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Biomedical subjects

A Alm

Publications and source records attributed to A Alm.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of latanoprost and dipivefrin, alone or combined, on intraocular pressure and on blood-aqueous barrier permeability.

AIM: To investigate the effect on intraocular pressure (IOP) and aqueous flare of topical applications of latanoprost and dipivefrin alone or combined. METHODS: 22 patients with open angle glaucoma or ocular hypertension were included in a 4 week open label study. Median age was 68 years (range 50-79). They were allocated to either 2 weeks' treatment with once daily evening administration of latanoprost monotherapy (50 micrograms/ml) or twice daily dipivefrin monotherapy (1 mg/ml), followed by 2 weeks' combination therapy with both drugs. RESULTS: Latanoprost alone reduced IOP from 19.3 (SD 1.4) to 14.8 (0.9) mm Hg (p < 0.01). Addition of dipivefrin caused a further reduction to 12.4 (0.9) mm Hg (p < 0.01 compared with latanoprost alone). In the group where the treatment started with dipivefrin IOP was reduced from 22.3 (1.2) to 18.4 (1.0) mm Hg (p < 0.01) and with the combination to 14.9 (0.9) mm Hg (p < 0.01). No change in aqueous flare was observed with either drug, alone or in combination. A slight increase in conjunctival hyperaemia was observed when the two drugs were combined. CONCLUSIONS: Latanoprost and dipivefrin have an additive effect on IOP and no clinically significant effect on the permeability to proteins of the blood-aqueous barrier. This implies that the two drugs can be a useful combination for the treatment of glaucoma.

Adrenergic Agonists↗
PubMed1998

Costs of treating primary open-angle glaucoma and ocular hypertension: a retrospective, observational two-year chart review of newly diagnosed patients in Sweden and the United States.

PURPOSE: The objective of this study was to investigate what treatment strategies prevail in different countries for patients newly diagnosed with primary open-angle glaucoma (POAG) or ocular hypertension (OH) only and initiated on treatment with beta-blockers, and to estimate the total direct cost of treatment for two years. In addition, differences in costs between and within the countries and the determinants of variations in costs across patients were examined. MATERIALS AND METHODS: The authors performed a retrospective medical record analysis in several academic and office-based study centers in Sweden and the United States. Standard costs for each resource item were determined and applied to all centers within the country. Differences in treatment costs within the countries are thus the effect of differences in treatment strategies, not of differences in prices. RESULTS: There was considerable variation between the centers of each country. Sweden had a higher number of surgical interventions, which may be explained by the fact that the Swedish cohort had a higher mean intraocular pressure (IOP) at baseline and a higher proportion of patients with definite POAG and exfoliation glaucoma. However, in both countries the mean IOP at study end was approximately 18 mm Hg. Total direct costs for two years were 15,119 SEK (US$2,160; $1US = 7 SEK) and $2,109, respectively. In a multiple regression analysis, the estimated effects of baseline IOP and of IOP change after treatment initiation on treatment costs were positively and negatively significant, respectively, in both countries. CONCLUSION: Despite differences in baseline diagnosis and in treatment strategies, mean IOP was decreased to 18 mm Hg in both countries. Baseline IOP was positively correlated with treatment costs, while the initial IOP-lowering effect of treatment was negatively correlated with two-year costs.

Adrenergic beta-Antagonists↗
PubMed1998

Latanoprost twice daily is less effective than once daily: indication of receptor subsensitivity?

