathetic nerve fibres that supply the salivary glands and the sensory nerve fibres that innervate the anterior two-third of the tongue. Anatomically, it passes between the internal jugular vein and internal carotid artery as it travels anteriorly. The greater petrosal nerve that contains parasympathetic nerve fibres to the lacrimal nerve exits the nervus intermedius at the geniculate body and therefore is not part of the chorda tympani.
TRIALS
I = SAFETY AND SE
II = DOSING AND EFFICACY
III= EFFICACY VS GOLD STANDARD
IV = SURVEILLANCE - EFFECTIVITY AND SIDE EFFECTS
CORNEAL ENDOTHEILIAL COUNT
KIDS - 3500/mm2
ADULTS = 2500/mm2
ELDERLY = 2000/mm2
BCC
- NODULAR
well circumscribed
clear peripheral palisading
easily excised; - SUPERFICIAL
appear as lobules localised to the dermal–epidermal junction;
3.INFILTRATIVE
grow aggressively in strands with reduced peripheral palisading
indistinct border;
- MUTLINODULAR multiple small nodular aggregates of tumour.
Both infiltrative BCCs and micronodular BCCs have an increased tendency for subclinical spread and caution should be taken to ensure clear margins.
