Evaluation of the onset and duration of effect of azelastine eye drops (0.05%) versus placebo in patients with allergic conjunctivitis using an allergen challenge model.

OBJECTIVE: The trial evaluated the effectiveness of the investigational antihistaminic and antiallergic compound Azelastine Eye Drops (AZE) in the treatment of allergic conjunctivitis using an allergen challenge model. DESIGN: Randomized, double-blind, placebo-controlled, paired-eye study. PARTICIPANTS: Adults with a history of allergic conjunctivitis (>/=2 years) who were asymptomatic throughout the trial, had a positive skin test (cat dander, grass, or ragweed pollen within the last year), and had a positive conjunctival reaction (score 2+ or more for itching and redness in both eyes on a 0-4 scale) during two separate conjunctival provocation tests (CPT) before randomization. METHODS: Eighty patients underwent a 2-week screening period (visits 1 and 2) that included a CPT during visit 1 to establish the allergen threshold dose and a second confirmatory CPT performed at visit 2. Eye symptom assessments for itching (evaluated by patient) and conjunctival redness (evaluated by physician) were performed 5 and 10 minutes after CPT using a 5-point scale (from 0 = none to 4+ = severe). Qualified patients were randomized to receive one drop of AZE (0.015 mg of azelastine hydrochloride) in one eye and one drop of placebo in the other eye 20 minutes before CPT at visit 3 (onset) and 8 or 10 hours before CPT at visit 4 (duration). MAIN OUTCOME MEASURES: Individual severity scores for itching (evaluated by patient) and conjunctival redness (evaluated by physician) for each eye at 3, 5, and 10 minutes after CPT at visits 3 and 4 using a 5-point scale (0 = none to 4+ = very severe). RESULTS: Each of the 80 randomized patients completed the trial. Mean itching and conjunctival redness scores at visit 3 (onset) were significantly lower (P: < 0.001) in the AZE-treated eyes than in the placebo-treated eyes. At visit 4 (duration), mean itching and conjunctival redness scores (P:

Twice-a-day versus four-times-a-day ofloxacin treatment of external ocular infection.

PURPOSE: The purpose of this study was to compare the efficacies of 0.3% ofloxacin eyedrops, when given twice-a-day (BID) versus four-times-a-day (QID), for the treatment of external ocular disease. METHOD: Fifty patients with blepharitis, conjuctivitis, or blepharoconjunctivitis were randomly assigned to treatment with 0.3% ofloxacin eyedrops, BID or QID, for 10 days. Signs, symptoms, and cultures were evaluated at the beginning and at the end of the study. RESULTS: The clinical outcome was virtually identical in the two groups. There was a significant decrease in clinical scores in the BID and QID groups by days 3 to 5 (2.6-3.0 points) and a further decrease by day 11 (4.3-5.0 points). There was no significant difference between the two groups at any time interval. Microbiologic studies showed a reduction in colony-forming units in 87% of the BID group and in 80% of the QID group. CONCLUSION: The treatment of external ocular disease with 0.3% ofloxacin eyedrops was equally effective when given BID or QID.

The current and future therapy of allergic conjunctivitis.

A wealth of antiallergic drugs is available for ocular allergy, and many new drugs will soon be approved. Pharmaceutical companies frequently seek approval of anti-inflammatory drugs for allergic indications, because it is relatively easy to perform clinical trials for ocular allergy. Extremely safe drugs for mild to moderate degrees of allergic conjunctivitis include antihistamines, mast cell stabilizers, and nonsteroidal anti-inflammatory agents. Topical corticosteroids, preferably those with reduced side effects, are available for more severe forms of ocular allergy. The choice of an antiallergic drug may be guided by the indication for which the drug was approved. The ultimate selection will be made based on the patient's symptoms, the drug's availability, and its cost.

A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis. The Loteprednol Etabonate Giant Papillary Conjunctivitis Study Group I.

