MID SEMESTER EXAM Flashcards
Pathophysiology of emmetropisation:
Hyperopic defocus (not accommodated over) > decreases amplitude of neural response > altered signals pass RPE+Choroid > Scleral fibroblast gene expression altered > ECM remodelled > ^creep rate > elongation
Types of myopia:
Simple myopia: progresses 0.5D per year till 20 years
Pathologic myopia: excessive axial elongation > myopic maculopathy/ optic neuropathy
Pseudomyopia: over-reactive accommodation from ciliary spasm
Nocturnal myopia: poor visual cures > tonic accommodation > myopic blur (night driving)
Myopic shift secondary to cataracts
Theories for myopia development:
Dopamine: Decreased sun > poor activation of dopamine receptors in eye > myopic development
Hyperopic defocus: peripheral hyperopic defocus (accom lag / interior walls) > emmetropization process > axial elongation to resolve peripheral blur > foveal blur
Risk factors for myopia:
Genetic (7/20/40%) : Specific MYP genes or general emmetropisation/structure inheritance
Environmental (dopamine/peripheral blur) : time inside/study/education
Risk factors for myopia:
Genetic (7/20/40%) : Specific MYP genes or general emmetropisation/structure inheritance
Environmental (dopamine/peripheral blur) : time inside/study/education
Atropine myopia control:
0.05% daily (ATOM2/LAMP) muscarinic antagonist against sclera
Causes photophobia/blur/rebound, still needing glasses
OrthoK myopia control:
Steepens periphery/flatten centre via neg-pressure
ROMIO study > 50% reduction
Causes discomfort
Convergence process in accommodation:
Blur/disparity activates supraocular motor nuclei > innervating oculomotor nuclei > axons sent to medial longitudinal fasiculus > contraction of medial rectus via CN3 > convergence while accommodating
MF soft CL myopia control:
Plus power in periphery > hyperopic defocus correction
MiSight lenses have 55% reduction
Risk infection/requires compliance
Stellest myopia control:
Lenslets in peripheral lens reduces hyperopic defocus
Reduces myopic progression (in dioptres) by 50%
May be combined with atropine if significant progression
Very costly
Stable myopia control:
Specs
Soft CLs (daily-monthly)
RGPs
OrthoK
Laser(PRK/LASIK/SMILE)
Clear lens extraction
Hyperopia development:
Genetic factors causing poor emmetropisation, flat cornea, short axial length
Accommodation process:
Blur signal received by visual cortex > bilateral Edinger Westphal nuclei (CN3 oculomotor) in midbrain > preganglionic parasympathetic fibres move with CN3 to ciliary ganglion to synapse to postganglionic neurons > neurons travel with CNV1 ciliary nerves to ciliary muscle and pupillary sphincter muscle > activation of muscarinic receptors by Ach > contraction of ciliary muscle and sphincter muscle
Hyperopia and aging:
Latent becomes manifest as accommodation decreases. Noted increase in asthenopia (fatigue)
Commonly produces esophoria (sometimes tropia) > inward turn
Management of hyperopia:
Cyclopentolate > full hyperopia measurement
Education for small latent hyperopia
Specs for symptomatic (asthenopia/esophoria/strabismus/amblyopia/blur)
Lens anatomy:
Capsule: elastic membrane, binds zonules, molds lens
Epithelium: single layer cuboidal, equatorial mitosis, nutrient transport, secretes capsule
Fibers: formed from epithelia, contains crystallins a/b/y (soluble proteins with RI)
Mechanisms of cataract formation:
1: Cell proliferation/differentiation disruption (Growth factors)
2: Metabolic disturbance/osmotic regulation (Na/Ca)
3: Calpains
4: Post-translational modification (lens proteins)
5: Oxidative damage
6: Loss of defense mechanisms
Patho of cortical cataract:
Mechanisms 2/3
Dysfunctional Na/K from damage > NA/K homeostasis loss > Ca/Na influx > overhydration/ calpain activation
Crystallin proteolysis > soluble protein decrease (relative insoluble increase) > ray-like space opacify
Patho of nuclear cataracts:
Mechanisms 1-6
PTM glycation of tryptophan cause fluorescent chromophore
Cortex-nucleus barrier to glutathione
Patho of PSC:
Mechanism 1
DM / Cort. / age > Change in GF expression (FGF) > aberrant epith. Proliferation at germinative zone
Dysfunctional cells collate with adjacent fibers forming balloon cells
Poor Na/K atpase transport > swelling > vacuoles / extracellular granular material
Nuclear cataract effect on vision:
Myopic shift (protein aggregation)
Decreased VA/contrast sense
Tritan defect (blue blocked by yellowing additive PTM)
PSC effect on vision:
Decreased VA/contrast sense
Worse in day/near
Vacuoles in flux
Cortical cataract effect on vision:
Decreased contrast sense
Astigmatism (localised RI change)
Worse in night
Complications of cataracts surgery:
Post. Capsule opacity (PCO) 50% by 2y: proliferation/migration of remaining lens epith.
