Eye (]991) 5, 390-394

Pilocarpine to Prevent Acute Pressure Increase Following Primary Laser Trabeculoplasty

T. ELSAs , * H. JOHNSEN** AND 0. STANG" Trondhehn, Norway.

Summary The effect of pilocarpine pretreatment on the transient pressure elevations immedi­ ately following primary laser trabeculoplasty was investigated in a prospective, ran­ domised study. Fifty eyes of 50 patients, 33 with exfoliative and 17 with simple glaucoma, were treated in 3600 of the trabecular meshwork. The mean maximum

pressure increase was 2.4 (SO = 4.4)mm Hg with pilocarpine pretreatment and 12.8

(SD = 11.2)mm Hg without pretreatment (p<0.05). Except in two cases, all peak pressures appeared during the first two hours after treatment . The degree of cham­ ber angle pigmentation was predictive of the magnitude of the post laser hyperten­ sive pressure response in eyes without pretreatment (p<0.05).

The most frequent and serious complication Material and methods after laser trabeculoplasty (LTP) is acute pres­ Fifty eyes of 50 patients were included, 33 sure elevation. I There are several reports of with exfoliative glaucoma and 17 with simple visual field loss following LTP probably glaucoma. The mean age of the patients was caused by pressure increase.2--1 Laser trabecu­ 69 (SO = 9.9) years in the pilocarpine pre­ loplasty was originally introduced as an alter­ treatment group and 71.9 (SO = 7.1) years in native to filtrationsurgery," and there are now the untreated group. several studies showing promising results with To be included in the study, the patients had LTP as the initial treatment for glaucomah-N to meet the following criteria: (a) Intraocular pressure �25mm Hg meas­ Pressure reducing agents such as pilocarpine ,'J iii ured by applanation tonometry at the acetazolamide, and apraclonidine" reduce initial evaluation by one of the authors the pressure increase of LTP in glaucoma (TE) and just before laser treatment. The patients on medication prior to treatment. mean of these two was taken as prelaser while anti-inflammatory drugs seem to have 1 4 lOP. no effect. 2 1 We are only aware of one study (b) Glaucomatous disc damage andlor visual on medical prophylaxis to prevent post­ field defects. operative pressure elevations in primary LTP. (c) No earlier glaucoma treatment. Odberg'5 recorded no cases of pressure The optic disc was evaluated by contact lens increase in an uncontrolled study of 27 eyes examination and nonstereo fundus photogra­ pretreated with timolol. phy by one of the authors (TE) according to Fifty eyes of 50 patients were investigated the recommendations of Schwartz. 10 Glauco­ in the present randomised study to determine matous disc damage was defined as vertical the influence of pilocarpine pretreatment on cup-disc ratio �().5 and at least one of the fol­ post laser pressure elevation in primary LTP. lowing criteria:

From: Departments of Ophthalmology' and Clinical Chen11Stry·'··. UniverSity of Twndheim, Norway.

Correspondence to: T. Fisas, Department of Ophthalmo]ogv. University of Trondheim, N-7()()(,. Norway. PRIMARY LASER TRAI3ECLJLOPLASTY 391

