Effect of topical ketorolac tromethamine and topical nepafenac on maintaining pupillary dilation during phacoemulsification

Transcription

1 PHILIPPINE JOURNAL OF Ohthalmology Vol. 36 No. 1 Ja n ua r y June 2011 ORIGINAL ARTICLE Richard Atanis, MD Prosero Ma. Tuaño, MD Jay Vicencio, MD Jose Ma. Martinez, MD Lee Verzosa, MD International Eye Institute St. Luke s Medical Center Quezon City, Philiines Effect of toical ketorolac tromethamine and toical neafenac on maintaining uillary dilation during hacoemulsification ABSTRACT Objective This study comared the effectiveness of rohylactic administration of toical ketorolac tromethamine 0.5% and neafenac 0.1% on maintaining mydriasis during hacomulsification. Methods This is a rosective, randomized, double-masked comarative study involving adult cataract atients given toical NSAIDs (ketorolac or neafenac) or balanced salt solution (control) rior to hacoemulsification and casular bag intraocular-lens (IOL) imlantation at a tertiary hosital. Horizontal and vertical diameters of uil were measured at different stages of cataract surgery and the mean values were comared across the three grous. Corresondence to Richard B. Atanis, MD 2 Chamagne St., SSS Village Concecion Dos, Marikina City Philiines Telefax : richard_atanis@yahoo.com No financial assistance was received for this study. The authors have no rorietary or financial interest in any roduct used or cited in this study. Presented at the annual meeting of the Philiine Academy of Ohthalmology, Manila, Philiines, November Results A total of 47 eyes of 44 cataract surgery atients, 13 males and 34 females, with a mean age of ± 8.87 years, were included in the study. The mean horizontal and vertical diameters of the three grous were similar at the start of surgery. Significant differences were seen after IOL imlantation, with the neafenac grou having the largest mean diameters in both horizontal ( = 0.012) and vertical ( = 0.012) uil measurements. Conclusion Toical neafenac has been shown to be a more effective inhibitor of miosis during hacoemulsification and rovides a more stable mydriatic effect throughout the surgical rocedure comared to toical ketorolac and lacebo. Keywords: Cataract, Phacoemulsification, Mydriasis, Toical NSAIDs,, Phili J Ohthalmol 2011; 36(1):

2 PHACOEMULSIFICATION with intraocular-lens (IOL) imlantation is the current surgical treatment of choice for cataract extraction. 1-3 To revent comlications during surgery, there should be adequate uillary dilation for better visualization of the osterior chamber. Evidence has shown that intraocular maniulation can trigger the inflammatory cascade, releasing cyclooxygenase (COX) and rostaglandins within the eye causing miosis. During cataract surgery, maintenance of mydriasis is necessary to facilitate roer incision of the anterior casule, safe removal of the cataract, and imlantation of intraocular lens. Mydriatics and antirostaglandins are routinely alied reoeratively to facilitate cataract extraction and revent intraoerative miosis. 4 Previous studies have demonstrated the effectiveness of various toical nonsteroidal antiinflammatory drugs (NSAIDs) (indomethacin, flurbrirofen, surofen) in reventing miosis during cataract surgery comared to lacebo. 5 Newer toical NSAIDs also showed similar favorable effects. Coste 6 showed that neafenac given 3 times a day 1 day before cataract surgery was suerior to tobramycindexamethasone eye dros in maintaining intraoerative mydriasis measured at 4 different stages of the surgery. Solomon 5 comared the effects of toical 0.5% ketorolac tromethamine ohthalmic solution with toical 0.03% flurbirofen sodium on the inhibition of surgically induced miosis during hacoemulsification. rovided a more stable mydriatic effect throughout the surgical rocedure. This study comared the effect of 2 newer toical NSAIDs widely available in the Philiines ketorolac 0.5% and neafenac 0.1%. Secifically, this study determined the horizontal and vertical uillary diameters in 4 different stages of hacoemulsification; comared uillary diameter measurements among the ketorolac, neafenac, and lacebo grous; and determined the total loss and ercent total loss of mydriasis. METHODOLOGY We conducted a rosective, randomized, doublemasked comarative study involving 47 eyes of 44 Filiino atients