Apraclonidine Effects on Ocular Responses to YAG Loser Irradiation to the Rabbit Iris Kazuhiso Sugiyama, Yoshiaki Kirazawa, and Kenji Kawai

Home , Apraclonidine

Apraclonidine (p-aminoclonidine) ophthalmic solution effectively reduces the rise in intraocular pressure (IOP) following anterior segment laser surgery. We tested the effect of topical 0.5% apraclondine

on intraocular pressure and on protein and prostaglandin (PG) E2 concentrations in aqueous humor following Q-switched Nd:YAG laser irradiation to the iris of albino rabbits, at an energy level of 2 to 200 mJ. IOP was measured prior to and for 24 hr after irradiation. Aqueous humor was withdrawn

before and 1 hr after laser irradiation for determining protein (Lowry method) and PGE2 (radioimmu- noassay). Four to seven rabbits were used for each experiment. The increase in IOP and protein concentration following laser irradiation was demonstrated to be dependent on the amount of laser energy. Apraclonidine completely abolished the IOP rise, and significantly reduced the elevation of

protein content. Apraclonidine failed to affect the increase in PGE2. Invest Ophthalmol Vis Sci 31:708-714,1990

The Q-switched Nd:YAG laser is widely used to following anterior segment laser surgery,18 the mech- perform iridotomy on patients with pupillary block anism^) of inhibition remains to be elucidated. angle-closure glaucoma. Although there are many In the present investigation, we determined in rab- benefits from this new therapeutic method, serious bits the dose-response relationship between the post- complications have been reported. The major com- laser IOP rise, the concentration of aqueous humor plications include postoperative elevation in intraoc- protein, and the energy level of Q-switched Nd:YAG ular pressure (IOP), iris hemorrhage, and iritis.1'7 laser applied to the iris, and estimated the ability of Previous studies have indicated that the IOP rise is topically administered apraclonidine to modulate causally related to breakdown of the blood-aqueous this dose-response relationship. We also measured barrier induced by disruption of iris tissue. This has concentrations of prostaglandin E2 (PGE2) in been shown, in rabbits, to be associated with an in- aqueous humor from normal rabbit eyes and from crease in the concentrations of prostaglandins (PGs) those subjected to Q-switched Nd:YAG laser irradia- and protein in the aqueous humor following argon tion of the iris, with and without topical administra- laser iris photocoagulation or NdrYAG laser application of apraclonidine. tion.8'12 To extend the results of these studies, various inhibitors of PG synthesis were evaluated in terms of Materials and Methods their efficacy in limiting the IOP rise after laser application to the iris or the trabecular meshwork in Animals and Experimental Procedures humans and animals. However, results thus far have We used New Zealand albino rabbits of either sex, not been favorable enough for such inhibitors to be weighing at least 2.0 kg. All eyes were initially exam- recommended for this specific clinical indication.13"15 ined with a slit lamp, and only animals without signs Recently, apraclonidine hydrochloride (p-amino- of ocular inflammation were used for the study. We clonidine hydrochloride) was demonstrated to effec- measured IOP with a calibrated pneumatonometer tively minimize acute postoperative IOP elevation (Alcon Inc., Fort Worth, TX). Aqueous humor sam- after argon and Q-switched Nd:YAG laser iridot- ples were obtained via a 27-gauge needle for the mea- 1617 omy. Although this new compound is currently in surement of protein and PGE2 in normal rabbits and wide clinical use for the prevention of acute IOP rise at various time intervals after Q-switched Nd:YAG laser irradiation of the iris. These animal investiga- tions conform to the ARVO Resolution on the Use of From the Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan. Animals in Research. Submitted for publication: April 7, 1989; accepted August 7, 1989. Preliminary Experiments Reprint requests: Yoshiaki Kjtazawa, MD, Department of Oph- thalmology, Gifu University School of Medicine, 40 Tsukasa- In the first series of preliminary experiments, we machi, Gifu-shi 500, Japan. evaluated the effect of topical administration of 0.5%

