About diabetic changes in the eye. An important cause for defective vision

1. Dr. K. Vasantha M.S., F.R.C.S
Director ,
Regional Institute of Ophthalmology Chennai Rtd

2.  Macular edema can be present in any stage of the
diabetic retinopathy
 Edema can be present anywhere in the retina but if it is
present in the macular area the vision will be affected
more

3.  Chronic polyol pathway hyperactivity causes increase in
protein kinase C
 Protein kinase C-beta increases the vascular
permeability. This also causes increase in basement
membrane thickness and prolonged retinal circulation
time

4.  Vascular endothelial growth factor (VEGF)is normally
present in the retina. It increases when there is hypoxia
 The receptors for VEGF are located in the endothelial
cells and promotes endothelial cell proliferation,
migration, apoptosis and vascular tube formation
 Causes retinal edema by causing changes in the tight
junctions of the endothelial cells
 It may also contribute to the inflammatory component by
up regulating intercellular adhesion molecule 1 (ICAM 1)

5.  1. Thickening of the retina at or within 500 micro meter of
the center of the macula
 2. Hard exudates at or within 500 micro m of the center of
the macula
a. if associated with thickening of adjacent retina
b. no residual hard exudates remaining after the
disappearance of retinal thickening
 3. Zone or zones of retinal thickening of 1 disc area or
larger – any part of which is within 1DD of the center of
macula

6.  Hard exudates within
500 microns of the
center of macula with
retinal edema
 Edema one DD or
larger part of which is
within one DD from the
center of macula

8. Edema and hard exudates –
lower temporal Leakage from microaneurysms

9. 1. Sponge-like retinal thickening
2. Cystoid Macular edema
3. Sub-foveal serous retinal detachment
4. Foveal tractional retinal detachment
5. Taut posterior hyaloid membrane

15.  In eyes with SND increased inflammatory cytokines esp.
interleukin 6 was seen in the vitreous and aqueous.
 Prognosis is poor
 In these cases ELM will often be disrupted
 ? Impaired choroidal blood flow

17.  Macular edema has to be treated 6 to 8 weeks earlier
than PRP, if PRP is also planned
 Follow up every 4 months
 Retreatment for persistent or recurrent lesions like CSME
new neovascularization, rarely feeder vessels to NVD
 May be additional scatter , local laser to NVE or focal
laser to edema will be needed

18.  Exact mechanism of action of laser induced resolution of
macular edema is not known
 May be it is due to destruction of oxygen consuming
photoreceptors. The oxygen now supplies the inner
retina thus relieving hypoxia.
 Or as the number of total leaking vessels is reduced by
being destroyed the edema comes down
 Or as the size of the vessels comes down due to
increased oxygenation leak also is reduced
 Due to improved blood retinal barrier by the spreading
RPE cells which will cover the small defect made by laser

19. Pre Laser Post Laser

21.  If there is extensive non
perfusion areas with large
foveal avascular zone, laser
will not help – poor
prognosis

22.  Full thickness retinal break
 Choroidal neovascularisation
 Sub retinal fibrosis
 Symptomatic scotoma
 Can cause symptomatic visual loss
 It must be remembered that only 3% of patients had
improvement of 3 or more lines during 3 year follow up
and 10 to 15% had continued loss of vision

23.  Vitreous traction play an important role in macular
edema
 The other reason is up regulation of VEGF in the Muller
cells causing increased vascular permeability
 By removing the vitreous the advanced glycation end
products accumulated in the vitreous are removed and
thus inflammation is reduced
 So AGE ligand induced traction between posterior
cortical vitreous and ILM of macula is relieved

24.  Peribulbar steroid injections will suppress the activation
of VEGF and reduce the induction of VEGF. But
significant benefits were not noted
 Intravitreal steroids or laser coagulation was studied.
Laser was found to be better
 For refractory cases not responding to laser intravitreal
implants are found to be useful
 Cataract, glaucoma and possibility of infection if
repeated injections are given are the major problems

25.  Vascular endothelial factor – A is the major mediator of
retinal permeability
 Blockage of VEGF can be achieved by inhibiting Protein
Kinase C (PKC) like pegaptanib or antibodies like
Ranibizumab or Bevacizumab which act against VEGF

26.  READ – Ranibizumab for Edema of mAcula in Diabetes
 0.5 mg of Ranibizumab on entry, 1, 2, 4, 6 months
 Ranibizumab was found to be effective

27.  Group 1 – Ranibizumab0.5 mg baseline, 1, 3, 5th month
 Group 2 – focal/grid laser baseline and after 3 months if
needed
 Group 3 – 0.5mg Ranibizumab with focal/grid laser
baseline and after 3 months if needed
 Study found that treatment with Ranibizumab was better

28.  Studied efficacy of Ranibizumab, Aflibercept and
Bevacizumab
 Found most of the patients were not receiving the
required number of injections specified in the previous
studies
 Because of this the results were not optimal
 Laser or steroid injections were given later if the
response was not good with anti VEGFs

29.  Intra vitreal Aflibercept was given every 4 weeks or 8
weeks after initial 5 monthly doses or laser for edema
 After 52 weeks it was found both 4 weekly injections and
8 weekly injections were better than laser

30.  Double masked, sham injection controlled study
 Ranibizumab 0.5 or 0.3 g or sham were given
 Found Ranibizumab reverses loss of vision due to
macular edema
 Benefits were seen as early as 7 days after treatment
 In addition fewer patients developed PDR and its
resultant complications

31.  Similar to READ
 Ranibizumab monotherapy and with laser
 Both together provided superior visual acuity gain over
laser alone
 After one year there was no difference between
Ranibizumab alone and with laser
 Both Ranibizumab and laser were found to be safe

32.  BOLT study was done for Bevacizumab or laser
 Bevacizumab was found to be effective

33.  Frequent injections
 Cost factor
 Vitreous hemorrhage
 Retinal detachment
 Infection
 It must be remembered that VEGF is a neuro protective
agent

34. Intra Vitreal Triamcinalone – IVTA is considered for
 Failed laser – focal parafoveal leak
 Wide spread diffuse leak
 Co existent high risk PDR
 Uncontrolled edema prior to cataract surgery
 Juxta foveal hard exudates with heavy leak

35. THANK YOU