Improving the therapeutic index of topical phenylephrine by reducing drop volume

This study examined the effect of reducing eyedrop volume on the efficacy and systemic absorption of a given quantity of phenylephrine hydrochloride. Aqueous phenylephrine hydrochloride (2.5%) given in the commercially available drop volume of 32 microliters was compared with 10% aqueous phenylephrine given in an 8-microliters volume. Both preparations contained the same total amount of phenylephrine per drop. Ten subjects had both eyes dilated with each of the phenylephrine solutions according to a randomized, double-crossover sequence. The mean final pupillary diameter was nearly 1.0 mm larger for the 8-microliters drop (P = 0.0033). Nine of ten subjects achieved a larger pupillary diameter with the 8-microliters drop. Systemic absorption, as measured by plasma phenylephrine level, was similar for the two drop volumes. Thus, the 8-microliters drop achieved a significantly larger pupillary dilation without an increase in systemic absorption. Phenylephrine may have the most favorable risk-benefit ratio when administered as a high concentration in a small volume.     

A comparison of the short-term hypotensive effects and side effects of unilateral brimonidine and apraclonidine in patients with elevated intraocular pressure

PURPOSE: To compare the short-term ocular hypotensive efficacy and side effects of 0.2% brimonidine and 0.5% apraclonidine in patients with elevated intraocular pressure (IOP). METHODS: We performed a double-masked, placebo-controlled study to compare the efficacy of the application of 0.2% brimonidine and 0.5% apraclonidine for the effect of IOP, systemic blood pressure and heart rate in 20 newly diagnosed ocular hypertensive patients. Effects on the untreated fellow eye and ocular side effects were also determined. All measurements were performed 1, 2, 4, 6 and 8 h after the instillation of one drop. RESULTS: Brimonidine and apraclonidine significantly reduced IOP from baseline at all observation times. No significant difference was observed between the treatment groups. IOP decreased significantly in the untreated fellow eye in the brimonidine group at 4-, 6- and 8-hour checks and at 6-hour checks in the apraclonidine group when compared with placebo. Blood pressure and heart rate decreased significantly in the brimonidine group compared with placebo. Apraclonidine did not affect blood pressure or heart rate any differently than placebo. The pupil diameter and the interpalpebral fissure width significantly increased in the apraclonidine group, but not in the brimonidine group. There were no significant differences in the overall incidence of foreign body sensation, burning and stinging and dry mouth in the treatment groups. CONCLUSIONS: In the short-term, brimonidine was effective in reducing IOP in patients with elevated IOP and was equivalent in efficacy to apraclonidine. On the other hand, a significant change in blood pressure and heart rate was observed with brimonidine; there was no change at all in the apraclonidine group.     

Additive effect of 1% apraclonidine hydrochloride to nonselective beta-blockers.

The short-term additive effect and side effects of adding 1% apraclonidine hydrochloride to nonselective beta-blockers were investigated in 21 patients with ocular hypertension or early primary open-angle glaucoma. After a unilateral single dose application of topical 1% apraclonidine hydrochloride, intraocular pressure (IOP), heart rate, and interpalpebral distance were measured. The mean IOP of treated eyes showed a decline from a baseline of 20.0 +/- 3.0 mmHg to 18.1 +/- 3.2 mmHg at 1 hour (P less than 0.005), 16.5 +/- 2.6 mmHg at 2 hours (P less than 0.001), 15.2 +/- 2.5 mmHg at 3 hours (P less than 0.001), 18.5 +/- 3.0 mmHg at 12 hours (P = 0.02), and 19.2 +/- 2.9 mmHg at 24 hours (P = 0.2). No statistically significant change in the heart rate was seen. The interpalpebral distance of the treated eyes showed a significant increase (P less than 0.05) at all time intervals except 24 hours (P = 0.17). The authors conclude that 1% apraclonidine hydrochloride provides an additive pressure-lowering effect to nonselective beta-blockers for at least 12 hours after a single application, and shows promise as a useful adjunctive agent for short-term use in glaucoma therapy.     

Morphologic and physiologic effects of artificial tear formulations on corneal epithelial derived cells.

