Placebo Eye Drops Research Articles

Nedocromil sodium treats symptoms of perennial allergic conjunctivitis not fully controlled by sodium cromoglycate A double-masked placebo controlled group comparative study

In a double-masked group comparative study, 20 patients received 2% nedocromil sodium four times daily and 23 placebo eye drops, for treatment of perennial allergic conjunctivitis (PAC). All had at least a one-year diagnosis of bilateral PAC and remained symptomatic despite using 2% sodium cromoglycate eye drops four times daily for at least 14 days Symptom severity (0-4) during sodium cromoglycate monotherapy was then recorded in a one-week baseline prior to randomisation, a minimum total score of 11 being mandatory. During the trial, no eye medication was allowed other than the test treatment. Clinic examinations were made before and after baseline and after one, three and six weeks' treatment, and patients kept daily diary cards of eye symptom severity. Compared to placebo, nedocromil sodium significantly (p<0.05) improved diary scores for itching (weeks 3, 4, 5, 6), total symptoms (weeks 5, 6) and general eye condition (week 6). Mean scores over the final four weeks, allowing a two-week washout, showed similar improvements in itching (p = 0.01), total symptoms (p = 0.05) and general eye condition (p = 0.04). Clinical assessments again favoured nedocromil sodium, which improved itching (week 3, p = 0.002), burning (week 6, p = 0.007), overall eye condition (weeks 3-6, p<0.05). and conjunctival thickening and hyperaemia (weeks 3-6, p<0.05). Finally, both patient (p = 0.02) and clinician (p = 0.0015) opinions of efficacy favoured nedocromil sodium over placebo. These results show nedocromil sodium to be effective in controlling symptoms of perennial allergic conjunctivitis which persisted during treatment with sodium cromoglycate.

Double-masked, paired-comparison clinical study of ketorolac tromethamine 0.5% ophthalmic solution compared with placebo eyedrops in the treatment of seasonal allergic conjunctivitis

In a multicenter, double-masked, clinical study, we compared the ocular safety and efficacy of ketorolac 0.5% ophthalmic solution with placebo in alleviating the signs and symptoms of allergic conjunctivitis. The study was conducted in 93 patients who received one drop of the appropriate treatments in each eye, four times a day, for seven days. Of these subjects, 74 were evaluated for efficacy. The principal clinical sign of allergic conjunctivitis, conjunctival inflammation, and six allergic symptoms (itching, swollen eyes, burning or stinging, discharge or tearing, foreign body sensation, and photophobia) were evaluated by the investigators at midweek (day 3 or 4) and at the end of the study (day 7 or 8). Ketorolac was superior to placebo in reducing conjunctival inflammation (p = 0.003) and itchin (p = 0.020), the principal clinical symptom, at the final examination. In addition, ketorolac was favored over placebo in reducing the other five symptoms evaluated. On the day of final examination, overall therapeutic response evaluated by the investigators rated ketorolac as superior to placebo (p = 0.007). A significant placebo effect was noted in this study, as has been previously reported in clinical studies of allergic conjunctivitis patients. Results of this study demonstrate that 0.5% ketorolac ophthalmic solution used topically four times daily, for seven days, was effective in alleviating the principal sign and the symptoms associated with allergic conjunctivitis.

Levocabastine compared with sodium cromoglygate eyedrops in children with both birch and grass pollen allergy