(a) cupping of the optic nerve head extending measurements one week and one, three, and to the margin of the disc. six months after laser surgery. Topical anti­ (b) a difference of vertical cup-disc ratio of glaucomatous medication was instituted if �0.2 between the two eyes. lOP was �40 mm Hg the day after treatment, (c) different degrees of disc pallor in the two �25 mm Hg after one week and >22 mm Hg eyes with no other explanation. after that. The visual field was examined with the We used the blue-green light of a Coherent Humphry visual field analyser using the argon laser photocoagulator. About a hun­ C-30-2 program before and one, three, and six dred burns were evenly spaced around 3600 of months after treatment. Glaucomatous visual the trabecular meshwork just in front of the field defects were defined as having at least scleral spur. We used the following settings: three contiguous spots with a depth of �5 dB n.l sec. power duration, 50 �L spot size and a within the 300 central field. Three patients mean power level of 1.0 (SD = 0.2) W. All who did not cooperate when tested by auto­ treatments were performed by one of the mated perimetry had their fields plotted with authors (TE) to maintain uniformity during the Goldmann perimeter. MO, the mean ele­ the study. vation or depression of the patient's overall The study took place from September 1989 field compared to the normal reference field to December 1990. Informed consent was in the STATPAC program of the Humphry obtained from all patients. visual field analyser, was used as an index of Multifactor analysis of variance (ANOVA) the degree of visual field damage. The visual with two-way interaction was used to evaluate fieldchanges following L TP will be the subject the effect of chamber angle pigmentation, of a separate study. glaucoma type, and prelaser pilocarpine The degree of chamber angle pigmenta­ treatment on pressure increase after treat­ tion in the 6 o'clock position was graded ment. For comparison of two mean values and according to Scheie on a scale from 0 to 4.17 of two frequencies, the t-test or binomial test Patients were randomly assigned to two was performed. A p-value less than 0.05 was drops of pilocarpine 2 '/"o pretreatment one considered significant. hour before LTP or to no pretreatment. In cases with bilateral disease one eye was ran­ Results domised to LTP. The study was not masked Various prelaser and laser treatment para­ because the pilocarpine induced miosis was meters are listed in Table I. There is no evi­ very obvious to the investigators. dence of dissimilarities between the two Intraocular pressure was measured one, groups. two, four, six, eight, and 24 hours after treat­ Data related to pressure increase are sum­ ment with the Goldmann applanation tonom­ marised in Table II and Figure 1. The mean eter. If the pressure was �50 mm Hg, the maximum pressure increase was 2.4 patient received glycerol, acetazolamide and (SO = 4.4) mm Hg in the pilocarpine group

limolol. The patients returned for repeat and 12.8 (SO = 11.2) mm Hg in the group not

Table I. Prelaser and LTP parameters.

Pilocarpine No pilocarpine pretreatment pretreatment n =25 n =25

Mean prelascr [OP (mm Hg) 34.9 (SO=R.1) 33.3 (SO= 5.6) Mean age 69 (SO= 9.9) 71.9 (SO=7.1) Number of eyes with exfoliative glaucoma 16 17 Number of eyes with simple glaucoma 9 8

- Mean visual field defect (MO)(d8) -6.7 (SO= RA) 6 . 0 (SO= 9.7) Cup-disc ratio 0.7 (SO=O.I7) 0.7 (SO=O.I7) Pigmentation of chamber angle 2.2 (SO= 0.9) 2.3 (SO =O.R) Laser power (W) 0.94 (SO= 0.2) 1.03 (SO = 0.2) :-Jumber of laser burns 109 (SO= 15) 104 (SO= 17) 392 T ELSAs ET Al

Table II. Pressure increase following primary LTP

Pilocarpine No pilocarpine pretreatment pretreatment n =25 n =25 p-\'a/lle

Mean maximum pressure increase (mm Hg) 2.4 (SD =4.4) 12.R (SD = 11.2) <(J.OS �P", lOmm Hg n=3 n= 13 <0.05 �P"'20mmHg n=O n = R <(J.05 Peak lOP ",SO mm Hg n = 1 n = 10 <0.05