The biological effects of four commercially available artificial tear formulations were evaluated using sensitive in vitro techniques. Two of the formulations contained ingredients implicated in cell damage; the other two products were not chemically preserved, and their components have not been reported to damage corneal tissue. We assayed the effects of these formulations on viability, morphology, and physiology in corneal cell (SIRC) cultures. Their effect on the hydration of excised rabbit corneas was also determined. In all formulations, cell viability declined with time relative to control cells, but the time course varied significantly. Viability remained at 100% for 6 h in an unpreserved carboxymethylcellulose-based product (CMC-U), and decreased to 50% after greater than 16 hours. Viability decreased to 50% in 3 h for the other unpreserved, polyvinyl alcohol-based product (PVA-U), and in 1 h for a hydroxypropylmethylcellulose formulation (HPMC-P) that contains edetate disodium (EDTA). Cells in a preserved formulation (PVA-P), using polyvinyl alcohol as the polymer and containing EDTA and benzalkonium chloride (BAK), failed to survive even 15 min of treatment. Overall, cells treated with the unpreserved products were nearly indistinguishable from those in the control solution with respect to morphology, electrophysiology, and corneal hydration. Also, the relative ranking from least to most deleterious (control less than CMC-U less than PVA-U less than HPMC-P less than PVA-P) was consistent across several measures. Of the preserved formulations, HPMC-P, which contains the chelating agent EDTA as an additive, was less damaging than was PVA-P, which contains two chemicals, EDTA and BAK, that reportedly damage cells.     

Adjunctive glaucoma therapy. A comparison of apraclonidine to dipivefrin when added to timolol maleate

The authors compared the additive intraocular pressure (IOP)-lowering effects of two different topical medications, apraclonidine hydrochloride and dipivefrin hydrochloride, when used in conjunction with timolol maleate. Eighteen patients with elevated IOPs entered a randomized, double-masked, cross-over study. Each used apraclonidine 1.0%, dipivefrin 0.1%, or placebo, twice daily for 3 weeks each, in addition to timolol 0.5% twice daily. Only apraclonidine produced a significant additional IOP lowering over timolol treatment alone at all time intervals (P less than 0.001). Its additive effect was significantly greater than that seen with dipivefrin at all time intervals (P less than 0.01), with the exception of day 22 (P = 0.061). No significant change in pulse rate or blood pressure was seen during apraclonidine administration. Apraclonidine may be a useful adjunctive agent in patients with poorly controlled glaucoma.     

Apraclonidine 0.5% versus brimonidine 0.2% for the control of intraocular pressure elevation following anterior segment laser procedures

BACKGROUND AND OBJECTIVE: Both apraclonidine hydrochloride 0.5% and brimonidine tartrate 0.5% are potent alpha-2 agonists, effective in controlling the intraocular pressure (IOP) rise following argon laser trabeculoplasty (ALT). Brimonidine has recently become available commercially as a 0.2% solution. Our goal in this study was to compare the efficacy and side effect profile of 0.2% brimonidine to that of 0.5% apraclonidine in the prevention of IOP spikes following anterior segment laser procedures. PATIENTS AND METHODS: Patients undergoing argon laser trabeculoplasty, Nd:Yag peripheral iridectomy or posterior capsulotomy were prospectively randomized to receive either apraclonidine 0.5% or brimonidine 0.2%, approximately 10 minutes prior to laser surgery. Intraocular pressure was measured by a masked observer, using Goldmann applanation tonometry, before and 1 hour after the treatment. RESULTS: 51 ALTs, 21 peripheral iridectomies, and 13 posterior capsulotomies were performed. The incidence of an IOP rise greater than 5 mmHg was 3/43 (7.0%) in the brimonidine group and 0/42 (0%) in the apraclonidine group (P = 0.08, chi-squared). There were no IOP elevations greater than 8 mmHg. All IOP rises of greater than 5 mmHg occurred in the ALT sub-group, and within this sub-group, the mean change in IOP from pre- to post-op was -4.00 +/- 5.87 in the brimonidine group versus -4.29 +/- 3.86 in the apraclonidine group (P = 0.84). There was a statistically significant decrease in IOP from baseline in both drug groups (P < .0001). CONCLUSIONS: Both drugs are highly effective in controlling IOP spikes following anterior segment laser procedures. There is a tendency toward higher risk of IOP rise following argon laser trabeculoplasty with 0.2% brimonidine as compared to 0.5% apraclonidine, however, this was not statistically significant.     

