8 Herpes Flashcards
Herpes simplex keratitis:
HSV type 1 > most common cause of infectious blindness in developed world
Infects any part of eye (epithelia > stroma > endothelia)
HSV 2 > STD related, keratitis in neonates
Commonly unilateral unless immunocompromised
HSV-1 structure:
Alpha subfamily of herpesvirus
dsDNA in icosahedral caspid
Inner mRNA/protein, outer bilayer with glycoproteins
HSV life cycle:
Membrane glycoproteins allow penetration of capsid through host membrane
Herpes viral entry mediator (HVEM) or nectin-1 delivers capsid to cytoplasm
DNA polymerase forms virons
Release via host heparanase
Enters latency by moving to trigeminal ganglion via corneal nerves
Exists in CD8+ T cells
HSV epidemiology:
50% prevalence in UV > 90% in Africa, decreasing
50% keratitis recurrence 5y > 60% in 20y
Major entry via direct host mucus contact
Herpes keratitis risk:
Asthma, cardiovascular disease, corticosteroids
HIV positive
HSV transmission:
Children/young adults via mucous membrane contact
HSV reactivation:
HSV moves via anterograde axonal transport
Occurs at high sensory tissue (cornea/oral) via ophthalmic branch
Risk decreased by oral acyclovir
HSV reactivation triggers:
Stress, fever, UV, allergies, corticosteroids, laser treatment
immunocompromisation
HSV epithelial keratitis clinical presentation:
Commonly unilateral, 20% bilateral in immunosuppressed
Pain, tearing, redness, FBS, DED
Dendritic keratitis > bulb-lesions/geographic ulcer (fluroscein)
Corneal denervation > neurotrophic keatopathy > corneal melt
HSV epithelial lesions::
Punctate keratopathy > dendritic keratitis (follow nerve plexus) > terminal bulb enlargement > geographic ulcer (central dead cells)
HSV epithelial lesion staining:
Fluorescein > central dendritic staining
Rose bengal/lissamine > edge lesion (dead cells)
HSV epithelial keratitis immune function:
Infected epithelial cells secrete type 1 interferon (IFN-a/b) and IgG/sigA in tear film limit viral spread.
Contribute to spontaneous lesion resolving
Immunocompromised/corticosteroids > basement membrane invasion
Epithelial Herpetic keratitis DDX:
Misdiagnosed as acanthamoeba keratitis
HZO does not have terminal bulbs
Tested with PCR
HSV endothelial keratitis clinical presentation:
Disciform> most common, central oedema disc
Diffuse> wide oedema
Linear> limbal oedema
HSV stromal keratitis (HSK) clinical presentation:
20-50% of recurrent cases
Corneal vascularisation, stromal oedema/opacity, irreversible scaring
Necrotizing: stromal infiltration/ring, epithelial ulcer > corneal melt
Disciform: stromal oedema > neovascularisation
HSV stromal keratitis treatment
Topical corticosteroid Prednefrin Forte 1% (6/day, 10 weeks)
With oral valaciclovir (antiviral)
Dosage increased with epithelial defects
Always tapered
HSK immune procedure:
Trigeminal virus reactivation > corneal innate immune signalling > cytokine/chemokines from stroma > 24h neutrophil/NK cell aggregation
Dendritic cells phagocytose virus > present antigen to lymph nodes > 7-21d CD4+T cells aggregate > IFN-g / IL-17 secretion
Inflammatory cells > corneal clouding
HSV endothelitis / uveitis clinical presentation:
Endothelial oedema / precipitates
High IOP (trabeculitis)
Iris atrophy
Immune cells in ocular HSV infection
Neutrophils > earliest responder, cause corneal opacity
Macrophage, NK cells > innate phagocytes
Dendritic cells > adaptive phagocyte
CD4+T cells > IL2/IFN, drive lesion development
CD8+T cells > controls recurrence via T cell receptor
Immune factors in ocular HSV infection:
Toll-like receptors > innate PAMP detector, drives cytokine production and opacity
Cytokine/Chemokine > IFN a/b stimulate antiviral genes, IFN y stimulates inflammation
Heparanase > removes harparan sulfate allowing virion release to other cells
HSV Corneal neovascularisation pathology:
Neutrophils form metalloproteases > extracellular matrix breakdown > vascularisation mediated by VEGF
Infection depletes VEGF receptors > increase in VEGF
HSV effect on corneal surface:
Loss of sub-basal nerve plexus > desensitisation (neurotrophic keratopathy)
NK > Tear reduction > DED
Frequent recurrence > neuropathic pain, corneal melt, superinfection
HSV antiviral treatment:
Systemic > acyclovir, valacyclovir, famciclovir
Tropical > acyclovir, trifluridine, ganciclovir
Acyclovir HSV treatment:
Most common
Nucleoside analog > DNA polymerase inhibition > HSV replication inhibition
HSV enzyme can mutate for resistance
Highest HSV affinity > less toxicity for non-infected cells
Anti-inflammatory treatment of HSV:
Focused treatment for HSV inflammatory damage
Corticosteroids > endothelitis/uveitis
Varicella zoster virus:
Contagious DNA virus; causes
Chickenpox (Varicella) > lifelong trigeminal infection
Shingles > reactivation of VZV
Varicella zoster epidemiology:
3/1000/year > 30% lifetime attack
Increased rate> age (80>50), immunocompromised, HIV
Varicella zoster pathophysiology:
Enters upper res. > proliferates to pharyngeal lymph > skin (varicella)
HZO skin lesions:
Vessicle rash, healed in 4 weeks
Upper face lesion > first trigeminal branch
Nose and below lesion > second branch lesion
HZO lid manifestations:
Hyperemia, oedema > lagophthalmos
Blepharitis (staph)
HZO conjunctiva manifestation:
Membraneous / follicular response
Hyperemia / oedema
Resolving in 1 week
Antibiotics prevent bacterial infection
HZO corneal manifestations:
Punctate epithelial keratitis (focal lesions with fluroscein)
Tapered dendritic lesions
Photophobia, pain
HZO uvea manifestations
Usually unilateral
Iris atrophy/synechiae, IOP increase, cataract formation
HZO acute retinal necrosis (ARN):
Fast retinal lesion/necrosis progression
Vitreous inflammation
Immunosuppression > Progressive outer retinal necrosis (white retinal patches) > retinal detachment
HZV complications:
Cutaneous > post-herpetic neuralgia (skin pain following rash)
Visceral
Neurological > neuropathy/palsy
Ocular > superinfection
HZV treatment:
Antiviral therapy > acyclovir, ganciclovir, famciclovir, (7d for HZ rash)
Analgesics > lidocaine (pain)
Intravenous acyclovir > ARN/PORN, immunocompromised
HZV acyclovir treatment procedure:
800mg orally 5/day
Administer within 72 hours of rash, for 7 days
Or 3% gel
