Effects of topical mydriatics and vasoconstrictors on prostaglandin-E2-induced aqueous flare elevation in pigmented rabbits

We evaluated the effects of topical instillation of mydriatics and vasoconstrictors on prostaglandin E2 (PGE2) induced aqueous flare elevation in pigmented rabbits. Transcorneal diffusion of PGE2 (25 microg/ml) by means of a glass cylinder produced aqueous flare elevation. Mydriatics (atropine sulfate, tropicamide, tropicamide plus phenylephrine hydrochloride, phenylephrine hydrochloride, and cyclopentolate hydrochloride) or vasoconstrictors (naphazoline nitrate and tramazoline hydrochloride) were topically administered before PGE2 application. Aqueous flare was measured with a laser flare-cell meter. One or two instillations of atropine sulfate 1.0%, tropicamide 0.4%, tropicamide 0.5% plus phenylephrine hydrochloride 0.5%, phenylephrine hydrochloride 5.0%, cyclopentrate hydrochloride 1.0%, and naphazoline nitrate 0.05% did not inhibit PGE2-induced aqueous flare elevation. Tramazoline hydrochloride 0.118% inhibited significantly (p < 0.05) PGE2-induced aqueous flare elevation. It is possible that vasoconstriction may be involved partly in inhibition of PGE2-induced aqueous flare elevation by some drugs in pigmented rabbits.     

Effect of topical iganidipine on experimental elevation of aqueous flare induced by prostaglandin E(2) and EP agonists in pigmented rabbits

We evaluated the role of topical iganidipine on experimental aqueous flare elevation in rabbits. Transcorneal diffusion of prostaglandin E(2) (PGE(2)), 25 microg/ml or 7.09 x 10(-2) mmol/l, or highly selective agonists for prostaglandin E(2) receptor subtypes (EP), 25 microg/ml, was achieved with the use of a glass cylinder to produce aqueous flare elevation in pigmented rabbits. Iganidipine was topically administered before application of PGE(2) or EP agonists. Aqueous flare was measured with a laser flare cell meter. Topical instillation of 0.1% iganidipine once or twice inhibited 64 +/- 8% (p < 0.01) and 84 +/- 9% (p < 0.01) of PGE(2)-induced aqueous flare elevation, respectively. Two instillations of 0.1% iganidipine inhibited 95 +/- 5% (p < 0.01) of EP2-agonist(ONO-AE1-259-01)-induced flare elevation and 98 +/- 3% (p < 0.01) of EP4-agonist(ONO-AE1-392)-induced flare rise. Topical iganidipine may have anti-inflammatory activity in the eye.     

Effects of topical instillation of traditional herbal medicines,herbal extracts,and their components on prostaglandin E2-induced aqueous flare elevation in pigmented rabbits

PURPOSE: To evaluate the effect of topical instillation of traditional herbal medicines, herbal extracts, and their components on the elevation of aqueous flare induced by prostaglandin E(2) (PGE(2)) in pigmented rabbits. METHODS: Transcorneal diffusion of 25 micro g/mL of PGE(2) was carried out through a glass cylinder placed on the cornea to induce aqueous flare elevation in pigmented rabbits. Traditional herbal medicines, herbal extracts, and their components were topically instilled before the PGE(2) application. Aqueous flare was measured with a laser flare-cell meter. RESULTS: Two instillations, 60 and 30 minutes before PGE(2), of Kakkon-to, Sairei-to, Orengedoku-to, Senkanmeimoku-to, Scutellariae radix extract, Coptidis rhizoma extract, Gardeniae fructus extract, Phellodendri cortex extract, baicalein, baicalin, wogonin, crocetin, berberine, or glycyrrhizine did not inhibit the elevation induced by PGE(2). Two instillations, 60 and 30 minutes before PGE(2), of a Ligusticum wallichii extract (100 mg/mL) inhibited the elevation by 20%. Two instillations (5 and 3 hours before PGE(2)) of baicalein (1 mg/mL) or baicalin (5 mg/mL) inhibited the elevation by 16% and 24%, respectively. Two instillations, 5 and 3 hours before PGE(2), of wogonin, crocetin, berberine, or glycyrrhizine did not inhibit the elevation. CONCLUSION: Two instillations of Ligusticum wallichii extract 60 and 30 minutes before the PGE(2), and two instillations of baicalein or baicalin, 5 and 3 hours before the PGE(2), inhibited the PGE(2)-induced aqueous flare elevation in pigmented rabbits.     

