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Management of Increased Intraocular Pressure After Cataract Extraction
Management of Increased Intraocular Pressure After Cataract Extraction Richard S. Ruiz, M.D., Charles A. Wilson, M.D., Kathryn H. Musgrove, M.D., and Thomas C. Prager, Ph.D.
We measured the change in intraocular pres sure prospectively after extracapsular cataract extraction in 80 eyes after treatment with ei ther pilocarpine gel, pilocarpine 4% solution, timolol 0.5% solution, or placebo. Intraocular pressure, pupil size, and anterior chamber cellular reaction were measured in a masked fashion on the first day after surgery. A signifi cant increase in intraocular pressure was found in all groups postoperatively when com pared with baseline values (P < .001). Eyes treated with pilocarpine gel had an average intraocular pressure increase of 4.2 ± 2.1 mm Hg (mean ± 1 S.E.), eyes treated with pilocarpine 4% eyedrops had an average in crease of 9.8 ± 2.8 mm Hg, and eyes treated with timolol demonstrated an intraocular pres sure increase of 8.25 ± 3.19. The intraocular pressure in untreated eyes (controls) increased by an average of 12.9 ± 2.7 mm Hg. Only the difference in intraocular pressure change be tween the eyes treated with pilocarpine gel and control eyes was statistically significant (P = .025). Postsurgical intraocular pressure ex ceeding 25 mm Hg was observed in three of 20 pilocarpine gel treated eyes (15%) and 11 of 20 control eyes (55%). Pilocarpine treatment was not associated with noticeable changes in in traocular inflammatory response, nor were sig nificant ocular or systemic adverse reactions observed. A single administration of pilocar pine gel is effective in reducing increased intraocular pressure for the first 24 hours after extracapsular cataract extraction. INTRAOCULAR PRESSURE was first reported to increase in the immediate period after cataract
Accepted for publication Jan. 9, 1987 From the Hermann Eye Center, University of Texas Health Science Center, Houston, Texas. This study was supported in part by the Hermann Eye Fund. Reprint requests to Richard S. Ruiz, M.D., Hermann Eye Center, 1203 Ross Sterling Ave., Houston, TX 77030.
extraction by Gormaz in 1962.' Using a water tight wound closure, Rich2 later found that a significant increase in intraocular pressure was characteristic after cataract extraction. He showed that alpha-chymotrypsin was not re quired for this increase. This study also repudi ated beliefs that hypotony was normal after cataract extraction. Rich, Radtke, and Cohen 3 described the kinetics of the early postsurgery intraocular pressure surge and found that in traocular pressure reached an average peak of 39.3 mm Hg at a mean time of 6.8 hours after surgery. Intraocular pressure then decreased to an average of 23.1 mm Hg at 24 hours. Rapidly increasing intraocular pressure was associated with pain and corneal edema, but lingering increased intraocular pressure was frequently present in the absence of these features. 3 Hayreh 4 has associated increased postsurgi cal intraocular pressure with the development of anterior ischemic optic neuropathy. In Hayreh's series, after postcataract surgery anterior ischemic optic neuropathy in the first eye, the risk of anterior ischemic optic neuropa thy increased after surgery on the second eye. Intraocular pressure may be increased after surgery by the introduction of sodium hyaluronate (Healon) into the anterior chamber.5-6 Olivius and Thorburn" have shown that sodium hyaluronate induced increased intraocular pressure is partially reversible by removal or dilution of viscoelastic material by irrigation. The most commonly used drugs to control intraocular pressure after cataract surgery are timolol and acetazolamide. 4,5813 In a recent study, timolol treatment did not lead to a sig nificant decrease in intraocular pressure in the early period after extracapsular cataract extrac tion with the use of sodium hyaluronate. 8 Acet azolamide produces side effects that limit its routine use. Miotics are frequently used to constrict the pupil after placement of a posteri or chamber intraocular lens, but they have not been evaluated for effectiveness in controlling early postsurgical ocular hypertension.
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Viscous pilocarpine 4% is a recently intro duced vehicle for pilocarpine administration that is reportedly effective for 24 hours. 1415 This longer effect may improve its suitability for use after cataract extraction. Aqueous pilocarpine has been shown to produce a dose related decrease in intraocular pressure up to a concen tration of 4%. I6 Drance, Bensted, and Schulzer" showed that 4% aqueous pilocarpine produces a significant decrease in intraocular pressure as long as 15 hours after administration. Timolol also has been shown to decrease intraocular pressure for 24 hours. 18 We investigated the effect of pilocarpine gel, pilocarpine solution, and timolol on increased intraocular pressure after extracapsular cataract extraction with the use of sodium hyaluronate.
