33. Herpetic Keratitis

Question 1

Varicella-Zoster Virus (VZV) is commonly known as .... Primary VZV infection usually occurs in .... VZV is highly ... and is ....
Px will experience ... with ... that crust over after ... days. VZV can become latent in the ... and .... There are ... available for VZV to prevent infection.
Reactivation of VZV causes ..., this is more common in ... and ... individuals. However, 90% of px with shingles are not .... It is found in the US that 96% of adults have ... for VZV and 30% of px will have ....

Answer 1

Varicella-Zoster Virus (VZV) is commonly known as chickenpox. Primary VZV infection usually occurs in early childhood. VZV is highly contagious and is airborne.
Px will experience itchy rash with vesicles that crust over after 5 days. VZV can become latent in the spinal dosal root and cranial nerve ganglia. There are vaccines available for VZV to prevent infection.
Reactivation of VZV causes shingles, this is more common in elderly and immunocompromised individuals. However, 90% of px with shingles are not immunosuppressed. It is found in the US that 96% of adults have antibodies for VZV and 30% of px will have reactivation of VZV.

Question 2

How is VZV transmitted? Who should px with active Herpes Zoster avoid?

Answer 2

Via active Herpes Zoster vesicles & airborne.
Avoid contact with pregnant individuals, babies younger than 18 months and anyone immunosuppressed.

Question 3

What are the 7 risk factors of VZV?

Answer 3

• Female
• Caucasian
• 1 family relative with Hx of HZ
• Autoimmune disease
• Stress
• Traumatic brain injury
• Heart failure

Question 4

How effective are Herpes Zoster vaccines? What side effects of VZV can it help with?

Answer 4

Protect 90% people >60yo from developing Herpes Zoster and may reduce the severity of Herpes Zoster and subsequent postherpetic neuralgia (PHN) - pain persisting for greater than 3 months.

Question 5

What are shingles?

Answer 5

Shingles are painful, unilateral blistering/rash that can occur anywhere on the body, often on the face or torso. 50% on lower thoracic and upper lumbar nerves, 13-20% on cranial nerves.

Question 6

VZV Stages:
Prodromal stage = ...days before rashes appear
* Acute ... - aching, ..., stabbing/shock-like (...% px)
* pain provoked by ... stimuli
* along the affected ...
* pain usually persists through ... of shingles
* ... and ... (20% px)
* unbearable ...
​
Acute stage
* ... - blisters that crust over in ...days
* no longer ... once vesicles crust over
​
Resolution stage (... weeks)
* if vesicles have burst, ... may occur

Answer 6

VZV Stages:
Prodromal stage = 1-4days before rashes appear
* Acute neuralgia - aching, burning, stabbing/shock-like (70-80% px)
* pain provoked by trivial stimuli
* along the affected dermatome
* pain usually persists through all stages of shingles
* Fever and headache (20% px)
* unbearable itching

Acute stage
* Rash - blisters that crust over in 7-10days
* no longer infectious once vesicles crust over

Resolution stage (2-4 weeks)
* if vesicles have burst, scarring may occur

Question 7

What are the 7 complications of VZV?

Answer 7

• Postherpetic neuralgia (PHN) - occurs in 35% cases, mostly >65yo, pain last >3 months after rash onset
• Vision loss - Herpes Zoster Ophthalmicus (HZO)
• Encephalitis
• Meningitis
• Pneumonia
• Hearing loss & balance problems - Ramsay Hunt Syndrome/ Herpes Zoster Oticus
• Skin infection

Question 8

Herpes Zoster Ophthalmicus (HZO) is the ... in the ... division (V1) of the ... nerve. This division innervates ..., ..., ... skin and skin of the .... This division has 3 terminal branches - ..., frontal and .... ... innervates skin of ..., which divides into ... that innervate ... and ....

Answer 8

Herpes Zoster Ophthalmicus (HZO) is the reactivation of VZV in the ophthalmic division (V1) of the trigeminal nerve. This division innervates eyelid, eyebrow, forehead skin and skin of the tip of the nose. This division has 3 terminal branches - lacrimal, frontal and nasociliary. Naso-ciliary innervates skin of tip of the nose, which divides into long ciliary nerves that innervate cornea and uvea.

Question 9

What are the 9 conditions that can be caused from HZO?

Answer 9

• Keratitis
• Scleritis
• Uveitis
• Trabeculitis
• Choroiditis
• Acute retinal necrosis
• Optic neuritis
• Nerve palsies
• Cavernous sinus thrombosis

Question 10

...% of herpes zoster px will develop herpes zoster ophthalmicus. ...% with HZO will develop ocular complications. Vesicular rash respects the ..., this is known as the .... This is a vesicular rash of the ..., which indicates involvment of the ... nerve. This has increased risk of ocular inflammation due to their .... Px with ... are ...% at risk of ocular inflammation.

Answer 10

10-15% of herpes zoster px will develop herpes zoster ophthalmicus. 50% with HZO will develop ocular complications. Vesicular rash respects the vertical midline, this is known as the Hutchinson's sign. This is a vesicular rash of the tip of the nose, which indicates involvment of the nasociliary nerve. This has increased risk of ocular inflammation due to their shared innervation. Px with Hutchinson's sign are 76% at risk of ocular inflammation.

