- What’s New, What’s Now, and What’s Next
- 60 Minutes Retina
- Update on Laser Cataract Surgery
- Managing Glaucoma Patients With Electronic Health Records
- Successful In-Office Techniques for Educating Patients
- Managing Spherical Aberration With Contact Lenses
- Controlling Inflammation in the Perioperative Period of Cataract and Refractive Surgery
- The High Cost of Saving Money: Risks Associated With Generic Drugs
- Rethinking the Diagnostic Evaluation of Inflammation
- Mounting Evidence Underscores the Role of Nutrition in Ocular Surface Disease
- Attacking Dry Eye: Five New Weapons
- Biomarkers of Dry Eye
- Taking Ownership of the Management of Ocular Allergies
- Introducing New Technology With an Eye on Sustainability
- Industry News and Innovations
- Gene Therapy Moves Closer to Clinical Applicability
Although controlling inflammation in the perioperative period for cataract and refractive surgery is often seamless, at times it can be quite a challenge. Given all of the options eye care practitioners have for treating inflammation, finding the most effective therapeutic regimen can be a daunting task.
TREATING INFLAMMATION DURING CATARACT SURGERY
Common inflammation-induced complications related to cataract surgery include corneal edema, uveitis, pain, and cystoid macular edema. Inadequate treatment of inflammation may result in patients’ discomfort, delayed recovery, and suboptimal visual results. The most common treatment modalities for battling inflammation include corticosteroids, which can be administered topically, subconjunctivally, intracamerally, systemically, and intravitreally. Corticosteroids can be used alone or in combination with topical nonsteroidal anti-inflammatory drugs (NSAIDs) during the perioperative period. These inhibit the formation of prostaglandin by cyclooxygenases (COX). Several agents in this class have been approved for the treatment of postoperative pain and inflammation following cataract surgery as well as for cystoid macular edema.
The most commonly used topical corticosteroids in the perioperative period to control inflammation in cataract surgery are prednisolone acetate 0.12% or 1%, loteprednol 0.5% (Lotemax; Bausch + Lomb), fluorometholone 0.1%, dexamethasone, difluprednate 0.05% (Durezol; Alcon Laboratories, Inc.), and dexamethasone 0.1% (Maxidex; Alcon Laboratories, Inc.) (Table 1). Routinely used topical NSAIDs include bromfenac 0.9% (Bromday; Ista Pharmaceuticals, Inc.), ketorolac 0.4% (Acular; Allergan, Inc.), nepafenac 0.1% (Nevanac; Alcon Pharmaceuticals, Inc.), and diclofenac 0.1% (Voltaren; Novartis) (Table 2).
Addition of NSAIDs
Patients undergoing uncomplicated cataract surgery in our practice start by taking Nevanac q.i.d. or diclofenac 0.1% q.i.d. 3 days prior to surgery. On the day of surgery, the patient receives a subconjunctival injection of dexamethasone 1 mg (combined with cefazolin [Ancef; Baxter Healthcare] 25 mg for additional antibacterial prophylaxis). On postoperative day 0 or 1, the patient begins a 4 to 6 week tapered course of topical corticosteroids in combination with topical NSAIDs to minimize inflammation. The taper will usually be difluprednate, loteprednol, or prednisolone 1% (Pred Forte; Allergan, Inc.) and nepafenac or diclofenac q.i.d. for 1 week, t.i.d. for 1 week, and b.i.d. for 2 weeks (see Table 3). The NSAID may not be administered if the patient has epitheliopathy (superficial punctate staining or any type of corneal epithelial defect) during postoperative week 1. The NSAID is often resumed after the resolution of these signs. Recently, surgeons have reported corneal melts related to topical generic ketorolac, so they may want to carefully watch their patients that are on generic NSAIDs. A new website for reporting adverse events associated with generic agents is available at www.reportgenerics.com. In patients older than 60 years or in those with the Crystalens (Bausch + Lomb), the taper is extended for an additional 2 weeks at b.i.d. dosing.
Common practice for controlling inflammation in the perioperative period is with combination corticosteroids and NSAIDs. Several studies confirm the utility of combined prednisolone acetate 1% and an NSAID, including diclofenac, ketorolac, bromfenac, or nepafenac, in controlling one or more of the commonly encountered inflammatory issues surrounding cataract surgery.1-13 Wittpen et al demonstrated that combination Pred Forte with topical NSAIDs has a synergistic effect to reduce macular swelling compared to Pred Forte alone.14 It may also be possible to prescribe a patient one class of medication, either an NSAID or corticosteroid, to control inflammation, pain, cystoid macular edema, and uveitis.15-17 Hossain et al showed that there was no statistical difference in control of postoperative inflammation between two groups of patients taking either diclofenac or prednisolone.15 Other common mechanisms for administering corticosteroids include a subconjunctival or sub-Tenon depot steroid injection (typically triamcinolone or betamethasone) or an intracameral injection of triamcinolone. Evidence suggests that such injections alone at the time of surgery may be as effective at controlling inflammation as a more prolonged topical treatment regimen.18-22
New Delivery Methods
Newer avenues for the delivery of anti-inflammatory medications such as transscleral iontophoresis or a dexamethasone-coated IOL are in development.23,24 Oral anti-inflammatory agents such as naproxen may also have relevance in this setting.25 These alternative options become important in cases of ocular surface abnormalities related to the preservatives found in topical medications. 26 A several-week course of topical medications seems to be the most popular approach at the present time. Future advances in biopharmaceuticals capable of sustained activity after a single dose, coupled with new and improved routes of intraocular administration, may alter this paradigm.
