Diabetic Macular edema- Retinal edema, Macular edema Treatment

Diabetic Macular edema
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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.

 

Retinal edema

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.

Retinal Edema
              Retinal Edema

 

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

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.

 

Pathophysiology

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.

 

Differential Diagnosis

  • ARMD, Exduative
  • Branch retinal vein occlusion
  • Central retinal vein occlusion
  • Uveitis, evulation & Treatment
  • Hypertension
  • Macular edema, Irvine-gass

 

Treatment

  • 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.

 

Steroids

– 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 study

– 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.

 

READ 2

– 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

 

RESTORE study

– 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
  • Infection
  • 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.

 

diabetic macular edema

 

 

 


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