on pilocarpine (P<0.05). Table II demon­ primary LTP. He found no cases of post­ strates that pressure increase ;310 mm Hg and operative pressure increase in an uncon­ ;320 mm Hg and pressure peaks ;350 mm Hg trolled study of 27 timolol pretreated eyes were more frequent without pilocarpine pre­ with LTP over 1800• The disadvantage of tim- treatment (P<0.05). There were no cases of 0101 is that it cannot be used in patients with permanently elevated pressure following obstructive lung disease, and should be used LTP. with caution in cardiac patients. IH Robinll ANaYA showed that pilocarpine pretreat­ reported that apraclonidine was superior to ment and chamber angle pigmentation were dipivefrin, timolol, acetazolamide and pil­ factors with significant effect on pressure ocarpine in preventing postlaser pressure ele­ increase after laser treatment (p<0.05). vations in patients on glaucoma medication. Specifically, pilocarpine generally reduced the We are aware of no such comparative studies pressure increase, and the reduction was on the efficacy of different drugs in primary higher the more pigmented the angle. This laser °trabeculoplasty. Ofner et al.9 reported observation is clearly shown in Figure 1. that pilocarpine reduced the acute pressure increase after laser trabeculoplasty in patients Discussion on medication. Leung and Gilliesl9 observed a Our study demonstrates that pilocarpine pre­ trend towards diminished pressure increase in treatment decreases the magnitude of the pilocarpine pretreated patients, but they did pressure rise after primary laser trabeculo­ not consider it significant. plasty. To our knowledge only Odbergl5 has In our study all except two patients experi­ studied the influence of medical pretreatment enced the pressure peaks during the first two on the immediate pressure response following hours after treatment. These two patients had 20 maximum pressures three and five hours after laser trabeculoplasty. Even if most pressure 18 ...... spikes occur during the first hours after laser tl) J: 16 surgery, delayed pressure peaks may occur as E 14 late as 24 hours after treatment. 13 There was E 12 no difference in the time course of the pres­ Q) U) sure increase between the pilocarpine and ." 10 Q) non pilocarpine group in our study. .... 0 8 c: There are several theories that attempt to 6 explain the hypertensive pressure response /l. 0 4 following LTP. Possible mechanisms are 2 mechanical blockage of the outflow channels by trabecular tissue damage, obstruction of 0 2 3 trabecular flowby entrapment of pigment and Pigmentation grade cellular debris, prostaglandine mediated pres­ sure increase, and neuropeptide induced Fig. 1. Pressure increase following primary LTP versus the degree of chamber angle pigmentation ill pressure rise."Ii"1 The relationship between pilocarpine pretreated eyes (black coilimns) and eyes the degree of chamber angle pigmentation receiving no pretreatment (hatched coillmns). and the magnitude of the pressure increase PRIMARY LASER TRABECULOPLASTY 393 observed in our study and other reports22,23 5 Wise JB: Long-term control of adult opcn angle glaucoma by argon laser treatment. Ophthal­ may support the theory of mechanical block­ mology 1981, 88: 197-202. age. Laser treatment of heavily pigmented °Tuulonen A. Niva AK, Alanko HI: A controllcd angles will often lead to release of pigment five-year follow-up study of laser trabeculoplasty that can plug the trabecular meshwork. as primary therapy for open-angle glaucoma. Am Heavy pigmentation of the angle will prob­ J Ophthalmol1987, 104: 334-8. 7 Elsas T and 10hnsen H: Long-term efficacy of ably increase the absorption of energy and in primary laser trabeculoplasty. Br J Ophthalmol this way lead to a more marked inflammatory 1991, 75: 34-7. reaction whch can contribute to the occlusion H Thc glaucoma laser trial research group: The glau­ of outflow channels. coma laser trial (GLT), 2. Results of argon laser Weinreb et al. reported less pressure trabeculoplasty versus topical medicines. Oph­ thalmology 1990.97: 140 3-1 3. increase over 1800 than over 3600 LTP in glau­ Y Ofner S, Samples JR, Van Buskirk EM: Pilocarpine coma eyes on medication prior to treatment.3 and the increase in intraocular pressure after tra­ Primary LTP over 3600 seems to be far more beculoplasty. Am J Ophthalmol1984, 97: 647-9. efficient than treatment of 1800 of the trabec­ II) Metcalfe TW and Etchells DE: Prevention of the immediate intraocular pressure rise following ular meshwork.24 Dividing 3600 primary LTP argon laser trabeculoplasty. Br J Ophthalmol 1800 in two sessions did not reduce the post­ 1989,73: 612"'{}. II laser hypertensive response when the lOP rise Robin AL: The role of apraclonidine hydrochloride in both 1800 sessions is taken into in laser therapy for glaucoma. TransAm Ophthal­ consideration.2s mol Soc1990, 87: 729"'{}1. 