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Postoperative Cystoid Macular Edema: Diagnosis, Prevention, and Treatment
Robert I. Park, MD · Jeffrey S. Heier, MD
Cystoid macular edema (CME) is a disease entity that has been studied in ophthalmic literature. CME is a disruption of the blood-retinal barrier that leads to the accumulation of fluid in the retinal extracellular space and the development of fluid filled (cystoid) spaces in the outer plexiform layer and the inner nuclear layer of the retina. The term cystoid rather than cystic is used because the fluid-filled spaces do not possess the epithelial layer that is present in a true cyst. Many cases of CME are subclinical and evident only on fluorescein angiography; in clinically significant cases, patients may complain of decreased vision or of visual distortion. Earlier studies of post-cataract extraction CME defined clinically-significant CME as cystic macular changes with characteristic angiographic findings associated with visual decline to 20/40 or worse. However, as our techniques and instrumentation have advanced, our expectations have become greater as well. Therefore, many anterior segment surgeons believe any degree of visual loss, no matter how small, is clinically significant.
A number of entities may cause CME, including diabetic retinopathy, venous occlusive disease, hypertension, choroidal neovascularization, retinal vascular malformations, tumors, radiation retinopathy, uveitis, epiretinal membranes, retinitis pigmentosa, dominant CME and intraocular surgery. This tutorial focuses on postoperative CME.
Postoperative CME was initially described in 1953 by Irvine, who noted the development of macular changes and decreased vision following intracapsular cataract extraction. Symptoms of the syndrome included rupture of the anterior hyaloid face, vitreous adhesions to the surgical wound, vitreous opacities, macular changes, and irritability of the eye. 1 In 1966, Gass and Norton described the fluorescein angiographic characteristics of postoperative CME. 2 Consequently, postoperative or more correctly postcataract extraction CME has become known as Irvine-Gass Syndrome.
Clinically significant CME generally occurs within 4 to 12 weeks after surgery although it has been reported to occasionally occur months to years after surgery.
The reported incidence of postoperative CME varies. Early studies demonstrated a 5% to 15% incidence of clinically significant CME after intracapsular cataract extraction. Studies using fluorescein angiography demonstrated an overall incidence of 36% to 60% following aphakic intracapsular cataract extraction.3-6 Patients undergoing extracapsular cataract extraction carry a 10% to 20 % risk of developing angiographically evident CME,7-9 but the exact incidence of clinically significant CME has not been determined and varies based upon study design and the definition of clinically-significant CME. The incidence of chronic CME is 1%.10
The occurrence of CME increases with capsular rupture, rupture of the anterior hyaloid face, or adherence of vitreous to the surgical wound. While the use of intraocular lenses (IOLs) does not increase the incidence of CME,11,12 placement of sutured or iris-supported IOLs increases the risk for CME.13,14 Early capsulotomies have been demonstrated to increase the incidence of CME.7,15
No correlation between sex or operated eye and CME has been reported although an increased incidence of CME in older patients has been found. The relationship between race and CME has not been determined. Systemic hypertension and diabetes may place patients at higher risk for chronic CME.
Although the histopathologic changes in CME have been well documented, the exact mechanism of breakdown of the blood-retinal barrier mechanism in CME is not well understood. A number of mechanisms have been postulated and are summarized below:
Mechanical Traction Theory
Vitreoretinal adhesion is reported to be strongest at the vitreous base, optic nerve, and macula. Proponents of this theory purport the
increased traction in the macular region, specifically on the Muller cells, may induce CME. The exact mechanism by which leakage occurs
is not hypothesized.
Increased Prostaglandin Production
Anterior segment inflammation induced during surgery results in increased leakage of iris vessels and increased prostaglandin production.
The prostaglandins are believed to induce the inflammatory changes in the macula.
Light Exposure
The production of free radicals secondary to light exposure is hypothesized to stimulate the production of prostaglandins. The use of UV-absorbing IOLs was found to reduce CME in a large study by Kraff and colleagues.9 However, these results were not supported
in a number of other smaller studies.16 Use of filters in operating microscopes was not found to decrease the incidence of
CME.17,18
Research efforts in CME are directed toward the prevention or decrease of overall inflammation as well as towards specific targeting of prostaglandins. CME is often present in cases without evidence of mechanical traction (and in patients with posterior vitreous separation). Efforts at prostaglandin inhibition have demonstrated efficacy against CME, both in prevention and treatment.
History
Generally, CME presents 4 to 12 weeks after cataract extraction, whether complicated or uncomplicated, but it can occur many years
after surgery.
Symptoms
Patients may be asymptomatic or may present with decreased visual acuity, generally in the range of 20/30 to 20/70, but may be as poor as
20/200. Patients may be 20/20 and still complain of metamorphopsia. Patients may also present with photophobia, ocular irritation, and floaters.
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Findings on Examination
Patients may present with some or all of the following (Slide 1):
Anterior segment: limbal conjunctival injection, anterior segment cell and flare, iris peaking, vitreoiridal adhesions, anterior chamber vitreous, vitreous incarceration in surgical wound and capsular rupture.
Posterior segment: vitreous cells or flare, vitreous syneresis, vitreomacular adhesions, blunted foveal reflex, white-yellow foveal spot, mild papilledema (possible), macular/foveal cysts, occasional microaneurysm, or small intraretinal hemorrhage.
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Atrophy or hyperpigmentation of the retinal pigment epithelia (RPE) may occur in chronic cases. Cystoid degeneration and macular holes may develop in chronic cases.
