|Year : 1992 | Volume
| Issue : 4 | Page : 109-114
Preoperative topical flurbiprofen-Na+ in extracapsular lens extraction role in maintaining intraoperative pupillary dilatation
KP Chaudhary, BK Sofat
Department of Ophthalmology, Indira Gandhi Medical College, Shimla-171001, India
K P Chaudhary
Department of Ophthalmology, I.G. Medical College, Shimla - 171001
Source of Support: None, Conflict of Interest: None
Induction of intraoperative pupillary constriction, is predominantly a prostaglandin mediated process. The most potent antiprostaglandin NSAID, Flurbiprofen was used topically to study its efficacy against the above. In a prospective double blind clinical study, 50 brown eyes undergoing planned E.C.C.E., the pupils were dilated with 10% phenylephrine and 2% homatropine 1%/tropicamide. 25 eyes received 0.03% Flurbiprofen-Na+ eye drops 1/2 hourly starting two hours before surgery. The maintained intraoperative mydriasis in the two groups before anterior chamber entry (stage I) vs at the end of complete cortex wash (stage III) was: in control group (stage I) 8.46 +/- 0.48 mm vs (stage III) 3.56 +/- 0.43 mm (highly SS); in flurbiprofen group (stage I) 8.60 +/- 0.48 mm vs (stage III) 8.01 +/- 0.63 mm (NSS). The pupillary area available for surgical manipulation in the control group was significantly decreased from 56.18 mm2 in state I to 9.94 mm2 in stage III, while in flurbiprofen group it changed insignificantly from 58.05 mm2 in stage I to 50.24 mm2 in stage III. Postoperatively after cataract was observed in 44% eyes of control group as compared to only 8% of eyes of flurbiprofen group. Thus a maintained intraoperative mydriasis in flurbiprofen group led to better E.C.L.E. which is a mandatory prerequisite to preferred and better present day posterior chamber IOL implantation.
Keywords: C - Control, F - Flurbiprofen; NSAID - Non steroidal an-tiinflammatory drug; AA - Arachidonic acid; Co - Cylo-oxygenase; PG - Prostaglandin; SE - Standard error of difference between two means. IOL - Intraocular lens implant. ECLE - Extra capsular lens extraction
|How to cite this article:|
Chaudhary K P, Sofat B K. Preoperative topical flurbiprofen-Na+ in extracapsular lens extraction role in maintaining intraoperative pupillary dilatation. Indian J Ophthalmol 1992;40:109-14
| Introduction|| |
The present day pendulum of cataract surgery has shifted in the favour of extra capsular lens extraction  due to better posterior chamber intraocular lens implantation and reduced endophthalmodonesis . The successful planned E.C.L.E whether by can-opening technique or phecoemulsification needs a mandatory prerequisite, a sustained intraoperative mydriasis in a preoperatively dilated pupil . But traumatic injuries including intraoperative manipulations are known to produce an atropine resistant miosis at the operation table ,,, The occurrence of intraoperative miosis is mediated by prostaglandin (PGE 2 ) ,, neural mechanism  and substance-P. ,,,. The neural mechanism induced miosis is blocked by most of the locally used anaesthetic agents and doubtfully by retrobulbar anaesthetic agent ,.Capsacin which depletes the substance-P causes initial miosis and is too irritant to be of clinical use . The prostaglandin synthesis inhibitors like nonsteroidal anti-inflammatory drugs (NSAID) have been shown to block miosis following ocular trauma in both animals ,,, and human beings ,,. To overcome the above, the intracameral use of epinephrine may produce in advertent complications ,,.
As discussed, intraoperative induced miosis in E.C.L.E. is mainly a prostaglandin mediated process ,,. In the biosynthesis of prostaglandins, the involved cyclo-oxygenase enzyme is inhibited by all NSAID, thus resulting in decreased prostaglandin concentration in tissues ,,,,,, Flurbiprofen, a phenylalkanoic acid (Sodium (±) - 2 - fluoro - methyl 1-4-biphenyl acetate dihydrate) is known to be one of the most potent NSAID ,. Topically flurbiprofen is effective in a concentration ranging from 0.01% to 2% and has 4% intraocular penetration of the instilled drug ,.Oral administration has been reported to produce visual hallucinations, confusions, abdominal pain and vomiting. But many clinical trials of flurbiprofen have established its efficacy both in systemic and local use ,,, over several years.