Question 11

Clinical manifestation of HZO at Onset phase
Lids:
* ... rash that heals after ... weeks
* Severe lid ... with ... accompanies the rash and can be mistaken for ...
* May develop a secondary ...
* May develop cicatricial ... changes resulting in ...

Conjunctiva:
* Conjunctival ... and ...
* Unilateral ...
* Fine dissipated conjunctival ...
* If severe, may develop ..., ...
* Periorbital ...

Cornea - Acute ...(25-30% Px with HZO)
* Can occur up to ... following the onset of dermatitis
* ... onset 2-7 days
* ... (4-6 days) = healed up ... cells that exhibit ... staining that results from ... collecting at the edges of the ...
* anterior stromal keratitis with ...
* Stromal infiltrates may coalesce to form a ... = mulitple small ciruclar white opacities in the anterior stroma, opacities are an ...-mediated stromal reaction to ...

Anterior uveitis (onset 2 weeks-years)
* ...% px with HZO
* Isolated or associated with ... keratitis
* May result in elevated ... at presentation

Answer 11

Clinical manifestation of HZO at Onset phase
Lids:
* Vesicular rash that heals after 2-3 weeks
* Severe lid oedema with hyperaemia accompanies the rash and can be mistaken for preseptal cellulitis
* May develop a secondary bacterial infection
* May develop cicatricial skin changes resulting in lid malposition

Conjunctiva:
* Conjunctival hyperaemia and chemosis
* Unilateral follicular conjunctivitis
* Fine dissipated conjunctival haemorrhages
* If severe, may develop scarring, symblepharon
* Periorbital oedema

Cornea - Acute keratitis(25-30% Px with HZO)
* Can occur up to one month following the onset of dermatitis
* Superficial punctate keratitis onset 2-7 days
* Pseudo-dendrites (4-6 days) = healed up epithelial cells that exhibit negative staining that results from fluorescein collecting at the edges of the epithelium
* anterior stromal keratitis with stromal infiltrates
* Stromal infiltrates may coalesce to form a nummular keratitis = mulitple small ciruclae white opacities in the anterior stroma, opacities are an immune-mediated stromal reaction to viral antigens

Anterior uveitis (onset 2 weeks-years)
* 40% px with HZO
* Isolated or associated with nummular keratitis
* May result in elevated IOP at presentation

Question 12

*Clinical manifestation of HZO at Delayed phase
*Cornea - Mucous plaque keratitis (onset 2 months - 2 years):
* ... - elevated, ropy greyish ... lesions with minimal underlying ..., stain with ..., easily wiped from the cornea
* Underlying ... is intact, but poorly ...
* Usually ... or ...

Deep stromal keratitis (onset 1 month - years)
* ... results in ...
* Elevated ... due to trabeculitis
* Associated ... with fine ... under oedematous stroma

Interstitial keratopathy
* May develop ... allowing lipid leakage that can cause significant corneal ...

Serpiginous Keratitis
* Peripehral ... ulcerative keratitis - ... and corneal thinning next to a zone of ..., may progress to neovascularisation of ...

Sclera
* ...
* ...
* may develop ... and ...

Answer 12

Clinical manifestation of HZO at Delayed phase
Cornea - Mucous plaque keratitis (onset 2 months - 2 years):
* Mucous epithelial plaques - elevated, ropy greyish branching lesions with minimal underlying inflammation, stain with rose bengal, easily wiped from the cornea
* Underlying epithelium is intact, but poorly adherent
* Usually linear or branching

Deep stromal keratitis (onset 1 month - years)
* Endotheliitis results in disciform keratitis
* Elevated IOP due to trabeculitis
* Associated iritis with fine keratic precipirates under oedematous stroma

Interstitial keratopathy
* May develop vascularisation allowing lipid leakage that can cause significant corneal opacification

**Serpiginous Keratitis **
* Peripehral arcuate ulcerative keratitis - infiltrates and corneal thinning next to a zone of limbal vasculitis, may progress to neovascularisation of perforation

Sclera
* episcleritis
* scleritis
* may develop scleral thinning and atrophy

Question 13

Clinical manifestation of HZO at Chronic phase
Lids
* May develop cicatricial ... changes resulting in ... and ...
* May develop ... from associated nerve palsy

Cornea - Repeated Neurotrophic Ulcers
* ...% px within the first year after infection
* Profound corneal ... can result from a single episode of HZO
* ..., persistent epithelial defects with ..., and possible ...
* Risk of secondary ... infection
Cornea - Persistent Stromal Keratitis
* Corneal ..., ..., vascularisation, ... overlying epithelial irregularitiy

Iris
* Sectorial ... atrophy, ... puppill, mild ... (pupil displacement)
* Reduced direct ... response

Post Herpetic Neuralgia (PHN) (10-30% px with HZO)
* Risk factors: increasing ..., prodromal ..., severity of ..., greater ..., ... involvment
* Maybe severe and unrelenting - increased risk of ... and ...
* ...% resolve after 2 months, ...% resolve after one year
* May result from ... persisting in ... pathways

