eMedicine Specialties > Ophthalmology > Retina
Macular Edema, Irvine-Gass
Updated: Feb 25, 2008
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
Differential Diagnoses
Macular Edema, Diabetic
Retinitis Pigmentosa
Retinoschisis, Juvenile
Other Problems to Be Considered
Vitreomacular traction syndrome
Epiretinal membrane
Goldmann-Favre syndrome
Macular cyst
Foveal schisis in high myopes
Nicotinic acid maculopathy
Workup
Laboratory Studies
- Laboratory studies are guided by the suspected etiology.
- Fasting blood sugar, blood pressure, and lipid profile are indicated if diabetes or retinal vein occlusion is suspected.
- Further workup for hypercoagulable state may be initiated based on the suspected etiology.
Imaging Studies
Retinal imaging can be helpful in establishing a diagnosis, an etiology, and a prognosis. In addition, it is helpful for the measurement of therapeutic response.
- Fluorescein angiography
- Early and mid phase parafoveal retinal capillary leakage occurs in most cases.
- In the late phases of the fluorescein angiogram, a petaloid pattern of leakage in the macula occurs.
- Leakage of the optic disc late in fluorescein angiography can occur in Irvine-Gass syndrome (after cataract surgery).
- Optical coherence tomography (OCT)
- OCT is helpful in establishing a diagnosis and in measuring the therapeutic response.
- Retinal thickening and cystic spaces are seen.
Histologic Findings
In the inner nuclear and outer plexiform layers of the retina, the extracellular cystic spaces are filled with serous fluid. Intracellular fluid has also been found by electron microscopy within expanded Müller cell processes. Various inflammatory cells have been found in eyes with CME with immunohistological studies.
Treatment
Medical Care
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 Care
Surgical 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.
Medication
Medical therapy of Irvine-Gass syndrome includes NSAIDs, corticosteroids, and carbonic anhydrase inhibitors.
Nonsteroidal anti-inflammatory drugs
NSAIDs inhibit enzyme cyclooxygenase and also can be used in the prevention of CME. NSAIDs are administered topically usually for 3-4 months.
Diclofenac (Voltaren)
Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which in turn decreases formation of prostaglandin precursors. Commonly used in the treatment of CME and for postoperative inflammation in patients who have undergone cataract extraction.
Dosing
Adult
1 gtt qid
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity to diclofenac, ketorolac, or related products
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Recently, cases of corneal stromal thinning or melting have been reported in patients receiving diclofenac drops for extended period of time
Ketorolac (Acular)
For treatment of CME and postoperative inflammation in patients who have undergone cataract extraction. Inhibits prostaglandin synthesis by decreasing activity of the enzyme, cyclooxygenase, which results in decreased formation of prostaglandin precursors, which in turn results in reduced inflammation.
Dosing
Adult
1 gtt qid
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity to ketorolac, diclofenac, or related products
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Long-term use may delay wound healing; perform ophthalmologic studies in patients who develop eye complaints during therapy; discontinue therapy if changes are noted; changes may include blurred or diminished vision, corneal deposits, retinal disturbances, scotomata, changes in color vision, and macula degeneration
Nepafenac (Nevanac)
Newer agent used for treatment of CME and postoperative inflammation. Inhibits prostaglandin formation by decreasing activity of the enzyme, cyclooxygenase.
Dosing
Adult
1 gtt tid
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity to diclofenac, ketorolac, or related products
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Long-term use may cause impaired wound healing, corneal thinning
Carbonic anhydrase inhibitors
Carbonic anhydrase is present on both the apical and basal surfaces of the RPE cell membrane. CAIs enhance the pumping action of RPE cells and change ion flux, which affects the cellular environment in the retina.
Acetazolamide (Diamox)
Effective in the treatment of CME. Commonly used in lowering IOP in the therapy of glaucoma.
Dosing
Adult
250 mg PO bid/qid
Pediatric
Not established
Interactions
Can decrease therapeutic levels of lithium and alter excretion of drugs (amphetamines, quinidine, phenobarbital, salicylates) by alkalinizing urine
Contraindications
Documented hypersensitivity; depressed potassium and/or sodium levels in blood serum; liver and/or kidney dysfunction; hyperchloremic acidosis; suprarenal gland failure
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adverse reactions common to all sulfonamide derivatives may occur; patients with impaired hepatic function may go into coma; may cause substantial increase in blood glucose in some diabetic patients
Corticosteroids
Inhibit the enzyme phospholipase and have a primary role in treatment of CME secondary to uveitis. Can be administered topically, orally, or injected in the sub-Tenon space.
