represents the single most common form of ocular allergic disease.1 Acute
allergic conjunctivitis describes the abrupt and immediate response
seen in sensitized individuals after exposure to a particular allergen
or sensitizing agent. Two forms are recognized: seasonal allergic
conjunctivitis (SAC), which coincides with pollen blooms such as
ragweed, and perennial allergic conjunctivitis (PAC), in which exposure
may occur at any time throughout the year (e.g., allergies to cat
dander or dust mites). In the majority of cases, allergic conjunctivitis
is a bilateral phenomenon, but may be asymmetric.
response classically involves several signs and symptoms, all of
which may vary in intensity. Ocular itching remains the hallmark
symptom; tearing is also an exceedingly common complaint, particularly
after rubbing the eyes in response to itching. More severe reactions
may prompt symptoms of ocular burning, foreign-body sensation or
photophobia, though these are relatively rare. Clinical evaluation
reveals variable conjunctival hyperemia and chemosis. Ocular discharge
is watery, though mucus may accumulate in the fornices or collect
on the lash margin in the form of "crusts," especially during sleep.
Eversion of the eyelids may reveal a fine papillary response, particularly
along the upper tarsal plate. Externally, the eyelids may be red,
swollen and edematous, with a pseudoptosis in pronounced cases. A
palpable preauricular lymph node is noticeably absent. If questioned,
the patient will often reveal a personal or family history of allergies.
Concurrent symptoms of allergic rhinitis, post-nasal drip, or sinus
congestion may be present, especially in SAC.
response is classically considered to be an over-reaction of the
body's immune system to foreign substances (allergens). The response
can be innate or acquired. The key component to the ocular allergic
response is the mast cell. When mast cells interact with specific
allergens, the cell membrane opens, much like a lock being opened
by a key. This response is known as degranulation, and the process
causes a discharge of chemical mediators into the surrounding tissues.
The primary chemical mediator released during degranulation is histamine,
which is responsible for increased vascular permeability, vasodilation,
bronchial contraction and increased secretion of mucus. Heparin,
chymase, tryptase and other substances are also released from mast
cells. In severe or prolonged allergic reactions, a "late- phase" response
may occur in which cell membranes begin to break down into arachidonic
acid, which is further degraded to form prostaglandins, leukotrienes
and thromboxane (powerful mediators of inflammation that initiate
stimulation of pain receptors and migration of white blood cells).
This late phase is far more common in disorders such as atopic and
vernal keratoconjunctivitis, however. In acute allergic conjunctivitis,
less than 2% of cases show this type of severe inflammatory reaction.2
of ocular allergic reactions is primarily aimed at reducing symptomology
and quelling any significant inflammation. The most effective treatment
for allergic conjunctivitis is elimination or avoidance of the potentially
offending allergen, although this may not always be possible or practical.
Artificial tear solutions serve to soothe, lubricate and flush or
dilute the antigens from the ocular surface; these may be used on
an as-needed basis. Cold compresses and topical decongestants help
to produce vasoconstriction, reducing hyperemia, chemosis and other
symptoms by retarding the release of the chemical mediators into
the tissues from the blood stream. Decongestant solutions (containing
one of the following: naphazoline, antazoline, tetrahydrozaline or
phenylephrine) are available as over-the-counter preparations, either
alone or in combination with a mild topical antihistamine (e.g. pheniramine
maleate or antazoline phosphate). These agents are the treatment
used by the vast majority of patients with ocular allergies who self-medicate.
Unfortunately, these OTC preparations have been associated with significant
tachyphylaxis as well as chronic follicular conjunctivitis and eczematoid
blepharoconjunctivitis.3,4 An OTC medication that may
give palliative relief without the adverse effects of the decongestant
solutions is the homeopathic allergy eye drop Similisan #2.
A variety of
prescription ophthalmic medications are available for the management
of allergic conjunctivitis. Overall, five distinct classes or categories
of topical drugs are recognized; these include: (1) antihistamines,
e.g. Livostin (0.05% levocabastine hydrochloride, Novartis) and Emadine
(0.05% emedastine dif umarate,
Alcon); (2) mast cell stabilizers, e.g. Opticrom (4% cromolyn sodium,
Allergan), Alomide (0.1% lodoxamide tromethamine, Alcon), Alocril
(2% nedocromil sodium, Allergan), and Alamast (0.1% pemirolast postassium,
Santen); (3) antihistamine/mast cell stabilizer combinations, e.g.