Effect of apraclonidine hydrochloride on acute introacular pressure rise after argon laser iridotomy.

To determine the effect of apraclonidine hydrochloride on the acute intraocular pressure (IOP) rise after argon laser iridotomy (ALI), a double-masked comparative study was carried out. Twenty-nine eyes (20 patients) with angle-closure glaucoma underwent ALI. Eighteen eyes were treated with apraclonidine, and the remainder received a placebo 1 hour before and immediately after ALI. The mean IOP increase in the apraclonidine group was lower than that in the placebo group at each postlaser interval (p less than 0.01). Although the average value of the maximal increases of IOP after ALI in the apraclonidine group was 4 mmHg, that in the placebo group was 16 mmHg. In the placebo group, 27.3% (3 out of 11 eyes) experienced an IOP rise greater than or equal to 10 mmHg. However, that kind of IOP rise was not found in the apraclonidine group (0 out of 18 eyes) (p less than 0.01). Ocular or systemic side effects were not found in a series of examinations in both groups. Therefore, apraclonidine proved to be effective in lowering the IOP rise after ALI.     

Control of intraocular pressure with apraclonidine hydrochloride after cataract extraction

We conducted a randomly assigned, double-masked, controlled clinical trial to assess the efficacy of 1% apraclonidine hydrochloride in controlling postoperative intraocular pressure increases in patients undergoing extracapsular cataract extraction. Apraclonidine hydrochloride was given either one hour preoperatively or immediately after uncomplicated, extracapsular cataract extraction with posterior chamber intraocular lens implantation and compared with artificial tears given immediately postoperatively. Those who received apraclonidine hydrochloride preoperatively had significantly lower mean intraocular pressure at the first postoperative reading (P = .0005). After preoperative and postoperative apraclonidine hydrochloride, the mean early postoperative intraocular pressure was 19.8 mm Hg and 32.0 mm Hg, respectively, and 27.6 mm Hg after artificial tears. No patient who received preoperative apraclonidine hydrochloride had an intraocular pressure increase to 30 mm Hg or higher postoperatively. Nine of 20 patients (45%) who received postoperative apraclonidine hydrochloride and eight of 18 patients (44%) who received postoperative artificial tears had an increase of intraocular pressure to 30 mm Hg or higher in the early postoperative period. These differences were also highly significant (P = .0005).     

Brimonidine 0.15% versus apraclonidine 0.5% for prevention of intraocular pressure elevation after anterior segment laser surgery

PURPOSE: To compare the efficacy and safety of brimonidine 0.15% with those of apraclonidine 0.5% in preventing intraocular pressure (IOP) elevations after anterior segment laser surgery. SETTING: Massachusetts Eye and Ear Infirmary, Glaucoma Service, Boston, Massachusetts, USA. METHODS: This double-masked randomized trial 80 eyes of 80 patients who had laser peripheral iridotomy, argon laser trabeculoplasty, or neodymium:YAG laser capsulotomy. Eyes received 1 drop of brimonidine 0.15% or apraclonidine 0.5% before laser surgery. Intraocular pressure, heart rate, and blood pressure were measured before laser surgery and at 1 hour, 3 hours, 24 hours, and 1 week after laser surgery. RESULTS: Before laser treatment, 41 patients received brimonidine 0.15% and 39 received apraclonidine 0.5%. Thirteen (31.7%) patients in the brimonidine group and 11 (28.2%) in the apraclonidine group had postoperative IOP elevations of 5 mm Hg or more (P = .5). Four patients (9.8%) in the brimonidine group and 3 (7.7%) in the apraclonidine group had IOP increases of 10 mm Hg or more (P = .5). There were no statistically significant changes in mean heart rate or blood pressure in either group except a slight reduction in diastolic blood pressure at 1 hour in the brimonidine group (-4.7 +/- 9.2 mm Hg) compared with that in the apraclonidine group (-0.1 +/- 9.1 mm Hg) (P = .01). No clinically significant side effects were noted in either group. CONCLUSION: A single preoperative drop of brimonidine 0.15% had similar efficacy and safety as apraclonidine 0.5% in preventing IOP elevations immediately after anterior segment laser surgery.     