Material and Methods Eighty patients who were scheduled for rou tine extracapsular cataract extraction and pos terior chamber lens implantation were random ized to one of the following treatment groups: (1) pilocarpine 4% gel, (2) pilocarpine 4% solu tion, (3) timolol 0.5% solution, or (4) balanced salt 0.5% solution (placebo). Each treatment group admitted data from 20 eyes. Criteria for acceptance into the study included no history of intraocular surgery, retinal detachment re pair, or uveitis; no history of glaucoma or chronic need for ocular medications; no record of intraocular pressure in excess of 22 mm Hg in either eye; cataract best treated by extracapsu lar surgery; and no contraindication to the use of a posterior chamber intraocular lens or to the use of viscous sodium hyaluronate (Healon). One of us (K.H.M.), who was masked to the treatment group, measured all intraocular pressures by applanation tonometry using the same Goldmann tonometer. Intraocular pres sure measurements were taken for each patient visit with the tonometer prism oriented hori zontally and vertically to correct for corneal astigmatism. Five minutes were allowed be tween consecutive measurements to avoid artifactually lowering intraocular pressure. The or thogonal measurements were averaged to find the corrected intraocular pressure and record ed as data. A third, horizontal, measurement was taken, which served as a quality control. When the horizontal measurements were in disagreement (a difference of > 2 mm Hg), measurements were repeated until the horizon
tal pressure readings were within 2 mm Hg of one another. Baseline intraocular pressures were mea sured the day before surgery between 8 A.M. and 2 P.M. Postoperative pressures were mea sured approximately 24 hours (20 to 28 hours) after surgery. Anterior chamber cells were graded on a scale of 1+ to 4+ by slit-lamp examination. Pupil size was measured under controlled illumination. All patients underwent extracapsular cata ract extraction and implantation of a Sinskytype posterior chamber intraocular lens under retrobulbar anesthesia performed by one of us (R.S.R.). Pupils were dilated preoperatively with tropicamide 1% and phenylephrine 2Vz%, given in three sets at approximately 15-minute intervals. All patients received epinephrine ir rigation into the anterior chamber to enhance pupillary dilation during surgery. Sodium hy aluronate was introduced into the anterior chamber before intraocular lens implantation in all cases. Aqueous acetylcholine solution was used to constrict the pupil after insertion of the posterior chamber lens. All viscoelastic material was removed from the anterior and posterior chambers using an irrigationaspiration device. The surgical wound was closed "watertight" using four interrupted 10-0 Prolene sutures and two 8-0 Vicryl su tures. One half milliliter of betamethasone was injected subconjunctivally. Each eye was then randomly assigned to receive pilocarpine 4% gel, pilocarpine 4% solution, timolol 0.5% solu tion, or placebo administered onto the surface of the cornea before eyelid closure and patch ing. Drug dosages were as follows: pilocarpine 4% gel, 1 inch; pilocarpine 4% solution, two drops; timolol 0.5% solution, two drops; bal anced salt solution (placebo), two drops.
Results Eyes treated with pilocarpine gel developed a mean intraocular pressure increase of 4.2 ± 2.1 mm Hg (mean ± 1 S.E.), eyes treated with pilocarpine solution increased by 9.8 ± 2.8 mm Hg, eyes treated with timolol solution in creased intraocular pressure by 6.8 ± 1.96, and untreated eyes increased by 12.9 ± 2.7 mm Hg (Fig. 1). The difference between the pilocarpine gel treated eyes and the untreated eyes was statistically significant (P = .025, pairwise f-test). Eyes treated with either pilocarpine or
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PLACEBO
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TIMOLOL
DROPS PLACEBO
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PILO
TIMOLOL
Fig. 1 (Ruiz and associates). Intraocular pressure difference (24 hours postsurgery intraocular pres sure minus presurgery intraocular pressure). Mean ± 1 S.E. of the mean is plotted for placebo, pilocar pine gel, pilocarpine eyedrops, and timolol treat ment groups.
timolol were not statistically different from one another or from the placebo group. The mean baseline intraocular pressure (presurgery values) did not differ significantly among the four groups (Fig. 2), although a comparison of preoperative vs postoperative intraocular pressure measurements (data for all groups combined) was highly significant (P < .00001). Mean postoperative intraocular pressure varied according to treatment group and averaged under 20 mm Hg in the pilocarpine gel treated group (19.4 ± 2.2 mm Hg). The average intraocular pressure for the timolol treated group was 22.93 ± 1.96 mm Hg and for the pilocarpine solution treated group, 24.38 ± 2.74 mm Hg. Control eyes (placebo group) averaged 28.1 ± 2.9 mm Hg after surgery. Postoperative intraocular pressures in excess of 25 mm Hg occurred in three of 20 eyes given pilocarpine gel (15%), eight of 20 eyes given pilocarpine eyedrops (40%), eight of 20 eyes given timolol (40%), and 11 of 20 control eyes (55%). Anterior chamber cells were not found to correlate significantly with intraocular pressure change within the treatment groups. Intraocu lar inflammation, as measured by anterior
Fig. 2 (Ruiz and associates). Intraocular pressure minus presurgery intraocular pressure vs intraocular pressure minus 24 hours postsurgery intraocular pressure for placebo, pilocarpine gel, pilocarpine eyedrops, and timolol treatment groups. Mean ± 1 S.E. of the mean is plotted.
