Diabetic Macular Edema

Sakhanit Leelaprasasne 23 July 2010

Outline
Definition Pathogenesis Diagnosis and classification Investigation Treatment Prognosis

Definition and clinical description

- Diabetic macula edema is the retinal thickening caused by the accumulation of intraretinal fluid that resulted from hyperpermeability of retinal vasculature - Can be present with any level of diabetic retinopathy

Epidemiology
- 10% of all DM - 40% of these have CSME - 3% in mild NPDR have CSME - 38% in moderate to severe NPDR have CSME - 71% in PDR have CSME

Epidemiology
Duration of hyperglycemia, prevalence

- DM > 20 yr. 20-30% of IDDM and 30-35% of NIDDM (insulin use) have DME

Factors affecting DME

Incidence of DME increases with : Elevated levels of Hb A1C Level of severity of DR Duration of DM Elevated diastolic blood pressure Gender (more frequent in females)

Definition and clinical description

- Whats CSME?

- Its defined as one of the following conditions :

Clinically significant macular edema

- Retinal thickening at or within 500 m of the center of the macula - Hard exudates at or within 500 m of the center of the macula if associated with thickening of the adjacent retina - Zone of retinal thickening larger than 1 disc area in size at least part of which is within 1 disk diameter of macular center

CSME

CSME : by ETDRS
- Treated 754, Deferred 1490 - After 3 yr. visual loss 12% in treated, 24% in untreated - When centre of macula was involved, treatment effect was more significant at 3 yr. visual loss 13% against 33%

Pathogenesis
Macular thickening is mainly resulted from : - Vascular leakage - Disruption of blood-retinal barrier - Non-perfusion of capillaries - Vitreotraction on the macula - Combination of above

Pathogenesis
Sustained hyperglycemia Activation of vasoactive factors
VEGF PKC (protein kinase C) : PKC-beta Angiotensin II , histamine, MMPs PEDF,PDGF,b-FGF

- Increased vascular permeability - Disruption of blood retinal barrier

Leakage

Pathogenesis
- Changes in structural and functional of tight junction,glial cell - Pericyte loss, endothelial cell loss - Retinal vessel leukostasis - AGEs (Advanced glycation end product) Capillaries non-perfusion

Macular ischemia

- Increased vascular permeability - Disruption of blood retinal barrier

Macular edema

Pathogenesis
Vitreomacular traction AGEs

- Posterior vitreous detachment - Posterior precortical vitreous pocket - Thickened and taut posterior hyaloid

Macular edema

Classification
1. Focal macular edema 2. Diffuse macular edema

Classification
1. Focal macular edema : - Area of focal well-defined leakage from microaneurysm - Microaneurysm surrounded by circinate ring of hard exudates - FA will clearly show the source of leakage

Classification
2. Diffuse macular edema : - Widespread and poorly demarcated leakage from reinal capillary abnormalities (diated capillary bed,IRMA,aterioles or venules)

- associated with extensive breakdown of inner blood-retina barrier lead to fluid accumulation and result in cystoid macular edema

Imaging modalities
1. Fundus Fluorescein angiography (FFA) 2. Optical Coherence Tomography (OCT) 3. Retinal thickness analyzer

Imaging modalities
1. Fluorescein angiography (FA) - Once diagnosis of CSME, FA should be performed to identify the treatable leaking lesions and to evaluate ischemic area - Ischemic maculopathy is diagnosed when capillary non-perfusion is seen on FA

Imaging modalities
2. Optical Coherence Tomography (OCT) - Three basic structural changes in OCT of DME : retinal swelling, CME, and serous retinal detachment

Imaging modalities
3. Retinal thickness analyzer - Accurate and very sensitive imaging technique for diagnosing and monitoring a large spectrum of macular disease - May play important role in identifying subclinical thickening

Treatment options
1. 2. 3. 4. Laser photocoagulation Vitreous surgery Medical treatment Others : systemic treatment

Laser Photocoagulation
- Standard treatment - Indicated for CSME - 2 techniques Focal : treat areas of discrete leakage Grid : treat areas of diffuse leakage - Focal-Grid : combination of the above

Laser Photocoagulation :
Focal leakage : Focal laser - Green-yellow wavelength - Area 500-3000 microns from center of macula - 50-100 microns spot size - 0.1 second

Laser Photocoagulation :
Diffuse leakage : Grid laser - Green-yellow wavelength - Area of macular edema, 500 microns from center of macula and temporal to optic disc 500 microns - 50-100 microns spot size - Spot interval = 1 spot size - 0.1 second

