No, not all patients with allergic con-
junctivitis need prescription eyedrops.
For mild symptoms, basic nonpharmaco-
logic eye care often suf ces. Advise the patient
to avoid rubbing the eyes, to use arti cial tears
as needed, to apply cold compresses, to limit
or temporarily discontinue contact lens wear,
and to avoid exposure to known allergens.
Topical therapy with an over-the-counter
eyedrop that combines an antihistamine and a
mast cell stabilizer is another rst-line measure.
Prescription eyedrops are usually reserved
for patients who have persistent bothersome
symptoms despite use of over-the-counter eye-
drops. Also, some patients have dif culty with
the regimens for over-the-counter eyedrops,
since most must be applied two to four times
per day. In addition, patients with concomi-
tant allergic rhinitis may bene t from an in-
tranasal corticosteroid.
■ ALLERGIC CONJUNCTIVITIS:
A BRIEF OVERVIEW
Allergic conjunctivitis, caused by exposure of
the eye to airborne allergens, affects up to 40%
of the US population, predominantly young
adults.
1
Bilateral pruritus is the chief symp-
tom. The absence of pruritus should prompt
consideration of a more serious eye condition.
Other common symptoms of allergic con-
junctivitis include redness, tearing (a clear,
watery discharge), eyelid edema, burning, and
mild photophobia. Some patients may have
infraorbital edema and darkening around the
eye, dubbed an “allergic shiner.”
1
Allergic conjunctivitis can be acute, with
sudden onset of symptoms upon exposure to
an isolated allergen. It can be seasonal, from
exposure to pollen and with a more gradual
onset. It can also be perennial, from year-
round exposure to indoor allergens such as
animal dander, dust mites, and mold.
Allergic conjunctivitis often occurs togeth-
er with allergic rhinitis, which is also caused
by exposure to aeroallergens and is character-
ized by nasal congestion, pruritus, rhinorrhea
(anterior and posterior), and sneezing.
2
Pollen is more commonly associated with
rhinoconjunctivitis, whereas dust mite allergy
is more likely to cause rhinitis alone.
An immunoglobulin E-mediated reaction
Allergic conjunctivitis is a type I immunoglob-
ulin E-mediated immediate hypersensitivity
reaction. In the early phase, ie, within minutes
of allergen exposure, previously sensitized mast
cells are exposed to an allergen, causing de-
granulation and release of in ammatory media-
tors, primarily histamine. The late phase, ie, 6
to 10 hours after the initial exposure, involves
an in ux of in ammatory cells such as eosino-
phils, basophils, and neutrophils.
3
Differential diagnosis
The differential diagnosis of allergic con-
junctivitis includes infectious conjunctivitis,
chronic dry eye, preservative toxicity, giant
papillary conjunctivitis, atopic keratocon-
junctivitis, and vernal keratoconjunctivitis.
3
Giant papillary conjunctivitis is an in am-
matory reaction to a foreign substance, such
as a contact lens. Atopic keratoconjuncti-
vitis and vernal keratoconjunctivitis can be
vision-threatening and require referral to an
ophthalmologist. Atopic keratoconjuncti-
vitis is associated with eczematous lesions
of the lids and skin, and vernal keratocon-
junctivitis involves chronic in ammation of
the palpebral conjunctivae. Warning signs
include photophobia, pain, abnormal nd-
doi:10.3949/ccjm.82a.14162
BRIEF ANSWERS
TO SPECIFIC
CLINICAL
QUESTIONS
For most
patients,
basic eye care
measures
are suffi cient
Q: Does allergic conjunctivitis always require
prescription eyedrops?
A:
810
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 82 • NUMBER 12 DECEMBER 2015
ALEXEI GONZALEZ-ESTRADA, MD
Assistant Professor, Department of Internal Medicine,
Quillen College of Medicine, East Tennessee State
University, Johnson City
1-MINUTE CONSULT
LISANNE P. NEWTON, MD
Department of Allergy and Immunology,
Pediatric Institute, Cleveland Clinic
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CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 82 • NUMBER 12 DECEMBER 2015
811
GONZALEZ-ESTRADA AND NEWTON
ings on pupillary examination, blurred vi-
sion (unrelated to excessively watery eyes),
unilateral eye complaints, and ciliary ush.
2
Bacterial conjunctivitis is highly conta-
gious and usually presents with hyperemia,
“stuck eye” upon awakening, and thick, puru-
lent discharge. It is usually unilateral. Symp-
toms include burning, foreign-body sensation,
and discomfort rather than pruritus. Patients
with allergic conjunctivitis may have con-
comitant bacterial conjunctivitis and so re-
quire a topical antibiotic as well as treatment
for allergic conjunctivitis.
Viral conjunctivitis usually affects one eye,
is self-limited, and typically presents with oth-
er symptoms of a viral syndrome.
■ MANAGEMENT OPTIONS
Management of allergic conjunctivitis consists
of basic eye care, avoidance of allergy triggers,
and over
-the-counter and prescription topical
and systemic therapies, as well as allergen im-
munotherapy.