PURPOSE: It is known that twice daily dosing of latanoprost is less effective in reducing intraocular pressure (IOP) than once daily applications. The aim of the present study was to investigate this phenomenon further in order to see if the results could be compatible with a subsensitivity of the FP-receptor. METHODS: Latanoprost, 50 microg/ml, was instilled once daily (8 PM) in one eye of 40 healthy volunteers and twice daily (8 AM and 8 PM) in the fellow eye in a randomized, masked fashion for 2 weeks, with the last drop on the evening of Day 15. IOP was determined at 8 AM, noon and 4 PM on Days 0, 2, 15 and 16. Also, the effect of a single dose of latanoprost was measured 6-11 months after cessation of treatment. RESULTS: There was a significant reduction of mean diurnal IOP from Day 2 (p < 0.001), with both dose regimens. Once-daily dosing resulted in a significantly lower IOP compared with twice-daily dosing on Day 15 (p < 0.001) but not on Day 2. The difference remained (p < 0.001) on Day 16 when no morning dose had been given, but was not present after a single application 6-11 months later. CONCLUSIONS: The results of the present study are compatible with development of subsensitivity, at the level of the FP-receptor or its associated intracellular signaling pathways, with twice- but not with once-daily dosing of latanoprost. This effect is reversible.

Adolescent↗
PubMed1997

Latanoprost and physostigmine have mostly additive ocular hypotensive effects in human eyes.

OBJECTIVE: To investigate if a pronounced ciliary muscle contraction, induced by physostigmine salicylate, can abolish the ocular hypotensive effect of latanoprost, a prostaglandin analogue, via inhibition of the uveoscleral outflow. DESIGN: A randomized, crossover study that was double-masked for latanoprost. Physostigmine was the second factor in a 2(2) factorial experiment. PARTICIPANTS: A total of 20 male and female healthy volunteers (median age, 25 years; age range, 17-30 years). INTERVENTIONS: Between 7 AM and 7 PM, 1 drop of physostigmine salicylate (8 mg/mL) was instilled in 1 eye every other hour. At 8 AM, 1 drop of either latanoprost (50 mg/L) or placebo was instilled in both eyes. This protocol was repeated a second time with latanoprost administered to previously placebo-treated eyes and vice versa. MAIN OUTCOME MEASURES: Intraocular pressure differences were measured with Goldmann applanation tonometry hourly for 13 hours. RESULTS: Latanoprost reduced the intraocular pressure significantly at 3 to 12 hours after application with a maximal effect at 8 hours after the administration of the dose. The reduction that was obtained with physostigmine administered every other hour was more pronounced, was observed at 1 hour after the administration of the first dose, and increased throughout the day. A significant interaction was seen between 3 and 6 PM (i.e., at 7-10 hours after application of latanoprost). CONCLUSIONS: Latanoprost and physostigmine have a mainly additive ocular hypotensive effect. Thus, high doses of physostigmine did not abolish the eye pressure-lowering effect of latanoprost, but some interaction was seen at low intraocular pressures. It was concluded that any mechanical effect on the uveoscleral flow achieved with physostigmine is short-lasting compared with the effect obtained with latanoprost, and that latanoprost and miotics can be combined.

Administration, Topical↗
PubMed1997

Comparison of dorzolamide and timolol as suppressors of aqueous humor flow in humans.

OBJECTIVES: To measure the effectiveness of topical 2% dorzolamide hydrochloride (Trusopt, Merck & Co Inc, Whitehouse Station, NJ) as a suppressor of aqueous humor flow in the human eye as compared with the effectiveness of 0.5% timolol maleate (Timoptic, Merck & Co Inc) and to measure the additivity of the 2 drugs. DESIGN: A randomized, double-masked, placebo-controlled study of 40 human subjects was carried out in 2 academic centers (Mayo Clinic, Rochester, Minn, and University of Uppsala, Uppsala, Sweden). The rate of aqueous flow was measured from 8 AM to 4 PM by means of fluorophotometry after administration of doses of each drug singly and both drugs together. RESULTS: Dorzolamide reduced aqueous flow from 3.07 +/- 0.63 microL/min (mean +/- SD) to 2.53 +/- 0.60 microL/min, a reduction of 18% (P < .001). Timolol reduced aqueous flow from the same beginning rate to 1.64 +/- 0.35 microL/min, a reduction of 47% (P < .001). The inhibitory effect of timolol was 2.6 times the inhibitory effect of dorzolamide (P < .001). The 2 drugs were almost completely additive, and together reduced the flow to 1.37 +/- 0.33 microL/min, a reduction of 55%. Consistent effects were observed on intraocular pressure. CONCLUSIONS: Timolol is more effective than dorzolamide as a suppressor of aqueous humor flow in the normal human eye. Timolol and dorzolamide are additive in their effects, both on aqueous flow and intraocular pressure.

