- Email: [email protected]
Topical ketorolac tromethamine 0.5% versus diclofenac sodium 0.1% to inhibit miosis during cataract surgery
Topical ketorolac tromethamine 0.5% versus diclofenac sodium 0.1% to inhibit miosis during cataract surgery Renuka Srinivasan, MS, Madhavaranga, MP, MS, DNB, ABSTRACT Purpose: To compare the effect of topical ketorolac tromethamine 0.5% solution and topical diclofenac sodium 0.1% solution on the inhibition of surgically induced miosis. Setting: Tertiary care teaching hospital in South India. Methods: Fifty-one patients were prospectively randomized to receive ketorolac 0.5% or diclofenac 0.1% at 3 intervals preoperatively. Patients with diabetes mellitus, pseudoexfoliation, or local pupil abnormalities were excluded from the study. Mydriatics comprising homatropine 1% plus phenylephrine 10% were instilled in all patients 1 hour before the peribulbar block at 5 intervals. Horizontal pupil diameters were obtained at the beginning of surgery, after capsulotomy, after intraocular lens (IOL) implantation, and at the end of surgery. Results: The mean horizontal pupil diameter was 7.40 mm at the start of surgery in both groups. The ketorolac group showed a consistent trend toward larger pupil diameters at subsequent surgical intervals. Changes from baseline also indicated more significant inhibition of miosis in the ketorolac group. Conclusions: Topical ketorolac was a more effective inhibitor of miosis than topical diclofenac during extracapsular cataract extraction and IOL implantation. It also provided a more stable mydriatic effect throughout surgery. J Cataract Refract Surg 2002; 28:517–520 © 2002 ASCRS and ESCRS
M
odern cataract surgery requires stable and adequate mydriasis lasting throughout the procedure for performing continuous curvilinear capsulorhexis, complete removal of lens cortical remnants, and placement of an intraocular lens (IOL) in the capsular bag. Currently, preoperative sympathomimetics and anticholinergics are used topically and intraoperative epinephrine is used intracamerally to maintain dilation
Accepted for publication July 20, 2001. From the Department of Ophthalmology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India. Reprint requests to Dr. Renuka Srinivasan, Professor, Department of Ophthalmology, JIPMER, Pondicherry-605 006, India. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
during cataract surgery.1,2 In addition, topical flurbiprofen sodium 0.03%, a nonsteroidal antiinflammatory drug (NSAID), is administered preoperatively to reduce surgically induced miosis.3–5 Prostaglandins are synthesized in the iris and ciliary body in response to trauma or anterior segment surgery.6 –9 Nonsteroidal antiinflammatory drugs inhibit prostaglandins by suppressing cyclooxygenase, the enzyme that transforms arachidonic acid to prostaglandin precursors. Prostaglandins are released routinely during cataract surgery. This release is potentiated by iris manipulation during surgery. The release is associated with an increased inflammatory response and miosis.10,11 Pretreatment with cyclooxygenase inhibitors suppresses 0886-3350/02/$–see front matter PII S0886-3350(01)01115-4
SURGICALLY INDUCED MIOSIS
prostaglandin synthesis and thus attempts to block surgically induced miosis.3,6 Many NSAIDs are available on the market. They have been approved for a variety of uses. Topical flurbiprofen 0.03% is widely used preoperatively to inhibit surgically induced miosis. Topical ketorolac tromethamine 0.5% is clinically effective for ocular allergies12 and to control cystoid macular edema (CME).13 Our study compared the effects of topical ketorolac 0.5% ophthalmic solution (Ketlur威) with diclofenac sodium 0.1% ophthalmic solution (Vorac威) on the inhibition of miosis during routine cataract surgery.
