Can NSAIDs and prostaglandin analogues be combined?
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
A Alm
Publications and source records attributed to A Alm.
How much is the brain involved in glaucoma?
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Animals↗
The efficacy and safety of unfixed and fixed combinations of latanoprost and other antiglaucoma medications.
Adjunctive therapy for the management of glaucoma is commonly used. Unfixed combinations of the prostaglandin analog latanoprost and other glaucoma medications have been demonstrated to effectively lower intraocular pressure (IOP). The range of reported additional reductions in IOP compared to a monotherapy baseline are as follows: latanoprost-timolol (13-37%), latanoprost-pilocarpine 2% (7-14%), latanoprost and carbonic anhydrase inhibitors (15-24.1%), and latanoprost and dipivefrin (15-28%). There is a fixed combination of latanoprost (0.005%) and timolol (0.5%) that has been investigated in Phase III trials in Europe and the United States. In these trials, it was noted that the efficacy of the fixed combination was superior to either of the monotherapy components. After 12 months of follow-up of patients on fixed combination, there was no evidence of long-term drift. The new formulation appears to be safe and does not demonstrate any more side effects than either of the components. The convenience of a fixed combination may enhance patient compliance. Unfixed combination therapy with latanoprost and other antiglaucoma medications and the fixed combination formulation of latanoprost and timolol provide an effective and safe option for lowering IOP in glaucoma patients.
Adrenergic beta-Antagonists↗
Analysis of mean retinal transit time from fluorescein angiography in human eyes: normal values and reproducibility.
OBJECTIVE: To evaluate three different techniques to quantify retinal blood flow transit times in normal human eyes from fluorescein angiograms. SUBJECTS AND METHODS: Fluorescein angiograms were recorded on two different occasions in 18 normal individuals with a scanning laser ophthalmoscope. The angiograms were digitized (5 frames per second) and the images were aligned. Mean transit times (MTT) were analysed with a newly developed technique based on an impulse-response analysis (MTTIR) and again with the conventional technique (MTTSLOPE). Arterio-venous passage times (AVP) were also calculated. RESULTS: At the first determination, mean values (SD) for MTTIR, MTTSLOPE, and AVP were 3.22 (0.78), 4.88 (1.86), and 1.46 (0.57) seconds, respectively. Detection of an increase of 25% with a power of 80% requires groups of 12, 86 and 17 individuals for the three techniques, respectively. CONCLUSIONS: Mean transit time is a well-defined physiological parameter. The technique based on impulse-response analysis allows for analysis of even badly defined dye curves. We found this technique to be superior to the conventional technique in terms of reproducibility.
Adult↗
Measurement of ocular blood flow.
Many of these techniques have been adapted to investigate hemodynamic alterations, not only in glaucoma, but in diverse disorders such as diabetic retinopathy, macular degeneration, retinal dystrophies, and nonglaucomatous optic neuropathies. However, each of these techniques has limitations and there is not a single methods that provides comprehensive measurements for all the ocular tissues. Our enhanced understanding of ocular vascular anatomy has helped to direct our hemodynamic investigations of the various vascular beds within the eye. However, many of the techniques have lacked validation (reproducibility and accuracy) prior to clinical implementation. Understanding the limitations and the theoretical assumptions of each of these techniques will allow more prudent application in the clinical arena in the future.
Blood Flow Velocity↗
The effect on intraocular pressure of latanoprost once or four times daily.
AIMS: To compare the effect on intraocular pressure (IOP) of latanoprost applied once daily with four times daily and to study if the difference persisted when treatment changed to once daily. METHODS: IOP was followed in 28 healthy volunteers in a double masked randomised 52 day study. Latanoprost 50 microg/ml was administered once daily in one eye and four times daily in the other during 2 weeks. Subsequently both eyes received one daily drop for 2 weeks. After another 3 weeks without treatment, a single drop was instilled in each eye. RESULTS: The IOP reduction on days 2 and 3 was greater in the eyes treated with four daily doses (p<0.01). During the following period there were no statistically significant differences between the eyes. After 3 weeks without treatment the IOP was lower than pretreatment (p<0.001). A single dose of latanoprost on day 50 resulted in a similar decrease in IOP in both eyes. Transient photophobia, mild flare, and/or a few cells occurred in 15 subjects. Two subjects were withdrawn because of photophobia and/or signs of anterior uveitis. CONCLUSION: Latanoprost four times daily caused an IOP reducing effect which was similar to once daily dosing, except for the first 2 days of treatment when it was more effective. Transient photophobia, cells, and flare were common during the four dose regimen, but resolved spontaneously without cessation of treatment.