diagnosed with mature cataract who underwent cataract surgery by hacoemulsification and casular bag IOL imlantation in a tertiary hosital from March to August Included were atients who: were 40 years of age or older, had been diagnosed with mature cataract according to the Lens Oacities Classification System (LOCS III), with classification NO and/or NC 2 3, were scheduled for cataract surgery by hacoemulsification and casular bag IOL imlantation, had normal funduscoic exam (if retina view was ossible), had history of unremarkable hacoemulsification with casular-bag IOL imlantation to the contralateral eye, and had continuous, circular casulorhexis of 5 to 6 mm diameter. The exclusion criteria included: history of ocular inflammatory or infectious eye disease, treatment of eye infection within 30 days rior to inclusion in the study, alterations of the ocular surface (e.g., dry eye), history of isilateral ocular surgery and/or trauma, history of any neuro-ohthalmologic athologies, knowledge or susicion of allergy or hyersensitivity to the reservatives, steroids, toical NSAIDs, or any other comonent of the study medication, use of toical ohthalmic medications, use of toical or systemic steroids within 30 days rior to inclusion in the study, use of toical or systemic NSAIDs within 14 days rior to inclusion in the study, diagnosis of diabetes mellitus with/without diabetic retinoathy and/or macular edema, reoerative mydriasis less than 6 mm rior to the study, Phaco time of >1.5 minutes, intraoerative osterior casular rent with or without vitreous loss, use of intraoerative intracameral einehrine, ocular alteration reventing adequate mydriasis (eg. synechiae, iris atrohy), use of contact lens at anytime before the surgery, surgical events that may hasten uillary constriction (eg. inadvertent maniulation/asiration of the iris, incarceration of iris into the main wound secondary to an accidentally shortened or mis-angled main corneal tunnel), use of tamsulosin or other analogous systemic medications that may induce increased tendency for miosis intra-oeratively (intra-oerative floy iris syndrome or IFIS). Preoeratively, all subjects underwent a thorough ohthalmic examination. Past medical and surgical history, and use of concurrent medications were extensively reviewed. Best-corrected visual acuity (BCVA) using the ETDRS chart, slit-lam biomicroscoy, intraocular ressure by Goldmann alanation tonometry, and dilatedfundus examination were done. A general surgical consent form was obtained from all atients. Patients who underwent hacoemulsification 24 Phili J Ohthalmol Vol. 36 No. 1 January June 2011

3 were eligible for inclusion. They were randomly assigned to each of the 3 grous based on which of the 3 sealed enveloes was chosen by a junior resident at the time of surgery. Patients received 1 dro of the assigned toical NSAID or balanced salt solution (BSS) (control grou) every 15 minutes for 4 doses (~20ml) to the oerative site one hour rior to the scheduled oeration. Five minutes later, troicamide 0.5% with henylehrine 0.5%, 1 dro every 15 minutes for 4 doses was instilled in all treatment grous. The surgeons and the atients were unaware of the tye of test dros given. All subjects underwent cataract surgery by hacoemulsification using the Millenium machine (Microsurgical System, Houston, TX, USA). A one-iece, monofocal, foldable acrylic IOL imlantation inside the casular bag under toical anesthesia (roaracaine) was done by 4 surgeons (one consultant and three senior residents). The surgeons used the same oerative technique on all atients A C as follows. Two 1-mm side-orts, a 2.75-mm temoral clear corneal incision, and a 5- to 6-mm continuous curvilinear casulorhexis were made. Phacoemulsification arameters were established rior to all surgeries and were the same in all atients. Balanced salt solution without einehrine was used for corneal irrigation. The corneal incisions were left unsutured at the close of surgery. To ensure the standardization of illumination during uillary measurement, all surgeons used the same microscoe (Carl Zeiss OPMI VISU 210 S88) and the illumination was ket constant (0.5 to 0.7) in all cases. The rincial author measured the horizontal and vertical uillary diameters. A sterile calier was laced over the cornea and measurements