Cystoid macular edema (CME) is still the most frequent cause of decreased vision after cataract surgery, although its incidence has declined with advances in surgical techniques (most notably, the change from intracapsular to extracapsular cataract extraction [ECCE]). Clinical CME has historically been defined as a reduction in vision to 20/40 or less that is attributable to ophthalmoscopically or angiographically visible CME. The condition occurs in as many as 1% to 6% of patients after uncomplicated phaco surgery.1,2

Advances in technique, instrumentation, and pharmacology have increased expectations for surgical outcomes, from both the patient's and the surgeon's perspective. Less dramatic visual deficits than 20/40 may be considered clinically significant today. For example, a patient may be symptomatic with a visual acuity of 20/25 or 20/30 or subtle metamorphopsia. Angiographic CME, in which visual acuity is unaffected but CME is present on fluorescein angiography, is seen in up to 19% of these patients.3 The incidence may be higher in patients with a greater degree of postoperative inflammation.4 Pseudophakic CME classically presents 4 to 6 weeks after cataract surgery, but it has occurred as early as 3 weeks or as late as 6 months postoperatively.5

MECHANISM

Uveal stimulation or the release of lens epithelial cells during intraocular surgery promotes prostaglandin synthesis in the anterior chamber.6 Prostaglandins disrupt the blood-aqueous barrier and thus permit cytokines and other inflammatory mediators to enter the anterior chamber.6 The prostaglandins and inflammatory mediators are then believed to diffuse through the vitreous to the retina, where they result in a breakdown of the blood-retinal barrier that leads to CME. Older patients and those with various other ocular conditions (including diabetes mellitus, uveitis, and retinal vascular occlusions) may be more susceptible to a breakdown of the blood-retinal barrier.6 The relative contributions of the inflammatory mediators and other predisposing factors are still unknown.

RISK FACTORS
Surgical

The risk of pseudophakic CME appears to be lower with phaco surgery than with either ECCE or intracapsular cataract extraction, perhaps because of reduced postoperative inflammation.7 The amount of inflammation, and hence the risk of CME, is greater with higher phaco power (>1 J).8

Surgical complications dramatically increase the risk of CME. A ruptured posterior capsule is associated with an 11.5% to 20% incidence of clinical CME in patients undergoing phacoemulsification.4,9 In those undergoing ECCE, the incidence may be as high as 30.8%.10 Retained lens fragments further increase the risk of clinical CME to as much as 29% after phacoemulsification.11 Immediate pars plana vitrectomy, although often not possible, may reduce this risk.12

Chronic CME in the setting of complicated cataract surgery may be due to mechanical traction on the retina or persistent inflammation. The former may be caused by vitreous strands adherent to the cataract wound. In the past, chronic inflammation was often seen with rigid ACIOLs as a result of iris trauma. Today, the incidence of CME with a well-positioned, open-looped ACIOL is much lower, although certain patients may still do better with sutured-in PCIOLs.13

Approximately 1% of patients may develop CME after Nd:YAG capsulotomy.14 This complication often occurs 1 to 5 months later and is believed to be related to opening the posterior capsule rather than to the energy of the Nd:YAG laser.15

Retinal Pathology

Patients with diabetes are at an increased risk of both clinically significant diabetic macular edema and CME following cataract surgery. In individuals with diabetic retinopathy but no macular edema prior to ECCE, the incidence of clinical CME may be as high as 75%.13 If no diabetic retinopathy is present prior to surgery, the incidence of clinical CME is much lower (11%).16 CME is also more likely to persist longer in diabetics, whether or not retinopathy is present.16 Specifically, chronic (>6 months) postoperative CME is more likely in patients with systemic hypertension or diabetes, probably because of a greater permeability of the blood-retinal barrier.17

Other underlying retinal pathology may cause CME. A recent study reported a 17% incidence of CME in pseudophakic patients after pars plana vitrectomy for retinal detachment.18 In the investigators' personal experience (ongoing study), patients who have previously undergone repair of retinal detachment are at a higher risk of CME after cataract extraction. This risk is present independent of whether the patient developed CME after the previous retinal surgery. The investigators have also observed an increased risk of CME in eyes that have had previous retinal venous occlusions (regardless of past macular edema) and in patients whose fellow eye had CME. Epiretinal membranes and idiopathic juxtafoveal telangiectasia may also cause CME, which often will not respond to pharmacotherapy.

In patients with a history of uveitis, CME is an important cause of poor vision postoperatively. The incidence of CME in pars planitis may be as high as 50% after phacoemulsification with the implantation of a PCIOL.19 The condition is often refractory to topical therapy alone in these patients and may require peri- or intraocular steroid injections.

Medication

The perioperative use of antiglaucoma eye drops such as epinephrine, dipivefrin, and the prostaglandin analogues has been shown to increase the risk of CME.8,20 Recently, the preservative benzalkonium chloride, which is found in many other ocular medications as well, has been independently associated with an increased incidence of CME, an effect attributed to the release of prostaglandins and other inflammatory mediators.20 The relative contributions of these medications and their preservatives are not fully understood.

