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DOI: 10.5301/ejo.5000147 Eur J Ophthalmol 2012; 22 ( 6 ): 1008-1012 ORIGINAL ARTICLE Shortening ocular pain duration following intravitreal injections Lana Rifkin, Shlomit Schaal Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky - USA Purpose. To determine ocular pain duration after routine in-office intravitreal injection and to determine whether topical eyedrops are beneficial in increasing patient comfort. Methods. Forty injection-naïve patients receiving routine intravitreal injections of bevacizumab for agerelated macular degeneration were randomized into 3 groups: group 1 (control, no drops), group 2 (generic artificial tears), and group 3 (ketorolac tromethamine 0.4% eyedrops). Those who received topical medications were given a Visual Analog Pain score survey and asked to record their pain on a scale from 0 (no distress) to 10 (unbearable distress) daily until a score of 0 was achieved, at which point they were instructed to discontinue use of their given drops. Self-reported pain scores were assessed. Results. Pain after routine intravitreal injection lasts on average between 3 and 7 days. Patients receiving topical ketorolac eyedrops reported the fewest average number of pain days (2.25±1.22) vs patients receiving artificial tears (3.54±1.13) or those who received no postprocedure eyedrops (5.13±1.25); p<0.05. At most, patients receiving ketorolac eyedrops reported 3 days of recordable pain. Those who received artificial tears reported at most 5 days of recordable pain, and patients who did not receive any postprocedure eyedrops reported at most 7 days of recordable pain. Conclusions. Pain after intravitreal injection is generally mild, may be reduced by postinjection topical ketorolac eyedrops, and lasts less than 1 week. Key Words. Age-related macular degeneration, Artificial tears, Intravitreal injection, Nonsteroidal antiinflammatory drugs, Ocular pain Accepted: February 27, 2012 INTRODUCTION Intravitreal injections are widely used nowadays as an inoffice procedure to deliver anti-infectious, anti-inflammatory, anticancer, anti-VEGF medications, as well as gas into the eye (1). One of the most common side effects due to this treatment is discomfort or pain at the site of injection. Although pain and intraocular procedures, such as cataract surgery (2) and vitrectomy (3), have been studied, until recently, factors alleviating patients’ discomfort during intravitreal injections were unknown. However, several studies have recently been published, investi1008 gating the differences in methods of anesthesia, as well as specific factors associated with decreased pain perception during intravitreal injection. Blaha et al showed that the overall pain experience is similar, regardless of method used: proparacaine topical eyedrops, tetracaine topical eyedrops, lidocaine pledget, or subconjunctival lidocaine (4). Yau et al also showed no difference between topical anesthetic agents for intravitreal injection (5). Our study demonstrated that pain associated with intravitreal injection is mild and may be associated with certain factors, such as gender, age, and perceived visual improvement. We also showed that pain decreases significantly with each consecutive injection (6). © 2012 Wichtig Editore - ISSN 1120-6721 Rifkin and Schaal This prospective, randomized study is the first to aim at identifying a class of eyedrops given postprocedure that would decrease the pain intensity after intravitreal injections as well as decrease the number of days of recordable pain. Artificial tears are often used as an eye lubricant to treat ocular surface disorders such as dry eyes by reestablishing the ocular surface and thereby reducing irritation (7). Topical nonsteroidal anti-inflammatory agents such as ketorolac work by presumably inhibiting prostaglandin synthesis, specifically, the cyclooxygenase pathway (8), and are currently indicated to decrease ocular pain and irritation associated with corneal refractive surgery (Acular package insert). Although systemic side effects of ketorolac exist and include headache, dizziness, nausea, tachycardia, unusual bleeding or bruising, as well as others (9), the use of topical ketorolac is quite common and has been shown to be safe and effective in treating both inflammation and pain following cataract surgery (10), after femtosecond laser in situ keratomileusis (11), as well as after excimer photorefractive keratectomy (12). METHODS This prospective, randomized study included 40 patients in a single center receiving routine intravitreal injections of bevacizumab (1.25 mg/0.1 cc) for age-related macular degeneration. After informed consent was properly obtained, each patient was randomized and assigned to one of 3 groups: group 1 (control: no postprocedure drops), group 2 (generic sterile artificial tears lubricant eyedrops, McKesson, San Francisco, CA), and group 3 (ketorolac tromethamine 0.4%, Apotex, Weston, FL, USA). Patient demographics are shown in Table I. Injections were performed by a single surgeon (S.S.) and standard procedure for intravitreal injection was followed (13). All patients were naïve to this procedure prior to enrollment and each received one drop of povidone before and after the intravitreal