The document discusses diabetic maculopathy, detailing its pathogenesis, risk factors, classification, and treatment options. It highlights the significance of managing systemic conditions such as diabetes and hypertension to prevent and treat diabetic macular edema (DME), as well as outlining various therapeutic interventions including medical therapies and laser treatments. The document also reviews the importance of diagnostic tools like fluorescein angiography and OCT in assessing the severity of DME and guiding treatment.

1. Diabetic Maculopathy
Dr.Shah-Noor Hassan
FCPS,FRCS

2. Pathogenesis of Diabetic Maculopathy
Anatomic Change Pathophysiology
Intraretinal
Macular edema Increased retinal vascular
permeability & retinal vascular
occlusion
Macular hard exudate
Macular ischemia
Preretinal and Vitreoretinal
Thickened posterior hyaloid Proliferation and shrinkage of
fibrous, glial, and fibrovascular
tissue
Thickened preretinal membrane
Macular traction
- Surface wrinkling retinopathy
- TRD of macula
- Macular ectopia

3. Incidence of DME
More common in NIDDM(3/4) than IDDM(1/4)
Occurs in 10% of all patients of DR
Can occur at any stage or DR
- 3% in Mild NPDR
- 38% in Moderate/Severe NPDR
- 71% in PDR
(OCNA 2002)

4. Risk factors for DME
Duration
- 3% in patients with DM<5 years
- 28% in >20 years (WESDR)
Level of Hyperglycemia
- 18.1% when HbA1C 6.8 - 9.7%
- 36.4% when HbA1C 13.2-19.2% - (WESDER)
Hypertension
Hyperlipidemia
Others
 Pregnancy, renal disease, PRP & cataract extraction

5. classification
Non clinically significant macular odema
Clinically significant macular odema
Ischemic maculopathy
Cystoid macular odema

6. CLINICAL
CSME is a clinical diagnosis
Best done with 78 or 90 D bio microscopy
Stereo fundus photography
Macular oedema-
thickening of the macula with
blurring of the underlying choroidal pattern,
loss of foveolar light reflex when fovea is involved
presence of cystoid spaces in severe cases

7. Clinically Significant Macular Edema
 Thickening of the retina located
≤ 500 microns from the center
of the macula
 Hard exudates ≤ 500 microns
from the center of the macula
with thickening of the adjacent
retina
 A zone of retinal thickening, 1
disc area or larger in size, any
portion of which is ≤ 1 disc
diameter from the center of the
macula.

8. International Clinical Diabetic Macular edema
severity scale
1.Diabetic macular edema: absent
No retinal thickening or hard exudates in posterior pole.
2.Diabetic macular edema :mild
Some retinal thickening or hard exudates in posterior pole
but distant from the center of the macula

9. International Clinical Diabetic Macular edema
severity scale
Diabetic macular edema: moderate
Retinal thickening or hard exudates
approaching the center of the macula
but not involving the center.
Diabetic macular edema: Severe
Retinal thickening or hard exudates
involving the center of the macula.

10. Options
Medical therapy
Laser
Periocular / Intravitreal steroids
Intra vitreal Anti VEGFs
Vitrectomy
Systemic control
(Bld sugar, HT, Lipids)

11. Systemic control of DM
Metabolic control of diabetes( blood sugar and HbA1c)
 Endocrinologist
 for HbA1c <7%,
HT <130/80 mm Hg
Nephropathy
 Fluid retention ,progression of maculopathy and DR
Hyperlipidemia
- Increased exudation
- LDL Lipoproteins are and < 100mg/dl
Anemia
Resolution of micro aneurysms with correction of anemia (BJO Feb 2005)

12. Systemic control
DCCT- To know the effect of intensive blood sugar
control in type 1 DM
Reduction of mean risk of DME by 29%,CSME by 23%
Complications secondary to hypoglycemia noted as well
UKPDS - To know the effect of intensive blood sugar
and HT control in type 2 DM
slowed progression of retinopathy
reduced risk of microvascular complications of DM.