Dislocated IOL
Retinal tear
Endophthalmitis
Risk increased with DM/high myopes
Other types of cataracts:
Congenital (blue dot)
Trauma (Rosette)
Metabolic (myotonic dyst. > Christmas)
Disease (Uveitis > PSC)
Toxic (cort. > modified Na/K)
Aqueous layer formation:
97% of film from lacrimal gland (95%) / Krause & Wolfring
From inner/upper lid
Lipid layer:
Thin outer meibum layer from sebaceous glands in tarsal plate (Meibomian glands) secreted during blink
Prevent evapouration, acts as surfactant (spreads film)
Non-polar cholesterol, esters, phospholipids, alcohols
Aqueous layer Components:
Water, electrolytes, proteins, growth factors, pro-inflammatory interleukin cytokines (accumulate during sleep), Lysozyme, lactoferrin, urea, glucose, ions (Ca/Mg/Na/K), IgA
Aqueous layer function:
O2 > Cornea
IgA / Lactoferrin / Lysozyme > Antimicrobial activity
Maintain moisture of non-keratinized corneal epith.
Leukocyte transport after injury
Smoothens optical surface
Flushes debris
Types of mucins:
MUC1/4/16: membrane bound, with galectin glue to glycolax
MUC7 / MUC5AC: secretory to prevent strands of mucous (light scatter)
Mucin layer composition
Thinnest layer of mucus from goblet cells in conj. / plica semilunaris / glands of henle & Manz
Hydrophilic High mol. Wgt. Mucin glycoproteins (transmembrane or secretory)
Transmembrane mucins bind glycolax from corneal epith.
Secretory are soluble in aqueous forming gel
Mucin layer function
Turns hydrophobic corneal epith. Hydrophilic > corneal wetting
Attaches film to cornea, allows lubrication
Definition of dry eye disease (DEWS 2):
Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles
Causes of ADDE:
Sjrogren’s syndrome (autoimmune against exocrine glands)
Lacrimal gland dysfunction: Primary (age/genetics) or secondary (AIDS/Lymphoma)
Lacrimal gland duct obstruction
Alteration in stimulation (reflex block)
Causes of EDE:
Lid dysfunction:
MGD, poor closure, poor blink rate, damaged
Surface dysfunction:
Cls, lesions, Vit A def., allergy/infection
ADDE from secretion stimulation alteration:
Reflex hyposecretion from reflex sensory block (CLs/LASIK/herpes/diabetes) or reflex motor block (CN 7 lesion)
Blockage of para/sympathetic nerves to lacrimal gland
Decreased androgen from hormone loss (age)
Exposure to anti depressants/histamines/birth control
hyperosmolarity
Loss of aqueous or evaporation > hyperosmolarity > epithelial irritation > Mitogen-activated protein kinase (MAPK) & NFkB activation > inflammatory mediator release (IL-1 & TNF-1/MMPs) > Matrix metalloproteinases damage epithelium / goblet cells > epitheliopathy (corneal epithelium loss) > pain > reflex stimulation
DEWS step 1:
Education (condition, diet)
Environment change
Eliminated offending medication
Lubricant (lipid drops of MGD)
Lid hygiene/warm compress
DEWS step 2:
Non pres lubricants
TT oil for demodex
Punctal occlusion
Over night ointment
Chlorsig for bleph
Blepharitis:
Lid inflammation from Staphyloccal or dermatitis
Ant. Affects zeis glands/lash follicles (crusty scales) > bleph debris decreases tear quality
Pos. affects meibomian glands (meibum capping) > EDE + inflammatory mediator passage from lid
Schirmer test:
5mm fold in Whatman filter inserted under lower lid (temporal side), don’t touch cornea/lash
Px closes eyes over filter
Remove paper after 5min
<10mm without anesthesia / <6 with ana. Indicates abnormal
TFBUT:
NaFl instilled with Wratten #12 cobalt filter lens
Px blinks before holding eyes open
Timed appearance of black spots
<10s abnormal, repeated breakup in given area indicates localized surface abnormality
Non neoplasic lesions of the lids:
Hordeolum
Chalazion
Cyst of zeiss/moll
Epidermal inclusion cyst
Dermoid
Xanthelasma
Molluscum contagiosum
Benign lid lesions:
Verruca vulgaris
SC/BC papilloma
Actinic keratosis
Freckle
Naevi
Cap. Hemangioma
Port-wine stain
Pyogenic granuloma
Neurofibroma
Malignant lid lesions
