Apraclonidine Prophylaxis for Postcycloplegic Intraocular Pressure Spikes RICHARD A. HILL, MD,t DON S. MINCKLER, MD/ MARTHA LEE, PhD,3 DALE K. HEUER, MD,2 GEORGE BAERVELDT, MD,2 JAMES F. MARTONE, MD2
Abstract: A randomized, prospective, double-masked study was undertaken to determine the risk of postcycloplegic intraocular pressure spikes in patients with open-angle glaucoma and to evaluate apraclonidine prophylaxis in minimizing these spikes. Patients were stratified as miotic treated or untreated and each group was randomized to receive either placebo (artificial tears) or apraclonidine in both eyes before instillation of tropicamide. In both the miotic treated and untreated groups that received placebo, there was a high incidence, (37% and 38%, respectively) of clinically significant (~ 6 mmHg) intraocular pressure spikes after instillation of tropicamide. In both the miotic treated and untreated groups, there was a statistically significant difference in postcycloplegic intraocular pressure between the subgroup that received placebo and the group that received apraclonidine prophylaxis (P = 0.003 and P = 0.006, respectively). Additionally, four eyes that received placebo had a spike of over 10 mmHg (range, 12 to 27 mmHg), while only one eye had an increase of greater than 10 mmHg (12 mmHg) in the apraclonidine group. Thus, apraclonidine appears to be a useful agent for minimizing precipitous increases in intraocular pressure after cycloplegia in eyes of open-angle glaucoma patients prone to this complication of cycloplegia. Ophthalmology 1991; 98: 1083-1 086
Many factors influence intraocular pressure (lOP), including mydriasis with cycloplegic agents for the purpose Originally received: January 4, 1991. Revision accepted: March 25, 1991. Department of Ophthalmology. University of California at Irvine College of Medicine, Irvine. 2 Department of Ophthalmology, University of Southern California School of Medicine and the Doheny Eye Institute. Los Angeles. 3 Department of Preventive Medicine, University of Southern California, School of Medicine, Los Angeles. 1
Presented in part at the international symposium "Pharmacology of the Eye," Wurzburg, Germany, November 1990. The authors have no commercial, proprietary, or financial interest (as consultant, reviewer, or evaluator) in apraclonidine or Alcon Surgical. Furthermore, neither the authors' spouses, minor children, or blood relatives living in their households have any financial interest in, nor are the authors aware of any financial interest held by their employers, partners, or business associates in Alcon Surgical. Reprint requests to Richard A. Hill, MD, Department of Ophthalmology, Medical Plaza, University of California Irvine, Irvine, CA, 92717.
of diagnostic examinations. In 2% of a control population, a clinically significant (~ 6 mmHg) elevation in lOP has been detected after dilation with cycloplegic agents. This incidence increases to 23% to 32% in populations with documented open-angle glaucoma,I,2 and may occur in as many as 33% to 50% of patients undergoing strong miotic therapy. 3,4 In the latter group of patients, postcycloplegic lOP spikes can reach extraordinary levels, equivalent to those in acute angle-closure episodes, even though the angles remain open. If the patient has a damaged optic nerve or is currently undergoing maximum medical therapy, the risk of aggravating existing optic nerve damage is presumed to be heightened. Apraclonidine is an alpha-adrenergic agonist that is widely used before and after anterior segment laser procedures as prophylaxis against lOP spikes. 5- 8 Before its recent approval by the United States Food and Drug Administration for this use, it had been proven safe in healthy volunteer subjects who used it continuously for a period of 4 weeks. 9 We have used this agent as an alternative to oral or intravenous hyperosmotic therapy in emergent
1083
OPHTHALMOLOGY
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JULY 1991
Table 1. Open-angle Glaucoma without Miotic therapy
•
VOLUME 98
•
NUMBER 7
situations involving patients with postcycloplegic lOP spikes. The purpose of this study is to evaluate the effect of apraclonidine prophylaxis on the incidence and severity of postcycloplegic lOP spikes in patients with open-angle glaucoma.