chamber cells, also was not different in eyes treated with pilocarpine (gel or solution) or timolol when compared with untreated eyes. Average anterior chamber cells were graded in each of the four treatment groups. In seven of 19 eyes (37%) examined in the pilocarpine gel treated group, in six of 20 eyes (30%) in the pilocarpine solution treated group, in three of 20 eyes (15%) in the timolol group, and in six of 18 eyes (33%) in the untreated group, 4+ cells were recorded. Postoperative pupil diameter appeared to parallel intraocular pressure changes according to treatment group. Pilocarpine gel treated eyes measured 2.2 ± 0.6 mm, aqueous pilocar pine 4% treated eyes measured 2.6 ± 0.7 mm, ti molol treated eyes measured 2.5 ± 0.22 mm, and untreated eyes measured 3.0 ± 1.2 mm. Intraocular pressure changes correlated signifi cantly (r = .66) with postoperative pupil diame ter only in control eyes (P = .007). This effect was a result primarily of the high intraocular pressure changes that were associated with pupil sizes of 4.0 mm or greater (Fig. 3). No serious ocular or systemic side effects caused by pilocarpine or timolol treatment were observed. Patients frequently complained of mild brow ache the morning after surgery, but this generally disappeared by the second postoperative day.
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Discussion Rich, Radtke, and Cohen 3 observed intraocu lar pressures as high as 50 mm Hg in patients 24 hours after intracapsular cataract extraction without the use of alpha-chymotrypsin. Intra ocular pressures of this magnitude may in crease the risk of anterior ischemic optic neu ropathy. 4 We report four eyes with intraocular pressure exceeding 50 mm Hg after extracapsular cataract extraction and posterior chamber lens implantation performed using sodium hyaluronate. Of these four eyes, two eyes were not treated with pilocarpine, one eye received pilocarpine gel, and one eye received pilocar pine eyedrops. Our results demonstrate that the frequency of 24-hour postoperative intraocular pressures in excess of 25 mm Hg varied according to group: pilocarpine gel, 15%; timolol 0.5%, 35%; pilocarpine solution, 40%; placebo, 55%. Pilo carpine gel was the longest acting agent at 24 hours. Although timolol has been shown to lower effectively postsurgical increased intra ocular pressure after intracapsular cataract ex traction,10'11 Timoda, Tuberville, and Wood8 have shown it to be ineffective after extracapsular cataract extraction and the use of sodium hyaluronate. Our findings indicated that timo lol was partially effective, but not significantly different than the control group, with an aver age intraocular pressure increase of 6.8 mm Hg when sodium hyaluronate is used but re moved. The significant decrease in mean intra ocular pressure change in this study with the
1—
1
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use of pilocarpine gel suggests that this is the drug of choice for treatment of postextracapsular cataract extraction intraocular pressure increase in the first 24 hours after surgery when sodium hyaluronate is used. A trend toward lower intraocular pressure change was found among eyes in this study that were given pilo carpine 4% eyedrops. A 14% to 15% reduction in intraocular pressure has been observed with pilocarpine 4% and 8% solutions as long as 15 hours after administration. 17 A trend toward lower intraocular pressure was found in those postsurgical eyes treated with timolol. Timolol has been associated with exacerba tion of congestive heart failure, worsening of asthma, and central nervous system side ef fects. 1923 The decreased heart rate caused by timolol administration may also decrease ocu lar perfusion pressure and increase the possi bility of anterior ischemic optic neuropathy. Pilocarpine has been associated with only two reported cases of serious systemic toxicit v 24,25 j n both cases, large doses were adminis tered within a short period of time for the treatment of acute narrow-angle glaucoma. Rhegmatogenous retinal detachment has also been reported after the use of miotics.6,26'27 Pape and Forbes26 proposed that this may be the result of the anterior movement of the ora serrata and anterior vitreous that physiologi cally accompanies accomodation. The risk of a retinal tear might then be expected to diminish with age and gradual loss of accomodation. Miosis is usually desired during extracapsular cataract surgery for proper positioning of an intraocular lens in the posterior chamber and
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for clearing t h e iris from t h e surgical incision. This can be a c c o m p l i s h e d by i n t r a c a m e r a l injec tion of s h o r t - a c t i n g a g e n t s , s u c h as a c e t y l c h o line that w a s u s e d in this s t u d y . O u r r e s u l t s in control eyes i n d i c a t e t h a t t h e p u p i l often be comes m i d - d i l a t e d t h e d a y after s u r g e r y . Post operative pupillary diameters greater than 3 m m o c c u r r e d in five of 15 p l a c e b o eyes in w h i c h m e a s u r e m e n t s w e r e t a k e n (33%). Intraocular pressures recorded postsurgically in t h e s e five eyes w e r e g e n e r a l l y h i g h e r t h a n t h o s e r e c o r d e d in t h e o t h e r c o n t r o l eyes (Fig. 3). N o c o r r e l a t i o n w a s f o u n d b e t w e e n p u p i l size a n d i n t r a o c u l a r p r e s s u r e c h a n g e in pilocarpine t r e a t e d e y e s , since m o s t p u p i l s w e r e miotic. A l t h o u g h s t r o n g miotic t r e a t m e n t after sur gery m i g h t be e x p e c t e d to i n c r e a s e iritis a n d p r e d i s p o s e to s e c o n d a r y m e m b r a n e f o r m a t i o n , a d m i n i s t r a t i o n of p i l o c a r p i n e gel or e y e d r o p s as d e s c r i b e d d i d n o t increase a n t e r i o r c h a m b e r cell reaction to a n y m e a s u r a b l e d e g r e e . N o s e c o n d a r y m e m b r a n e s or p o s t e r i o r s y n e c h i a e occurred.