BCC
SCC
SGC
Malignant melanoma
Lid BCC patho:
UV on pluripotent stem cells > tumor mutations > unregulated proliferation of abnormal basal cells
Patched mutations / Sonic hedgehog pathway: altered “patched/smoothend” genes > sonic signalling pathway upregulation > ^activation of genes for cell differentiation
Mutations in detox proteins: altered genes for glutathione-S-peroxidase enzyme > decreased skin oxidation defence
Mutation in p53 ts gene > unregulated abnormal cell growth (noted in 50%)
BCC signs/symptoms and treatment:
Superficial: red patch, may crust/sting
Nodular: pearly/translucent bump
Sclerosing: white scar area
Biopsy > +/- Moh’s
SCC patho:
UV > proliferation (^mutation) / gene alteration / immunosupression > p53 / melanocortin-1 receptor gene alteration > Immunosuppression, unregulated proliferation of squamous epith., decreased apoptosis
SCC signs/symptoms and treatment
Initial erythematous tender red nodule w/hyper keratosis
Develops with ulceration and expansion
Requires cryo + biopsy (solar keratosis)
+/- Moh’s for remaining lesion
Benign conjuntival lesions:
Pingueculu/pterygium
Psuedopterygium
Inclusion cyst/dermoid
Papilloma
Actinic keratosis
Cap. Hemangioma
Conj. Naevus
Racial melanosis
Ocular melanocytosis
OSSN patho:
HPV/UV > squamous proliferation > CIN (partial replacement) > SCC (dysplastic cells pass basement into stroma)
Conjuntival naevus:
Clustered melanocytes in basal epith. From UV/genetics
Solidary raised pigmented lesion, can develop with age
Usually asymptomatic, photography monitored for <1% malignant transformation
Malignant conj. Lesions:
OSSN
PAM
Conj. Melanoma
OSSN presentation:
Leukoplakic: localised thickening with white plaque
Papilomatous: highly vascular mass w/ corkscrew BV
Gelatenous: transparent thickening of squamous epith.
Parasympathetic pupil pathway:
Edinger Westphal > with CN3 (accommodative axons) > cavernous sinus > synapse at ciliary ganglion > with short ciliary via subarachnoid space > iris sphincter > bilateral / equal constriction
Afferent pupil pathway:
Retinal light input > Ganglion cell axions > optic tract > split at chiasm > split before LGN > sup. Colliculus > synapse with olivary pretectal nucleus.
Afferent (retina) / efferent (light reflex) integrated > ipsi/contralateral EW nuclei of CN3
Sympathetic pupil pathway:
1st neuron: hypothalamus > ciliospinal Centre of bulge and Waller (C8/T2)
2nd: preganglionic fibers pass stellate ganglion (lung apex) > sup. Cervical gang. (jaw)
3rd: postganglionic fibers plexus with carotid > cavernous sinus > SO fiss. With nasociliary of CN5 > long ciliary in suprachoroidal space > dilatory > mydriasis
Also innervate mullers. facial innervation splits before sup. Cervical G.
PERRLA examination (first test):
Pupils Equal Round Reactive to Light (direct/consensual) and Accommodative
1. Direct response: light activates ipsilateral EW (afferent) > ipsilateral pupil constriction (efferent)
2. Consensual: light activates ipsilateral EW > contralateral EW activation > contraction
Accommodative: Near response triad > visual cortex / pupillomotor Centre in midbrain response
Signs of choroidal naevus developing to malignant melanoma:
Documented growth
Blur, metamorphopsia, VF loss, photopsia
>5mm diameter, >1mm deep
Presence of orange lipofuscin
Located near OD
Associated serous RD
Causes of anisocoria:
Efferent pupil pathway dysfunction:
Physiological (EW asymmetric inhibition)
CN3 palsy
Adies tonic
Aberrant regen (CN3p / adies)
Pharmacological
Pupil damage (trauma/Sx)
AAGC
Horners syndrome symptoms:
Disruption of sympathetic innervation to pupil dilator / mullers / ciliary body / facial sweat glands.
Causes Miosis / partial ptosis (1mm) / anhidrosis (not 3rd order) / accommodative excess / Conj. BV dilation
Congenital cases > Lighter/Darker Brown/Blue eyes
RAPD examination (second test):
Swinging flash test for Relative Afferent Pupil Defect.
