ACUTE ALLERGIC CONJUNCTIVITIS

Signs and Symptoms

Mild allergic conjunctivitis.

Allergic conjunctivitis 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.

The allergic 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.

Pathophysiology

The allergic 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

Management

The management 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.

Moderate allergic conjunctivitis with chemosis.

Severe allergic conjunctivitis with watch glass crystal conjunctiva.
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.

Topical corticosteroids 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.

Clinical Pearls

  • 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 eyes.
  • Given the vast array of excellent topical prescription medications now available for allergic conjunctivitis, practitioners have little reason to ever recommend over-the-counter decongestant products. There is evidence that these OTC products are quite inferior and potentially harmful.4
  • 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 from red, itchy, watery eyes. The safety and efficacy of today's medications allow for proactive prescribing, even months before symptoms arise.

OVERVIEW OF NEW OCULAR ALLERGY PRODUCTS

IT IS 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).

Elestat 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 hours.3

The new 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

The future 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

With all 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 therapy.

  1. Torkidsen 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.
  2. Abelson MB, Ghosh P, Bradford R, et al. Safety and efficacy of ophthalmic epinastine in patients with allergic conjunctivitis. Poster presented at the 60th Anniversary Meeting of the American Academy of Allergy, Asthma, & Immunology; Denver, CO. March, 2003.
  3. Crampton HJ, Abelson MB, Gomes P, et al. Efficacy and safety of ophthalmic epinastine evaluated by conjunctival allergen challenge. Poster presented at the14th Congress of the European Society of Ophthalmology (SOE); Madrid, Spain. June, 2003.
  4. Abelson MB, Gomes P, Welch DL. Olopatadine reduces ocular signs and symptoms associated with allergic conjunctivitis 16 hours after instillation. Poster presented at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO); Fort Lauderdale, May 2003.
  5. Greiner JV, Spindel GP, Gomes PJ, et al. Olopatadine is effective for the prevention and treatment of the signs and symptoms of allergic conjunctivitis. Poster presented at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO); Fort Lauderdale, May 2003.
  6. Velasco 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.

 

  1. Abelson MB, George MA, Garofalo C. Differential diagnosis of ocular allergic disorders. Ann Allergy 1993; 70(2):95-107.
  2. 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.
  3. Abelson MB, Butrus SI, Weston JH, Rosner B. Tolerance and absence of rebound vasodilation following topical ocular decongestant usage. Ophthalmology 1984; 91(11):1364-7.
  4. Soparkar CN, Wilhelmus KR, Koch DD, et al. Acute and chronic conjunctivitis due to over-the-counter ophthalmic decongestants. Arch Ophthalmol 1997; 115(1):34-8.
  5. Gengo F, Gabos C, Miller JK. The pharmacodynamics of diphenhydramine-induced drowsiness and changes in mental performance. Clin Pharmacol Ther 1989; 45(1):15-21.
  6. 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.
  7. 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.

Other reports in this section

 

Eyelids & Eyelashes | Conjunctiva & Sclera | Cornea
Uvea | Vitreous & Retina | Neuro-Ophthalmic Disease | Oculosystemic Disease

Handbook Main Page