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Prevention and treatment of cystoid macular edema

ByKeith A. Warren, MD

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Cystoid macular edema (CME) is a devastating complication for patients, especially those with premium IOLs, because CME often results in vision loss. Studies have shown that 12% of patients may have retinal thickening following uncomplicated cataract surgery.¹ Retinal thickening most commonly occurs 4 to 6 weeks following cataract surgery and is believed to be caused by a prostaglandin-mediated breach of the blood-retinal barrier.²

Although retinal specialists may debate about the exact definition of CME, any retinal thickening should be considered significant. — Keith A. Warren, MD

Although retinal specialists may debate about the exact definition of CME, any retinal thickening should be considered significant. Optical coherence tomography (OCT) may help an ophthalmologist make the appropriate diagnosis (Figures 1 and 2), and, equally as important, OCT can monitor a patient’s response to topical nonsteroidal anti-inflammatory drugs and steroidal therapy used for the treatment of CME.

NSAID studies

NSAIDs were first considered for therapy of CME after Kapin’s study on the efficacy of NSAIDs for the prevention of retinal edema in an animal model.³ Kapin and his colleagues induced experimental retinal edema by injecting concanavalin A, a powerful mitogen, into rabbits. The animals were pretreated with nepafenac, diclofenac or ketorolac 1 day prior to the injection of concanavalin A and were continued on the treatment for 3 days following the concanavalin A injection. The study showed that nepafenac inhibited prostaglandin synthesis, which would reduce posterior segment inflammation, at a greater rate and was significantly more potent than diclofenac or ketorolac.³

Bucci and colleagues studied prostaglandin inhibition and the aqueous concentration of ketorolac and nepafenac in patients undergoing phacoemulsification.⁴ In the study, 132 patients received ketorolac or nepafenac four times daily for 2 days prior to cataract surgery. Aqueous samples obtained at the time of surgery indicated 61% of eyes treated preoperatively with ketorolac had undetectable levels of prostaglandin synthesis, while 17% of eyes treated preoperatively with nepafenac had undetectable levels of prostaglandin synthesis. Although both NSAIDs penetrated the cornea, ketorolac inhibited the prostaglandin and penetrated into the aqueous more than nepafenac.⁴

Wolf and colleagues studied the prophylactic effects of nepafenac on pseudophakic macular edema after uneventful phacoemulsification.⁵ Two groups of patients were treated preoperatively with prednisolone acetate and nepafenac. Two hundred ten patients were treated postoperatively with prednisolone acetate and nepafenac, and 240 patients were treated postoperatively with prednisolone acetate alone. Patients treated with both prednisolone acetate and nepafenac did not develop CME, compared to five cases of CME in patients who were treated with prednisolone acetate alone (2.1%, P = .0354).⁵

Figure 1. An OCT image of a patient with CME. Although retinal specialists may debate about the exact definition of CME, any retinal thickening should be considered significant. Image: Warren KA

An additional study by McColgin and Raizman indicates that the postoperative combination of diclofenac and corticosteroid is more effective at preventing CME than corticosteroid alone.⁶ Of 60 patients undergoing cataract surgery, the group who received postoperative diclofenac plus corticosteroid had a 0% incidence of CME at week 6; however, the patient group that received postoperative corticosteroid alone had a 12% incidence of CME at week 6.⁶

Multiple studies have demonstrated that NSAIDs should be added to corticosteroid therapy for treatment of postoperative CME. Combination therapy appears to be more efficacious and may provide a better visual outcome than corticosteroid therapy alone.^7,8

CME treatment

For most retina specialists, the current primary treatment modality for CME consists of both a corticosteroid and an NSAID, administered topically. Prior to the development of NSAIDs that have improved posterior segment penetration, many retina specialists did not use topical NSAIDs. Treatment strategies have changed with the evolution of the currently available NSAIDs that offer better penetration, are effective in treating CME and may have an important role in reducing the incidence of CME.

Multiple studies have demonstrated that NSAIDs should be added to corticosteroid therapy for treatment of postoperative CME. — Keith A. Warren, MD

If topical combination treatment fails, then patients are often treated with a posterior subtenon injection of 20 mg triamcinolone. If the initial treatment of corticosteroid and NSAID fails, most retinal specialists will treat patients with parenteral steroids because of the ability to achieve a high concentration of the steroid to the target tissue. Intraocular steroid injections are useful for resistant CME, but most retinal specialists do not use intraocular steroid injections as an initial treatment.

