Background

Although the most common cause of cystoid macular edema (CME) is due to Irvine-Gass syndrome of CME after cataract extraction or other intraocular surgery, numerous other conditions are associated with the clinical appearance of fluid-filled, cystoid spaces in the macular region. CME is a final common pathway of many intraocular diseases, usually involving the retinal vasculature. The appearance can differ somewhat, depending on the etiology; however, CME can appear as a nonspecific clinical finding. If the cause of CME is not obvious, detailed ophthalmoscopy and, occasionally, ancillary testing may be necessary to identify the cause.

Cystoid macular edema due to nonproliferative diabetic retinopathy is shown in the image below.

Fundus photograph of nonproliferative diabetic retinopathy with clinically significant macular edema and cystoid macular edema.

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Pathophysiology

Macular edema is excessive fluid within the layers of the retina, distinct from the accumulation of fluid under or between the retinal layers (eg, subsensory fluid, serous retinal detachment). The amount of fluid normally present in the retina is maintained according to osmotic and hydrostatic pressures between the retina and the surrounding vasculature, which are compartmentalized by the blood-retinal barrier. A breakdown in the blood-retinal barrier allows for fluid to accumulate in cystoid spaces within the retina. Pathologic evidence of cell loss and Müller cell abnormalities may contribute to the resulting CME.

Several mechanisms have been proposed to explain how CME develops. The characteristic distribution of vascular leakage and retinal edema may be explained best by the diffusion of mediators (eg, prostaglandins) released in the eye. These mediators of inflammation cause increased permeability of retinal blood vessels, resulting in extravasion. This theory is supported by evidence that cyclooxygenase inhibitors (eg, indomethacin, other nonsteroidal anti-inflammatory drugs) reduce the incidence of angiographic CME. However, this finding has only been extensively reported on in pseudophakic CME associated with surgical trauma to the anterior segment. A 2013 case report described a phakic patient with idiopathic macular telangiectasia type 1 whose CME reacted robustly to the administration of NSAIDs and would reoccur in the absence of treatment.^[1]

The major determinant of fluid movement in the retina is the Müller cell. Müller cells have bicarbonate-related transport mechanisms that control movement of potassium and sodium ions (and thus fluid), partly explaining the role for carbonic anhydrase inhibitors such as acetazolamide in the treatment of cystoid macular edema. Additional routes of ion control are achieved through the Kir2.1 and Kir4.1 channels that buffer changes in intracellular potassium.

In addition, evidence shows that the reduced outflow of fluid from the retina is responsible for the buildup of edema. In particular, reduced or absent flow to the deep vascular plexus of the retina has been described. This decreased flow can result from ischemia or inflammation and is mediated by integrins, selectins, and other adhesion molecules. Extravasated leukocytes have the ability to plug capillaries, thus blocking blood flow.^[2]

Another mechanism emphasizes the role of mechanical factors, such as tractional forces on the macula from disruption of the normal vitreoretinal interface. Even according to this theory, it is believed that local forces induce a release of mediators that lead to a breakdown of the blood-retinal barrier, resulting in the clinical appearance of CME.

Photic injury has been implicated in the development of pseudophakic CME; however, there is no scientific evidence that light damage to the retina causes CME.

Frequency

United States

Frequency of CME that is unassociated with cataract surgery varies widely, both in the United States and internationally, depending on the etiology or underlying condition leading to CME. Incidence figures vary because of difficulty in observing subtle CME clinically, surgeon bias in reporting CME, and a lack in performing fluorescein angiography (FA) or optical coherence tomography (OCT) tests that would detect CME.

Mortality/Morbidity

CME from any etiology often leads to significant central visual loss, typically in the 20/40 to 20/200 range.

Race

No racial predilection has been associated with CME.

Sex

CME is distributed equally among males and females.

Age

Age of incidence of nonpseudophakic CME varies according to etiology. Since diabetic CME is secondary to diabetic retinopathy, it occurs in persons aged 40 years and older.

Prognosis

Visual prognosis in eyes with CME depends on the etiology of the CME. If the CME resolves with treatment, visual acuity of 20/40 or better is common. However, in long-standing CME, vision is often 20/100 to 20/200.

Clinical Presentation

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Media Gallery

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.
Fundus photograph of nonproliferative diabetic retinopathy with clinically significant macular edema and cystoid macular edema.
Fluorescein angiogram of same eye as in the image above, revealing both cystoid macular edema and leakage from microaneurysms associated with diabetic retinopathy.
Ocular coherence tomographic image of cystoid macular edema in a patient with uveitis.
Cystoid macular edema in patient with diabetic retinopathy.
Eye in previous image with diabetic CME after injection with 4 mg of intravitreal triamcinolone.
Ocular coherence tomographic image of cystoid macular edema in an eye with nonproliferative diabetic retinopathy.

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Author

Hamoon Eshraghi, MD Resident Physician, Transitional Year, St Luke’s Hospital

Hamoon Eshraghi, MD is a member of the following medical societies: Medical Society of New Jersey

Disclosure: Nothing to disclose.

Coauthor(s)

Howard F Fine, MD, MHSc Partner, Associated Retina Consultants, Retina Vitreous Center, PA; Co-founder and Chairman of Scientific Advisory Board, Auris Surgical Robotics, Inc

Howard F Fine, MD, MHSc is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, Association for Research in Vision and Ophthalmology, American Society of Retina Specialists

Disclosure: Nothing to disclose.

Specialty Editor Board

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society

Disclosure: Nothing to disclose.

Steve Charles, MD Founder and CEO of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine

Disclosure: Received royalty and consulting fees for: Alcon Laboratories.

Chief Editor

Hampton Roy, Sr, MD † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

V Al Pakalnis, MD, PhD Professor of Ophthalmology, University of South Carolina School of Medicine; Chief of Ophthalmology, Dorn Veterans Affairs Medical Center

V Al Pakalnis, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, South Carolina Medical Association

Disclosure: Nothing to disclose.

Daniel B Roth, MD Assistant Professor, Department of Ophthalmology, Retina Vitreous Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School

Daniel B Roth, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Society of Retina Specialists, Retina Society, American Medical Association

Disclosure: Nothing to disclose.