Preproliferative diabetic retinopathy

This describes increasing ischaemia superimposed on background diabetic retinopathy.

Diabetic retinopathy in its earliest stages is also called nonproliferative diabetic retinopathy.

The most conspicuous feature are cotton wool spots - "soft" exudates representing microinfarcts in the nerve fibre layer.

Non proliferative diabetic retinopathy (NPDR) is the earliest stage in disease progression (1).

• In the international (AAO) classification, NPDR is graded as:
  • mild
  • moderate
  • severe.
• In the National Screening Committee (NSC)-UK classification, NPDR is graded as:
  • background (Level R1)
  • pre-proliferative (Level R2).

The nonproliferative stages of diabetic retinopathy are characterized by

• microaneurysms
  • the first clinical signs of diabetic retinopathy caused by isolated capillary occlusion with adjacent non-occluded capillaries forming saccular or fusiform swellings.
  • these appear as isolated, spherical, red dots of varying size
  • individual microaneurysms may leak resulting in dot haemorrhage, oedema and exudate
    • dot haemorrhages cannot always be differentiated from microaneurysms as they are similar in appearance but with varying size
      
• retinal thickening (oedema) and lipid deposits (hard exudates)
  • caused by increased retinal vascular permeability
  • may occur during these or later stages of retinopathy
    
• as DR progresses, progressive capillary occlusion leads to the development of
  • blot haemorrhages
    • where clusters of capillaries occlude, intraretinal blot haemorrhages develop
    • such haemorrhages may occur throughout the full thickness of the retina
    • they are considered to represent a deep retinal infarct
  • intraretinal microvascular anomalies
    • dilated pre-existing capillaries
  • venous changes
    • venous beading - occurs when veins run through areas of extensive capillary closure
    • venous loop - are infrequent and though to develop due to small vessel occlusion and opening of alternative circulation
    • venous reduplication - is rare and usually occurs in conjunction with venous beading
      
• cotton wool spots
  • are believed to represent the swollen ends of interrupted axons where build-up of axoplasmic flow occurs at the edge of the infarct (1,2).

The rate of progression to proliferative diabetic retinopathy after 10 years is 6.6% (3).

In those with preproliferatic retinopathy at baseline, the cumulative incidence of sight-threatening maculopathy or retinopathy after 6 years was 70% (4).

Reference:

1. The Royal College of Ophthalmologists (RCOphth) 2012. Diabetic retinopathy guidelines
2. American Academy of Ophthalmology (AAO) 2019. Preferred Practice Pattern guidelines. Diabetic retinopathy.
3. Ockrim Z, Yorston D. Managing diabetic retinopathy. BMJ. 2010;341:c5400.
4. Younis N, Broadbent DM, Vora JP, Harding SP.; Liverpool Diabetic Eye Study Incidence of sight-threatening retinopathy in patients with type 2 diabetes in the Liverpool Diabetic Eye Study: a cohort study. Lancet 2003;361:195-200