3
Avoidance
Triggers for the allergic reaction, such as pol-
len, can be identi ed with aeroallergen skin
testing by an allergist. But simple avoidance
measures are helpful, such as closing windows,
using air conditioning, limiting exposure to
the outdoors when pollen counts are high,
wearing sunglasses, showering before bedtime,
avoiding exposure to animal dander, and us-
ing zippered casings for bedding to minimize
exposure to dust mites.
3
Patients who wear contact lenses should
reduce or discontinue their use, as allergens
adhere to contact lens surfaces.
Topical therapies
If avoidance is not feasible or if symptoms
persist despite avoidance measures, patients
should be started on eyedrops.
Eyedrops for allergic conjunctivitis are
classi ed by mechanism of action: topical
anti histamines, mast-cell stabilizers, and com-
bination preparations of antihistamine and
mast-cell stabilizer (Table 1). Algorithms for
Tailor
treatment
to symptoms,
allergen profi le,
and patient
preferences
TABLE 1
Eyedrops for allergic conjunctivitis
Dose
Over the
counter? Estimated cost
a
Topical antihistamine
Emedastine difumarate (Emadine) 5 mL 1 drop every 6 hours No $124
Mast-cell stabilizers
Cromolyn sodium (Crolom, Opticrom) 10 mL 1 drop every 6 hours Yes $38–$51
Lodoxamide tromethamine (Alomide) 10 mL 1 drop every 6 hours No $141
Nedocromil sodium (Alocril) 5 mL 1–2 drops every 12 hours No $152
Pemirolast (Alamast) 10 mL 1–2 drops every 6 hours No $119
Combination topical antihistamine
and mast-cell stabilizer eyedrops
Alcaftadine (Lastacaft) 3 mL 1 drop daily No $149
Azelastine HCl 0.05% (Optivar) 6 mL 1 drop every 12 hours No $43
Bepostastine besilate (Bepreve) 5 mL 1 drop every 12 hours No $173
Epinastine HCl (Elestat) 5 mL 1 drop every 12 hours No $61
Ketotifen 0.025% (Alaway 10 mL, Zaditor 5 mL) 1 drop every 12 hours Yes $15–$70
Olopatadine HCl 0.1% (Patanol) 5 mL 1 drop every 6–8 hours No $212
Olopatadine HCl 0.2% (Pataday) 2.5 mL 1 drop daily No $156
a
Estimated costs, August 2015, Cleveland, OH.
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CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 82 • NUMBER 12 DECEMBER 2015
ALLERGIC CONJUNCTIVITIS
managing allergic conjunctivitis exist
2
but are
based on expert consensus, since there are no
randomized clinical trials with head-to-head
comparisons of topical agents for allergic con-
junctivitis.
In our practice, we use a three-step ap-
proach to treat allergic conjunctivitis (Table
2). Combination antihistamine and mast-cell
stabilizer eyedrops are the rst line, used as
needed, daily, seasonally, or year-round, based
on the patient’s symptoms and allergen pro-
le. Antihistamine or combination eyedrops
are preferred as they have a faster onset of ac-
tion than mast-cell stabilizers alone,
3
which
have an onset of action of 3 to 5 days. The
combination drops provide an effect on the
late-phase response and a longer duration of
action.
Currently, the only over-the-counter eye-
drops for allergic conjunctivitis are cromolyn
(a mast-cell stabilizer) and ketotifen 0.025%
(a combination antihistamine and mast-cell
stabilizer). Most drops for allergic conjuncti-
vitis are taken two to four times a day. Two
once-daily eyedrop formulations for allergic
conjunctivitis—available only by prescrip-
tion—are olopatadine 0.2% and alcaftadine.
However, these are very expensive (Table 1)
and so may not be an appropriate choice for
some patients. On the other hand, a study
from the United Kingdom
4
found that pa-
tients using olopatadine made fewer visits to
their general practitioner than patients using
cromolyn, resulting in lower overall cost of
healthcare. Results of studies of patient prefer-
ences and ef cacy of olopatadine 0.1% (twice-
daily preparation) vs ketotifen 0.025% are
mixed,
5–8
and no study has compared olopata-
dine 0.2% (once-daily preparation) with over-
the-counter ketotifen.
Adverse effects of eyedrops
Common adverse effects include stinging and
burning immediately after use; this effect may
be reduced by keeping the eyedrops in the re-
frigerator. Patients who wear contact lenses
should remove them before using eyedrops
for allergic conjunctivitis, and wait at least 10
minutes to replace them if the eye is no longer
red.
2
Antihistamine drops are contraindicated
in patients at risk for angle-closure glaucoma.
Whenever possible, patients with seasonal
allergic conjunctivitis should begin treatment
2 to 4 weeks before the relevant pollen season,
as guided by the patient’s experience in past
seasons or by the results of aeroallergen skin
testing. This modi es the “priming” effect, in
which the amount of allergen required to in-
duce an immediate allergic response decreases
with repeated exposure to the allergen.