vided they: (1) did not have systemic hypotension; (2) were not undergoing monoamine oxidase inhibitor therapy; (3) were not pregnant; (4) were not younger than 18 years old; (5) were willing and able to give informed consent; (6) had not undergone bilateral glaucoma filtering surgery or penetrating keratoplasty; (7) had not undergone argon laser trabeculoplasty; and (8) had no history or findings consistent with angle-closure glaucoma. Eligible patients were stratified initially as miotic treated or not miotic treated. Patients in each group were then randomized to receive placebo (artificial tears) or apraclonidine in both eyes before the instillation oftropicamide. Group 1 consisted of patients with open-angle glaucoma, not undergoing miotic therapy, and were treated with placebo; group 2 consisted of patients with open-angle glaucoma, not undergoing miotic therapy, and were treated prophylactically with apraclonidine; group 3 consisted of patients with open-angle glaucoma, undergoing miotic therapy, and who received placebo; and group 4 consisted of patients with open-angle glaucoma, undergoing miotic therapy, and who received apraclonidine prophylaxis. Additional medication data were collected, including whether a beta-blocker and/or carbonic anhydrase inhibitor also were used by the patient. In groups 3 and 4, fellow eyes not receiving miotic therapy were not included in the study. Goldmann applanation tonometry, as described in the Glaucoma Laser Trial, JO was then performed by a qualified ophthalmic technician. Zeiss gonioscopy (under topical proparacaine anesthesia) was performed by an ophthalmologist, and patients in whom the angles could be occluded (Shaffer grade 2 or narrower) were excluded from the study. The patients were then pretreated with apraclonidine or placebo; this was followed in 10 minutes by both a cycloplegic agent (tropicamide 1%) and a sympathomimetic agent (phenylephrine 2.5%). Treatment with phenylephrine has been shown to have little effect on lOP elevation after mydriasis,4 and the drug was included to mask the effects (vasoconstriction, vasodilation, lid elevation, and mydriasis) of apraclonidine. Intraocular pressure was checked between 1 and 2 hours after cycloplegia induction, and Zeiss gonioscopy was repeated in all patients. For the purpose of this study, a clinically significant rise in lOP was defined as greater than or equal to 6 mmHg. If a clinically hazardous lOP spike occurred, miotics were instilled and other conventional therapy was given.
PATIENTS AND METHODS
RESULTS
Before initiation of this study, approval was obtained from the Human Studies Institutional Review Board Committee of the University of Southern California. Patients with open-angle glaucoma, undergoing or not undergoing miotic therapy, who required the use of mydriatic agents for diagnostic purposes were offered participation in the study. Patients were then entered in the study, pro-
A total of 67 patients were entered into this study. Incomplete data were available on five patients. In eight cases, only one eye was included in the study. Seven of these eyes were fellow eyes of patients receiving miotic therapy in only one eye. One additional patient in this group had undergone unilateral filtration surgery. Data from 62 patients (116 eyes) were ultimately used in the
No. of patients No. of eyes No. of eyes with elevated lOP (;:::6 mmHg) [(P = 0.003); 10 of 26 versus 2 of 32 (chi-square)] No. of spikes over 10 mmHg (range) lOP mmHg change all eyes (mean mmHg ±SO) [P= 0.0001] lOP
Group 1 (Placebo)
Group 2 (Apraclonidine)
Total
13 26
16 32
29 58
10
2
12
4 (12-27) '
1 (12)
6.0 ± 6.4
-0.5 ± 4.8
5
= intraocular pressure; SO = standard deviation. Table 2. Open-angle Glaucoma with Miotic therapy
No. of patients No. of eyes No. of eyes with elevated lOP (;:::6 mmHg) [(P = 0.006); 9 of 25 versus 3 of 33 (chi-square)] No. of spikes over 10 mmHg lOP mmHg change all eyes (mean mmHg ±SO) [P= 0.0001] lOP
1084
Group 3 (Placebo)
Group 4 (Apraclonidine)
Total
15 25
18 33
33 58
9
3
12
5 (10-15)
0
5
3.5 ± 5.0
-2.1 ± 5.4
= intraocular pressure; SO = standard deviation.
