Herpes Simpex
Subjective
A 65-year-old white woman presents with an increasingly irritated
right eye for the past four days (Fig.
1, Fig. 2). She is currently
under chronic care for her advanced dry eye syndrome.
She uses preservative-free (PF) artificial tears inconsistently
for her ocular surface disease.
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Fig. 1 While it is obvious that this woman has severe
dry eyes, as evidenced by rose bengal staining, her chief
complaint was that her right eye was hurting.
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Fig. 2 Upon more careful inspection of her right cornea,
it can be seen that she has classic herpes epithelial keratitis
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Objective
- 2+ conjunctival injection OD; 1+ OS
- 2+ rose bengal staining OU
Assessment
- Epithelial herpes simplex keratitis (HSK) OD
- Bilateral keratoconjunctivitis sicca
Plan
- Trifluridine (Viroptic) ophthalmic solution 1 gt. OD q2h.
x 4 days
- Unit dose TheraTears Liquid Gel q.i.d. OU
- Return to clinic in 4 days
First Follow-Up Visit
Subjective
Objective
- Herpetic lesions 80% improved
Assessment
- HSK responding nicely to antiviral therapy
Plan
- Decrease trifluridine to q.i.d. OD x 4 days
- Continue unit doseTheraTears Liquid Gel q.i.d. OU
- Return to clinic in 4 more days
Second Follow-Up Visit
Subjective
- Both eyes feel "much better"
Objective
- Corneal epithelium renormalized OD
- BUT: 6 to 7 seconds OU
- Modest reduction in rose bengal staining pattern
Assessment
- Resolved HSK
- Chronic keratoconjunctivitis sicca with chronic ocular surface
disease
Plan
- Discontinue trifluridine
- Continue unit dose TheraTears Liquid Gel q.i.d. OU
- Re-evaluate patient in one month to assess ocular surface
status. At that time, decide whether to modify topical therapy
and/or insert punctal plugs
Comments: This rather straightforward diagnosis is complicated
by the underlying dry eyes. Since all topically applied antivirals
are potentially toxic to the cornea, concurrent use of artificial
tears is useful when treating HSK. Because this patient had
preexisting keratoconjunctival epithelial tissue compromise,
it was important to use a more viscous product, such as TheraTears
Liquid Gel hourly. Advise the patient that there is a 25% to
50% chance of HSK recurrence and to return promptly if the
symptoms reappear. Timely, proper therapy usually results in
little or no scarring. (Note: While trifluridine is properly
stored under refrigeration, once the drug is dispensed to a
patient, it does not have to be kept refrigerated.)
Clinical Observations of Epithelial Disease
- Cornea may initially show coarse, punctate, superficial punctate
keratitis-like lesions, which usually coalesce to form linear
or dendriform appearance (Fig. 3), or less commonly, a geographic
lesion
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Fig 3. Typical dendritic keratitis |
- Hypoesthesia is experienced in the affected cornea (Q-tip sensitivity
test can occasionally be helpful)
- Pain is usually not severe because of subdued corneal afferent
neuronal sensitivity (via the nasociliary pathway)
- Fluorescein tends to stain the central ulcer bed, whereas
rose bengal or lissamine green tends to stain the leading edges
of viral proliferation
bout 90% of adults harbor this neurotrophic virus following
a usually asymptomatic primary infection as a child
- Latent virus resides in Gasserian (trigeminal) ganglion
- Two common types: I and II, of which type II is usually genital
- Opportunistic virus reactivation risk factors: fever, stress,
menstruation, sunburn, prostaglandin-eyedrops, trauma, corticosteroid
use, or any immuno-compromising condition.
- Following the first secondary (epithelial) infection, there
is a 25% chance of a recurrence; the chance of subsequent recurrences
increases to about 40% to 45%.
Men have a slightly greater tendency to recurrences than women
- The genome, or DNA uniqueness, of the various herpes strains
is thought to direct the clinical behavior and clinical expression
of the infecting virus (i.e., end-bulbs versus bifurcations
and branches without end-bulbs, serious versus mild pathogenicity,
causing stromal disease versus nonstromal involvement, steroidal
exacerbation of disease versus nonsteroidal exacerbation, etc.)
- Factors that complicate and prolong the natural history
and clinical management:
- infectious foci near the limbus
- prior treatment with corticosteroids
- delay in seeking care by the patient
- underlying stromal inflammation
General Observations
- About 50,000 new cases each year in the U.S.
- Leading cause of corneal opacification
- Common cause of unilateral red eye with tearing, photophobia,
irritation, and sometimes decreased vision
- Fellow eye is not at risk to develop infection
- History of cold sores or fever blisters is occasionally helpful
in diagnosis
- Fluorescein tends to stain the central ulcer bed, whereas
rose bengal or lissamine green tends to stain the leading edges
of viral proliferation
Medical Management of Epithelial Disease
- Trifluridine solution is administered one drop every two hours
until the epithelial lesion is mostly healed, usually 4 to
7 days, then 4 to 5 times daily for 4 to 7 more days. Preservative-Free
artificial tears can be added every hour or two between the
trifluridine drops. Adding artificial tears to any medical
treatment is helpful in re-establishing corneal tissue integrity
- If patient is-or becomes-allergic to tripluridine, then systemic
antiviral therapy with acyclovir (or Famvir or Valtrex) at
½ the mg. dosage used in zoster therapy can be successfully
used. For example, acyclovir is dosed at 800 mg 5xD for 7 days
when treating herpes zoster ophthalmicus. When treating herpes
simplex disease, 400 mg 5xD for 7 days would be used.
- Always cycloplege (usually with 5% homatropine) if there is
any significant corneal involvement or anterior chamber reaction
Clinical Observations of Stromal Disease
- Stromal involvement, when it does occur, can significantly
complicate the management of herpetic keratitis
- Even minor stromal involvement can retard the rate and quality
of re-epithelialization
- Seen in about one-fifth of cases, and can be concurrent, but
is usually delayed weeks or months after an episode of epithelial
disease
- Focal stromal opacification is a critical slit-lamp finding.
This usually occurs beneath the epithelial lesion (or where
the epithelial lesion was located)
- Stromal inflammatory disease can be antigen-antibody-complement
mediated and/or delayed, cell-mediated (lymphocyte-plasma cell)
hypersensitivity in nature; both of which are generally responsive
to steroids
Medical Management of Stromal Disease
- It is the judicious use of topical corticosteroids initially
along with topical antiviral coverage that is critical in the
management of stromal disease. Once the frequency of topical
corticosteroid drops is tapered to 2 or 3 instillations per
day, it is usual to stop or taper the antiviral coverage
- Once the stroma becomes involved, a mild secondary iridocyclitis
is a common accompaniment and the iridocyclitis is managed
largely via cycloplegia
- Tapering the topical corticosteroid eye drops usually is a
long, tedious process often taking many months. Most patients
have to maintain daily or every other day administration indefinitely
- Once the active stromal inflammation is under control,
prophylax against recurrence with an oral antiviral. For
patients having 2 or more recurrent herpetic episodes within
a relatively short time frame (for example, less than 3 To
4 months apart), it has become standard-of-care to "treat" these
patients with 400 mg of acyclovir (ACV) b.i.d. for a year
or two.
Such prophylactic intervention has been shown to decrease
the rate of herptic reoccurrence be 40 to 50%. This knowledge
was originally published in the July 30, 1998 New England Journal
of Medicine and established this new standard of patient management.
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