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apraclonidine ophthalmic solution on IOP in con- Administration of Alpha 2-Agonist Apraclonidine scious normal rabbits. In each of six rabbits, one eye and Alpha 1-Agonist Phenylephrine received 30 /il of apraclonidine and the other eye received the same amount of vehicle in a double- Thirty microliters of 0.5% apraclonidine ophthal- blind, randomized manner. IOP was measured with mic solution (Alcon) were used 1 hr prior to and the pneumatonometer before and 30, 60, 120, 240, immediately after the laser irradiation in all experi- 360 min, and 24 hr after apraclonidine or vehicle ments. In an experiment designed to evaluate the in- administration. In the second series of preliminary fluence of the adrenergic alpha-1 agonist phenyleph- experiments, we first evaluated the protein concen- rine on the aqueous protein concentration after laser tration in aqueous humor in a total of seven eyes of iris irradiation, 30 /xl of 5% phenylephrine ophthal- seven normal rabbits. Next, we identified the time at mic solution (Kowa Medical Inc., Tokyo, Japan) was which the concentration of aqueous protein reached used. its peak after laser irradiation of the iris. For this purpose, we studied 34 eyes of 17 rabbits and lasered Paracentesis the iris with 16 mJ (8 mJ X 2 pulses/burst) in one At the designated times after irradiation, about 100 randomly selected eye of each animal; the contralat- lA of aqueous humor was withdrawn with a 27-gauge eral eye was left untreated to serve as a control. An needle and a tuberculin syringe. Ten minutes before aqueous sample was obtained from each eye by para- paracentesis, 0.4% oxybuprocaine hydrochloride centesis at 30, 60, 120 and 240 min following laser ophthalmic solution was repeatedly instilled for anes- application. The aqueous samples were taken from thesia. Paracentesis was performed only once in each three to six rabbits at each designated time. eye at a specific time interval, after which the animals After determining that the peak concentration of were sacrificed by intravenous injection of a lethal aqueous protein was reached at 60 min after laser dose of sodium pentobarbital. irradiation, we decided to examine the influence of laser irradiation with 2, 24, 48, 80 and 200 mJ on the Protein protein concentration at 60 min following irradia- 19 tion. Four to seven rabbits were studied for each en- The method of Lowry et al was used for assay of ergy level. protein. Prostaglandin E Assay Laser Irradiation 2 We measured PGE2 by sensitive and specific radio- In all experiments, a Q-switched Nd:YAG laser immunoassays which have been described in detail (Topaz, LASAG AG, Thun, Switzerland) was used elsewhere.20'21 with a Fankhauser's contact lens (LASAG AG) for iridotomy. The irradiation administered was multi- Statistics modal, with a wavelength of 1064 nm and a pulse duration of 12 nsec. Under local anesthesia (0.4% The results are presented as mean ± SD. The com- oxybuprocaine hydrochloride ophthalmic solution; parison of measured value with the baseline was Santen Pharmaceutical Co., Ltd., Osaka, Japan), a made using a paired t-test. The values among groups contact lens was placed over the cornea to focus the were compared using the student t-test and the Wil- laser beam. Laser foci were placed about 2 mm from coxon rank sum test. A value of P < 0.05 was consid- the pupillary margin. The laser energy was set at 2, ered significant. 16, 24, 48 or 80 mJ to determine the effect of laser irradiation on IOP and the concentration of PGE2 in Results aqueous humor. In addition, laser irradiation with 200 mJ was employed to evaluate the effect of laser Preliminary Experiments energy on protein concentration in aqueous humor. Effect of topical apraclonidine on intraocular pressure in normal rabbits. A small but statistically signif- Intraocular Pressure icant increase in IOP was noted in the apraclonidine- treated and the vehicle-treated eyes at 30 min after Using a calibrated pneumatonometer, IOP was instillation of apraclonidine or its vehicle (P < 0.05). measured just prior to laser application and then at Thereafter, IOP in the apraclonidine-treated eyes 30, 60, 120, 240 and 360 min, and 24 hr post-laser gradually decreased, and by 4 hr after treatment IOP irradiation. was reduced to below the baseline level. The decrease