PURPOSE: To evaluate the safety and effectiveness of loteprednol etabonate 0.5% ophthalmic suspension in reducing the ocular signs and symptoms accompanying contact lens-associated giant papillary conjunctivitis. METHODS: In a randomized, double-masked, placebo-controlled, parallel-group study conducted at 14 academic or private practice clinics, 223 adults with contact lens-associated giant papillary conjunctivitis received either loteprednol or the loteprednol vehicle (placebo), one drop, four times daily for 6 weeks. Papillae, itching, contact lens intolerance, other signs and symptoms of giant papillary conjunctivitis (O-to-3 or O-to-4 grade scales), and intraocular pressure were measured. RESULTS: The proportion of patients treated with loteprednol who at final visit demonstrated an improvement in papillae of at least one grade (78%, 85/109) was significantly greater than the proportion of those treated with placebo (51%, 56/110; P = .001). A treatment difference favoring loteprednol was seen with improvement in itching (95% vs 81%, 104/109 vs 89/110; P < .001) and lens intolerance (87% vs 77%, 95/109 vs 85/110; P = .053). Eight of 109 patients (7%, all taking loteprednol) had an intraocular pressure increase of 10 mm Hg or more on at least one visit during treatment. After discontinuation of loteprednol, intraocular pressure returned to normal levels. Both treatments were well tolerated, and no serious unexpected treatment-related medical events were reported. CONCLUSIONS: The rapid therapeutic response combined with the low incidence and transient nature of any intraocular pressure increase suggests that loteprednol is an appropriate treatment for giant papillary conjunctivitis.

Characterization of receptor subtypes involved in prostanoid-induced conjunctival pruritus and their role in mediating allergic conjunctival itching.

Topically administered ketorolac (Acular), a cyclooxygenase inhibitor, has recently been reported as clinically beneficial for treating allergic conjunctivitis. The ability of ketorolac to relieve the itching associated with allergic conjunctivitis is intriguing because cyclooxygenase inhibitors are not regarded as useful in treating allergic dermatoses and prostaglandins (PG) do not elicit an itch response in human skin. To gain further insight into the mechanisms involved in the antipruritic activity of ketorolac, we used a method of reproducibly assessing ocular surface itch responses in the guinea pig. The measurement of conjunctival pruritus involved a recently developed behavioral model whereby hind limb scratching episodes directed toward the afflicted area were quantified. Itch-scratch episodes have previously been delineated from foreign body and pain sensations, which do not evoke such a behavioral response. Ketorolac significantly inhibited the itching associated with experimental allergic conjunctivitis. The basis of this antipruritic activity may be ascribed to preventing the biosynthesis of itch-producing PGs because ketorolac inhibited arachidonic acid-induced pruritus. In contrast to skin studies, PGE2 and PGI2 were found to be potent pruritogens at the guinea pig ocular surface. PGD2 was a weak pruritogen, and PGF2 alpha and the thromboxane-mimetic U-46619 produced no meaningful response. Further studies involving selective agonists and antagonists suggested that EP1 receptors, IP receptors and PGD2-sensitive receptors may mediate prostanoid-induced conjunctival itching. No evidence for the involvement of other prostanoid receptor subtypes was obtained. Although the EP1 receptor antagonist AH 6809 and the DP receptor antagonist BW A868C inhibited PGE2- and PGD2-induced itching, respectively, neither antagonist alone significantly affected the itching associated with experimental allergic conjunctivitis. A combination of AH 6809 and BW A868C, however, did exhibit antipruritic activity. It appears that for effective relief of itching in allergic conjunctivitis, it is not sufficient to block the effects of a single pruritogenic PG. It is preferable to reduce the participation of all pruritogenic PGs by either using combined receptor antagonists or by using a cyclooxygenase inhibitor such as ketorolac to block their biosynthesis.

