History
Clinical presentation
Cystoid macular edema (CME) typically presents with a complaint of painless visual loss in one eye. It can be bilateral, depending on the etiology. The onset of symptoms is usually gradual; however, patients often only notice it suddenly, when they check one eye separately. Different causes of CME have different clinical presentations. The most common entities are discussed below.
Uveitis/inflammation
Chronic uveitis, especially pars planitis, is associated with CME, most likely because of a breakdown in the blood-retinal barrier. [3] The chronic inflammation disrupts the competence of the perimacular blood vessels, allowing for the development of the cystoid spaces. A clinical entity distinct from pars planitis has been described, characterized by CME, retinal periphlebitis, and vitreous inflammation. This condition typically is bilateral, affecting middle-aged women. Most patients maintain good vision over a prolonged time period.
Birdshot retinochoroidopathy, a severe form of posterior uveitis, presents with multiple, small, round or oval hypopigmented spots at the level of the choroid or RPE. Vitreous cells, disc edema, and leakage of fluorescein from retinal vessels are common features. CME can occur in conjunction with this condition.
CME has been reported in association with orbital pseudotumor, the swelling of tissues within the orbit. The edema resolved after treatment of the orbital condition.
CME has been associated with cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS) and immunocompetent patients. In some patients, CME develops specifically while the CMV retinitis resolves. A separate entity of CME has been described in patients with inactive CMV retinitis after immune recovery and improvement of their CD4 counts because of highly active antiretroviral therapy (HAART).
Diabetic maculopathy
Diabetic maculopathy affects the capillaries in the macular region, leading to macular edema. Occasionally, a CME component of the macular edema develops, with cystoid changes in the foveal region. This is more common in cases of diffuse and chronic diabetic macular edema, and the vision may be reduced to the 20/200 level.
When eyes with clinically significant macular edema (ie, edema overwhelming the homeostasis of the retina causing noticeable thickening) are treated early, before the onset of diffuse edema, CME possibly can be avoided if the patient maintains excellent control of the underlying medical problems.
CME, in association with diabetic macular edema, has also been correlated to the presence of an attached posterior hyaloid, whereas patients with a posterior vitreous separation are much less likely to develop a component of CME. This may support a mechanical mechanism of the development of CME, where tractional forces induce the formation of cystoid spaces in the macula. Alternatively, the traction on the macula may lift the retina away from the RPE pump, causing CME. Occasionally, even in the absence of an attached posterior hyaloid, a preretinal membrane can exert tractional forces and lead to CME.
Age-related macular degeneration
Age-related macular degeneration (ARMD) can present in 1 of 2 forms: atrophic or exudative (dry or wet). Atrophic macular degeneration without exudative changes does not generally lead to CME. The exudative form of ARMD, with choroidal neovascularization, can cause a serous detachment of the overlying retina and resultant CME. [4, 5]
CME is more common if the serous detachment of the macula has been present for 3-6 months or if the choroidal neovascular membrane has involved most of the subfoveal region. In such cases, the likelihood of restoring good vision is low.
Retinal vein occlusions
Retinal vein occlusion, a branch retinal vein occlusion (BRVO) or a central retinal vein occlusion (CRVO), can cause macular edema resulting from breakdown of the capillary endothelium associated with increased intravascular hydrostatic pressure. [6] The damaged vessels leak fluid into the intercellular spaces, and, eventually, intraretinal cystoid spaces can be seen. This form of CME can be associated with further visual loss and usually results in some permanent visual loss if the situation persists for more than 6 months. However, it can improve with earlier resolution of the macular edema.
Choroidal melanoma
Choroidal tumors, such as malignant melanoma, choroidal nevus, or capillary hemangioma, have been associated with CME. These cystoid changes can occur overlying the tumor and in the macula, even when the tumor is located some distance from the macula, a phenomenon known as the Wise theory of macular accentuation. The source of CME at the level of the retinal capillary network results from intraretinal microvascular abnormalities resembling endothelial cell proliferation. See Choroidal Melanoma.