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was statistically significant at 4, 6 and 24 hr after .2 10 (6) treatment (P < 0.05-0.005). In contrast, the vehicle- treated eyes showed no significant change in IOP at (4) any time except at 30 min after treatment (Fig. 1). « 7.5 Temporal course of the aqueous humor protein concentration after Q-switched Nd.YAG laser iris irradiation with 16 mJ. Compared with the contralat- (3) eral control eye, the aqueous humor protein in- 2.5 creased within 30 min after laser irradiation. It (7) reached a peak at 60 min and then decreased during m the subsequent examination period (Fig. 2). 0.5 Time (hours)

Response of Intraocular Pressure to Laser Fig. 2. Effect of Nd.YAG laser irradiation (16 mJ) on aqueous Irradiation of Normal Rabbit Iris protein concentration. The ordinate indicates the ratio of protein concentration between the laser-treated and contralateral un- In each rabbit, the iris of one eye received Q- treated eyes. The abscissa indicates the time after laser irradiation. switched Nd:YAG laser irradiation at the designated Time 0 denotes no laser irradiation. Values are mean ± SD. Paren- energy levels and the contralateral eye was left un- thesis indicates the number of animals. Asterisks indicate statisti- treated to serve as a control. Four rabbits were used cally significant difference from Time 0 (Wilcoxon rank sum test, only once for each energy level. The IOP response to *:P < 0.025, **:P < 0.01, ***:P < 0.005). different energy levels is shown in Table 1. With an energy level of 16 mJ or higher, IOP significantly Response of Intraocular Pressure to Laser increased within 30 min as compared to the pre-laser Irradiation of the Iris With and Without value in the lasered eye. The increase in IOP, ex- Apraclonidine Treatment pressed as the IOP difference (maximum IOP - baseline IOP) was directly proportional to the applied log In each rabbit, one eye was treated with topical energy level (r = 0.8796, P < 0.05) (Fig. 3). Based on apraclonidine and the contralateral eye received the the determined dose-response relationship, the mini- vehicle; the same amount of laser energy was applied mum laser energy required to elicit the IOP rise was to both eyes in each rabbit. The IOP responses to estimated to be 9.3 mJ. In contrast, neither a signifi- different energy levels are shown in Table 2. With 24 cant IOP increase nor a significant correlation be- mJ or higher, IOP significantly increased as com- tween IOP change and the laser energy applied was pared with the pre-laser level in the vehicle-treated noted in the untreated control eyes. eye at 30 min. This increase was linearly correlated with the applied log energy level (r = 0.9456, P < 0.025) (Fig. 4). The IOP failed to increase following laser irradiation at each energy level in the apraclonidine-treated eyes. In the vehicle-treated eyes, the minimum energy required to elicit IOP rise was estimated to be 12.8 mJ by extrapolating the dose-response regression line. Because the energy levels employed in this study (maximum energy: 80 mJ) failed to induce an IOP rise in the apraclonidine-treated eyes, it was not possible to quantitate the capacity of this compound to suppress the IOP rise after Nd:YAG laser application. It can only be estimated that the dose-response relationship was shifted by at least 0.6 log unit. In the vehicle-treated eyes, at all energy levels used except for 2 mJ, IOP showed a significant decrease as

10- compared with the baseline level, regardless of the preceding IOP rise. The onset of IOP decrease varied 0 0.5 1 4 6 Time (hours) with the energy level from 1 to 6 hr after the laser irradiation, and lasted for a variable length of time Fig. 1. Effect of apraclonidine (closed circles) or vehicle (open ranging from 1 to 24 hr. In the apraclonidine-treated circles) on IOP in rabbits. Values indicate mean ± SD. Asterisks indicate statistically significant difference from baseline value eyes, IOP showed a significant decrease following the (paired t-test, *:P < 0.05, **:P < 0.01, ***:P < 0.005). laser application at all the energy levels employed

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Table 1. IOP following laser irradiation to the iris