Effect of topical betaxolol on acute rise of aqueous flare induced by prostaglandin E(2) in pigmented rabbits.

PURPOSE: To evaluate the effects of topical betaxolol on experimental ocular inflammation. METHODS: Transcorneal diffusion of 25 microg/mL (7.09 x 10(-2) mmol/L) of prostaglandin E(2) (PGE(2)), placed in a glass cylinder, was employed to induce aqueous flare elevation in pigmented rabbits. Betaxolol was administered topically before PGE(2) application. Aqueous flare was measured with a laser flare cell meter. RESULTS: Four-, two-, and one-time topical instillations of betaxolol inhibited the PGE(2)-induced aqueous flare elevation by 44% +/- 8%, 32 +/- 7%, and 8 +/- 6%(mean +/- SD), respectively. The inhibition of flare elevation was dependent on the number of betaxolol instillations. CONCLUSION: Topical betaxolol has an inhibitory effect on PGE(2)-induced aqueous flare elevation in rabbit eyes.     

Effect of topical betaxolol on the acute rise of aqueous flare induced by highly selective agonists for prostaglandin E2 receptor subtypes in pigmented rabbits

PURPOSE: To evaluate the role of topical betaxolol on experimental ocular inflammation in rabbits. METHOD: Transcorneal diffusion of highly selective agonists for prostaglandin E2 receptor subtypes (EP), 25 microg/ml, with the use of a glass cylinder, was performed to produce aqueous flare elevation in pigmented rabbits. Betaxolol was topically administered before EP agonist application. Aqueous flare was measured with a laser flare cell meter. RESULTS: Performing topical instillation of 0.5% betaxolol 4 times inhibited 52 +/- 9% of EP2-agonist (ONO-AE1-259-01)-induced aqueous flare elevation. The inhibition of flare elevation was dependent on the number of betaxolol instillations. Betaxolol did not suppress the elevation induced by an EP4 agonist (ONO-AE1-392). CONCLUSION: Betaxolol inhibited EP2-agonist-induced aqueous flare elevation in pigmented rabbits.     

Effects of isopropyl unoprostone, latanoprost, and prostaglandin E(2) on acute rise of aqueous flare in pigmented rabbits

PURPOSE: To evaluate the effect of isopropyl unoprostone, latanoprost, and prostaglandin E(2) (PGE(2)) on aqueous flare elevation. METHODS: Isopropyl unoprostone (0.12%) or latanoprost (0.005%) was topically instilled. Transcorneal diffusion of PGE(2), 25 microg/ml, using a glass cylinder, was achieved in pigmented rabbits. Aqueous flare was measured with a laser flare cell meter. RESULTS: Topical instillation of isopropyl unoprostone induced aqueous flare elevation in rabbit eyes. Also, topical isopropyl unoprostone additionally induced aqueous flare elevation in eyes with transcorneal diffusion of PGE(2). Latanoprost did not induce flare elevation. CONCLUSION: Isopropyl unoprostone induced aqueous flare elevation in rabbits, and latanoprost did not produce aqueous flare elevation.     

Effects of topical corticosteroids and nonsteroidal anti-inflammatory drugs on prostaglandin e2-induced aqueous flare elevation in pigmented rabbits

We evaluated the effects of anti-inflammatory potency of corticosteroids and nonsteroidal anti-inflammatory drugs on prostaglandin E2 (PGE2)-induced aqueous flare elevation in pigmented rabbits. Transcorneal diffusion of PGE2, 25 microg/ml (7.09 x 10(-2) mmol/l), with the use of a glass cylinder was achieved to produce aqueous flare elevation. Anti-inflammatory drugs were topically administered once before PGE2 application. Aqueous flare was measured with a laser flare-cell meter. Topical single instillation of dexamethasone sodium metasulfobenzoate 0.1%, dexamethasone sodium phosphate 0.1%, and fluorometholone 0.1% 6 h before PGE2 application inhibited 56, 59, and 43% of flare elevation, respectively. Topical single instillation of bromfenac sodium 0.1% and pranoprofen 0.1% 1 h before PGE2 application inhibited 33 and 15% of flare elevation, respectively. Indomethacin 0.5% did not inhibit flare elevation. Corticosteroid eyedrops needed several hours from topical instillation to exhibit inhibition of flare elevation. Most nonsteroidal anti-inflammatory drug eyedrops inhibited aqueous flare elevation when instilled 1 h before PGE2 application.     