Patients and Methods Fifty-one patients having conventional extracapsular cataract extraction with posterior chamber IOL implantation were included in the study. Patients with diabetes mellitus, pseudoexfoliation, or local pupil abnormalities were excluded. Patients were prospectively randomized into 2 groups. One group received ketorolac (n ⫽ 25) and the other, diclofenac (n ⫽ 26). Patients received 1 drop (approximately 20 L) of ketorolac or diclofenac every 15 minutes for 3 intervals beginning 1 hour before surgery. The surgeon was masked to patient randomization. All patients received a standard preoperative regimen of 1 drop each of homatropine 2% and phenylephrine hydrochloride 10% every 10 minutes for 5 intervals 1 hour before the peribulbar block. In addition, 0.5 mL of 1:1000 epinephrine was added to each 500 mL bag of
Ringer’s lactate to be used as an irrigating solution during surgery. Surgery began with peribulbar anesthesia of lidocaine 2% with bupivacaine and hyaluronidase. The horizontal pupil diameter was measured using Castroviejo surgical calipers at the beginning of surgery; after capsulotomy, irrigation/aspiration (I/A), nucleus delivery, and IOL implantation; and at the end of the procedure. All measurements were obtained after the viscoelastic material was removed. Based on the results of a pilot study estimating a standard deviation of 0.70 mm and assuming a 0.50 mm difference in horizontal pupil diameter between the 2 groups to be clinically significant, Altman’s nomogram was used to estimate the number of patients needed in each study group to equal 25. An unpaired Student t test was used to compare the mean horizontal pupil diameters between the 2 groups.
Results Table 1 shows the mean horizontal pupil diameters in both groups at various surgical stages. Table 2 shows the decrease in mean horizontal pupil diameters at various surgical stages. The ketorolac group had fewer miotic changes than the diclofenac group during the entire surgical procedure (Figure 1). The difference in the mean horizontal pupil diameter between groups was statistically significant, especially after nucleus delivery (P ⫽ .022).
Discussion Fatty acid precursors produce prostaglandins at various sites in the eye including the conjunctiva, iris, cili-
Table 1. Mean horizontal pupil diameters at various stages of surgery. Mean Pupil Diameter (mm) ⴞ SD Ketorolac Group (n ⴝ 25)
Diclofenac Group (n ⴝ 26)
Beginning of surgery
7.40 ⫾ 0.78
7.42 ⫾ 0.72
.25*
End of capsulotomy
6.75 ⫾ 0.97
6.01 ⫾ 0.91
.13*
After nucleus delivery
6.48 ⫾ 1.30
5.84 ⫾ 1.23
.022
Stage
P Value
End of I/A
6.56 ⫾ 0.86
6.15 ⫾ 0.68
.015
After IOL implantation
6.38 ⫾ 0.71
6.12 ⫾ 0.76
.77*
End of surgery
6.34 ⫾ 0.68
6.13 ⫾ 1.02
.98*
I/A ⫽ irrigation/aspiration; IOL ⫽ intraocular lens *Not significant
518
J CATARACT REFRACT SURG—VOL 28, MARCH 2002
SURGICALLY INDUCED MIOSIS
Table 2. Mean decrease in pupil diameter from baseline at various stages of surgery. Mean Decrease (mm) ⴞ SD Stage
Ketorolac Group Diclofenac Group (n ⴝ 25) (n ⴝ 26)
End of capsulotomy
0.65
1.40
After nucleus delivery
0.92
1.57
End of I/A
1.08
1.26
After IOL implantation
1.02
1.29
End of surgery
1.06
1.28
I/A ⫽ irrigation/aspiration; IOL ⫽ intraocular lens
ary body, and retina.6,7 This production can occur in response to surgical trauma to the anterior segment. As a result, there is breakdown of the blood–aqueous barrier and an increase in aqueous protein concentration. Irritative ocular responses are triggered including miosis and an increase in intraocular pressure.10,11 Exogenous administration of prostaglandins also causes miosis and inflammation.14 Prostaglandin synthesis inhibitors can suppress the effects of these irritative ocular responses by blocking cyclooxygenase.15,16 This has been demonstrated in both rabbits and humans.17 Topical NSAIDs have various clinical uses such as to treat seasonal allergic conjunctivitis,12 as prophylaxis against CME after cataract surgery,18 to manage chronic CME,18 and to suppress pain after photorefractive keratectomy.19