Laser Time (hr) energy (mJ) Eye Baseline 0.5 1 2 4 6 24

T 18.3 ±2.9 17.8 ± 1.7 15.8±3.4f 15.4 ± 1.8* 15.3 ±0.9* 17.6 ±2.4 18.1 ±2.8 2 mJ C 17.5 ±2.1 18.0 ±2.9 16.5 ±3.1 16.0 ± 1.8 17.0 ±0.8 18.8 ± 1.7* 17.8 ±2.2 T 19.5 ±2.4 21.5 ±3.9* 19.3 ±3.8 14.3 ± 1.3* 14.5 ± 1.9* 14.5 ±0.6* 15.8 ± 1.0* 16 mJ C 20.3 ± 2.4 20.8 ± 1.3 19.5 ±2.5 19.3 ±2.2 19.5 ±2.4 21.3 ±2.2 16.8 ± 1.7 T 20.0 ± 2.5 28.9 ± 3.0f 24.5 ± 3.4* 12.5 ±2.4* 11.4±2.6t 11.1 ±2.0§ 17.8 ±7.3 24 mJ C 19.9 ± 1.9 19.5 ±0.6 17.5 ±0.6* 17.0 ± 1.8* 18.5 ±3.3 18.3 ±4.7 16.8 ± 3.0 T 21.3 ±4.5 37.5 ±4.1* 31.5 ±9.0* 26.4 ± 7.3 18.9 ±7.7 15.5 ±2.0* 14.0 ±4.2* 48 mJ C 20.5 ± 5.3 22.8 ± 2.9 21.8 ±2.2 19.4 ±2.4 21.3 ±2.5 20.6 ± 2.4 20.3 ± 2.8 T 18.3 ±3.1 32.3 ± 3.0§ 25.3 ± 5.6t 18.5 ±5.7 16.1 ±3.5* 16.3 ±3.6 14.1 ±4.9 80 mJ C 18.9 ±3.2 17.5 ±2.7 17.8 ±2.8 15.8 ± 1.7 18.3 ±2.2 19.6 ±3.1 17.4 ±3.8

Mean ± SD (mm Hg) (n = 4). Symbols indicate statistically significant differences from the baseline T: lasered eye, C: control eye. value (*/> < 0.05, f/> < 0.01, tP < 0.005, §f < 0.001).

except for 2 mJ, starting within 30 to 120 min after Response of Aqueous Protein Concentration to Iris irradiation and lasting for 24 hr (Table 2). Laser Irradiation With and Without Phenylephrine In four rabbits, one eye received 30 iA of 5% phen- Response of the Aqueous Protein Concentration to ylephrine ophthalmic solution and the contralateral Laser Irradiation of the Iris With and Without Apraclonidine Treatment 20- In each of 42 rabbits, one eye was treated with topical apraclonidine and the contralateral eye received vehicle only. The same amount of laser energy was delivered to both eyes in each rabbit. Six or seven

rabbits were used only once for each energy level. The 15- protein concentrations at 1 hr following laser irradiation with different amounts of energy are shown in Table 3. Without irradiation, the aqueous protein concentration was almost identical in the apracloni- Q. dine-treated and the vehicle-treated eyes at 1 hr after O 10- treatment. In contrast, Nd:YAG laser irradiation of E the iris at 2 to 200 mJ caused the aqueous protein 3 E concentration to increase in rabbits that received apraclonidine treatment in one eye and vehicle administration to the contralateral eye. However, the increase in protein was significantly less in the apraclonidine-treated eyes than in the vehicle-treated eyes 5- after laser irradiation at any energy level (Wilcoxon rank sum test, P < 0.05-0.005) (Table 3). This laser- induced increase in the protein concentration was directly proportional to the amount of applied log laser energy in both the treated and the untreated eyes (r = 0.9519, P < 0.005 in apraclonidine-treated, r 10° 10' 102 = 0.9390, P < 0.005 in vehicle-treated eyes). The Laser energy (mJ) minimum energy required to elicit the rise in aqueous protein concentration was estimated to be 1.7 mJ in Fig. 3. IOP rise expressed as the maximum post-laser IOP minus pre-laser IOP after laser irradiation of the rabbit iris with 2, 16, 24, the vehicle-treated and 13.9 mJ in the apraclonidine- 48 or 80 mJ. Solid circles indicate lasered eyes and open circles treated eyes (Fig. 5). denote untreated eyes.