Effects of topical clonidine on prostaglandin-E(2)-induced aqueous flare elevation in pigmented rabbits

We evaluated the role of topical clonidine on experimental ocular inflammation. Transcorneal diffusion of prostaglandin (PG) E(2), 7. 09 x 10(-2) mmol/l, with the use of a glass cylinder was employed to produce aqueous flare elevation in pigmented rabbits. Clonidine was topically administered and yohimbine was injected intravenously. Aqueous flare was measured with a laser flare cell meter. Topical instillation of 0.25% clonidine inhibited 89% of PGE(2)-induced aqueous flare elevation. Instillation of clonidine at 60 or 30 min before and 10 min after PGE(2) inhibited flare significantly. Pretreatment with intravenous yohimbine decreased the clonidine-induced inhibition of the flare elevation in a dose-dependent manner. It is possible that the anti-inflammatory action of topical clonidine may be mediated partly by alpha(2)-receptors.     

Effects of intravenous administration of FR122047 (a selective cyclooxygenase 1 inhibitor) and FR188582 (a selective cyclooxygenase 2 inhibitor) on prostaglandin-E2-induced aqueous flare elevation in pigmented rabbits

PURPOSE: Two isoforms of cyclooxygenase (COX-1 and COX-2) exist. To determine in vivo effects of the intravenous administration of FR122047 (a selective COX-1 inhibitor), FR188582 (a selective COX-2 inhibitor), diclofenac sodium or dexamethasone phosphate disodium on prostaglandin-E2 (PGE2)-induced aqueous flare elevation and mRNA levels for COX-1 and COX-2 in pigmented rabbits. METHODS: To produce aqueous flare elevation in rabbits, PGE2, 25 microg/ml, was applied to the cornea with the use of a glass cylinder. FR122047, FR188582, diclofenac sodium or dexamethasone phosphate disodium was intravenously injected before PGE2 application. Aqueous flare was measured with a laser flare-cell meter. The mRNA levels for COX-1 and COX-2 in the iris-ciliary body were determined by real-time polymerase chain reaction. RESULTS: FR122047, FR188582 and diclofenac sodium (15 micromol/kg each) injected intravenously 30 min before PGE2 application inhibited 29 +/- 5, 40 +/- 12 and 50 +/- 9% of aqueous flare elevation, respectively. Simultaneous injection of FR122047 (15 micromol/kg) and FR188582 (15 micromol/kg) 30 min before PGE2 application inhibited 61 +/- 8% of flare elevation. Dexamethasone phosphate disodium (15 micromol/kg) injected intravenously 300 min before PGE2 application inhibited 68 +/- 8% of aqueous flare elevation. Less than 3-fold changes in mRNA levels for COX-1 and COX-2 in the iris-ciliary body were noted after PGE2, FR122047, FR188582, diclofenac sodium or dexamethasone phosphate disodium treatment. CONCLUSION: It is possible that enzyme activities of both COX-1 and COX-2 may be involved in the mechanism of PGE2-induced aqueous flare elevation in pigmented rabbits.     

Effects of scutellariae radix extract and its components (baicalein, baicalin, and wogonin) on the experimental elevation of aqueous flare in pigmented rabbits

