Introduction
34.6% globally within the diabetic community, has DR
- Worldwide has 93 million, with 10% vision threatening
- In developed countries like Australia, it is the most common cause of blindness for people ages 20-74
- Presence of DR associates with 75% greater 10 year mortality rate
- 98% is preventable
Pathophysiologically has an origin through hyperglycaemia
- 4,4 rule:
4 different pathways (polyol, PKC, Advanced glycosylation end-products (AGE), Hexosamine) all lead to oxidative stress, inflammation, ischaemia and vascular dysfunction
- Consequently upregulates growth factors and cytokines
Dead Giveaways
There are a couple signs that you can look for all diagnosis between the different forms of DR.
DR can be non-proliferative or proliferative, and if non-proliferative, can have numerous levels of severity
Mild Non-Proliferative DR
Manifests with ONLY microaneurysms, which appear as little dots
Notice the dots, and flame haemorrhage in the superior-temporal
Moderate Non-Proliferative DR
As unhelpful as it sounds, it is anything in between mild and severe
Does not fulfill 4:2:1, but is more than just MA
Severe Non-Proliferative DR
Uses the 4:2:1 rule, where only 1 is required for a diagnosis
4 Quadrants must contain over 20 MAs (1/3 of all of these lie outside the 7 standard fields)
2 Quadrants must have prominent venous beading
1 Quadrant must have prominent IRMA
Lesions which occur outside the 7 standard fields are associated with a 4.7x increase in risk of progression
There is no haemorrhaging, and thus not PDR, but that is a lot of haemorrhages
Proliferative DR
Neovascularisation, or presence of a vitreous/pre-retinal haemorrhage
This is because a vitreous or pre-retinal haemorrhage assumes neovascularisation
Note the pre-retinal haemorrhage
Associated with DR can also be macular oedema, which can be graded in a similar fashion
Macular oedema primarily focuses on presence of permanent hard exudates, and self-resolving cystic spaces
Absent
No retinal thickening or hard exudates in posterior pole
Non-centre involving
The classification of macular oedema occurring within 1000um and 6000um of the fovea
Mild
Some retinal thickening/hard exudates, but not in centre
Moderate
Begins to approach the centre
Centre involving
Within the 1000um of the fovea, with thickening or hard exudates
If there is a cystic space, it is currently active, and if it isn't at the macular, it's called retinal oedema
Hypo-reflective cystic space
The best giveaway however is simply a good patient history.
diagnostic features
Microaneurysms (MA)
These are the earliest signs of DR, and are outpouches due to the loss of pericytes
Seen on fundus images as a dot, in OCT-A as a hyperreflective dot
In OCT is visualised as an oval that maybe encapsulated, located in the superficial or deep capillary plexus
Dot and Blot Haemorrhages
Occurs when the MA erupts, and bursts
Dot haemorrhages are smaller and appear as dots and are typically deeper in the retina compared to the blots
Refer above for an image
Flame Haemorrhage
A subtle type of haemorrhage that looks like a feather
Appears straited as it occurs with the RNFL, and thus is linear
Appearance is not quite pre-retinal
Cotton Wool Spots
Occurs as a white cloud-like lesion in the RNFL, usually following localised ischaemia
Usually > 1/3 Disc Diameter in size
Self resolving in 6-12 weeks
Blocks axoplasmic flow, and appears in OCT-A as a region of no flow
Note the white spot just near the macular. On an OCT-A, will show no blood flow there, and rests near the RNFL and GCL
Venous Beading
Occurs due to vascular remodelling
Veins appear like sausages due to alternating constrictions and dilations, but can also have a loop like feature
Clearly shows the beading effect, as well as the looping effect
Intraretinal Microvascular Abnormalities (IRMA)
Abnormal intraretinal shunt vessels
Appears adjacent to areas of capillary dropout. In response to VEGF, and is similar to neovascularisation
Fairly obvious in OCT-A due to a missing area of signal --> Capillary dropout
Typically indicates poor retinal profusion or severe hypoxia
Unlike NVE, IRMA is located in the ILM creating an outpouching, and will not grow into the posterior hyaloid
The tiny white dot is the IRMA, next to a massive dropout area
NV Sequelae
Vitreous Haemorrhage. Note that it is cloudy, unclear, and not at the same level as the retina 
Pre-retinal Haemorrhage. Note how the top follows the blood vessels, and the bottom forms a D-shape 
The yellow-white is the fibrovascular scaffolding which grows with NVE. It contracts over time, causing tractional retinal detachment, which is rheumatogenous. If this grows at the iris, can cause glaucoma due to TM obstruction
Anterior Segment Associations:
Poor corneal healing, less tearing and lacrimation occurs
MAs occur in conjunctiva
Diabetic cataracts may occur causing Rx changes
Nerve Palsies:
7.5x more likely than a non-diabetic patient, and primarily affects the 3rd, 4th and 6th nerve
3rd Nerve = Ptosis, exo-hypo-tropia with pupil sparing
4th Nerve = Vertical diplopia
6th Nerve = Esotropia and diplopia
Whilst pupil is spared, reactions are sluggish and usually miotic, requiring more phenylephrine to achieve adequate dilation
Colour Vision:
Altered colour perception, usually tritan errors, in 50% of Px with diabetes
CV defect increases likelihood with DR and age
Glaucoma:
A 48% increased relative risk of open angle glaucoma
Diabetes is associated with an increased IOP of 0.18mmHg
Diabetic Papillopathy
Swelling of the optic disc, typically resolving without Tx + acuity > 6/9
Usually in younger diabetic patients, and is independent of DR severity or glycemic control
Non-Arteritic Anterior Ischaemic Optic Neuropathy (NAAION)
Swelling of ON due to small crowded disk
Usually in older Px, and due to the cramming of nerves and BV in a smaller than usual opening, blockage of a capillary can occur
This can swell nerve fibres in proximity, causing ischaemia
This further compression exacerbates the situation, leading to vision loss following GC death