ARTICLE
Incidence of acute postoperative cystoid macular edema in clinical practice Mark Packer, MD, CPI, Jennifer Lowe, BA, Howard Fine, MD
PURPOSE: To measure the incidence of acute postoperative cystoid macular edema (CME) in clinical practice. SETTING: Private clinical practice, Eugene, Oregon, USA. DESIGN: Retrospective chart review. METHODS: The electronic medical records database was searched for the charts of all patients having cataract surgery during a recent 5-year period. Each chart was then examined for a diagnosis of CME within the 3-month postoperative period. RESULTS: From March 1, 2007, through March 31, 2012, 2862 phacoemulsification cataract extraction and intraocular lens implantation procedures were performed. Of these, 3 cases (0.1%) of acute postoperative CME were confirmed by diagnosis within 90 days after surgery. CONCLUSIONS: This chart review found a 0.1% cumulative incidence of acute postoperative CME. Prophylaxis with topical steroidal and nonsteroidal agents may help reduce the incidence of CME. If the incidence of CME in this study applies generally, it would be harder to successfully and ethically perform a randomized trial of medical prophylaxis. Financial Disclosure: Dr. Packer is a consultant to Advanced Medical Optics, Inc., Allergan, Inc., Bausch & Lomb Surgical, Inc., and Ista Pharmaceuticals, Inc. No other author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2012; 38:2108–2111 Q 2012 ASCRS and ESCRS
Postoperative cystoid macular edema (CME) (IrvineGass syndrome1,2) continues to harbor a mystery, occurring as it does occasionally in completely routine cases and more commonly in complicated ones. Despite a cogent theory of pathogenesis involving migratory inflammatory mediators and breakdown of the blood–retinal barrier,3,4 evidence-based medicine still regards prophylaxis and treatment with antiinflammatory agents as unproven.5–7 Nevertheless, the use of topical steroids and nonsteroidal medications for prophylaxis and treatment may safely be said to pass for the standard of care.8
Submitted: June 25, 2012. Final revision submitted: July 10, 2012. Accepted: July 11, 2012. From the Oregon Health and Sciences University School of Medicine, Eugene, Oregon, USA. Corresponding author: Mark Packer, MD, CPI, 1550 Oak Street, Suite 5, Eugene, Oregon 97401, USA. E-mail:
[email protected].
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Q 2012 ASCRS and ESCRS Published by Elsevier Inc.
Recent changes in the sampling practices of pharmaceutical companiesA have led to increased concern in the United States about the safety and effectiveness of generic formulations of antiinflammatory medications.9 In this environment of lingering doubt, it is appropriate to gather more information about today's real-world clinical practices and thereby increase the ophthalmic database on the clinical status of CME prophylaxis and treatment from a retrospective, descriptive, and inductive perspective. PATIENTS AND METHODS A chart review was performed by searching the patient database of a 4-doctor anterior segment group practice to find cases of postoperative CME occurring within 3 months of the date of cataract surgery. The charts of all patients whose accounts were charged for current procedural terminology (CPT) code 66984 (phacoemulsification with intraocular lens [IOL]) or 66982 (complicated cataract) were searched for a diagnosis of CME within the 90-day global period. The method of diagnosis varied somewhat by clinician but all cases involved clinical findings of a subjective decrease in the quality and acuity of vision, loss of foveal reflex, or 0886-3350/$ - see front matter http://dx.doi.org/10.1016/j.jcrs.2012.07.029