Brimonidine 0.2% versus apraclonidine 0.5% for prevention of intraocular pressure elevations after anterior segment laser surgery

OBJECTIVE: To compare the efficacy of brimonidine 0.2% with apraclonidine 0.5% in preventing intraocular pressure (IOP) elevations after anterior segment laser surgery. DESIGN: Double-masked, randomized clinical trial. PARTICIPANTS: Sixty-six patients underwent either laser peripheral iridotomy, argon laser trabeculoplasty, or neodymium:yttrium-aluminum-garnet laser capsulotomy. INTERVENTION: Eyes received either one drop of brimonidine 0.2% or apraclonidine 0.5% before laser surgery. MAIN OUTCOME MEASURES: Intraocular pressure, heart rate, and blood pressure were measured before laser surgery and at 1 hour, 3 hours, 24 hours, and 1 week after laser surgery. RESULTS: Before the laser treatment, 33 patients (50.0%) received brimonidine 0.2% and 33 patients (50.0%) received apraclonidine 0.5%. Eight of 33 patients (24.2%) in the brimonidine-treated group and 9 of 33 patients (27.3%) in the apraclonidine group had postoperative IOP increases of 5 mmHg or more. This was not statistically different (P = 0.80). By the time of last follow-up examination, 3 of 33 patients (9.1%) in the brimonidine-treated group and 3 of 33 patients (9.1%) in the apraclonidine group had IOP increases of 10 mmHg or more. This was also not statistically different (P > or = 0.95). The mean IOP reduction from baseline in the brimonidine group (-2.8 +/- 2.8 mmHg) was not statistically different (P = 0.55) compared with the mean IOP reduction in the apraclonidine group (-3.6 +/- 3.3 mmHg). There were no statistically significant changes in mean heart rate or blood pressure in either group except for a slight reduction in diastolic blood pressure at 1 hour (P = 0.005) in the brimonidine group (-5.2 +/- 7.4 mmHg) compared with the apraclonidine group (-0.2 +/- 6.4 mmHg). There were no clinically significant side effects noted in either group. CONCLUSIONS: A single preoperative drop of brimonidine 0.2% is as effective as apraclonidine 0.5% in preventing IOP elevation immediately after anterior segment laser surgery.     

Effect of 0.5% apraclonidine on ptosis in Horner syndrome

To demonstrate the effect of apraclonidine on anisocoria and ptosis in Horner syndrome, one drop of 0.5% apraclonidine was instilled in both eyes of 3 patients who presented with acute Horner syndrome, and the effect on ptosis and anisocoria was documented. As reported in the literature, one drop of 0.5% apraclonidine reverses the anisocoria of Horner syndrome. In addition, 0.5% apraclonidine leads to a complete resolution of the ptosis associated with Horner syndrome, a finding reported once in the literature. Apraclonidine is a safe and readily available alternative to cocaine for the diagnosis of Horner syndrome.     

Apraclonidine and clonidine: a comparison of efficacy and side effects in normal and ocular hypertensive volunteers

We performed a prospective, randomized double blind study comparing the cardiovascular and intraocular pressure (IOP) effects of unilateral therapy with clonidine 0.125% and apraclonidine hydrochloride 1.0% in 15 normal and 15 ocular hypertensive volunteers. Baseline values were obtained prior to instillation. One drop of test medication (clonidine, apraclonidine or placebo) was instilled unilaterally, and the postinstillation measurements were taken at 1, 2, 4, 6 and 8 hours. Apraclonidine 1% produced a maximum 31.4%±6.9% (4.83±1.17mmHg) decrease in mean IOP in ocular normotensive volunteers and 33.9%±6.9% (10.10±2.45 mmHg) in ocular hypertensive patients (p<0.001).These values were 22.1%±6.9% (2.90±1.94 mmHg) and 22.7%±6.9 (6.80±2.31 mmHg), respectively in clonidine group (p<0.001).In apraclonidine group, there were no changes in contralateral IOP, blood pressure or pulse rate. Clonidine produced a significant decrease in contralateral IOP, but this reduction was not statistically significantly different than that of placebo. In clonidine group, there was no change in pulse rate, but a significant decrease in blood pressure.Eyelid retraction, conjunctival blanching and mydriasis were noted in eyes treated with apraclonidine. However there were no statistically and clinically significant changes in pupil size or interpalpebral fissure width with clonidine.This study suggests that apraclonidine appears to be safer and more effective ocular hypotensive agent than clonidine in treatment of glaucoma.     

