DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1782 The more commonly reported infectious agents are adenovirus
and herpes simplex virus, followed by other viral (e.g.,
enterovirus, coxsackievirus, measles virus, varicella zoster virus,
vaccinia variola virus) and bacterial sources (e.g., Neisseria spp.,
Streptococcus pneumoniae, Haemophilus spp., S. aureus,
Moraxella lacunata, and chlamydial spp.). Rickettsia, fungi, and
parasites, in both cyst and trophozoite form, are rare causes of conjunctivitis.
Effective management is based on selection of an appropriate
antibiotic for suspected bacterial pathogens. Unless an
unusual causative organism is suspected, bacterial conjunctivitis is
treated empirically with a broad-spectrum topical antibiotic without
obtaining a culture.
SECTION IX
SPECIAL SYSTEMS PHARMACOLOGY
Keratitis, or corneal inflammation, can occur at
any level of the cornea (e.g., epithelium, subepithelium,
stroma, endothelium). It can be due to non-infectious or
infectious causes. Numerous microbial agents have been
identified as causes of infectious keratitis, including bacteria,
viruses, fungi, spirochetes, and cysts and trophozoites.
Severe infections with tissue loss (corneal ulcers)
generally are treated more aggressively than infections
without tissue loss (corneal infiltrates).
The mild, small, more peripheral infections usually are not
cultured, and the eyes are treated with broad-spectrum topical antibiotics.
In more severe, central, or larger infections, corneal scrapings
for smears, cultures, and sensitivities are performed, and the patient
is immediately started on intensive hourly, around-the-clock topical
antibiotic therapy. The goal of treatment is to eradicate the infection
and reduce the amount of corneal scarring and the chance of corneal
perforation and severe decreased vision or blindness. The initial medication
selection and dosage are adjusted according to the clinical
response and culture and sensitivity results.
Endophthalmitis is a potentially severe and devastating
inflammatory, and usually infectious, process
involving the intraocular tissues. When the inflammatory
process encompasses the entire globe, it is called
panophthalmitis. Endophthalmitis usually is caused by
bacteria or fungi, or rarely by spirochetes. The typical
case occurs during the early postoperative course (e.g.,
after cataract, glaucoma, cornea, or retinal surgery),
following trauma, or by endogenous seeding in an
immunocompromised host or intravenous drug user.
Acute postoperative endophthalmitis requires a prompt
vitreous tap for smears and cultures and empirical injection
of intravitreal antibiotics.
Immediate vitrectomy (i.e., specialized surgical removal of
the vitreous) is beneficial for patients who have light perception–only
vision (Endophthalmitis Vitrectomy Study Group, 1995). Vitrectomy
for other causes of endophthalmitis (e.g., glaucoma bleb related, posttraumatic,
or endogenous) may be beneficial (Schiedler et al., 2004).
In cases of endogenous seeding, parenteral antibiotics have a role in
eliminating the infectious source, but the efficacy of systemic antibiotics
with trauma is not well established.
Antiviral Agents
General Considerations. The various antiviral drugs
currently used in ophthalmology are summarized in
Table 64–5 (see Chapter 58 for additional details
about these agents).
Therapeutic Uses. The primary indications for the use of
antiviral drugs in ophthalmology are viral keratitis,
herpes zoster ophthalmicus (Liesegang, 1999; Chern
and Margolis, 1998), and retinitis. There currently are
no antiviral agents for the treatment of viral conjunctivitis
caused by adenoviruses, which usually has a selflimited
course and typically is treated by symptomatic
relief of irritation.
Viral keratitis, an infection of the cornea that may involve
either the epithelium or stroma, is most commonly caused by herpes
simplex type I and varicella zoster viruses. Less common viral etiologies
include herpes simplex type II, Epstein-Barr virus, and CMV.
Topical antiviral agents are indicated for the treatment of epithelial
disease due to herpes simplex infection. When treating viral keratitis
topically, there is a very narrow margin between the therapeutic
topical antiviral activity and the toxic effect on the cornea; hence,
patients must be followed very closely. The role of oral acyclovir
and glucocorticoids in herpetic corneal and external eye disease has
been examined in the Herpetic Eye Disease Study (Herpetic Eye
Disease Study Group, 1997; Herpetic Eye Disease Study Group,
1998). Topical glucocorticoids are contraindicated in herpetic epithelial
keratitis due to active viral replication. In contrast, for herpetic
disciform keratitis, which predominantly is presumed to involve a
cell-mediated immune reaction, topical glucocorticoids accelerate
recovery (Wilhelmus et al., 1994). For recurrent herpetic stromal
keratitis, there is clear benefit from treatment with oral acyclovir in
reducing the risk of recurrence (Herpetic Eye Disease Study Group,
1998). An ophthalmic formulation of trifluridine (VIROPTIC) is available
for treatment of keratoconjunctivitis and epithelial keratitis due
to herpes simplex viruses.
Herpes zoster ophthalmicus is a latent reactivation of a varicella
zoster infection in the first division of the trigeminal cranial
nerve. Systemic acyclovir, valacyclovir, and famciclovir are effective
in reducing the severity and complications of herpes zoster ophthalmicus
(Colin et al., 2000). Currently, there are no ophthalmic
preparations of acyclovir approved by the FDA, although an ophthalmic
ointment is available for investigational use.
Viral retinitis may be caused by herpes simplex virus, CMV,
adenovirus, and varicella zoster virus. With the highly active antiretroviral
therapy (HAART; see Chapter 59), CMV retinitis does not appear
to progress when specific anti-CMV therapy is discontinued, but some
patients develop an immune recovery uveitis (Jacobson et al., 2000;
Whitcup, 2000). Treatment usually involves long-term parenteral
administration of antiviral drugs. Intravitreal administration of ganciclovir
has been found to be an effective alternative to the systemic
route (Sanborn et al., 1992). Acute retinal necrosis and progressive
outer retinal necrosis, most often caused by varicella zoster virus, can
be treated by various combinations of oral, intravenous, intravitreal
injection of, and intravitreal implantation of antiviral medications
(Roig-Melo et al., 2001).