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History/Presentation
A 45-year-old female was referred for increasing blurred vision and photophobia in her right eye over the preceding week, with reduced foreign-body sensation. She had previously been referred to an ophthalmologist with similar symptoms.
RVA: 6/7.5
LVA: 6/5
Figure 1: Slit lamp image of right eye showing small subepithelial infiltrates.
What else is important to ask this patient?
Recent cold/flu-like illness
Recent or past history of cold sores
History of chicken pox and/or shingles (punctate keratitis and small pseudodendrites can occur up to 1/12 after V1 shingles)
Varicella zoster keratitis (history or recent shingles)
Bacterial/fungal (usually more fluffy with other red flags in patient history)
What other examination/tests would you like to do?
Fluorescein staining/eye drops
Corneal sensation (important in herpetic disease)
Iris atrophy/transillumination (sectoral versus patchy) – HSV/VZV
Always check the fundus for retinal/choroidal/vascular abnormalities
Figure 2: Fluorescein stain (right eye) confirms the presence of small epithelial defects
The patient reveals a history of cold sores, including a recent flare-up. Approximately 12 months ago, she had seen another ophthalmologist for the same symptoms and the patient notes confirmed she had been treated with Maxidex and Zovirax.
Diagnosis
Given her history and presence of small epithelial defects (but not dendrites), it is highly likely this patient has herpes simplex virus (HSV) keratouveitis.
Treatment
Start Maxidex (dexamethasone) and taper slowly over 4 weeks (qid, tds, bd, daily)
Zovirax 3% (aciclovir) ointment cover may decrease the risk of dendritic ulcer developing
Consider stopping Zovirax after 2 weeks as the risk of epithelial HSV is very low in true herpetic keratitis. Some clinicians only use topical steroids, but it’s probably safer to cover with Zovirax ointment for initial 1-2 weeks.
Oral famciclovir was discussed with the patient as an alternative anti-viral option. Compared to topical Zovirax, oral famciclovir offers quicker resolution of symptoms, less corneal toxicity and some added benefit if uveitis is present. However, the cost is often prohibitive for patients because it is not listed on the PBS for HSV.
Progress
2 weeks after presentation
Figure 3: Slit lamp examination of right eye 2 weeks after beginning treatment. No epithelial defects evident.
4 weeks after presentation
Figure 4: Slit lamp examination of right eye 4 weeks after initial presentation.
Figure 5: Fluorescein stain confirms the recurrence of small right epithelial defects. The patient admitted to stopping treatment after 3 weeks.
Managing HSV recurrence
Re-commenced topical Zovirax tds
Initiated Flarex eye drops (fluoromethalone) qid
Stressed importance of slow taper over 6–8 weeks
Flarex qid 1/52 with tds Zovirax
Flarex tds 1/52 with tds Zovirax
Flarex bd 1/52 with bd Zovirax
Flarex daily 2 weeks with daily Zovirax
Flarex alternate days 2 weeks with alternate day Zovirax
The patient was asked to return for a review in 1–2 weeks and again 2 weeks after stopping treatment (or ASAP if symptoms are worsening).
HSV keratitis nomenclature
Epithelium
HSV epithelial keratitis (dendritic epithelial ulcer or geographic epithelial ulcer)
HSV stromal keratitis with ulceration (necrotising keratitis)
Endothelium
HSV endothelial keratitis (disciform keratitis)
DENDRITIC ULCER
HERPETIC KERATOUVEITIS
RECURRENT INTERSTITIAL KERATITIS + NEW DISCIFORM
ENDOTHELIAL/DISCIFORM KERATITIS
Figure 6: Area of localised corneal oedema and a few keratic precipitates, consistent with a diagnosis of disciform keratitis. AC inflammation if minimal. If there is moderate AC inflammation (AC cells >1+), then a diagnosis of keratouveitis is likely.
HERPETIC SCARS
GEOGRAPHIC ATROPHY
HSV keratitis treatment protocol
Epithelial disease only
Topical corticosteroids should be avoided in the initial management of HSV epithelial keratitis.
Dendritic ulcer
Debride/debulk: LA-soaked cotton wool rolled over lesion
Topical acyclovir: 5 times per day day 7/7, tds 7/7 OR
Oral aciclovir, valaciclovir, famciclovir: 7–10 days then lower dose
Geographic ulcer
Topical aciclovir: 5 times per day until healing then tds 7/7
Watch for toxicity/non healing/worsening, which requires oral Rx
Intensive gel lubricants (e.g. Genteal Tears)
Oral antivirals (maximum dose): 2–3/52 (preferred as less corneal toxicity) but are expensive
Stromal disease
Without epithelial ulceration
Topical steroids: 4–6 times per day, tapering quickly at first and then more slowly (e.g. by 1 drop weekly for first 3–4 weeks then every second week for next 4–6 weeks)
May need 6–12 weeks of treatment, depending on response and history
Oral/topical antiviral cover: lower/prophylactic oral dose of acyclovir or famciclovir or bd–tds topical Zovirax cover
With epithelial ulceration
Antiviral cover: topical or oral using therapeutic (higher) dose
Topical steroids: lower dose (e.g. bd) until ulcer heals then increase as necessary OR
Withhold steroid for first 24–36 hours of antiviral therapy before commencing lower dose and increasing once ulcer heals
Taper steroids as above or based on disease response
Endothelial keratitis/disciform keratitis
Responds more quickly than stromal keratitis
Initiate therapeutic dose of antivirals for 7–10 days, then drop to prophylactic dose while on steroids
Topical steroids 4–6 times per day for 7–10 days, then taper over 3–4 weeks based on response
If AC inflammation is severe, steroids may need to be administered more frequently.
HSV long-term oral prophylaxis
Prophylaxis is considered in patients with:
>1 recurrence within 12 months
Scar/vascularisation getting close to visual axis
Pre/post-operative patient with a history of HSV keratitis (e.g. undergoing corneal graft, refractive other ocular surgery)
Immunocompromised (e.g. on chemotherapy).
Key message:
Herpes viruses, including HSV1, HSV2 and VSV, can all affect the eye. The possible diagnosis of such conditions should always be kept in the back of the mind in any patient presenting with corneal inflammatory changes (oedema, infiltrates, epithelial defect) and/or uveitis. Any patient with suspected corneal herpetic disease must have a dilated exam to look for intraocular involvement.
Dr Nima Pakrou is an experienced ophthalmologist with expertise across a range of eye conditions. His subspecialty areas include medical retinal diseases, cataracts, intraocular inflammation and oculoplastics. He practises at Vision Eye Institute Footscray.
This article is for educational and informational purposes only and may not be directly applicable to your individual patients.
Date last reviewed: 2023-08-14 | Date for next review: 2025-08-14