Adrenergic beta-Antagonists↗
PubMed1997

Initial clinical studies with prostaglandins and their analogues.

Several prostaglandins (PGs), their prodrugs, and their analogues have been shown to reduce intraocular pressure (IOP) in normotensive volunteers and in patients with elevated IOP. Initial clinical trials demonstrated efficacy with most of these agents, but a PGE2 analogue, PGD2, and BW245C (an analogue selective for the DP-receptor) cause an initial rise in IOP with a minimal subsequent reduction. Although PGF2 alpha tromethamine salt, PGF2 alpha-isopropyl ester (PGF2 alpha-IE), and 15-propionate-PGF2 alpha-IE are all very effective in reducing IOP, they produce unacceptable side effects, including conjunctival hyperemia and ocular irritation. Isopropyl unoprostone, a 22-carbon chain PGF2 alpha metabolite, produces a 10-25% reduction in IOP lasting approximately 2-5 hours, is well tolerated, and is commercially available for use in Japan. 17-phenyl substituted PGF2 alpha-IE analogues, such as PhXA34 or latanoprost, effectively reduce IOP by 30-40% for at least 24 hours, and are very well tolerated with minimal conjunctival hyperemia and without irritation. Latanoprost is the more potent 15R-epimer of PhXA34, and has become a useful agent in glaucoma therapy.

Animals↗
PubMed1997

The additive intraocular pressure-lowering effect of latanoprost in combined therapy with other ocular hypotensive agents.

Latanoprost, a prostaglandin F2 alpha analogue prodrug, has been shown to be an effective ocular hypotensive agent when used alone on ocular hypertensive or open angle glaucoma patients. In various studies, the ocular hypotensive effects of latanoprost have also been evaluated when used in addition to, or in combination with, other ocular hypotensive agents. Latanoprost produces an additional reduction of intraocular pressure (IOP) when used in combination with timolol, pilocarpine, acetazolamide and dipivefrin. These represent four different classes of glaucoma drugs-beta-adrenergic antagonists, cholinergic agonists, carbonic anhydrase inhibitors, and adrenergic agonists-all of which reduce the IOP by different mechanisms (reduction of aqueous humor production, increased outflow facility, or by a mixed effect on aqueous humor dynamics). All the available evidence shows that latanoprost produces a clinically significant additive ocular hypotensive effect when used in combination with any currently available ocular hypotensive agent.

Acetazolamide↗
PubMed1997

Phase III latanoprost studies in Scandinavia, the United Kingdom and the United States.

Three large, masked, multicenter studies are reviewed comparing the safety and efficacy of 0.005% latanoprost eyedrops given once daily to 0.5% timolol eyedrops given twice daily for six months in patients with elevated intraocular pressure (IOP). A total of 829 patients were recruited from centers in Scandinavia, the United Kingdom (UK) and the United States of America (USA). In addition, data are reviewed from the first 198 of these patients to complete an additional six months of latanoprost treatment in an openlabel study. In all centers, both latanoprost and timolol were very effective in reducing the diurnal IOP. In the UK, both drugs reduced the IOP by 34%. In the USA, latanoprost was more effective than timolol, reducing IOP by 27% compared to 20%. In Scandinavia, latanoprost was given for three months in the evening and for three months in the morning while timolol was given twice daily for six months. Latanoprost given in the evening reduced IOP (35% reduction) significantly (p < 0.001) more than latanoprost given in the morning (31% reduction) and timolol given twice daily (27% reduction). Darkening of the iris color occurred in 7% of eyes treated with latanoprost for six months. A clinical evaluation of eyes with increased pigmentation, as well as preclinical studies; suggest that this side effect is a cosmetic problem in patients treated unilaterally. Other side effects were slight and not clinically significant. After one year of treatment with latanoprost in 198 patients, the IOP reduction of 32% was maintained. There was no loss of efficacy and no significant increase in the incidence of side effects or adverse events other than iris color darkening, which occurred or was suspected in 12%. These results demonstrate that latanoprost is a valuable drug for the treatment of chronic open angle glaucoma.