阿普可乐定防止Nd：YAG激光虹膜切除术后眼压升高

目的 了解阿普可乐定是否有效降低棕色虹膜人种激光肛膜切除术后眼压急性升高。方法 ４８只原发性闭角型青光眼,按年龄、性别进行匹配,分为治疗组和对照组。治疗组术前１小时和术后即刻滴用１％阿普可乐定,对照组滴用安慰剂。术后０．５、１．０、１．５、２．０、３．５小时观察眼压和其他情况。结果 激光治疗后,治疗组和对照组眼压最大升高值分别为０．６２±０．６７ｋＰａ（１ｋＰａ＝７．５ｍｍＨｇ）和１．１３±０．８     

Optic nerve vasomotor effects of topical apraclonidine hydrochloride.

AIMS: To examine, in vivo, the anterior optic nerve vasomotor effects of chronic apraclonidine hydrochloride in rabbits. METHODS: After local treatment in one randomly chosen eye with apraclonidine hydrochloride 0.5% over 21 days, the microvasculature of the optic nerve was examined in five rabbits using an intraluminal microvascular corrosion casting technique. The investigators were masked as to which eye was treated. The vasoconstriction near the branching point of arterioles supplying the optic nerve was calculated as a percentage of the downstream vessel calibre. An average constriction was calculated and compared between the treated and the contralateral, untreated, eyes by means of a two tailed t test for paired variables. Constriction values of a total of 72 arterioles supplying the optic nerve were obtained for the five rabbits. RESULTS: The average constriction in the treated and the control eyes was comparable (p = 0.96). CONCLUSION: Chronic administration of apraclonidine hydrochloride 0.5% produces no observable optic nerve vasomotor effects in the rabbit eye.     

Clonidine provides an allergy-free alternative in glaucoma patients with proven allergy to apraclonidine

· Purpose: The aim of this study was to determine allergic responses to clonidine hydrochloride 0.25% in glaucoma patients with proven allergic reaction to apraclonidine 0.5%. · Methods: Fifteen consecutive glaucoma patients with allergic reaction to apraclonidine were prospectively challenged with clonidine hydrochloride 0.25% and evaluated for recurrence of allergic reactions and efficacy of treatment. Intraocular pressure (IOP), conjunctival hyperemia, blood pressure and resting pulse rate were determined at baseline and after 1, 3, 6 and 12 months. · Results: None of the patients developed ocular allergic reaction during 12 months on clonidine therapy. Blood pressure and pulse rate did not change significantly with clonidine treatment. Clonidine caused a significant reduction of IOP from baseline. In one patient, topical clonidine caused fatigue, dizziness and dry mouth. · Conclusion: Clonidine did not cause allergic reaction in patients with proven allergy to apraclonidine, indicating that there is no cross-reactivity with apraclonidine. Due to the small series, however, we cannot assume that allergy will not occur with clonidine 0.25% given time and a larger number of patients. Received: 21 January 1999 Revised: 28 June 1999 Accepted: 29 July 1999     

Effectiveness of apraclonidine 1% in preventing intraocular pressure rise following macular hole surgery