Efficacy and safety of rimexolone 1% ophthalmic suspension vs 1% prednisolone acetate in the treatment of uveitis.

PURPOSE: Two multicenter studies compared the efficacy and safety of rimexolone 1% ophthalmic suspension (Vexol 1%, Alcon) and 1% prednisolone acetate (Pred Forte, Allergan). METHODS: Patients with acute uveitis, recurrent iridocyclitis, or chronic uveitis treatable by topical corticosteroid were enrolled. Treatment regimen was one or two drops every hour during Week 1, every two hours during Week 2, four times a day during Week 3, and once a day for the last three days. Efficacy and safety were determined on Days 3, 4, 7 to 10, 14, 21, and 28. A poststudy evaluation was conducted 36 to 72 hours after treatment was stopped. RESULTS: When anterior chamber cell and flare were measured, rimexolone 1% was found to be as effective as 1% prednisolone. The largest difference observed between treatments was 0.5 score unit, not clinically significant. There were no statistically significant differences in cell scores in either study (P > .05). No statistically significant differences in flare scores were found except at Day 28 in Study One (P = .04). Also, prednisolone was found to be more likely than rimexolone to cause a clinically significant increase (10 mm Hg or more) in intraocular pressure (1.7 times more likely in Study One, eight times more likely in Study Two). CONCLUSION: Rimexolone 1% ophthalmic suspension is safe and effective for the treatment of uveitis.

Contact lens induced conjunctivitis: a model of human ocular inflammation.

PURPOSE: To demonstrate the usefulness of contact lens induced conjunctivitis as a model of human ocular inflammation and to evaluate the effect of antiallergic eyedrops on this model. METHODS: We recruited 40 subjects with contact lens induced conjunctivitis. Half were treated with ketorolac tromethamine (KT), and half with iodoxamide tromethamine (LT). Signs, symptoms, contact lens wearing time, and wearing time until discomfort developed were evaluated at baseline, day 7, and day 14. RESULTS: The group receiving LT showed improvement of symptoms 7 days after beginning the study (P = 0.016), and both the LT and KT groups showed improvement from baseline on day 14 (P = 0.001 and P = 0.004, respectively). Signs improved for both the KT group (P = 0.011) and the LT group (P = 0.043) on day 7 and day 14 (P = 0.033 and P = 0.007, respectively). Mean contact lens wearing time improved on day 14 for the group treated with KT (P = 0.001). CONCLUSIONS: Contact lens induced conjunctivitis appears to be a useful model of human ocular inflammation. Both antiallergics KT and LT improve contact lens tolerance in subjects with contact lens induced conjunctivitis. Two weeks of treatment may be required to demonstrate therapeutic benefits of antiallergic drops.

Controlled comparison of two fluorometholone formulations in the antigen challenge model of allergic conjunctivitis.

We compared the safety and efficacy of MethaSite, a gel-forming suspension (0.1% fluorometholone), to a commercially available 0.1% fluorometholone ointment, FML S.O.P., using an antigen challenge model. Subjects with known allergic histories were exposed to increasing concentrations of cat dander, ragweed, or grass at visits 1 and 2. Allergic responses of conjunctival injection, chemosis, and subjective itching were quantified on a scale from zero to 3; the sum of these ratings constituted the total allergic score. At visit 3, 105 subjects with total scores of > or = 5 received a drop of MethaSite in one eye and a 0.5 inch ribbon of FML ointment in the other eye. Three and 6 hours postdose, the eyes were challenged with the antigen concentration that provoked significant allergic response at visit 2. We determined safety by evaluating changes in visual acuity, intraocular pressure, and biomicroscopy that occurred between visits 1 and 3. Eyes treated with MethaSite and FML responded similarly to the antigen challenges. Both groups demonstrated suppression of allergic response 3 and 6 hours postdose through equivalent and significant reductions in total allergy scores and individual ratings of injection, chemosis, and itching. In this population, MethaSite was equivalent to FML ointment in safety and efficacy.