TREATING INFLAMMATION AFTER CORNEAL REFRACTIVE SURGERY
A Different Approach From Cataract Surgery
The approach to treating inflammation in the perioperative period for refractive surgery is materially different than that following cataract surgery. Common LASIK-induced inflammatory-related issues include pain, diffuse lamellar keratitis, subepithelial infiltrates, and conjunctival inflammation secondary to the suction device. Inflammation-related complications related to PRK include pain, subepithelial infiltrates, and, rarely, chemical conjunctivitis related to topical mitomycin C or alcohol.
Corticosteroids and Oral NSAIDs
Common treatments for managing inflammation associated with refractive surgery include topical corticosteroids, such as prednisolone, difluprednate, or loteprednol; oral anti-inflammatory medications including NSAIDs, which inhibit the COX-1 pathway, such as ibuprofen, naproxen, or ketorolac; as well as COX-2 inhibitors such as celecoxib (Celebrex; GD Searle). Other oral agents used to control pain include acetaminophen, with or without narcotic medications such as codeine, hydrocodone, or oxycodone. Unlike the perioperative period for cataract surgery, the role of topical NSAIDs after keratorefractive surgery is more limited. The incidence of pain is high, while intraocular conditions requiring more prolonged therapy, such as cystoid macular edema and uveitis, are rare complications after laser vision correction.
For LASIK patients, our medication protocol to control inflammation is as follows: difluprednate, loteprednol, or prednisolone 1% every 2 hours for 24 hours, then q.i.d. for 5 days, then b.i.d. for 1 week. On the day of and the day after surgery, PRK patients receive one dose of bromfenac 0.9% in addition to topical corticosteroids q.i.d. PRK patients follow the regimen of topical corticosteroids, either prednisolone or loteprednol q.i.d for 1 week, then b.i.d. for 4 weeks. PRK patients not receiving intraoperative mitomycin C 0.02% will proceed with a slower steroid taper of approximately 8 weeks. Additionally, intraoperatively, PRK patients receive a 15 cc lavage of chilled balanced salt solution (BSS; Alcon Laboratories, Inc.) over the eye after completion of the excimer portion of the case and prior to the insertion of a bandage contact lens. Either oral ibuprofen 800 mg b.i.d. or naproxen 440 mg b.i.d. is prescribed as mandatory rather than as needed. A summary is listed in Table 4.
As with cataract surgery, there is a wide variation among medication regimens prescribed for patients undergoing laser vision correction. Although many do not, some surgeons use NSAIDs in LASIK patients postoperatively. In one study by Vantesone et al, there was no statistical difference between patients taking diclofenac compared to prednisolone after LASIK.27 Price et al showed no statistical difference in refractive accuracy, best-corrected or uncorrected visual acuity, or safety in patients taking artificial tears compared with patients taking corticosteroids after LASIK, demonstrating that corticosteroids may not be needed at all after routine LASIK cases.28
For PRK patients, NSAIDs may have an important, although somewhat controversial, role in the preoperative and postoperative period. Topical ketorolac 0.4% was found in one study to reduce postoperative pain and was ultimately approved by the FDA for this indication. 29 Another study showed that use of topical diclofenac prior to surgery reduced the postoperative pain associated with PRK.30 There is concern as to whether NSAIDs, while beneficial in terms of postoperative pain after PRK, can cause delayed reepithelialization and/or sterile inflammatory infiltrates. There are several studies demonstrating little to no delay in reepithelialization in the NSAID class drugs examined when used for finite periods of time and less then q.i.d. dosing.31-33 It is possible, however, that high dose NSAIDs after PRK, could result in corneal ulceration and even perforation.34 Nepafenac, for example, when placed on the cornea prior to the placement of a contact lens, was found to result in delays in epithelial healing after PRK.35 Other medications, however, including ketorolac, bromfenac, and diclofenac may be used for longer periods of time, even up to 5 days, after PRK to control pain and inflammation.36
Minimizing inflammation-related complications after cataract and refractive surgery is important for positive patient outcomes. It is incumbent upon the surgeon to constantly strive to control these specific issues while minimizing drug toxicity and side effects associated with these treatments.
instructor of ophthalmology at the Alpert Medical School of Brown University in Providence, Rhode Island, and is in private practice with Talamo Laser Eye Consultants in Waltham, Massachusetts. She is a consultant to Bausch + Lomb and Nexi Vision. Dr. Hatch may be reached at (781) 890-1023; email@example.com.