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Table 2. IOP following laser irradiation to the iris with and without apraclonidine treatment

Laser Time (hr) energy (mJ) Eye Baseline 0.5 1 2 4 6 24

T 15.3 ±2.1 14.8 ± 0.5 13.5 ±2.1 12.0 ±2.6* 15.0 ± 1.8 15.5 ± 1.9 2 mJ 15.5 ± 1.9 C 16.0 ±2.4 15.8 + 2.6 14.8 ± 3.2 12.8 ±2.1 14.5 ± 1.3 15.0 ±0.8 15.3 ±2.5 T 17.8 ±2.1 11.3 + 2.2* 11.0 ±3.2* 12.5 ± 1.7§ 16 mJ 11.0 ± 2.4t 11.0±0.8t 11.5 ±2.4* C 17.8 ± 1.5 16.8 + 2.1 14.5 ± 1.9* 11.5± 1.9* 12.5 ±3.1* 12.5 ± 1.3f 13.3 ± 1.3f T 17.8 ± 1.3 14.8 ± 2.1* 13.3 ± 1.7* 12.8 ± 1.0* 12.0 ± 1.6f 24 mJ 13.8 ± 1.7f 12.5 ±2.5* C 18.5 ±0.6 22.8 ± 2.5* 18.3 ±2.2 15.8 ±3.0 15.3 ± 1.0* 15.0 ±0.8* 15.0 ±2.9 T 23.1 ±0.6 17.8 ± 6.6 16.8 ±6.2 14.5 ± 1.3§ 14.0 ±2.9* 12.5 ±2.9* 18.3 ±3.9* 48 mJ C 22.6 ± 2.6 26.4 + 2.1* 21.8 ±5.3 15.5 ±6.7 15.3 ±3.4* 16.6 ±5.6 23.3 ± 2.4 T 20.0 ± 2.2 13.5 + 2.7§ 12.1 ± 1.8§ 12.5 ± 1.9* 12.0 ± 1.8* 11.9± 1.4* 11.5=+= 1.3* 80 mJ C 19.1 ±3.0 24.1 ± 2.3t 23.0 ± 5.4 23.2 ± 8.2 17.3 ±3.2 13.3 ±2.9* 12.3 ±0.5*

Mean ± SD (mm Hg) (n = 4). treatment. T: lasered eye with apraclonidine treatment, C: lasered eye without apara- Symbols indicate statistically significant differences from the baseline clonidine treatment. value (•/> < 0.05, t^ < 0.01, $P < 0.005, §/> < 0.001). Baseline IOP is the value measured immediately before apraclonidine

eye was treated with the same amount of physiologi- same amount of vehicle. Both irises of each rabbit cal saline 1 hr before and immediately after Nd: YAG received the same amount of laser energy at 1 hr after laser iris irradiation at an energy of 16 mJ for each the topical administration of either apraclonidine or eye. Laser treatment caused the aqueous protein con- vehicle. Aqueous samples were obtained at 1 hr after centration to rise, regardless of topical administration laser irradiation and four rabbits were used only once of phenylephrine, at 1 hr following irradiation; pro- for each energy level. Laser irradiation elevated the tein concentration was 325.6 ± 246.5 mg/dl in the PGE2 concentration in aqueous humor, and no sig- phenylephrine-treated and 570.8 ± 315.4 mg/dl in nificant difference was noted between the apracloni- the saline-treated eyes (P > 0.10). dine-treated and the vehicle-treated eyes (Table 4). The most striking rise of PGE2 concentration was Response of Aqueous Prostaglandin E2 induced with 16 mJ; a further increase in energy level Concentration to Nd:YAG Laser Iris Irradiation failed to cause a further increase in PGE2 concentra- With and Without Apraclonidine Treatment tion. One eye of each rabbit received 30 /x\ of topical apraclonidine and the contralateral eye received the Discussion In the present study, we have shown in rabbits that topical apraclonidine reduced the IOP and that the 10 laser-induced increase in aqueous humor protein concentrations was suppressed by topical administra-

Table 3. The amount of laser energy and the aqueous protein concentration with and without apraclonidine treatment O5 Aqueous protein concentration (mg/dl) E Laser E energy Apraclonidine- x (mJ) treated eye Placebo-treated eye P-value