injection. Standard eye calipers were used to measure the distance from the limbus (3.5 mm for pseudophakic patients and 4.0 mm for phakic patients). All patients were anesthetized with topical tetracaine HCl ophthalmic solution (Alcon Surgical, Fort Worth, TX, USA). All injections were performed in the superotemporal quadrant of each eye with a 32-gauge needle. Following treatment, patients were given either no postinjection eyedrop, generic artificial tears, or ketorolac eyedrops, based on their randomly assigned group. Those who received topical medications were given instructions to place one drop in the injected eye twice daily and record on a Visual Analog Pain score survey their pain on a scale from 0 to 10, where 0 = no pain/no distress and 10 = agonizing pain/unbearable distress, until a score of 0 was achieved. When a score of 0 was reached, patients were instructed to discontinue use of their given drops. Patients were not given information on the mechanism of action of the drops they were receiving. The Visual Analog Pain Scale used in this study has been demonstrated to be a reliable and reproducible method of measuring patient pain (14, 15). Thirty-five patient surveys were included, as 5 patients failed to complete and return their surveys. Patients with any prior eye surgery other than routine and uncomplicated cataract surgery and patients with known dry eye disease or a history of keratopathy or keratitis were excluded. Patients with diabetes, peripheral neuropathy, and those diagnosed with povidone-induced keratitis were also excluded. Statistical analysis was performed using SPSS software (11.0) for Windows. Analysis of variance with the Bonferroni correction was used to compare the groups. TABLE I - DEMOGRAPHICS OF STUDY PARTICIPANTS No. of participants No. male No. female Age, y Caucasian Group 1 (Control) Group 2 (artificial tears) Group 3 (ketorolac) 15 6 9 75.7 15 13 5 8 75.3 13 12 4 8 74.2 12 © 2012 Wichtig Editore - ISSN 1120-6721 1009 Ocular pain after intravitreal injections RESULTS Overall pain duration The duration of pain after intravitreal injection is demonstrated in Figure 1. A statistically significant difference was found between the last recordable pain day among all 3 groups (p<0.05), with the duration of pain being longest for group 1 (5.07±1.16 days). For group 2 pain duration was 3.54±1.13 days. Pain duration was shortest for group 3 (1.75±0.75 days). The duration of pain was found to differ significantly between group 3 (p<0.05) and the other 2 groups, but not between group 1 and group 2. Difference in pain sensation according to age and sex Pain duration was no different in older and younger patients among the 3 groups (p=0.32) nor between men and women’s postinjection pain sensation in all 3 groups (group 1: p=0.41, group 2: p=0.36, group 3: p= 0.44). Pattern of decrease in pain sensation during the first postinjection week Decrease in pain sensation following an intravitreal injection followed a different pattern in the 3 groups (Fig. 2). For group 1, the average pain score decreased significantly with each day for the first 2 days (p<0.05), but not thereafter. For group 2, the average pain score also decreased Fig. 1 - Comparison of average last recordable pain day for patients receiving no postprocedure eyedrops (group 1), patients receiving artificial tears (group 2), and patients receiving ketorolac (group 3) after injection. Analysis of variance detected a statistically significant difference among the 3 groups. The duration of pain was different significantly between group 3 (p=0.02) and the other 2 groups, but not between group 1 and group 2. significantly with each day for the first 2 days (p<0.05), but not thereafter. For group 3, the average pain score did not decrease significantly (p=0.07) as time went by. DISCUSSION Intravitreal injections have become an invaluable treatment option for patients being treated for age-related macular degeneration, diabetic macular edema (16), uveitis (17), Fig. 2 - Comparison of average pain recorded for patients in each of the 3 groups, until a pain score of 0 was reached. For patients in group 1, the average pain score decreased significantly with each day for the first 2 days (p<0.05), but not thereafter. For patients in group 2, the average pain score also decreased significantly with each day for the first 2 days (p<0.05), but not thereafter. For patients in group 3, the average pain score did not decrease significantly (p=0.07) as time went by. 1010 © 2012 Wichtig Editore - ISSN 1120-6721 Rifkin and Schaal and macular edema due to vein occlusion (18). As it has become such a widely used procedure, the physician must identify factors that may lessen the discomfort associated with this treatment. Recent studies have elucidated factors associated with pain during intravitreal injection; however, this is the first randomized, prospective study shedding light on the duration of pain after intravitreal injection and on identifying topical eyedrops that may decrease postprocedural pain. Our results indicate that ketorolac not only decreased the average pain score over time, but also significantly shortened the duration of pain for patients after intravitreal injection. A recent study by Donnenfeld et al (10) showed that