Prednisolone acetate (AK-Pred, Pred Forte)
Indicated in several conditions of steroid-responsive intraocular inflammation including CME.
Dosing
Adult
1% solution: 1 gtt qid
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity; active eye infection, including fungal, viral, or mycobacterial
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Prolonged use of corticosteroids may result in glaucoma, optic nerve damage, posterior subcapsular cataract, increased risk of secondary ocular infections, and corneal thinning (monitor ocular pressure regularly)
Triamcinolone acetonide (Kenalog)
Indicated in several conditions of steroid-responsive intraocular inflammation and CME.
Dosing
Adult
Intravitreal injection dose: 4 mg (typical); off-label use
Sub-Tenon injection dose: 40 mg (typical); off-label use
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity; active eye infection, including fungal, viral, or mycobacterial
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Prolonged use of corticosteroids may result in glaucoma, optic nerve damage, posterior subcapsular cataract, increased risk of secondary ocular infections, and corneal thinning
Follow-up
Further Outpatient Care
- Patients with CME are treated on an outpatient basis with regular follow-up visits to monitor for any signs of clinical improvement.
- If steroids are used as a treatment, it is critical to closely monitor intraocular pressure, as glaucoma is a serious complication.
Deterrence/Prevention
- The risk of CME can be decreased by avoiding intraoperative complications, such as posterior capsule rupture, vitreous loss, vitreous to the wound, iris prolapse, or dislocated lens.
- Preoperative NSAIDs may decrease the incidence of CME associated with cataract surgery.
Complications
- Persistent macular edema or multiple remissions and exacerbations can result in foveolar photoreceptor damage with permanent impairment of vision.
Prognosis
- The prognosis is variable. Pseudophakic CME typically has the best prognosis, with 90% of eyes improving to 20/40 or better visual acuity. Other cases of CME can be chronic, requiring long-term treatment.
Patient Education
- For excellent patient education resources, visit eMedicine's Eye and Vision Center. Also, see eMedicine's patient education article How to Instill Your Eyedrops.
Multimedia
Media file 1: Fundus photo of the right eye in a patient with cystoid macular edema.
Media file 2: Fluorescein angiography of the right eye (late phase) showing central macular leakage in cystic spaces around the fovea (same patient as in Media file 1).
Media file 3: Optical coherence tomography (OCT) of the right eye showing central macular cystic spaces in cross-section (same patient as in Media file 1).
Media file 4: Fundus photo of the right eye in a patient with cystoid macular edema from diabetic retinopathy.
Media file 5: Fluorescein angiography of the right eye (late phase) showing central macular leakage in cystic spaces around the fovea (same patient as in Media file 4).
Media file 6: Optical coherence tomography (OCT) of the right eye showing central macular cystic spaces in cross-section (same patient as in Media file 4).
References
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Keywords
Irvine-Gass syndrome, cystoid macular edema, CME, macular fluid accumulation, cataract surgery, ocular surgery
Contributor Information and Disclosures
Author
David G Telander, MD, PhD, Assistant Professor, Department of Ophthalmology and Vision Science, Division of Vitreo-Retinal Diseases and Surgery, University of California Davis School of Medicine
David G Telander, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, American Society of Cataract and Refractive Surgery, and Association for Research in Vision and Ophthalmology
Disclosure: OSI/Eyetech Consulting fee Consulting
Coauthor(s)
Christopher T Cessna, DO, Vitreo-Retinal Fellow, University of California, Davis Medical Center
Christopher T Cessna, DO is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.
Medical Editor
Brian A Phillpotts, MD, Former Vitreo-Retinal Service Director, Former Program Director, Clinical Assistant Professor, Department of Ophthalmology, Howard University College of Medicine
Brian A Phillpotts, MD is a member of the following medical societies: American Academy of Ophthalmology, American Diabetes Association, American Medical Association, and National Medical Association
Disclosure: Nothing to disclose.
Pharmacy Editor
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.
Managing Editor
Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine
Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Club Jules Gonin, Macula Society, and Retina Society
Disclosure: Alcon Laboratories Consulting fee Consulting; OptiMedica Ownership interest Consulting
CME Editor
Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.
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, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.