0 46.4 ± 6.4 51.1 ±7.0(4)* NS 2 88.0 ± 40.4 221.7 ±82.6 (7) P < 0.005 16 89.5 ± 49.3 412.6 ± 186.9(7) P < 0.025 2 24 146.3 ± 134.4 691.9 ±550.9 (6) P < 0.025 10' 10 48 313.5 ±357.3 1031.9 ±742.9 (6) P < 0.05 Laser energy (mJ) 80 327.7 ± 308.2 1038.6 ± 447.3 (6) P < 0.05 200 791.4 ±433.8 1588.4 ±701.2 (7) P < 0.025 Fig. 4. IOP after laser irradiation of bilateral irides in rabbits with 2, 16, 24, 48 or 80 mJ. Solid circles indicate the apraclonidine- Mean ± SD. treated eyes and open circles denote the vehicle-treated eyes. * ( ): number of animals.

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200(h Apraclonidine reduces IOP in normal human sub- jects23 as well as in rabbits, as demonstrated in the present study. Hence, it is possible that the suppres- sion of the post-laser IOP rise is at least in part attrib- utable to the hypotensive effect of this compound. 1,500- The mechanisms by which the IOP rise was blunted in the contralateral, fellow eye, which was s lasered without apraclonidine treatment while the other eye received topical apraclonidine, are hard to I explain (Table 2). Apraclonidine has a markedly s 1,000 polar structure and penetrates the blood-brain bar- o 24 o rier only poorly as compared with clonidine. There o is some evidence, however, that it exerts central ner- I vous system effects when it is topically or systemically 25 26 o administered in humans and animals. ' Hence, the 500 possibility exists that this contralateral effect is me- Q. diated by the central nervous system. To clarify the mechanisms of the contralateral effect, further inves- | tigations, including repeating the experiments in cr sympathectomized animals are needed.

1 2 Apraclonidine possesses a strong capacity to con- 10° IO 1O strict peripheral blood vessels by acting on alpha-2 receptors.27 It is noteworthy that clonidine, which has Laser energy (mj) a stronger central nervous system effect and a weaker Fig. 5. Protein concentration in aqueous humor 60 min after laser irradiation of rabbit iris with 2, 16, 24,48, 80 or 200 mJ. Solid peripheral vasoconstrictive action, exerts a similar circles indicate the apraclonidine-treated eyes and open circles de- but less conspicuous influence on the response of IOP note the vehicle-treated eyes. Six or seven rabbits were used only and aqueous protein to Nd:YAG laser irradiation of once for each energy level. the iris.28 The more potent peripheral vascular effect of apraclonidine may be responsible for its greater tion of the alpha-2 adrenergic agonist apraclonidine, ability to preserve the integrity of the blood-aqueous a derivative of clonidine. This was accompanied by a barrier. The failure of the alpha-1 agonist phenyleph- remarkable blunting of the IOP rise, not only in the rine, with its marked vasoconstrictive action, to influ- apraclonidine-treated eyes but in the untreated, fel- ence the response of the aqueous protein concentra- low eye when both eyes received laser irradiation of tion to laser treatment of the iris is intriguing and the iris. warrants further investigation. The results strongly suggest the following two pos- PGE2 is known to be the predominant prostanoid sibilities: first, apraclonidine prevents the breakdown released into the aqueous humor after argon laser iris of the blood-aqueous barrier, which has been docu- photocoagulation.8 An inability of apraclonidine to mented to follow laser-induced trauma to the influence the response of this prostanoid to laser irra- iris.9"'22 Second, the ocular hypotensive effect of diation is conceivable, in light of our present knowl- apraclonidine plays a significant role in suppressing edge of the prostaglandin cascade. Further study the acute IOP rise after laser irradiation to the iris. should be directed towards clarification of the mecha- Weinreb and associates documented in rabbits that the IOP rise following argon laser photocoagulation is Table 4. The amount of laser energy directly correlated with the increase in protein con- and PGE concentration tent of the aqueous humor.8 With Nd:YAG laser, 2 Schrems and co-workers demonstrated that the Prostaglandin E2 concentration (pg/ml) aqueous protein concentration elevates concurrently 9 Laser Apraclonidine- with the IOP rise after laser application to the iris. " energy treated Placebo-treated P-value The results of these studies8'911 support the notion 0 37.8 ± 3.4 32.8 ± 3.4 NS that apraclonidine acts to minimize the breakdown of 2 400.0 ±226.1 332.5 ± 164.2 NS the integrity of the blood-aqueous barrier, thereby 16 2124.0 ± 1024.3 1865.0 ±756.0 NS preventing the IOP from elevating in response to laser 24 1075.0 ± 263.0 950.0 ± 56.0 NS iris irradiation in rabbits and laser iridotomy in 80 1100.0 ±81.6 910.0 ± 108.6 NS humans. Mean ± SD (n = 4).