Careful examination for other causes of macular edema should be performed, such as epiretinal membrane or clinically significant diabetic macular edema.
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Fluorescein Angiogram
A rapid sequence fluorescein angiogram should be performed (Slide 2, Slide 3A,
Slide 3B, Slide 3C, Slide 3D, and Slide 3E).
Early phase photos will demonstrate leakage from
parafoveal capillaries. Later frames will demonstrate gradually increasing hyperfluorescence in a petalloid pattern around the fovea.
Late frame photographs typically show staining and pooling at the macula with hyperfluorescence of the optic nerve (Slide 4).
The degree of leakage does not correlate to visual symptoms. It is critical to evaluate the angiogram at 10 minutes, as a relatively normal
angiogram may be present until the late frames.
The early hyperfluorescence corresponds to leakage of the parafoveal capillaries. As fluorescein diffuses into the cystoid spaces in the inner nuclear layer and outer plexiform layer, the classic petalloid pattern develops. Late staining of the fovea occurs from leakage of the retinal capillaries and from the cystoid pools. Staining of the optic disc occurs from leakage of the peripapillary capillaries. The presence or absence of optic disc staining is often helpful in differentiating pseudophakic CME from other causes of CME. Pseudophakic CME is typically associated with disc staining, while many other common causes of CME such as diabetic macular edema, epiretinal fibrosis, and exudative macular degeneration are not.
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Optical Coherence Tomography and Retinal Thickness Analysis
Optical coherence tomography (OCT) and retinal thickness analysis (RTA) are techniques for the determination of retinal thickness
which may be useful in quantifying the degree of macular edema rather than the leakage of vessels.21,22 OCT and RTA
determine retinal thickness by illumination of the retina with a monochromatic laser beam. In OCT, interferometry is used to determine the
retinal thickness while in RTA images of the retina (illuminated much like through a slit lamp) are captured, digitized and analyzed through a
computer algorithm to determine thickness. Although RTA and OCT are not widely used, they may be useful in allowing quantification of
CME before, during and after therapy.
The iris is believed to be the primary source of prostaglandins in CME. Topical medications show good penetration into the anterior chamber to the iris and may be more efficacious than peribulbar injection (Slide 5A and Slide 5B).
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Topical Anti-inflammatories
Nonsteroidal anti-inflammatory drugs (NSAIDs). Topical NSAIDs are cyclooxygenase inhibitors (COIs) that have been shown to block the
conversion of arachidonic acid to prostaglandins such as ketorolac, diclofenac, flurbiprofen and suprofen. Topical COIs have been shown
to improve visual acuity in established CME in double-masked, randomized, placebo-controlled studies in aphakic and pseudophakic patients.
Ocular penetration is better with topical COIs; oral NSAIDs have not been demonstrated to be of benefit in CME.23,24-26
Corticosteroids
Corticosteroids (e.g., prednisolone acetate 1%) block the release of arachidonic acid from cell membranes and, thus, inhibit the formation
of prostaglandins. Topical corticosteroids have shown good penetration into ocular tissues but systemic corticosteroids have demonstrated a
more consistent anti-inflammatory effect at high doses. Side effects include corticosteroid-induced IOP elevation, cataract formation and
immunosuppression. Corticosteroids may be more beneficial in CME associated with uveitis than CME associated with pseudophakia.
Systemic Medications
Corticosteroids. High dose systemic corticosteroids demonstrate a more consistent anti-inflammatory effect but at the cost of increased
side effects and risks. These possible risks include osteoporosis, immune suppression, aseptic necrosis of the femoral head, exacerbation of
diabetes, etc. Systemic corticosteroids have demonstrated efficacy against uveitic CME.
Carbonic anhydrase inhibitors (CAIs). CAIs stimulate the pumping action of the RPE, reducing the amount of fluid within the macula in CME.27 Recurrence of CME is common upon discontinuation of CAIs and the effect of CAIs on inflammatory processes has not been studied. Topical CAIs have not been evaluated for effectiveness in CME. Small case studies have demonstrated the efficacy of CAIs for treatment of CME associated with pseudophakia and retinitis pigmentosa, but in these cases CME recurs with discontinuation of the treatment. The side effects may be poorly tolerated by patients.
Peribulbar Injection
Subtenon’s injections of corticosteroids theoretically deliver a higher dose of corticosteroids to the macula. However, there is a risk of penetration
of the globe, orbital complications and prolonged elevation of intraocular pressure (in corticosteroid-responsive patients). Several series have
documented beneficial effects of corticosteroid injections in patients refractory to topical treatment, but the definition of "refractory
treatment" is not clear in these studies, and many patients may have been inadequately treated prior to injection.
Surgical Intervention
Surgical intervention is aimed at reducing vitreoiridal adhesions with the goal of decreasing iris irritation.
Guidelines for treatment appear below. Each additional step becomes necessary if previous treatment is unsuccessful. Decisions regarding a specific course and possible surgical intervention must be made on a case-by-case basis.
Surgical intervention may be considered at any point along the above pathway and will be dependent on the clinical situation.
There is a growing trend toward the use of topical COIs 1 to 3 days prior to surgery. The inhibition of prostaglandin release has been shown to decrease postoperative inflammation, which likely leads to a decrease in CME. Similarly, postsurgical use of topical COIs has been shown to decrease the incidence of CME, which has been demonstrated in a number of studies.23-25,32 However, only ketorolac tromethamine 0.5% has been demonstrated to improve visual acuity in a randomized, prospective, double masked, placebo controlled study of chronic aphakic and pseudophakic CME.26
