Although treatment of typical bacterial conjunctivitis such as this is empirical, a
culture should be obtained. Other ophthalmic antibiotic drops or ointments, such as
antimicrobials, such as the ocular quinolones, may be used for bacterial
conjunctivitis, these agents should be reserved as second-line therapies because of
cost and the potential development of resistance. Proper management of this infection
also includes mechanical cleaning of the eyelids and hygienic measures that prevent
spreading the infection to other children. The deposits should be removed as often as
possible with moist cotton swabs or cotton-tipped applicators. A mild baby shampoo
can be used to moisten the applicator. Firm adherent crusts may be softened with
warm, moist compresses. Because this material is infectious, it should be disposed of
in a sanitary fashion. The common use of washcloths by several individuals will
spread bacterial conjunctivitis.
eyes often because they itch. What treatment is best for N.V.’s allergic conjunctivitis?
Topical vasoconstrictors (e.g., naphazoline, tetrahydrozoline) with or without
antihistamines (e.g., antazoline, pheniramine) may be used to treat hyperemia, but
they should not be used excessively because rebound congestion can occur. Use of
topical vasoconstrictors for longer than 72 hours is not recommended owing to the
potential for rebound congestion and masking of more serious ocular inflammatory
conditions. Antihistamine tablets or syrup can provide considerable, but temporary,
relief. Several ophthalmic histamine H1
-receptor antagonists are effective in the
treatment of allergic conjunctivitis. Levocabastine 0.05% is administered BID to
QID, olopatadine 0.1% BID (separating doses by 6–8 hours) or 0.2% once daily,
emedastine 0.05% QID, ketotifen 0.025% BID to QID, bepotastine 1.5% BID, and
115–117 Ketotifen, olopatadine, azelastine, epinastine,
and alcaftadine exhibit both antihistamine and mast cell stabilizing effects.
Emedastine was more efficacious than levocabastine when used BID for 6 weeks in
adult and pediatric patients with seasonal allergic conjunctivitis.
provided superior efficacy and a more rapid resolution of the signs and symptoms of
allergic conjunctivitis when compared with ketotifen in a small trial involving adult
119 Azelastine has a slightly quicker onset of therapeutic effect when
compared with olopatadine and placebo.
120 Bepotastine 1.5% BID provided better
relief of evening ocular and nasal symptoms than olopatadine 0.2% administered
121 Alcaftadine 0.25% and olopatadine 0.2% administered
once daily provided relief of ocular itching at 16 and 24 hours postinstallation with
alcaftadine also providing significant relief from chemosis.
insufficient to definitively recommend one of these products as superior to the others.
The ideal treatment would be removal of the allergen, but this usually is impossible
when the conjunctivitis is secondary to seasonal allergies. Topical corticosteroids
provide dramatic relief, but their use must be limited because of potential adverse
effects (see Ophthalmic Corticosteroids section).
Cromolyn sodium ophthalmic, a drug that inhibits the release of histamine in
response to antigen, may be effective as an alternative for patients who fail to
respond to more conservative measures. Lodoxamide, pemirolast, and nedocromil
have a similar mechanism of action to cromolyn sodium ophthalmic, but these agents
also decrease chemotaxis and activation of eosinophils. In comparative studies,
lodoxamide tromethamine 0.1% is at least as effective as cromolyn sodium
ophthalmic 2% to 4% in treating allergic ocular disorders, including vernal
123,124 Patients in these studies demonstrated more rapid and
greater response when treated with lodoxamide, one drop QID. In a 2-week
crossover study of nedocromil and olopatadine involving 28 patients of 7 years of
age and older, patient acceptance of nedocromil BID was better than for olopatadine
BID, but treatment outcomes were essentially equal.
this therapy, and how can the patient obtain it?
The initial choice of therapy for bacterial corneal ulcers commonly is based on a
Gram stain and clinical impression of the severity of the ulcer. Single or combination
antimicrobial therapy can be prescribed. Although commercial antimicrobial
ophthalmic formulations are available, the antimicrobial concentrations in these
products might be inadequate to effectively treat bacterial corneal ulcers.