Adrenergic beta-Antagonists↗
PubMed1997

Physostigmine increases aqueous humor production in human eyes.

PURPOSE: To investigate if part of the progressive reduction of intraocular pressure (IOP), seen when physostigmine is applied on alternate hours, is due to a reduced aqueous flow. METHODS: In a randomized, open study, one drop of physostigmine salicylate, 8 mg/ml, was instilled at 7 AM in one randomly assigned eye in each of twenty healthy volunteers. Instillations were repeated on alternate hours throughout the day. Each subject's untreated eye served as control. Fluorophotometry of the anterior segment was performed hourly between 7 Am and 8 PM and aqueous flow was calculated. Subsequently, the subjects underwent tomography and tonometry. The change in anterior chamber depth and volume induced by physostigmine was assessed separately. RESULTS: The mean aqueous flow during the day was 25-28% higher in the physostigmine-treated eye than in the control eye. The difference was statistically significant from 9 AM (p < 0.05-p < 0.001). Each dose caused a further increase. The mean outflow facility increased by 0.14 microliters/min/mm Hg with 95% confidence interval (CI) 0.09-0.18. Although the increase in outflow facility was small, there was a marked reduction of IOP with a mean difference between treated and untreated eye of 3.2 mm Hg (95% CI: 2.3-4.0). CONCLUSIONS: Repeated administrations of physostigmine increase the aqueous flow and outflow facility. The combined effect is a marked reduction of IOP.

Adult↗
PubMed1997

Retinal mean transit time determined with an impulse-response analysis from video fluorescein angiograms.

PURPOSE: To evaluate a new technique for determining the Mean Transit Time (MTT) of retinal circulation, based on an impulse-response analysis. The results obtained were compared to those obtained with a conventional method based on semilogarithmic extrapolation. METHODS: 128 frames at a rate of 5 frames per second were digitized from video fluorescein angiograms and processed with a specially designed image analysis system. The MTT was determined from 25 curve pairs from 12 eyes in 8 young, healthy volunteers by the conventional technique (MTT[SLOPE]) and by our newly developed Impulse-Response analysis (MTT[IR]). RESULTS: MTT(SLOPE) and MTT(IR) calculated for the 25 curve pairs were 3.54 +/- 1.00 and 2.67 +/- 0.88 seconds, respectively (Mean +/- SD). There was a good correlation between the two techniques (r2 = 0.81, p < 0.001). Unlike MTT(SLOPE), MTT(IR) could be calculated also from curves with a badly defined bolus. CONCLUSION: We conclude that MTT(IR)-analysis of the retinal circulation may be used for clinical studies on retinal blood flow from angiograms obtained in patients.

Blood Circulation↗
PubMed1997

Effects on intraocular pressure and aqueous flow of various dose regimens of latanoprost in human eyes.

PURPOSE: To examine if different dose regimens of latanoprost cause a difference in daytime intraocular pressure (IOP) in normal eyes and if such changes could be attributed to an increase in aqueous flow. METHODS: In a randomised, open, cross-over study latanoprost 50 microg/ml was instilled in one eye of 18 volunteers. Three dose regimens (one/three drops once daily or one drop twice daily) were evaluated. IOP was measured at the end of each 14-day treatment period. Aqueous flow and endothelial permeability were assessed by fluorophotometry. RESULTS: All dose regimens reduced IOP significantly (p < 0.001). Once daily applications reduced IOP more than twice daily (p < 0.01). No statistically significant difference in aqueous flow was detected between different treatments. One drop daily increased aqueous flow compared with control eyes (p < 0.05). A similar, but not statistically significant tendency was present with the other regimens. Corneal endothelial permeability was not affected. CONCLUSION: Once daily applications of latanoprost reduce IOP more effectively than twice daily in normal subjects. This cannot be explained by an increase in aqueous flow.