No RAPD: equal constriction W/O radiation excluding Hippus
Mild: affected pupil constricts and redilates
Moderate: affected pupil does not change, then dilates
Severe: immediate dilation of affected pupil
CN3 palsy symptoms:
Mydriasis: Pia BV compression > pupillomotor fiber ischemia
Full ptosis: sup. Levator innervation loss
Down/out turn: Sup/Inf/medial rectus, inf. Oblique innervation loss
Thunderclap headaches
Causes of CN3 palsy:
Pupil involving: compressive lesion/aneurysm on pia BV for parasym. fibers
Pupil sparing: DM/HT > main trunk ischemia
* Giant cell arteritis (temple pain) / Pos. communicating artery aneurysm / cavernous fistula common
Myasthenia gravis imitates pupil sparing palsy
Common causes of horners syndrome:
1st : brainstem/spinal disease (vascular/tumor), diabetic neuropathy
2nd: Pancoast tumor, carotid/aortic aneurysm, neck lesion
3rd: carotid aneurysm, cavernous sinus mass, cluster headaches
Common pharmacologic mydriasis/miosis:
Tropicamide: Muscarinic antagonists > Ach receptor block > sphincter paralysis
Phenylephrine: adrenergic 1 agonist
Pilocarpine: muscarinic agonist > Ach receptor upregulation > miosis
Apraclondine: Alpha agonist > dilation (weak a1, strong a2)
Tamulosin: Alpha antagonist > adrenaline receptor block > dilator paralysis
Types of ptosis:
Myogenic (MG, simple congenital, blepharophimosis)
Neurogenic (CN3, horner, marcus gunn)
Mechanical
Aponeurotic (LPS disinsertion)
Pseudooptosis
Assessing anisocoria greater in light:
Greater in light > parasym. Loss > CN3 palsy / adies
0.1% pilocarpine > great constriction of affect pupil in early adies (<2w) from Ach upregulation
1% pilocarpine > constriction of CN3 palsy
Faliure to constrict > pharmacological/atrophic mydriasis
Measuring ptosis:
Margin reflex distance: 4mm from corneal reflex and upper lid
Palpebral fissure: difference between eyes: 2/3/4mm mild/moderate/severe
Levator function: pressure brow, measure upper lid change from downgaze and upgaze (15mm normal)
Upper lid crease: distance between lid margin and crease in downgaze (8mm normal)
Assessing anisocoria greater in dark:
Greater in dark > sym. Loss > horners/aberrant regen (CN3/adies)
0.5% apreclonidine > pupil dilation of affected eye. Requires 1w post onset for a1 upregulation
1% hydroxyamphetamine > dilation of affected eye if 1/2 order neuron lesion (release of 3rd neuron noradrenaline)
Myasthenia gravis:
Autoimmune disorder > auto antibodies against Ach receptors of striated muscle > weakness
Causes limb weakness, lack of expression, ptosis +_ diplopia worsening over the day.
Tested via 1minute upgaze, or ice pack for 2m (improves neurotransmission)
Functions of the conjunctiva:
Connect lids to eye (enclosed sac)
Mucin/aqueous production
Immune function (Macrophages, langerhans cells)
Mediates passive/active immunity
DDX red eye:
CL related: CLARE/CLPU/GPC/Tight lens syndrome/DED
Corneal defect: Keratitis/abrasion/erosion/FB
AC disease: Uveitis/AACG
Wall inflammation: Scleritis/episcleritis/conjuntivitis
Orbital cellulitis/sub. Conj. Heam.
Structure of conjunctiva:
Epithelium: columnar W/ goblet apocrine glands and langerhan immune cells
Substantia propria: lymphoid layer (neutrophil/mast/Tcells) and fibrous layer (BV/nerves)
Types of allergic conjunctivitis:
SAC/PAC
Atopic
Vernal
GPC
Signs of conj. Inflammation:
Hyperaemia: from prostglandin release
Oedema: serous leakage from BV tight jun. via prost. release
Membranes: pseudo/true
Cicatrisation: scarring
Follicles/papillae
Follicles and papillae:
F (viral/toxic): lymphocyte hyperplasia at fornix/tarsal > grey (macrophage) masses
P (bac./allergic): epith. Hyperplasia w/ infiltrate mast cells/eosinophils/fibroblasts > tarsal vascular cobblestones
Types of infectious conjuntivitis:
Bacterial (hyper-/acute/chronic)
Adenoviral (follicular/PCF/EKC)
HSV
Chlamydial (adult inclusion/trachoma)
Fungal / parasitic / protozoan
Neonatorum
Actue bacterial conjuntivitis
Gram+: Staph/strep aureus/pneumoniae
Gram-: haemophilus
Burning, mucopurulent, diffuse hyperemia, papillae
Associted fever/respiratory infection
Self limiting 3w, chlorsig .5% qid 1w reduce symptoms
Types of discharge in conjunctivitis:
Watery (viral/acute allergic): serous exudate / tears
Mucoid (chronic allergic / DED): mucoid from inflamed goblet cell
Mucopurulent (chlamydial / bacterial): mucoid and pus (leukocytes)
Purulent (gonococcal): pus
Adenoviral conjuntivitis:
FAC/PCF/EKC
Epiphoria, hyperemia, ocular discomfort
Follicles
Superficial punctiate keratitis
Lid oedema
Preauricular lymph adenopathy
Associated URTI
Types of non-infectious conjunctivitis:
Toxic follicular
Molluscum contagiosum
Stevens-johnson syndrome
Graft vs. host disease
Ocular cicatrical pemphigoid
Sup. Limbic kerato-
EKC management:
Self limiting 1-3w.