PROPHYLAXIS

Topical steroids alone do not suppress the synthesis of inflammatory mediators, such as the prostaglandins.21 Topical NSAIDs, by suppressing the cyclooxygenase pathway responsible for prostaglandin production, have been shown to reduce aqueous flare and the development of CME when used after cataract surgery.21 Starting a topical NSAID such as ketorolac (Acular; Allergan, Inc., Irvine, CA) or diclofenac (Voltaren; Novartis Pharmaceuticals Corporation, East Hanover, NJ) q.i.d. for 3 days prior to cataract surgery and maintaining the patient on the NSAID for a minimum of 1 month postoperatively may be the best routine prophylaxis against CME.22

If possible, one should halt prostaglandin analogues perioperatively, because endogenous prostaglandins have been implicated in the mechanism of CME.6 A recent study in the United Kingdom found that 40% of the 519 ophthalmologists surveyed stopped these agents in at least some of their patients prior to cataract surgery.23 Most stopped the drug less than 1 week before surgery and did not resume it until 30 to 60 days after surgery.23

For uveitic patients, most important is maximum control of their intraocular inflammation with topical or oral steroids or with systemic immunosuppressants, if necessary. One may manage patients with refractory or recurrent uveitis or pars planitis with oral prednisolone (0.5mg/kg) initiated 2 weeks prior to surgery and tapered gradually postoperatively.24 This regimen has been shown to decrease aqueous flare and inflammation.24

Postoperatively, patients at high risk for CME should be treated prophylactically with topical NSAIDs for at least 6 to 12 weeks.

DIAGNOSIS
OCT of CME shows intraretinal cystic spaces and occasionally a small amount of subretinal fluid (Figure 1). OCT may be sufficient for diagnosis in patients whose presentation is classic. In diabetics or patients with an atypical presentation, however, fluorescein angiography assists the diagnosis by ruling out other causes of macular edema such as diabetic retinopathy, venous occlusive disease, choroidal neovascularization, or idiopathic juxtafoveal retinal telangiectasia.

In CME, the fluorescein angiogram shows a petaloid pattern of late leakage in the fovea (Figure 2). Hyperfluorescence of the optic disc is typically present in pseudophakic CME, but this clinical sign is often absent in other etiologies, including clinically significant diabetic macular edema, epiretinal membrane, or age-related macular degeneration.

It is important to consider other conditions that may mimic CME but will not respond to topical treatment. Cataract extraction may worsen diabetic macular edema. Patients with diabetes or with a history of prior retinal detachment or retinal vascular occlusion may develop an epiretinal membrane, often best appreciated on OCT. This technology is also helpful in diagnosing vitreomacular traction. Finally, choroidal neovascular membranes and juxtafoveal telangiectasia may cause intraretinal edema, both of which are best evaluated by fluorescein angiography.

TREATMENT
Initial Approach
After a confirmed diagnosis of pseudophakic CME, OCT is an objective and relatively sensitive method of monitoring the patient's response to treatment. We initiate topical therapy consisting of prednisolone acetate and an NSAID q.i.d. for at least 6 weeks in all patients with pseudophakic CME. If we observe a treatment response, the patient continues therapy until the edema resolves, which may take several months. Once the swelling abates, we taper the drops by one drop per week.25 Acular and Voltaren appear to be equally effective NSAIDs.26 Acular LS (0.4%; Allergan, Inc.) is generally preferred over Acular 0.5% because it causes less ocular irritation.

It is still not known whether topical NSAIDs alone are as effective as the combination of topical NSAIDs and steroids. A recent small study found no statistically significant difference in the response of pseudophakic CME to ketorolac alone versus ketorolac and prednisolone.27 An earlier study, however, found a statistical benefit with the combination of topical steroids and NSAIDs.25 It is possible that these drugs may act synergistically to restore the blood-retinal barrier by blocking prostaglandin synthesis (NSAIDs) and decreasing intraocular inflammation (steroids).

The FDA recently approved a new twice-daily topical NSAID (bromfenac 0.09% [Xibrom; Ista Pharmaceuticals, Inc., Irvine, CA]) for controlling inflammation after cataract surgery.28 Its effectiveness for the treatment of CME has not been studied. If effective, it may increase patients' compliance.
CME in patients on prostaglandin analogues usually responds favorably to the cessation of the prostaglandin drug and the initiation of therapy with a topical NSAID.

If Topical Therapy Fails

Topical therapy alone is usually effective in treating routine pseudophakic CME, but it may fail in patients who have other risk factors. If no improvement occurs after 6 weeks of strict compliance, one may consider periocular or intravitreal steroids. For refractory pseudophakic CME, intravitreal Kenalog (Bristol-Myers Squibb Company, New York, NY) may reduce macular edema and improve vision, but this effect may only last 2 to 4 months.29

Pars plana vitrectomy may be indicated when macular edema is associated with epiretinal membranes, suspected retained lens fragments, or pars planitis that is unresponsive to maximum medical therapy. Even in the absence of vitreoretinal abnormalities or the aforementioned surgical indications, research has shown that pars plana vitrectomy resolves chronic CME in some patients.30 

Jeffrey S. Heier, MD, is a vitreoretinal surgeon at Ophthalmic Consultants of Boston and President of the Center for Eye Research & Education Foundation. He is a member of the Allergan US Vitreoretinal Advisory Board. Dr. Heier may be reached at (617) 314-2611; jsheier@eyeboston.com.
Tina A. Scheufele, MD, is a vitreoretinal fellow at Ophthalmic Consultants of Boston and at Tufts University School of Medicine/New England Eye Center. She states that she holds no financial interest in any product or company mentioned herein. Dr. Scheufele may be reached at (617) 314-2611; tascheufele@eyeboston.com.

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