Ketorolac tromethamine is the first parenteral NSAID available for analgesic use in the United States.18 This cyclooxygenase inhibitor was more effective and less toxic than many other cyclooxygenase inhibitors when tested after topical applications in laboratory experiments.20 It has excellent ocular absorbance after topical administration.21 It decreases corneal sensitivity soon after its topical application and hence is tolerated better.22 It is also available at a higher concentration (0.5%) than diclofenac sodium (0.1%). In our study, the ketorolac group showed a consistent trend toward larger pupil diameters, especially during I/A, thereby aiding the surgeon in complete removal of lens cortex and in-the-bag IOL fixation. Pupil diameters were the smallest before I/A, probably because no intracameral epinephrine was used before this step. After nucleus delivery and during I/A, epinephrine in the irrigating solution also maintained mydriasis. Although intracameral epinephrine has a clear role in maintaining mydriasis, NSAIDs play a part in preventing miosis.23 Intraocular mydriatics such as epinephrine together with prostaglandin inhibitors such as ketorolac may have an additional, if not a synergistic effect on miosis inhibition during routine cataract surgery.23 Our study, which compared the effectiveness of ketorolac and diclofenac in preventing surgically induced miosis, found a statistically significant difference in the mean horizontal pupil diameters between the 2 groups
Figure 1. (Srinivasan) Horizontal pupil diameters at different surgical stages (light bars ⫽ ketorolac group; dark bars ⫽ diclofenac group). J CATARACT REFRACT SURG—VOL 28, MARCH 2002
519
SURGICALLY INDUCED MIOSIS
after nucleus delivery (P ⫽ .022) and during I/A (P ⫽ .015). This result is consistent with that of Solomon et al.23 We concur with the opinion of Solomon et al. that ketorolac can be given preoperatively to patients having cataract surgery to inhibit miosis and can be given after surgery to reduce postoperative inflammation. In conclusion, topical ketorolac tromethamine 0.5% was better than topical diclofenac sodium 0.1% in inhibiting surgically induced miosis. Topical ketorolac has an additive effect to intracameral epinephrine in maintaining stable mydriasis during conventional cataract surgery.
References 1. Girard LJ, Hawkins RS. Cataract extraction by ultrasonic aspiration; vitrectomy by ultrasonic aspiration. Trans Am Acad Ophthalmol Otolaryngol 1974; 78:OP50 –OP59 2. Freeman JM, Gettelfinger TC. Maintaining pupillary dilitation during lens implant surgery. Am Intra-Ocular Implant Soc J 1981; 7:172–173 3. Podos SM. Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease. Trans Am Ophthalmol Soc 1976; 74:637– 660 4. Keates RH, McGowan KA. Clinical trial of flurbiprofen to maintain pupillary dilation during cataract surgery. Ann Ophthalmol 1984; 16:919 –921 5. Hillman JS, Frank GJ, Kheskani MB. Flurbiprofen and human intraocular inflammation. Adv Prostaglandin Thromboxane Res 1980; 8:1723–1725 6. Bhattacherjee P, Eakins KE. Inhibition of the prostaglandin synthetase systems in ocular tissues by indomethacin. Br J Pharmacol 1974; 50:227–230 7. Ambache N, Brummer HC. A Simple chemical procedure for distinguishing E from F prostaglandins with application to tissue extracts. Br J Pharmacol 1968; 33: 162–170 8. Ambache N, Kavanagh L, Whiting J. Effect of mechanical stimulation on rabbits eyes: release of active substance in anterior chamber perfusates. J Physiol 1965; 176:378 – 408 9. Anggard E, Samuelsson B. Smooth muscle stimulating lipids in sheep iris: the identification of prostaglandin F2 ␣. Biochem Pharmacol 1964; 13:281–283
520