ketorolac effectively treated both inflammation and pain following cataract surgery. Nonsteroidal anti-inflammatory agents have also been shown to be effective and safe in the management of pain after femtosecond laser in situ keratomileusis (11) as well as after excimer photorefractive keratectomy (12). This is the first study to demonstrate that ketorolac may be used to shorten the duration of pain following intravitreal injection. Shortcomings of this study include the fact that baseline pain levels were not obtained prior to initiating treatment. Despite the results of our previous study showing a decrease in report of pain intensity with consecutive injection (6), patients who underwent uncomplicated cataract surgery were included in the current study, as we are not aware of any studies that have indicated prior surgery to be a factor in decreasing pain perception. Also, compliance with given medication was not measured. Previous glaucoma studies have shown that compliance with medications is quite low (19), and may be influenced by age (although not a consistent risk factor), cost of medication, and complicated dosing strategies (20). The average age of the patients in our study was 75 years and they were both physically and mentally capable of instilling drops themselves or had caregivers who were able to instill for them. The cost of medication was not an issue as we provided a sample of both generic artificial tears and ketorolac to those who were assigned to these groups. Patients can be informed that pain duration is expected to decrease significantly during the first several days after intravitreal injection, and that pain duration rarely exceeds 1 week. Based on this study, it may be advisable to supply patients with topical ketorolac eyedrops for the day of the injection and 1 day after. This may be especially useful for patients who complain of ocular sensitivity and increased pain sensation after previous ophthalmic procedures. The authors report no proprietary interest or financial support. Address for correspondence: Shlomit Schaal, MD, PhD 301E Muhammad Ali Blvd. Louisville, KY 40202, USA [email protected] REFERENCES 1. 2. 3. 4. 5. Peyman GA, Lad EM, Moshfeghi DM. Intravitreal injection of therapeutic agents. Retina 2009; 29: 875-912. Ezra DG, Allan BD. Topical anesthesia alone versus topical anaesthesia with intracameral lidocaine for phacoemulsification. Cochrane Database Syst Rev 2007; 3: CD 005276. Gill VS, Presland AH, Lord JA, Bunce C, Xing W, Charteris DG. Two-quadrant high-volume sub-Tenon’s anaesthesia for vitrectomy: a randomised controlled trial. Br J Ophthalmol 2012; 96: 189-92. Blaha GR, Tilton EP, Barouch FC, Marx JL. Randomized trial of anesthetic methods for intravitreal injections. Retina 2011; 31: 535-9. Yau GL, Jackman CS, Hooper PL, Sheidow TJ. Intravit- 6. 7. 8. 9. real injection anesthesia: comparison of different topical agents: a prospective randomized controlled trial. Am J Ophthalmol 2011; 151: 333-7. Rifkin LM, Schaal S. Factors affecting patients’ pain intensity during in office intravitreal injection procedure. Retina 2012; 32(4): 696-700. Pflugfelder SC, Solomon A, Stern ME. The diagnosis and management of dry eye: a twenty-five-year review. Cornea 2000; 19: 644-9. Flach AJ. Cyclo-oxygenase inhibitors in ophthalmology. Surv Ophthalmol 1992; 36: 259-84. Ketorolac. Medline Plus. Updated 10/01/2010. Available at: www.nlm.nih.gov/medlineplus/druginfo/meds/a693001. html#side-effects. Accessed September 11, 2011. © 2012 Wichtig Editore - ISSN 1120-6721 1011 Ocular pain after intravitreal injections 10. Donnenfeld ED, Nichamin LD, Hardten DR, et al. Twicedaily, preservative-free ketorolac 0.45% for treatment of inflammation and pain after cataract surgery. Am J Ophthalmol 2011; 151: 420-6. 11. Parker J, Tandon A, Shtein RM, et al. Management of pain with diclofenac after femtosecond-assisted laser in situ keratomileusis. J Cataract Refract Surg 2011; 37: 569-73. 12. Tutton MK, Cherry PM, Raj PS, Fsadni MG. Efficacy and safety of topical diclofenac in reducing ocular pain after excimer photorefractive keratectomy. J Cataract Refract Surg 1996; 22: 536-41. 13. Rosenfeld PJ, Brown DM, Heier JS, et al; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006; 355: 1419-31. 14. Huskisson EC. Measurement of pain. Lancet 1974; 304: 1127-31. 15. Price DD, McGrath PA, Rafii A, Buckingham B. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain 1983; 17: 45-56. 1012 16. Parravano M, Menchini F, Virgili G. Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for diabetic macular oedema. Cochrane Database Syst Rev 2009; 4: CD007419. 17. Kok H, Lau C, Maycock N, McCluskey P, Lightman S. Outcome of intravitreal triamcinolone in uveitis. Ophthalmology 2005; 112: 1916. 18. Stahl A, Agostini H, Hansen LL, Feltgen N. Bevacizumab in retinal vein occlusion-results of a prospective case series. Graefes Arch Clin Exp Ophthalmol 2007; 245: 142936. 19. Okeke CO, Quigley HA, Jampel HD, et al. Adherence with topical glaucoma medication monitored electronically the Travatan Dosing Aid study. Ophthalmology 2009; 116: 191-9. 20. Tsai JC. A comprehensive perspective on patient adherence to topical glaucoma therapy. Ophthalmology 2009; 116 (Suppl): S30-6. © 2012 Wichtig Editore - ISSN 1120-6721