Retina Companion Note
Diabetic Macular Oedema
Pathophysiology, symptoms and classification
Diabetic macular oedema (DME) is diabetes-related retinal thickening caused by the accumulation of intraretinal—and sometimes subretinal—fluid in the macular region. It may occur at any stage of diabetic retinopathy, so DME and the severity of NPDR or PDR must be assessed separately. [1]
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Diabetic Macular Oedema
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What Is Diabetic Macular Oedema?
Chronic diabetes damages the retinal neurovascular unit and disrupts the normal control of fluid movement across the blood–retinal barrier.
The resulting vascular leakage may produce:
Visual loss depends particularly on whether the foveal centre is involved and whether retinal structure and function remain preserved. [1] [2]
Why Does Fluid Accumulate?
Diabetic macular oedema develops when retinal vascular leakage exceeds the retina’s ability to remove fluid.
Loss of tight-junction integrity weakens the inner blood–retinal barrier.
Vascular endothelial growth factor (VEGF) is both pro-angiogenic and permeability-promoting. Inflammation, altered hydrostatic and oncotic forces, endothelial dysfunction and impaired retinal pigment epithelium fluid transport may also contribute to DME. [2]
An epiretinal membrane or vitreomacular traction may mechanically distort the macula and aggravate oedema in selected eyes.
Who Is More Likely to Develop DME?
The likelihood of diabetic macular oedema increases with longer and more severe systemic diabetic disease.
Longer duration and poor glycaemic control
Hypertension and dyslipidaemia
Diabetic nephropathy or albuminuria
Greater overall diabetic-retinopathy severity
Diabetic retinopathy or pre-existing DME may also worsen during pregnancy or following intraocular surgery. [1]
How Does the Patient Present?
Symptoms depend mainly on whether the oedema involves the foveal centre and disrupts central retinal function.
Metamorphopsia is distortion of the perceived shape of an object. Straight lines may appear bent, curved or irregular because retinal swelling disturbs the normal alignment of the photoreceptors.
DME may remain asymptomatic when retinal thickening is mild or does not involve the foveal centre.
An Amsler grid may be given for home monitoring so that the patient can recognise new distortion or waviness and seek review sooner. It remains an adjunct and does not replace scheduled diabetic-retinopathy screening, dilated retinal examination or optical coherence tomography.
One Disease, Several Classification Systems
Different DME classifications answer different clinical questions. They should not be used interchangeably.
| Classification | What does it assess? | When is it useful? |
|---|---|---|
| ETDRS clinically significant macular oedema | Whether thickening or hard exudates are sufficiently close to, or sufficiently extensive near, the foveal centre | Examination questions, clinical assessment and understanding historical laser eligibility |
| CI-DME or NCI-DME | Whether OCT-detected thickening involves the central 1-mm subfield | Current clinical description, treatment planning and follow-up |
| International clinical DME scale | How close retinal thickening or hard exudates lie to the macular centre | Clinical grading, screening and assessment when OCT is unavailable |
| Fluorescein angiography | Leakage pattern and macular perfusion | Selected cases, focal laser planning and suspected macular ischaemia |
Clinical proximity?
Think CSME or the international clinical scale.
OCT centre involvement?
Think CI-DME or NCI-DME.
Leakage source and perfusion?
Think fluorescein angiography.
Clinically Significant Macular Oedema
Clinically significant macular oedema (CSME) is an ETDRS clinical definition developed during the focal/grid laser era. It remains highly examination-relevant. [4] [5]
CSME is present when any one of the following criteria is met:
Retinal thickening near the centre
Retinal thickening at or within 500 µm of the centre of the macula.
Hard exudates near the centre
Hard exudates at or within 500 µm of the centre of the macula, when associated with adjacent retinal thickening.
Hard exudates alone do not fulfil this criterion.
Approximately 1.5 mm or 1,500 µm.
An area of retinal thickening equivalent in size to the area of the normal optic disc.
Centre-Involved and Non-Centre-Involved DME
Current DME terminology focuses on whether retinal thickening involves the central 1-mm OCT subfield. [1]
Non-Centre-Involved DME
Macular retinal thickening is present, but the central 1-mm subfield is not involved.
Central visual acuity may remain preserved when the foveal centre is spared.