In view of the above, the present study was planned to evaluate the efficacy of topical flurbiprofen in maintaining intraoperative mydriasis during E.C.L.E. in brown human eyes.
| Material and methods|| |
Between March, 1988 to August, 88 in a prospective double blind study, the protocol required a group of 25 patients each with brown eyes in the control group and flurbiprofen group, which belonged to any age and either sex, but needed lens extraction. Preoperative slit lamp examination after dilatation was performed in all cases, and those showing signs of uveitis and posterior synechiae were excluded. The patients with history of allergy to NSAID were also excluded. X 2 test showed no significant difference between the two groups [Table - 1].
In all of the above cases planned extracapsular lens extraction was planned. Preoperatively, in both groups the pupils were dilated with 10% Phenylepherine and 2% Homatropine 1% / Tropicamide. The flurbiprofen group in addition to the above received four instillations of 0.03% of flurbiprofen eye drop (B-8-783, supplied by FDC, Bombay), in sodium salt solution (ph 7.0), 50 ul of each drop 1/2 hourly, starting two hours before surgery. The patients were selected randomly to be placed in either group. One patient with nuclear cataract in both eyes was placed for each eye in both the groups. All cases were operated under magnification by can-opening technique with 26G needle after topical, facial block and retrobulbar anaesthesia. The apparent pupillary diameter was measured by placing Castroviejo's calipers in front of the cornea which has fractions upto 0.5 mm.
Intraoperative mydriasis was measured at the following stages :- Stage I - Before anterior chamber entry.
Stage II - Anterior chamber entry to anterior capsulectomy and nucleus delivery
Stage III - Nucleus delivery to complete cortex wash. Irrigation and suction of the lens matter was done with ringer lactate plain solution. In the immediate postoperative period the eyes were observed for the presence of after cataract in a fully dilated pupil. Operative details and any complications were recorded on the evaluation sheet.
| Results|| |
The present study involved 50 patients comprising 25 patients each in the control as well as in the flurbiprofen group. The pupil of each patient was dilated as described, but each flurbiprofen group patient also received 0.03% of flurbiprofen eye drops 1/2 hourly beginning two hours before surgery. The present study was a double blind prospective study undertaken to evaluate the degree of maintained intraoperative mydriasis during extracapsular lens extraction.
The mean maintained intraoperative mydriasis in the control group was, as indicated on [Table - 2] and [Figure - 1]: Stage I 8.46 ± 0.48 mm, Stage II 5.81 ± 0.55 mm and Stage III 3.56 ± 0.43 mm. Standard error of difference between two means in Stage I verses Stage II (high SS), Stage II vs Stage III (high SS) and Stage I vs Stage III (very high SS). In the control group the pupillary area of 56.18 mm 2 in Stage I was reduced to 9.94 mm 2sub in Stage III. The percentage (%) change of pupil size and pupillary area beginning from State I to Stage III was - 4.9 (57.9%) and - 45.24 (82.3%) respectively [Table - 6].
The mean maintained intraoperative mydriasis in flurbiprofen group is indicated on [Table - 3], [Figure - 2]: Stage I - 8.60 ± 0.48 mm, Stage II - 8.44 ± 0.83mm and Stage III 8.01 ± 0.63 mm. The S.E. of difference in Stage I vs II, Stage II vs III and Stage I vs III is insignificant. In the flurbiprofen group the pupillary area of 58.05 mm 2 in Stage I was merely reduced to 50.24 mm 2 in Stage III. The percentage (%) change of pupil size and pupillary area beginning stage I to stage II was -0.59(6.8%) and -7.81 (13.45%) respectively [Table - 6]
Standard error of difference of maintained intraoperative mydriasis in control vs flurbiprofen group as shown on [Table - 4], [Figure - 3] is : Stage I 8.46 ± 0.48 vs Stage 18.60 ± 0.48 (NSS); Stage II 5.81 ± 0.55 vs Stage II 8.44 ± 0.83 (highly SS) and Stage Ill 3.56 ± 0.43 vs Stage Ill 8.01 ± 0.63 (very high SS). The pupillary area in control vs flurbiprofen as in [Table - 6] : in Stage I is 56.18 mm 2 vs 58.05 mm 2 and Stage Ill is 9.94 mm 2 vs 50.24 mm 2.
The mean pupillary constricter responses are as in [Table - 5] in control group are from Stage I to Stage II 2.6 mm, State II to Stage Ill 2.25 mm and Stage I to Stage Ill 4.9 mm. Flurbiprofen group showed the above response from Stage I to Stage II 0.16 mm, Stage II to Stage Ill 0.43 mm and Stage I to State Ill 0.59 mm.