Answer 13

Clinical manifestation of HZO at Chronic phase
Lids
* May develop cicatricial skin changes resulting in lid malposition and trichiasis
* May develop lagophthalmos from associated nerve palsy

Cornea - Repeated Neurotrophic Ulcers
* 20-40% px within the first year after infection
* Profound corneal hypoesthesia can result from a single episode of HZO
* Superficial punctate keratitis, persistent epithelial defects with vascularisation, and possible perforation
* Risk of secondary bacterial infection
Cornea - Persistent Stromal Keratitis
* Corneal oedema, infiltrates, vascularisation, scarring overlying epithelial irregularitiy

Iris
* Sectorial iris atrophy, irregular puppill, mild corectopia (pupil displacement)
* Reduced direct pupil response

Post Herpetic Neuralgia (PHN) (10-30% px with HZO)
* Risk factors: increasing age, prodromal pain, severity of vesicular rash, greater acute pain, ophthalmic involvment
* Maybe severe and unrelenting - increased risk of depression and suicide
* 50% resolve after 2 months, 80% resolve after one year
* May result from chronic inflammation persisting in trigeminal pathways

Question 14

Other Clinical Manifestations of HZO
Neuro ophthalmic
* Cranial nerve palsies - ... and ... (most common), ... and ... (rare)
* Orbital ...
* Ocular ... (inflammation of one or more EOMs) - causing ...
* EOM palsies (...)
* Optic ...
* ... - parasympathetic denervation (reduced constriction to light) - damage to the ...
* ...

Retina
Necrotising Herpetic Retinopathy
* Acute retinal ... (ARN) - mulltifocal ... areas with discrete borders spreading ... from the mid peripheral retina, ... and ..., ... common

Progressive Outer Retinal Necrosis (PORN)
* Rapid progression of necrosis of the ... in severely ... px

• Central retinal ... occlusion + Central retinal ... occlusion (...+...)
• Retinitis
• ...

Answer 14

Other Clinical Manifestations of HZO
Neuro ophthalmic
* Cranial nerve palsies - 7th and 3rd (most common), 4th and 6th (rare)
* Orbital inflammation
* Ocular myositis (inflammation of one or more EOMs) - causing diplopia
* EOM palsies (ophthalmoplegia)
* Optic neuritis
* Adies tonic pupil - parasympathetic denervation (reduced constriction to light) - damage to the parasympathetic ciliary ganglion
* Exophthalmos

Retina
Necrotising Herpetic Retinopathy
* Acute retinal necrosis (ARN) - mulltifocal necrotic areas with discrete borders spreading peripherally from the mid peripheral retina, occlusive vasculitis and vitreous inflammation, retinal detachment common

Progressive Outer Retinal Necrosis (PORN)
* Rapid progression of necrosis of the outer retina in severely immunocompromised px

• Central retinal vein occlusion + Central retinal artery occlusion (CRVO+CRAO)
• Retinitis
• Choroiditis

Question 15

Treatment & Management of VZV

• Minimise the duration and severity of the rash
• Manage the associated pain

Vesicles
* Cover with ... dressing, avoid ... and ...
* ... lotion can give symptomatic relief
* May require ... ointment if develops a secondary ... infection

Oral Anti-virals
* Treatment should be initiated within ... hours of the onset of symptoms to be effective
* May still be considered up to ... days after onset, if has severe symptoms or ...(may require intravenous antiviral)
* All are extremely safe and well tolerated, safe in ... and ...
* * Reduce the duration of ...
* Reduce ... formation
* Shorten the duration of the ...
* Reduces the occurence of ...
* Does not significantly reduce the incidence of ...
* Does reduce the ... and ... of acute pain

Answer 15

Treatment & Management of VZV

• Minimise the duration and severity of the rash
• Manage the associated pain

Vesicles
* Cover with absorbent dressing, avoid touching and scratching
* Calamine lotion can give symptomatic relief
* May require antibiotic ointment if develops a secondary bacterial infection

Oral Anti-virals
* Treatment should be initiated within 72 hours of the onset of symptoms to be effective
* May still be considered up to 7 days after onset, if has severe symptoms or immunocompromised(may require intravenous antiviral)
* All are extremely safe and well tolerated, safe in pregnancy and breastfeeding
* Reduce the duration of viral shedding
* Reduce new vesicle formation
* Shorten the duration of the rash
* Reduces the occurence of chronic eye disease
* Does not significantly reduce the incidence of postherpetic neuralgia
* Does reduce the severity and duration of acute pain

Question 16

What are the 3 oral anti-virals that can be used for VZV?

Answer 16

• Valaciclovir 1000mg TID for 7-10 days
• Aciclovir 800mg 5 times a day for 7-10 days
• Famiciclovir 500mg TID for 7-10 days

Question 17

What are the 7 pain medications that can be prescribed for VZV?