10. Cole DF, Unger WG. Prostaglandins as mediators for the responses of the eye to trauma. Exp Eye Res 1973; 17: 357–368 11. Eakins KE. Prostaglandin and non-prostaglandin mediated breakdown of blood-aqueous barrier. Exp Eye Res 1977; 25(suppl):483– 498 12. Ballas Z, Blumenthal M, Tinkelman DG, et al. Clinical evaluation of ketorolac tromethamine 0.5% ophthalmic solution for the treatment of seasonal allergic conjunctivitis. Surv Ophthalmol 1993; 38:141–148 13. Flach AJ, Dolan BJ, Irvine AR. Effectiveness of ketorolac tromethamine 0.5% ophthalmic solution for chronic aphakic and pseudophakic cystoid macular edema. Am J Ophthalmol 1987; 103:479 – 486 14. Bhattacherjee P, Eakins KE. Inhibition of the ocular effects of sodium arachidonate by anti-inflammatory compounds. Prostaglandins 1975; 9:175–182 15. Sawa M, Masuda K. Topical indomethacin in soft cataract aspiration. Jpn J Ophthalmol 1976; 20:514 –519 16. Podos SM, Becker B. Comparison of ocular prostaglandin synthesis inhibitors. Invest Ophthalmol 1976; 15: 841– 844 17. Klug RD, Krohn DL, Breitfeller JM, Dieterich D. Inhibition of trauma-induced miosis by indoxole. Ophthalmic Res 1981; 13:122–128 18. Flach AJ, Jampol LM, Weinberg D, et al. Improvement in visual acuity in chronic aphakic and pseudophakic cystoid macular edema after treatment with topical 0.5% ketorolac tromethamine. Am J Ophthalmol 1991; 112: 514 –519 19. Cherry PMH, Tutton MK, Adhikary H, et al. The treatment of pain following photorefractive keratectomy. J Refract Corneal Surg 1994; 10(suppl):S222–S225 20. Rooks WH II, Maloney PJ, Shott LD, et al. The analgesic and anti-inflammatory profile of ketorolac and its tromethamine salt. Drugs Exp Clin Res 1985; 11:479 – 492 21. Rooks WH II. The pharmacologic activity of ketorolac tromethamine. Pharmacotherapy 1990; 10(pt 2):30S– 32S 22. Seitz B, Sorken K, LaBree LD, et al. Corneal sensitivity and burning sensation; comparing topical ketorolac and diclofenac. Arch Ophthalmol 1996; 114:921–924 23. Solomon KD, Turkalj JW, Whiteside SB, et al. Topical 0.5% ketorolac vs 0.03% flurbiprofen for inhibition of miosis during cataract surgery. Arch Ophthalmol 1997; 115:1119 –1122
J CATARACT REFRACT SURG—VOL 28, MARCH 2002
M
odern cataract surgery requires stable and adequate mydriasis lasting throughout the procedure for performing continuous curvilinear capsulorhexis, complete removal of lens cortical remnants, and placement of an intraocular lens (IOL) in the capsular bag. Currently, preoperative sympathomimetics and anticholinergics are used topically and intraoperative epinephrine is used intracamerally to maintain dilation
Accepted for publication July 20, 2001. From the Department of Ophthalmology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India. Reprint requests to Dr. Renuka Srinivasan, Professor, Department of Ophthalmology, JIPMER, Pondicherry-605 006, India. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
during cataract surgery.1,2 In addition, topical flurbiprofen sodium 0.03%, a nonsteroidal antiinflammatory drug (NSAID), is administered preoperatively to reduce surgically induced miosis.3–5 Prostaglandins are synthesized in the iris and ciliary body in response to trauma or anterior segment surgery.6 –9 Nonsteroidal antiinflammatory drugs inhibit prostaglandins by suppressing cyclooxygenase, the enzyme that transforms arachidonic acid to prostaglandin precursors. Prostaglandins are released routinely during cataract surgery. This release is potentiated by iris manipulation during surgery. The release is associated with an increased inflammatory response and miosis.10,11 Pretreatment with cyclooxygenase inhibitors suppresses 0886-3350/02/$–see front matter PII S0886-3350(01)01115-4
SURGICALLY INDUCED MIOSIS
prostaglandin synthesis and thus attempts to block surgically induced miosis.3,6 Many NSAIDs are available on the market. They have been approved for a variety of uses. Topical flurbiprofen 0.03% is widely used preoperatively to inhibit surgically induced miosis. Topical ketorolac tromethamine 0.5% is clinically effective for ocular allergies12 and to control cystoid macular edema (CME).13 Our study compared the effects of topical ketorolac 0.5% ophthalmic solution (Ketlur威) with diclofenac sodium 0.1% ophthalmic solution (Vorac威) on the inhibition of miosis during routine cataract surgery.
