DIABETIC MACULAR EDEMA

OVERVIEW• Most common cause of visual loss in DM• Prevelance 11.1% (2-10%)• Incidence (10 year rate: 20.1%; 25.4%; 13.9%)

CLINICAL ASSOCIATONS

• Severity of DR• Duration of diabetes and glycemic control• Proteinuria, • Hypertension, • Dyslipidemia• Pregnancy, • Intraocular surgery• Pan retinal photocoagulation

ANATOMY

ANATOMY

PATHOPHYSIOLOGY

• ALDOSE REDUCTASE• VASOPROLFERATIVE FACTORS• PLATELET DYSFUNCTION

PATHOPHYSIOLOGY

• Capillary damage and raised permeability(breakdown of inner blood retinal barrier)– Pericyte loss (oxidative damage and AGEs)– Disorganisation of tight junctions– Increased transcelluar endocytosis– VEGF– Protein kinase cβ

• Microaneurysms • IRMAs

PATHOPHYSIOLOGY• Extracellular fluid accumulation• Cystoid spaces in the outer plexiform layer• May occupy entire thickness• Tissue disorganisation• Atrophic changes

PATHOPHYSIOLOGY

• Hard exudates (HE):– Lipoproteinaceous deposits– Transudation – Outer plexiform layer

• Subretinal fluid• Subretinal fibrosis

PRESENTATION

• Depends on central macular involvement– Paracentral scotomas– Gradual progressive loss of vision (weeks to

months)– Color vision loss– Metamorphopsia– Fluctuation of vision– Contrast sensitivity– Prolonged adaptation

EXAMINATION

• Clinically best detected by 60 D, 78 D lenses• Decreased translucency• Loss of foveolar reflex• Patterns :– Diffuse– Focal; circinate pattern– Ischemic– Mixed

EXAMINATION

• Stereoscopic fundus photography• Fluorescein angiography– Macular perfusion– Extent and location of capillary leakage

• OCT– Documenting macular thickness– Monitoring progression

CSME

• Retinal thickening at the center of macula• Retinal thickening

and/or adjacent hard exudates at or within 500 u of center of macula• Retinal thickening ≥ 1

disc area, any part of which is within 1 DD of the center of macula

THERAPY

• Medical• LASER photocoagulation• Triancinolone acetonide• Anti-VEGF therapy• Protein kinase c inhibtion• Vitrectomy

LASER photocoagulation

• ETDRS gave conclusive supporting proof• Focal laser for leaking microaneurysm atleast

500 u from the fovea – (aim : closure of leak)

• Grid laser for diffuse retinal thickening/ areas of ischemia – (aim : stimulate retinochoroidal pump)

Treatable lesions

• Focal leaks >500 u from center of macula causing thickening/exudation

• Focal leaks 300-500 u from center if t/t is not likely to damage perifoveal capillary network

• Areas of diffuse leakage• Abnormal avasular zone

ETDRS protocolFocal Grid

Spot size 50-100 u <200u

Exposure time 0.05 – 0.1 s

Intensity Whitening/darkening of microaneurysms (80 - 120

mW)

80 – 180 mW

Number of burns Coagulate all leaking foci All zones of diffuse leakage

Placement 500 – 3000 u from center sparing papillomacular bundle

Sessions 1

Argon green laser (514 nm) and Goldmann 3 mirror lensAvoid argon blue-green (488 nm)Follow up after 4 weeks, if lesions missed then treat after 4 monthsSpacing is one burn width apart

LASER photocoagulation

• Adverse effects– Foveal burns– Subretinal hemorrhage– Vitreous hemorrhage– RPE creep– CNV– Paradoxically increased HE

TRIANCINOLONE ACETONIDE

• Intravitreal route• Needs repeated injections• Duration of effect : 2-3 months with 4mg• Complications – Raised iop– Endophthalmitis– Cataracts

• Peribulbar route

ANTI-VEGF therapy

• Bevacizumab (Avastin)• Ranibizumab (Lucentis)– Fusion proteins with human antibody backbone– Bind all VEGF subtypes– Intravitreal route– No definite schedule

• Pegaptinib (Macugen)– Engineered RNA fragment – Specific sites for VEGF binding

PROTEIN KINASE C Inhibitors

• PKCβ– Ruboxistaurin– Oral administration