13. Elevation of total and LDL cholesterol is associated with
greater severity of hard exudates in the macular area
(WESDER Report XIII & ETDRS Report 22)
Treatment of hyperlipidemia is associated with decreased
incidence of macular hard exudation
 (Amod Gupta et al (AJO 2004)

14. Decision making
Intravitreal / subtenons steroids
intravitreal anti VEGF agents
Laser
LASER
Or
PHARMACOTHERAPY
?

15. Tailor a treatment plan
Based on
FFA
OCT
Visual acuity

16. SIGNIFICANCE OF FFA
Distinguishing the type of maculopathy
- Is there a discrete or deep diffuse leakage
- Not absolutely necessary in eyes with localized edema
(especially within discrete circinate rings – ETDRS Report 2)
- Essential to diagnose macular ischemia
Not needed for diagnosis of CSME, guide for treating
CSME
Recommended to identify treatable lesions

17. Focal macular oedema:
areas of individual or cluster of
microaneurysms which show
leakage in late phase.

18. Leakage from generalised dilated
capillary bed along with
microaneurysms.
Diffuse Macular Oedema:

19. Often accompanied by diffuse macular oedema
as large amount of extracellular fluid
accumulates in OPL.
petalloid pattern on late phase
Cystoid macular oedema:

20. Ischemic maculopathy
Represents closure / nonperfusion of perifoveal capillaries
and often in type 1 DM
Positive correlation between FAZ size and advancing level
of retinopathy
Multiple dot-blot hemorrhages
Presence of multiple CWS
Visual acuity not corresponding to macular findings

21. Macular ischemia Angiographic
features
Irregularities of the avascular
zone margins
Abnormally tortuous capillaries
budding into the FAZ
Terminal arterioles/venules
directly abutting FAZ margins
Enlargement of intercapillary
spaces
Longest diameter of FAZ more
than 1000 µ

23. ROLE OF OCT IN DME
Can detect subtle edema
Defining the disease pattern
Measure the retinal volume and central foveal thickness
in microns
Defining the treatment and indications for vitrectomy.
Longitudinal tracking of tissue alteration following an
intervention.
OCT categorizes DME - tractional vs. non-tractional
- Tractional macular edema always needs PPV.
- Non-tractional macular edema may require the presence of
cystic spaces, massive retinal thickening

24. PATTERNS
1. Sponge like thickening
2. Cystoid macular edema
3. Subfoveal serous detachment
4. Foveal TRD
5. Taut post hyaloid

25. Spongy Thickness
Diffuse homogenous intraretinal swelling with reduced
reflectivity.
fluid accumulation throughout the neurosensory retina.
Confined mainly to outer retinal layers
responds well to laser treatment (focal oedema on FA)

27. Cystoid Macular Oedema
• Appear as optically clear cystic spaces with bridging
elements between them.(diffuse oedema on FA)
• Initially may be confined to outer retina mainly
• cysts may fuse to involve almost entire thickness of the
retina.

28. Cystoid Macular Oedema
• Visual loss in CME correlates more with degree of
macular thickening then with leakage seen on FA
• Responds poorly/ may worsen to laser
• Usually warrants periocular or intravitreal steroids

30. Subfoveal serous retinal detachment
An area of hyporeflectivity in the subfoveal region
Usually not appreciated clinically or on FA

31. Tractional retinal detachment
An indication for pars plana vitrectomy to
release the traction.
Laser photocoagulation - may worsen the macular
oedema

32. Taut Posterior Hyaloid Membrane
• may result in recalcitrant macular oedema with foveal
detachment
• usually do not respond to laser treatment

33.  Improvement in vision and
macular edema following PPV and
posterior hyaloid removal.

34. What are treatable lesions ?
 Focal leaks greater than 500um from
the centre of macula causing retinal
thickening/hard exudates.
 Focal leaks within 300um-500um
from the centre of macula thought to
be causing retinal thickening/hard
exudates
 Areas of diffuse leakage from
microaneurysms and capillary leak
 Avascular zones, other than FAZ, not
previously treated.

