Diabetic retinopathy progression

David Kinshuck


Retinopathy progression and sudden lowering of HbA1c , etc

Generally retinopathy progresses according to the parameters below. There are very few exceptions. Once background retinopathy develops, unless diabetic control is improved as below, the retinopathy will deteriorate, laser will be needed, and even with laser sight may be affected.

Certain clinical situations are recognised:

A typical scenario

A patient has poorly controlled diabetes (HbA1c 9%) for many years, and gradually develops retinopathy. She may have mild retinopathy, is told how important it is to control her retinopathy, and then becomes very frightened, starts to control the diabetes very well, and the retinopathy starts to get rapidly worse. She develops macular oedema that becomes diffuse and will not respond to laser. Gradually the retinopathy becomes under control but there will have been permanent macular damage and her sight is markedly reduced.

Illustrated graphically:

progression rate of diabetic retinopathy

Enlarge  A 3% drop in HbA1c may increase the progression rate for 1-3 years. But after 3-4 years of good control, progression rates drops significantly (lilac line). In the long term, good control causes much less progression.


If the diabetes is well controlled, retinopathy may progress, but  much slower than the 'average' person with diabetes.





retinopathy progresses more quickly is blood pressure risesEnlarge


If blood pressure rises, as may happen if renal failure starts or a patient stops their blood pressure medication, the retinopathy starts to progress more quickly.

a sudden improvement in diabetic control incrses retinopathy in the short term, but helps in the long term



A sudden improvement of control, perhaps with a 3% HbA1c drops, causes an increase in retinopathy progression for 1-3 years.
After 3-4 years of very good control retinopathy usually stops progressing completely and most patients will never need laser again (our patients are discharged back to the retinopathy screening service).


Prevent this rapid progression

Ophthalmologists are aware of this scenario and it was discussed in detail at the EASDec meeting 2003. In order to prevent this scenario happening over and over again, it is important to

  1. never let the diabetes get out of control in the first place! (But unfortunately this does not seem possible in most clinics).
  2. if somebody who is poorly controlled has background retinopathy, and then starts to tighten their control, their eyes need checking every 3-4 months to see if laser is needed. (By 'control', I mean HbA1c, BP, and cholesterol.)
  3. there is probably no such rebound effect if someone stops smoking, only benefit. Similarly, there is only benefit if blood pressure and cholesterol are reduced.
  4. screening of retinopathy is important: any patient with macular oedema should be referred as it will get much worse if the control tightens.
  5. (My view) any retinopathy suggests poor control, so any patient with background retinopathy detected on a screening program should be considered to have poor diabetic control until proved otherwise, and appropriate action taken.
  6. An extremely low blood pressure is probably helpful, as low as possible as long as the patient feels well.
  7. It is probably safer to lower the HbA1c gradually, over a year if necessary, as below. There is no hard evidence that this will help, but logical argument. This paper, the DCCT study here , and Sivas above describes the problems. This paper  advises laser in patients with severe pre-proliferative retinopathy, and this prevented 60% of the visual loss (which will be due to macular oedema or scarring).
    If such a patient with florid retinopathy caused by a rapid change in HbA1c is allowed poorer control and a higher HbA1c, the retinopathy progression slows, see.
  8. Prof Harding recommends (2011, Manchester) dropping the HbA1c gradually at the rate of 1% a year. But this seems too gradual to me. We know from the DCCT study that good control helps in the long term, so why delay good control so long? However, by dropping he HbA1c quicker than this does result in progress on of retinopathy, and some patients do develop severe macular problems and sight is not so clear. Nevertheless I think it is preferable to accept this rather than delaying good control several more years.

So as a person tightens their control, they may develop severe retinopathy (maculopathy or new vessels), which cannot be controlled. This was discussed at the EASDec meeting in 2003 by Massin as below, and also reviewed by Ellis, at the Royal College meeting 2003 here.

We are now learning to take this into account when planning laser see .

Ellis (described in detail here) demonstrated that if florid proliferation is present, and it does not respond to laser, even without fibrovascular traction, vitrectomy can be very helpful. The case he showed demonstrated a complete resolution of proliferation after surgery.

Massin presented a case (~2003): A patient (age 40y) with poorly controlled diabetes and background retinopathy underwent rapid control of her diabetes. Her retinopathy became proliferative. She was lasered, but developed macular oedema. This did not respond to grid laser. Intravitreal triamcinolone was effective at reducing the macular oedema (anti-VEGF would be used in 2014).


Treatment of rapid progression

Rapid progression needs to be predicted and taken into account when planning laser, as a lot more laser will be needed. A low blood pressure, not smoking, with regular exercise will slow progression (see paragraphs above).


The mechanism for this rapid progression with rapid HbA1c lowering

It is well recognised that diabetes causes an increase in retinal perfusion and blood flow, and this flow is directly related to glucose levels. We know that neovascularisation is caused by ischaemic retina (which releases growth factors such as VEGF).

The hyper-perfused retina develops microvascular damage and becomes slightly ischaemic..but as soon as the glucose levels drops, perfusion drops, and the retina becomes even more ischaemic. This induces a rapid growth of new vessels.

We do not know the rate at which should be lowered in an individual patient. 32% of patients with retinopathy progressed as their HbA1c was lowered, here, whereas only 2% of those with no retinopathy progressed. May be those with higher IGF1 levels will do worse, as here. In the DCCT, some patients retinopathy deteriorated before stabilising, see here. Logically high risk patients will need careful supervision....anti-VEGF drugs may help.

At Good Hope we will now recommend gradual HbA1c control in patients with retinopathy (although in practive this is nearly impossible to achieve). We hope this will allow time for the retinal vasculature to remodel and slow down the progression, but we do not know whether this will work. Have you any ideas?


Type 2 diabetes, changing to insulin, & retinopathy progression

retinopathy porgresses after changing to insulin

Sivas (EASDec 2005), presented this data from about 300 patients, from her previous clinic in St Petersburg. 90% of diabetes is type 2, and 50% of type 2 patients eventually need insulin 5-10 years after becoming diabetic.

After converting to insulin, of those who developed or already had retinopathy, 60% progressed in the first year, 20 % the second, as shown. Of the 50% that progressed, half of these already had retinopathy, and half developed it.  


Diabetes control has a long-term memory

However, this data does not exactly agree with the DCCT  data. Even after 10 years a period of intensive control (10 years) can significantly reduce retinopathy (retinopathy has along-term memory). So after 10 years of intensive (one group) or bad control (the other group), then another 10 years of mediocre control (HbA1c 8%, both groups) there was a 56% difference in progression rates between the intensive and bad controlled groups. This is called the 'legacy' effect.


retinopathy progresses more with high blood pressue & dyslipidaemia

Retinopathy progression

Blood pressure and dyslipidaemia also increased progression.



retinopathy progresses more if you are obese


Progression rate was also linked to obesity.







MODY diabetes and progression

Some types of MODY diabetes have much less retinopathy. This was reviewed by Guillausseau , at the EASDec 2005 meeting. He also found that genetic variants of the angiotensin 11 gene significantly alter the retinopathy risk (x6). The VEGF gene, x2.6.


Carotid artery progression

If the retinopathy progresses despite lots of laser, and particularly if it asymmetrical, then occasionally carotid artery occlusion is responsible. Acta 11  1990