Adult↗
Should antiproliferatives be used in filtering surgery of normal tension glaucoma?
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Antineoplastic Agents↗
Comparison of retinal transit times and retinal blood flow: a study in monkeys.
PURPOSE: To determine the correlation between transit times of retinal blood flow calculated from fluorescein angiograms and retinal blood flow determined by the microsphere method. METHODS: Two fluorescein angiograms were obtained in each eye of six monkeys, followed by determination of retinal blood flow with labeled microspheres. Angiograms in 10 eyes were analyzed for mean transit time (MTT) and arteriovenous passage time (AVP). MTT was determined in two ways: from dye curves reconstructed by extrapolation of semilogarithmic plots of the recorded curves (MTT(slope)) and by a new technique based on an impulse-response analysis (MTT(ir)). RESULTS: Mean values (+/-SD) for retinal blood flow in 10 eyes were 23.2 +/- 6.9 mg/min. Corresponding values for MTT(ir), MTT(slope), and AVP were 2.22 +/- 0.38, 4.89 +/- 5.89, and 1.08 +/- 0.14 seconds. There was a weak, but not statistically significant, correlation between retinal blood flow and MTT(ir) (r = -0.60, P = 0.06) but no useful correlation between retinal blood flow and either MTT(slope) or AVP. CONCLUSIONS: The relationship between retinal blood flow and transit times determined from fluorescein angiograms is weak. Of the three transit parameters tested, MTT(ir), determined with the recently developed impulse-response technique, had the best correlation with retinal blood flow. Further studies are needed to determine the ability of these transit parameters to detect a change in retinal blood flow and the possibility that transit times may provide useful clinical information unrelated to absolute values of retinal blood flow.
Animals↗
Ocular blood flow and retinal metabolism in abyssinian cats with hereditary retinal degeneration.
PURPOSE: To investigate if retinal blood flow decreases with progression of the disease in Abyssinian cats with progressive retinal atrophy (PRA), to examine if the choroidal blood flow was affected by the disease, and to determine the uptake of glucose and formation of lactate in the outer retina. METHODS: Local blood flow in different parts of the eye was determined with radioactive microspheres, in 9 normal cats and in 10 cats at different stages of PRA. Three blood flow determinations were made in each animal, during control conditions, after IV administration of indomethacin and after subsequent administration of N(omega)-nitro-L-arginine (L-NA). Blood samples from a choroidal vein and a femoral artery were collected to determine the retinal formation of lactate and uptake of glucose. RESULTS: In Abyssinian cats with PRA (n = 10), the retinal blood flow was significantly (P < or = 0.01) lower than in normal cats (n = 9) during control conditions, 6.4 +/- 1.7 compared with 14.1 +/- 1.9 g min(-1) x (100 g)(-1). The vascular resistance in the iris and ciliary body was significantly higher in the cats at a late stage of PRA, both compared with normal cats and to cats at an early stage of the disease, whereas the choroidal vascular resistance was not significantly affected. Indomethacin had no effect on ocular blood flows in normal cats, but in cats with PRA, iridal blood flow was more than doubled after indomethacin. The retinal formation of lactate was significantly (P < or = 0.001) lower in cats with PRA than in normal cats, 0.111 +/- 0.035 (n = 8) compared with 0.318 +/- 0.024 (n = 8) micromol x min(-1). The uptake of glucose was not significantly different in cats with PRA. CONCLUSIONS: Retinal blood flow is severely decreased in Abyssinian cats at a late stage of retinal degeneration, whereas the choroidal microcirculation is not significantly affected by the disease. At a late stage of retinal degeneration, vascular resistance in the iris is significantly increased, which at least in part could be caused by cyxlooxygenase products.