Jonathan H. Talamo, MD, is an associate clinical professor of ophthalmology at Harvard Medical School in Boston and is in private practice at Talamo Laser Eye Consultants in Waltham, Massachusetts. He is a consultant to Allergan Inc.; Bausch + Lomb; Ikona Corporation; Nexis Vision; and OptiMedica Corporation. Dr. Talamo may be reached at firstname.lastname@example.org.
- Perry HD, Donnenfeld ED. An update on the use of ophthalmic ketorolac tromethamine 0.4%. Expert Opin Pharmacother. 2006;7(1):99-107.
- Jones J, Francis P. Ophthalmic utility of topical bromfenac, a twice-daily nonsteroidal anti-inflammatory agent. Expert Opin Pharmacother. 2009;10(14):2379-85.
- Henderson BA, Gayton JL, Chandler SP, et al; Bromfenac Ophthalmic Solution (Bromday) Once Daily Study Group. Safety and efficacy of bromfenac ophthalmic solution (Bromday) dosed once daily for postoperative ocular inflammation and pain. Ophthalmology. 2011;118(11):2120-2127.
- Cho H, Wolf KJ, Wolf EJ. Management of ocular inflammation and pain following cataract surgery: focus on bromfenac ophthalmic solution. Clin Ophthalmol. 2009;3:199-210. Epub 2009 Jun 2.
- Donnenfeld ED, Nichamin LD, Hardten DR, et al. Twice-daily, preservative-free ketorolac 0.45% for treatment of inflammation and pain after cataract surgery. Am J Ophthalmol. 2011;151(3):420-426.e1. Epub 2010 Dec 9.
- Gow JA, Song CK, McNamara TR. Nepafenac dosing frequency for ocular pain and inflammation associated with cataract surgery. J Ocul Pharmacol Ther. 2009;25(4):385-386; author reply 386.
- Miyanaga M, Miyai T, Nejima R, et al. Effect of bromfenac ophthalmic solution on ocular inflammation following cataract surgery. Acta Ophthalmol. 2009;87(3):300-305. Epub 2009 Jan 31.
- Maxwell WA, Reiser HJ, Stewart RH, et al. Nepafenac dosing frequency for ocular pain and inflammation associated with cataract surgery. J Ocul Pharmacol Ther. 2008;24(6):593-599.
- Lorenz K, Dick B, Jehkul A, et al. Inflammatory response after phacoemulsification treated with 0.5% prednisolone acetate or vehicle. Arch Clin Exp Ophthalmol. 2008;246(11):1617-1622.
- Donnenfeld ED, Holland EJ, Stewart RH, et al. Bromfenac ophthalmic solution 0.09% (Xibrom) for postoperative ocular pain and inflammation. Bromfenac Ophthalmic Solution 0.09% (Xibrom) Study Group. Ophthalmology. 2007;114(9):1653-1662.
- Lane SS, Modi SS, Lehmann RP, et al. Nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular inflammation associated with cataract surgery. J Cataract Refract Surg. 2007;33(1):53- 58. Erratum in: J Cataract Refract Surg. 2007;33(4):564.
- Stewart RH, Grillone LR, Shiffman ML, et al; Bromfenac Ophthalmic Solution 0.09% Study Group. The systemic safety of bromfenac ophthalmic solution 0.09%.. J Ocul Pharmacol Ther. 2007;23(6):601-612.
- Hariprasad SM, Callanan D, Gainey S, et al. Cystoid and diabetic macular edema treated with nepafenac 0.1%. J Ocul Pharmacol Ther. 2007;23(6):585-590.
- Wittpenn J, Silverstein S, Hunkeler J, et al. A masked comparison of Acular LS plus steroid versus steroid alone for the prevention of macular leakage in cataract patients. Presented at: 2006 Joint Meeting of the American Academy of Ophthalmology (AAO) and the Asia Pacific Academy of Ophthalmology (APAO); November 11-14, 2006; Las Vegas, NV.
- Hossain MM, Mohiuddin AA, Hossain MA, et al. Diclofenac sodium and prednisolone acetate ophthalmic solution in controlling inflammation after cataract surgery. Mymensingh Med J. 2010;19(3):343-347.
- DeCroos FC, Afshari NA. Perioperative antibiotics and anti-inflammatory agents in cataract surgery. Curr Opin Ophthalmol. 2008;19(1):22-26.