My treatment regimen for patients includes a posterior subtenon injection of 20 mg of triamcinolone and topical nepafenac four times a day for 6 weeks; the drug is then tapered over the next 6 weeks. I reserve treatment with intraocular steroids for patients who are unresponsive to this treatment regimen at week 6.

The most frequent complication of steroid treatment, particularly in patients who received an intraocular steroid, is increased IOP, which occurs in more than one-third of patients.⁹ However, the most significant and frequent complication of CME is reduced visual function, including reduced contrast sensitivity and color desaturation. Therefore, it appears that prevention of CME may reduce the morbidity associated with this disorder to a greater extent than treating CME after it has occurred.

Figure 2. An OCT image depicting a healthy macula. In addition to diagnosis, OCT may help monitor a patient’s response to topical nonsteroidal anti-inflammatory drugs and steroidal therapy used for the treatment of CME. Image: Warren KA

My colleagues and I conducted a study on the use of NSAIDs as a treatment alternative for steroid responders.¹⁰ The study consisted of 15 patients who were known steroid responders. Eleven patients were recent pseudophakes, and four patients had CME secondary to disease of the vitreoretinal interface, either epiretinal membrane or vitreous traction. The pseudophakic patients presented to us 3 weeks postoperatively, on average, and the vitreoretinal interface patients had CME for at least 4 weeks. All patients were treated with nepafenac alone for 6 weeks, and then the NSAID was tapered over an additional 6 weeks. Treatment resulted in no further vision loss in any of the patients.

The mean pretreatment Snellen vision acuity of the patients was 20/74, and the mean posttreatment Snellen visual acuity was 20/39, for an average improvement of 2.54 lines (P = .001). The average retinal thickness was 528 µm prior to treatment and was reduced to 335 µm after treatment, for a difference of 196 µm (P = .002).¹⁰

Conclusions

CME prevention and treatment are important concepts for ophthalmologists to understand; CME treatment usually results in decreased visual function, emphasizing the importance of preventing CME. — Keith A. Warren, MD

CME prevention and treatment are important concepts for ophthalmologists to understand; CME treatment usually results in decreased visual function, emphasizing the importance of preventing CME. Preoperative NSAIDs help to reduce the risk of postoperative CME. CME is most commonly and effectively treated with a combination of an NSAID and corticosteroid. The ability of the newer generation NSAIDs to penetrate into the target tissue has improved their efficacy and utility in preventing and treating this debilitating disorder.

References

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2. Mishima H, Masuda K, Miyake K. The putative role of prostaglandins in cystoid macular edema. Prog Clin Biol Res. 1989;312:251-264.
3. Kapin MA, Yanni JM, Brady MT, et al. Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac. Inflammation. 2003;27:281-291.
4. Bucci FA Jr., Waterbury LD, Amico LM. Prostaglandin E2 inhibition and aqueous concentration of ketorolac 0.4% (Acular LS) and nepafenac 0.1% (Nevanac) in patients undergoing phacoemulsification. Am J Ophthalmol. 2007;144:146-147.
5. Wolf EJ, Braunstein A, Shih C, Braunstein RE. Incidence of visually significant pseudophakic macular edema after uneventful phacoemulsification in patients treated with nepafenac. J Cataract Refract Surg. 2007;33:1546-1549.
6. McColgin AZ, Raizman MB. Efficacy of topical Voltaren in reducing the incidence of postoperative cystoid macular edema. Invest Opthalmol Vis Sci. 1999;40(Suppl):S289.
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8. Heier JS, Topping TM, Dirks MS, Chern S. Ketorolac versus prednisolone versus combination therapy in the treatment of acute pseudophakic cystoid macular edema. Ophthalmology. 200;107:2034-2039.
9. Rhee DJ, Peck RE, Belmont J, et al. Intraocular pressure alterations following intravitreal triamcinolone acetonide. Br J Ophthalmol. 2006;90:999-1003.
10. Warren KA. Topical nepafenac as an alternate treatment for cystoid macular edema in steroid responsive patients. Retina. In press.