Animals↗
Acetylsalicylic acid does not reduce the intraocular pressure variation in ocular hypertension or glaucoma.
The purpose of this study was to measure if intraocular pressure (IOP) and IOP variations in patients with ocular hypertension and glaucoma are decreased by acetylsalicylic acid (ASA). The hypothesis to be tested was that short-term fluctuations in the IOP are caused by breaks of the inner wall of Schlemm's canal that are repaired by platelets inducing a cycle of breaks and repair. Furthermore, prostaglandins affect uveoscleral outflow and ASA inhibits prostaglandin biosynthesis and platelet aggregation. This implies that ASA may have complex effects on the IOP and its variations.In 28 patients with ocular hypertension or glaucoma the IOP was measured seven times during 2 hr on two succeeding days. Five hundred mg ASA or placebo was administrated orally in a masked fashion 15 hr prior to the second session. After wash-out, this procedure was repeated with a cross-over design. The same study outline was used in 28 glaucoma patients except for the cross-over design. There were no statistically significant differences in the mean IOP or in the IOP variations between the placebo treated and the ASA treated eyes in either group, and there were no significant differences between the day before and after treatment in any group. The results suggest that ASA does not affect IOP variations in a clinically significant way and that a single dose of ASA has no significant effect on mean IOP.
Aged↗
Latanoprost: experience of 2-year treatment in Scandinavia.
PURPOSE: The aim of the study was to assess efficacy and side effects of latanoprost during two years of treatment. METHODS: 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. RESULTS: 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<0.005). 46 patients were withdrawn from the study, mostly due to increased iris pigmentation or an iris color with known high risk of developing increased pigmentation. 22 patients developed increased pigmentation of the iris. The follow-up revealed no previously unknown ocular or systemic side effects. CONCLUSION: Once daily applications of latanoprost cause a marked and sustained reduction of the IOP. The only clinically significant side effect noted was the increased pigmentation of the iris, most frequently seen in irides with a mixture of brown and blue/gray or green colors. No systemic side effect was observed.
Adrenergic beta-Antagonists↗
Retinopathy in diabetic patients aged 15-50 years in the county of Umeå, Sweden.
PURPOSE: To examine the prevalence of diabetic retinopathy and its relation to certain risk factors (glycosylated hemoglobin, blood pressure, serum creatinine, proteinuria, smoking) in a population-based study on a specific age-group of patients with diabetes mellitus in the county of Umeå, Sweden. METHODS: All diabetic patients aged 15-50 years living in the county of Umeå were invited to the study. A standard clinical and eye examination was performed, and seven-field stereoscopic photographs were taken of each eye. Blood and urine samples were collected. Univariate and multivariate statistical analyses were performed. RESULTS: Of the eligible 395 patients 285 (91%) participated in the study. 285 patients (79%) had diabetes mellitus type 1, 71 (20%) subjects had diabetes mellitus type 2, and 3 patients (1%) had secondary diabetes. In the statistical analysis performed on patients with type 1 diabetes mellitus, duration, presence of hypertension, systolic blood pressure, plasma glucose, glycosylated hemoglobin, serum creatinine, proteinuria and smoking all were significantly related to increasing degree of retinopathy when a univariate model was applied. However, when a multivariate analysis was performed only duration, proteinuria, glycosylated hemoglobin and male gender were statistically significantly associated with severeness of retinopathy. CONCLUSION: Increased duration of diabetes, inadequate metabolic control as measured by glycosylated hemoglobin, proteinuria and male gender are factors that are associated with a higher incidence of diabetic retinopathy in diabetes mellitus type 1.
Adolescent↗
The association of hyperlipidemia with retinopathy in diabetic patients aged 15-50 years in the county of Umeå.
