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.
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.
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.
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.
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.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.CausesThe 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)
Chronic renal failure
Other eye conditions
Retinal vein occlusion
Preexisting ocular inflammation or uveitis
Radiation exposure to eye (history of radiation to head or neck)
Systemic medications (eg, nicotinic acid, docetaxel)
Topical prostaglandin analogs for glaucoma (eg, latanoprost, travoprost, bimatoprost)
Long-term topical epinephrine or dipivefrin therapyTreatment & Medication
Treatment is aimed at the underlying etiology; however, several of the common treatments may help different causes of CME.
Medical treatment modalities include the following:
Corticosteroids directly inhibit the enzyme phospholipase, blocking the formation of prostaglandins. They are considered the primary treatment of CME in many instances, specifically in the treatment of CME secondary to uveitis. Corticosteroids can be administered topically or orally; they can also be injected intravitreally (off-label use) or injected into the sub-Tenon space (off-label use). However, corticosteroids have many systemic and ocular adverse effects, and some patients become intolerant to them as a result.
NSAIDs inhibit the enzyme cyclooxygenase and can be used in the prevention and treatment of CME.
NSAIDs are usually administered topically for approximately 3-4 months and on an as-needed basis.
In a large, multicenter, prospective, double-masked, study of ketorolac versus placebo in the treatment of 120 patients with chronic aphakic or pseudophakic CME, statistically significant improvement in visual acuity occurred in patients that received ketorolac versus placebo.
The RPE is important in the maintenance of the blood-retinal barrier and in the prevention of a surplus of extracellular and intracellular fluid within the retina. The enzyme carbonic anhydrase is present on the apical and basal surfaces of the RPE cell membrane. Carbonic anhydrase inhibitors (CAIs), such as acetazolamide, enhance the pumping action of RPE cells, facilitating the transport of fluid across the RPE.
When vitreous is captured in the corneal wound following complicated cataract surgery, YAG laser lysis of the vitreous strands has been used with some success.
Surgical CareSurgical therapy includes pars plana vitrectomy (PPV).
PPV is useful in the treatment of CME in several instances, as follows:
Remove vitreous strands tracking to the surgical wound or pupil status after complicated ocular surgery or trauma.
Peeling of the posterior hyaloid face from the surface of the macula in vitreomacular traction syndrome or chronic CME cases unresponsive to medical treatment.
Peeling of epiretinal membranes from the surface of the macula when associated with CME.
Removal of inflammatory mediators from the vitreous cavity.
Removal of retained nuclear lens fragments.
Repositioning of a dislocated or subluxed IOL.
Multiple studies have reported improvement of CME after PPV in cases of aphakic, pseudophakic, or uveitis-related CME.
Filed under Featured Article, Macular Degeneration | Tags: ARMD, corticosteroids, diabetes, drug, eye, laser, macula, macula edema, retina, surgery | Comment Below