Answer 17

• Paracetamol
• NSAID
• Codeine
• Amitriptyline
• Tramadol
• Morphine
• Gabapentin

Question 18

What are the 4 management and 1 treatment plan for Herpes Zoster Ophthalmicus?

Answer 18

Management
* Treatment of active infection
* Treatment of post-infectious inflammation
* Treatment of corneal neurotrophy
* Disease prevention
Treatment - oral anti-virals

Question 19

Herpes Zoster Ophthalmicus Treatment
Lids:
* ... ointment ... to vesicles to control ... bacterial infection
* Treat ... malposition - ...

Cornea
* ... drops if significant corneal epithelial defect
* ... - drops or ointment for ..., ...
* Bandage/ scleral CLs, ..., or ... serum drops for ...
* Topical steroids e.g. ..., ... for stromal keratitis, ...

Answer 19

Herpes Zoster Ophthalmicus Treatment
Lids:
* Chloramphenicol ointment TID to vesicles to control secondary bacterial infection
* Treat lid malposition - Sx

Cornea
* Chloramphenicol drops if significant corneal epithelial defect
* Lubricants - drops or ointment for SPK, pseudodendrites
* Bandage/ scleral CLs, amniotic membrane, or autologous serum drops for neurotrophic keratitis
* Topical steroids e.g. FML, Prednefrin Forte for stromal keratitis, uveitis

Question 20

Varicella Zoster Virus vaccine is recommended for over ... years of age, or anyone over ... who live in the same household as someone who is .... The suppy is free in Australia for ...yo. The vaccine helps reduce incidence of HZ by ...%, severity of symptoms of HZ by ...% and ... by 66%. Vaccine is not indicated during ... disease. Px who have had previous episodes of HZO with ... may be at risk of reactivation of ... following vaccination. e.g. checking any ... in px >60yo.

Answer 20

Varicella Zoster Virus vaccine is recommended for over 60 years of age, or anyone over 50 who live in the same household as someone who is immunocompromised. The suppy is free in Australia for 70-79yo. The vaccine helps reduce incidence of HZ by 50%, severity of symptoms of HZ by 60% and postherpetic neuralgia by 66%. Vaccine is not indicated during acute disease. Px who have had previous episodes of HZO with ocular involvment may be at risk of reactivation of ocular disease following vaccination. e.g. checking any unilateral uveitis in px >60yo.

Question 21

Ophthalmic branch of the ...th cranial nerve innervates the .... Corneal sensation is the greatest in the ..., and least sensitive in the ... quadrant. This decreases with ... and is unaffected by .... Single episode of HZO can cause profound corneal .... Decreased corneal sensitivity following ... is greater with ... than .... Decreased corneal sensitivity is proportional to the ....

Answer 21

Ophthalmic branch of the 5th cranial nerve innervates the cornea. Corneal sensation is the greatest in the central cornea, and least sensitive in the superior quadrant. This decreases with age and is unaffected by iris colour. Single episode of HZO can cause profound corneal hypoaesthesia. Decreased corneal sensitivity following keratitis is greater with VZV than HZV. Decreased corneal sensitivity is proportional to the number of recurrent HSV keratitis episodes.

Question 22

How is corneal sensitvitiy detected qualitatively (3) and quantitatively (2)?

Answer 22

Qualitative - using a wisp of cotton-tipped applicator on the cornea
* Approach px from the side & test all 4 quadrants
* Record each quadrant as normal, reduced or absent
* Compare to the other eye

Quantitative - handheld asthesiometer (Cochet-Bonnet)
* Retractable, nylon monofilament
* as the length is decreased, the pressure is increased

Question 23

Herpes Virus

Comes in two types: ... and .... ... are the only natural host for these and they are the most common virus in ....

Answer 23

Herpes Virus

Comes in two types: Herpes Simplex Virus and Varicella-Zoster Virus. Humans are the only natural host for these and they are the most common virus in humans.

Question 24

Herpes Simplex Virus (1)

Structure: ... DNA virus with a ...-...nm diameter.
Two types: 1st is ... result in ..., ..., and ... lesions and is becoming increasingly more .... 2nd is ... results in ... herpes and ... conjunctivitis and is ... transmitted.
Both are trasmitted via ... or at ... in the skin and are ... infections. Both can ... at site of infection.

Answer 24

Herpes Simplex Virus (1)

Structure: Double-stranded DNA virus with a 150-200nm diameter.
Two types: 1st is HSV-1 result in ocular, facial, and oral lesions and is becoming increasingly more common. 2nd is HSV-2 results in genital herpes and neonatal conjunctivitis and is sexually transmitted.
Both are trasmitted via mucosal surfaces or at breaks in the skin and are lifelong infections. Both can reactivate at site of infection.

Question 25

Herpes Simplex Virus (2)
Global prevalence of ...-...% but only ...% of cases results in ocular disease. Herpes infections are most contagious when symptoms are ... but can still transmit otherwise. ... medications can reduce ... and ... of symptoms, but do not ... the infection. Vast majority of HSV-1 are ... herpes.
Most ... and ... herpes are asymptomatic. HSV infects the ... and travels by .... to the sensory ganglia. HSV-1 lies dormant in ... and ... ganglia and does not ... neuronal cells in this ... and becomes ....