After cataract was observed in 11 (44%) of the control group and 2 (8%) of flurbiprofen group eyes respectively [Table - 6].
| Discussion|| |
The first aim of all ophthalmic surgeons is to undertake successful extra capsular lens extraction to meet the present day need of posterior chamber IOL implantation .The above requires a sustained intraoperative mydriasis, whether it is done by canopening or phacoemulsification technique . But at the operation table most of the ophthalmic surgeons face induction of intraoperative miosis after opening of the anterior chamber, inspite of vigorous preoperative pupillary dilatation with both anticholinergic and sympathomimetic agents . The induced intraoperative miosis occurs because of various manipulations like surgical incision, iris manipulations, anterior chamber shallowing and prolonged irrigation, which may complicate posterior chamber IOL implantation. To overcome the above, the intracameral use of epinephrine may lead to inadvertent complication ,, like endothelial damage; and also sensitises myocardium to catecholamines during halothane and cyclopropane induced general anaesthesia. The three mechanisms inducing intraoperative miosis are as follows:
1. Prostaglandin (PGE 2 ) mediated ,,
2. Neural mechanism 
3. Substance-P ,,, (Peptide neurotransmitter)
As investigated by initial investigators like Ambache et al ., the miotic mediator was named IRIN. It was later found to be a prostaglandin, producing atropine resistant miosis. The neural mechanism which is blocked by topical and probably by retrobulbar anaesthetic agent, is related to their anaesthetic action at the sensory nerve terminals in the eye, which may inhibit the release or action of miotic substances . Neural mechanism if any, was blocked in both of our control and flurbiprofen group, where we used topical as well as retrobulbar anaesthetic agents. Inspite of this, the control group showed mean pupillary constriction of 4.9 mm as compared to 0.59 mm by flurbiprofen group, starting from Stage I to end of Stage III [Table - 4][Table - 5]; [Figure - 1][Figure - 2][Figure - 3]. Hence the neural mechanism does not appear to be one of the important mechanism in most of our cases, inhibiting the intraoperative miotic response. Although Van Rij et al. have shown partial blockage of intraoperative induced miosis with 0.4% Oxybuprocain .
The third mechanism is mediated by substance-P, which is believed to be a peptide neurotransmitter and is released upon antidromic nerve stimulation ,,,, Alternatively it might be an intermediary in the prostaglandin response as well, because destruction of the trigeminal nerve in rabbit abolishes the ocular response to prostaglandin E but not to substance-P as shown by Butler and coworkers ,. Substance-P depletor capsaicin is clinically an impractical proposition as yet, because of induction of initial miosis and being highly irritant .However substance-P fails to constrict pupil in baboons and humans, because inter species difference exist for antidromic reflex .
Nonsteroidal anti-inflammatory drugs (NSAID) which inhibit cyclo-oxygenase enzyme are prostaglandin synthesis inhibitors in both animals ,,,and human beings ,,. Flurbiprofen being one of the most potent NSAID ,,,,,, was used in a concentration of 0.03% to evaluate its effect in maintaining intraoperative mydriasis, which as discussed appears as the major mechanism in most of our cases. Prostaglandin synthesis from various sources are 50% and inhibited at a flurbiprofen concentration ranging from 4 to 98 ng/ml ,, while 4% of topically administered drug is intraocularly absorbed .The above shows that probably it was present in sufficient concentration in most of the eyes to have desirable therapeutic effects. The pupillary diameter in flurbiprofen group from Stage 18.48 ± 0.48 mm shows no significant difference in Stage III 8.01 + 0.63 mm, while control group shows significant miosis from Stage 18.46 ± 0.48 mm to Stage III 3.56 ± 0.43 mm [Table - 2][Table - 3][Table - 4]; [Figure - 1][Figure - 2][Figure - 3].
[Table - 6] shows that while comparing our data with Keats and McGowan  (1984) in human eyes, the percentage (%) change in pupil size of flurbiprofen group is -0.59 (6.8%) vs -2.5 (30.1%); and percentage (%) change of pupillary area is -7.81(13.45%) vs -27.67 (51.2%) beginning Stage I (Initial) to Stage III (Final) of E.C.L.E. procedure. These observation clearly indicate better maintained intraoperative mydriasis in our cases, which may be because present study included only brown eyes. These NSAID like miotics and mydriatics may have modified pharmacokinetic response in brown eyes because of ocular pigmentation as discussed by Mishima. 
The findings show that the flurbiprofen has been able to maintain a significant sustained mydriasis and available pupillary area for surgical manipulation, which was also supported by the fact that in the immediate postoperative period only 2 (8%) of eyes of this group showed the presence of after cataract in comparison to 11 (44%) eyes of the control group [Table - 6].