HILL et al
•
APRACLONIOINE PROPHYLAXIS
study. Among the 4 groups, group I (no miotic treatment, placebo) had the highest spikes in lOP (21 and 27 mmHg), with 4 patients having lOP increases over 10 mmHg. In group 2 (no miotic treatment, prophylactic apraclonidine), only I patient had a pressure rise of greater than 10 mmHg (12 mmHg). Within the miotic therapy groups, only group 3 (miotic therapy, placebo) had patients (5 individuals), who experienced elevations in lOP greater than 10 mmHg. Clinically significant differences (~ 6 mmHg) in postcycloplegic lOP elevations were seen in groups not receiving miotics (group I versus 2 (P = 0.003]) and in those receiving miotics (group 3 versus 4 [P = 0.006]) (Tables I, 2), with the better results in those patients receiving apraclonidine. The overall lOP changes (group I versus 2 and group 3 versus 4) were statistically significantly different (P = 0.0001), again with the better results in the groups receiving apraclonidine (Tables I, 2).
DISCUSSION The standard of practice for our glaucoma services has been to use 1% tropicamide (usually without 2.5% NeoSynephrine) routinely to dilate the eyes of follow-up or new patients to permit stereoscopic funduscopy, photography, visual field testing, and peripheral retinal examination. In addition, before the initiation of this study, postcycloplegic lOP was not routinely checked on all patients. Neo-Synephrine is never used in patients with anatomically narrow filtration angles. Although Neo-Synephrine alone is a possible alternative to cycloplegic agents, dilation is slower and may not be adequately stable for stereoscopic posterior pole examination. The risk to the patient of any dilating agent should be considered before its use. If the risk of angle closure is judged high, we defer dilation until after an iridectomy has been performed. Apraclonidine is a nonspecific alpha-adrenergic agonist. Although conflicting data and theories exist, the alpha-2 response may lower lOP by an adenyl cyclase-mediated reduction in aqueous production by the ciliary epithelium. II Other theories that have been advanced include a decrease in aqueous humor production secondary to decreased ciliary body blood flow or decreased episcleral venous pressure. 12 ,13 Contradictory findings have been described regarding the effects of apraclonidine on prdstaglandin concentrations and lOP response l4 (Sulewski et al, McCannel et al; unpublished data, presented at the 1990 AR VO Annual Meeting). The onset of action of apraclonidine occurs within I hour, and maximum reduction of lOP occurs 3 to 5 hours after application of a single dose. 8.9 Its use as a prophylactic agent is logical, as its duration of action (12 hours) exceeds that of tropic amide, and it has a low incidence of allergic reactions. s. ls Ocular side effects are limited primarily to transient upper lid elevation (1.3%), conjunctival blanching (0.4%), mydriasis (0.4%), and/or a transient burning or foreign body sensation. IS Congestion (vasodilation) of conjunctival vessels also can occur infrequently.
Apraclonidine may be useful in the acute treatment of any emergent high-pressure glaucoma such as neovascular glaucoma or acute angle-closure glaucoma. 16 Other possible uses include treatment of transient elevation ofIOP after cataract surgery, 17 panretinal photocoagulation, and vitreoretinal surgery. 18 Apraclonidine is an obvious alternative to oral hyperosmotics in the nauseated patient with elevated lOP. Our incidence of clinically significant lOP spikes was somewhat higher than that previously reported by other investigators l ,2 for patients receiving the placebo and no miotic. (10 of 26, 38%) but consistent with previous findings 3,4 for patients receiving placebo plus miotic therapy (9 of 25, 36%). Of the lOP spikes over 10 mmHg, only I (12 mmHg) was encountered in the apraclonidinetreated groups, suggesting that apraclonidine both minimizes the occurrence and blunts the height of these spikes. In the placebo groups, 6 patients had spikes of greater than 10 mmHg (range, 12 to 27 mmHg), 2 of which were greater than 20 mmHg (group 2; 21, 27 mmHg). High (>20 mmHg) lOP spikes can occur with cycloplegia and are believed to be secondary to an acute decrease in outflow facility.19 Within our study population, high lOP spikes (>20 mmHg) were seen in the placebo-treated groups. High lOP spikes induced by cycloplegia may aggravate optic nerve damage in eyes with advanced glaucomatous injury or fragile vascular supply. The data collected on the concurrent use of beta blockers and carbonic anhydrase inhibitors failed to reveal any relationship between the use of these agents and the incidence of postcycloplegic lOP elevations. We suggest, as a clinical routine, that (I) all patients (especially those with glaucoma) have their postcycloplegic lOP measured before being dismissed from the clinic (30 to 60 minutes after cycloplegia), and that (2) prophylaxis with apraclonidine or other agents as appropriate, be given only to glaucoma patients who have previously had documented postcycloplegic lOP spikes before administering cycloplegics for diagnostic purposes.