Patients and Methods Fifty-one patients having conventional extracapsular cataract extraction with posterior chamber IOL implantation were included in the study. Patients with diabetes mellitus, pseudoexfoliation, or local pupil abnormalities were excluded. Patients were prospectively randomized into 2 groups. One group received ketorolac (n ⫽ 25) and the other, diclofenac (n ⫽ 26). Patients received 1 drop (approximately 20 L) of ketorolac or diclofenac every 15 minutes for 3 intervals beginning 1 hour before surgery. The surgeon was masked to patient randomization. All patients received a standard preoperative regimen of 1 drop each of homatropine 2% and phenylephrine hydrochloride 10% every 10 minutes for 5 intervals 1 hour before the peribulbar block. In addition, 0.5 mL of 1:1000 epinephrine was added to each 500 mL bag of
Ringer’s lactate to be used as an irrigating solution during surgery. Surgery began with peribulbar anesthesia of lidocaine 2% with bupivacaine and hyaluronidase. The horizontal pupil diameter was measured using Castroviejo surgical calipers at the beginning of surgery; after capsulotomy, irrigation/aspiration (I/A), nucleus delivery, and IOL implantation; and at the end of the procedure. All measurements were obtained after the viscoelastic material was removed. Based on the results of a pilot study estimating a standard deviation of 0.70 mm and assuming a 0.50 mm difference in horizontal pupil diameter between the 2 groups to be clinically significant, Altman’s nomogram was used to estimate the number of patients needed in each study group to equal 25. An unpaired Student t test was used to compare the mean horizontal pupil diameters between the 2 groups.
Results Table 1 shows the mean horizontal pupil diameters in both groups at various surgical stages. Table 2 shows the decrease in mean horizontal pupil diameters at various surgical stages. The ketorolac group had fewer miotic changes than the diclofenac group during the entire surgical procedure (Figure 1). The difference in the mean horizontal pupil diameter between groups was statistically significant, especially after nucleus delivery (P ⫽ .022).