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frank macular edema on funduscopic examination and confirmatory imaging with fluorescein angiography and/or optical coherence tomography (OCT). Only cases in which a diagnosis of CME (International Codes of Diseases 9 362.53) was entered into the medical record were included. Chronic cases and recurrent cases as well as those associated with other retinal pathology (eg, branch retinal vein occlusion) were excluded. The perioperative medication regimen and preparation technique used in these cases varied little and have been described.B Biaxial microincision phacoemulsification techniques were used in most cases and have also been thoroughly described.10 The regimens prescribed for these patients were typical of those used during the years under study. Patients who had implantation of an anterior chamber IOL and diabetic patients started topical prophylaxis 1 day postoperatively with prednisolone acetate [Pred Forte] and ketorolac tromethamine 0.4% (Acular LS) 4 times a day for 4 weeks. These cases occurred in 2009; subsequently, a practice change was instituted so that prophylactic antiinflammatory topical medications were started 3 days before surgery along with the topical antibiotic agent.11
RESULTS From March 1, 2007, through March 31, 2012, 2862 phacoemulsification procedures were performed. Of these, 3 cases (0.1%) of acute postoperative CME were confirmed. Preoperative Characteristics One patient had a history of background diabetic retinopathy treated with focal macular photocoagulation 22 months before cataract surgery. The other 2 patients had no significant ocular pathology other than cataract. Surgical Technique Topical nonsteroidal agents were included in the anesthetic cocktail (proparacaine 0.5%, phenylephrine 10.0%, tropicamide 1.0%, diclofenac 0.3%, cyclopentolate 2.0%, gatifloxacin 0.3%) delivered via a pledget in the superior fornix. Biaxial microincision phacoemulsification techniques were used in most cases. Two hundred seventy-four cases (9.6%) were billed as CPT code 66982, indicating the use of capsule dye, iris expansion device, or capsular tension ring. In 2 cases, uneventful phacoemulsification procedures resulted in the placement of a posterior chamber IOL (Tecnis ZCB00, Advanced Medical Optics, Inc.) in the capsule. In 1 case, damage to the capsule resulted in placement of an anterior chamber IOL (MTA2, Alcon Laboratories, Inc.). Medical Prophylaxis The patient who had a routine case presented more recently (in 2012) and therefore began both topical
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steroid and nonsteroidal antiinflammatory drugs (NSAIDs) (prednisolone acetate 1% and ketorolac tromethamine 0.4% 4 times a day) 3 days before surgery. In general, patients operated on during the period under study were examined routinely 1 day and 2 weeks postoperatively. Unscheduled visits may have occurred in the interim, and medications or dosages may have been adjusted in response to changes in the patients' conditions. For example, an eye with persistent inflammation would be carefully examined for retained lens fragments and prescribed an increased frequency of medication or a more potent medication. Postoperative Course Case 1: Anterior Chamber Intraocular Lens The operative report noted that phacoemulsification in the capsular bag was accomplished; however, zonular dialysis occurred nasally with loss of capsule support. The uncorrected distance visual acuity (UDVA) on the first postoperative day was 20/70 with 1C corneal edema. The corrected distance visual acuity gradually improved to 20/30 by 1 month, and the topical medications were discontinued. However, 3 weeks later (50 days postoperatively), the corrected distance visual acuity (CDVA) had fallen to 20/70. Examination showed central elevation of the macula. Optical coherence tomography showed a foveal thickness of 554 mm and confirmed the diagnosis of CME (Figure 1). The patient was started on bromfenac 0.09% (Xibrom) twice a day and prednisolone acetate 1.0% 4 times a day. In the 2-week follow-up, foveal thickness (281 mm) decreased and the CDVA improved (20/50C2). Three weeks later, there was a significant improvement in the subjective quality of vision and the CDVA reached 20/40. A 2-week taper of the topical steroid was initiated while the bromfenac was continued. When the patient returned 4 weeks later, however, the CDVA had fallen to 20/60 2 and the fovea had thickened to 472 mm. There was a question of poor
Figure 1. Macular OCT in Case 1.