Fifty–five children 6–16 years old with allergic rhinoconjunctivitis due to both birch and grass pollinosis were randomized into 2 parallel groups, treated in double–blind fashion with either levocabastinc (LEV) eye–drops twice daily plus placebo eyedrops twice daily or sodium cromoglycate (SCG) eyedrops 4 times daily for 3 months. Spersallerg® (antazolini chloride + tetryzolini chloride) eyedrops were allowed as rescue medicine. All children received basic treatment with an antihistamine (terfenadine) during the complete trial period, and a local nasal corticosteroid if needed. Eye symptoms were recorded daily by the patients and at 4 visits by the investigator, at start and after 4, 10 and 13 weeks. Pollen counts were performed and a blood sample was collected at start and end of the treatment. The global evaluation of treatment was similar for the 2 groups, and there was no significant difference in any effect parameter except for the symptom, itchy eyes, which had lower score in the SCG group as evaluated by the investigator after 4 weeks. On days with low pollen counts the patients in the SCG group had fewer days with moderate or severe eye symptoms. It is concluded that even though LEV and SCG eyedrops were given in addition to systemic treatment with an antihistamine, no consistently significant differences in clinical effect were found between the 2 treatment groups, but the SCG group experienced slightly less eye symptoms throughout the trial. LEV eye–drops appear safe in long–term treatment in children, and no signs of tachyphylaxis were recorded.

Effects of phosphonylmethoxyalkyl-purine and -pyrimidine derivatives on TK + and TK − HSV-1 keratitis in rabbits

The phosphonylmethoxyalkyl derivatives HPMPA [( S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine], HPMPC [( S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] and PMEA [9-(2-phosphonylmethoxyethyl)adenine] were evaluated as 0.2% eyedrops for their efficacy in the treatment of experimental herpes simplex virus type 1 (HSV-1) keratitis in the rabbit model. BVDU 0.2% eyedrops were used as the reference treatment. HPMPA, HPMPC, PMEA and BVDU eyedrops showed a rapid and highly significant healing effect ( P < 0.005) on keratitis caused by TK + HSV-1 (McIntyre strain) when compared with placebo eyedrops, whereas BVDU treatment did not affect the course of TK − HSV-1 (VMW-1837) keratitis. HPMPA and HPMPC treatment again caused a highly significant healing ( P < 0.005, compared with placebo eyedrops). Although PMEA eyedrops were less effective than HPMPA or HPMPC eyedrops, the effect of PMEA eyedrops was significantly ( P < 0.05) different from the effect of either BVDU or placebo eyedrops.

Design and organization of the herpetic eye disease study (HEDS)

The Herpetic Eye Disease Study (HEDS) includes three double-masked, placebo-controlled clinical trials for potentially blinding herpes simplex virus (HSV) eye infections. One study compares a tapering dosage of topical prednisolone or placebo eye drops for HSV stromal keratitis (HEDS-SKN). Two other trials compare oral acyclovir to placebo capsules for HSV stromal keratitis (HEDS-SKS) or iridocyclitis (HEDS-IRT) in patients on a tapering dosage of topical prednisolone drops. All medications are administered for 10 weeks. Outcome is judged by time to recurrent disease or treatment failure. This paper presents the design, estimated sample size and recruitment as of July 25, 1990.

Systemic effects of three β-blocker eyedrops: Comparison in healthy volunteers of β1- and β2-adrenoreceptor inhibition

The beta 1- and beta 2-adrenoreceptor blockade by means of the systemic diffusion of three beta-blocker eyedrops--timolol, carteolol, and betaxolol--was evaluated in a randomized, single-blind, three-way crossover study in 18 volunteers. The blockade was evaluated by analyzing the variations of the beta 1- and beta 2-blockade effects of isoproterenol before and after instillation of one drop in each eye. The beta 1-blockade effect was judged on the variation of heart rate, and the beta 2-blockade effect was judged on the change in peripheral blood flow measured by veno-occlusive plethysmography. Comparison of the blockade by these drops showed that carteolol and timolol totally inhibited the beta 1 and beta 2 effects of a dose of isoproterenol able to increase heart rate by 50% (placebo eyedrops were used as a control). Betaxolol differ significantly because it allowed the same effects with the same dose of isoproterenol. Intensity of the blockade was measured by comparison of the effective doses of isoproterenol. Carteolol and timolol were shown to be four times more inhibitory.

Cardiovascular responses to metipranolol and timolol eyedrops in healthy volunteers.

