Chapter 12

Core Messages

■Diabetic macular edema (DME) was defined in Early Treatment Diabetic Retinopathy Study (ETDRS) studies on the basis of central retinal thickening and hard exudates using fundus stereophotography or biomicroscopy (FP/FB). Clinically significant macular edema (CSME) is the more severe form of DME and needs to be treated. Compared with FP/FB, optical coherence tomography (OCT) provides imaging of retinal thickness and morphology, as well as of the vitreoretinal interface.

■Clinical examination using FP/FB is cheap and readily available, but is also a subjective method. When biomicroscopy is used, there is no recording of the amount of thickening, and thus, it cannot reliably monitor CSME except for a gross judgment on its presence or absence.

■Advantages of OCT when compared with FP/FB in patients with DME are its ability to obtain an objective and highly reliable quantitative measure of retinal thickness on a continuous scale, as well as to provide additional morphological details.

■Clinician suspecting CSME requiring treatment can use Stratus central subfield thickness values below 250 mm to rule out CSME, and values above 300 mm to rule in CSME. Thickness values between 250 and 300 mm still suggest CSME, but treatment decision should be based, even more

than usual, on patient’s symptoms and preferences as well as on other clinical features that an ophthalmologist may use to decide on potential treatment outcome.

■Add 50 mm to the thresholds suggested above when using Cirrus (and possibly other spectral domain) OCT (no CSME: below 300 mm; CSME: above 350 mm); confirmatory research is needed on this correction factor for each spectral-domain device.

■Retinal-thickness measurement should not be a surrogate for visual acuity measurement in patients with DME.

■OCT-based predictors of outcome after photocoagulation, vitrectomy, and intravitreal triamcinolone have been proposed, and the prognosis of cases with subclinical macular edema (i.e., thickening using OCT not found using FP/FB) have been studied in case series and need further investigation.

■Using Stratus OCT, a change in the central subfield thickness exceeding ±11% is likely to represent a true change in a subject if the quality of the scans is acceptable.

■The repeatability of spectral-domain OCTs is expected to be comparable or better than that of the Stratus OCT in patients with DME, but further research is needed.

12.1  Introduction: Diabetic Macular Edema,

Fundus Photography, and Optical

Coherence Tomography

12.1.1  Incidence and Natural History

In developed countries, diabetic retinopathy (DR) represents the leading cause of blindness in the working age population [1]. It is expected that diabetes mellitus will

reach epidemic proportion by the year 2025, with the total number of people with diabetes estimated to rise to 300 millions [2]. Diabetes mellitus and its complications will continue to represent a significant public health challenge. Among diabetes ocular complications, diabetic macular edema (DME) currently represents the major contributor to visual loss. DME can occur at any stage of diabetes and its onset is usually insidious and painless, often leading to a deferred diagnosis. It is characterized

by increased vascular permeability secondary to the disruption of the blood–retinal barrier, which leads to intraretinal fluid accumulation.

The risk of developing DME increases with the dura- 12  tion of diabetes: the prevalence is 5% within the first 5 years after diagnosis and 15% at 15 years [3]. If untreated, DME increases the risk of moderate visual loss by 30–50% depending on the level of baseline visual acuity [4]; with

current treatment, the risk drops by 50%.

12.1.2  Classification: Early Treatment Diabetic

Retinopathy Study Grading

The best validated grading system for DR is the extension of the Airlie House Classification that was developed for the Early Treatment Diabetic Retinopathy Study (ETDRS) [5]. This classification has become the basis for detailed grading of DR and DME, and was used in all the major studies of risk factors and trials of different treatment modalities. It was based on grading seven 30° stereoscopic photographic fields. In the ETDRS classification, macular edema is graded separately: using a grid overlay on one photograph in field 2 (centered on the center of the macula) stereo pair, size, and location of retinal thickening are graded. The ETDRS defined DME as thickening and/or hard exudates within one disc diameter of the center of the macula. When the edema involves or threatens the center of the macula, even if visual acuity is not reduced, it is classified as clinically significant macular edema (CSME). The term CSME represents the threshold level at which laser photocoagulation is recommended and is defined as:

■Retinal thickening at or within 500 µm of the center of the macula

■Hard exudates at or within 500 µm of the center of the macula, if associated with thickening of the adjacent retina

■A zone or zones of retinal thickening one disc area in size, at least part of which is within one disc diameter of the center of the macula

DME grading has a practical application in fundus photographic assessment of DR, where photography substitutes for examination by an ophthalmologist. Comprehensive, regular clinical examination by a trained ophthalmologist, with fundus photography used for documentation only, is the best standard of care. Fundus stereophotography (FP), although validated, is complicated and time-consuming, placing considerable demand on the patients and physicians/photographers, and therefore, its use in everyday clinical practice is unpractical. In clinical setting, fundus biomicroscopy with contact is

commonly used and it was found to be in close agreement with stereophotography. However, both methods are relatively insensitive in determining subtle changes in retinal thickness, especially in the absence of hard exudates.

From now on, in this chapter, we will use the acronym FP/FB to refer to fundus photography and fundus biomicroscopy jointly. In fact, while photography is the preferred method for fundus examination in ophthalmic research, biomicroscopy and especially non ­contact biomicroscopy, is routinely used in clinical practice.

12.1.3  Optical Coherence Tomography

and Diabetic Macular Edema

Optical Coherence Tomography (OCT) is a relatively new imaging modality, providing high-resolution, cross-­ sectional images of the retina, with a resolution of up to 5 µm. It allows in vivo assessment of retinal morphology and thickness, and in the past decade, has gained widespread acceptance as a complementary tool for the diagnosis and management of several macular pathologies, including DME. Retinal thickness by OCT has been recently included in clinical trials assessing the use of different therapeutic modalities for DME: the presence of a minimal retinal thickness (250 or 300 µm according to different trials) constitutes an inclusion criteria, while its change over time is used as a means to assess anatomical efficacy of treatment, which often represents a clinical outcome. According to a previous study [6], normal retinal thickness with OCT 2000 is approximately 130 µm, while the mean central foveal thickness in healthy eyes with Stratus OCT is slightly higher, 182 ± 23 µm (both instruments were manufactured by Carl Zeiss Meditec, Inc.). Studies of CSME (defined according to the ETDRS) with OCT have revealed three basic morphological changes: retinal swelling with sponge-like appearance, cystoid pattern, and serous retinal detachment (see Fig. 12.1) [7]. Compared with FP/FB, OCT provides an objective and quantitative measure of retinal thickness in patients with DME, and it is especially useful in identifying the presence of vitreomacular adherence (see Fig. 12.1) [8].

Summary for the Clinician

■DME was defined in ETDRS studies on the basis of central retinal thickening and hard exudates using FP/FB. CSME is the more severe form of DME and needs to be treated. Compared with FP/FB, OCT provides imaging of retinal thickness and morphology, as well as the vitreoretinal interface.