Hence the present study indicates that the maintained intraoperative mydriasis led to better lens matter wash in flurbiprofen group as compared to the control group thus leading to better E.C.L.E. In view of the above the routine use of topical flurbiprofen is recommended by all ophthalmologists contemplating successful I OL implantation owing to obvious advantage of maintained intraoperative mydriasis.
| Acknowledgements|| |
I am thankful to the faculty and residents of the Ophthalmology Department for their co-operation. I am also thankful to Mr. T.C. Dogra for photography work; Mr. P.N. Chauhan and Mr. Bhupesh Thakur for artistic work; and Mr. P.L. Nanda for typing work. Flurbiprofen salt was supplied by FDC, Bombay (India). (B-8-783). Author has no commercial or proprietary interest in the pharmacological agent used in this study.
| References|| |
Tasman, W. Are there any retinal contraindications to cataract surgery and posterior chamber lens implants?
Binkhorst,CD. Corneal and retinal complications after cataract extraction : the mechanical aspect of endophthalmodonesis. Ophthalmology, 1980; 84 : 609-617.
Jaffe, N.S. Quoted in book titled. Cataract surgery and its complications. 4th Ed. chapter 3, p 74.
Mishima s, Masuda K, Tamura R. The drugs influencing the intraocular pressure. In Dickstein S (ed) : cell pharmacology of the eye. Chap 4, p 128. S Karger AG, 1977.
Watzman MB. Possible new concepts relating prostaglandins to various ocular functions. Surv. Ophthalmol, 1970; 14 : 301.
Perkins E S. Prostaglandins and the eye. Adv. Ophthalmol, 1975; 29 : 2.
Ambache N, Kavanaugh L, Whiting J. Effect of mechanical stimulation on rabbits eyes : Release of active substances in anterior chamber perfusate. J. Physiol, 1965; 176 : 378.
Cole DF, Urger WG. Prostaglandins on mediator for the responses of the eye to trauma. Exp. Eye Res., 1973;17 : 357-68.
Watzman MB, King CS. Prostaglandin influences on intraocular pressure and pupil size. Am. J. Physiol, 1967; 212 . 329-34.
Camras CB. Bito LZ. The pathophysiological aspect of nitrogen mustard on the rabbit eye. 1. The biphasic intraocular pressure response and role of prostaglandin. Exp. Eye Res., 1980; 30 41-52.
Bill A, Stjernschantz J, Mandahl A, et al. Substance-P release on trigeminal nerve stimulation, effects in eye. Acta Physiol Scand., 1979; 106 : 371-3.
Stjernschantz J, Sears M, Stjernschantz L. Intraocular effects of substance-P in the rabbit. Invest Ophthalmol Vis Sci., 1981; 20 : 53-60.
Bito LZ, Baroody RA, Backerman A. The ocular hypertensive effect of physalacmin (PA), the miotic potency of poly-peptides and the development of subsensitivity to the miotic effect of substance-P. ARVO abstracts. Invest Ophthal Vis Sci., 1981; 20 (Suppl):64.
Butler JM, Unger wG, Cole DF. Axon reflex in ocular injury: sensory mediation of the response of the rabbit eye to laser irradiation of the iris. J. Exp. Physiol., 1980;65:261-72.
Unger WG, Cole DF, Bars MS. Prostaglandin and neurogenically mediated ocular response to laser irradiation of the rabbit iris. Exp Eye Res, 1977; 25:209-20
Havener WH. Ocular pharmacology, 4th ed. St. Louis, CV Mosby, 1978;68.
Duffin RM, Cameas CB and Gardner SK et al. Inhibitors of surgically induced miosis. Ophthalmology, 1982; 89:966-979.
Podos SM and Becker B. Comparison of ocular prostaglandin synthesis inhibitors. Invest Ophthalmol, 1976; 15:841-4.
Podos SM. Prostaglandins, Nonsteroidal anti-inflammatory agents and eye disease. Trans Am Ophthalmol Soc, 1976;74:637-60.
Sawa M and Masuda K. Topical indomethacin in soft cataract aspiration. Jpn J Ophthalmol 1976; 20:514-9.
Keates RH and Mc Gowan KA. Clinical trial of flurbiprofen to maintain pupillary dilation during cataract surgery. Ann. Ophthalmol. 1984; 16:919.
Keulen de Vos HCJ, Van Rij G, Renardel De Lavalette JCG et al. Effect of indomethacin in preventing surgically induced miosis. Br. J. Ophthalmol 1983;67:94-96.
Hull DS, Chemotti MT, Edelhauser HF et al. Effect of epinephrine on the corneal endothelium. Am. J. Ophthalmol 1975; 79:245-50.
