Introduction
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 vision.
CME is a relatively common condition and is frequently associated with various ocular conditions, such as cataract surgery, age-related macular degeneration (ARMD), uveitis, eye injury, diabetes, retinal vein occlusion, or drug toxicity. 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.
Chronic CME or multiple recurrences may result in macular photoreceptor damage with permanent impairment of central vision.
Pathophysiology
The primary cause of 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.
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 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.
Other ocular conditions, such as exudative ARMD, cause CME by the growth of neovascular membranes, which are inherently leaky.
Frequency
United States
- Incidence of CME depends on the etiology.
- The incidence following cataract surgery (Irvine-Gass syndrome) is approximately 1% after modern phacoemulsification surgery. The frequency was more common in older types of cataract surgery, such as extracapsular cataract extraction, where CME could occur in up to 20% of patients.
- From other causes, the frequency varies. For example, most patients with wet ARMD have some component of CME. (No CME is found in dry ARMD.) Diabetic macular edema itself is the most common cause of vision loss in patients with nonproliferative diabetic retinopathy. 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.
Mortality/Morbidity
The natural history depends on the etiology.
CME following cataract surgery, although usually treated medically, has been shown to often resolve spontaneously, with 90% of eyes improving 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.
Clinical
History
- Patients with CME usually present with decreased or blurry vision.
- Patients presenting with CME often have a history of cataract surgery, diabetes, retinal vein occlusion, or uveitis.
Physical
- Slit lamp biomicroscopy reveals blunted or irregular foveal light reflex, retinal thickening, and/or intraretinal cysts in the foveal region.
- Additional examination can help elicit the cause for CME:
- Uveitis: Evidence of intraocular inflammation manifested by anterior chamber cells and flare and vitreous cells may be present in some cases.
- Epiretinal membrane/macular pucker: Dilated fundus examination can help reveal the membrane on the retinal surface.
- Diabetes: Retinal examination reveals diabetic retinopathy associated with the diabetic retinal edema.
- Optic disc edema is also classically present in Irvine-Gass syndrome.
Causes
The following risk factors have been associated with CME:
- Previous ocular surgical procedure
- Cataract surgery - Increased frequency with complicated intraocular surgery involving the rupture of the posterior capsule or vitreous loss
- Penetrating keratoplasty (corneal transplant)
- Retinal surgery - Pars plana vitrectomy
- YAG capsulotomy (rarely associated with CME)
- Systemic disease
- Diabetes
- Chronic renal failure
- Hypertension (rarely)
- Other eye conditions
- Retinal vein occlusion
- Preexisting ocular inflammation or uveitis
- Exudative ARMD
- Radiation exposure to eye (history of radiation to head or neck)
- Retinitis pigmentosa
- Epiretinal membrane
- Drug toxicity
- Systemic medications (eg, nicotinic acid, docetaxel)
- Topical prostaglandin analogs for glaucoma (eg, latanoprost, travoprost, bimatoprost)
- Long-term topical epinephrine or dipivefrin therapy
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References
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Further Reading
Keywords
Irvine-Gass syndrome, cystoid macular edema, CME, macular fluid accumulation, cataract surgery, ocular surgery