35. Laser treatment
works best in eyes with-
Discrete areas of leakage on FA
Mild to moderate thickening on OCT
No vitreo-macular interface abnormalities on OCT
Visual acuity good or with only a mild to moderate
decrease
Ischemic maculopathy does not respond to laser

36. Pharmacotherapy
(Steroids, anti-VEGFs)
Eyes with diffuse leakage on FA with moderate to
severe thickening,
cystoid macular oedema (CME) or
serous macular detachment on OCT,
Moderate to severe decrease in visual acuity
Alternative - laser in combination with these agents

37. Laser treatment consideratons
• Informed Consent
• Goal of treatment is to stabilize the VA
• Risk of moderate vision loss is reduced by > 50%
• Need for periodic follow up, repeated FA/OCT and the
possibility of further t/t
• Eyes with CSME with severe NPDR/PDR
-Treatment for the macular edema first followed by PRP
after 4-6 weeks

38. Direct Focal Laser
 Directly over all focal FA leaks
 MA, IRMAs, capillary segments
 Goal:
 Obliteration of leak
 Endpoint: Whitening/blanching of MA
 Protocol:
 Spot size: 50-200micron
 Area: 500-3000micron from centre of
macula
 Duration: 0.1sec or less

39. Mechanism of Action of Laser
Changes in the metabolic activity of the RPE
Release of signals that reduce vascular leakage
Facilitate fluid absorption
on follow up - If macular edema persists
- focal leaks within 300-500µ treated provided there
is a good perifoveal network

40. Grid treatment
Thickened retina with diffuse leak or capillary drop-out
 100-200 microns spot size
 0.1 seconds duration
 Power adequate to produce faint white burn
 1 burn width apart in the areas of thickening
 Grid
 Not placed within 500µ of the foveal center and margins of the
optic disc
 Papillomacular bundle is usually avoided
 Could extend upto 2 DD from the center of the macula

41. MODIFIED GRID
• Grid + focal
• Given only to areas of non-
perfusion / thickening
• 100 micron burns near the FAZ
• 200 microns outside these
• Papillomacular bundle spared- C
shape

42. Ischemic maculopathy
Laser - not indicated for eyes with visual loss solely
due to ischemic maculopathy.
If oedema and ischemia co-exist - the oedema may
be treated after explaining the guarded prognosis.
No more than 6 clock hours of juxtafoveal capillary
nonperfusion on FFA
Laser’s in ophthalmic surgery: David b karlin : blackwell 1995 P. 105

43. Re-Treatment
• Re-evaluation at 3 months
• Focal/grid treatment supplemented, if CSME persists
• Temporary increase in the HE following treatment can occur
• Oedema & exudates subside in 4-6 mths, if persist do FFA
• Most patients require more than one treatment session
• Recalcitrant CSME - more than 3 treatment sittings
- requires alternative pharmacological agents

44. Clinical Guidelines
Clinically Significant Macular Edema Treatment
First-line therapy
• Focal or modified ETDRS grid photocoagulation for focal or diffuse CSME
• Intravitreal pharmacotherapies ± photocoagulation for more advanced,
diffuse CSME
For persistent or recurrent CSME (visual acuity <20/40)
• Repeat photocoagulation
• IVTA or IV anti VEGF agent

45. Micropulse Diode Laser
 Iris Oculight Micropulse 810 nm diode laser
 Spot size : 200 - 500
 Micropulse :
On time - 100 - 300 microsec
Off time - 1900-1700microsec
 Power initially adjusted till a barely visible burn
is seen
 Power then set at half that value and treatment
started
 Conventional grid pattern done in areas of
retinal thickening
• Subthreshold micropulse diode laser and conventionalargon laser
treatment showed an equally good effect on visualacuity
• Stabilisingor even improving effect on macular oedema
• combinationof primary diode laser and supplementary argon laser
might beparticularly favourable in reducing diabetic macular oedema
British Journal of Ophthalmology 2004;88:1173-1179