Practice good hand hygiene
Cold compress / lubricants (comfort)
Topical cortico. (flarex 0.1% qid) for corneal subepithelial infiltrates
Herpes simplex conjuntivitis
Common HSV-1 (ocular) initial infection (<5yo).
Irritation, Watery, follicles, preauricular lymphadenopathy, HSV vessicles (lids),
Dendritic ulcer
Self-limiting 1-2w
Corneal involvement > acyclovir 3% 5/d 1w
No steroids
Acute inclusion conjuntivitis:
Chlamydia trachomatis bacteria serotye D-K (1-2w incubation)
Unilateral hyperemia, watery, purulent
Large follicles w/papillary hypertrophy (tarsal conj.) > pannus
Swolen preauricular lymph
Rare SPEE/stromal infiltrate/limbal swelling
GP systemic azithromysin 1g.
Trachoma cause/symptoms:
C.trachomatis bacteria serotype A/B/C
Initial infection (1w incubation) > mild mucopurulent conjuntivitis
Recurrent infection > active chronic inflammation
Late stage > inactive inflammation
Trachoma active inflammation:
Irritation, DED, blur
Follicles w/papillary hypertrophy > pannus
Thickening of tarsal conj.
SPEE, limbal follicles
Trachoma treatment:
Initial infection > self limiting
Recurrent > single dose of azithromycin 20mg/kg up to 1g
Molluscum contagiosum conjuntivitis:
Poxvirus nodules containing intracytoplasmic inclusions toxic to conj.
Common 2-4yo
Lid umbilated nodules
Conj. Hyperemia, follicles, mucoid
Self limiting 3-12m, lid nodule excision if needed
Trachoma inactive inflammation:
Cicatrical fibrosis of conj. > entropion > corneal scarring
Fibrosis/fusion of conj. > symblepharon
Tarsal scarring > white lines (arlt’s line)
DED from meibomian/goblet loss
VKC patho:
Severe in spring, males under 20 w/atopy
Exposure to allergen (pollent/dust) > type 1 HS reaction w/T-cell activation > IgE binding > mast cell degranulation > histamine/prostglandin release > itch/pain and BV dilation
Profuse burning, ropey mucous, itching
Dissuse papillary hypertrophy w/mucous deposits
+/- tarantas dots, corneal pannus/SPEE, sheild ulcer
SAC/PAC patho:
Seasonal/year long exposure to allergen (pollen) > type 1 immediate HS reaction > allergen binds IgE on mast cells > degranulation > histamine/prostglandin release > itch/pain and BV dilation
Causes hyperemia, tearing, mucoid discharge, lid oedema, chemosis, papillary response
Associated nasal symptoms
AKC patho:
Rare, atopy related, >20y, resolves by 50
Allergen exposure > type 1 / 4 HS reaction > activation/infiltration of T cells > severe chronic inflammation
Severe itching, mucoid, hyperemia, chemosis, macerated lids, narrow fissure, chronic bleph., papillae
+/- cicatration > symblpharon, SPEE > erosions
Ocular defences:
Lids: physical/flushing
Tear film: IgG/A, lactoferrin, lysozyme
Cornea epith.: immunoglobins (IgG/A) defer microbe adhesion
Mucin: trap microbes
Innate immune: complement protein system
Tight junctions: prevent passage
GPC patho:
Allergic/mechanical reaction, associated atopy / CLs
Primary: type 1 HS reaction to alleregens
Secondary: environmental antigens adhere to mucus/proteins on CLs > repeated contact w/tarsal conj. On blink
Irritation, itching, hyperemia, Papillae, mucous
+/- debris on CLs, loss of CL tolerance (symptoms worsen after CL removal)
Allergic conjuntivitis treatment:
- OTC vasoconstrictor: oxymetazoline 20mg/spray
- Histamine antagonist Levocabastine HCl 0.05%
- Mast cell stabilisers lodoxamide 0.1%
- Combined (2/3) Ketotifen Fumarate 0.025% (Zaditen)
- NSAIDs ketorolac 0.5%
Cool compress, shower before bed, avoid allergen
Process of microbial keratitis:
Loss of defence (glycolax loss) > breach in integrity allowing microbial colonisation (usually staph)
Antigen-antibody immune reaction > immune cell influx (neuto/macro) > stromal infiltrate
Stromal collagen degraded via microbial Enzymes (proteases) > thinning/scarring
Damage continues until microbe is removed
CL risk of keratitis:
1/proportional to Dk/t value
Least with RGP lenses
From hypoxia > bacterial/epithelial adhesion
CL related lesions (CLARE/CLPU) > epith. Break > microbial vulnerability
Usually gram- psuedomonas aeruginosa
Risk factors for keratitis:
CLs
Sx/trauma
DED/bleph
Co-infection (acanthamoeba/HSV)
Blink dysfunction
Immunosuppression
Immune loss (DM/malnutrition)
Signs of keratitis:
BV dilation (prostglandins)
Corneal oedema (prostaglandins)
Discharge: water/mucopurulent > CNV activation/bacteria
Pain (severe/increasing)
Epith. Defect (microbe induced apoptosis/immune infiltrates)
AC reaction (Low IOP from low ciliary secretion, or high IOP from trabecular block)
Bacterial keratitis symptoms:
Pain severe/increasing
Soggy infiltrate, centrally
Hyperemia, oedema, mucopurulent
+/- Ac reaction (low IOP, hypopyon)
Fungal keratitis symptoms:
Pain gradual onset
Hyperemia, photophobia, mucopurulent (bac superin.)