PURPOSE: To evaluate the possible inhibitory effects of hot water extract of Scutellariae radix and its major components (baicalein, baicalin, and wogonin) on experimental elevation of aqueous flare in pigmented rabbits. METHODS: To produce aqueous flare elevation in rabbits, prostaglandin E(2) (PGE(2)), 25 microg/mL, was applied to the cornea with the use of a glass cylinder, or lipopolysaccharides (LPS), 0.5 microg/kg, were injected into an ear vein. Animals were pretreated by the oral administration of 150 g/day of food containing 0.02%, 0.07%, or 0.2% (w/w) extract of Scutellariae radix for 5 days, or by intravenous injection of baicalein, baicalin, or wogonin, 60 microg/kg or 600 microg/kg, 30 minutes before experimental uveitis was induced. Aqueous flare was measured with a laser flare-cell meter. Aqueous flare intensity was expressed as the area under the curve (AUC) in arbitrary units. RESULTS: The AUC of PGE(2)- and LPS-induced aqueous flare elevation was 1,343 and 5,066 arbitrary units, respectively. Pretreatment by oral administration of 0.07% or 0.2% extract of Scutellariae radix did not inhibit PGE(2)-induced aqueous flare elevation (AUC: 1,252 and 1,210, respectively), but it did inhibit LPS-induced aqueous flare elevation (AUC: 2,248 and 1,973, respectively). Pretreatment by intravenous injection of 600 microg/kg of baicalein, baicalin, or wogonin inhibited LPS-induced aqueous flare elevation (AUC: 2,289, 2,163, and 1,509, respectively). Pretreatment with 60 microg/kg of wogonin also inhibited LPS-induced aqueous flare elevation (AUC: 1,980). CONCLUSION: Hot water extract of Scutellariae radix may have an inhibitory effect on experimental anterior uveitis induced by LPS in pigmented rabbits.     

Effects of tetramethylpyrazine on prostaglandin E(2)- and prostaglandin E(2) receptor agonist-induced disruption of blood-aqueous barrier in pigmented rabbits

PURPOSE: To evaluate the effect of tetramethylpyrazine on the elevation of aqueous flare and intraocular pressure (IOP) induced by prostaglandin (PG) E(2) and PGE(2) receptor (EP) agonists. METHODS: PGE(2) or EP agonists (11-deoxy PGE(1), EP(2) agonist; 17-phenyl trinor PGE(2), EP(1) and EP(3) agonist; or sulprostone, EP(1) and EP(3) agonist), 25 microg/mL, were transcorneally administered to pigmented rabbits. Animals were pretreated with tetramethylpyrazine intravenously (10 or 30 mg/kg) or topically (0.1% solution). Aqueous flare was measured using a laser flare-cell meter, and the intensity was expressed as the area under the curve (AUC). Intraocular pressure was measured using a noncontact tonometer. RESULTS: After administration of PGE(2), aqueous flare and IOP increased and then gradually decreased. The AUC of eyes pretreated with tetramethylpyrazine, 10 or 30 mg/kg, intravenously, or topical 0.1% solution, was significantly smaller than that of the controls. The mean Delta IOP of eyes pretreated with tetramethylpyrazine, 30 mg/kg intravenously, was significantly lower than that of the controls. After administration of 11-deoxy PGE(1), aqueous flare increased and then gradually decreased. 17-phenyl trinor PGE(2) and sulprostone did not disrupt the blood-aqueous barrier. The AUC of eyes pretreated with tetramethylpyrazine, 10 or 30 mg/kg, intravenously, before 11-deoxy PGE(1) application was significantly smaller than that of the controls. CONCLUSION: The results indicated that tetramethylpyrazine inhibited PGE(2)- or 11-deoxy PGE(1)-induced elevation of aqueous flare and IOP.     

Effects of Kakkon-to and Sairei-to on experimental elevation of aqueous flare in pigmented rabbits.

PURPOSE: To evaluate the possible inhibitory effects of Kakkon-to and Sairei-to, traditional Sino-Japanese herbal medicines, on experimental aqueous flare elevation in pigmented rabbits. METHODS: Anterior uveitis was induced either by an application of prostaglandin E2 (PGE2), 10 microg/mL, to the cornea, or an intravenous injection of lipopolysaccharides (LPS), 0.5 microg/kg, in an ear vein. Dose dependency of experimental uveitis induced by LPS (0.1, 0.25, 0.5, or 1.0 microg/kg) was also determined. For pretreatment, about 150 g/day of food containing Kakkon-to (1% w/w) or Sairei-to (0.6% or 2% w/w) was given to two groups of animals for 5 days before experimental uveitis was induced. A third group of animals underwent pretreatment with betamethasone, 130 microg/kg, injection into an ear vein 4 hours before experimental uveitis was induced. A fourth group of rabbits with no herbal medicine or betamethasone pretreatment served as controls. Aqueous flare was measured using a laser flare-cell meter. Aqueous flare intensity was expressed as the area under the curve (AUC) in arbitrary units. RESULTS: The increase in aqueous flare induced by LPS was dose-dependent. The AUC of PGE2 (10 microg/mL) and LPS (0.5 microg/mL) induced aqueous flare elevations were 1,119 and 4,950 arbitrary units, respectively. Kakkon-to (AUC, 1,055) and Sairei-to (AUC, 965) did not inhibit the aqueous flare elevation induced by PGE2. Beta-methasone did inhibit the elevation (AUC, 271). Kakkon-to (AUC, 4,495) did not suppress the aqueous flare elevation induced by LPS. Both 0.6% and 2% Sairei-to (AUC, 2,478, and 978) and beta-methasone (AUC, 443) did suppress the aqueous flare elevation induced by LPS significantly (P < .05). CONCLUSION: Sairei-to could have an inhibitory effect on experimental anterior uveitis induced by LPS.     