REFERENCES 1. Harris LS. Cycloplegic-induced intraocular pressure elevations. A study of normal and open-angle glaucomatous eyes. Arch OphthalmoI1968; 79:242-6. 2. Shaw BR, Lewis RA Intraocular pressure elevation after pupillary dilation in open angle glaucoma. Arch Ophthalmol 1986;104: 1185-8. 3. Harris LS, Galin MA Cycloplegic provocative testing: effect of miotic therapy. Arch Ophthalmol1969; 81:544-7. 4. Schimek RA, Lieberman WJ. The influence of Cyclogyl® and Neosynephrine® on tonographic studies of miotic control in open-angle glaucoma. Am J OphthalmoI1961; 51 :781-4. 5. Weinreb RN, Ruderman J, Juster R, Zweig K. Immediate intraocular pressure response to argon laser trabeculoplasty. Am J Ophthalmol 1983; 95:279-86. 6. Hoskins HO Jr, Hetherington J Jr, Minckler OS, et al. Complications of laser trabeculoplasty . Ophthalmology 1983; 90:796-9. 7. Robin AL, Pollack IP, House B, Enger C. Effects of ALO 2145 on
1085
OPHTHALMOLOGY
•
JULY 1991
intraocular pressure following argon laser trabeculoplasty. Arch Ophthalmol1987; 105:646-50. 8. Robin AL, Pollack IP, deFalier JM. Effects of topical ALO 2145 (paminocionidine hydrochloride) on the acute intraocular pressure rise after argon laser iridotomy. Arch Ophthalmol1987; 105:1208-11. 9. Abrams DA, Robin AL, Pollack IP, et al. The safety and efficacy of topical 1% ALO 2145 (p-aminoclonidine hydrochloride) in normal volunteers. Arch Ophthalmol1987; 105:1205-7. 10. Glaucoma Laser Trial Research Group. Handbook. March, 1985. Available from: National Technical Information SeNice. 5285 Port Royal Rd, Springfield, VA 22161. (Accession #PB86-1 01 037-XAB). 11. Gharagozloo NZ, Relf SJ, Brubaker RF. Aqueous flow is reduced by the alpha-adrenergic agonist, apraclonidine hydrochloride (ALO 2145). Ophthalmology 1988; 95:1217-20. 12. Van Buskirk EM, Bacon DR, Fahrenbach WHo Ciliary vasoconstriction after topical adrenergic drugs. Am J Ophthalmolol1990; 109:511-7.
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•
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•
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13. Coleman AL, Robin AL, Pollack IP. Apraclonidine hydrochloride. Ophthalmol Clin North Am 1989; 2:97-108. 14. Camras CB, Podos SM. The role of endogenous prostaglandins in clinically-used and investigational glaucoma therapy. Prog Clin Bioi Res 1989; 312:459-75. 15. Alcon Laboratories package insert: lopidine@> (apraclonidine hydrochloride). 16. Krawitz PL, Podos SM. Use of apraclonidine in the treatment of acute angle-closure glaucoma [letter]: Arch Ophthalmol. 1990; 108: 1208-9. 17. Wiles SB, MacKenzie 0, Ide CH. Control of intraocular pressure with apraclonidine hydrochloride after cataract extraction. Am J Ophthalmol 1991; 111 :184-8. 18. Pulido JS, Mallick KS, Sneed SR, Blodi CF. Apraclonidine hydrochloride in vitreoretinal surgery [letter]. Arch Ophthalmol. 1989; 107:316-7. 19. Galin MA. The mydriasis provocative test. Arch Ophthalmol1961 ; 66: 353-5.