Patanol (olopatadine hydrochloride, Alcon), Zaditor (ketotifen fumarate,
Novartis), and Optivar (0.05% azelastine
hydrochloride, Bausch & Lomb); (4) corticosteroids, e.g. Alrex (0.2% loteprednol
etabonate, Bausch & Lomb), Vexol (1% rimexolone, Alcon), and Pred Forte
(1% prednisolone ace-tate, Allergan); and (5) non-steroidal anti-inflammatory
agents (NSAIDs), e.g. Acular (0.5% keto-rolac tromethamine, Allergan). In general,
all of these medications are beneficial to some degree. Topical antihistamines
provide prompt symptomatic relief, but their effects are short-lived (i.e.,
~ 6 hours). Mast cell stabilizers prevent degranulation and hence eliminate
the allergic response, but they may take several days to a week in order to
achieve full efficacy. Antihistamine/mast cell stabilizer combinations provide
the benefits of both of these categories and are by far the most common choice
among eye care practitioners; these drugs also have the unique advantage of
bid dosing, as compared to most other medications, which require qid administration.
allergic conjunctivitis with chemosis.
allergic conjunctivitis with watch glass crystal conjunctiva.
may serve to quell inflammation and offer relief to those patients
with more severe, late-phase responses, although this is relatively
rare with acute allergic conjunctivitis.2 Also, the risk
of cataractogenesis and ocular hypertension with prolonged use of
topical corticosteroids is well known. Topical NSAIDs are likely
the least effective options for ocular allergy. While they may provide
mild symptomatic relief, they do not directly address mast cell degranulation
or the histamine response, and inhibit only a portion of the inflammatory
cascade. Oral antihistamines are rarely required for the treatment
of acute allergic conjunctivitis, unless there is associated rhinitis,
sinusitis, urticaria, or other manifestations of systemic allergy.
Some of the older, over-the-counter antihistamines such as Benedryl
(diphenhydramine hydrochloride 25mg, Parke-Davis) and Chlor-Trimeton
(chlorpheniramine maleate 8mg, Schering-Plough), are effective but
can induce drowsiness and functional impairment.5,6 In
late 2002, loratadine 10mg, formerly a prescription medication, was
approved by the FDA as an over-the-counter product under various
trade names, including Claritin, Alavert, Tavist ND, and Dimetapp
ND. This drug is considered to be a non-sedating antihistamine, similar
in efficacy to other prescription medications such as Clarinex (desloratadine
5mg, Schering-Plough), Allegra (fexofenadine 60mg and 180mg, Aventis),
and Zyrtec (cetirizine 5 and 10mg, Pfizer). The sedative effect of
these drugs is greatly diminished as compared to drugs such as diphenhydramine,
though it is not entirely eliminated. Other side effects also exist
with systemic antihistamines that are not of concern with topical
agents. Most importantly, orals may predispose patients to dryness
of the mucosal membranes of the mouth, nose and eyes.7
Expect to see
at least two new allergy medications sometime after 2004: Elestat
(0.05% epinastine hydrochloride) is a new antihistamine/mast cell
stabilizer combination from Inspire, which received FDA approval
in October 2003. In addition, Alcon has developed a 0.2% formulation
of olopatadine hydrochloride (Patanol) for once-daily use.
- When evaluating
patients with presumed allergic conjunctivitis, pay attention to
the inferior fornix and medial canthus. In many cases, the caruncle
and plica semiluminaris may demonstrate marked hyperemia or inflammation.
This is presumably because of the accumulation of histamine-laden
tears in the area of the lacrimal puncta.
- In differentiating
allergic conjunctivitis from other forms of ocular surface disease,
a helpful question may be "What happens when you rub your eyes?" Most "itchy" surface
disorders such as dry eye and blepharitis generally improve with
digital manipulation, because it stimulates the flow of additional
tears. However, allergy is a vascular mediated event; rubbing the
eyes creates vasodilation, which induces further release of histamines
and other toxins into the ocular tissues. Hence, patients with true
allergies almost always say their symptoms worsen when they rub their
- Given the
vast array of excellent topical prescription medications now
available for allergic conjunctivitis, practitioners have little
ever recommend over-the-counter decongestant products. There
is evidence that these OTC products are quite inferior and potentially
- Seasonal allergic
conjunctivitis usually occurs around the same time each year,
and may last for only a month or two. Therefore, patients who present
for examination during other times of the year may go undiagnosed.
It is important to ask not only whether the patient is experiencing
symptoms at the time of the exam, but also if they ever suffer
red, itchy, watery eyes. The safety and efficacy of today's medications
allow for proactive prescribing, even months before symptoms
OF NEW OCULAR ALLERGY PRODUCTS
ESTIMATED that millions of Americans suffer from ocular allergies.