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compliance with the medication schedule, and the patient was instructed to resume bromfenac twice a day and prednisolone acetate 4 times a day. Within 2 weeks, the CDVA had improved to 20/30 and the foveal thickness measured 276 mm. Medications were continued, and the steroid was gradually tapered. By 6 months, the visual acuity stabilized at 20/25 3 and the medications were discontinued.
thickness of 495 mm (Figure 3). The medical regimen was changed to difluprednate 0.05% (Durezol) 3 times a day and bromfenac 0.09% (Bromday) 3 times a day. Within 2 weeks, the CDVA had improved to 20/25. Medications were continued and 1 month later, the CDVA measured 20/20 and the foveal thickness had decreased to 333 mm. Medications were tapered over the following 3 weeks.
The patient with a history of diabetic retinopathy achieved 20/30 UDVA with 1C anterior chamber cell on the first postoperative day. Prophylaxis with ketorolac tromethamine 0.4% and prednisolone acetate 1.0% 4 times a day was started. However, the patient made an unscheduled return visit 10 days later with pain, tearing, and photophobia. The UDVA was 20/25 2, and trace cell was noted in the anterior chamber. The steroid dosage was increased to every hour for 2 to 3 days and was then reduced to every 2 hours. Five days later, the eye remained uncomfortable and the CDVA had fallen to 20/70. Mild conjunctival injection was noted on slitlamp examination. The steroid dosage was maintained, and the NSAID was changed to nepafenac 0.1% (Nevanac). One week later, the acuity had improved to 20/40 and the eye was more comfortable. Four weeks later, the vision remained stable; the topical medications were discontinued. However, during a previously scheduled appointment with the patient's retina surgeon 3 weeks later, CME was diagnosed. The UDVA was 20/60. Foveal thickness by OCT measured 336 mm (Figure 2). Fluorescein angiography showed a central, wreath-like cystic hyperfluorescence. The retina surgeon prescribed bromfenac 0.09% twice a day. Over the course of the next 3 months, the UDVA improved to 20/30 and the foveal thickness decreased to 261 mm.
DISCUSSION The U.S. Food and Drug Administration Grid of Historical Controls specifies standards for the occurrence of adverse events in the clinical investigation of IOLs.12 An IOL that does not perform statistically significantly worse than these standards is deemed safe. For pseudophakic CME, the grid lists a cumulative incidence of 3.0% and persistence at 1 year of 0.5%.C Wittpenn et al.8 report an overall rate of 1.8% and a zero incidence among patients receiving prophylaxis with both steroid and nonsteroidal agents. In our review, 0.1% of patients having cataract surgery developed postoperative CME within 3 months. One of these patients had a capsule complication and 1 had a history of diabetic retinopathy; both factors predispose to the development of CME.7 This retrospective chart review found a 0.1% cumulative incidence of acute postoperative CME. Although not a randomized prospective study, we believe this finding will help substantiate the widely held view that topical steroidal and nonsteroidal agents help reduce the frequency of CME. Many other variables may also play a role in the occurrence of CME, including surgical techniques and perioperative medications. If the incidence of CME in this study applies generally, it would be harder to successfully and ethically perform a randomized trial of medical prophylaxis.
Case 2: Diabetic Retinopathy
Case 3: Routine The UDVA on postoperative day 1 was 20/20. At the 2-week examination, the CDVA had fallen to 20/60 and OCT showed a foveal
Figure 2. Macular OCT in Case 2.
Figure 3. Macular OCT in Case 3 shows retinal thickening and cystic spaces. J CATARACT REFRACT SURG - VOL 38, DECEMBER 2012
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WHAT WAS KNOWN Postoperative CME has an incidence of 1% to 3%. Topical antiinflammatory agents may have a role in prophylaxis.
9. 10.
WHAT THIS PAPER ADDS The incidence of postoperative CME in a clinical practice routinely using topical antiinflammatory prophylaxis was lower than previously reported.
11.
12.