Abstract: A randomized, prospective, double-masked study was undertaken to determine the risk of postcycloplegic intraocular pressure spikes in patients with open-angle glaucoma and to evaluate apraclonidine prophylaxis in minimizing these spikes. Patients were stratified as miotic treated or untreated and each group was randomized to receive either placebo (artificial tears) or apraclonidine in both eyes before instillation of tropicamide. In both the miotic treated and untreated groups that received placebo, there was a high incidence, (37% and 38%, respectively) of clinically significant (~ 6 mmHg) intraocular pressure spikes after instillation of tropicamide. In both the miotic treated and untreated groups, there was a statistically significant difference in postcycloplegic intraocular pressure between the subgroup that received placebo and the group that received apraclonidine prophylaxis (P = 0.003 and P = 0.006, respectively). Additionally, four eyes that received placebo had a spike of over 10 mmHg (range, 12 to 27 mmHg), while only one eye had an increase of greater than 10 mmHg (12 mmHg) in the apraclonidine group. Thus, apraclonidine appears to be a useful agent for minimizing precipitous increases in intraocular pressure after cycloplegia in eyes of open-angle glaucoma patients prone to this complication of cycloplegia. Ophthalmology 1991; 98: 1083-1 086
Many factors influence intraocular pressure (lOP), including mydriasis with cycloplegic agents for the purpose Originally received: January 4, 1991. Revision accepted: March 25, 1991. Department of Ophthalmology. University of California at Irvine College of Medicine, Irvine. 2 Department of Ophthalmology, University of Southern California School of Medicine and the Doheny Eye Institute. Los Angeles. 3 Department of Preventive Medicine, University of Southern California, School of Medicine, Los Angeles. 1
Presented in part at the international symposium "Pharmacology of the Eye," Wurzburg, Germany, November 1990. The authors have no commercial, proprietary, or financial interest (as consultant, reviewer, or evaluator) in apraclonidine or Alcon Surgical. Furthermore, neither the authors' spouses, minor children, or blood relatives living in their households have any financial interest in, nor are the authors aware of any financial interest held by their employers, partners, or business associates in Alcon Surgical. Reprint requests to Richard A. Hill, MD, Department of Ophthalmology, Medical Plaza, University of California Irvine, Irvine, CA, 92717.
of diagnostic examinations. In 2% of a control population, a clinically significant (~ 6 mmHg) elevation in lOP has been detected after dilation with cycloplegic agents. This incidence increases to 23% to 32% in populations with documented open-angle glaucoma,I,2 and may occur in as many as 33% to 50% of patients undergoing strong miotic therapy. 3,4 In the latter group of patients, postcycloplegic lOP spikes can reach extraordinary levels, equivalent to those in acute angle-closure episodes, even though the angles remain open. If the patient has a damaged optic nerve or is currently undergoing maximum medical therapy, the risk of aggravating existing optic nerve damage is presumed to be heightened. Apraclonidine is an alpha-adrenergic agonist that is widely used before and after anterior segment laser procedures as prophylaxis against lOP spikes. 5- 8 Before its recent approval by the United States Food and Drug Administration for this use, it had been proven safe in healthy volunteer subjects who used it continuously for a period of 4 weeks. 9 We have used this agent as an alternative to oral or intravenous hyperosmotic therapy in emergent
1083
OPHTHALMOLOGY
•
JULY 1991
Table 1. Open-angle Glaucoma without Miotic therapy
•
VOLUME 98
•
NUMBER 7
situations involving patients with postcycloplegic lOP spikes. The purpose of this study is to evaluate the effect of apraclonidine prophylaxis on the incidence and severity of postcycloplegic lOP spikes in patients with open-angle glaucoma.