Effects of alpha(2)-adrenergic agonists on lipopolysaccharide-induced aqueous flare elevation in pigmented rabbits

PURPOSE: To evaluate the effects of the alpha(2)-adrenergic agonists (clonidine, apraclonidine, and guanfacine) on lipopolysaccharide (LPS)-induced aqueous flare elevation in pigmented rabbits. METHODS: Anterior uveitis was induced with an intravenous injection of LPS (0.5 microg/kg) in an ear vein. The reproducibility of experimental uveitis induced by LPS (0.5 microg/kg) was also determined. Clonidine (0.01, 0.05, 0.25, or 1%), apraclonidine (1%), or guanfacine (1%) was topically instilled in the right eye 30 and 5 minutes before and 30 minutes after LPS application (N = 6 animals, respectively). Clonidine (0.25%) was topically administered three times at 30-minute intervals from 240 or 120 minutes before, or 120 or 240 minutes after LPS application (N = 6 animals, respectively). Then 1 mg/kg of yohimbine was injected into an ear vein 30 minutes before each topical three-time instillation of clonidine 1%, apraclonidine 1% or guanfacine 1% (N = 6 animals, respectively). Aqueous flare was measured with a laser flare-cell meter. Aqueous flare elevation was expressed as the area under the curve (AUC) in arbitrary units. Rabbits received the first LPS intravenous injection, and the control values of the AUC were obtained. Three months later, the alpha(2)-agonist and the second LPS administration were given to the same animals. RESULTS: The AUCs (5,184 +/- 1,255 units) after the first application of LPS were similar to those (5,033 +/- 1,290) after the second application 3 months after the first administration. Topical instillation of clonidine inhibited LPS-induced aqueous flare elevation in a dose-dependent manner (0.01-0.25%). Topical instillation of clonidine 1%, apraclonidine 1% or guanfacine 1% inhibited LPS-induced aqueous flare elevation by 98 +/- 2.0% (mean +/- SD), 86 +/- 14% and 94 +/- 5.7%, respectively. Pretreatment with intravenous yohimbine prevented the inhibitory effect on flare elevation induced by each agent. CONCLUSION: The present findings suggested that topical instillation of some alpha(2)-agonists may have an inhibitory effect on ocular inflammation, which is mediated in part by alpha(2)-receptors.     

Effect of topical epinephrine on permeability of blood-aqueous barrier in human eyes.

The time-course of changes in the effects of topical epinephrine on the aqueous flow and the coefficient of protein entry into the anterior chamber (k(in)) were determined in 12 normal human subjects. Before and after instillation of 1.25% epinephrine in one eye, protein concentration in the anterior chamber (Ca) was determined from aqueous flare intensity using the laser flare-cell meter, and aqueous flow rate was determined by fluorophotometry. The k(in) was calculated from the Ca, plasma protein concentration, and aqueous flow rate. A single instillation of epinephrine affected neither the Ca nor the aqueous flow rate significantly. The calculated value of the k(in) showed no significant changes at any time of determination, which implied that a single instillation of epinephrine is insufficient to affect the permeability of the blood-aqueous barrier to plasma protein in the normal human eye.     