REFERENCES 1. Irvine SR. A newly defined vitreous syndrome following cataract surgery; interpreted according to recent concepts of the structure of the vitreous; the Seventh Francis I. Proctor Lecture. Am J Ophthalmol 1953; 36:599–619 2. Gass JDM, Norton EWD. Cystoid macular edema and papilledema following cataract extraction; a fluorescein fundoscopic and angiographic study. Arch Ophthalmol 1966; 76:646–661. Available at: http://archopht.jamanetwork.com/data/Journals/ OPHTH/17738/archopht_76_5_005.pdf. Accessed July 31, 2012 3. Lobo CL, Faria PM, Soares MA, Bernardes RC, Cunha-Vaz JG. Macular alterations after small-incision cataract surgery. J Cataract Refract Surg 2004; 30:752–760 4. Xu H, Chen M, Forrester JV, Lois N. Cataract surgery induces retinal pro-inflammatory gene expression and protein secretion. Invest Ophthalmol Vis Sci 2011; 52:249–255. Available at: http:// www.iovs.org/content/52/1/249.full.pdf. Accessed July 31, 2012 5. Sivaprasad S, Bunce C, Crosby-Nwaobi R. Non-steroidal antiinflammatory agents for treating cystoid macular oedema following cataract surgery. Cochrane Database Syst Rev 2012 Issue 2. Art. No. CD004239 6. Yilmaz T, Cordero-Coma M, Gallagher MJ. Ketorolac therapy for the prevention of acute pseudophakic cystoid macular edema: a systematic review. Eye 2012; 26:252–258 7. Yonekawa Y, Kim IK. Pseudophakic cystoid macular edema. Curr Opin Ophthalmol 2012; 23:26–32 8. Wittpenn JR, Silverstein S, Heier J, Kenyon KR, Hunkeler JD, Earl M, for the Acular LS for Cystoid Macular Edema (ACME)
Study Group. A randomized, masked comparison of topical ketorolac 0.4% plus steroid vs steroid alone in low-risk cataract surgery patients. Am J Ophthalmol 2008; 146:554–560 Chambers WA. Ophthalmic generics – are they really the same? [editorial] Ophthalmology 2012; 119:1095–1096 Packer M, Fine IH, Hoffman RS. Bimanual ultrasound phacoemulsification. In: Fine IH, Packer M, Hoffman RS, eds, Refractive Lens Surgery. Berlin, German, Springer-Verlag, 2005; 193–198 Donnenfeld ED, Perry HD, Wittpenn JR, Solomon R, Nattis A, Chou T. Preoperative ketorolac tromethamine 0.4% in phacoemulsification outcomes: pharmacokinetic-response curve. J Cataract Refract Surg 2006; 32:1474–1482 International Organization for Standardization. Ophthalmic Implants – Intraocular Lenses – Part 7. Clinical investigations. Geneva, Switzerland, ISO, 2006; (IS0 11979–7)
OTHER CITED MATERIAL A. Daily S, “Changes to Companies’ Pharmaceutical Sampling Policies,” Cataract & Refractive Surgery Today March 2011. Available at: http://bmctoday.net/crstoday/2011/03/article.asp? fZchanges-to-companiespharmaceutical-sampling-policies. Accessed July 31, 2012 B. Packer M, Hoffman RS, Fine IH, “Perfecting Your Protocol for Infection Prophylaxis,” Ophthalmology Management March 2008; pages 27–28,30,33–34. Available at: http://www. ophmanagement.com/article.aspx?articleZ101484. Accessed July 31, 2012 C. U.S. Food and Drug Administration. Center for Devices and Radiological Health. Intraocular and Corneal Implants Branch. Division of Ophthalmic Devices. Guidance for Industry and for FDA Reviewers. Intraocular Lens Guidance. Available at: http://www.fda.gov/OHRMS/DOCKETS/98fr/994052gd.pdf. Accessed July 31, 2012
J CATARACT REFRACT SURG - VOL 38, DECEMBER 2012
First author: Mark Packer, MD, CPI Oregon Health and Sciences University School of Medicine, Eugene, Oregon, USA