■ OTHER TREATMENT OPTIONS
V
asoconstrictor or decongestant eyedrops are in-
dicated to relieve eye redness but have little or
no effect on pruritus, and prolonged use may lead
to rebound hyperemia. Thus, they are not gen-
erally recommended for long-term treatment of
allergic conjunctivitis.
3
Also, patients with glau-
coma should be advised against long-term use of
over-the-counter vasoconstrictor eyedrops.
TABLE 2
Three steps to treating allergic conjunctivitis
Step 1
Avoid allergens (guided by allergy testing, if available)
Avoid rubbing the eyes
Use artifi cial tears
Limit contact lens use
Apply cold compresses
Step 2
Continue Step 1 recommendations
Over-the-counter eyedrops
(combination antihistamine and mast-cell stabilizer)
Intranasal corticosteroid for concomitant allergic rhinitis
Step 3
Prescription eyedrops
(combination antihistamine and mast-cell stabilizer)
Intranasal corticosteroid for concomitant allergic rhinitis
Consider referral
a
Consider allergen immunotherapy
b
Consider a short course of an oral corticosteroid if symptoms
are severe, acute, or persistent
a
Consider referral to an allergist at any step to identify allergic triggers, including
relevant pollens for timing of medications before season onset; see text for differential
diagnosis and red fl ags that should prompt a referral to an ophthalmologist; topical
corticosteroid eye drops should only be prescribed with close follow-up with an
ophthalmologist.
b
For refractory cases or cases in which medications have undesirable side effects, are
limited by adherence, or are undesired; allergen immunotherapy is the only disease-
modifying treatment available; not indicated for acute relief of symptoms.
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GONZALEZ-ESTRADA AND NEWTON
Corticosteroid eyedrops are reserved for
refractory and severe cases. Their use requires
close follow-up with an ophthalmologist to
monitor for complications such as increased
intraocular pressure, infection, and cataracts.
2
Patients presenting with an acute severe
episode of allergic conjunctivitis that has not
responded to oral antihistamines or combi-
nation eyedrops may be treated with a short
course of an oral corticosteroid, if the bene t
outweighs the risk in that patient.
Oral antihistamines are generally less effec-
tive than topical ophthalmic agents in reliev-
ing ocular allergy symptoms and have a slower
onset of action.
2
They are useful in patients
who have an aversion to instilling eyedrops on
a regular basis or who wear contact lenses.
For patients who have associated allergic rhi-
nitis—ie, most patients with allergic conjuncti-
vitis—intranasal corticosteroids and intranasal
antihistamines are the most effective treatments
for rhinitis and are also effective for allergic
conjunctivitis. Monotherapy with an intranasal
medication may provide suf cient relief of con-
junctivitis symptoms or allow ocular medica-
tions to be used on a less frequent basis.
Allergen immunotherapy
Referral to an allergist for consideration of al-
lergen immunotherapy is an option when avoid-
ance measures are ineffective or unfeasible, when
rst-line treatments are ineffective, and when the
patient does not wish to use medications.
Allergen immunotherapy is the only disease-
modifying therapy available for allergic con-
junctivitis. Two forms are available: traditional
subcutaneous immunotherapy, and sublingual
tablet immunotherapy, recently approved by the
US Food and Drug Administration.
9
Subcuta-
neous immunotherapy targets speci c aeroaller-
gens for patients allergic to multiple allergens.
The new sublingual immunotherapy tablets tar-
get only grass pollen and ragweed pollen.
9
Most
patients in the United States are polysensi-
tized.
10
Both forms of immunotherapy can result
in sustained effectiveness following discontinu-
ation. Sub lingual therapy may be administered
year-round, before allergy season, or during al-
lergy season (depending on the type of allergy).
■ TAILORING TREATMENT
We recommend a case-by-case approach to the
management of patients with allergic conjunc-
tivitis, tailoring treatment to the patient’s symp-
toms, allergen pro le, and personal preferences.
For example, if adherence is a challenge
we recommend a once-daily combination
eyedrop (olopatadine 0.2%, or alcaftadine). If
cost is a barrier, we recommend the combina-
tion over-the-counter drop (ketotifen).
Medications may be used during allergy
season or year-round depending on the pa-
tient’s symptom and allergen pro le. Patients
whose symptoms are not relieved with these
measures should be referred to an allergist for
further evaluation and management, or to an
ophthalmologist to monitor for complications
of topical steroid use and other warning signs,
as discussed earlier, or to weigh in on the dif-
ferential diagnosis.
■
■ REFERENCES
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North Am 2008; 28:43–58.
2. Bielory L, Meltzer EO, Nichols KK, Melton R, Thomas RK, Bartlett JD. An
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ADDRESS: Lisanne P. Newton, MD, Department of Allergy and Clinical
Immunology, Respiratory Institute, A120, Cleveland Clinic, 9500 Euclid
Avenue, Cleveland, OH 44195; e-mail: [email protected]
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