References 1. Gormaz, A.: Ocular tension after cataract sur gery. Am. J. Ophthalmol. 53:832, 1962. 2. Rich, W. J.: Intraocular pressure and wound closure after cataract extraction. Trans. Ophthalmol. Soc. U.K. 88:437, 1968. 3. Rich, W. J., Radtke, N. D., and Cohen, B. E.: Early ocular hypertension after cataract extraction. Br. J. Ophthalmol. 58:725, 1974. 4. Hayreh, S. S.: Anterior ischemic optic neuropa thy. IV. Occurrence after cataract surgery. Arch. Ophthalmol. 98:1410, 1980. 5. Binkhorst, C. D.: Inflammation and intraocular pressure after the use of Healon in intraocular lens surgery. Am. Intraocular Implant Soc. J. 6:340, 1980. 6. Alpar, J. J.: Miotics and retinal detachment. A survey and case report. Ann. Ophthalmol. 11:395, 1979. 7. Olivius, E., and Thorburn, W.: Intraocular pres sure after surgery with Healon. Am. Intraocular Implant Soc. J. 11:480, 1985. 8. Timoda, T., Tuberville, A. W., and Wood, T. O.: Timolol and postoperative intraocular pres sure. Am. Intraocular Implant Soc. J. 10:180, 1984. 9. Tuberville, A. W., Nissenkorn, I., Tomoda, T., and Wood, T. O.: Postsurgical intraocular pressure elevation. Am. Intraocular Implant Soc. J. 9:309, 1983.
491
10. Obstbaum, S. A., and Galin, M. A.: The ef fects of timolol on cataract extraction and intraocular pressure. Am. J. Ophthalmol. 88:1017, 1979. 11. Haimann, M. H., and Phelps, C. D.: Prophylac tic timolol for the prevention of high intraocular pressure after cataract extraction. A randomized, prospective, double-blind trial. Ophthalmology 88:233, 1981. 12. Biedner, B. Z., Rosenblatt, I., David, R., and Sacks, U.: The effect of timolol on early increased intraocular pressure after cataract extraction. Glau coma 4:53, 1982. 13. Miller, D., and Stegmann, R.: Secondary intra ocular lens implantation using sodium hyaluronate. Ann. Ophthalmol. 14:621, 1982. 14. March, W. F., Stewart, R. M., Mandell, A. I., and Bruce, L. A.: Duration of effect of pilocarpine gel. Arch. Ophthalmol. 100:1270, 1982. 15. Stewart, R. H., Kimbrough, R. L., Smith, J. P., and Ward, R.: Long acting pilocarpine gel. A doseresponse in ocular hypertensive subjects. Glaucoma 6:182, 1984. 16. Drance, S. M., and Nash, P. A.: The dose response of human intraocular pressure to pilocar pine. Can. J. Ophthalmol. 6:9, 1971. 17. Drance, S. M., Bensted, M., and Schulzer, M.: Pilocarpine and intraocular pressure. Duration of effectiveness of 4% and 8% pilocarpine instillation. Arch. Ophthalmol. 91:104, 1974. 18. Zimmerman, T. J., and Kaufman, H. E.: Tim olol dose response and duration of action. Arch. Ophthalmol. 95:605, 1977. 19. McMahon, C. D., Shaffer, R. N., Hoskins, H. D., and Hetherington, J.: Adverse effects experi enced by patients taking timolol. Am. J. Ophthalmol. 88:736, 1979. 20. Van Buskirk, E. M.: Adverse reactions from timolol administration. Ophthalmology 87:447, 1980. 21. Fraunfelder, F. T.: Interim report. National registry of possible drug-induced ocular side effects. Ophthalmology 87:87, 1980. 22. Britman, N. A.: Cardiac effects of topical timolol. N. Engl. J. Med. 300:566, 1979. 23. Wilson, R. P., Spaeth, G. L., and Poryzees, E.: The place of timolol in the practice of ophthalmolo gy. Ophthalmology 87:451, 1980. 24. Greco, J. J., and Kelman, C. D.: Systemic pilo carpine toxicity in the treatment of angle closure glaucoma. Ann. Ophthalmol. 5:57, 1973. 25. Epstein, E., and Kaufman, I.: Systemic pilocar pine toxicity from overdosage in treatment of an attack of angle-closure glaucoma. Am. J. Ophthal mol. 59:109, 1965. 26. Pape, L. G., and Forbes, M.: Retinal detach ment and miotic therapy. Am. J. Ophthalmol. 85:558, 1978. 27. Beasley, H., and Fraunfelder, F. T.: Retinal detachments and topical ocular miotics. Ophthal mology 86:95, 1979.
