by Shadi Awwad, MD

Introduction:
The prevalence of Diabetic retinopathy (DR) is higher in IDDs(40%) than in NIDDs(20%)
DR is the most common cause of legal blindness in individuals between the age of 20 and 65 years.
The risk factors for DR are:
1. Duration of DM:
     -The most important factor
     -Patients diagnosed before age 30 years: the incidence of DR after 10 years is 50 %, and after 30 years 90 %
     -It is very rare for DR to develop within the first 5 years of onset of DM, but 5 % of NIDDs already have background DR at time of presentation
2. Metabolic control:
      -Doesn't prevent DR, but delays its progression
3. Miscellaneous factors:
      -Pregnancy, systemic hypertension, renal disease, anemia
Pathogenesis:
A. Ischemia: From thickening of the capillary basement membrane, injury and proliferation of the endothelial cells, decrease in the RBC O2 transport, and abnormally increased platelet adhesion and aggregation.
Ischemia can hinder the advancement of the energy driven rapid axoplasmic flow along the nerve fiber layer, resulting in piling of the axoplasmic products at the watershed area, producing what ew see on ophthalmoscopy as cotton wool spots.
Neovessels as well as AV shunts (Intra Retinal Microvascular Abnormalities-IRMAs) develop due to angiogenic factors secreted by the ischemic retina. IRMAs are by definition intra-retinal whereas neovessels typically proliferate into the vitreous. These latter can bleed, causing vitreous hemorrhage as well as retrohyaloid hemorrhage (behind the posterior face of the vitreous). They can also contract due to the fibrous component in them, pulling the vessels and the retina, resulting into a tractional retinal detachment.
B. Leakage: injury to the endothelial cells, together with pericyte drop out would lead to aneurysmal dilatation of the capillaries, leading to thrombosis, as well as rupture with hemorrhage. If the hemorrhage occur in the deep retinal layers( inner nuclear cell layer), it would appear as dot or blot hemorrhage. If the hemorrhage occur superficially at the nerve fiber layer-typical in hypertension rather than diabetes, it produces a flame shape hemorrhage.
Leakage from the blood vessels will also lead to lipid deposition later on. This is known as hard exudates. They typically appear as yellowish lesions with distinct margins that sometimes encircle an aneurysm(seen as a red dot on ophthalmoscopy, like the hemorrhage): we call it circinate exudates.
Leakage can be focal, or diffuse. Diffuse leakage around the macula would produce macular edema from the excess fluid as well as the exudates. Certain criteria are needed to fulfill the diagnosis of Clinically Significant Macular Edema, (CSME), which requires laser treatment.

Clinical Classification 
A. Background Diabetic Retinopathy:
Diagnosed by the presence of any of the following:
       -Dot and blot hemorrhages
       -Aneurysms
       -Hard exudates
       -CSME might be present and this is the cause of decrease in vision in this entity

       Fig.1 : Background Diabetic Retinopathy: notice the hard exudates, dot  hemorrhages, and aneurysms

       Fig. 1: Annotated
B. Pre-proliferative Diabetic Retinopathy :
       -IRMAs
       -Cotton wool spots
       -beading and looping of the capillaries
C. Proliferative
        -Development of frank neovessels in the retina or on the iris( Rubeosis Iridis)

Treatment

A. Metabolic control slows the progression, but does not prevent the development of DR
B. Laser treatment( Grid laser) is necessary if CSME develops. The laser shots are delivered in a grid manner over the diffusely edematous area, avoiding the perifoveal area. The shots are spaced half a shot distance from each other. This will stimulate the RPE( which contain pigments and would absorb the light at the specified wavelength) to pump the excess fluid.
C. Pan-Retinal Photocoagulation (PRP): is to be done in case of neovessel proliferation. The laser is delivered to the retinal periphery, sparing the posterior pole. The rationale behind such a treatment is to literally to  kill as much as possible of the ischemic retina, to decrease the production of the angiogenic factors. The neovessels are supposed to shrink back after such therapy, except for the fibrous component. PRP are delivered with a distance of one shot between a couple.
D. Vitrectomy: in case of a non-resolving vitreous hemorrhage obscuring vision, or if a retinal detachment develops.