1. Intraocular pressure and cardiovascular responses to metipranolol 0.1% and 0.3% and timolol 0.25% eyedrops were measured in a balanced single dose placebo-controlled crossover study in eight healthy volunteers aged 34-58 years. 2. Timolol 0.25% and metipranolol 0.3% reduced intraocular pressure throughout the 6 h period of observation to a similar extent. Metipranolol 0.1% was marginally less effective, significantly reducing pressure up to 4 h only. 3. No drug treatment significantly altered resting heart rate or blood pressure. Timolol 0.25% significantly reduced exercise tachycardia (P less than 0.05), an effect which was not shown by metipranolol 0.1 or 0.3%. Exertional pain in the legs occurred more frequently after timolol 0.25% and metipranolol 0.3% than after metipranolol 0.1% or placebo eyedrops. 4. Octan-1-ol/pH 7.4 buffer distribution coefficients at 37 degrees C were found to be: metipranolol 5.19, timolol 0.84, indicating that metipranolol has an approximately 6-fold greater lipid solubility. 5. It is concluded that, by comparison with timolol, metipranolol in eyedrop concentrations up to 0.3%, despite its greater lipid solubility, reaches concentrations in the systemic circulation which are less likely to affect the heart.

Thymoxamine Reverses Phenylephrine-Induced Mydriasis

We performed a randomized double-masked evaluation of the alpha-adrenergic blocking agent thymoxamine (0.1%) as compared to placebo for the reversal of phenylephrine-induced mydriasis. Topically applied thymoxamine reversed the mydriasis from a single drop of 2.5% phenylephrine in 36 of 40 eyes (90%) within one hour. The mydriasis was completely reversed in 25 of 40 eyes (63%). Eyes with blue irides responded more quickly and more completely than did those with brown irides. The 40 contralateral eyes, which had also been dilated with phenylephrine, remained dilated or dilated further after receiving a placebo eyedrop. Twenty subjects (50%) reported mild transient ocular irritation upon instillation of thymoxamine. Thymoxamine was useful in individuals with narrow anterior chamber angles who were at risk of acute closed-angle glaucoma following dilation with an adrenergic agent.

Mitomycin Eye Drops as Treatment for Pterygium

The authors used an anti neoplastic-antibiotic agent, mitomycin, in the form of eye drops as adjunctive treatment for primary and recurrent pterygia after surgical excision. Sixteen primary and four recurrent pterygia were treated with 1.0 mg/ml mitomycin eye drops, 14 primary and 10 recurrent pterygia were treated with 0.4 mg/ml mitomycin eye drops, and 18 primary pterygia were treated with placebo eye drops. Postoperative follow-up for the eyes treated with mitomycin eye drops ranged from 3 to 34 weeks (mean, 23 weeks). One of 44 pterygia treated with mitomycin recurred after 5 months (recurrence rate, 2.3%), whereas 16 of 18 primary pterygia treated with placebo eye drops developed postoperative granulomas and recurrent pterygia with a mean postoperative period of 6 weeks (recurrence rate, 88.9%). Topical mitomycin (1.0 mg/ml) caused conjunctival irritation, excessive lacrimation, and mild superficial punctate keratitis. These topical side effects were minimized with the 0.4 mg/ml mitomycin dosage. No systemic toxicity was noted with either dosage. The authors believe that mitomycin eye drops is a safe and effective adjunct to surgical excision in the treatment of primary or recurrent pterygia, or both.

Experimental thymidine kinase-deficient HSV-1 keratitis: therapeutic attempts.

