diabetic macular edema

**Pathophysiology** - Chronic hyperglycemia leads to pericyte loss, basement membrane thickening, endothelial dysfunction, and breakdown of the inner blood-retinal barrier (tight junctions between retinal capillary endothelial cells). - Mechanisms include the polyol pathway (aldose reductase converts glucose to sorbitol), AGE accumulation, PKC activation, oxidative stress, and inflammation. - Retinal hypoxia and inflammation raise VEGF, which increases vascular permeability. Fluid and lipid (hard exudates) leak into the macula, causing thickening. - It can occur at any stage of diabetic retinopathy (NPDR or PDR) and in both type 1 and type 2 DM. Risk factors are duration of diabetes, poor glycemic control, hypertension, dyslipidemia, nephropathy, and pregnancy.

**Clinical presentation** - Painless blurred central vision, metamorphopsia (distortion), micropsia, reduced contrast and color vision. Peripheral vision is preserved. - Early disease may be asymptomatic, so screening matters. - Fundoscopy shows retinal thickening, hard exudates (often in a ring or circinate pattern), microaneurysms, and dot-blot hemorrhages near the macula.

**Diagnosis** - Optical coherence tomography (OCT) is the test of choice. It shows central subfield thickening and intraretinal cysts, and it is used to monitor treatment response. - Fluorescein angiography shows leakage and identifies ischemia or neovascularization. - Clinically significant macular edema (ETDRS definition) includes any of: retinal thickening within 500 µm of the foveal center, hard exudates within 500 µm with adjacent thickening, or a thickening zone ≥1 disc area within 1 disc diameter of the center.

**Management** - Systemic control comes first: glucose (HbA1c), blood pressure, and lipids. - Intravitreal anti-VEGF agents (ranibizumab, aflibercept, bevacizumab off-label, faricimab) are first line for center-involving DME. - Intravitreal corticosteroids (dexamethasone implant, fluocinolone, triamcinolone) are second line, especially in pseudophakic or anti-VEGF-refractory patients. Adverse effects are cataract and elevated IOP or glaucoma. - Focal or grid laser photocoagulation is used for non-center-involving DME. It is less common now. - Panretinal photocoagulation treats proliferative disease (neovascularization), not edema itself.

**Screening** - Type 1 DM: dilated eye exam within 5 years of diagnosis. - Type 2 DM: dilated eye exam at diagnosis. - Pregnant patients with preexisting DM: exam in the first trimester. - Repeat yearly, or more often if retinopathy is present.

**High-yield boards points** - DME is the most common cause of vision loss in diabetic retinopathy. Proliferative disease causes vision loss through vitreous hemorrhage and tractional retinal detachment. - Anti-VEGF treats both DME and neovascularization. - Differential for macular edema includes retinal vein occlusion, post-cataract surgery (Irvine-Gass syndrome), uveitis, and wet AMD. - Hard exudates are lipid deposits. Cotton wool spots are nerve fiber layer infarcts, which indicate ischemia. - Fluid is in the outer plexiform layer (Henle fiber layer), forming cystoid spaces.