were taken, in millimeters, under the microscoe at the following stages of surgery: 1) before creating side orts, 2) after nuclear emulsification, 3) following cortex asiration, and 4) after imlantation of an acrylic foldable IOL with viscoelastic removal (Figure 1A-D). The reset standard B D Figure 1. Puillary diameters at different stages of the surgery: before creating the sideorts (A), after nuclear emulsification (B), after cortical removal (C), and after intraocular-lens imlantation and viscoelastic removal (D). magnification (0,75x) of the oerating microscoe was ensured at each of the 4 time oints. The rimary outcome measures were the mean horizontal and vertical diameters of the uil during the four different stages of hacoemulsification. Other data collected were age, gender, laterality of the eye oerated on, and the corresonding category to which they were assigned. Frequency, ercentage, mean and standard deviation were used to describe demograhic characteristics and values of uillary measurements. Comarisons of categorical variables were analyzed using chi square or Fisher exact tests, where alicable. Analysis of variance (ANOVA) was used to determine differences between grous at each stage of surgery, as well as changes from baseline. All analyses were two-tailed, with <0.05 considered as significant. Analyses were erformed using Statistical Package for Social Sciences (SPSS) for Windows, version RESULTS A total of 47 eyes of 44 atients, 13 males and 34 females, were included in the study. The mean age was ± 8.87 years. There was no significant difference in age, gender, and laterality of eye oerated on among the three grous (Table 1). Significant differences among the three grous were seen after IOL imlantation, with the neafenac grou having the largest mean diameters in both horizontal ( = 0.012) and vertical ( = 0.012) uil measurements (Tables 2 and 3). Comarison of total loss of mydriasis, which is the difference between uil diameter before surgery and after IOL imlantation, revealed significant differences in both horizontal ( = 0.005) and vertical ( = 0.009) uil measurements with the neafenac grou having the least change from baseline. The Phili J Ohthalmol Vol. 36 No. 1 January June

4 Table 1. Demograhic characteristics of the study oulation. Parameter (N = 15) (N = 18) (N = 14) Age (Years) Mean ± SD ± ± ± Gender, N (%) Male 4 (26.70) 5 (27.80) 4 (28.60) 1.00 Female 11 (73.30) 13 (72.20) 10 (71.40) Eye, N (%) Right eye 5 (33.30) 9 (50.00) 10 (71.40) 0.12 Left eye 10 (66.70) 9 (50.00) 4 (28.60) Table 2. Mean horizontal diameter of the uil at different stages of cataract surgery. Surgery stages Before surgery 8.20 ± ± ± After nuclear emulsification Mean ± SD 7.00 ± ± ± Change from baseline ± ± ± After cortex asiration Mean ± SD 6.43 ± ± ± Change from baseline ± ± ± After IOL imlantation Mean ± SD 5.77 ± ± ± * Change from baseline (Total Loss of mydriasis) ± ± ± * Percent total loss % % % 0.002* Table 3. Mean vertical diameter of the uil at different stages of cataract surgery. Surgery stages Before surgery 8.13 ± ± ± After nuclear emulsification Mean ± SD 6.97 ± ± ± Change from baseline ± ± ± After cortex asiration Mean ± SD 6.40 ± ± ± Change from baseline ± ± ± After IOL imlantation Mean ± SD 5.80 ± ± ± * Change from baseline (Total Loss of mydriasis) ± ± ± * Percent total loss % % % 0.003* least loss in mydriasis in horizontal uil diameter was observed in the neafenac grou with 17.69% loss which was significantly lower ( = 0.002) comared to 29.89% and 30.02% losses of the control and ketorolac grous resectively (Table 2). Similarly, the vertical uil measurements showed significant differences in ercent of total loss with the neafenac grou having 17.32% comared with the 27.89% and 28.80% total losses of the mydriasis of the ketorolac and control grous resectively (Table 3). DISCUSSION Mechanical ocular trauma from hacoemulsification can cause various ocular changes, such as conjunctival hyeremia, inflammation, ain, cystoid macular edema, breakdown of the blood aqueous barrier, rise in intraocular ressure, and most esecially surgically-induced miosis creating access for cataract removal difficult. 7-8 Prostaglandins lay an imortant role in these changes. NSAIDs inhibit COX enzymes that romote rostaglandin roduction; hence, roviding both analgesic and antiinflammatory activities. 