Filamentuous: feathery
Yeast ligh: button
Acanthamoeba keratitis symptoms:
Following days of incubation.
Early stage:
FBS, blur, photophobia, signigicant pain (radial keratoneuritis), epiphora, epith. Hazy
Late stage (weeks): stromal “wessely” infiltrates, extreme pain, hyperemia
Acanthamoeba patho:
Corneal epith. irritation > mannose glycoprotein upregulation > Acan. trophozoites adhere via acanthapodia > protease MIP133 release > epith. Cytolysis > stromal invasion / degregation
Immune neutro/macro. Influx > immune proteases > ring infiltrates
Acan. Cluster nerves > immune/anti-microbial response > form dormant cysts
Fungal keratitis patho:
Ahesion following epith. Dysfunction > proteolytic enzyme release > epith. Necrosis > stromal collagen dissolution
^size > poor neutophil phagocytosis
Usually present with bacterial co-infection
Acanthamoeba keratitis risks:
Present in water sources
Poor CL use > biofilm build up
Secondary to damage/HSV
Symptoms of HSK:
Hx prior HSK
FBS, photophobia, epiphora, blur, hyperemia
desensitization
Dendritic lesion
IOP increase (trabeculitis)
Lid HSV vessicles
Acanthamoeba treatment:
Cease CLs and see ophthal.
Cocktail of polyhexamethylene biguanide (PHMB) with Hexamidine 0.1% and Neomycin tapered from hourly>quaterly from 2-6 months
Management of bacterial keratitis:
Fluoroquinolone mono w/ciprofloxacin 0.3%
Q10m for first hour > qhour for 24h > review > qhour for 24h > q2hour
Unresponsive/complex needs referal
Fungal keratitis treatment:
Ophthal referal
Topical natamycin 5% per 1/2hour for 24h then qid for months
Paired BS antibiotics prevent co-infection
Cycloplegic for ciliary spasm
Never steroids (increase fungal replication)
CL complications:
Hypoxia
Neovasc
CL asso. DE
3-9 stain
Sup. Epith. Arcuate lesions (SEALs)
Tight lens syndrome
Toxic/allergic keratoconjuntivitis
CL asso. GPC
CL asso. Acute red eye (CLARE)
Culture neg. Periph. Ulcer (CNPU/CLPU)
Microbial keratitis
CL corneal hypoxia:
Low Dk/t CLs, sleeping
Hypoxia > anaerobic respiration > ^LA (low pH)/ATP loss > pump dysfunction > oedema
Causes blur, pain, photophobia, tearing, corneal haze, stromal thickening
Requires CL ceassation, lubrication, refit higher Dk/t lenses
CL corneal neovasc
Extended wear of low Dk/t lenses, sleeping
Hypoxia > conj. Vessel growth
Visual extension of conj. Vessels
Requires refit of Cl with hight Dk/t
Switch to daily lenses
CL associated dry eye:
CLs split tear film / absorb moisture > Tear instability
Causes FBF, tearing, burning, worse at end of day
Requires lubricants, lens change/cessation
3/9 oclock staining of CLs
Mechanical abrasion of RGP on limbus, abnormal blink
Causes intolerance, gritty, punctate epith. Loss at 3/9
Requires education on light blinking, lubricants, refit
Tight lens syndrome:
Tightnening of CL during wear
Causes pain, photophobia, blur, hyperemia, satining limbus
Requires cessation, lubricants, prophylactic antibiotic (epith. Break)
Toxic/allergic CL conjuntivitis:
Acute chemical toxicity from peroxide solution / preservatives in solution > type 1 HS or type 4 (long term)
Causes acute pain on insertion, hyperemia/chemosis, diffuse epithelial punctate stain w/ scattered infiltrates