46. PPV
Intravitreal triamcinolone
 OCT can help in decision making
Recalcitrant CSME:
• Despite focal laser photocoagulation,
• Diffuse Retinal thickening
• Macular ischemia +
• Taut, Opaque Persistent hyaloid
• CME
Limited treatment options :

47. Steroids
Anti-VEGF
Intravitreal Injections

48. Triamcinalone
Indications
- Diffuse/ cystoid diabetic macular edema
- Refractory diabetic macular edema
 Dose – 4mg / 0.1 ml
Longer retention time
 41 days in a non-vitrectomised eye
 17 days in vitrectomised eye

49. Mechanism of action
ability to inhibit arachidonic acid pathway
Stabilize retinal vascular endothelial tight junctions,
which decreases permeability
Inhibits inflammatory mediators and VEGF
Transient increase in IOP may favourably alter the
haemodynamics within the eye
Induction of PVD
• Contraindications
- Local infections
- Glaucoma patients
- Steroid responders
- Systemically uncontrolled diabetes

50. Post operative monitoring
Head-end elevation/sitting for 1 day
IOP monitoring
Check for inflammation
Antibiotic eye drops qid x 5 days
• Increase in IOP – 19 to 50%
• Dispersal leading to visual axis blockage
• Endophthalmitis
• RD
• Vitreous haemorrhage
• Cataract
Complications

51. Symptoms & signs of inflammation are
masked
Pseudohypopyon after 2days
White, crystalline corneal endothelial
precipitates after 1day

52. Triamcinalone

53. STUDIES
Intravitreal triamcinolone (4 mg in 0.1ml) in refractory
diabetic macular edema.
- Improvement in visual acuity with decrease in central macular thickness
as measured by OCT
- Re-injection was performed after 6 months in 37% because of recurrence
of DME
Martidis et. al -

54. Combined IVTA and PRP for diabetic macular edema and
proliferative diabetic retinopathy.
Provide benefit in patients with diffuse diabetic macular edema who
require urgent PRP for proliferative diabetic retinopathy by preventing
exacerbation of macular edema
Retina. 2005 Feb-Mar;25(2):135-40
Posterior subtenon triamcinolone acetonide for refractory
DME
VA remained stable or improved over a 12-month period There was a
statistically significant improvement in visual acuity at 1 month.
Am J Ophthalmol. 2005 Feb;139(2):290-4
STUDIES

55. FLUCINOLONE ACETONIDE IMPLANT
drug pellet
- (2 x 2 x 6 mm) surgically placed inside the eye
- releases flucinolone at a constant rate over a 3 yr period.
A multi centric, masked randomized controlled trial –
80 patients of DME (BCVA of >20/400 and less than 20/50), with a history of
one episode of laser treatment 3 months back
RESULTS –
- complete resolution of macular edema in 54% of eyes with
implant compared to control group at 24 months
- decrease in retinal thickness in 46% of treatment groups
compared to 15% in control group.
 SIDE EFFECTS - increased IOP in 32%
increased incidence of cataract

56. Ozurdex
 Dexamethasone biodegradable posterior
seg. Drug delivery system.
 It’s use is FDA approved in macular
edema of retinal vein occlusions and post.
Noninfectious uveitis
 But ongoing research for use in DME .
 0.7mg dexamthasone implant had
significant improvement in v/a and
retinal thickness compared to control
group
phase 2 trial kupperman et
al AAO2003

57. Role of VEGF
 Produced by glial cells, RPE.
 Is normally present in retina and vitreous in low
levels
 Upregulation of VEGF ⇒ by hypoxia
 Pro inflammatory effect
 Breakdown of blood retinal barrier ⇒
-Increased vascular permeability - edema
 Endothelial cell growth & Neovascularisation