6 Ohthalmic NSAIDs are used to decrease the various changes brought about by intraocular surgeries. Due to the toical nature of this drug class, systemic absortion is minimal. 0.1%, after toical dosing, is subsequently converted by ocular tissue hydrolases to amfenac, which is thought to inhibit the action of the cyclooxygenase rostaglandin H synthase % met its rimary objective in this resent study by showing advantage over the control grou in terms of maintaining mydriasis during hacoemulsification. In addition, neafenac 0.1% has also shown to be more effective than lacebo at maintaining mydriasis at every stage of the surgery. 26 Phili J Ohthalmol Vol. 36 No. 1 January June 2011

5 Most interesting, however, is the comarison between neafenac 0.1% and ketorolac 0.5%. Previous studies have established the effectiveness of ketorolac 0.5% for the treatment of both ain and inflammation following cataract surgery. 10 Consequently, ketorolac 0.5% was used as a standard against which the efficacy of neafenac 0.1% was measured. In this study, neafenac 0.1% reached statistical sueriority comared to ketorolac 0.5% in all four stages of hacoemulsification. has been shown to enetrate the cornea raidly and rovides a comlete and longer-lasting inhibition of rostaglandin synthesis and vascular ermeability Perhas, this advantage in absortion and bioavailability was the reason behind its sueriority in maintenance of mydriasis seen in this study. Prescribing a consistent technique as well as dictating microscoe illumination minimized the confounding effects of surgeon variability. Surgeons were, likewise, able to erform the rocedure with relative ease since the hacoemulsification time was within accetable limits. Although a single surgeon series would have been ideal, we feel that the quality of the surgeries in this series came very close in terms of consistency. A larger samle size would have allowed us to analyze the results with a higher confidence level. Future studies can evaluate the diameter of the uil when other tyes of acrylic intraocular lenses are used (e.g. accommodating IOLs, multifocal IOLs). In conclusion, toical neafenac 0.1% has been shown to be a more effective inhibitor of miosis during hacoemulsification with IOL imlantation comared with toical ketorolac or BSS. References 1. Linebarger EJ, Hardten DR, Shah GK, et al. Phacoemulsification and modern cataract surgery. Surv Ohthalmol 1999; 44: Gogate PM, Kulkarni SR, Krishnaiah S, et al. Safety and efficacy of hacoemulsification comared with manual small-incision cataract surgery by a randomized controlled clinical trial: six-week results. Ohthalmology 2005;112: Riaz Y, Mehta JS, Wormald R, et al. Surgical interventions for age-related cataract. Cochrane Database Syst Rev 2006; 4: CD Guta VP, Dhaliwal U, Prasad N. tromethamine in the maintenance of intraoerative mydriasis. Ohthalmic Surg Lasers 1997; 28: Solomon K, Turkalj JW, Whiteside SB. Toical 0.5% ketorolac vs 0.03% flurbirofen for inhibition of miosis during cataract surgery. Arch Ohthalmol 1997; 115: Cervantes-Coste G, Sanchez-Castro YG, Orozco-Carroll M, et al. Inhibition of surgically induced miosis and revention of ostoerative macular edema with neafenac. Clin Ohthalmol 2009; 3: Duffin RM, Camras CB, Gardner SK, et al. Inhibitors of surgically induced miosis. Ohthalmology 1982; 89: Podos SM. Prostaglandins, nonsteroidal antiinflammatory agents and eye disease. Trans Am Ohthalmol Soc 1976; 74: Flach AJ, Lavelle CJ, Olander KW, et al. The effect of ketorolac tromethamine solution 0.5% in reducing ostoerative inflammation after cataract extraction and intraocular-lens imlantation. Ohthalmology 1988; 95: Ohthalmic Nonsteroidal Anti Inflammatory Drugs Drug Class Review. July htt://vaww.bm.va.gov (accessed Feb 22, 2010). 11. Ohthalmic NSAIDs Review. Set htts://nevada.fhsc.com/downloads/ rovider/nvrx_dcr_ _ohthalmic_nsaids.df (accessed Oct 3, 2010). 12. Bucci FA Jr, Waterbury LD, Amico LM, et al. Prostaglandin E2 inhibition and aqueous concentration of ketorolac 0.4% (Acular LS) and neafenac 0.1% (Nevanac) in atients undergoing hacoemulsification. Am J Ohthalmol 2007; 144: Acknowledgment The authors thank Ms. Kaice Cristobal for the statistical analyses. Phili J Ohthalmol Vol. 36 No. 1 January June