Adult↗
PubMed1997

Effects on IOP restoration and blood-aqueous barrier after long-term treatment with latanoprost in open angle glaucoma and ocular hypertension.

AIMS: To evaluate whether long-term treatment with the prostaglandin analogue latanoprost has a deleterious effect on the blood-aqueous barrier (BAB) and to determine the duration of the effect on intraocular pressure (IOP) after withdrawal of treatment. METHODS: Patients with ocular hypertension or glaucoma were topically treated with latanoprost 50 micrograms/ml once daily for 6-12 months. In 26 patients IOP was followed for 14 days after withdrawal of treatment. Aqueous flare was measured with a laser flare meter during 6-12 months' treatment in 16 patients. RESULTS: On the last day of treatment IOP was 6.9 mm Hg (95% CI 5.3-8.5) lower than before treatment. It increased slowly during the follow up period but was still 1.3 mm Hg (95% CI 0.2-2.5) lower than pretreatment IOP 14 days after cessation of treatment. No change in aqueous flare was seen throughout the study. CONCLUSION: Latanoprost has no clinically significant effect on the permeability of the BAB and IOP will return to pretreatment levels within a few weeks, indicating that latanoprost is safe for long-term treatment.

Aged↗
PubMed1997

Effect of consecutively applied fluorescein eye drops on corneal and aqueous concentrations of fluorescein.

The main objective of this study was to determine the intraocular concentration of fluorescein after applying five eye drops with only 1-min intervals in human eyes. The concentration of fluorescein in corea and aqueous was studied with fluorophotometry in 11 healthy volunteers. Five 10-microliter drops of 2% fluorescein solution were administered with 1-min intervals, and the intraocular concentrations that were achieved were compared with those obtained with just one eye drop. Five consecutive fluorescein drops caused a 2.6- to 3.1-fold increase in fluorescein concentrations of the anterior chamber 1-8 h after application compared with a single eye drop (p < 0.05). Corresponding values for the cornea were 2.1-2.8. As a conclusion, administration of five eye drops applied consecutively significantly increases intraocular drug concentration during 8 h in humans.

Adult↗
PubMed1997

Ocular blood flow in experimental glaucoma: a study in cynomolgus monkeys.

Experimental glaucoma was induced in 1 eye of 6 cynomolgus monkeys by laser treatment of the trabecular meshwork. In 5 of the 6 monkeys the increased intraocular pressure (IOP) caused marked glaucomatous damage in the experimental eye. Ocular blood flow was determined with labeled microspheres 4 years after the laser treatment. IOP was regulated with an external reservoir. With the same perfusion pressure in both eyes no statistically significant difference was observed between the 2 eyes for total ocular blood flow or for blood flow through any of the ocular tissues. Total ocular blood flow was 343.5 +/- 61.4 mg/min (mean +/- SEM) in the control eye and 385.3 +/- 107.7 mg/min in the experimental eye.

Animals↗
PubMed1996

Latanoprost, a prostaglandin analog, for glaucoma therapy. Efficacy and safety after 1 year of treatment in 198 patients. Latanoprost Study Groups.