vided they: (1) did not have systemic hypotension; (2) were not undergoing monoamine oxidase inhibitor therapy; (3) were not pregnant; (4) were not younger than 18 years old; (5) were willing and able to give informed consent; (6) had not undergone bilateral glaucoma filtering surgery or penetrating keratoplasty; (7) had not undergone argon laser trabeculoplasty; and (8) had no history or findings consistent with angle-closure glaucoma. Eligible patients were stratified initially as miotic treated or not miotic treated. Patients in each group were then randomized to receive placebo (artificial tears) or apraclonidine in both eyes before the instillation oftropicamide. Group 1 consisted of patients with open-angle glaucoma, not undergoing miotic therapy, and were treated with placebo; group 2 consisted of patients with open-angle glaucoma, not undergoing miotic therapy, and were treated prophylactically with apraclonidine; group 3 consisted of patients with open-angle glaucoma, undergoing miotic therapy, and who received placebo; and group 4 consisted of patients with open-angle glaucoma, undergoing miotic therapy, and who received apraclonidine prophylaxis. Additional medication data were collected, including whether a beta-blocker and/or carbonic anhydrase inhibitor also were used by the patient. In groups 3 and 4, fellow eyes not receiving miotic therapy were not included in the study. Goldmann applanation tonometry, as described in the Glaucoma Laser Trial, JO was then performed by a qualified ophthalmic technician. Zeiss gonioscopy (under topical proparacaine anesthesia) was performed by an ophthalmologist, and patients in whom the angles could be occluded (Shaffer grade 2 or narrower) were excluded from the study. The patients were then pretreated with apraclonidine or placebo; this was followed in 10 minutes by both a cycloplegic agent (tropicamide 1%) and a sympathomimetic agent (phenylephrine 2.5%). Treatment with phenylephrine has been shown to have little effect on lOP elevation after mydriasis,4 and the drug was included to mask the effects (vasoconstriction, vasodilation, lid elevation, and mydriasis) of apraclonidine. Intraocular pressure was checked between 1 and 2 hours after cycloplegia induction, and Zeiss gonioscopy was repeated in all patients. For the purpose of this study, a clinically significant rise in lOP was defined as greater than or equal to 6 mmHg. If a clinically hazardous lOP spike occurred, miotics were instilled and other conventional therapy was given.
PATIENTS AND METHODS
RESULTS
Before initiation of this study, approval was obtained from the Human Studies Institutional Review Board Committee of the University of Southern California. Patients with open-angle glaucoma, undergoing or not undergoing miotic therapy, who required the use of mydriatic agents for diagnostic purposes were offered participation in the study. Patients were then entered in the study, pro-
A total of 67 patients were entered into this study. Incomplete data were available on five patients. In eight cases, only one eye was included in the study. Seven of these eyes were fellow eyes of patients receiving miotic therapy in only one eye. One additional patient in this group had undergone unilateral filtration surgery. Data from 62 patients (116 eyes) were ultimately used in the
No. of patients No. of eyes No. of eyes with elevated lOP (;:::6 mmHg) [(P = 0.003); 10 of 26 versus 2 of 32 (chi-square)] No. of spikes over 10 mmHg (range) lOP mmHg change all eyes (mean mmHg ±SO) [P= 0.0001] lOP
Group 1 (Placebo)
Group 2 (Apraclonidine)
Total
13 26
16 32
29 58
10
2
12
4 (12-27) '
1 (12)
6.0 ± 6.4
-0.5 ± 4.8
5
= intraocular pressure; SO = standard deviation. Table 2. Open-angle Glaucoma with Miotic therapy
No. of patients No. of eyes No. of eyes with elevated lOP (;:::6 mmHg) [(P = 0.006); 9 of 25 versus 3 of 33 (chi-square)] No. of spikes over 10 mmHg lOP mmHg change all eyes (mean mmHg ±SO) [P= 0.0001] lOP
1084
Group 3 (Placebo)
Group 4 (Apraclonidine)
Total
15 25
18 33
33 58
9
3
12
5 (10-15)
0
5
3.5 ± 5.0
-2.1 ± 5.4
= intraocular pressure; SO = standard deviation.