- Colin J. The role of NSAIDs in the management of postoperative ophthalmic inflammation. Drugs. 2007;67(9):1291-308.
- Dieleman M, Wubbels RJ, van Kooten-Noordzij M, de Waard PW. Single perioperative subconjunctival steroid depot versus postoperative steroid eyedrops to prevent intraocular inflammation and macular edema after cataract surgery. J Cataract Refract Surg. 2011;37(9):1589-1597.
- Simaroj P, Sinsawad P, Lekhanont K. Effects of intracameral triamcinolone and gentamicin injections following cataract surgery. J Med Assoc Thai. 2011;94(7):819-825.
- Paganelli F, Cardillo JA, Melo LA Jr, et al.Brazilian Ocular Pharmacology and Pharmaceutical Technology Research Group. A single intraoperative sub-tenon’s capsule injection of triamcinolone and ciprofloxacin in a controlled-release system for cataract surgery. Invest Ophthalmol Vis Sci. 2009;50(7):3041-3047.
- Karalezli A, Borazan M, Akova YA. Intracameral triamcinolone acetonide to control postoperative inflammation following cataract surgery with phacoemulsification. Acta Ophthalmol. 2008;86(2):183-187.
- Lacmanović Loncar V, Petric I, Vatavuk Z, et al. Triamcinolone acetonide in the treatment of inflammation after cataract surgery. Acta Med Croatica. 2006;60(2):125-128.
- Paganelli F, Cardillo JA, Dare AR, et al; Brazilian Ocular Pharmacology and Pharmaceutical Technology Research Group. Controlled transscleral drug delivery formulations to the eye: establishing new concepts and paradigms in ocular anti-inflammatory therapeutics and antibacterial prophylaxis. Expert Opin Drug Deliv. 2010;7(8):955-965.
- Kugelberg M, Shafiei K, van der Ploeg I, et al. Intraocular lens as a drug delivery system for dexamethasone. Acta Ophthalmol. 2010;88(2):241-244.
- Russo P, Papa V, Russo S, et al; Naproxen Study Group. Topical nonsteroidal anti-inflammatory drugs in uncomplicated cataract surgery: effect of sodium naproxen. Eur J Ophthalmol. 2005;15(5):598-606.
- Ayaki M, Taguchi Y, Soda M, et al. Cytotoxicity of topical medications used for infection and inflammation control after cataract surgery in cultured corneal endothelial cells. Biocontrol Sci. 2010;15(3):97-102.
- Vantesone DL, Luna JD, Muiño JC, et al. Effects of topical diclofenac and prednisolone eyedrops in laser in situ keratomileusis patients. J Cataract Refract Surg. 1999;25(6):836-841.
- Price FW Jr, Willes L, Price M, et al. A prospective, randomized comparison of the use versus non-use of topical corticosteroids after laser in situ keratomileusis. Ophthalmology. 2001;108(7):1236-1244.
- Sher NA, Golben MP, Bond W, et al. Topical bromfenac 0.09% vs ketorolac 0.4% for the control of pain, photophobia, and discomfort following PRK. J Refract Surg. 2009;25(2):214-220.
- Mohammadpour M, Jabbarvand M, Nikdel M, et al. Effect of preemptive topical diclofenac on postoperative pain relief after photorefractive keratectomy. J Cataract Refract Surg. 2011;37(4):633-637.
- Jalali S, Yuen LH, Boxer Wachler BS. Effect of nepafenac sodium 0.1% on delayed corneal epithelial healing and haze after photorefractive keratectomy: retrospective comparative study. J Cataract Refract Surg. 2008;34(9):1542-1545.
- Caldwell M, Reilly C. Effects of topical nepafenac on corneal epithelial healing time and postoperative pain after PRK: a bilateral, prospective, randomized, masked trial. J Refract Surg. 2008;24(4):377-382.
- Durrie DS, Kennard MG, Boghossian AJ. Effects of nonsteroidal ophthalmic drops on epithelial healing and pain in patients undergoing bilateral photorefractive keratectomy (PRK). Adv Ther. 2007;24(6):1278- 1285
- Mian SI, Gupta A, Pineda, R II. Corneal ulceration and perforation with ketorolac tromethamine (Acular) use after PRK. Cornea. 2006;25(2):232-234.
- Trattler W, Stulting D, Abad J, et al. Delayed epithelial healing with nepafenac 0.1% ophthalmic suspension. Presented at: 2006 Joint Meeting of the American Academy of Ophthalmology (AAO) and the Asia Pacific Academy of Ophthalmology (APAO); November 11-14, 2006; Las Vegas, NV.
- Trattler WB, McDonald M. Double-masked comparison of ketorolac tromethamine 0.4% versus nepafenac sodium 0.1% for postoperative healing rates and pain control in eyes undergoing surface ablation. Cornea. 2007;26(6):665-669.