We measured the change in intraocular pres sure prospectively after extracapsular cataract extraction in 80 eyes after treatment with ei ther pilocarpine gel, pilocarpine 4% solution, timolol 0.5% solution, or placebo. Intraocular pressure, pupil size, and anterior chamber cellular reaction were measured in a masked fashion on the first day after surgery. A signifi cant increase in intraocular pressure was found in all groups postoperatively when com pared with baseline values (P < .001). Eyes treated with pilocarpine gel had an average intraocular pressure increase of 4.2 ± 2.1 mm Hg (mean ± 1 S.E.), eyes treated with pilocarpine 4% eyedrops had an average in crease of 9.8 ± 2.8 mm Hg, and eyes treated with timolol demonstrated an intraocular pres sure increase of 8.25 ± 3.19. The intraocular pressure in untreated eyes (controls) increased by an average of 12.9 ± 2.7 mm Hg. Only the difference in intraocular pressure change be tween the eyes treated with pilocarpine gel and control eyes was statistically significant (P = .025). Postsurgical intraocular pressure ex ceeding 25 mm Hg was observed in three of 20 pilocarpine gel treated eyes (15%) and 11 of 20 control eyes (55%). Pilocarpine treatment was not associated with noticeable changes in in traocular inflammatory response, nor were sig nificant ocular or systemic adverse reactions observed. A single administration of pilocar pine gel is effective in reducing increased intraocular pressure for the first 24 hours after extracapsular cataract extraction. INTRAOCULAR PRESSURE was first reported to increase in the immediate period after cataract
Accepted for publication Jan. 9, 1987 From the Hermann Eye Center, University of Texas Health Science Center, Houston, Texas. This study was supported in part by the Hermann Eye Fund. Reprint requests to Richard S. Ruiz, M.D., Hermann Eye Center, 1203 Ross Sterling Ave., Houston, TX 77030.
extraction by Gormaz in 1962.' Using a water tight wound closure, Rich2 later found that a significant increase in intraocular pressure was characteristic after cataract extraction. He showed that alpha-chymotrypsin was not re quired for this increase. This study also repudi ated beliefs that hypotony was normal after cataract extraction. Rich, Radtke, and Cohen 3 described the kinetics of the early postsurgery intraocular pressure surge and found that in traocular pressure reached an average peak of 39.3 mm Hg at a mean time of 6.8 hours after surgery. Intraocular pressure then decreased to an average of 23.1 mm Hg at 24 hours. Rapidly increasing intraocular pressure was associated with pain and corneal edema, but lingering increased intraocular pressure was frequently present in the absence of these features. 3 Hayreh 4 has associated increased postsurgi cal intraocular pressure with the development of anterior ischemic optic neuropathy. In Hayreh's series, after postcataract surgery anterior ischemic optic neuropathy in the first eye, the risk of anterior ischemic optic neuropa thy increased after surgery on the second eye. Intraocular pressure may be increased after surgery by the introduction of sodium hyaluronate (Healon) into the anterior chamber.5-6 Olivius and Thorburn" have shown that sodium hyaluronate induced increased intraocular pressure is partially reversible by removal or dilution of viscoelastic material by irrigation. The most commonly used drugs to control intraocular pressure after cataract surgery are timolol and acetazolamide. 4,5813 In a recent study, timolol treatment did not lead to a sig nificant decrease in intraocular pressure in the early period after extracapsular cataract extrac tion with the use of sodium hyaluronate. 8 Acet azolamide produces side effects that limit its routine use. Miotics are frequently used to constrict the pupil after placement of a posteri or chamber intraocular lens, but they have not been evaluated for effectiveness in controlling early postsurgical ocular hypertension.
©AMERICAN JOURNAL OF OPHTHALMOLOGY 103:487-491, APRIL, 1987
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Viscous pilocarpine 4% is a recently intro duced vehicle for pilocarpine administration that is reportedly effective for 24 hours. 1415 This longer effect may improve its suitability for use after cataract extraction. Aqueous pilocarpine has been shown to produce a dose related decrease in intraocular pressure up to a concen tration of 4%. I6 Drance, Bensted, and Schulzer" showed that 4% aqueous pilocarpine produces a significant decrease in intraocular pressure as long as 15 hours after administration. Timolol also has been shown to decrease intraocular pressure for 24 hours. 18 We investigated the effect of pilocarpine gel, pilocarpine solution, and timolol on increased intraocular pressure after extracapsular cataract extraction with the use of sodium hyaluronate.
