[Adverse effects of local use of beta-blockaders in glaucoma. A literature review and a survey of reports to the adverse drug reaction authority 1986-95]
The review is based on a survey of studies on adverse reactions related to topical administration of beta-blockers for glaucoma. Locally applied beta-blocking agents are partially resorbed from the nasal mucosa. Concentrations which give rise to systemic effects occur invariably. Several reports exist of congestive heart failure, arrhythmias, severe respiratory symptoms, depression, hallucinations and confusion provoked by topical use of beta-blockers, especially timolol. It is impossible to estimate from the literature how often the various adverse effects occur. One has the impression, however, that adverse effects in the pulmonary and central nervous systems have not been fully considered. Between 1986 and 1995 the Norwegian Medicines Control Authority received reports on adverse reactions related to topical use of beta-blockers in 17 patients. Six of these patients had cardiovascular and four of them severe respiratory symptoms. The latter group also included three fatal cases. The adverse effects seem to occur most frequently in the elderly, and it has been suggested that timolol should not be used in elderly people. Adverse effects related to treatment with topical beta-blockers are probably underreported in Norway.
PURPOSE: To confirm whether long-term administration of prednisolone sodium succinate (prednisolone) alone is able to induce cataract in rat eyes. MATERIALS AND METHODS: A 1% solution of prednisolone was administered topically as eye drops to Brown Norway rat eyes, and a systemic pulse administration of 10 mg/kg/day was given via the tail vein. Both administration methods were applied in different combinations. Eighty-three 6-week-old male rats were divided into 8 groups: group 1 = control; group 2 = topical instillation every day; group 3 = single pulse; group 4 = single pulse + eye drops; group 5 = 3 times pulse; group 6 = 3 times pulse + eye drops; group 7 = 3 times pulse per 2 months; group 8 = 3 times pulse per 2 months + eye drops. Observations for changes of lens transparency were made by slitlamp microscopy and documented by an anterior eye segment analysis system (Nidek EAS-1000) from the onset of drug administration to a maximum period of 16 months. RESULTS: Lens opacity in the shallow anterior and posterior lens layers developed from the tenth month following commencement of prednisolone administration. The incidence of anterior and/or posterior cortical cataract at the sixteenth month was 15% in group 2, 12.5% in group 5, 25% in group 6, 17.9% in group 7 and 35.3% in group 8. The lenses of groups 1, 3 and 4 maintained their transparency throughout the observation period. Light scattering intensity in groups 8 and 7 was the highest, followed by groups 6 and 5, then groups 2, 4, 3 and 1. CONCLUSION: Cortical cataract was successfully induced in Brown Norway rat eyes by sustained administration of prednisolone succinate alone applied as systemic pulse.
282 (564 eyes) premature infants born at mean 27 +/- 2,5 weeks of gestation with birth weight 914+/- 247g were enrolled in the study. Comparative study showed preventive treatment with histochrome in infants with risk of retinopathy of prematurity (RP) to decrease the incidence of RP compared to infants treated with emoxipine and no antioxidant therapy. Incidence of RP in infants preventively treated with combination antioxidant agents (dicynon and emoxipine) was significantly lower compared to the group without preventive antioxidant treatment. Use of histochrome in treatment of RP via periocular injections and forced instillations promoted more favorable outcome of the disease.
PURPOSE: To investigate whether treatment with artificial tears inhibits the development of experimental immune-mediated blepharoconjunctivitis (EC). METHODS: Brown Norway rats were immunized with ovalbumin (OVA) or ragweed (RW) emulsified in complete Freund's adjuvant. Fourteen days after immunization, the rats were challenged with the same antigen (Ag) in eye drops. Treated rats were administered artificial tears by eye drops immediately after, 15 min after, or 30 min after the Ag challenge. Treatment doses of 2, 4, or 8 drops per eye were evaluated. Twenty-four hours after the Ag challenge, the rats were killed and their eyes were harvested for histological studies. RESULTS: Treatment with artificial tears immediately after and 15 min after challenge with partially insoluble RW Ag suppressed infiltration of inflammatory cells into the conjunctiva. Inhibition was not observed at any time following challenge with OVA Ag, which is a soluble protein. The treatment dose of artificial tears administered did not affect the extent of inhibition of EC following challenge with either Ag. CONCLUSIONS: Treatment with artificial tears by eye drops inhibited the development of EC induced by the partially insoluble RW Ag when administered within 15 min of the Ag challenge.
To evaluate the correlation between changes in the susceptibility of bacteria and mutations in the quinolone-resistance determining region (QRDR) after 3 weeks of continuous fluoroquinolone instillation.
Miyata Eye Hospital, Miyazaki, Japan.
In this prospective randomized study, gatifloxacin 0.3% eyedrops or levofloxacin 0.5% eyedrops were administered for 1 week before cataract surgery and for 2 weeks after surgery. Samples were collected from the conjunctival sac before instillation of the antibiotic agent and 14 days after surgery. Susceptibility to the fluoroquinolones and gene mutations in the QRDR of the isolated Staphylococcus epidermidis were analyzed.