Answer 25

Herpes Simplex Virus (2)
Global prevalence of 65-90% but only 1% of cases results in ocular disease. Herpes infections are most contagious when symptoms are present but can still transmit otherwise. Antiviral medications can reduce severity and frequency of symptoms, but do not cure the infection. Vast majority of HSV-1 are oral herpes.
Most oral and genital herpes are asymptomatic. HSV infects the nerve endings and travels by retrograde axonal transport to the sensory ganglia. HSV-1 lies dormant in trigeminal and superior cervical ganglia and does not destroy neuronal cells in this state and becomes invisible.

Question 26

Herpes Simplex Virus - Primary Infection

Mostly occurs in ... and ... and is usually non-specific ... ... .... The cornea is usually ....

Systemic signs; ..., ..., and ....

Ocular signs are more .... Blepharoconjunctivitis - ... discharge, ... conjunctivitis, with ... and ... on skin and lids. If lid vesicles ..., they shed virus for ... days and resolve without scarring over ...-... weeks. Ocular symptoms include ..., ..., ..., and .... Keratitis may present with ..., ..., or a ...; corneal involvement is ....

Answer 26

Herpes Simplex Virus - Primary Infection

Mostly occurs in children and teenagers and is usually non-specific unilateral self-limiting conjunctivitis. The cornea is usually spared.

Systemic signs; skin lesions, fever, and preauricular lymphadenopathy.

Ocular signs are more mild. Blepharoconjunctivitis - watery discharge, follicular conjunctivitis, with vesicles and ulcers on skin and lids. If lid vesicles ulcerate, they shed virus for 10 days and resolve without scarring over 2-3 weeks. Ocular symptoms include foreign body sensation, lacrimation, photophobia, and conjunctiva hyperaemia. Keratitis may present with punctate epithelial keratitis, marginal infiltrates, or a dendritic ulcer; corneal involvement is epithelial.

Question 27

Herpes Simplex Virus - Primary Infection Treatment

Aim: to ... from cornea and adjacent structures
Epithelial disease: lots of ... and a small amount of ...

Mx:
* Drug method dose% to skin lesions and/or cornea regimen for duration
* Drug class if patient is symptomatic (drug dosage% regimen or drug dose% regimen).
* Drug class ointment is necessary if .... Review in ...-... days.

Answer 27

Herpes Simplex Virus - Primary Infection Treatment

Aim: to eliminate live HSV from cornea and adjacent structures
Epithelial disease: lots of viral replication and a small amount of inflammation

Mx:
* Aciclovir ointment 3% to skin lesions and/or cornea 5x/day for 2 weeks
* Cycloplegia if patient is symptomatic (atropine 1% bid or cyclopentolate 1% tid).
* Antibiotic ointment is necessary if suspected secondary bacterial infection. Review in 2-3 days.

Question 28

Herpes Simplex Virus - Reactivation (1)

Reactivation causes the virus to migrate from ... to .... The cornea is also capable of ... and ....
Reactivation triggers are: ..., ... ..., ..., and ....
There’s an increase of reactivation in patients with ..., ..., ..., ..., and ....
Reactivation can recur at ... or .... Can produce asymptomatic ... or ... ranging from ... to ....

Answer 28

Herpes Simplex Virus - Reactivation (1)

Reactivation causes the virus to migrate from ganglia to target site. The cornea is also capable of latency and later reactivation.
Reactivation triggers are: sunlight, fever physical injury, immunosuppression, and ophthalmic surgery.
There’s an increase of reactivation in patients with asthma, cardiovascular disease, long term corticosteroid inhalers/cream, immunocompromised patients, and atopy.
Reactivation can recur at original site or another site that is innervated by infected ganglia. Can produce asymptomatic virus shedding or symptoms ranging from neuropathic tingling to recurrent ulceration.

Question 29

Herpes Simplex Virus - Reactivation (2)

... of HSV within the ... allows development of subsequent .. without ever having a primary ocular infection. Frequency of recurrence is ...% at 1 year, ...% at 5 years, and ...% at 20 years and ... with number of recurrences.

Three types of engagement: epithelial is caused by ...; stromal is caused by ..., and endothelial is caused by .... Recurrent HSV keratitis can cause ..., ..., and ... which results in .... Recurrent viral replication ... in which it is replicated which can result in ...; characteristic of HSK.

Answer 29

Herpes Simplex Virus - Reactivation (2)

Interneuronal spread of HSV within the trigeminal nerve allows development of subsequent ocular disease without ever having a primary ocular infection. Frequency of recurrence is 25% at 1 year, 50% at 5 years, and 65% at 20 years and increase with number of recurrences.

Three types of engagement: epithelial is caused by actively replicated virus; stromal is caused by immune mechanisms, and endothelial is caused by chronic inflammation. Recurrent HSV keratitis can cause corneal scarring, ulceration, and perforation which results in permanent vision loss. Recurrent viral replication destroys the ganglion cell in which it is replicated which can result in corneal hypoaesthesia; characteristic of HSK.