AIM: To determine the efficacy of apraclonidine hydrochloride 1% in preventing intraocular pressure (IOP) spikes following idiopathic macular hole (IMH) surgery with platelet adjunct and intraocular gas tamponade. METHODS: This is a prospective, double masked, randomised study to compare apraclonidine hydrochloride 1%, an alpha(2) agonist, with a placebo in the prevention of IOP rises following macular hole surgery. Each patient was randomly selected to receive either the study drug or the placebo; one drop was instilled in the conjunctival sac 2 hours preoperatively and on completion of the procedure. IOP was measured at baseline and at 1, 3, 6, 24, 48 hours, and 2 weeks postoperatively. Blood pressure and heart rate were also recorded at baseline and at 3 and 24 hours postoperatively. Macular hole repair surgery was performed as standardised in the unit with a vitrectomy, platelet concentrate, and complete fill of the vitreous cavity with perfluoropropane gas (C(3)F(8)) at a concentration of 16%. RESULTS: 25 patients (26 eyes) were enrolled. 12 eyes received apraclonidine hydrochloride 1% (mean age 70.7; range 62-78 years) and 14 eyes received the placebo (mean age 70.0; range 57-81 years). At baseline evaluation the mean IOP was 15.6 mm Hg for the study group and 14.3 mm Hg for the placebo group. The mean postoperative IOP at 1 hour, 3 hours, 6 hours, and 24 hours was 10.6, 9.6, 8.2, and 14.0 mm Hg in the apraclonidine group. In the control group at the same time intervals the mean IOP was 23.4, 17.5, 19.2, and 24.7 mm Hg. These readings were statistically significant different: 1 hour (p=0.0001); 3 hours (p=0.0015); 6 hours (p<0.0001); and 24 hours (p=0.019), the readings at 48 hours and 2 weeks were not statistically significant different (p=0.15 and p=0.59). Only one of the patients in the study group had an IOP above 25 mm Hg at any time. In the control group an IOP above 25 mm Hg was found in seven patients (50%) at the 1 hour postoperative measurement. At 2 weeks the IOP was recorded below 25 mm Hg in all patients. No statistically significantly difference was noted between the two groups regarding the systolic or diastolic blood pressure values and the heart rate records. No local or systemic adverse reactions were observed. CONCLUSIONS: Apraclonidine hydrochloride 1% appears to be an efficacious and safe drug in the prophylaxis of early postoperative IOP elevations in patients undergoing macular hole surgery.     

A limited comparison of apraclonidine's dose response in subjects with normal or increased intraocular pressure

We performed a multicentered, placebo-controlled, randomized, crossover study comparing the efficacy of 0.5% and 1.0% apraclonidine hydrochloride in 15 normal volunteers and 17 subjects with increased intraocular pressure. Apraclonidine 1% produced a maximum 30.4% +/- 14.0% (4.7 +/- 2.4 mm Hg) decrease in mean intraocular pressure in normal eyes and a 31.3% +/- 16.5% (7.6 +/- 4.2 mm Hg) decrease in eyes with increased pressure. Apraclonidine 0.5% produced a maximum 25.8% +/- 9.7% (4.0 +/- 1.7 mm Hg) decrease in mean intraocular pressure in normal eyes and a 27.4% +/- 16.0% (6.8 +/- 4.5 mm Hg) decrease in eyes with increased pressure. There was no statistically significant difference in mean percent intraocular pressure lowering effect between the 0.5% and 1.0% apraclonidine concentrations. Most subjects treated with apraclonidine had a greater than or equal to 20% reduction in intraocular pressure from baseline. Twelve hours after instillation of apraclonidine, nine of the normal volunteers had an intraocular pressure of 10 mm Hg or less. Apraclonidine produced the same percent intraocular pressure decrease regardless of the initial level of intraocular pressure.     

Long-term brimonidine therapy in glaucoma patients with apraclonidine allergy

PURPOSE: To report the use of brimonidine in patients with a documented ocular allergy to apraclonidine. METHODS: We conducted a prospective, open-label study on the use of long-term brimonidine therapy in 57 patients with chronic glaucoma with documented allergy to apraclonidine. The study patients were placed on brimonidine tartrate 0.2%, 1 drop three times daily in one or both eyes, either as additive therapy to a medical regimen devoid of apraclonidine for further lowering of intraocular pressure (25 patients) or as a replacement for apraclonidine at the time of diagnosis of apraclonidine ocular allergy for maintenance of intraocular pressure control (32 patients). Clinical symptoms and signs of ocular allergy to brimonidine were monitored for up to 18 months. RESULTS: During the treatment period of up to 18 months, six (10.5%) of 57 patients developed slit-lamp biomicroscopic findings and subjective symptoms of an ocular allergic reaction that led to discontinuation of brimonidine treatment. All six patients developed ocular allergy to topical brimonidine 0.2% during the first 4 months of therapy. The addition of brimonidine 0.2% topical medication or the replacement of apraclonidine with brimonidine resulted in a significant decrease in mean intraocular pressure from 20.5+/-5.3 to 16.5+/-4.2 mm Hg (P < .0001) at the mean treatment period of 10.6+/-4.6 months (range, 0.5 to 18.0 months in all 57 patients: 5 to 18 months in the 51 patients without brimonidine allergy and 0.5 to 3.8 months in the six patients who developed brimonidine allergy. CONCLUSIONS: The incidence of ocular allergy after the use of brimonidine 0.2% topical medication for up to 18 months was 10.5% in patients with a documented history of apraclonidine allergy. Therefore, it is generally safe as well as efficacious to administer brimonidine to patients with an ocular allergy to apraclonidine.     

