W8 herpes & healing

Question 1

HSV:

Answer 1

HSV-1: upper infection, reactivates via trigeminal
HSV-2: lower infection, rarely eyes

Question 2

HSV initial infection:

Answer 2

Direct via secretions (cold sores) > epith. Replication > primary manifestation > blepharokeratoconjuntivitis > retrograde transport to trigeminal ganglion

Question 2

Reactivation of HSV:

Answer 2

Travel via long and short ciliary branches of CN V1:
Epithelial (ulcer)
Stromal (keratitis)
Endothelial (endothelitis)
Ant. Chamber

Question 3

Causes of HSV reactivation:

Answer 3

UV (induced immunosuppression)
Trauma
CLs
Stress

Question 3

HSK dendritic ulcer:

Answer 3

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

Question 4

HSK Geographic ulcer:

Answer 4

Immunocompromised Px enlarged ulcer. Larger risk of co-infection
3% aciclovir ointment 5/d until re-epith.
Lissamine stains only periphery

Question 4

Neurotrophic ulcer:

Answer 4

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

Question 5

Metaherpetic ulcer:

Answer 5

Poor healing of geo. Ulcer
Lissamine stains central ulcer
Requires refferal

Question 6

HSK stroma affliction:

Answer 6

Antibody cascade against inactive viral antigens
Nummular infiltrates, oedema, diffuse/focal opacity
Leads to stromal thinning, scarring, opacification, ghost vessels

Question 7

Herpes Zoster description:

Answer 7

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

Question 7

HSK keratouveitis:

Answer 7

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

Question 7

Herpes Zoster reactivation management:

Answer 7

Oral acyclovir 800mg 5/d for 1w

Question 7

HSK necrotising keratitis:

Answer 7

Immune reaction to live viral particles in stroma
Neutrophil/macrophage influx > viral removal via proteolytic enzymes > stromal loss
Dense infiltrates, oedema, necrosis/melting/thinning

Question 7

Endothelial HSK:

Answer 7

Inactive viral antigens in endo. Post initial manifestation
Keratic precipitates, stromal oedema, ant. Chamber reaction/flare
Stromal white wessely ring > light haloes

Question 8

Herpes zoster epithelial keratitis:

Answer 8

epith. Damage via invasion/replication/cell lysis
Initial punctate epith. Keratitis (several lesions of live virus)
Forms pseudo-dendrites (5d)
Requires 800mg acyclovir 1w

Question 9

Clinical presentation of HZO:

Answer 9

Lid vessicles/edema/inflammation
Conjuntivitis w/ papillae/follicles/membranes
Epi/scleritis
Keratitis
Epitheliopathy (pseudo-dend.)
Uveitis
Optic neuritis
Post-herpetic neuralgia

Question 9

Herpes Zoster reactivation:

Answer 9

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

Question 10

Nummular stromal keratitis from HZO:

Answer 10

Antigen-antibody response > stromal neutrophil/macrophages
Several granular infiltrates, usually under epith. Ulcers
Requires FML qid w/ acyclovir 3%

Question 10

Herpes zoster disciform stromal keratitis:

Answer 10

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)

Question 11

HSK keratouveitis:

Answer 11

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)

Question 12

Post-herpetic neuralga

Answer 12

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

Question 13

Corneal epithelium structure:

Answer 13

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

Question 14

Corneal epithelium basement layer:

Answer 14

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

Question 15

Corneal epith. Replacement:

Answer 15

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

Question 16

Bowmans membrane:

Answer 16

10um acellular membrane of woven collagen fibrils

Question 16

Stroma:

Answer 16

500um (90% cornea) of uniform collagen fibrils secreted by keratocytes (fibroblasts).
Fibrils form bundles (lamellae) spaced by glycosaminoglycans

Question 17

Decemets membrane:

Answer 17

Endo. Basement.
Matrix of collagen fibrils, GAGs, proteoglycans secreted from endo.
Thickens throughout life and w/ endo. Stress

Question 18

Corneal innervation and blood supply:

Answer 18

Innervated via short/long ciliary nerves of CNV1
Supplied via tears, limbal vasculature, aqueous

Question 19

Epithelial wound healing migration phase:

Answer 19

Surrounding cells migrate via filapodia > monolayer
Multilayer migration follows w/ ^glycoprotein synthesis
Migration rate of 0.05mm/h

Question 19

Phases of epithelial wound healing:

Answer 19

Latent
Migration
Proliferation
Attachment

Question 19

Epithelial wound healing latent phase:

Answer 19

^metabolic activity
Damaged apoptosis
Gap junction loss, desmosome remodelling, hemidesmosome disconnection
Fibronectin matrix forms in lesion to aid migration

Question 20

Stromal wound healing:

Answer 20

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

Question 20

Epithelial wound healing proliferation phase:

Answer 20

Proliferation/differentiation > density/structure restoration
Limbal cells produce amplifying cells forming basal layer
Gap/tight junctions reformed

Question 21

Epithelial wound healing attachment phase:

Answer 21

Hemidesmosome reattachment
If lesion passes stroma, complex reformation take 1-3mo w/risk of corneal erosions

Question 22

Complications in stromal wound healing:

Answer 22

Myofibroblasts apoptosis / fibroblast innactivation > transparent scar
Myofibroblasts can remain > excess ECM > hypercellular scar > refractive changes (a-SMA stress)

Question 23

Endothelial wound healing:

Answer 23

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)

Question 24

Barriers to corneal wound healing:

Answer 24

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