PURPOSE: To study possible associations between serum lipid levels and degree of retinopathy in a population-based study on a specific age-group of patients with diabetes mellitus in the county of Umeå, Sweden. METHODS: All patients with diabetes mellitus aged 15-50 years living in the county of Umeå were invited to the study. The participating subjects had a standard clinical examination and an eye examination performed. Seven-field stereoscopic photographs were taken of each eye, and the photos were sent to Grading Center, Hammersmith Hospital, London, U.K. for grading of the retinopathy. Blood samples were drawn for analysis of lipoprotein(a), high density lipoprotein (HDL) cholesterol, cholesterol and triglycerides. Univariate and multivariate statistical analyses were performed. RESULTS: In the present study only patients with type 1 diabetes mellitus were included, and 285 of the invited 308 diabetic subjects (93%) took part. When univariate analysis was applied we found statistically significant associations between higher lipoprotein(a) levels, higher triglyceride levels, higher cholesterol levels, lower HDL cholesterol/total cholesterol ratios and increasing severeness of retinopathy. However, in the multivariate analysis triglyceride levels lost their importance while all other significant associations were still present. CONCLUSION: Associations were found between higher levels of serum total cholesterol, declining ratios of high density lipoprotein (HDL) cholesterol/total cholesterol, higher levels of serum lipoprotein(a) and more severe retinopathy in diabetes mellitus type 1. No such association was found between serum triglycerides and degree of retinopathy.
Adolescent↗
Prostaglandin analogues in the treatment of glaucoma.
Prostaglandin (PG) analogues are a new class of ocular hypotensive drugs that have been developed for the treatment of open angle glaucoma. Two of these drugs, latanoprost and unoprostone, are presently commercially available. Latanoprost was introduced in 1996 in the US and Europe. Presently it enjoys the most widespread use and is the most well documented drug of this group. It reduces the intraocular pressure (IOP) by a mechanism of action different from other drugs; namely by increasing the uveoscleral outflow. The aqueous inflow is not affected. The optimal dose regimen is one drop of 50 microg/ml once daily, which reduces the IOP by approximately 30% in patients with glaucoma. A more pronounced ocular hypotensive effect is demonstrated when latanoprost is combined with other glaucoma therapies, including beta-blockers, adrenergic and cholinergic agonists or carbonic anhydrase inhibitors. Latanoprost is well tolerated. The drug reaches a plasma concentration below that needed for stimulation of the FP-receptor, which may explain its favourable systemic tolerability profile. The major ocular adverse effect is increased iris pigmentation, which is due to increased synthesis of melanin in the melanocytes of the iris stroma. It is most frequently seen in green-brown eyes and it is probably permanent. A low frequency of cystoid macular oedema has also been reported, predominantly in predisposed eyes. Unoprostone was launched in Japan in 1994, but there is little experience with this drug outside the Japanese market and the documentation is more limited. Its main mechanism of action is on outflow, but this is not yet fully elucidated. The recommended dosage regimen is 1 drop of 1.2 mg/ml twice daily. No comparative studies in humans between the 2 drugs have yet been published.
Animals↗
Aqueous humor flow in human eyes treated with dorzolamide and different doses of acetazolamide.
OBJECTIVE: To measure the effect of topically applied 2% dorzolamide hydrochloride (Trusopt, Merck & Co Inc, Whitehouse Station, NJ) and different doses of orally administered acetazolamide (Diamox, Lederle Ophthalmic Pharmaceuticals, Pearl River, NY), alone and in combination, on aqueous humor flow. DESIGN: A randomized, double-masked, placebo-controlled study of 20 human subjects was carried out. Aqueous humor flow was measured by clearance of topically applied fluorescein. Serum standard bicarbonate and serum acetazolamide levels were analyzed. RESULTS: Treatment with dorzolamide reduced aqueous flow by 17%, and a maximum dose of acetazolamide alone reduced flow by 29%. Increasing doses of acetazolamide alone gradually decreased flow, while small doses of acetazolamide did not suppress flow further when dorzolamide was already applied topically. Serum acetazolamide concentrations rose with increasing doses of acetazolamide. Serum standard bicarbonate levels were all in the normal range. CONCLUSIONS: Treatment with dorzolamide reduced aqueous humor flow statistically significantly (2.50 microL/min vs 3.00 microL/min; P=.001) compared with placebo, but less than a maximum dose ofacetazolamide. Small doses of acetazolamide added to dorzolamide treatment did not further enhance the decrease in flow. Since there was no metabolic acidosis as measured by plasma levels of standard bicarbonate, the decrease in aqueous flow could be attributed to the direct action of the carbonic anhydrase inhibitors on the carbonic anhydrase enzymes. It is concluded that the smaller effect of dorzolamide, as compared with acetazolamide, is due to insufficient inhibition of at least 1 of the 2 carbonic anhydrase isozymes involved in aqueous humor production.