Trifluridine (TFT) and a structurally related analogue, 5-fluoro-2'-deoxyuridine (FDU), were investigated for their efficacy in the topical treatment of experimental keratitis caused by thymidine kinase-positive (TK+) and thymidine kinase-deficient (TK-) herpes simplex virus type 1 (HSV-1) strains. Bromovinyldeoxyuridine (BVDU) was used as a reference compound. Both 0.2% BVDU and 0.2% TFT eyedrops produced a highly significant healing of TK+HSV-1 keratitis as compared to the placebo and 0.2% FDU eyedrops (P much less than 0.005), whereas the latter compound did not differ from placebo eyedrops. In the treatment of TK HSV-1 keratitis, none of the drugs exhibited a beneficial healing effect, although the virus strain used was inhibited in vitro by TFT and FDU at a very low concentration (0.02-0.04 microgram/mL).

Pulmonary and Heart Rate Changes Associated with Nonselective Beta-Blocker Glaucoma Therapy

AbstractSix ophthalmic beta-blockers-betaxolol, timolol, levobunolol, pindolol, befunolol, and metipranolol-and placebo eyedrops were tested in six normal volunteers for their effect on exercise heart rate, blood pressure, and electrocardiogram tracings. None of the solutions affected blood pressure or electrocardiogram results. Betaxolol and placebo did not affect heart rate. However, all the other agents significantly (p < 0.05) suppressed the heart's ability to respond to exercise.These same formulations were tested by spirometry in six asdimatic patients. Betaxolol and placebo had no effect on forced expiratory volume at 1 sec (FEV,), whereas all the other agents significantly (p < 0.05) depressed vital lung function.

Effects of Topical Betaxolol, Timolol, and Placebo on Pulmonary Function in Asthmatic Bronchitis

To evaluate the effects of two beta-adrenergic blocking agents on cardiopulmonary function, we investigated two topical ophthalmologic preparations, betaxolol 1% and timolol 0.5%, in nine patients (eight men and one woman, ranging in age from 25 to 69 years) with reactive airway disease. The randomized, double-masked, crossover study used placebo eyedrops as the control, and each drug was tested on separate days. Spirometric measurements, respiratory rate, pulse rate, and blood pressure were observed at frequent intervals for four hours after the test solutions were instilled. At the end of the test, an inhaled beta-adrenergic stimulant (isoproterenol) was administered, and the measurements were repeated. Timolol produced a significant decrease in airflow, measured by forced expiratory volume in one second (FEV1) and the ratio of FEV1 to vital capacity at each observation time beyond 15 minutes. Betaxolol and placebo eyedrops produced no significant change from control values. These results suggested that timolol can adversely affect patients with reactive airway disease. Betaxolol eyedrops, conversely, caused no decrease in airflow in the same patients with proven airway disease.

Topical Corticosteroid Therapy for Corneal Toxicity from Systemically Administered Cytarabine

Eleven patients with leukemia refractory to conventional therapy were treated with high doses of cytarabine (3 g/m2 intravenously every 12 hours for six days) followed by daunorubicin (30 mg/m2/day intravenously for three days). Each patient received, in a double-masked, randomized manner, either 1% prednisolone phosphate or placebo eyedrops in each eye 12 hours before and along with the cytarabine so that we could determine whether a topical corticosteroid prevents corneal toxicity from systemic cytarabine. Ten of the 11 patients had a significant reduction in the intensity and duration of the symptoms and signs of corneal toxicity in the corticosteroid-treated eye (P less than .0005). In the placebo-treated eye, pain, photophobia, and tearing occurred at a median time of 6.5 days after initiation of therapy but resolved in approximately one week. Patients receiving high doses of intravenously administered cytarabine should receive topical corticosteroid prophylaxis to reduce the corneal toxicity associated with this treatment.

Corticosteroid Therapy for the Reduction of Postoperative Inflammation After Cataract Extraction

In an random, double-masked multicentric clinical trial, topical betamethasone phosphate 0.1% or placebo eyedrops were used five times daily for the first two weeks after uncomplicated intracapsular cataract extraction in 107 patients who had moderate to severe postoperative inflammation on the first postoperative day. Topical corticosteroid solution was significantly more effective than placebo in the reduction of postoperative ocular inflammation. There were no ocular complications of corticosteroid treatment.