Topical antimicrobials for the treatment of bacterial corneal ulcers can be
prepared from parenteral antimicrobials or by the addition of parenteral
antimicrobials to “fortify” commercially available products. Commonly prescribed
products include bacitracin 5,000 to 10,000 units/mL, cefazolin 33 to 100 mg/mL,
gentamicin or tobramycin 9.1 to 13.6 mg/mL, and vancomycin 25 to 50 mg/mL.
Fortified gentamicin has been prepared by adding 80 mg of parenteral gentamicin to
the commercially available gentamicin ophthalmic solution. The final concentration
of this solution is 13.6 mg/mL. Cefazolin ophthalmic solution is prepared by
reconstituting 500 mg parenteral cefazolin with 2 mL of sterile normal saline. Two
milliliters of artificial tears solution are removed from a commercially available 15-
mL bottle and replaced with the 2-mL reconstituted cefazolin solution (resulting in a
final cefazolin concentration of 33 mg/mL). Therapy initially can be administered as
frequently as every 15 to 30 minutes with extension of intervals as the ulcer
128 The preparation of extemporaneously compounded ophthalmic products
must adhere to established federal and state agency guidelines, and must address
quality control concerns (e.g., pH, tonicity, sterility, particulate matter). The
formulation of sterile products should not be undertaken without due consideration of
well-established practice standards. In most situations, these products are prepared
Comparison of Preparations and Clinical Use
QUESTION 1: S.S. has undergone cataract extraction from his left eye. Prednisolone acetate 1%
administered 4 times daily has been prescribed. Is prednisolone acetate an appropriate choice?
The topical ophthalmic corticosteroid preparations are described in Table 54-4.
The salt form affects the ability of the preparation to penetrate the cornea. For
example, biphasic salts penetrate the intact cornea better than water-soluble salts.
The ability of a formulation to penetrate the cornea, however, does not indicate
increased therapeutic effectiveness. Prednisolone acetate 1% and fluorometholone
acetate 0.1% have the best anti-inflammatory effects.
prescribed ophthalmic corticosteroid is prednisolone acetate because of its
availability in generic form and generally lower cost.
Low Potency Intermediate Potency High Potency
Clobetasone 0.1%a Clobetasone 0.5%a
Dexamethasone alcohol 0.1% (Maxidex) Fluorometholone acetate 0.1%
Medrysone 1% (HMS) Fluorometholone 0.1% (FML)
Fluorometholone 0.25% (FML Forte)
Prednisolone acetate 0.12% (Pred Mild)
Prednisolone sodium phosphate 0.125%
Prednisolone sodium phosphate 1%
aNot commercially available in the United States.
Topical ophthalmic corticosteroids are used for a variety of conditions associated
with inflammation of the conjunctiva, cornea, and within the anterior segment of the
eye. They are generally contraindicated in individuals with ocular varicella,
vaccinia, herpes simplex, and mycobacterial infections.
INCREASED INTRAOCULAR PRESSURE
IOP was 16 mm Hg in the right eye and 26 mm Hg in the left eye. Assess these observations.
S.S.’s elevated IOP could be related to topical steroid therapy. In one study, the
ophthalmic administration of corticosteroid preparations (Table 54-5) increased IOP
in three genetically distinct subgroups.
104,105,132 Fluorometholone acetate increased
IOP by more than 10 mm Hg in known steroid responders in 29.5 days (median),
whereas dexamethasone did the same in 22.7 days (median).
follow-up, 13% of high-corticosteroid responders developed POAG and 63.8%
developed ocular hypertension. No low responders developed POAG, and only
2.4% developed ocular hypertension.
133 Although corticosteroid-induced increases in
IOP are associated most frequently with topical ophthalmic preparations, systemic
corticosteroids may cause a similar response, although the magnitude is somewhat
134 The risk for corticosteroid-induced ocular hypertension is greater in patients
with high myopia, diabetes mellitus, or connective tissue disease (particularly
Topical corticosteroids exert their effects by decreasing aqueous humor outflow,
whereas systemic corticosteroids may increase aqueous humor production.
effects on IOP apparently are unrelated to the ability of the corticosteroid to penetrate
the cornea. Dexamethasone has been associated with the greatest IOP increase.