Discussion Fatty acid precursors produce prostaglandins at various sites in the eye including the conjunctiva, iris, cili-
Table 1. Mean horizontal pupil diameters at various stages of surgery. Mean Pupil Diameter (mm) ⴞ SD Ketorolac Group (n ⴝ 25)
Diclofenac Group (n ⴝ 26)
Beginning of surgery
7.40 ⫾ 0.78
7.42 ⫾ 0.72
.25*
End of capsulotomy
6.75 ⫾ 0.97
6.01 ⫾ 0.91
.13*
After nucleus delivery
6.48 ⫾ 1.30
5.84 ⫾ 1.23
.022
Stage
P Value
End of I/A
6.56 ⫾ 0.86
6.15 ⫾ 0.68
.015
After IOL implantation
6.38 ⫾ 0.71
6.12 ⫾ 0.76
.77*
End of surgery
6.34 ⫾ 0.68
6.13 ⫾ 1.02
.98*
I/A ⫽ irrigation/aspiration; IOL ⫽ intraocular lens *Not significant
518
J CATARACT REFRACT SURG—VOL 28, MARCH 2002
SURGICALLY INDUCED MIOSIS
Table 2. Mean decrease in pupil diameter from baseline at various stages of surgery. Mean Decrease (mm) ⴞ SD Stage
Ketorolac Group Diclofenac Group (n ⴝ 25) (n ⴝ 26)
End of capsulotomy
0.65
1.40
After nucleus delivery
0.92
1.57
End of I/A
1.08
1.26
After IOL implantation
1.02
1.29
End of surgery
1.06
1.28
I/A ⫽ irrigation/aspiration; IOL ⫽ intraocular lens
ary body, and retina.6,7 This production can occur in response to surgical trauma to the anterior segment. As a result, there is breakdown of the blood–aqueous barrier and an increase in aqueous protein concentration. Irritative ocular responses are triggered including miosis and an increase in intraocular pressure.10,11 Exogenous administration of prostaglandins also causes miosis and inflammation.14 Prostaglandin synthesis inhibitors can suppress the effects of these irritative ocular responses by blocking cyclooxygenase.15,16 This has been demonstrated in both rabbits and humans.17 Topical NSAIDs have various clinical uses such as to treat seasonal allergic conjunctivitis,12 as prophylaxis against CME after cataract surgery,18 to manage chronic CME,18 and to suppress pain after photorefractive keratectomy.19
Ketorolac tromethamine is the first parenteral NSAID available for analgesic use in the United States.18 This cyclooxygenase inhibitor was more effective and less toxic than many other cyclooxygenase inhibitors when tested after topical applications in laboratory experiments.20 It has excellent ocular absorbance after topical administration.21 It decreases corneal sensitivity soon after its topical application and hence is tolerated better.22 It is also available at a higher concentration (0.5%) than diclofenac sodium (0.1%). In our study, the ketorolac group showed a consistent trend toward larger pupil diameters, especially during I/A, thereby aiding the surgeon in complete removal of lens cortex and in-the-bag IOL fixation. Pupil diameters were the smallest before I/A, probably because no intracameral epinephrine was used before this step. After nucleus delivery and during I/A, epinephrine in the irrigating solution also maintained mydriasis. Although intracameral epinephrine has a clear role in maintaining mydriasis, NSAIDs play a part in preventing miosis.23 Intraocular mydriatics such as epinephrine together with prostaglandin inhibitors such as ketorolac may have an additional, if not a synergistic effect on miosis inhibition during routine cataract surgery.23 Our study, which compared the effectiveness of ketorolac and diclofenac in preventing surgically induced miosis, found a statistically significant difference in the mean horizontal pupil diameters between the 2 groups
Figure 1. (Srinivasan) Horizontal pupil diameters at different surgical stages (light bars ⫽ ketorolac group; dark bars ⫽ diclofenac group). J CATARACT REFRACT SURG—VOL 28, MARCH 2002
519
SURGICALLY INDUCED MIOSIS
after nucleus delivery (P ⫽ .022) and during I/A (P ⫽ .015). This result is consistent with that of Solomon et al.23 We concur with the opinion of Solomon et al. that ketorolac can be given preoperatively to patients having cataract surgery to inhibit miosis and can be given after surgery to reduce postoperative inflammation. In conclusion, topical ketorolac tromethamine 0.5% was better than topical diclofenac sodium 0.1% in inhibiting surgically induced miosis. Topical ketorolac has an additive effect to intracameral epinephrine in maintaining stable mydriasis during conventional cataract surgery.
