Perspective
Diabetic Macular Edema: What Is Focal and What Is Diffuse?

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Purpose

To review the available information on classification of diabetic macular edema (DME) as focal or diffuse.

Design

Interpretive essay.

Methods

Literature review and interpretation.

Results

The terms focal diabetic macular edema and diffuse diabetic macular edema frequently are used without clear definitions. Published definitions often use different examination methods and often are inconsistent. Evaluating published information on the prevalence of focal and diffuse DME, the responses of focal and diffuse DME to treatments, and the importance of focal and diffuse DME in assessing prognosis is hindered because the terms are used inconsistently. A newer vocabulary may be more constructive, one that describes discrete components of the concepts such as extent and location of macular thickening, involvement of the center of the macula, quantity and pattern of lipid exudates, source of fluorescein leakage, and regional variation in macular thickening and that distinguishes these terms from the use of the term focal when describing one type of photocoagulation technique. Developing methods for assessing component variables that can be used in clinical practice and establishing reproducibility of the methods are important tasks.

Conclusions

Little evidence exists that characteristics of DME described by the terms focal and diffuse help to explain variation in visual acuity or response to treatment. It is unresolved whether a concept of focal and diffuse DME will prove clinically useful despite frequent use of the terms when describing management of DME. Further studies to address the issues are needed.

Section snippets

Clinical Examination

SUPPLEMENTAL TABLE 1, SUPPLEMENTAL TABLE 2, SUPPLEMENTAL TABLE 3, SUPPLEMENTAL TABLE 4, SUPPLEMENTAL TABLE 5, SUPPLEMENTAL TABLE 6, SUPPLEMENTAL TABLE 7 (available at AJO.com) summarize the frequency with which various definitions have been used for the different methods. The ETDRS defined clinically significant DME as edema satisfying any one of the following three criteria: 1) any retinal thickening within 500 μm of the center of the macula, 2) hard exudates within 500 μm of the center of the

Color Fundus Photographs

Definitions involving color fundus photographs often involve area criteria. Larssen and associates state that “[d]iffuse macular edema was defined as having two or more disc areas of retinal thickening and involving the center of the macula” and that “[f]ocal edema was defined as an area of retinal thickening less than 2 disc areas in diameter not affecting the center of the macula.”50 The cutpoint for area and the necessity of involvement of the macular center for defining diffuse edema have

Fluorescein Angiography

In the ETDRS, DME was defined clinically from stereoscopic biomicroscopy without reference to focal or diffuse descriptions of that clinical examination. As stated in ETDRS Report No. 5, “Fluorescein leakage without retinal thickening was not included as part of the definition of macular edema in the ETDRS.”51 However, FAs were analyzed by a reading center and the source of fluorescein leakage was graded categorically by proportion of leakage originating from microaneurysms for classification

Optical Coherence Tomography

The use of OCT to define edema as focal or diffuse has been developed from two differing perspectives—that of the regional map and that of cross-sectional scans. In the false color map, a sense of focality can be obtained when isolated islands of hot colors are surrounded by larger areas of cool colors, but this is difficult to quantitate. Browning and Fraser suggested that diffuse DME be understood to imply an increasing number of elevated subfields on the map display.65 Sadda and associates

Hybrid Definitions

Hybrid definitions have been used frequently to define diffuse DME, but not focal DME. The definitions can be categorized into a subgroup using clinical examination and FA criteria and a subgroup using clinical examination, FA, and OCT criteria. The differences in criteria between the studies are summarized in SUPPLEMENTAL TABLE 1, SUPPLEMENTAL TABLE 2 available at AJO.com, along with undefined terms. Broadly speaking, the definitions differ in how much of the macula must be thickened or

Potential Problems With Different Definitions

Lobo and associates simultaneously obtained color fundus photographs, images with the Retinal Leakage Analyzer (Talia Technology, Lod, Israel) and thickness measurements with the Retinal Thickness Analyzer (Talia Technology) in diabetic eyes without and with retinopathy.77, 78 They found that the areas of retinal leakage frequently did not coincide with the areas of increased retinal thickness. They also found, counterintuitively, that microaneurysms showed relatively little leakage and over

Claims About Diffuse and Focal Diabetic Macular Edema

Many authors have claimed that diffuse DME is refractory to macular photocoagulation and that diffuse DME is a prognostic factor for poorer VA at follow-up, but the evidence for these claims comes from case series and not prospective clinical trials in which strict definitions were applied.2, 16, 24, 57, 79, 80 Others have suggested that diffuse DME responds better to intravitreal triamcinolone injection and focal DME to focal laser photocoagulation.43, 62, 81 The evidence to support the claims

A Fresh Look at the Definitions

Within the DRCR.net, a working group has been attempting to clarify the terms focal DME and diffuse DME. Its purpose is to determine if definitions can be developed that are clinically applicable and reproducible. Because of a variety of associations attached to the terms focal DME and diffuse DME, it may be more constructive to recast the discussion with newer terms describing discrete parts of the concepts such as extent and location of thickening, involvement or not of the center of the

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