Fluorometholone, medrysone, rimexolone, and loteprednol have been associated with
lower, although sometimes significant, increases in IOP.
often is reversible when the offending agent is discontinued. In subjects with
prolonged IOP elevation, glaucomatous field defects are more likely to develop in
corticosteroid-responsive patients.
examination revealed early cataract formation. Why could this be related to the prednisone?
Systemic and topical ophthalmic corticosteroids have been associated with the
development of cataracts. About 23% of patients treated with 10 to 16 mg/day of
prednisone orally (or its equivalent dose) for 1 year or more developed posterior
140,141 The estimated occurrence of PSC in patients
treated with more than 16 mg/day of prednisone for more than a year increased to
more than 70% during the same period. Patients receiving less than 10 mg/day
prednisone or its equivalent are unlikely to develop PSC, although some contend that
the concept of a “safe” dosage should be abandoned because of variable patient
sensitivity to this side effect.
142 As illustrated by G.A., the cataracts cause few
subjective complaints and little measurable decrease in visual acuity. Although
systemic corticosteroids primarily are implicated, use of topical corticosteroids also
has been associated with PSC formation.
143 Patients treated with alternate-day dosing
of oral corticosteroids may be at lower risk for PSC formation.
receiving long-term corticosteroids should receive routine ophthalmic follow-up.
Intraocular Pressure Response to Topical Steroids in Random Populations
SYSTEMIC SIDE EFFECTS FROM OPHTHALMIC
topical ophthalmic medications have been associated with systemic effects?
In 33 cases, possible adverse effects have been associated with topical
In a double-blind study, no statistically significant differences
were observed in blood pressure or pulse rate between experimental and control
groups when phenylephrine 10% or tropicamide (Mydriacyl) 1% was administered
146 Nevertheless, care should be taken when phenylephrine 10% is
administered in patients with hypertension or cardiac abnormalities in whom
systemic absorption could be hazardous. No similar reports have been associated
with topical use of phenylephrine 2.5%.
In addition to the systemic effects from topical administration of cholinergic
agents, epinephrine, and timolol that were previously described, topical atropine,
cyclopentolate (Cyclogyl), and scopolamine have been associated with
147–149 Fatalities have been associated with topical atropine,
occurred with topical homatropine, and one case of unconsciousness with
Topical chloramphenicol-polymyxin-B sulfate ophthalmic ointment has been
associated with bone marrow aplasia after intermittent use for 4 months.
cushingoid reaction has been reported in a 30-month-old baby girl treated with
dexamethasone alcohol (Maxidex) 4 times a day in both eyes for 14 months.
The administration of ophthalmic prostaglandins and PGAs are associated with
systemic side effects (Table 54-1).
OCULAR NONSTEROIDAL ANTIINFLAMMATORY DRUGS
includes only diclofenac 0.1%. Is this a suitable alternative to flurbiprofen?
Commercially available ophthalmic nonsteroidal anti-inflammatory drugs (e.g.,
bromfenac, diclofenac, flurbiprofen, ketorolac and nepafenac) share a similar
mechanism of action involving inhibition of prostaglandin synthesis and reduction of
prostaglandin-mediated ocular effects.
154 Minor clinical differences, which probably
are insignificant, exist and approved indications differ (Table 54-6).
agents are generally well tolerated, but they can cause transient burning and stinging
on instillation. Diclofenac is not approved for prevention of intraoperative miosis,
but various dosage regimens have been reported as effective for this use.
OCULAR HERPES SIMPLEX VIRUS INFECTIONS
hallmark of ocular herpes simplex (type 1) infection. What is the therapy of choice for P.B.?
Ocular herpes is common and can be caused by herpes simplex virus or, less
commonly, by the varicella-zoster virus (herpes zoster ophthalmicus). Herpes
simplex of the eye typically affects the eyelids, conjunctiva, and cornea, and patients
often present with symptoms of pain, tearing, eye redness, sensitivity to light, and
irritation or a foreign body sensation. When herpes affects the epithelium of the
cornea (herpes keratitis), it generally heals without scarring. Occasionally, deeper
layers of the cornea are affected (stromal keratitis), and scarring can lead to
blindness. Trifluridine is the drug of choice for P.B.
