Cystoid Macular Edema

Background

Cystoid macular edema is a condition in which swelling develops in the center of the retina (macula). It can occur in many situations, but most commonly will occur with inflammatory diseases, with certain medications, and after eye surgery. Exactly why this happens is not clear. It is felt that local inflammation causes release of factors that increase the permeability (leakage) of capillaries in the macula. When blood passes through these vessels, fluid leaks into the surrounding tissue through the abnormal blood vessel walls. There are numerous causes of macular edema, but only the post-surgical form will be discussed here.

Causes of Macular Edema

• Diabetic retinopathy
• Irvine-Gass syndrome (post-cataract and post-surgical)
• Propine/Epinephrine and Prostaglandins
• Retinitis pigmentosa
• Inflammatory (pars planitis, sarcoidosis, JRA, birdshot retinochoroidopathy)
• Vascular diseases (BRVO, CRVO, parafoveal telangiectasis)
• Epiretinal membrane
• Nicotinic acid
• Tumors, choroidal
• Age-Related Macular Degeneration

In severe cases, the swelling may persist despite treatment. Chronic CME may cause structural changes in the retina, including retinal thinning and scarring. Chronic cases can also lead to lamellar (partial-thickness) macular hole formation.

Post-Cataract Surgery

Prevalence

It is estimated that around 8-12% of cataract patients will develop clinically significant CME after uncomplicated cataract surgery. A larger percentage (25-39%) will show angiographic CME which is leakage on a dye test called a fluorescein angiogram. Diabetes may predispose to CME after cataract surgery. One study showed CME in 32% of diabetics without retinopathy, and in 81% of diabetics with retinopathy at the time of cataract surgery. Diabetic with pre-existing diabetic macular edema are often treated prophylactically before cataract surgery with laser or with intravitreal steroid injections.

Symptoms

A patient with CME often complains of decreased vision since cataract surgery. They often feel that the initial improvement with surgery gradually disappears. This typically occurs 2-8 weeks after cataract surgery, and is painless.

Diagnosis of CME

A dilated eye examination will often reveal a central yellow spot and loss of the normal foveal reflex. Sometimes cystic changes or spoke-like radial striae in fovea are seen depending on the amount of fluid accumulation.

Fluorescein Angiography

A fluorescein angiogram is a dye test where sodium fluorescein is injected into an arm or hand vein and photographs of the retina are taken to determine circulatory and structural abnormalities. Cases of CME show "petalloid" leakage late in angiogram (about 10 minutes). Often, there is associated disc hyperfluorescence - mostly with post-cataract CME. This feature may predict a better response to anti-inflammatory medications. The amount of clinical leakage does not correlate with visual acuity or visual loss.

Fluorescein angiogram of a patient with postoperative CME. This person shows the classic “petalloid” appearance due to leakage of dye (central white areas) into the outer plexiform layer of the retina. The edema resolved with topical pharmacologic therapy (drops).

Optical Coherence Tomography

Optical coherence tomography (OCT) is a non-invasive imaging technique that gives a cross-sectional image of macula. The amount of thickening has been reported to correlate with visual loss, but this has not always been our experience. Edema causes mechanical stress on the retina, but the visual pathways remain intact because the fluid is outside the cells (extracellular). It is extremely valuable in following a patient's response to therapy and determining whether or not more treatment is necessary.

Pharmacologic Treatment (Drops)

Generally, CME is mild and over 90% of patients will have spontaneous resolution. For those who do not, treatment is generally instituted in a stepwise fashion. Since prostaglandin-mediated inflammation is thought to play a key role in the development of CME, the current focus is on prevention of prostaglandin synthesis. Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids have sites of action in the prostaglandin pathways.

Ocular penetration of topical NSAID drops is superior to oral NSAIDs. Oral NSAIDs (i.e., aspirin, naproxen, indomethacin, and ibuprofen) do not reach high enough concentrations in the eye to significantly benefit patients with CME.

Ketorolac (Acular) is the only NSAID shown by two randomized studies to help treat chronic pseudophakic CME and is the drug of choice for CME. Other topical NSAIDs (Voltaren and Ocufen) are of unknown benefit but can be used in certain cases.

Newer NSAIDs Nevanac (nepafenac 0.1%) and Xibrom (bromfenac 0.09%) claim higher penetration to the posterior part of the eye and a less frequent dosing schedule, but have not yet been studied for CME.

Corticosteroids are also used in conjunction with NSAIDs in the treatment of CME. Corticosteroids block release of arachidonic acid from cell membranes which inhibits prostaglandin formation. Topical corticosteroid treatment is probably no more effective than topical NSAIDs, but are often used because of the efficacy of periocular steroids.

Unlike NASIDs, there are no good randomized controlled studies of steroids in pseudophakic (post-cataract) CME. Systemic steroids only have a role in inflammatory CME such as pars planitis and sarcoidosis.

Pharmacologic Treatment (Injections)

For those patients with severe edema or edema that doesn't respond to 1-2 months of drops, injection of a long-acting steroid, triamcinolone acetate (Kenalog) can be done. Depending on the reason for the edema, the first step is an injection into the subconjunctival/subtenon's space. This potential space is outside of the eyeball. After topical anesthetic gel, approximately 1 cc of Kenalog is injected into the subconjunctival/subtenon's space. This is not visible unless a patient looks down and has their eyelid lifted.

For those patients with a poor response to periocular steroids, a direct intravitreal injection of Kenalog can be performed. After topical and subconjunctival anesthetic, and small amount (0.1 cc) of Kenalog is injected directly into the vitreous cavity. Although most patients are very apprehensive, this is a painless procedure.

Vitrectomy

There are two major studies that have shown that the vitreous plays a role in the pathogenesis of CME. It is felt that, based on these studies, vitrectomy should be considered in patients with chronic CME, CME unresponsive to medications, and those with vitreous adhesions to anterior segment structures. In practice, patients rarely need this intervention, but for those special situations, this can be extremely helpful.