PURPOSE: To determine efficacy and safety of latanoprost, a prostaglandin analog for glaucoma, during 1 year of treatment. METHODS: After baseline measurements, 0.005% latanoprost was topically applied once daily for 12 months in patients from Scandinavia, the United Kingdom, and the United States who had elevated intraocular pressure (IOP). Diagnoses included ocular hypertension, chronic open-angle glaucoma, exfoliation syndrome, and pigment dispersion syndrome. Treatment was masked for the first 6 months and open-label during the second 6 months. RESULTS: Of the 272 patients initially enrolled, withdrawals were due to inadequate IOP control (1%), increased iris pigmentation (5%), other ocular problems (3%), systemic medical problems (3%), and nonmedical reasons (14%). Latanoprost significantly (P < 0.0001) reduced diumal IOP from 25.3 +/- 3.0 mmHg (mean +/- standard deviation) at baseline to 17.4 +/- 2.7 mmHg (32% reduction) at 12 months in the 198 patients who completed 1 year of treatment. The IOP reduction was maintained at a consistent level throughout the 12 months without evidence of drift, and was not affected by sex, age, race, or eye color. Overall, latanoprost caused a possible or definite increase in iris pigmentation in 12% of the 272 patients, all of whom had multicolored irides at baseline. One half of these patients with increased pigmentation withdrew before completing 1 year of therapy. Visual field, optic disc cupping, visual acuity, refractive error, conjunctival hyperemia, aqueous flare, anterior chamber cellular response, lens examination, blood pressure, heart rate, blood tests, and urinalysis were not appreciably altered. CONCLUSION: Latanoprost safely and effectively reduces IOP for 1 year in patients of diverse nationalities, providing further evidence for its usefulness in chronic glaucoma therapy.

Administration, Topical↗
PubMed1996

Latanoprost as a new horizon in the medical management of glaucoma.

Latanoprost is a new prostaglandin F2 alpha analogue specifically developed for the treatment of glaucoma. Latanoprost is a selective FP receptor agonist, with a primary mode of action of increased uveoscleral outflow of aqueous humor. A dose of 50 micrograms/mL (0.005%) once daily has been found optimal in clinical trials. Latanoprost reduces the nocturnal intraocular pressure in addition to the diurnal, and has been shown to be additive to other glaucoma medication. In long-term phase III clinical trials, latanoprost 0.005% once daily has been proven to be at least as effective as timolol 0.5% twice a day. The main side effect of latanoprost is increased iridial pigmentation, which is relatively frequent in patients with mixed color of the iris. This unique side effect is based on the ability of prostaglandins to stimulate melanin formation in melanocytes. The advantages of latanoprost compared with other glaucoma medication comprise different mode of action, good intraocular pressure-reducing effect, once-daily dosing, and absence of systemic side effects. The long-term consequences of increased iridial pigmentation need to be further studied.

Animals↗
PubMed1995

Effects on intraocular pressure and side effects of 0.005% latanoprost applied once daily, evening or morning. A comparison with timolol. Scandinavian Latanoprost Study Group.

PURPOSE: To compare the effect on intraocular pressure (IOP) and side effects of 0.005% latanoprost applied once daily, morning or evening, with 0.5% timolol applied twice daily. METHODS: A 6-month randomized, double-masked, multicenter study with three parallel groups was undertaken. Two hundred sixty-seven patients were randomized, 84 to timolol, 89 to latanoprost in the morning for 3 months and then in the evening for another 3 months, and 94 to latanoprost with the treatment schedule reversed. RESULTS: After 6 months, timolol reduced diurnal IOP from 24.6 to 17.9 mmHg (27%); latanoprost applied in the morning, from 25.5 to 17.7 mmHg (31%); and latanoprost applied in the evening, from 24.8 to 16.2 mmHg (35%). The efficacy of latanoprost applied in the evening was statistically superior to latanoprost applied in the morning and to timolol (P < 0.001). Latanoprost induced a slight increase in conjunctival hyperemia in 31.4% of treated patients, compared with 15.9% for timolol. Sporadic episodes of mild punctate corneal epithelial erosions were three times as frequent in latanoprost-treated eyes as in timolol-treated eyes. The most significant ocular side effect was increased pigmentation of the iris observed in five and suspected in seven more latanoprost-treated eyes. All these eyes had a mixed green-brown or blue/gray-brown iris color. Timolol reduced heart rate by 3 beats/minute (P < 0.005). CONCLUSIONS: The effect on diurnal IOP of latanoprost applied once daily in the evening is superior to that of timolol. The main difference in side effects is increased pigmentation of the iris induced by latanoprost, most likely due to stimulation of melanogenesis in iris stromal melanocytes.

Adrenergic beta-Antagonists↗