Material and Methods Eighty patients who were scheduled for rou tine extracapsular cataract extraction and pos terior chamber lens implantation were random ized to one of the following treatment groups: (1) pilocarpine 4% gel, (2) pilocarpine 4% solu tion, (3) timolol 0.5% solution, or (4) balanced salt 0.5% solution (placebo). Each treatment group admitted data from 20 eyes. Criteria for acceptance into the study included no history of intraocular surgery, retinal detachment re pair, or uveitis; no history of glaucoma or chronic need for ocular medications; no record of intraocular pressure in excess of 22 mm Hg in either eye; cataract best treated by extracapsu lar surgery; and no contraindication to the use of a posterior chamber intraocular lens or to the use of viscous sodium hyaluronate (Healon). One of us (K.H.M.), who was masked to the treatment group, measured all intraocular pressures by applanation tonometry using the same Goldmann tonometer. Intraocular pres sure measurements were taken for each patient visit with the tonometer prism oriented hori zontally and vertically to correct for corneal astigmatism. Five minutes were allowed be tween consecutive measurements to avoid artifactually lowering intraocular pressure. The or thogonal measurements were averaged to find the corrected intraocular pressure and record ed as data. A third, horizontal, measurement was taken, which served as a quality control. When the horizontal measurements were in disagreement (a difference of > 2 mm Hg), measurements were repeated until the horizon
tal pressure readings were within 2 mm Hg of one another. Baseline intraocular pressures were mea sured the day before surgery between 8 A.M. and 2 P.M. Postoperative pressures were mea sured approximately 24 hours (20 to 28 hours) after surgery. Anterior chamber cells were graded on a scale of 1+ to 4+ by slit-lamp examination. Pupil size was measured under controlled illumination. All patients underwent extracapsular cata ract extraction and implantation of a Sinskytype posterior chamber intraocular lens under retrobulbar anesthesia performed by one of us (R.S.R.). Pupils were dilated preoperatively with tropicamide 1% and phenylephrine 2Vz%, given in three sets at approximately 15-minute intervals. All patients received epinephrine ir rigation into the anterior chamber to enhance pupillary dilation during surgery. Sodium hy aluronate was introduced into the anterior chamber before intraocular lens implantation in all cases. Aqueous acetylcholine solution was used to constrict the pupil after insertion of the posterior chamber lens. All viscoelastic material was removed from the anterior and posterior chambers using an irrigationaspiration device. The surgical wound was closed "watertight" using four interrupted 10-0 Prolene sutures and two 8-0 Vicryl su tures. One half milliliter of betamethasone was injected subconjunctivally. Each eye was then randomly assigned to receive pilocarpine 4% gel, pilocarpine 4% solution, timolol 0.5% solu tion, or placebo administered onto the surface of the cornea before eyelid closure and patch ing. Drug dosages were as follows: pilocarpine 4% gel, 1 inch; pilocarpine 4% solution, two drops; timolol 0.5% solution, two drops; bal anced salt solution (placebo), two drops.
Results Eyes treated with pilocarpine gel developed a mean intraocular pressure increase of 4.2 ± 2.1 mm Hg (mean ± 1 S.E.), eyes treated with pilocarpine solution increased by 9.8 ± 2.8 mm Hg, eyes treated with timolol solution in creased intraocular pressure by 6.8 ± 1.96, and untreated eyes increased by 12.9 ± 2.7 mm Hg (Fig. 1). The difference between the pilocarpine gel treated eyes and the untreated eyes was statistically significant (P = .025, pairwise f-test). Eyes treated with either pilocarpine or
Intraocular Pressure After Cataract Extraction
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I 0 P DIFFERENCE
(POST - PRE)
35 j post
(MEAN + 1 SE) 20
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0
'/
1 [ z
PLACEBO
GEL
PILO
TIMOLOL
DROPS PLACEBO
GEL
PILO
TIMOLOL
Fig. 1 (Ruiz and associates). Intraocular pressure difference (24 hours postsurgery intraocular pres sure minus presurgery intraocular pressure). Mean ± 1 S.E. of the mean is plotted for placebo, pilocar pine gel, pilocarpine eyedrops, and timolol treat ment groups.
