Background
Cystoid macular edema (CME) is a painless condition in which swelling or thickening occurs of the central retina (macula) and is usually associated with blurred or distorted central vision. Less common symptoms include metamorphopsia, micropsia, scotomata, and photophobia.
CME is a relatively common condition and is frequently associated with various ocular conditions, such as age-related macular degeneration (ARMD), uveitis, epiretinal membrane, vitreomacular traction, diabetes, retinal vein occlusion, medicine-related, or following ocular surgery. When CME develops following cataract surgery and its cause is thought to be directly related to the surgery, it is referred to as Irvine-Gass syndrome or pseudophakic CME.
Postcataract CME is usually self-limited, but for chronic CME or in cases of multiple recurrences, photoreceptor damage with permanent impairment of central vision may result.
Pathophysiology
The primary cause of cystoid macular edema (CME) depends on the underlying disease process, but most pathways eventually lead to vascular instability and breakdown of the blood-retinal barrier. The Müller cells in the retina become overwhelmed with fluid leading to their lysis. This results in an accumulation of fluid in the outer plexiform and inner nuclear layers of the retina. Diabetes and retinal vein occlusion can both lead to CME by causing vascular instability directly (vascular endothelial cell damage). Alternatively, CME associated with uveitis or following cataract surgery is most likely caused by the cytokines released by activated inflammatory cells. These molecules lead to breakdown of the blood-retinal barrier and capillary leakage. [1]
Inflammatory cause
In the inflammatory pathway, the enzyme phospholipase causes the release of arachidonic acid. Subsequently, cyclooxygenase converts arachidonic acid to prostaglandin. Prostaglandins can cause breakdown of the blood-retinal barrier, including vasodilation, increased capillary permeability from compromise of tight endothelial junctions in the retinal capillaries, and decreased removal of fluid by the retinal pigment epithelium (RPE). The enzyme phospholipase can be inhibited by steroids and thereby blocks the formation of prostaglandins and their effects. The cyclooxygenase pathway is specifically inhibited by aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs).
Another product of arachidonic acid breakdown involves the enzyme lipoxygenase, which alternately converts arachidonic acid to leukotriene, a chemotactic agent. The exact role of leukotriene in CME remains unclear, and, currently, no lipoxygenase specific blocking agents are approved for use in the treatment of CME.
Other causes
Patients with systemic disorders, such as diabetes or renal failure, may develop CME from breakdown of the blood-retinal barrier primarily due to vascular compromise. In diabetes, endothelial cells are damaged by advance glycosylation end-products. In addition, cytokines, such as vascular endothelial growth factor (VEGF), accumulate in the vitreous cavity of diabetic patients and lead to capillary leakage. CME can also be caused by mechanical forces (ie, epiretinal membrane, vitreomacular traction) pulling on the retinal surface, leading to vascular compromise and breakdown of the blood-retinal barrier.
Patients with a history of retinal vein occlusion (RVO), epiretinal membrane (ERM), and even prostaglandin analogs were found to have increased rates of pseudophakic CME. [2, 3, 4]
Other ocular conditions, such as exudative ARMD, cause CME by the growth of neovascular membranes, which are inherently leaky.
Epidemiology
Frequency
United States
The incidence following cataract surgery (Irvine-Gass syndrome) of clinically significant CME with decreased vision is only 0.2-1.4% after modern phacoemulsification surgery. The frequency was more common in older types of cataract surgery, where CME could occur in 20-60% of patients. Using more sensitive methods to detect macular edema such as optical CT (OCT) current rates have been estimated between 4-40%. [5, 6]
A 2014 study by Hunter et al found the incidence of pseudophakic CME at 1.5% of those patients undergoing routine cataract surgery at an academic center, and, interestingly, 27% of these patients had a best-corrected vision of less than 20/20 even after resolution of the CME. [7]
The frequency varies when other comorbidities such as diabetes are included. For example, patients with wet ARMD typically have some component of CME. Diabetic macular edema is the most common cause of vision loss in patients with nonproliferative diabetic retinopathy, and patients with a history of diabetic macular edema have higher rates of macular edema following cataract surgery. [8] CME is also a common cause of vision loss in patients with uveitis.
International
Studies have reported a similar incidence of CME and Irvine-Gass syndrome worldwide. [9, 10, 11]
Mortality/Morbidity
CME following cataract surgery, although usually treated medically, has been shown to often resolve spontaneously within 6 months. Ninety percent of eyes improve to a visual acuity of 20/40 or better in cases with a posterior chamber intraocular lens (IOL). However, remissions and exacerbations of macular edema can result in photoreceptor damage with permanent impairment of vision.
CME due to diabetes, retina vein occlusion, or chronic uveitis tends to be chronic with periods of remission and exacerbation.
Race
No significant racial predilection exists.
Sex
No sexual predilection exists.
Age
CME can occur at any age depending on the etiology. Advanced age has been reported as a risk factor for the development of Irvine-Gass syndrome.
Prognosis
The majority of patients who have pseudophakic CME eventually achieve vision of 20/30 or better. Other cases of CME can be chronic, requiring long-term treatment.
Patient Education
For excellent patient education resources, visit eMedicineHealth's Eye and Vision Center. Also, see eMedicineHealth's patient education article How to Instill Your Eyedrops.
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Fundus photo of the right eye in a patient with cystoid macular edema.
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Fluorescein angiography of the right eye (late phase) showing central macular leakage in cystic spaces around the fovea.
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Optical coherence tomography (OCT) of the right eye showing central macular cystic spaces in cross-section.
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Fundus photo of the right eye in a patient with cystoid macular edema from diabetic retinopathy.
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Fluorescein angiography of the right eye (late phase) showing central macular leakage in cystic spaces around the fovea.
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Optical coherence tomography (OCT) of the right eye showing central macular cystic spaces in cross-section.