Katz RL, Matteo RS and Papper EM. The injection of epinephrine during general anaesthesia with hyaluronated hydrocarbons and cyclopropane in man:il Halothane. Anesthesiology 1962; 23:597.
Higgs GA. Moncada S and Vane JR. Eicosanoids in inflammation. Ann of Clinical Research 1978; 16:287-299.
Adams SS and Buckles JW. Ibuprofen and flurbiprofen. Clin Rheum Dis 1979; 5: 359-79.
Van Miest AS and van Duinc. The antipyretic effect of flurbiprofen. Eur J Pharmacol 1977,44:197.
Anderson JA, Chen CC, Vita JR et al. Disposition of topical flurbiprofen in normal and aphakic rabbits eyes. Arch. Ophthalmol. 1982; 100:642645.
Sabiston DW and Robinson IG. An evaluation of the anti-inflammatory effect of flurbiprofen after cataract extraction. Br. J. Ophthalmol 1987; 71:418-421.
Weintreb RN, Robin AL, Baerve!dt G et al. Flurbiprofen pretreatment in argon laser trabeculoplasty for primary open angle glaucoma. Arch. Ophthalmol 1984; 102: 1629.
Gerser DK, Hodapp E, Goldberg I et al. Flurbiprofen and intraocular pressure. Ann. Ophthalmol 1981, 13: 831-3.
Miller D, Gruenberg P, Miller R et al. Topical flurbiprofen or prednisolone : effect on corneal wound healing on rabbits. Arch. Ophthalmol 1981; 99:681-2.
Stark WJ, Whitney CE and Chandler JW et al. Trends in intraocular leans implantation in the Unites States. Arch. Ophthalmol 1986; 104:1769-70.
Van Rij G, De Lavalette R, Baarsma GS and Jansen JTG. Effect of oxybuprocain 0.4% in preventing surgically induced miosis. Br. J. Ophthalmol 1984; 68:248-251.
Stone RA, Laties AM and Brecha NC. Substance-P like immunoreactive nerves in the anterior segment rabbit, cat and monkey eye. Neurol Science 1982; 7: 2459-2468.
Satristan D, Tessler H and Suners K et al. Reduction of inflammation following cataract surgery by NSAID, Flurbiprofen. Ophthalmic Surg. 1987; 18:873.
Bizzeto MF. Defranco I and Carillo F. Efficacy of flurbiprofen versus placebo on postoperative course following cataract extraction Drugs Exp. Clin. Res. 1984; 10:421.
Araie M, Sawa M and Takase M. Topical flurbiprofen and didoferae supresses blood aqueous barrier breakdown in cataract surgery. A flurophotometric study. Jpn. J. Ophthalmol 1983; 27:535.
Crook D, Collins AJ and Rose AJ. A comparison of the effects of flurbiprofen on prostaglandin synthetase from rheumatoid synovium and enzymatically active tissues. J. Pharm. Sci. 1977; 66: 219-224.
Mishima S. Clinical pharmakinetics of the eye. Investi. Ophthalmoi. Vis. Sci. 1981; 24:504.
[Figure - 1], [Figure - 2], [Figure - 3]
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6]
|This article has been cited by|
||Pupil dilation using a standard cataract surgery regimen alone or with atropine 1.0% pretreatment. Prospective comparative evaluation
| ||Narváez, J., Kronberg, B.P., Park, H., Zumwalt, J.R., Wong, B., Bacon, G., Rauser, M., (...), Zimmerman, G. |
| ||Journal of Cataract and Refractive Surgery. 2010; 36(4): 563-567 |
||Ketorolac tromethamine in the maintenance of intraoperative mydriasis
| ||Gupta, V.P., Dhaliwal, U., Prasad, N. |
| ||Ophthalmic Surgery and Lasers. 1997; 28(9): 731-738 |
||Comparative efficacy of topically applied flurbiprofen, diclofenac, tolmetin, and suprofen for the treatment of experimentally induced blood-aqueous barrier disruption in dogs
| ||Ward, D.A. |
| ||American Journal of Veterinary Research. 1996; 57(6): 875-878 |
||Anti-inflammatory effects and aqueous humour concentrations of different nonsteroidal anti-inflammatory drugs in extracapsular cataract surgery | [Entzündungshemmende effekte und kammerwasser-konzentrationen verschiedener nichtsteroidaler antiphlogistika bei extrakapsulärer kataraktchirurgie]
| ||Hessemer, V., Schmitt, K., Jacobi, A. |
| ||Klinische Monatsblatter fur Augenheilkunde. 1996; 208(3): 161-166 |