Pre-Laser

Post-Laser

Laser Photocoagulation
Mechanism : - Direct closure of leaking vascular anomalies - Laser-induced endovascular thrombosis - Heat-induced contraction of vessel wall - Destruction of oxygen consuming photoreceptor increase inner retinal oxygenation

Laser Photocoagulation
Mechanism : - Reduction of abnormal leaking vessels - Restoration of RPE barrier by photocoagulation debridement - Decreasing the total surface area of leaking retinal vessels

Laser Photocoagulation :

ETDRS

1. Decreased risk of moderate visual loss (doubling of initial visual angle) to 50% - At 1 yr. 5% of treated eyes occur significant visual loss compared to 8% of untreated eyes - At 2 yr. 7% compared to 16% - At 3 yr. 12% compared to 24%

Laser Photocoagulation : ETDRS

2. Increased chance of moderate visual gain (halving of initial visual angle) - 40% of treated eyes increased of at lease 1 line compared to 20% of untreated eyes 3. Reduced retinal thickening

Laser Photocoagulation : ETDRS

Risk of significant visual loss was greatest in CSME that involved the macular center or threatened by retinal thickening and associated hard exudates 13% of treated eyes Vs 33% of untreated eyes at 1 yr. of follow up

Laser Photocoagulation

Laser Photocoagulation
Clinical features associated with poor outcome after laser treatment : - diffuse with prolong macula edema - diffuse with center-involved - diffuse fluorescein leakage - macular ischemia extensive perifoveal capillary non-perfusion) - hard exudates deposit in foveola - marked cystoid macular edema . DME from vitreomacular traction

Vitreous surgery for DME

- Posterior hyaloid and vitreous traction are ones of important risk factors of DME - Reduction of vitreomacular traction, increased oxygen supply

Vitreous surgery for DME

- PPV with ILM peeling help to reduce macular thickness - Conclusion : PPV in DME is useful in patient with evidence of posterior hyaloid traction and macular laser-non response

Medical treatment
- Subtenon/Intravitreal injection of triamcinolone acetonide - Anti-VEGF therapy - PKC selective inhibitor : Ruboxistaurin (RBX)

Corticosteroids
- Reduce break down of blood retinal barrier - Triamcinolone acetonide sub-tenon injection prefer intravitreous to

- Reduction in macular edema and improve VA significantly

Corticosteroids
- Reduction in central foveal thickness - onset of action : 1 wk. and duration 3-9 m. - adjunctive therapy with grid macular photocoagulation

Corticosteroids
- Macular thickness decreased by 55% and mean VA improved by 2.4 Snellen lines in 1 month (Martidis et al) - DRCRN focal/grid laser is a better treatment than IVTA in eyes with DME involving fovea with VA between 20/40 and 20/320

Anti-VEGF
- VEGF VEGF increased vascular permeability, block reduce leakage improve DME

- 3 available : Bevacizumab (Avastin), Ranibizumab (Lucentis) and Pegaptanib sodium (Macugen)

Anti-VEGF : Ranibizumab
- from pilot study at 7 m. thickness reduction - mean best corrected VA improved by 12.3 letters - need to be evaluated in long term benefits - ongoing study : READ-2 (Ranibizumab for Edema of the mAcula in Diabetes phase II) 85% of mean foveal

PKC selective inhibitor : Ruboxistaurin (RBX)

Increases: Basement matrix protein synthesis Activation of leukocytes Endothelial cell activation and proliferation Smooth muscle cell contraction Cytokine activation, TGF-F, VEGF, endothelin

Reduction of retinal vascular leakage

Systemic treatment
- Control blood sugar level and keep proper HbA1C - Control hypertension and lipid level - Control fluid retention-condition : CKD, CHF, Pregnancy

Conclusion
- DME is a major cause of visual loss in DM patient - Laser photocoagulation is still the standard treatment for CSME - Risk of significant visual loss is higher significantly in untreated patient

Conclusion
- Other treatment options may have benefit but still lack of long term study - Combined medical and surgical therapy may be the best approach in the future

References
American Academy of Ophthalmology. Basic and clinical science course section 12 Retina and Vtreous.2008-2009. 113-119 Bloom SM,Brucker AJ. Laser surgery of the posterior segment.1997.78, 78-97 Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 4 Int Ophthalmol Clin 1987; 27 25672.

- Klein.R, et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology 1998;105:1801-1815 - Elsevier Inc.Surway of ophthalmology. 2009 ; 54 (1)

Thank you