BASICS

DESCRIPTION

• The Early Treatment Diabetic Retinopathy Study (EDTRS) defined CSME as one of the 3 following criteria:

– 1) Any retinal thickening within 500 microns of the center of the fovea

– 2) Hard exudates within 500 microns of the center of the fovea, which has adjacent retinal thickening

– 3) Retinal thickening at least 1 disc area in size, any part of which is within 1 disc diameter of the center of the fovea

• CSME may be focal or diffuse:

– Focal CSME is caused primarily by focal leakage from individual microaneurysms or small clusters of microaneurysms and dilated retinal capillaries.

– Diffuse CSME is characterized by generalized leakage from the posterior retinal capillary bed due to a generalized breakdown of the inner blood-retinal barrier.

EPIDEMIOLOGY

Incidence

• CSME is the leading cause of visual loss in diabetic patients.

• Up to 4% of all patients with diabetes will develop CSME during their lifetime.

The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) showed that the 4 year incidence of CSME was 4.3%, 5.1%, and 1.3% in type I, insulin-treated type II, and non-insulin-treated type II patients respectively. The 10-year incidence was 20.1%, 25.4%, and 13.9% respectively. The 25 year incidence of CSME in type I diabetes was 17% (1).

Prevalence

Approximately 500,000 Americans have CSME.

RISK FACTORS

• Duration of diabetes

• Poor glycemic, blood pressure, and blood lipid control

• In adult onset diabetes, the use of insulin is a risk factor

• Proteinuria and nephropathy

• Level of diabetic retinopathy (CSME occurs in 3% mild non-proliferative diabetic retinopathy (NPDR) versus in 71% of patients with proliferative diabetic retinopathy (PDR)

Pregnancy Considerations

• Diabetic retinopathy and clinically significant diabetic macular edema (CSME) may accelerate during pregnancy. Consider a dilated eye examination and optimization of glucose control prior to pregnancy

• Dilated exam is recommended during the first trimester, then every 1–3 months thereafter, depending on the severity of the retinopathy. Retinopathy usually returns to baseline at 9–12 months postpartum

Genetics

Although there is a higher incidence of diabetic retinopathy in certain ethnic groups, diet and lifestyle factors outweigh these risks.

GENERAL PREVENTION

• Diabetic control – Glycosylated hemoglobin [HbA1c] should be less than 7%

• Control of systemic hypertension

• Normalization of triglycerides and lipids

• Regular exercise

PATHOPHYSIOLOGY

• Chronic hyperglycemia causes breakdown of the blood retinal barrier by a number of metabolic and cellular alterations:

– Accumulation of polyols and advanced glycosylation end products

– Overproduction of reactive oxygen intermediates

– Pathologic activation of protein kinase C

– Increased expression of multiple cytokines (VEGF, PDGF, TNF-a, and others)

– Thickening of the basement membrane, loss of pericytes, and increased leukostasis

– Diabetics are thought to be in a chronic state of subclinical inflammation

ETIOLOGY

• Chronic hyperglycemia

• Vitreomacular traction may contribute to the development of CSME.

DIAGNOSIS

HISTORY

• Duration and control of diabetes

• Insulin dependent?

• History of hypertension or hyperlipidemia?

• Renal insufficiency?

PHYSICAL EXAM

• CSME is a clinical diagnosis

• Macular thickening is visualized by slit-lamp biomicroscopy (contact lens exam may aid in diagnosis)

• Note the severity of diabetic retinopathy

• Note presence of vitreomacular interface abnormalities

DIAGNOSTIC TESTS & INTERPRETATION

Lab

Evaluation of Hb A1C, blood pressure and blood lipids, and renal function (BUN and creatinine).

Imaging

Initial approach

• Fluorescein angiography is not required for the diagnosis of CSME.

• Fluorescein angiography is obtained for the

• following reasons:

– To rule out central macular ischemia

– To identify the leaking microaneurysms

– To identify areas of diffuse capillary leakage

– To identify areas of capillary nonperfusion elsewhere in the macula

• Color stereo fundus photographs are useful to monitor long-term retinal changes.

• Optical coherence tomography is very helpful to rule out macular pucker/epiretinal membrane, vitreomacular traction, and to monitor response to therapy.

Follow-up & special considerations

• Close follow-up (every 1–3 months) while actively treating CSME.

• Continued monitoring is critical as CSME is frequently a chronic process.

• Regular communication and coordination of care with primary care provider and/or endocrinologist.

Pathological Findings

• Thickening of the basement membrane, loss of pericytes, and decreased cellularity of endothelium

• Accumulation of fluid can be extracellular or intracellular (Muller cells)

DIFFERENTIAL DIAGNOSIS

• Exudative ARMD

• Retinal vein occlusions

• Hypertensive retinopathy

• Cystoid macular edema, Irvine-Gass

• Uveitis

• Macular pucker

• Radiation retinopathy

TREATMENT

MEDICATION

First Line

• Control of blood glucose, blood pressure, and lipids

• Focal laser photocoagulation

Second Line

• As of the summer of 2010, none of the following are FDA approved treatments for CSME.

• Intravitreal anti-VEGF agents (ranibizumab, bevacizumab) alone or in combination with laser treatment may be superior to laser alone (2)[A], (3)[A].

• Intravitreal steroids may be a useful adjunct but when used alone are inferior to focal laser (4)[A]. However, among patients with poor visual acuity at baseline (approximately 20/200 or worse), intravitreal triamcinolone 4 mg was associated with better visual acuity outcomes than photocoagulation (4)[A].

• Periocular steroids may be used in cases of severe CSME, but is less effective than intravitreal steroids.

• Various sustained release steroid implants

(Retisert, Iluvien, Posurdex, I-vation) are in clinical trials.

• Additional pharmacotherapy agents are currently under investigation.

– Aflibercept (VEGF Trap-Eye) is a recombinant fusion protein active against all VEGF-A isoforms and placental growth factor.

– Sirolimus (rapamycin) is a macrolide antifungal with anti-VEGF activity.

ADDITIONAL TREATMENT

Issues for Referral

Consider referral to a vitreoretinal specialist, especially if there is diffuse CSME or CSME with vitreomacular interface abnormalities.

Additional Therapies

Fenofibrate, a fibric acid derivative with lipid modifying effects, may reduce the need for laser treatment for CSME in diabetic patients.

SURGERY/OTHER PROCEDURES

• Consider vitrectomy with membrane peeling for CSME (without refractory to laser and pharmacotherapy

• Membrane peeling (both epiretinal membrane and internal limiting membrane) may benefit patients with CSME and taut posterior hyaloid and/or macular pucker (5).

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Dilated eye exam every 3–4 months for severe NPDR and PDR.

DIET

ADA diet

PROGNOSIS

• 24% of patients with CSME will develop moderate visual loss (doubling of the visual angle) in 3 years.

• Focal laser photocoagulation reduces the risk of vision loss by 50%.

• Newer therapies and combination therapies may further improve visual outcome in patients with CSME.

Stay updated, free articles. Join our Telegram channel

Join