33. Herpetic Keratitis Flashcards

Question

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 1

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`.

Answer 2

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`.

Answer 3

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.

Answer 4

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`.

Answer 5

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.

Answer 6

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.

Answer 7

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` `500`mg `bid` for `a week` in those who are `immunocompromised`, non-compliant, unable to use, or exhibiting ocular toxicity to `aciclovir ointment`.

Answer 8

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`.

Answer 9

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`.

Answer 10

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` `500`mg `qd` during `steroid use` (also used `prophylactically`; `500`mg `qd` for up to `12` months) * Control `IOP` as required * `Cycloplegia` as required (topical `atropine` `1`% `bid` or `cyclopentolate` `1`% `tid`)

Answer 11

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` `1000`mg `tid` `7-10`days 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` `500`mg `qd` as a `prophylactic` dose for up to `12` months

Answer 12

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` `1000`mg `tid` `7-10`days (also used `prophylactically`; `500`mg `qd` for up to `12` months).

Answer 13

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` `1000`mg `tid` for `7-10` days as a `treatment` dose (also used `prophylactically`; `500`mg `qd` for up to `12` months) * Control `IOP` as required

Answer 14

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` `400`mg `bid` for `12` months reduced of HSV recurrence by `50`% and risk of `stromal` HSV by `50`%.

Answer 15

Herpes Eye Disease Study (HEDS) - Reactivation of HSV Best predictor of `stromal` HSV keratitis is a history of previous `stromal` HSV keratitis. Oral `aciclovir` `400`mg `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`.

Answer 16

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`.

Answer 17

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`).

Answer 18

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`.

33. Herpetic Keratitis Flashcards

(42 cards)