Question 30

HSV - Reactivation - HSK - Blepharoconjunctivitis

Lid ... along eyelid margin and skin. ... discharge, ... conjunctivitis, and ....

Mx:
* Drug method dose% to skin lesions and/or cornea regimen for duration
* ... if patient is symptomatic (drug dose% regimen or drug dose% regimen).
* Drug class ointment is necessary if .... Review in ...-... days.

Answer 30

HSV - Reactivation - HSK - Blepharoconjunctivitis

Lid vesicles along eyelid margin and skin. Watery discharge, follicular conjunctivitis, and preauricular lymphadenopathy.

Mx:
* Aciclovir ointment 3% to skin lesions and/or cornea 5x/day for 2 weeks
* Cycloplegia if patient is symptomatic (atropine 1% bid or cyclopentolate 1% tid).
* Antibiotic ointment is necessary if suspected secondary bacterial infection. Review in 2-3 days.

Question 31

HSV - Reactivation - HSK - Epithelial Disease (1)

Punctate epithelial opacities may coalesce centrally and form a ....

... result in ..., ... and .... Bed stains with ... and margins stain with ... or ....

... - expanding ... take on shape of ...

... is rare, resembles a ... but with more .... Has more underlying ... and may have deep ... with no clear zone between ... and ....

Mx:
* same as ... in terms of drugs.
* Aim is to ... and minimise ... and ....
* Aciclovir inhibits .... Debridement reduces ... and ....
* Can give additional drug dosemg regimen for duration in those who are ..., non-compliant, unable to use, or exhibiting ocular toxicity to ....

Answer 31

HSV - Reactivation - HSK - Epithelial Disease (1)

Punctate epithelial opacities may coalesce centrally and form a dendritic ulcer.

Dendritic ulcers result in mild epithelial haze, linear, dichotomous branching and terminal buds. Bed stains with flourescein and margins stain with rose bengal or lissamine green.

Geographic ulcer - expanding dendritic ulcers take on shape of country

Marginal keratitis is rare, resembles a staphylococcal marginal keratitis but with more pain. Has more underlying stromal inflammation and may have deep neovasc with no clear zone between infiltrate and limbus.

Mx:
* same as primary infection in terms of drugs.
* Aim is to eliminate live HSV and minimise scarring and stromal inflammation.
* Aciclovir inhibits synthesis of viral DNA. Debridement reduces viral load and better penetration.
* Can give additional oral valaciclovir 500mg bid for a week in those who are immunocompromised, non-compliant, unable to use, or exhibiting ocular toxicity to aciclovir ointment.

Question 32

HSV - Reactivation - HSK - Epithelial Disease (2)

Metaherpetic (...) ulcer is a .... Only form of epithelial ulceration that does not have any .... Caused by inability of ... to ..., caused by damage to the .... Has ... surrounding the ulcer that ... with Rose Bengal.

Causes: loss of ... and ... result in complete or partial ..., ..., underlying low-grade ..., toxicity from ..., any epithelial disease unresolved after ...-... weeks, ..., patients will be ....

Treatments include: intensive (every 15-30mins) ...., ..., ..., ... at night, ..., ..., ....

Answer 32

HSV - Reactivation - HSK - Epithelial Disease (2)

Metaherpetic (neurotrophic) ulcer is a persistent epithelial defect. Only form of epithelial ulceration that does not have any live virus. Caused by inability of epithelium to heal, caused by damage to the basement membrane. Has smooth greyish elevated borders surrounding the ulcer that do not with Rose Bengal.

Causes: loss of innervation and neural-derived growth factors result in complete or partial anaesthesia, poor tear film, underlying low-grade stromal inflammation, toxicity from anitiviral medications, any epithelial disease unresolved after 2-3 weeks, culture negative, patients will be asymptomatic.

Treatments include: intensive (every 15-30mins) preservative-free lubrication, bandage CL, patching with antibiotic ointment, taping eyelids closed at night, autologous serum drops, amniotic membrane, tarsorrhaphy.

Question 33

HSV - Reactivation - HSK - Stromal disease

Stromal HSK can occur either when the latent virus has been ... or from a ... and accounts for ...% of initial HSK presentations. It’s a potentially ... complication marked by ..., ..., ..., ..., with possible ... involvement. ... response to ... viral particles in the corneal stroma and NOT DUE to ... viral replication. There is usually a history of ... and ...-...% of recurrent disease is ... HSV.

Two types: non-necrotising (...%, stromal inflammation with ...) and necrotising (...%, more ... and intense overlying ..., ..., and ...).

Signs include: ..., ..., .../..., and ....

Answer 33

HSV - Reactivation - HSK - Stromal disease

Stromal HSK can occur either when the latent virus has been reactivated at the trigeminal ganglion or from a direct spread from the epithelium and accounts for 2% of initial HSK presentations. It’s a potentially blinding complication marked by stromal inflammation, uveitis, endotheliitis, trabeculitis, with possible epithelial involvement. Inflammatory response to non-replicating viral particles in the corneal stroma and NOT DUE to active viral replication. There is usually a history of HSV epithelial disease and 20-48% of recurrent disease is stromal HSV.