Juxtafoveal macular telangiectasis
Perifoveal retinal telangiectasis or Coats disease typically presents with irregularly dilated and incompetent retinal vessels. These telangiectatic changes can occur at the level of the arterioles, venules, or capillaries. The closer the findings are to the macula, the earlier symptoms present. A clinical picture of CME may occur due to leakage from incompetent retinal vessels. Idiopathic juxtafoveal telangiectasis is a milder form of retinal telangiectasis, typically involving the temporal macula. CME is less common in this condition.
Drug-induced and postoperative CME
Radiation retinopathy, a condition of vascular damage from prior radiation treatment to the eye or orbit, can mimic diabetic retinopathy in its appearance. A form of macular edema often develops that is quite similar to diabetic macular edema and may manifest as CME.
CME without leakage on FA has been reported in middle-aged men on high doses of niacin for treatment of hypercholesterolemia.
The presence of CME after successful retinal reattachment surgery has been reported to range from 30-43% during the first 4-6 weeks postoperatively. In aphakic eyes, incidence may be as high as 64%. Older patients are at a higher risk to develop CME after retinal detachment repair.
CME has been reported after corneal relaxing incisions for astigmatism.
CME after penetrating keratoplasty ranges from 20-43%. Aphakic eyes are at a much higher risk to develop postoperative CME. If an anterior vitrectomy was performed at the time of surgery, the risk of CME is 8-9 times more likely to occur.
Glaucoma treatment with latanoprost has been associated with the development of CME. The prostaglandin-like effect of latanoprost is believed to cause CME. CME typically resolves after discontinuation of the drug. In a study by Moroi et al of 7 patients with CME, after starting latanoprost therapy, all 7 patients had coexisting ocular conditions that may have placed these eyes at risk for prostaglandin-mediated blood-retinal barrier vascular insufficiency. [7]
CME inducing visual loss has been reported after the use of topical echothiophate iodide therapy.
Genetic disorders
Retinitis pigmentosa (RP) is associated with CME. [8, 9] Studies have found an increased permeability of the retinal pigment epithelium (RPE) and perifoveal capillaries to fluorescein in eyes with RP.A study found an increased presence of circulating antiretinal antibodies in patients who presented with RP and CME. This suggests a possibility of an autoimmune process mediating the development of CME in patients with RP.
Retinal neovascularization and CME have been reported in patients with punctata albescens retinopathy, a type of RP characterized by white retinal flecks. Dominantly inherited CME has been described as a macular dystrophy with an onset at middle age and a slow progression over ensuing decades. Pathologic studies of eyes with this condition suggest that the predominant changes occur in the inner nuclear layer and that this entity may present as a primary disease of the Müller cell.
Foveal X-linked retinoschisis has been mistakenly described as CME.
Epiretinal membranes
Epiretinal membranes can cause surface wrinkling of the underlying retina resulting from contracture of the membrane. [10] Occasionally, macular edema may develop due to distortion and traction on the surrounding intraretinal vessels. If the edema persists, breakdown of the intraretinal architecture can lead to cystoid spaces. This breakdown may be related to mechanical traction leading to edema, or it may be caused by the loss of apposition between the retina and the RPE pump. Ideally, surgical removal of a significant epiretinal membrane causing surface wrinkling retinopathy and macular edema reducing vision to the 20/60 to 20/80 level should be performed before irreversible CME develops.
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Fundus photograph of left eye with branch retinal vein occlusion and cystoid macular edema. Visual acuity was 20/50, and the patient was treated with a modified grid laser photocoagulation and posterior sub-Tenon injection of triamcinolone.
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Fundus photograph of nonproliferative diabetic retinopathy with clinically significant macular edema and cystoid macular edema.
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Fluorescein angiogram of same eye as in the image above, revealing both cystoid macular edema and leakage from microaneurysms associated with diabetic retinopathy.
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Ocular coherence tomographic image of cystoid macular edema in a patient with uveitis.
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Cystoid macular edema in patient with diabetic retinopathy.
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Eye in previous image with diabetic CME after injection with 4 mg of intravitreal triamcinolone.
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Ocular coherence tomographic image of cystoid macular edema in an eye with nonproliferative diabetic retinopathy.
