W8 herpes & healing Flashcards
HSV:
HSV-1: upper infection, reactivates via trigeminal
HSV-2: lower infection, rarely eyes
HSV initial infection:
Direct via secretions (cold sores) > epith. Replication > primary manifestation > blepharokeratoconjuntivitis > retrograde transport to trigeminal ganglion
Reactivation of HSV:
Travel via long and short ciliary branches of CN V1:
Epithelial (ulcer)
Stromal (keratitis)
Endothelial (endothelitis)
Ant. Chamber
Causes of HSV reactivation:
UV (induced immunosuppression)
Trauma
CLs
Stress
HSK dendritic ulcer:
Epithelial ulcer w/ stromal oedema, desensitisation, ^IOP
Limbal ulcer > ant. Stromal infil. (white BC)
Self limiting (3w), can be anaesthetised and debrided
3% aciclovir 5/d for 2w
HSK Geographic ulcer:
Immunocompromised Px enlarged ulcer. Larger risk of co-infection
3% aciclovir ointment 5/d until re-epith.
Lissamine stains only periphery
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
Metaherpetic ulcer:
Poor healing of geo. Ulcer
Lissamine stains central ulcer
Requires refferal
HSK stroma affliction:
Antibody cascade against inactive viral antigens
Nummular infiltrates, oedema, diffuse/focal opacity
Leads to stromal thinning, scarring, opacification, ghost vessels
Herpes Zoster description:
VZV is comprised of dsDNA in icosahedral capsid w/ lipid envelope of glycoproteins
Primary manifestation of chickenpox
Retrograde transport to dorsal root and sensory CN ganglia
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 reactivation management:
Oral acyclovir 800mg 5/d for 1w
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
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
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
Herpes Zoster reactivation:
Loss of cell mediated immunity against virus (stress/age) > Shingles
Causes promordal malaise, fever, fatigue, painful rash
HZO when virus travels opthalmic branch of CNV
Nummular stromal keratitis from HZO:
Antigen-antibody response > stromal neutrophil/macrophages
Several granular infiltrates, usually under epith. Ulcers
Requires FML qid w/ acyclovir 3%
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)
HSK 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
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
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
Bowmans membrane:
10um acellular membrane of woven collagen fibrils
Stroma:
500um (90% cornea) of uniform collagen fibrils secreted by keratocytes (fibroblasts).
Fibrils form bundles (lamellae) spaced by glycosaminoglycans
Decemets membrane:
Endo. Basement.
Matrix of collagen fibrils, GAGs, proteoglycans secreted from endo.
Thickens throughout life and w/ endo. Stress
Corneal innervation and blood supply:
Innervated via short/long ciliary nerves of CNV1
Supplied via tears, limbal vasculature, aqueous
Epithelial wound healing migration phase:
Surrounding cells migrate via filapodia > monolayer
Multilayer migration follows w/ ^glycoprotein synthesis
Migration rate of 0.05mm/h
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
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
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 attachment phase:
Hemidesmosome reattachment
If lesion passes stroma, complex reformation take 1-3mo w/risk of corneal erosions
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