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nism by which apraclonidine renders the blood- 14. Pappas HR, Berry DP, Partamian L, Hertzmark E, and Ep- aqueous barrier more stable in the presence of in- stein DL: Topical indomethacin therapy before argon laser creased PGE . trabeculoplasty. Am J Ophthalmol 99:571, 1985. 2 15. Weinreb RN, Robin AL, Baerveldt G, Drake M V, Blumenthal M, and Wilensky J: Flurbiprofen pretreatment in argon laser Key words: apraclonidine, Q-switched Nd.YAG laser iris trabeculoplasty for primary open-angle glaucoma. Arch irradiation, intraocular pressure, blood-aqueous barrier, Ophthalmol 102:1629, 1984. prostaglandin E2 16. Robin AL and Pollack IP: Effects of topical A10 2145 (p- aminoclonidine hydrochloride) on the acute intraocular pressure rise after argon laser iridotomy. Arch Ophthalmol References 105:1208, 1987. 17. Kitazawa Y, Taniguchi T, and Sugiyama K: Use of apracloni- 1. Robin AL and Pollack IP: A comparison of neodymium:YAG dine reduces acute intraocular pressure rise following Q- and argon laser iridotomies. Ophthalmology 91:1011, 1984. switched Nd:YAG laser iridotomy. Ophthalmic Surg 20:49, 2. Moster MR, Schwartz LW, Spaeth GL, Wilson RP, McAllister 1989. A, and Poryzees EM: Laser iridectomy: A controlled study 18. Brown AL and Pollack IP: Effects of topical ALO 2145 reduce comparing argon and neodymium YAG. Ophthalmology the intraocular pressure elevation after anterior segment laser 93:20, 1986. surgery. Ophthalmology 95:378, 1988. 3. Schrems W, Eichelbroenner O, and Krieglstein GK: The im- 19. Lowry OH, Rosebrough NJ, Farr AC, and Randall RJ: Protein mediate IOP response of ND-YAG-laser iridotomy and its measurements with the Folin phenol reagent. J Biol Chem prophylactic treatability. Acta Ophthalmol 62:673, 1984. 193:265, 1951. 4. Henry JC, Krupin T, Schultz J, and Wax M: Increased intraoc- 20. Powell WS: Rapid extraction of oxygenated metabolites of ular pressure following neodymium-YAG laser iridotomy. arachidonic acid from biological samples using octadecylsilyl Arch Ophthalmol 104:178, 1986. silica. Prostaglandins 20:947, 1980. 5. Schwartz LW, Moster MR, Spaeth GL, Wilson RP, and Pory- 21. Kawano K, Sugiya M, Oka M, and Tabata N: A simple, rapid zees E: Neodymium-YAG laser iridotomies in glaucoma asso- and simultaneous extraction of thromboxane B2, 6-keto-pros- ciated with closed or occludable angles. Am J Ophthalmol taglandin F| and prostaglandin E2. Japanese Journal of In- 102:41, 1986. flammation 7:511, 1987. 6. Taniguchi T, Rho SH, Gotoh Y, and Kitazawa Y: Intraocular 22. Unger WG, Perkins ES, and Bass MS: The response of the pressure rise following Q-switched neodymium:YAG laser iri- rabbit eye to laser irradiation of the iris. Exp Eye Res 19:367, dotomy. Ophthalmic Laser Therapy 2:99, 1987. 1974. 7. Shirato S, Yumita A, Yamamoto T, and Kitazawa Y: Q- 23. 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