In 2003, there were no less than 12 FDA-approved
prescription topical medications for the treatment of allergic conjunctivitis:
Acular, Alamast, Alocril, Alomide, Alrex, Crolom, Emadine, Livostin, Opticrom,
Optivar, Patanol and Zaditor. In 2004, however, Elestat (epinastine HCl 0.05%
ophthalmic solution, Inspire Pharma-ceuticals) became available as an ocular
allergy medication, and we can expect another new choice: a new once-daily
formulation of Patanol (0.2% olopatadine HCl ophthalmic solution, Alcon).
is a topically active, direct H1-receptor antagonist
and an inhibitor of the release of histamine from the mast
cell. It is selective for the histamine H1-receptor
but also has affinity for the H2 receptors. Essentially,
it is the fourth drug in the same family as Patanol, joining
the ranks of Zaditor and Optivar. Clinical studies have shown
it to be safe and effective in patients three years of age
and older, and it was found not to be significantly superior
to levocabastine (Livostin) for controlling symptoms of ocular
itching when administered twice daily.1,2 Other
studies demonstrated a rapid onset of action within three to
five minutes after conjunctival antigen challenge, and the
duration of effect was shown to be approximately eight to 12
0.2% formulation of olopatadine HCl promises to be a truly
unique addition to the ocular allergy arena. At double the
concentration of the original Patanol, this new agent offers
true once-daily dosing for sufferers of allergic conjunctivitis.
Studies show that 0.2% olopatadine possesses a rapid onset-of-action,
a prolonged duration of action, and is safe and well tolerated.4,5 Studies
also demonstrate that this formulation effectively controls
the signs and symptoms associated with allergic conjunctivitis
for at least 16 to 24 hours post-instillation.5
will likely see even more products introduced to combat ocular
allergies. Cyclosporine A (Restasis, Allergan), which was approved
for the treatment of keratoconjunctivitis sicca in 2003, may
someday be a treatment option for allergic conjunctivitis.
A recent study showed that management of allergic conjunctivitis
with topical cyclosporine had a satisfactory evolution in 83%
of patients, with 50% experiencing symptomatic relief with
the first week of treatment.6
of these new considerations, the pharmaceutical industries
will no doubt be promoting their products heavily in 2004.
With more direct-to-consumer marketing, patients may inquire
about a new treatment option. It is our obligation to be familiar
with these agents and to be proactive in choosing the best
GL, Paradis AJ, Welch DL, et al. Safety evaluation of ophthalmic
epinastine HCl in a healthy pediatric population. Poster
presented at the14th Congress of the European Society of Ophthalmology
(SOE); Madrid, Spain. June, 2003.
MB, Ghosh P, Bradford R, et al. Safety and efficacy of
ophthalmic epinastine in patients with allergic conjunctivitis.
presented at the 60th Anniversary Meeting of the American
Academy of Allergy, Asthma, & Immunology; Denver, CO. March,
HJ, Abelson MB, Gomes P, et al. Efficacy and safety of
ophthalmic epinastine evaluated by conjunctival allergen challenge.
presented at the14th Congress of the European Society of
Ophthalmology (SOE); Madrid, Spain. June, 2003.
MB, Gomes P, Welch DL. Olopatadine reduces ocular signs
and symptoms associated with allergic conjunctivitis 16 hours
instillation. Poster presented at the annual meeting of
the Association for Research in Vision and Ophthalmology (ARVO);
Fort Lauderdale, May 2003.
JV, Spindel GP, Gomes PJ, et al. Olopatadine is effective
for the prevention and treatment of the signs and symptoms of
conjunctivitis. Poster presented at the annual meeting
of the Association for Research in Vision and Ophthalmology (ARVO);
Fort Lauderdale, May 2003.
P, Baca O, Velasco R, et al. Topic cyclosporine "A" in the
management of allergic conjunctivitis. Poster presented at
the annual meeting of the Association for Research in Vision
and Ophthalmology (ARVO); Fort Lauderdale, May 2003.
Abelson MB, George MA, Garofalo C. Differential diagnosis of ocular
allergic disorders. Ann Allergy 1993; 70(2):95-107.
- Hingorani M, Calder V, Jolly G, et al. Eosinophil surface
antigen expression and cytokine production vary in different
ocular allergic diseases. J Allergy Clin Immunol 1998; 102(5):821-30.
MB, Butrus SI, Weston JH, Rosner B. Tolerance and absence of
rebound vasodilation following topical ocular decongestant
usage. Ophthalmology 1984; 91(11):1364-7.
- Soparkar CN, Wilhelmus
KR, Koch DD, et al. Acute and chronic conjunctivitis due to over-the-counter
Arch Ophthalmol 1997; 115(1):34-8.
- Gengo F, Gabos C, Miller
JK. The pharmacodynamics of diphenhydramine-induced drowsiness
and changes in mental performance. Clin Pharmacol Ther
- Bower EA, Moore JL, Moss M, et al.
The effects of single-dose fexofenadine, diphenhydramine, and
placebo on cognitive performance
in flight personnel. Aviat Space Environ Med 2003; 74(2):145-52.
- Welch D, Ousler GW 3rd, Nally LA, et al. Ocular drying associated
with oral antihistamines (loratadine) in the normal population
- an evaluation of exaggerated dose effect. Adv Exp
Med Biol 2002; 506(Pt B):1051-5.
reports in this section