Two types: non-necrotising (88%, stromal inflammation with intact epithelium) and necrotising (7%, more widespread and intense overlying epithelial defect, necrosis, and ulceration).

Signs include: blurred vision, halos, discomfort/pain, and red eye.

Question 34

HSV - Reactivation - HSK - Stromal disease - Non-necrotising
Also known as ... and ....

Signs: intact ... without ..., stromal ... with multifocal stromal ..., ..., stromal ..., epithelial ..., ..., and ... (... with ... due to ...)

Treatment: ... any live HSV, ... risk of reactivation, control ..., prevent ....

Drugs:
* Drug dose% regimen with ...
* Oral drug dosemg regimen during ... (also used ...; dosemg regimen for up to ... months)
* Control ... as required
* ... as required (topical drug dose% regimen or drug dose% regimen)

Answer 34

HSV - Reactivation - HSK - Stromal disease - Non-necrotising
Also known as interstitial keratitis and immune stromal keratitis.

Signs: intact epithelium without ulceration, stromal oedema with multifocal stromal opacities, anterior uveitis, stromal vascularisation, epithelial oedema, ciliary flush, and immune ring (circumferential with intrastromal sterile infiltrates due to antigen/antibody interactions)

Treatment: eliminate any live HSV, reduce risk of reactivation, control inflammation, prevent scarring.

Drugs:
* Prednefrin Forte 1% 4-6x/day with slow taper over months
* Oral valaciclovir 500mg qd during steroid use (also used prophylactically; 500mg qd for up to 12 months)
* Control IOP as required
* Cycloplegia as required (topical atropine 1% bid or cyclopentolate 1% tid)

Question 35

HSV - Reactivation - HSK - Stromal disease - Necrotising

Signs: defected ... with ..., severe ... to active ... within stromal keratocytes, following ... of HSV, stromal ... with multifocal stromal ..., ..., stromal ..., epithelial ..., ciliary ..., ..., stromal ... and corneal ... with high risk of ..., difficult to distinguish from ...

Treatment:
* Drug dose% regimen with ...
* Oral drug dosemg regimen durationdays as a ... dose
* ... and control ... as required
* Topical drug class (drug dose% regimen or drug dose% regimen) until negative ... and ... infection is confirmed
* Oral drug dosemg regimen as a ... dose for up to duration months

Answer 35

HSV - Reactivation - HSK - Stromal disease - Necrotising

Signs: defected epithelium with ulcer, severe inflammatory response to active viral replication within stromal keratocytes, following multiple recurrences of HSV, stromal oedema with multifocal stromal opacities, anterior uveitis, stromal vascularisation, epithelial oedema, ciliary flush, immune ring, stromal thinning and corneal melting with high risk of perforation, difficult to distinguish from microbial keratitis

Treatment:
* Prednefrin Forte 1% bid with slow taper over months
* Oral valaciclovir 1000mg tid 7-10days as a treatment dose
* Cycloplegia and control IOP as required
* Topical fluoroquinolone (ciprofloxacin 0.3% q1h day and night or ofloxacin 0.3% q1h day and night) until negative bacterial and fungal infection is confirmed
* Oral valaciclovir 500mg qd as a prophylactic dose for up to 12 months

Question 36

HSV - Reactivation - HSK - Stromal disease - Endotheliitis/Endothelial keratitis
Also called ..., not a primary form of ....

Signs: endothelial ... response to HSV ... in AC, stromal ... is present ... to endothelial ..., ... zone of minimal stromal ... may have overlying epithelial ..., keratic ... underlying stromal ..., no ... or ..., could have ... in Descemet’s membrane, ... may be elevated due to ..., reduced corneal ....
If untreated, can lead to intractable stromal ....

Treatment:
* Drug dose% regimen with ...
* Oral drug dosemg regimen durationdays (also used ...; dosemg regimen for up to duration months).

Answer 36

HSV - Reactivation - HSK - Stromal disease - Endotheliitis/Endothelial keratitis

Also called disciform keratitis, not a primary form of stromal keratitis.
Signs: endothelial inflammatory response to HSV antigen in AC, stromal oedema is present secondary to endothelial inflammation, round central zone of minimal stromal oedema may have overlying epithelial oedema, keratic precipatates underlying stromal oedema, no infiltrates or vascularisation, could have folds in Descemet’s membrane, IOP may be elevated due to trabeculitis, reduced corneal sensation.
If untreated, can lead to intractable stromal oedema.

Treatment:
* Prednefrin Forte 1% 4-6x/day with slow taper over months
* Oral valaciclovir 1000mg tid 7-10days (also used prophylactically; 500mg qd for up to 12 months).

Question 37

HSV - Reactivation - HSK - Stromal disease - Iridocyclitis, trabeculitis, acute secondary glaucoma

Can occur ... or ... history of ... and symptoms include ..., ..., ....

Signs: ... and ... reaction, ... atrophy due to ... of the iris stroma, trabeculitis often causes ... (due to blockage of outflow by ... or ...)