References 1. Girard LJ, Hawkins RS. Cataract extraction by ultrasonic aspiration; vitrectomy by ultrasonic aspiration. Trans Am Acad Ophthalmol Otolaryngol 1974; 78:OP50 –OP59 2. Freeman JM, Gettelfinger TC. Maintaining pupillary dilitation during lens implant surgery. Am Intra-Ocular Implant Soc J 1981; 7:172–173 3. Podos SM. Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease. Trans Am Ophthalmol Soc 1976; 74:637– 660 4. Keates RH, McGowan KA. Clinical trial of flurbiprofen to maintain pupillary dilation during cataract surgery. Ann Ophthalmol 1984; 16:919 –921 5. Hillman JS, Frank GJ, Kheskani MB. Flurbiprofen and human intraocular inflammation. Adv Prostaglandin Thromboxane Res 1980; 8:1723–1725 6. Bhattacherjee P, Eakins KE. Inhibition of the prostaglandin synthetase systems in ocular tissues by indomethacin. Br J Pharmacol 1974; 50:227–230 7. Ambache N, Brummer HC. A Simple chemical procedure for distinguishing E from F prostaglandins with application to tissue extracts. Br J Pharmacol 1968; 33: 162–170 8. Ambache N, Kavanagh L, Whiting J. Effect of mechanical stimulation on rabbits eyes: release of active substance in anterior chamber perfusates. J Physiol 1965; 176:378 – 408 9. Anggard E, Samuelsson B. Smooth muscle stimulating lipids in sheep iris: the identification of prostaglandin F2 ␣. Biochem Pharmacol 1964; 13:281–283
520
10. Cole DF, Unger WG. Prostaglandins as mediators for the responses of the eye to trauma. Exp Eye Res 1973; 17: 357–368 11. Eakins KE. Prostaglandin and non-prostaglandin mediated breakdown of blood-aqueous barrier. Exp Eye Res 1977; 25(suppl):483– 498 12. Ballas Z, Blumenthal M, Tinkelman DG, et al. Clinical evaluation of ketorolac tromethamine 0.5% ophthalmic solution for the treatment of seasonal allergic conjunctivitis. Surv Ophthalmol 1993; 38:141–148 13. Flach AJ, Dolan BJ, Irvine AR. Effectiveness of ketorolac tromethamine 0.5% ophthalmic solution for chronic aphakic and pseudophakic cystoid macular edema. Am J Ophthalmol 1987; 103:479 – 486 14. Bhattacherjee P, Eakins KE. Inhibition of the ocular effects of sodium arachidonate by anti-inflammatory compounds. Prostaglandins 1975; 9:175–182 15. Sawa M, Masuda K. Topical indomethacin in soft cataract aspiration. Jpn J Ophthalmol 1976; 20:514 –519 16. Podos SM, Becker B. Comparison of ocular prostaglandin synthesis inhibitors. Invest Ophthalmol 1976; 15: 841– 844 17. Klug RD, Krohn DL, Breitfeller JM, Dieterich D. Inhibition of trauma-induced miosis by indoxole. Ophthalmic Res 1981; 13:122–128 18. Flach AJ, Jampol LM, Weinberg D, et al. Improvement in visual acuity in chronic aphakic and pseudophakic cystoid macular edema after treatment with topical 0.5% ketorolac tromethamine. Am J Ophthalmol 1991; 112: 514 –519 19. Cherry PMH, Tutton MK, Adhikary H, et al. The treatment of pain following photorefractive keratectomy. J Refract Corneal Surg 1994; 10(suppl):S222–S225 20. Rooks WH II, Maloney PJ, Shott LD, et al. The analgesic and anti-inflammatory profile of ketorolac and its tromethamine salt. Drugs Exp Clin Res 1985; 11:479 – 492 21. Rooks WH II. The pharmacologic activity of ketorolac tromethamine. Pharmacotherapy 1990; 10(pt 2):30S– 32S 22. Seitz B, Sorken K, LaBree LD, et al. Corneal sensitivity and burning sensation; comparing topical ketorolac and diclofenac. Arch Ophthalmol 1996; 114:921–924 23. Solomon KD, Turkalj JW, Whiteside SB, et al. Topical 0.5% ketorolac vs 0.03% flurbiprofen for inhibition of miosis during cataract surgery. Arch Ophthalmol 1997; 115:1119 –1122
J CATARACT REFRACT SURG—VOL 28, MARCH 2002