Diabetic Retinopathy

Diabetic  Retinopathy

Discussion
   Diabetic retinopathy  is the most  common cause  of newly diagnosed legal blindness amongst  the working  population  in the  industrialized  world today. . Although majority  of diabetic patients have retinopathy of varying severity, approximately 25% of the  diabetic patients have sight - threatening diabetic  retinopathy which  leads  to legal  blindness  (best corrected visual acuity of 20/200 or worse ).  Blindness  due to retinopathy  is 25 times more common in the diabetic, when  compared to the non diabetic population.
    Approximately 10 % of the  diabetic  population has type  1 (insulin- dependent) diabetes mellitus, which is usually diagnosed before  the age of 30 years. The majority (90%) of diabetic patients, however have type 2 ( non- insulin- dependent )  diabetes mellitus, which is diagnosed after the age of 30 years. Diabetic retinopathy is a highly specific vascular  complication of both type 1 and type 2  diabetes mellitus, and the duration  of diabetes  is a significant risk factor for the development  of retinopathy.
   Macular oedema  represents  a common pathologic  sequel of the  retina associated  with a  broad spectrum  of potential  insults. Diabetic macular oedema (DME) can occur at virtually  any  stage during  diabetic  retinopathy  development , and it represents  the leading  cause of visual  impairment in people with diabetes.  One of the most common  causes of  macular oedema is diabetes mellitus, and it is the cause  of visual loss in the latter.  The duration of macular oedema could be an  important  factor for visual prognosis.

   Molecular  basis  of  diabetic retinopathy . The retinal changes in patients  with diabetes resulted from five fundamental processes:
I)  the  formation of retinal  capillary  micro aneurysms, The development
II) the development  of excessive vascular permeability,
III)  vascular  occlusion ,
IV) the proliferation  of new blood vessels and accompanying  fibrous tissue on  the  surface  of the retina  and  optic disk, and
V )  the  contraction of these  fibro vascular proliferations and the  vitreous.
   
  The  clinic pathological lesions  of diabetic  retinopathy have been  well  classified. Although a  multitude of pathogenic  mechanisms  have  been   proposed, the underlying  dysfunctional   biochemical and molecular  pathways that lead to  initiation and  progression  of DR still remains an enigma. Currently  four  major  biochemical  pathways  have been  hypothesized  to explain  the mechanism  of diabetic  eye diseases all starting initially from  hyperglycaemia  induced  vascular injury. These  mainly  include:

I) enhanced  glucose  flux through  the  polygon pathway,
II)  increased  intracellular  formation of advanced glycation  end- products (AGE),
 III )  activation of protein  Kinase C (PKC) is forms, and
IV)  stimulation of the  hexosamine pathway.
   
   Studies have suggested that  these  mechanisms  seem  to reflect  a hyperglycaemia  induced process initiated by superoxide  overproduction  by  mitochondrial  electron transport  chain. Studies  have shown that poor glycaemia  control and higher levels  of HbA 1 c are among the risk  factors for  the onset of DME.  The  Wisconsin Epidemiologic Study  of  Diabetic Retinopathy  found rates  progression to DME of 26% in patients with diabetes  for 14 Years  and 29 % at  20 years or longer after diagnosis.

 
   
  Diabetic  retinopathy (DR) is a  very  common , potentially preventable, long - term complication of type  1 diabetes and the leading cause of  acquired  loss of vision among working - age adults in  Europe  and North America. Most  vision loss  in diabetes is a  result  of  diabetic macular  oedema, which  results  after  breakdown of the blood retinal barrier. Diabetic  macular  oedema is the  result  of retinal  micro vascular changes that occur  in patients with diabetes.  Thickening  of the basement membrane  and  reduction  in the number  of  pericytes is  believed to lead  to  increased  permeability  and  incompetence of

retinal  vasculature.  This  compromise  of the  blood- retinal  barrier  leads  to the leakage  of  plasma  constituents in  the  surrounding  retina,  resulting  in retinal  oedema.  The  hypoxic  state  achieved  through  this  mechanism can also stimulate the production of vascular endothelial  growth  factor (VEGF).  Macular  oedema affects approximately 29% of patients with diabetes  who have  disease  duration  of 20 years  or longer  and  constitutes the primary  cause  of visual  impairment  in  this  population.  For 30  years  the standard  of  treatment  has been  glycaemia  control  and  photocoagulation.  Despite  this,  some patients  suffer  permanent  visual  loss  even  after  intensive  treatment.  Despite  intensive  study,  current  understanding  of the  pathogenesis  of  diabetic  macular  oedema  remains  incomplete.  Hyperglycaemia  is clearly  the  strongest  known risk  factor for  DR.  Nevertheless,  whereas  intensive  glucose  lowering  was  effective  in  substantially  reducing  the  incidence  and  progression  of  retinopathy  in  the  Diabetes  Control  and  Complication  Trial (DCCT), there  was no  statistically  significant  effect  on the  incidence  of clinically  significant  macular oedema (CSME) during  the trial.  Thus, other  factors are  likely  to  play  at least  a contributory  role  in the  pathogenesis of CSME.