timolol were not statistically different from one another or from the placebo group. The mean baseline intraocular pressure (presurgery values) did not differ significantly among the four groups (Fig. 2), although a comparison of preoperative vs postoperative intraocular pressure measurements (data for all groups combined) was highly significant (P < .00001). Mean postoperative intraocular pressure varied according to treatment group and averaged under 20 mm Hg in the pilocarpine gel treated group (19.4 ± 2.2 mm Hg). The average intraocular pressure for the timolol treated group was 22.93 ± 1.96 mm Hg and for the pilocarpine solution treated group, 24.38 ± 2.74 mm Hg. Control eyes (placebo group) averaged 28.1 ± 2.9 mm Hg after surgery. Postoperative intraocular pressures in excess of 25 mm Hg occurred in three of 20 eyes given pilocarpine gel (15%), eight of 20 eyes given pilocarpine eyedrops (40%), eight of 20 eyes given timolol (40%), and 11 of 20 control eyes (55%). Anterior chamber cells were not found to correlate significantly with intraocular pressure change within the treatment groups. Intraocu lar inflammation, as measured by anterior
Fig. 2 (Ruiz and associates). Intraocular pressure minus presurgery intraocular pressure vs intraocular pressure minus 24 hours postsurgery intraocular pressure for placebo, pilocarpine gel, pilocarpine eyedrops, and timolol treatment groups. Mean ± 1 S.E. of the mean is plotted.
chamber cells, also was not different in eyes treated with pilocarpine (gel or solution) or timolol when compared with untreated eyes. Average anterior chamber cells were graded in each of the four treatment groups. In seven of 19 eyes (37%) examined in the pilocarpine gel treated group, in six of 20 eyes (30%) in the pilocarpine solution treated group, in three of 20 eyes (15%) in the timolol group, and in six of 18 eyes (33%) in the untreated group, 4+ cells were recorded. Postoperative pupil diameter appeared to parallel intraocular pressure changes according to treatment group. Pilocarpine gel treated eyes measured 2.2 ± 0.6 mm, aqueous pilocar pine 4% treated eyes measured 2.6 ± 0.7 mm, ti molol treated eyes measured 2.5 ± 0.22 mm, and untreated eyes measured 3.0 ± 1.2 mm. Intraocular pressure changes correlated signifi cantly (r = .66) with postoperative pupil diame ter only in control eyes (P = .007). This effect was a result primarily of the high intraocular pressure changes that were associated with pupil sizes of 4.0 mm or greater (Fig. 3). No serious ocular or systemic side effects caused by pilocarpine or timolol treatment were observed. Patients frequently complained of mild brow ache the morning after surgery, but this generally disappeared by the second postoperative day.
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POSTOPERATIVE PUPIL DIAMETER
Discussion Rich, Radtke, and Cohen 3 observed intraocu lar pressures as high as 50 mm Hg in patients 24 hours after intracapsular cataract extraction without the use of alpha-chymotrypsin. Intra ocular pressures of this magnitude may in crease the risk of anterior ischemic optic neu ropathy. 4 We report four eyes with intraocular pressure exceeding 50 mm Hg after extracapsular cataract extraction and posterior chamber lens implantation performed using sodium hyaluronate. Of these four eyes, two eyes were not treated with pilocarpine, one eye received pilocarpine gel, and one eye received pilocar pine eyedrops. Our results demonstrate that the frequency of 24-hour postoperative intraocular pressures in excess of 25 mm Hg varied according to group: pilocarpine gel, 15%; timolol 0.5%, 35%; pilocarpine solution, 40%; placebo, 55%. Pilo carpine gel was the longest acting agent at 24 hours. Although timolol has been shown to lower effectively postsurgical increased intra ocular pressure after intracapsular cataract ex traction,10'11 Timoda, Tuberville, and Wood8 have shown it to be ineffective after extracapsular cataract extraction and the use of sodium hyaluronate. Our findings indicated that timo lol was partially effective, but not significantly different than the control group, with an aver age intraocular pressure increase of 6.8 mm Hg when sodium hyaluronate is used but re moved. The significant decrease in mean intra ocular pressure change in this study with the