Ocular hypotensive effects of cholinergic and adrenergic drugs may be influenced by prostaglandins E2 in the human and rabbit eye

PURPOSE: Increased PGE2 production by the iris and ciliary body regulate intraocular pressure (IOP) in vivo. Various cholinergic and adrenergic compounds are traditionally used as antiglaucoma drugs, and their effect on IOP reduction is antagonised by cyclooxygenase inhibitors, indicating a role for eicosanoids in their hypotensive activity. One of the most potent antiglaucoma drugs, PG2 alpha (Latanoprost), reduces IOP by increasing uveoscleral outflow and also increases PGE2 production by the iris and ciliary body in vivo. We investigated whether cholinergic and adrenergic antiglaucoma drugs induce the production of prostaglandin E2 (PGE2) in vitro by: 1) the iris-ciliary body (ICB) of rabbits and, 2) irises of glaucoma patients. METHODS: Pilocarpine 2%, epinephrine 1% and echothiophate iodide 0.125% were applied topically to both eyes of Albino rabbits. Control groups were treated with the corresponding vehicles, or untreated completely. Human iris specimens were obtained from nine untreated cataract eyes, and five eyes under antiglaucoma medication undergoing surgery. PGE2 were determined by a radioimmunoassay. RESULTS: PGE2 production by the ICB of treated rabbits in vitro was twice that of vehicle-treated or untreated rabbit eyes (p<0.001, for either group). In vitro PGE2 production by treated glaucoma patients' irises was three times higher (p<0.001) than in cataract control patients. CONCLUSIONS: The study found an increase in in vitro production of PGE2 by the irises of eyes treated with cholinergic and adrenergic antiglaucoma medications. This suggests a role for endogenous PG production in the hypotensive effect of both classes of drug.     

Cardiovascular effects of epinephrine and dipivefrin in patients using timolol: a single-dose study

Timolol and epinephrine may have cardiovascular effects when used alone topically. These drugs are partial pharmacologic antagonists at the adrenergic beta-receptor. When a placebo, 2% epinephrine hydrochloride or 0.1% dipivefrin hydrochloride was instilled in a randomized, double-blind fashion in eyes treated with timolol maleate no change in heart rate, intraocular pressure or rate of aqueous outflow was noted. The systolic blood pressure did not increase, but with epinephrine a slight increase in diastolic blood pressure was noted. Moreover, cardiac arrhythmias appeared after the use of epinephrine. The pupil enlarged after the instillation of epinephrine or dipivefrin.     

Repetitive instillation of 0.1% cyclosporin A eye drops induces miosis and anterior chamber inflammation-like reactions in monkey eyes

PURPOSE: Miosis and anterior chamber inflammation-like reactions were recognized after six instillations of 0.1% cyclosporin A eye drops every 30 minutes into rabbit conjunctival sacs. In order to consider species specificity, 0.1% cyclosporin A eye drops were applied by the same method in monkeys. METHODS: Eye drops were applied in five monkeys (monkey A, B, C, D, E); in one eye as control and in nine eyes with 0.1% cyclosporin A. We investigated the changes of pupil diameter, intraocular pressure, and anterior chamber flare before and after applying the eye drops. We also examined the effect on ocular tissue histopathologically. RESULTS: Miosis was recognized in six eyes, but no significant intraocular pressure change was observed in any eyes. In both eyes of monkey A anterior chamber flare increased significantly, and flare increased slightly in both eyes of monkeys B, C, and D. On the other hand, there was no change in either eye of monkey E, including the control eye. Localized necrosis of nonpigmented ciliary epithelium was recognized at the beginning of the ciliary process in both eyes of monkey A. Mild cystoid degeneration of nonpigmented ciliary epithelium was seen at the beginning of the ciliary process in the right eye of monkey C, and in the left eye of monkey D. CONCLUSION: No species specificity can be recognized in monkeys from the fact that there is the selective destruction of nonpigmented epithelium at the beginning of the ciliary process after repeated instillation of 0.1% cyclosporin A eye drops, although there was a difference in miosis and anterior chamber inflammation-like reaction in individual monkeys.     