Requires cessation, non-pres lubricants
CL associated GPC patho:
Allergic type 1/4 of tarsal conj. To antigens coating CL, or mechanical abrasion on blink > activation of mast/eosinophil/basophil > ^ cytokine/GF > fibroblast stimulation > Collagen production > Papillae
CL associated GPC signs and management:
Irritation, hyperaemia, CL intolerance (worsens without wear), papillae on sup/inf tarsal conj. Mucous
Requires cessation (1mo), change cleaning regieme
CL associated acute red eye (CLARE)
Sterile inflammation via colonisation of gram- psudomonas
Microbe adhereance > exotoxin release > antigen antibody response > inflammatory cascade > immune influc > infiltrates / hyperemia
Causes severe pain, photophobia, epiphoria, subepithelial infiltrates, SPEE
* No mucopurulent discharge
Requires cessation (days)
CL associated microbial keratitis:
CL wear > microtrauma / O2 disruption / CL colonisation > (if glycocalax breached) microbe colonises cornea > stromal collagen degraded via enzymes
Culture negative peripheral ulcer:
Sterial inflammation from gram + staph
Adherence > exotoxin release > Microbe adhereance > exotoxin release > antigen antibody response > inflammatory cascade > immune influc > infiltrates / hyperemia
Causes severe pain, photophobia, epiphoria, subepithelial infiltrates, SPEE
Infiltrates larger than epithelial defects, unlike microbial keratitis
+/- AC reaction
Requires cessation (days)
Distinguish CPLU and MK:
PEDALS
Pain: severe, increasing
Epithelial defect: boggy (oedema) / pesudodendrites (acan)
Discharge: mucopurulent in MK
AC reaction:
Location: central ulcers are infective
Size: defects > 2mm infections
HSV/VSV structure:
dsDNA
Icosahedral capsid
Viral glycoproteins on envelope
Initial HSV infection:
Direct via secretions (cold sores) > epith. Replication > primary manifestation > blepharokeratoconjuntivitis > retrograde transport to trigeminal ganglion
Causes of HSV reactivation:
UV (induced immunosuppression)
Trauma
CLs
Stress
VZV initial infection:
Chickenpox
Rash, fever, malaise, pneumonia
Traves to dorsal root/CN sensory ganglia (retrograde)
Lies dormant
Herpes Zoster reactivation:
Loss of cell mediated immunity against virus (stress/age) > Shingles
Causes prodromal malaise, fever, fatigue, painful rash
HZO when virus travels opthalmic branch of CNV
Clinical presentation of HZO:
Lid vessicles/edema/inflammation
Conjuntivitis w/ papillae/follicles/membranes
Epi/scleritis
Keratitis
Epitheliopathy (pseudo-dend.)
Uveitis
Optic neuritis
Post-herpetic neuralgia
HSK Geographic ulcer:
Immunocompromised Px enlarged ulcer. Larger risk of co-infection
3% aciclovir ointment 5/d until re-epith.
Lissamine stains only periphery
HSK dendritic ulcer:
Epithelial ulcer w/ stromal oedema, desensitisation, ^IOP
Limbal ulcer > ant. Stromal infil. (white BC)
Photophobia, slight hyperemia
Self limiting (3w), can be anaesthetised and debrided
3% aciclovir 5/d for 2w
Metaherpetic ulcer:
Poor healing of geo. Ulcer
Lissamine stains central ulcer
Requires refferal
Neurotrophic ulcer:
Spontaneous breakdown of epith. Secondary to nerve damage > poor GF delivery
From HSK, HZO, LASIK, DM
Appears as enlarged SPEE covering several layers of epith.