The detection rate of S. epidermidis was 27% in the gatifloxacin group (n=79 eyes) and 21% in the levofloxacin group (n=73 eyes) before instillation of the antibiotic and 6% and 19%, respectively, 14 days postoperatively. The susceptibility rates of S. epidermidis strains to levofloxacin were statistically significantly lower after instillation than before antibiotic instillation, and the number of gene mutations in the QRDR was statistically significantly higher after instillation. There was no difference in the gatifloxacin group between before and after antibiotic instillation. In the 9 eyes in which S. epidermidis was detected in samples taken before and after antibiotic instillation, most strains were genetically different from each other between the 2 time points.
Three-week continuous instillation of levofloxacin affected the indigenous bacterial flora in the conjunctival sac, suggesting possible induction of microbial substitution to fluoroquinolone-resistant S. epidermidis. However, there was no change with gatifloxacin.
BACKGROUND: Retinal leukostasis plays an important role in the pathogenesis of diabetic retinopathy. Objectives: We studied the effects of nipradilol, a topical antiglaucoma alphabeta-blocker and nitric oxide donor, on the retinal vascular leukocyte adhesion of rats with diabetes. METHODS: Diabetes was induced in seven Brown-Norway rats by one intravenous injection (65 mg/kg) of streptozotocin and confirmed by blood glucose levels >350 mg/dl 48 h after the injection. Nipradilol solution was instilled in the right eye and nipradilol-free base solution in the left eye for 3 weeks, after which the retinal microcirculation was evaluated by acridine orange leukocyte digital fluorography using laser scanning ophthalmoscopy. Leukocytes trapped in the retina were counted around the optic disc in a 5-disc-diameter area and compared between the right and the left eye. RESULTS: The mean retinal leukostasis count in the nipradilol-treated eyes (19 +/- 15 cells) was significantly lower than in the untreated eyes (49 +/- 19 cells; p
PURPOSE: To evaluate intracameral injection of mydriatics in phacoemulsification cataract surgery and compare the results with those of conventional topical mydriatics. SETTING: Department of Clinical Science/Ophthalmology, Umeå University Hospital, Umeå, Sweden. METHODS: This prospective randomized double-blind study included 60 patients who were given topical (topical group) or intracameral (intracameral group) mydriatics. The topical mydriatics comprised 3 drops of cyclopentolate 1% and phenylephrine 10% given 15 minutes apart and 150 microL intracameral lidocaine hydrochloride 1% (Xylocaine) and the intracameral mydriatics, placebo eyedrops and 150 microL intracameral cyclopentolate 0.1%, phenylephrine 1.5%, and Xylocaine 1%. The pupil size was recorded preoperatively, throughout surgery, and 1 day and 1 month postoperatively. Preoperative and postoperative corneal endothelial morphology, corneal thickness, intraocular pressure, visual acuity, aqueous cells and flare, phacoemulsification energy, duration of surgery, pulse, blood pressure, and intraoperative sensation of pain and glare were also recorded. RESULTS: With intracameral mydriatics, mydriasis reached 95% +/- 3% (SD) of its final value within 20 seconds. In the intracameral group, the pupils were smaller than in the topical group (mean 6.7 +/- 1.0 mm versus 7.7 +/- 1.0 mm, P
The aim of the study was to assess efficacy and side effects of latanoprost during two years of treatment.
The study was a randomized, parallel group, double-masked, multicenter comparison between latanoprost and timolol in patients with open angle glaucoma or ocular hypertension, followed by an open-label 18-month extension during which all patients were treated with latanoprost.
Latanoprost caused a marked and sustained reduction of the intraocular pressure (IOP). IOP was reduced from baseline levels 25.1+/-3.5 mm Hg (mean+/-SD) in 183 patients initially randomized to treatment with latanoprost to 17.4+/-2.9 mm Hg (n=66) after 24 months of treatment. For patients initially randomized to treatment with timolol the corresponding figures were 24.3+/-2.3 mm Hg (n=72) and 17.4+/-2.6 (n=41) mm Hg after 18 months of treatment with latanoprost. Two patients were withdrawn because of uncontrolled IOP and 11 patients required additional timolol treatment to maintain an adequate IOP control. Patients initially treated with timolol and switched to latanoprost had a further reduction of the IOP of 1.0 mm Hg after 6 months of treatment with latanoprost (p
Poor compliance with medication is a major concern in the management of glaucoma. Improper administration technique can lead to contamination and inaccurate dosing. This study estimates the prevalence and predictors of noncompliance and improper administration technique among Canadian glaucoma patients.
Data were collected using a standardized questionnaire. Noncompliance was defined as missing at least 1 drop of medication per week and (or) the inability to accurately describe the medication regimen. Patients were asked to indicate the most common reason for missing medication. Study personnel assessed drop administration technique as patients were applying eye drops. Physicians provided information, including measures of disease stability, regarding the patient's glaucoma. Predictors were assessed using odds ratios from a logistic regression model.
500 patients from 10 centers across Canada participated in the study. Of these, 25.6% reported missing at least 1 drop of medication per week, and 4.2% were unable to accurately describe their medication regimen. The overall proportion of noncompliance was 27.9%. With regard to drop administration, 6.8% missed their eye and 28.8% contaminated the bottle tip; overall, 33.8% demonstrated improper technique. The most common reasons given for missing eye drops were "forgetfulness" and "being away from drops." Formal education limited to elementary school and treatment duration of