In vitro, the mechanism of action of trifluridine is similar to that of idoxuridine
(IDU). Trifluridine also inhibits thymidylate synthase, an enzyme required for DNA
For the treatment of ocular herpes, one drop of trifluridine 1% ophthalmic solution
should be instilled into the affected eye every 2 hours while awake with a maximal
daily dose of nine drops. After re-epithelialization, application of trifluridine should
be continued for an additional 7 days at a reduced dosage of one drop every 4 hours
while awake with a minimum of five drops daily. Continuous administration for
periods exceeding 21 days is not recommended because of potential ocular toxicity.
Approximately 96% of treated herpetic corneal ulcers heal within 2 weeks.
Therapeutic levels of trifluridine can be found in the aqueous humor after topical
administration of a 1% solution, enhancing its possible effectiveness in the treatment
of stromal keratitis and uveitis. Trifluridine also is effective in treating herpes
simplex virus infections resistant to IDU or vidarabine.
Despite the apparent superiority of trifluridine compared with its antiviral
predecessors (IDU, vidarabine), it is not without disadvantages. Trifluridine is
activated by uninfected corneal cells and is incorporated into cellular as well as
viral DNA. Punctate lesions in the corneal epithelium are clinical manifestations of
164 However, these effects seem to occur less often with
trifluridine than with IDU and vidarabine.
Acyclovir in in vitro plaque inhibition assays has 5 to 10 times the activity of IDU
and trifluridine and more than 100 times the activity of vidarabine against strains of
type 1 and type 2 herpes simplex virus.
165 Acyclovir’s apparent superiority lies in its
lack of toxicity to normal host cells. In rabbits (rabbit eyes are similar to human
eyes), acyclovir 3% ointment healed established herpes simplex epithelial
ulcerations at a faster rate and eliminated the virus more effectively than 0.5% IDU
In humans, ulcerative corneal epithelial lesions
appear to respond similarly to acyclovir and IDU.
topical application of acyclovir or trifluridine resulted in a greater proportion of
subjects healing within 1 week and neither was superior for the treatment of dendritic
167 The dose usually is a 1-cm ribbon of ointment instilled 5 times
a day at 4-hour intervals for 14 days or for at least 3 days after healing is completed,
whichever is shorter. Detailed dosing instructions are available in product literature
of specific manufacturers, and brief reviews of acyclovir and acyclovir resistance
are presented in 77, Opportunistic Infections in HIV-Infected Patients, and Chapter
Ocular Nonsteroidal Anti-Inflammatory Drugs
Inhibition of intraoperative miosis Diclofenac 0.1% (Voltaren,
Three reported regimens; 1 drop
every 15–30 minutes for four doses; 1
drop TID for 2 preoperative days; 1
drop at 2 hours, 1 hour, and 15
One drop every 30 minutes for 2
Ketorolac 0.5% (Acular, U) One drop every 15 minutes beginning
Anti-inflammatory after cataract
Bromfenac 0.09% (Xibrom, A) One drop BID beginning 24 hours
after surgery and continuing through
the 2 weeks of the postoperative
One drop BID to QID, including 24
hours preoperative administration.
One drop TID beginning 1 day before
cataract surgery, continued on the day
of surgery and through the first 2
weeks of the postoperative period
(Nevanac prescribing information.
Alcon Laboratories, November 2006)
158 One drop TID, including 24 hours
Prevention/treatment of cystoid
159 Two drops 5 times preoperatively
followed by one drop 3–5 times daily
158,160 One drop TID or QID, including 24
hours preoperative administration
Ocular inflammatory conditions (iritis,
Diclofenac 0.1% (U) One drop QID
Seasonal allergic/vernal conjunctivitis Bromfenac 0.1% (U) One drop BID
Diclofenac 0.1% (U) One drop every 2 hours for 48 hours;
A, approved use; BID, twice daily; QID, 4 times a day; TID, 3 times a day; U, unapproved use.
Ganciclovir 0.05% and 0.15% gel have been shown to be equivalent to 3% acyclovir
ointment in the treatment of superficial herpes simplex keratitis.
ointment administered BID was equivalent to trifluridine administered 5 times daily
169 Cidofovir was more efficacious than 3% penciclovir ointment
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