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use of pilocarpine gel suggests that this is the drug of choice for treatment of postextracapsular cataract extraction intraocular pressure increase in the first 24 hours after surgery when sodium hyaluronate is used. A trend toward lower intraocular pressure change was found among eyes in this study that were given pilo carpine 4% eyedrops. A 14% to 15% reduction in intraocular pressure has been observed with pilocarpine 4% and 8% solutions as long as 15 hours after administration. 17 A trend toward lower intraocular pressure was found in those postsurgical eyes treated with timolol. Timolol has been associated with exacerba tion of congestive heart failure, worsening of asthma, and central nervous system side ef fects. 1923 The decreased heart rate caused by timolol administration may also decrease ocu lar perfusion pressure and increase the possi bility of anterior ischemic optic neuropathy. Pilocarpine has been associated with only two reported cases of serious systemic toxicit v 24,25 j n both cases, large doses were adminis tered within a short period of time for the treatment of acute narrow-angle glaucoma. Rhegmatogenous retinal detachment has also been reported after the use of miotics.6,26'27 Pape and Forbes26 proposed that this may be the result of the anterior movement of the ora serrata and anterior vitreous that physiologi cally accompanies accomodation. The risk of a retinal tear might then be expected to diminish with age and gradual loss of accomodation. Miosis is usually desired during extracapsular cataract surgery for proper positioning of an intraocular lens in the posterior chamber and
Intraocular Pressure After Cataract Extraction
Vol. 103, No. 4
for clearing t h e iris from t h e surgical incision. This can be a c c o m p l i s h e d by i n t r a c a m e r a l injec tion of s h o r t - a c t i n g a g e n t s , s u c h as a c e t y l c h o line that w a s u s e d in this s t u d y . O u r r e s u l t s in control eyes i n d i c a t e t h a t t h e p u p i l often be comes m i d - d i l a t e d t h e d a y after s u r g e r y . Post operative pupillary diameters greater than 3 m m o c c u r r e d in five of 15 p l a c e b o eyes in w h i c h m e a s u r e m e n t s w e r e t a k e n (33%). Intraocular pressures recorded postsurgically in t h e s e five eyes w e r e g e n e r a l l y h i g h e r t h a n t h o s e r e c o r d e d in t h e o t h e r c o n t r o l eyes (Fig. 3). N o c o r r e l a t i o n w a s f o u n d b e t w e e n p u p i l size a n d i n t r a o c u l a r p r e s s u r e c h a n g e in pilocarpine t r e a t e d e y e s , since m o s t p u p i l s w e r e miotic. A l t h o u g h s t r o n g miotic t r e a t m e n t after sur gery m i g h t be e x p e c t e d to i n c r e a s e iritis a n d p r e d i s p o s e to s e c o n d a r y m e m b r a n e f o r m a t i o n , a d m i n i s t r a t i o n of p i l o c a r p i n e gel or e y e d r o p s as d e s c r i b e d d i d n o t increase a n t e r i o r c h a m b e r cell reaction to a n y m e a s u r a b l e d e g r e e . N o s e c o n d a r y m e m b r a n e s or p o s t e r i o r s y n e c h i a e occurred.
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10. Obstbaum, S. A., and Galin, M. A.: The ef fects of timolol on cataract extraction and intraocular pressure. Am. J. Ophthalmol. 88:1017, 1979. 11. Haimann, M. H., and Phelps, C. D.: Prophylac tic timolol for the prevention of high intraocular pressure after cataract extraction. A randomized, prospective, double-blind trial. Ophthalmology 88:233, 1981. 12. Biedner, B. Z., Rosenblatt, I., David, R., and Sacks, U.: The effect of timolol on early increased intraocular pressure after cataract extraction. Glau coma 4:53, 1982. 13. Miller, D., and Stegmann, R.: Secondary intra ocular lens implantation using sodium hyaluronate. Ann. Ophthalmol. 14:621, 1982. 14. March, W. F., Stewart, R. M., Mandell, A. I., and Bruce, L. A.: Duration of effect of pilocarpine gel. Arch. Ophthalmol. 100:1270, 1982. 15. Stewart, R. H., Kimbrough, R. L., Smith, J. P., and Ward, R.: Long acting pilocarpine gel. A doseresponse in ocular hypertensive subjects. Glaucoma 6:182, 1984. 16. Drance, S. M., and Nash, P. A.: The dose response of human intraocular pressure to pilocar pine. Can. J. Ophthalmol. 6:9, 1971. 17. Drance, S. M., Bensted, M., and Schulzer, M.: Pilocarpine and intraocular pressure. Duration of effectiveness of 4% and 8% pilocarpine instillation. Arch. Ophthalmol. 91:104, 1974. 18. Zimmerman, T. J., and Kaufman, H. E.: Tim olol dose response and duration of action. Arch. Ophthalmol. 95:605, 1977. 19. McMahon, C. D., Shaffer, R. N., Hoskins, H. D., and Hetherington, J.: Adverse effects experi enced by patients taking timolol. Am. J. Ophthalmol. 88:736, 1979. 20. Van Buskirk, E. M.: Adverse reactions from timolol administration. Ophthalmology 87:447, 1980. 21. Fraunfelder, F. T.: Interim report. National registry of possible drug-induced ocular side effects. Ophthalmology 87:87, 1980. 22. Britman, N. A.: Cardiac effects of topical timolol. N. Engl. J. Med. 300:566, 1979. 23. Wilson, R. P., Spaeth, G. L., and Poryzees, E.: The place of timolol in the practice of ophthalmolo gy. Ophthalmology 87:451, 1980. 24. Greco, J. J., and Kelman, C. D.: Systemic pilo carpine toxicity in the treatment of angle closure glaucoma. Ann. Ophthalmol. 5:57, 1973. 25. Epstein, E., and Kaufman, I.: Systemic pilocar pine toxicity from overdosage in treatment of an attack of angle-closure glaucoma. Am. J. Ophthal mol. 59:109, 1965. 26. Pape, L. G., and Forbes, M.: Retinal detach ment and miotic therapy. Am. J. Ophthalmol. 85:558, 1978. 27. Beasley, H., and Fraunfelder, F. T.: Retinal detachments and topical ocular miotics. Ophthal mology 86:95, 1979.