Diabetic Macular Oedema

Diabetic macular oedema (DME) is retinal thickening and exudation in the macula caused by breakdown of the blood retinal barrier, and is the commonest cause of vision loss in diabetes (affecting about 7 percent of diabetic patients).

• Present at any stage of diabetic retinopathy; type 2 diabetes accounts for most cases.
• Mechanism: VEGF and inflammatory cytokines from hypoxic retina increase vascular leakage; hard exudates form from lipid leakage.
• Classification: centre involving DME (central subfield thickening of the macula) versus non-centre-involving; clinically significant macular oedema (retinal thickening within 500 micrometres of the foveal centre, hard exudates with adjacent thickening, or thickening 1 disc area or larger within 1 disc diameter of the centre).
• Risk factors: long duration, poor control, hypertension, dyslipidaemia, renal disease, pregnancy, glitazones (fluid retention).

• Blurred or distorted central vision, reduced contrast, difficulty reading; may be asymptomatic early.
• Retinal thickening, microaneurysms, hard exudates (circinate ring), haemorrhages, cystic spaces; macular ischaemia with enlarged foveal avascular zone.
• Associated vitreomacular traction or epiretinal membrane in some.
• Vision loss is variable and may be profound if there is ischaemia, atrophy, or subfoveal fibrosis.

• Visual acuity and slit lamp biomicroscopy with a contact or non-contact lens.
• Optical coherence tomography is the key test: central subfield thickness (above about 300 micrometres), intraretinal cysts, subretinal fluid, hyperreflective foci, disorganisation of inner retinal layers, vitreomacular traction; used to guide treatment and follow response.
• Fluorescein angiography for leakage, non-perfusion and microaneurysm location (to guide focal laser).
• Optical coherence tomography angiography for the foveal avascular zone.

• Treat systemic risk factors: HbA1c about 7 percent, blood pressure under 130/80 mmHg, statin, fenofibrate 145 mg daily in selected patients, stop glitazones if oedema is present, manage renal disease.
• Centre involving DME with reduced vision (6/9 or worse):
  • Intravitreal anti-VEGF is first line: aflibercept 2 mg (monthly for 5 doses, then every 8 weeks), ranibizumab 0.3 mg monthly, faricimab 6 mg every 4 weeks for 4 doses then every 8 to 16 weeks, brolucizumab 6 mg, or bevacizumab 1.25 mg (lower cost). Aflibercept, ranibizumab and faricimab give greater visual gains than bevacizumab when vision is 6/15 or worse at baseline.
  • Intravitreal corticosteroid for pseudophakic eyes, inadequate response to anti-VEGF, or when frequent injections are not possible: dexamethasone implant 0.7 mg every 4 to 6 months, fluocinolone acetonide implant 0.19 mg (lasting up to 3 years). Risks: cataract and raised intraocular pressure.
  • Laser: subthreshold micropulse laser or focal and grid macular laser for non-centre-involving oedema or as adjunct, applied to leaking microaneurysms outside 500 micrometres of the fovea.
• Observation with tight control when vision is good (6/6 to 6/7.5) and oedema is centre involving, with regular optical coherence tomography.
• Vitrectomy with internal limiting membrane peeling for vitreomacular traction or persistent oedema with epiretinal membrane.
• Monitor monthly during loading, then every 1 to 3 months; stop therapy if no improvement after 3 to 6 doses.
• Add panretinal photocoagulation or anti-VEGF when proliferative disease coexists.