58. Angiogenesis Inhibitors
Matrix Metalloproteinase
Inhibitors
a. Marimastat (BB2516)
b. Prinomastat (AG3340)
c. BMS 275291
d. BAY 12-9566
e. Neovastat (AE-941)
Novel Agents Inhibiting
Endothelial Cells
a. Thalidomide
b. Squalamine
c. Celecoxib
d. 2D6126
e. Integrin antagonists
Drugs Blocking
Endothelial Cell Signaling
a. RhuMAb VEGF
b. VEGF receptors Inhibitors
c. SU5416
d. SU6668
e. ZD6474
f. CP-547,632
g. Tyrosine kinase inhibitors
Endogenous inhibitors of
angiogenesis
a. Endostatin
b. Interferons

59. Role in DME
PDR with diabetic macular edema
Persistent NV despite extensive PRP
Used 2-5 days prior to vitrectomy - preparatory
Rubeosis
 Action lasts for 2-4 weeks
 Retinopathy recurs & at times with a vengeance
Grid laser may be done once edema decreases postGrid laser may be done once edema decreases post
intravitreal injectionintravitreal injection

60. Role in DR
 PRP removes the incentive for VEGF formation thus suppressing their
release
 Complimentary to each other
 IVTA has risk of cataract & secondary glaucoma
Trials have shown good efficacy:
 Pegaptanib sodium: Macugen Diabetic Retinopathy Group
 Ranibizumab: READ Study by Nguyen et al

61. Anti-VEGFs
Macugen (Pegaptanib sodium)
 Selective VEGF blocker
Lucentis (Ranibizumab)
 More efficacious
Avastin (Bevacizumab)
 Cheaper alternative
SIRNA (Bevaciranib)
VEGF-TRAP
VEGF-165

62. Avastin

63. 55 years male
DM and HTN since 17 years
S/P BEs CE + IOL x 3 years
PRP in 2001
IOP: OS-18
20 OCT 07 OS: AGS at Aravind
Last seen on
22 APR 2008
IOP: OD-20 OS-25
BCVA : OD: 6/36 OS: CF 3 MTR
Case 2(LE)
10 nov 2006
1 mar 2007
23 Apr 2007
30 May 2007
333 microns
326 MICRONS
871 MICRONS
525 MICRONS
CF 3 Meter
6/60
6/24
6/60
6/36
214 MICRONS
4 July 2007
15/12/2006 LE-PRP Aug WITH IVTA
15 mar 2007 LE- IV macugen given(1 st injection)
27/08/07
OS: PRP aug + IV Macugen (2nd injection) + s/t Kenacort given

64. PROTEIN KINASE C-beta Inhibitors
Ruboxistaurin Mesylate (oral selective PKC beta
inhibitor) - delay the progression of diabetic
retinopathy.
PKC-DMES
686 patients with diabetic macular edema,
BCVA 20/25 or better and no prior laser treatment.
At 36 months - excluding the patients with poor glycemic
control showed a reduction in progression of DME
Aiello RC et al, initial results of PKC beta inhibitor diabetic macular edema
study. D iabetologica 2003;46:A42

65. Avastin

66. Surgical
Treatment algorithm
for
Macular TRD, macular ectopia, VMT, Thickened posterior hyaloid & ERM
VITRECTOMY

67. Cataract and DR
DM ↑ incidence of Cataract
C/E cause progression of maculopathy and to some extent
retinopathy
Good peri-operative DM control
Prior laser PC if possible
Intravitreal anti VEGF can be given in suspicious cases
If not ⇒ early post-operative laser
Phacoemulsification
 Lesser inflammation
 Larger CCC (anterior capsular contraction)
 Large diameter non-silicone IOL
Combined with vitrectomy and endolaser

68. Thank You

69. TRACKING THE CHANGES
 Helps in quantifying the response to therapy & its
monitoring