A concise and brief description of basics and pathophysiology of maculopathy in diabetes mellitus and its management

1. DIABETIC MACULAR EDEMA

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

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

4. ANATOMY

5. ANATOMY

6. PATHOPHYSIOLOGY
• ALDOSE REDUCTASE
• VASOPROLFERATIVE FACTORS
• PLATELET DYSFUNCTION

7. 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

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

10. PATHOPHYSIOLOGY
• Hard exudates (HE):
– Lipoproteinaceous deposits
– Transudation
– Outer plexiform layer
• Subretinal fluid
• Subretinal fibrosis

11. 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

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

14. EXAMINATION
• Stereoscopic fundus photography
• Fluorescein angiography
– Macular perfusion
– Extent and location of capillary leakage
• OCT
– Documenting macular thickness
– Monitoring progression

15. 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

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

17. 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)

18. 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

19. ETDRS protocol
Focal
Spot size
Exposure time
Grid
50-100 u
<200u
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 lens
Avoid argon blue-green (488 nm)
Follow up after 4 weeks, if lesions missed then treat after 4 months
Spacing is one burn width apart

20. LASER photocoagulation
• Adverse effects
– Foveal burns
– Subretinal hemorrhage
– Vitreous hemorrhage
– RPE creep
– CNV
– Paradoxically increased HE

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

22. 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

23. PROTEIN KINASE C Inhibitors
• PKCβ
– Ruboxistaurin
– Oral administration