Centre-Involved DME
Retinal thickening involves the central 1-mm subfield.
Centre involvement increases the potential for central visual dysfunction, but does not automatically require immediate treatment.
Commonly Asked OCT Thickness Values
The following sex- and device-specific central subfield thickness values have been used in DRCR Retina Network studies:
| OCT device | Women | Men |
|---|---|---|
| Zeiss Stratus | ≥250 µm | ≥250 µm |
| Zeiss Cirrus | ≥290 µm | ≥305 µm |
| Heidelberg Spectralis | ≥305 µm | ≥320 µm |
Values differ between OCT platforms because segmentation boundaries and retinal-thickness measurements are not identical.
International Clinical DME Severity Scale
The international clinical scale grades DME according to how close retinal thickening or hard exudates lie to the macular centre. [3]
Mild DME
Some retinal thickening or hard exudates are present in the posterior pole but remain distant from the centre.
Moderate DME
Retinal thickening or hard exudates approach the centre but do not involve it.
Severe DME
Retinal thickening or hard exudates involve the centre.
What Does Fluorescein Angiography Add?
Optical coherence tomography shows the presence and distribution of retinal fluid. Fundus fluorescein angiography (FFA) answers two additional questions:
Focal and Diffuse Leakage
Focal Leakage
- Discrete leakage from identifiable vascular lesions
- Most commonly associated with leaking microaneurysms
- Localised retinal thickening
- Circinate hard exudates may be present
- Focal late hyperfluorescence on FFA
Diffuse Leakage
- Widespread capillary incompetence
- No single dominant leaking point
- Broad retinal thickening
- Poorly localised late hyperfluorescence
- A petaloid pattern may occur with cystoid spaces
Focal and diffuse patterns may coexist. Because published definitions have not always been uniform, it is better to describe the predominant angiographic leakage pattern. [8]
Is Macular Perfusion Impaired?
FFA may demonstrate:
Does the Leakage Pattern Influence Treatment?
The angiographic leakage pattern can refine treatment planning, especially when laser is being considered, but it does not independently determine whether anti-VEGF treatment should begin.
ETDRS Approach
Directed towards selected leaking microaneurysms.
Applied to areas of diffuse leakage and retinal thickening.
Focal/grid photocoagulation reduced the risk of moderate visual loss in eyes with clinically significant macular oedema. [4] [5]
Current Clinical Use
Contemporary treatment decisions are guided mainly by visual acuity, OCT-confirmed centre involvement, retinal fluid, morphology and clinical progression.
FFA remains particularly useful when:
Classification Snapshot
Historical ETDRS clinical definition based on retinal thickening or hard exudates near the macular centre.
Current OCT-based description according to whether the central 1-mm subfield is involved.
Clinical grading based on how close retinal thickening or hard exudates lie to the macular centre.
Describes the leakage pattern and assesses macular perfusion.
CSME is the historical clinical definition; CI-DME and NCI-DME are the current OCT-based descriptions; FFA characterises leakage and macular perfusion.
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References
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Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema: Early Treatment Diabetic Retinopathy Study Report Number 1. Arch Ophthalmol. 1985;103(12):1796–1806.
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Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema: Early Treatment Diabetic Retinopathy Study Report Number 2. Ophthalmology. 1987;94(7):761–774.
doi:10.1016/S0161-6420(87)33527-4 -
Sun JK, Josic K, Melia M, et al; DRCR Retina Network. Conversion of central subfield thickness measurements of diabetic macular edema across Cirrus and Spectralis optical coherence tomography instruments. Transl Vis Sci Technol. 2021;10(14):34.
doi:10.1167/tvst.10.14.34 -
Baker CW, Glassman AR, Beaulieu WT, et al; DRCR Retina Network. Effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular edema involving the center of the macula and good visual acuity: a randomized clinical trial. JAMA. 2019;321(19):1880–1894.
doi:10.1001/jama.2019.5790 -
Browning DJ, Altaweel MM, Bressler NM, Bressler SB, Scott IU; Diabetic Retinopathy Clinical Research Network. Diabetic macular edema: what is focal and what is diffuse? Am J Ophthalmol. 2008;146(5):649–655.e6.
doi:10.1016/j.ajo.2008.07.013