Treatment:
* Drug dose% regimen with ...
* Oral dose dosemg regimen for duration days as a ... dose (also used ...; dosemg regimen for up to ... months)
* Control ... as required

Answer 37

HSV - Reactivation - HSK - Stromal disease - Iridocyclitis, trabeculitis, acute secondary glaucoma

Can occur with or without history of keratitis and symptoms include photophobia, pain, ciliary flush.

Signs: keratic precipitates and anterior chamber cell reaction, segmental iris atrophy due to ischaemic necrosis of the iris stroma, trabeculitis often causes severe elevation of IOP (due to blockage of outflow by inflammatory cells or primary trabeculitis)

Treatment:
* Prednefrin Forte 1% 4-6x/day with slow taper over months
* Oral valaciclovir 1000mg tid for 7-10 days as a treatment dose (also used prophylactically; 500mg qd for up to 12 months)
* Control IOP as required

Question 38

Herpes Eye Disease Study (HEDS)

HEDS 1 - ... trial looking at the effectiveness of addition of topical ... and oral ... to topical antiviral treatment in ... HSK.
Addition of ... drops beneficial but no benefit from addition of oral ....

HEDS 2 - ... trial looking at the effect of oral ... on ... HSK and ... HSK recurrence.
No benefit of addition of oral ... on either preventing progression of ... HSV to ... HSV. Oral drug dosemg regimen for duration months reduced of HSV recurrence by ...% and risk of ... HSV by ...%.

Answer 38

Herpes Eye Disease Study (HEDS)

HEDS 1 - therapeutic trial looking at the effectiveness of addition of topical steroids and oral antivirals to topical antiviral treatment in stromal HSK.
Addition of steroid drops beneficial but no benefit from addition of oral aciclovir.

HEDS 2 - prevention trial looking at the effect of oral antivirals on active epithelial HSK and stromal HSK recurrence.
No benefit of addition of oral aciclovir on either preventing progression of epithelial HSV to stromal HSV. Oral aciclovir 400mg bid for 12 months reduced of HSV recurrence by 50% and risk of stromal HSV by 50%.

Question 39

Herpes Eye Disease Study (HEDS) - Reactivation of HSV

Best predictor of ... HSV keratitis is a history of previous ... HSV keratitis.
Oral drug dosemg regimen reduces risk of recurrence when used long term.

Should be offered to those who: have ... in one year, have ... close to visual axis, are using topical ... for ..., and are ....

Answer 39

Herpes Eye Disease Study (HEDS) - Reactivation of HSV

Best predictor of stromal HSV keratitis is a history of previous stromal HSV keratitis.
Oral aciclovir 400mg bid reduces risk of recurrence when used long term.

Should be offered to those who: have multiple recurrences in one year, have scarring close to visual axis, are using topical steroids for stromal disease, and are systematically immunocompromised.

Question 40

HSV - Reactivation - Australian Treatments

Oral ... are used to treat ... HSK in Australia which is a deviation from the ... protocol and ... aciclovir is as effective as ... aciclovir (useful as ... aciclovir may cause ...).

Oral ... is a prodrug and is converted in vivo to ...; it is more ... (..%) with fewer ... and improved compliance as the dosage is regimen. Another alternative is ....

Answer 40

HSV - Reactivation - Australian Treatments

Oral antivirals are used to treat stromal HSK in Australia which is a deviation from the HEDS protocol and oral aciclovir is as effective as topical aciclovir (useful as topical aciclovir may cause ocular surface toxicitiy).

Oral valaciclovir is a prodrug and is converted in vivo to aciclovir; it is more bioavailable (50%) with fewer side effects and improved compliance as the dosage is qd. Another alternative is famciclovir.

Question 41

HSV - Differential diagnoses

Epithelial HSK - ... (up to ...% is misdiagnosed as HSK), ..., and ...

Stromal HSK - ... (...)

Endothelial HSK - ... syndrome (..., ..., mild ... reaction), ..., ...).

Answer 41

HSV - Differential diagnoses

Epithelial HSK - acanthamoeba keratitis (up to 50% is misdiagnosed as HSK), herpes zoster, and RCEs

Stromal HSK - interstitial keratitis (syphilis)

Endothelial HSK - Posner-Schlossman syndrome (unilateral, elevated IOP, mild AC reaction), corneal graft rejection, cytomegalovirus).

Question 42

HSV - Pathology - Diagnostic Testing

... is the most common diagnostic test. It identifies ... with up to ...% sensitivity (can be identified in ..., ..., ..., and ...). Detects all ... and cannot differentiate between ... and ... HSV. Essential that the cornea is swabbed to detect ... rather than just ....

Can also do an ....

Answer 42

HSV - Pathology - Diagnostic Testing

PCR is the most common diagnostic test. It identifies HSV viral DNA with up to 100% sensitivity (can be identified in tear film, conjunctiva, cornea, and aqueous). Detects all viral DNA and cannot differentiate between latent and active HSV. Essential that the cornea is swabbed to detect corneal infection rather than just conjunctiva.

Can also do an immunoassay.