HILL et al
•
APRACLONIOINE PROPHYLAXIS
study. Among the 4 groups, group I (no miotic treatment, placebo) had the highest spikes in lOP (21 and 27 mmHg), with 4 patients having lOP increases over 10 mmHg. In group 2 (no miotic treatment, prophylactic apraclonidine), only I patient had a pressure rise of greater than 10 mmHg (12 mmHg). Within the miotic therapy groups, only group 3 (miotic therapy, placebo) had patients (5 individuals), who experienced elevations in lOP greater than 10 mmHg. Clinically significant differences (~ 6 mmHg) in postcycloplegic lOP elevations were seen in groups not receiving miotics (group I versus 2 (P = 0.003]) and in those receiving miotics (group 3 versus 4 [P = 0.006]) (Tables I, 2), with the better results in those patients receiving apraclonidine. The overall lOP changes (group I versus 2 and group 3 versus 4) were statistically significantly different (P = 0.0001), again with the better results in the groups receiving apraclonidine (Tables I, 2).
DISCUSSION The standard of practice for our glaucoma services has been to use 1% tropicamide (usually without 2.5% NeoSynephrine) routinely to dilate the eyes of follow-up or new patients to permit stereoscopic funduscopy, photography, visual field testing, and peripheral retinal examination. In addition, before the initiation of this study, postcycloplegic lOP was not routinely checked on all patients. Neo-Synephrine is never used in patients with anatomically narrow filtration angles. Although Neo-Synephrine alone is a possible alternative to cycloplegic agents, dilation is slower and may not be adequately stable for stereoscopic posterior pole examination. The risk to the patient of any dilating agent should be considered before its use. If the risk of angle closure is judged high, we defer dilation until after an iridectomy has been performed. Apraclonidine is a nonspecific alpha-adrenergic agonist. Although conflicting data and theories exist, the alpha-2 response may lower lOP by an adenyl cyclase-mediated reduction in aqueous production by the ciliary epithelium. II Other theories that have been advanced include a decrease in aqueous humor production secondary to decreased ciliary body blood flow or decreased episcleral venous pressure. 12 ,13 Contradictory findings have been described regarding the effects of apraclonidine on prdstaglandin concentrations and lOP response l4 (Sulewski et al, McCannel et al; unpublished data, presented at the 1990 AR VO Annual Meeting). The onset of action of apraclonidine occurs within I hour, and maximum reduction of lOP occurs 3 to 5 hours after application of a single dose. 8.9 Its use as a prophylactic agent is logical, as its duration of action (12 hours) exceeds that of tropic amide, and it has a low incidence of allergic reactions. s. ls Ocular side effects are limited primarily to transient upper lid elevation (1.3%), conjunctival blanching (0.4%), mydriasis (0.4%), and/or a transient burning or foreign body sensation. IS Congestion (vasodilation) of conjunctival vessels also can occur infrequently.
Apraclonidine may be useful in the acute treatment of any emergent high-pressure glaucoma such as neovascular glaucoma or acute angle-closure glaucoma. 16 Other possible uses include treatment of transient elevation ofIOP after cataract surgery, 17 panretinal photocoagulation, and vitreoretinal surgery. 18 Apraclonidine is an obvious alternative to oral hyperosmotics in the nauseated patient with elevated lOP. Our incidence of clinically significant lOP spikes was somewhat higher than that previously reported by other investigators l ,2 for patients receiving the placebo and no miotic. (10 of 26, 38%) but consistent with previous findings 3,4 for patients receiving placebo plus miotic therapy (9 of 25, 36%). Of the lOP spikes over 10 mmHg, only I (12 mmHg) was encountered in the apraclonidinetreated groups, suggesting that apraclonidine both minimizes the occurrence and blunts the height of these spikes. In the placebo groups, 6 patients had spikes of greater than 10 mmHg (range, 12 to 27 mmHg), 2 of which were greater than 20 mmHg (group 2; 21, 27 mmHg). High (>20 mmHg) lOP spikes can occur with cycloplegia and are believed to be secondary to an acute decrease in outflow facility.19 Within our study population, high lOP spikes (>20 mmHg) were seen in the placebo-treated groups. High lOP spikes induced by cycloplegia may aggravate optic nerve damage in eyes with advanced glaucomatous injury or fragile vascular supply. The data collected on the concurrent use of beta blockers and carbonic anhydrase inhibitors failed to reveal any relationship between the use of these agents and the incidence of postcycloplegic lOP elevations. We suggest, as a clinical routine, that (I) all patients (especially those with glaucoma) have their postcycloplegic lOP measured before being dismissed from the clinic (30 to 60 minutes after cycloplegia), and that (2) prophylaxis with apraclonidine or other agents as appropriate, be given only to glaucoma patients who have previously had documented postcycloplegic lOP spikes before administering cycloplegics for diagnostic purposes.