Preventing intraocular pressure increase after phacoemulsification and the role of perioperative apraclonidine

PURPOSE: To evaluate the effectiveness of prophylactic topical apraclonidine 1% in preventing an intraocular pressure (IOP) rise in the early period after uneventful phacoemulsification with intraocular lens (IOL) implantation. SETTING: District general hospital, United Kingdom. METHODS: In this prospective masked randomized trial, 61 patients had elective, routine, corneal tunnel, sutureless phacoemulsification with in-the-bag foldable IOL implantation. A single surgeon operated on all the patients. Patients were randomized to receive topical apraclonidine 1% eyedrops (n = 31) or artificial tears (control group, n = 30) 1 hour preoperatively and at the end of the surgery. An observer masked to the perioperative drops used measured the IOP preoperatively and 3 to 6 hours and 16 to 24 hours postoperatively. The primary outcome was the change in IOP between the baseline and the 2 postoperative intervals. The IOP changes within and between the groups were analyzed using the t test and chi-square test. RESULTS: The changes between the postoperative and preoperative IOPs in the study groups were statistically significant (apraclonidine, P = 0.018 and P = 0.007, respectively; artificial tears, P = 0.028 and P = 0.023, respectively; paired t test). There was no significant difference in the postoperative IOP between the apraclonidine and control groups 3 to 6 hours and 16 to 24 hours postoperatively (P = 0.717 and P = 0.497, respectively; independent t test). The mean difference was 0.2 mm Hg (95% confidence interval [CI], -3.4 to 3.1) in the apraclonidine group and 2.2 mm Hg (95% CI, -2.5 to 7.0) in the control group. In each group, a few patients had an IOP greater than 30 mm Hg in the first 24 hours. CONCLUSION: Prophylactic topical perioperative apraclonidine 1% did not cause a significant reduction in the postoperative IOP when compared with a control group.     

Efficacy of apraclonidine 1% versus pilocarpine 4% for prophylaxis of intraocular pressure spike after argon laser trabeculoplasty.

OBJECTIVE: The authors compared the efficacy of apraclonidine 1% versus pilocarpine 4% prophylaxis of post-argon laser trabeculoplasty (ALT) intraocular pressure (IOP) spike. DESIGN: Prospective randomized clinical trial. PARTICIPANTS: Two hundred twenty-eight eyes of 228 patients with primary open-angle glaucoma undergoing ALT were studied. INTERVENTION: Patients were given 1 drop of either apraclonidine 1% (n = 114) or pilocarpine 4% (n = 114) 15 minutes before ALT. MAIN OUTCOME MEASURES: Peri-ALT IOPs and incidences of post-ALT IOP spikes at 5 minutes, 1 hour, and 24 hours were compared between the two groups. RESULTS: The two groups were similar in age, race, and medical dependency. Post-ALT mean IOPs at 5 minutes, 1 hour, and 24 hours were significantly lower than pre-ALT mean IOPs in both apraclonidine (P < 0.001) and pilocarpine (P < 0.001) groups. Incidences of IOP spikes greater than 1, 3, and 5 mmHg at 1 hour post-ALT were 21.1%, 14.9%, and 8.8% for the apraclonidine group and 12.3%, 5.3%, and 4.4% for the pilocarpine group (P = 0.076, 0.015, and 0.18 chi-square test). In the apraclonidine prophylaxis group, patients on long-term apraclonidine showed significantly higher incidence of post-ALT IOP spike than the patients without such long-term apraclonidine use (35.7%, 15 of 42 eyes, vs. 12.5%, 9 of 72 eyes; P = 0.003). In addition, peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy but without statistical significance (17.4%, 8 of 46 eyes, vs. 9.4%, 6 of 64 eyes; P = 0.17). CONCLUSION: Peri-ALT pilocarpine 4% was at least as effective as, if not more effective than, apraclonidine 1% in post-ALT IOP spike prophylaxis. Peri-ALT apraclonidine prophylaxis was not effective in patients on long-term apraclonidine, and peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy. Pilocarpine 4% can be considered as a first-choice drug for post-ALT IOP spike prophylaxis, especially in patients under treatment with apraclonidine.