Requires topical lubricants per 2h w/ opthal refferal
HSK stroma affliction:
Antibody cascade against inactive viral antigens
Nummular infiltrates, oedema, diffuse/focal opacity
Leads to stromal thinning, scarring, opacification, ghost vessels
HSK necrotising keratitis:
Immune reaction to live viral particles in stroma
Neutrophil/macrophage influx > viral removal via proteolytic enzymes > stromal loss
Dense infiltrates, oedema, necrosis/melting/thinning
Endothelial HSK:
Inactive viral antigens in endo. Post initial manifestation
Keratic precipitates, stromal oedema, ant. Chamber reaction/flare
Stromal white wessely ring > light haloes
HSK keratouveitis:
Deeper infection leading to trabeculitis (^IOP), glaucoma, cataract
Noted endo. Precipitates, stromal oedema, descemets folds, synechiae, moth eaten iris atrophy
Requires refferal for cortico. Treatment
Herpes zoster epithelial keratitis:
epith. Damage via invasion/replication/cell lysis
Initial punctate epith. Keratitis (several lesions of live virus)
Forms pseudo-dendrites (5d)
Requires 800mg acyclovir 1w
Nummular stromal keratitis from HZO:
Antigen-antibody response > stromal neutrophil/macrophages
Several granular infiltrates, usually under epith. Ulcers
Requires FML qid w/ acyclovir 3%
Corneal epithelium basement layer:
Collagen, proteoglycans
2 layers: ant. Lamina lucida attaches to basal epith. Via hemidesmosomes. Posteria lamina dens w/ anchoring fibrils of collagen to plaques in bowmans/stroma
HZO keratouveitis:
T-cell mediated response in uvea
Causes blur (spasm)
Ant. Chamber flare/cells, iris synechaie, corneal oedema, trabeculitis (or blockage from white BC), iris atrophy
Requires pred-forte 1% per 2h, w/homatropine 2% (reduce spasm pain)
Post-herpetic neuralga
50% by 70y
Inflammation/damage of sensory nerves from viral reactivation > dysfunction of unmylenated nociceptors
Light hypersensitivity via mechanical nociceptor stimulation > severe pain (allodynia)
Sporadic pain w/o stimulation
Zostarvax vaccine is in the works
Corneal epithelium structure:
55um with 10 stratified layers at limbus and 5 over cornea
Superficial layer of non-keratinised squamous cells
Middle layers of polygonal wing cells
Basal layer of columnar cells attached to basement
Tight junctions/ desmosomes/ gap junctions laterally
Herpes zoster disciform stromal keratitis:
Late stage (1mo) from type 1 and 4 hypersensitivity > upregulated immune response
Inflammation of stroma (full depth), immune ring
Limbal vascular keratitis > ^IOP
Requires pred-forte 1% per 2h (opthal)
Bowmans membrane:
500um (90% cornea) of uniform collagen fibrils secreted by keratocytes (fibroblasts).
Fibrils form bundles (lamellae) spaced by glycosaminoglycans
Corneal epith. Replacement:
Basal cell mitosis at palisades of vogt at limbus > wing cell formation > differentiate into squamous cells > slough into the tears
Complete epith. Replacement per week
Corneal innervation and blood supply:
Innervated via short/long ciliary nerves of CNV1
Supplied via tears, limbal vasculature, aqueous
Decemets membrane:
Endo. Basement.
Matrix of collagen fibrils, GAGs, proteoglycans secreted from endo.
Thickens throughout life and w/ endo. Stress
Phases of epithelial wound healing:
Latent
Migration
Proliferation
Attachment
Epithelial wound healing latent phase:
^metabolic activity
Damaged apoptosis
Gap junction loss, desmosome remodelling, hemidesmosome disconnection
Fibronectin matrix forms in lesion to aid migration
Epithelial wound healing proliferation phase:
Proliferation/differentiation > density/structure restoration
Limbal cells produce amplifying cells forming basal layer
Gap/tight junctions reformed
Epithelial wound healing migration phase:
Surrounding cells migrate via filapodia > monolayer
Multilayer migration follows w/ ^glycoprotein synthesis
Migration rate of 0.05mm/h
Epithelial wound healing attachment phase:
Hemidesmosome reattachment
If lesion passes stroma, complex reformation take 1-3mo w/risk of corneal erosions
Stromal wound healing:
Basement membrane disruption > cytokine influx (IL-1 / TGF-b) > IL-1 activation of kerocytes > differentiation to fibroblasts > migrate to lesion edge
Transforming GF-b activation of fibroblasts > diff. To myofibroblasts containing a-SMA > wound closure
Fibroblasts secrete new collagen/ECM > opacity > ECM organisation via specific apoptosis
Takes 3-4 years to remodel
Complications in stromal wound healing:
Myofibroblasts apoptosis / fibroblast innactivation > transparent scar
Myofibroblasts can remain > excess ECM > hypercellular scar > refractive changes (a-SMA stress)
Endothelial wound healing:
Initial loss of endo. Barrier / pump > water influx to stroma > opacity
Cell migration across lesion > polymegethism (^size) / pleomorphism (shape) > barrier restoration
Response after 6h, progresses at 1mm/day (usual 1w to heal)
Barriers to corneal wound healing:
Nerve loss (DM/HSK) > substance-P/neurotrophic-GF loss
Basement membrane dysfunction (DM) > poor framework
Limbal loss (steven-johnson) > low epith. Production
Ocular surface inflammation (DED) > MMP-9 upregulation > epith. Damage
Lid abnormality > exposure > desiccation
Also hormone imbalance/CLs/malnutrition