Effects of dipivefrin and pilocarpine on pupil diameter, automated perimetry and LogMAR acuity

· Background: A study was carried out to ascertain, in ophthalmologically normal subjects, the short-term effects of dipivefrin hydrochloride 0.1% on visual performance and make comparisons with pilocarpine. · Methods: Twelve normal volunteers aged 20–26 years attended on three occasions. One eye, randomly selected, received one drop of either pilocarpine 2%, dipivefrin or saline 0.9%. High- and low-contrast LogMAR acuity at 6 m and pupil diameter (measured by infra-red pupillometry) were recorded at baseline (T0) and at intervals up to 90 min following instillation of drops. Program 30-2 of the Humphrey Visual Field Analyzer (HFA) was run at T0 and at 60 min after treatment instillation (T60). Saline was always instilled at visit 1, to allow for learning effects. On visits 2 and 3 either pilocarpine or dipivefrin was randomly instilled into the treated eye. · Results: Pilocarpine significantly worsened the field global indices mean deviation (P<0.001) and pattern standard deviation (P<0.01) compared with T0. There was no significant change with dipivefrin. A significant (P=0.01) pupil dilation from 5.44 mm (SD 0.79) at T0 to 6.19 mm (SD 1.09) at T90 occurred with dipivefrin. Pilocarpine caused significant miosis. No significant changes in LogMAR values were found with dipivefrin. Pilocarpine significantly (P<0.01) increased LogMAR values (i.e. reduced acuity) compared with dipivefrin. At T30 the mean increase in LogMAR was 0.76 (SD 0.30) for high and 0.83 (SD 0.11) for low contrast. By T90 recovery of acuity was virtually complete. · Conclusions: In normals dipivefrin causes mydriasis but does not affect the central visual field global indices (as assessed by STATPAC), or high- and low-contrast LogMAR acuity. Pilocarpine adversely affects the visual field and both measures of acuity. Knowledge of these effects is of value in glaucoma therapy and when monitoring the progression of visual loss. Received: 20 January 1998 Revised version received: 14 April 1998 Accepted: 4 May 1998     

Effects of nilvadipine, nicardipine and verapamil on acute rise of aqueous flare induced by iris photocoagulation or intravenous lipopolysaccharides in pigmented rabbits

The effects of nilvadipine, nicardipine and verapamil on the acute rise of aqueous flare induced by argon laser photocoagulation of the iris or by intravenous injection of lipopolysaccharides (LPS, 0.5 microg/kg) were investigated in pigmented rabbits. Nilvadipine, nicardipine and verapamil were injected intravenously. Aqueous flare was measured with a laser flare cell meter. Following photocoagulation, aqueous flare increased, reached its maximum at 45-75 min and then decreased. After administration of LPS, aqueous flare increased, reached its maximum at 4 h and then returned to baseline levels at about 24 h. Flare reactions were inhibited by nilvadipine in a dose-dependent manner. The elevations were maximally inhibited by nilvadipine 30 min before photocoagulation or intravenous LPS. Two hundred micrograms per kilogram of nilvadipine inhibited 81% of photocoagulation-induced flare elevation, while the same dose of nicardipine and verapamil inhibited 19 and 9% of the elevation, respectively. The same dose of nilvadipine inhibited 51% of LPS-induced flare elevation, while the same dose of nicardipine and verapamil inhibited 6 and 4% of the elevation, respectively. In conclusion, nilvadipine inhibited the experimental elevation of aqueous flare more effectively than did nicardipine and verapamil.     

Prevalence of ocular symptoms and signs with preserved and preservative free glaucoma medication

AIM: To determine the incidence of ocular toxicity of preservatives with glaucoma medications. METHODS: A prospective epidemiological survey was carried out in 1999 by 249 ophthalmologists on 4107 patients. Ocular symptoms, conjunctiva, cornea, and eyelids were assessed. A chi(2) test was used for differences between preserved eye drops (P) and preservative free eye drops (PF). RESULTS: 84% patients used P, 13% received PF, and 3% a combination of P and PF eye drops. All symptoms were more prevalent with P than with PF drops (p<0.001): discomfort upon instillation (43% versus 17%), and symptoms between instillations such as burning-stinging (40% versus 22%), foreign body sensation (31% versus 14%), dry eye sensation (23% versus 14%), tearing (21% versus 14%), and eyelid itching (18% versus 10%). An increased incidence (>2 times) of ocular signs was seen with P eye drops. The prevalence of signs and symptoms was dose dependent, increasing with the number of P drops. A reduction in the symptoms and signs was observed when patients changed from P to PF eye drops (p<0.001). CONCLUSIONS: Symptoms and signs are less prevalent when PF drops are used. Moreover, most of the adverse reactions induced by P glaucoma medication are reversible after removing preservatives.