12 Ruderman 1M, Zweig KO, Wilensky IT, Weinreb Our study was not masked because the pil­ RN: Effects of corticosteroid pretreatment on ocarpine induced miosis was very obvious. argon laser trabeculoplasty. Am J Ophthalmol Apraclonidine, another agent used to prevent 198 3, 96: 84-9. I 1 laser induced pressure elevations, ,26 may IJ Pappas HR, Berry DP, Partamian L, Hertzmark E, also give the investigators clues to which eyes Epstein DL: Topical indomethacin therapy before argon laser trabeculoplasty. Am J Ophthal­ are pretreated. It can produce eyelid retrac­ mol 1985,99: 57l-5. 6 tion, conjunctival blanching and mydriasis2 ,27 14Dorigo MT, Dodo 0, Cecchi nato A: Aqueous and in this way unmask double-blind studies. prostaglandine E, and intraocular pressure after We do not consider that the inherent bias in argon laser trabeculoplasty in glaucoma patients pretreated with topical piroxicam. Int J Tiss Reac our study introduced by the conspicious pil­ 1987, IX: 73-5. ocarpine miosis can explain the large differ­ 15 Odberg T: Primary argon laser trabeculoplasty after ence in pressure increase between the pretreatment with timolol. A safe and economic pilocarpine and the untreated groups. therapy of early glaucoma, Acta Ophthalmol We recommend considering pilocarpine 1990,68: 3l7-9. 10 Schwartz B: Cupping and pallur of the optic disc, pretreatment to reduce pressure increase in Arch Ophthalmol197 3,89: 272-7. primary LTP. All patients should be routinely 17 Scheie HG: Width and pigmentation of the angle of monitored for two hours after treatment and the anterior chamber. Arch Ophthalmol1957,58: patients with considerable glaucoma damage 510-2. IH Nelson FT, probably even longer to detect delayed pres­ WL, Fraunfelder Sills 1M, Arrowsmith IB, Kuritsky IN: Adverse respiratory and cardio­ gure spikes. vascular events attributed to timolol ophthalmic Key words: Glaucoma, laser, laser surgery, laser solution,1978-1985. Am J Ophthalmol1986, 102: trabeculoplasty. 606-11. IY References Leung KW and Gillies WE: The detection and Hoskins HD, Hetherington 1, Minckler OS, Lieber­ management of the acute rise in intraocular pres­ man MF, Shaffer RN: Complications of laser tra­ sure following laser trabeculoplasty, Aust NZ J beculoplasty. Ophthalmology198 3, 90: 796-9. Ophthalmol1986, 14: 259"'{}2. 0 Thomas IV, Simmons Rl, Belcher CD: Argon laser 2 Koss MC, March WF, Nordquist RE, Gherezghiher trabeculoplasty in the presurgical glaucoma T: Acute intraocular pressure elevation produced patient. Ophthalmology1982,89: 187-97. by argon laser trabeculoplaty in the cynomolgus 3Wcinreb RN, Ruderman 1, luster R, Zweig K: monkey. Arch Ophthalmol1984, 102: 1699-70 3. Immediate intraocular pressure response to argon 21 Greenidge KC, Rodrigues MM, Spaeth GL, Tra­ laser trabeculoplasty. Am J Ophthalmol198 3,95: verso CE, Weinreb S: Acute intraocular pressure 279-86. elevation after argon laser trabeculoplasty and iri­ Levene R: Major early complications of laser trabe­ dectomy: A clinicopathologic study. Ophthalmic culoplasty. Ophthalmic Surg198 3, 14: 947-5 3, Surg1984, 15: 105-10. 394 T. ELSAs ET AL.

22 Glaucoma laser trial research group:1. Acute effects 25 Elsas T, Johnsen H, Brevik TA: The immediate of argon laser trabeculoplasty on intraocular pres­ pressure response to primary laser trabeculo­ sure. Arch Ophthalmol1989, 107: 1135-42. plasty-comparison of one- and two-stage treat­ 23 Webers CAB and Hendrikse F: A prospective study ment. Acta Ophthalmol1989, 67: 664-8. 16 on variables in patients with intraocular pressure Brown RH, Stewart RH, Lynch MG, et al.: ALO rises following argon laser trabeculoplasty. Laser 2145 reduces the intra-ocular pressure elevation and Light in Ophthalmology1990, 3: 111-7. after anterior segment laser surgery. Ophthal­ 24 Elsas T: Primary laser trabeculoplasty : a comparison mology 1988,95: 378-84. of 50 spots in1800 and100 spots in 3600 of the tra­ n Robin AL: Short-term effects of unilateral1 % apra­ becular meshwork. Acta Ophthalmol 1987, 65: clonidine therapy. Arch Ophthal mol 1988, 106: 323-5. 912-5.