Management of ocular allergy.

OBJECTIVE: Ocular allergy is a frequent accompaniment of systemic allergy and in some situations ocular signs and symptoms are the most prominent features of allergic disease. This paper will describe an approach to ocular allergy intended to aid in the recognition, differentiation from other ocular conditions, and management of ocular allergic disease. DATA SOURCES: Ophthalmologists and allergists have contributed to the body of knowledge concerning ocular allergy during the last several decades. Recent investigations have provided better and more specific treatments for the safe and effective management of ocular allergy. STUDY SELECTION: The results of several review articles, investigation of certain aspects of ocular allergy, and clinical trials have contributed to the approach that ophthalmologists and allergists take in the diagnosis and management of ocular allergy. RESULTS: In most cases, it is not difficult to recognize ocular allergy because of its association with systemic allergy. On the other hand, numerous inflammatory ocular conditions can be confused with ocular allergy. It is important to recognize infectious ocular disease and severe ocular inflammatory disease, such as uveitis, to ensure appropriate treatment. CONCLUSIONS: Allergists and ophthalmologists should be able to recognize ocular allergy and distinguish it from other ocular inflammatory conditions. Most ocular allergy is mild and easily managed. Currently available medications allow for the safe and effective management of most cases of ocular allergy. Many situations can be managed with avoidance of allergens, supportive treatment such as cold compresses, or no treatment at all. It is rare that ocular allergy requires treatment with topical corticosteroids. When such severe circumstances occur, an ophthalmologist should monitor the intraocular pressure and the overall course of the ocular disease.

A review of the causes and treatment of bacterial and allergic conjunctivitis.

The most common causes of ocular inflammation are allergic or infectious in origin. A presumptive diagnosis can often be made through a comprehensive patient history and evaluation of presenting signs and symptoms, although the constellation and intensity of clinical findings may vary. Patients with allergic conjunctivitis often have itchy, red eyes, whereas patients with bacterial conjunctivitis often give a history of morning crusting and difficulty opening the eyelids. The treatment of patients with allergic conjunctivitis includes avoiding the offending allergen and applying topical antihistamines, mast cell stabilizers, or nonsteroidal anti-inflammatory agents. Streptococcus pneumoniae and Haemophilus influenzae are responsible for most cases of bacterial conjunctivitis in children. Staphylococcus species is the predominant organism in adults. Therefore, the treatment of patients with bacterial conjunctivitis consists of an antimicrobial agent with a broad spectrum of activity against most susceptible pathogens. Other causes of inflammation need to be considered in patients with atypical clinical signs and symptoms and in patients who do not respond to presumptive therapy.

The eye in immunologic disease.

The eye may be affected in a wide variety of systemic immunologic diseases. In many of these conditions, the eye examination may provide an important clue to the diagnosis and treatment of the systemic condition. It is important for the treating physician to work with the ophthalmologist to expedite the management of the patient with ocular manifestations of systemic disease.

Conjunctivitis of allergic origin: clinical presentation and differential diagnosis.

Conjunctivitis of allergic origin is associated with a diversity of clinical presentations. Common features include pronounced itching, a milky conjunctival appearance, a stringy or ropy discharge and papillary hypertrophy of the tarsal conjunctiva in severe cases, and a family history of allergy. The diagnosis should be based on thorough history-taking and careful ophthalmic examination, and, when necessary, confirmation by laboratory testing. An IgE-mediated immediate hypersensitivity mechanism is associated with most types of allergic conjunctivitis, although contact allergy is mediated by lymphocytes rather than antibody. Treatment is based on the diagnosis and severity of signs and symptoms. An array of medications is available to control symptoms, and the regimen of choice should be based on the response to milder forms of therapy and consideration of drug side effects.

Ocular manifestations of Sjögren's syndrome: keratoconjunctivitis sicca.

