E11.321-351 Diabetic Macular Edema

Diabetes

Diabetes mellitus is a complex, multifactorial and heterogeneous group of disorders characterized by endogenous insulin deficiency and/or insulin resistance.  The disease manifests itself as a state of chronic hyperglycemia with attendant microvascular and macrovascular complications. 

Diabetic Macular Edema

Macular edema may be present in any stage of diabetic retinopathy and is defined as any one of the following:

• Retinal thickening within 500 microns of the foveal center
• Hard exudates within 500 microns of the foveal center, if associated with the thickening of the adjacent retina
• Retinal thickening greater than one disc area in size, part of which is within one disc diameter of the center of the macul

Structural Damage to the Eye

• Walls of the blood vessels in the retina become fragile and weakened 
• Weakened blood vessels have an increase in vascular permeability
• Lipid deposits form in the retinal tissue secondary to chronic edema
• Fluid accumulates in the macula

Functional Damage to the Eye

• Distorted or blurred vision
• Report seeing spots or floaters in field of view
• Report dark or empty spot in the central vision
• Difficulty seeing at night

The main goal of the diagnostic evaluation in a patient with diabetic retinopathy is to accomplish the following:

• Determine the presence or absence of clinically significant macular edema 
• If present, classify the severity of the macular edema 
• Identify and exclude differential diagnosis
• Prescribe a treatment program

Patient History

The severity of the symptoms or signs is varied and depends on the level of control the patient has over their diabetes.  Patients can present with the following abnormal symptoms:

• Blurred vision (sudden or gradual)
• Distorted vision (sudden or gradual)
• Difficulty driving at night
• Floaters or dark spots in their field of view

Clinical Appearance of the Retina

The retinal changes associated with diabetic retinopathy include the following:

• Hemorrhages
• Microaneurysms
• Lipid deposits
• Cotton wool spots
• Edema
• Ischemia
• Venous beading
• Intraretinal microvascular abnormalities
• Retinal thickening
• Neovascularization
• Proliferative non-inflammatory degeneration

DIAGNOSTIC TESTS

Refraction

• A method to evaluate the function of the complete visual system
• The function loss of vision secondary to diabetic macular edema is usually determined by the quantification of best corrected visual acuity
• According to The Diabetic Retinopathy Clinical Research Network, a wide range of visual acuity may be observed with varying stages of diabetic macular edema, therefore changes in macular edema have low predictive value compared to visual acuity changes 

Fundus Photography

Hybrid retinal cameras allow the user to take color photography and one-shot Fundus Autofluorescence Imaging.

• To document the progress or lack of progress of diabetic retinopathy
• To assist in the early diagnosis of diabetic retinopathy
• To assist in staging the disease
• To document the delivery of treatment
• To document the response to treatment
• To help plan a treatment program

Fundus Autofluorescence (FAF) Imaging

• FAF imaging use infrared light rather than white light for illumination
• FAF imaging evaluates the structure of the retinal pigment epithelium and visualizes the distribution of lipofuscin 
• FAF imaging is considered a supplement to color fundus photography
• FAF image may reveal a retinal disorder where the color photograph or OCT does not show abnormality

Abnormal FAF imaging in Both Maculas

• Hyperautofluorescence in the macula of the right eye
• Hyperautofluorescence in the macula of the left eye

Abnormal Color Photography in the Right Macula

• Diabetic macular edema in the right eye (hard exudates at temporal edge of the macula)
• No apparent diabetic macular edema in the left eye

Abnormal OCT Macular Thickness Scan in the Right Macula

• Diabetic macular edema in the right eye (retinal thickening within 500 microns of the foveal center)
• No apparent diabetic macular edema in the left eye

Hyperautofluorescence in Diabetic Retinopathy

• Fundus autofluorescence recorded with a Canon CR-2 PLUS Hybrid Digital Retinal Camera
• In patients with diabetes, excess lipofuscin may be an indicator of oxidative damage within the retina
• Macular fundus autofluorescence increases in over 70% of patients with clinically significant diabetic macular edema
• Retinal sensitivity decreases in areas of hyperautofluorescence
• Patterns of hyperautoflourescence (multicystic, single cyst, and combined single- and multicystic)

FAF Image in Diabetic Retinopathy 50-year-old Black man 20-year history of diabetes Combined single- and multicystic hyperautofluorescence pattern FAF Image Interpretation Normal retinal tissue shows uniform gray color no fundus autofluorescence Diseased macula shows increased fundus autofluorescence (iFAF) hyperautofluorescence Normal macula shows mild hypoautofluorescence secondary to xanthophyll pigment absorbing the signal

Retinal Scanning Laser

• To measure the microscopic anatomy of the retina and vitreoretinal interface
• To measure the effectiveness of therapy
• To help in determining the need for ongoing therapy
• To determine the safety of cessation of therapy

Visual Field Examination

• Used to assess visual function and determine the size of any associated visual field defects
• Visual field may be affected depending on the size and location of retinal hemorrhaging
  the extent of the visual field defect depends on size of macular edema

Diabetic macular edema is classified base on the proximity of retinal thickening or hard exudates to the center of the macula.

		No Apparent Diabetic Retinopathy Mild nonprofliferative diabetic retinopathy No retinal thickening or hard exudates in the posterior pole
		Mild Diabetic Macular Edema Mild nonproliferative diabetic retinopathy Some retinal thickening or hard exudates in the posterior pole, but distant from the macula.
		Moderate Diabetic Macular Edema Moderate nonproliferative diabetic retinopathy Retinal thickening or hard exudates approaching the center of the macula, but not involving the center
		Severe Diabetic Macular Edema Severe nonproliferative diabetic retinopathy Retinal thickening or hard exudates involving the center of the macul

This would include any eye diseases that produce changes in the retinal vasculature such as hemorrhages, microaneurysms, edema, and exudates.

		Hypertensive Retinopathy Lipid andexudative deposits are similar to those seen in early non-proliferativediabetic retinopathy Cotton wool spots are seen in both diabetic retinopathy and hypertensive retinopathy
		Retinal Venous Obstruction Central retinal vein occlusion (CRVO) and Branch retinal vein occlusion (BRVO) can produce retinal hemorrhages similar in appearance, however the onset of CRVO and BRVO are sudden versus diabetic retinopathy is over time
		Retinal Telangectasia Pathologically dilated blood vessels leak fluid into the retinal tissue Exudative formation secondary to fluid retention is similar in appearance to the exudates found in diabetic retinopathy
		Leukemia Ocular manifestations of leukemia can produce the following retinal vessel changes microaneurysms blood vessel dilation neovacularization cotton wool spots

Most cases of clinically significant macular edema require laser surgery for effective treatment.

Pharmacologic Treatment

• Long term control of blood sugar either through oral medication or injection is important for preservation of vision, especially with no signs of diabetic retinopathy or the early stages of it

Surgical Treatment

Laser Therapy Focal grid laser treatment can stop the leakage of fluid into the macula

Vitrectomy is a technique in which the vitreous is surgically removed along with the posterior hyaloid. One theory is a vitrectomy may help reduce traction on the macula and this in turn reduces the macular edema. Another theory hypothesis that removing the vitreous removes the cytokines and VEGF associated with a venous occlusive episode. There is no evidence that a vitrectomy is the best treatment.

1.  Fabrykowski, MC.  Evolving therapies for diabetic macular edema.  Rev Optom 2013 Dec 15; 150(12): 52-56.