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Outline
Definition Pathogenesis Diagnosis and classification Investigation Treatment Prognosis
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
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
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
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
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
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
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
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
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)
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