Acetazolamide↗
Prostaglandin derivates as ocular hypotensive agents.
Low doses of naturally occurring prostaglandins reduce the intraocular pressure (IOP) in many species. Species differences do occur both in terms of efficiency and mechanism of action, and also among the different prostaglandins. Among the prostaglandins mainly PGF2 alpha has been tested in human eyes. Although it is an effective ocular hypotensive drug it is not clinically useful due to pronounced ocular side-effects, mainly conjunctival hyperemia and irritation, at doses that produce a maximal effect on IOP. Modification of the drug has resulted in two analogues that are now in clinical use, latanoprost and unoprostone. In long-term studies latanoprost, when applied as a once-daily dose of a 0.005% concentration, reduces IOP at least as effectively as adrenergic beta-receptor blockers. The reduction of IOP is due to increased outflow. This takes place mainly, or exclusively, through the uveoscleral routes, thus introducing a new pharmacological principle for the treatment of glaucoma. The drug reaches systemic concentrations that are below the level expected to stimulate FP-receptors outside the eye and it is rapidly eliminated with a half-life in plasma of 17 minutes, which explains why the clinical trials have not revealed any systemic side-effects with latanoprost. The most frequent side-effect observed with latanoprost is an increased pigmentation of the iris mainly in eyes with irides that are already partly brown. This effect is seen with several naturally occurring prostaglandins and is due to stimulation of melanin production in the melanocytes of the iridial stroma. No structural changes of the melanocytes have been observed in studies performed both in vivo and in vitro. The mechanism of action for unoprostone is the same as for latanoprost. No effect on iris colour has been reported for unoprostone but so far there is limited experience with the drug in eyes with a mixed iris colour.
Adrenergic Agonists↗
One year of prospective follow-up after carotid thrombendarterectomy--a clinical and duplex study.
OBJECTIVES: The aim of this study was to make a prospective evaluation of the carotid arteries after thrombendarterectomy by combined clinical and duplex examination, to define an exact time of development of postoperative restenosis/occlusion and to relate early morphological changes to occurrences of new neurological events. MATERIAL AND METHODS: Sixty-four patients (66 operations), 48 men and 16 women, mean age of 63+/-8 (SD) years, with transient ischaemic attacks or minor stroke were examined clinically 1 day before and after the carotid surgery. All except 3 patients had stenosis > or =50%. Duplex scanning and periorbital Doppler were performed before aortic arch angiography, within 2 weeks after operation and thereafter at 3, 6 and 12 months. RESULTS: 10 patients experienced minor stroke and one major stroke after operation, in 5 patients connected with occlusion on the operated side, which differed (P<0.01) from 56 patients with open vessels in whom 6 ipsilateral minor strokes occurred. Four of 6 patients with minor stroke, in whom the operated vessels were open, recovered, whereas the neurological deficits were permanent in all 5 patients with occlusion (P<0.05). Duplex scanning confirmed 10 new occlusions and 2 high grade stenoses >75% postoperatively. Persisting morbidity was 11% and no mortality at 3 months' control. At 12 months' control, 1 patient had stroke related to preoperatively diagnosed occlusion on the non-operated side and 14 flow reducing lesions >75% (11 occlusions and 3 stenoses >75%) were found in 57 (24.6%) of examined vessels. CONCLUSION: occlusion occurs in immediate postoperative period and seems to be a serious complication connected with significantly higher number of persistent neurological events than open vessels.
Aged↗