REFERENCES 1. Harris LS. Cycloplegic-induced intraocular pressure elevations. A study of normal and open-angle glaucomatous eyes. Arch OphthalmoI1968; 79:242-6. 2. Shaw BR, Lewis RA Intraocular pressure elevation after pupillary dilation in open angle glaucoma. Arch Ophthalmol 1986;104: 1185-8. 3. Harris LS, Galin MA Cycloplegic provocative testing: effect of miotic therapy. Arch Ophthalmol1969; 81:544-7. 4. Schimek RA, Lieberman WJ. The influence of Cyclogyl® and Neosynephrine® on tonographic studies of miotic control in open-angle glaucoma. Am J OphthalmoI1961; 51 :781-4. 5. Weinreb RN, Ruderman J, Juster R, Zweig K. Immediate intraocular pressure response to argon laser trabeculoplasty. Am J Ophthalmol 1983; 95:279-86. 6. Hoskins HO Jr, Hetherington J Jr, Minckler OS, et al. Complications of laser trabeculoplasty . Ophthalmology 1983; 90:796-9. 7. Robin AL, Pollack IP, House B, Enger C. Effects of ALO 2145 on
1085
OPHTHALMOLOGY
•
JULY 1991
intraocular pressure following argon laser trabeculoplasty. Arch Ophthalmol1987; 105:646-50. 8. Robin AL, Pollack IP, deFalier JM. Effects of topical ALO 2145 (paminocionidine hydrochloride) on the acute intraocular pressure rise after argon laser iridotomy. Arch Ophthalmol1987; 105:1208-11. 9. Abrams DA, Robin AL, Pollack IP, et al. The safety and efficacy of topical 1% ALO 2145 (p-aminoclonidine hydrochloride) in normal volunteers. Arch Ophthalmol1987; 105:1205-7. 10. Glaucoma Laser Trial Research Group. Handbook. March, 1985. Available from: National Technical Information SeNice. 5285 Port Royal Rd, Springfield, VA 22161. (Accession #PB86-1 01 037-XAB). 11. Gharagozloo NZ, Relf SJ, Brubaker RF. Aqueous flow is reduced by the alpha-adrenergic agonist, apraclonidine hydrochloride (ALO 2145). Ophthalmology 1988; 95:1217-20. 12. Van Buskirk EM, Bacon DR, Fahrenbach WHo Ciliary vasoconstriction after topical adrenergic drugs. Am J Ophthalmolol1990; 109:511-7.
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13. Coleman AL, Robin AL, Pollack IP. Apraclonidine hydrochloride. Ophthalmol Clin North Am 1989; 2:97-108. 14. Camras CB, Podos SM. The role of endogenous prostaglandins in clinically-used and investigational glaucoma therapy. Prog Clin Bioi Res 1989; 312:459-75. 15. Alcon Laboratories package insert: lopidine@> (apraclonidine hydrochloride). 16. Krawitz PL, Podos SM. Use of apraclonidine in the treatment of acute angle-closure glaucoma [letter]: Arch Ophthalmol. 1990; 108: 1208-9. 17. Wiles SB, MacKenzie 0, Ide CH. Control of intraocular pressure with apraclonidine hydrochloride after cataract extraction. Am J Ophthalmol 1991; 111 :184-8. 18. Pulido JS, Mallick KS, Sneed SR, Blodi CF. Apraclonidine hydrochloride in vitreoretinal surgery [letter]. Arch Ophthalmol. 1989; 107:316-7. 19. Galin MA. The mydriasis provocative test. Arch Ophthalmol1961 ; 66: 353-5.