As part of the triad of Sjögren's syndrome (SS), keratoconjunctivitis sicca (KCS) can be found in virtually all SS patients. This term emphasizes not only the reduced tear production but also the pathologic changes in the epithelial cells of the ocular surface. The symptoms of dry eye may vary from one patient to another depending on the severity of dryness, the ability of the diminished tear film to moisten the ocular surface, and the patient's tolerance for ocular discomfort. Treatment of the dry eyes is remarkably effective, and most patients benefit from moisturizing eyedrops to replace their own deficient tears. Major issues include the pathogenesis of decreased tear flow and ocular surface disturbances, as well as the roles of wound healing agents and anti-inflammatory medications in KCS therapy.

Current concepts in ocular allergy.

Ocular allergy is commonly encountered by the allergist, general physician, and ophthalmologist. Diagnosis can usually be made by history, especially a history of itching and an allergic background. The diagnosis can be confirmed by skin testing, in vitro testing, and conjunctival scrapings to look for eosinophils. Once the diagnosis is made, a decision can be reached as to whether treatment is necessary. Often, supportive treatment, or removal of the allergen is preferred. When pharmacologic treatment is necessary, it is advisable to choose a benign form of therapy such as topical vasoconstrictor-antihistamine eyedrops or cromolyn sodium. Topical steroids are rarely necessary and should be used with great caution since they can induce serious sight threatening complications. If topical steroids are required, the patient should be monitored by an ophthalmologist.

Lens implant surgery in pars planitis.

Intraocular lens (IOL) implantation is usually contraindicated in eyes with active inflammation, but patients with "burned-out" pars planitis also may be considered as candidates. Fifteen of 16 eyes in eight patients underwent extracapsular cataract extraction (ECCE) with posterior chamber IOL (PC IOL) implantation combined with pars plana vitrectomy for both cataracts and chronic cystoid macular edema (CME); 60% achieved visual acuity of 20/40 or better. Even with "low-grade" inflammation in these patients, however, a persistent veil of debris accumulated over the posterior and anterior surface of the IOL. One patient (patient 2) required 27 YAG procedures for two eyes, and another required 11 YAG procedures and eventual removal of the IOL. Another patient required surgical "brushing-off" of the IOL and vitrectomy. Even in eyes with "burned-out" uveitis, a continual low-grade inflammation may complicate the use of IOL implantation.

Inflammatory mediator release on conjunctival provocation of allergic subjects with allergen.

To evaluate the role of inflammatory mediators in the pathogenesis of the ocular allergic response, 23 subjects with positive histories of allergies to either cat dander or ragweed pollen and positive skin tests to the appropriate allergen extract were recruited and were subjected to conjunctival provocation. The tear duct of the left eye of each subject was blocked with a collagen plug while the right eye was left unplugged. In all cases, the eye was initially provoked with saline and subsequently with the appropriate allergen extract. Nonallergic subjects, or allergic subjects provoked with nonrelevant allergen, were used as control subjects. After each provocation, symptoms were recorded, and tears were collected with preweighed strips of filter paper (Schirmer strip). Each strip was placed into a tared tube containing fluid appropriate for the optimal preservation of the mediator to be measured. It was therefore possible to calculate the weight of tears collected and to express mediator levels per milliliter of tears. All allergic subjects demonstrated a positive symptomatic response to allergen challenge, whereas the control subjects remained asymptomatic. Blockage of the tear duct did not significantly alter the response. For allergic subjects, the levels of histamine, kinins, prostaglandin D2, albumin, and TAME-esterase activity were all significantly (p less than 0.005 in each case) greater after allergen challenge than after saline challenge. Furthermore, levels of each of these mediators after allergen challenge (expressed as increases above levels after saline provocation) were significantly greater for allergic subjects than for control subjects (p less than 0.005 in each case). Thus, the clinical response to conjunctival provocation with allergen is associated with increases in the levels of inflammatory mediators in tears.