Diabetic Macular edema
• Macular edema can be seen in any stages of the diabetic retinopathy.
• Edema can be seen anywhere in the retina of eye but if it is seen in the macular area the vision will be get affected more.
• Increase in protein kinase C because due to causes of chronic polyol pathway hyperactivity.
• Protein kinase c-beta increase the vascular permeability. This also causes increases in basement memberane thickness and prolonged retinal circulation time.
Increased vascular permeability-retinal edema
• Vascular endothelial growth factor is normally present in the retina. It increase where there is hypoxia.
• The receptor for VEGF are located in the endothelial cells and promotes endthelial cell proliferation, migration,apoptosis and vascular tube formation.
• Causes retinal edema by causing changes in the tight junction of the endothelial cells.
• It may also contribute to the inflammatory component by up regulating intracellular adhesion molecular 1 (ICAM1)
ETDRS classification of macular edema
• Thickening of the retina at or within 500 micro meter of the center of the macular.
• Hard exudates at or within 500 micro meter of the center of the macula.
• Associated with thickneing of the adjacent retina of eye.
• No residual hard exduates remaining after the disappearance of retinal thickening.
Macular edema is defined as accumulation of fluid in edema. Histologically, accumulation of fluid occur in intracellular space causing intracellular swelling.
Clinically, macular edema classified diffuse, with generalized leakage throughout posterior pole or focal, it discretes areas of retinal thickening are present.
DME is a result of microvascular changes in diabetic leading to incompetence of vessels edema.
OCT pattern in DME
• Sponge like retinal thickening
• Cystoid macular edema
• Sub-serous retinal detachment
– In eyes with SND get increased inflammatory cytokines esp. Interleukh 6 was present in the vitreous and aqueous.
• Prognosis is poor
• ELM will often be disrupted in these cases.
• Impaired choroidal blood flow
Signs & Symptoms
Often Asymptomatic in earliest stages
Common symptoms includes
- Colour that looks dull or washed out
- Blind spots or patches
- Blurriness in the center of the vision
- Straight line that looks wavy
- Loss of color perception or loss of detail vision.
- ARMD, Exduative
- Branch retinal vein occlusion
- Central retinal vein occlusion
- Uveitis, evulation & Treatment
- Macular edema, Irvine-gass
- Earlier than PRP, if PRP is also planned macula edema has to be treated 6 to 8 weeks.
- Follow up every 4 months.
- Retreatment for persistent or recurrent lesions like CSME new revascularization, rarely feeder vessels to NVD.
- Local laser to NVE or focal laser to edema or may be additional scatter will be needed.
Mechanism of action of laser
• Exact mechanism of action of laser induced r ees resolution of macular edema is not known.
• May be it us due to destruction of oxygen consuming photoreceptors. Oxygen now supplies the inner retina thus it will relieving hypoxia.
•Or number of total leaking vessels is decreased by being destroyed the edema comes down.
• Or as the size of the vessels come down due to increased oxygenation leak also is reduced.
•Due to improve blood retinal barrier by the spreading RPE cells which will cover the small defect made by laser.
Laser for diabetic maculopathy
– Pre laser
– Post laser
Laser done for macular edema
Laser foveal avascular zone
- If there will be a extensive non perfusion areas with large foveal avascular zone, laser will not help poor prognosis.
Complications of laser – macula edema
• Full thickness retinal break
• Choroidal neovascularisation
• Sub retinal fibrosis
• Symptomatic scotoma
• Can causes symptomatic visual loss
• It must be remembered that only 3 % of patient had improvement of 3 or more lines during 3 years follow up and 10 to 15% had continued loss of vision.
Vitreous surgery for macular edema
– In macular edema vitreous traction play an important role.
– By removing the vitreous the advancing glycation end products accumulated in the vitreous are removed and thus inflammation is reduced.
– So AGE ligand induced traction between posterior cortical vitreous & ILM of macula is relieved.
– In mcular edema peribulbar steriod injections will suppress the activation of VEGF & reduce the induction of VEGF. But significant benefits were not noted.
– Intravitreal steroid or laser coagulation was studied. Laser was found to be better.
– Cataract, glaucoma and possibility of infection if repeated injection are given are the major problems.
Anti VEGF therapy
– Blockage of VEGF can be rewarded by inhibiting protein kinase C (PKC) like antibodies like Ranibizumab or pegaptanib or Bevacizumab which act against the VEGF.
– READ- Edema of macula in diabetes for Ranibizumab.
– Ranibizumab of 0.5 mg on entry 1,2,4,6 months
– Ranibizumab was found to be beneficial & effective.
– Group 1- Ranibizumab 0.5 mg baseline 1,3,5th month
– Group 2- Focal/grid laser baseline & after 3 months if needed.
– Group 3- 0.5 mg Ranibizumab with focal/grid laser baseline and after 3 month if needed.
– Here Study found that treatment with Ranibizumab was better & effective.
DRCR.net protocal T study
– Studies efficacy of Ranibizumab, Affibercept and Bevacizumab
– Most of the patients were not receiving the required number of injections according to the previous studies.
– Because of this results were not accurate.
– Steroid injections or laser were given later if the response was not good with anti VEGFs.
VISTA and VIVA study
– Intra vitreal Afliibercept 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 injection were better than laser.
RISE and RIDE study
– Double masked, sham injection controlled study.
– Ranibizumab 0.3 or 0.5 g or sham were given to show effect.
– Benefits were present as early as 7 days after the treatment.
– Ranibizumab found reverses loss of vision due to macular edema.
– In addition fewer patients developed PDR and its resultant complication
– Similar to READ
– Ranibizumab monotherapy and with laser
– Both togther provided superior visual acuity gain over laser alone.
– After one year ther was no difference between Ranibizumab alone with laser.
– Ranibizumab & laser were found to be safe in restore study.
BOLT study can be done for laser or Bevacizumab
-Bevacizumab was found to be effective.
Complications of VEGF
- Frequent injection
- Cost factors
- Vitreous hemorrhage
- Retinal detachment
- VEGF is a neuro protective agent it must be remembered.
When is IVTA given
Intra vitreal Triamcinalone- IVTA considered for
- Failed laser – focal parafoveal leak
- Wide spread diffuse leak
- Co existent high risk PDR
- Uncontrolled edema prior to cataracts surgery.
- Juxta foveal hard exduates with heavy leak.