Primary prevention of diabetic retinopathy

Control of underlying diabetes is the most important management method for diabetic retinopathy (DR).

• Glycaemic control is the most effective method of reducing the risk of developing DR.
• It is recognised that the benefit of good glycaemic control may be seen at any stage in the development of retinopathy for preventing retinopathy, for regression in the early stages of retinopathy and for reducing the progression to proliferative retinopathy and to severe visual loss.
  • The Diabetes Control and Complications Trial (DCCT) showed that
    • tight glucose control (HbA1c) of <6% or 42.1 mmol/mol) in people with type 1 diabetes prevented the development of diabetic retinopathy by 76% and decreased progression of existing diabetic retinopathy by 54%.
  • The United Kingdom Prospective Diabetes Study (UKPDS) reported that
    • intensive glucose control (median HbA1c of 7.0% or 53 mmol/mol vs. 7.9% or 62.8 mmol/mol in conventional glucose control group) led to a 25% reduced rate of microvascular disease, including retinopathy, in patients with type 2 diabetes.
  • However, a meta analysis of clinical trials in people with type 2 diabetes concluded that
    • intensive control of blood glucose did not prevent the need for photocoagulation, nor the development of severe vision loss.
• Recommendations for management of glycaemia:
  • a personalised HbA1c target should be set, usually between 48-58 mmol/mol (6.5-7.5%). No threshold level of glycaemia has been shown in any of the larger studies of retinopathy
  • less strict targets should be set in patients with established cardiovascular disease and in older subjects
  • patients should receive an on-going review of treatment to minimise hypoglycaemia
  • pioglitazone should be avoided in the presence of macula oedema.

Management of the following risk factors have shown to reduce the risk of developing DR:

• blood pressure
  • the UKPDS showed that a reduction of mean systolic blood pressure from 154 to 144 mmHg reduced microaneurysm count at 4.5 years follow up, reduced hard exudates and cotton-wool spots at 7.5 years, and was associated with less need for photocoagulation
  • interestingly, the ACCORD Eye study failed to demonstrate a significant effect of intensive blood pressure control on the progression of retinopathy
  • guidelines for hypertension in diabetes:
    • intensify therapy aiming for systolic ≤130 mmHg in those with established retinopathy and/or nephropathy
    • encourage regular monitoring of blood pressure in a health care setting and at home if possible
    • recognise that lower pressures may be beneficial overall but evidence is lacking for retinopathy
    • specific therapies blocking the renin-angiotensin system (RAS) may have additional benefits, particularly for mild retinopathy, but should be discontinued during pregnancy
    • establish a personalised mean systolic blood pressure target in all patients who do not have retinopathy, usually <140 mmHg.
      
• lipid levels
  • LDL cholesterol and triglyceride levels have shown to be directly related to the incidence and severity of diabetic retinopathy, while HDL cholesterol level is indirectly relate
  • two studies (ACCORD and Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study) have shown that use of fenofibrates prevented progression of retinopathy
  • recommendations for lipid management in diabetes:
    • aim for total cholesterol <5.0 mmol/L (ideally <4.0 mmol/L)
    • aim for low-density lipoprotein cholesterol <3.0 mmol/L (ideally <2.0 mmol/L)
    • aim for triglycerides <2.3 mmol/L
    • commence statins in all individuals >40 years, or >19 years if there is coexisting retinopathy
    • consider statins in secondary prevention of macrovascular disease as well as in primary prevention
    • avoid statins in pregnancy
    • consider ezetimibe for patients intolerant of statins
    • consider adding fenofibrate to a statin for non-proliferative retinopathy in type 2 diabetes (1,2,3,4).

Reference:

1. Ghanchi F; Diabetic Retinopathy Guidelines Working Group. The Royal College of Ophthalmologists' clinical guidelines for diabetic retinopathy: a summary. Eye (Lond). 2013 Feb;27(2):285-7. doi: 10.1038/eye.2012.287.
2. Das A, Stroud S, Mehta A, Rangasamy S. New treatments for diabetic retinopathy. Diabetes Obes Metab. 2015 Mar;17(3):219-30. doi: 10.1111/dom.12384. Epub 2014 Oct 6. PMID: 25160598.
3. Broadbent D. Diabetic retinopathy: Fundamentals for primary care. Diabetes & Primary Care 2013;Vol 15 No 4
4. Ockrim Z, Yorston D. Managing diabetic retinopathy. BMJ. 2010;341:c5400.