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Management of diabetic retinopathy


 - Basic anatomy and physiology of the eye and how diabetes effects this
 - Degrees of retinopathy and what these mean
 - Controlling diabetes to avoid worsening retinopathy
Diabetic retinopathy is the retinal damage caused by high blood glucose levels in diabetes mellitus. It affects about 25% of people with diabetes, and without treatment usually leads to loss of sight and occasionally blindness. It starts after nine years of diabetes, and may become severe after 14 years.
Mechanism of retinopathy
In diabetes the lack of insulin from the pancreas leads to high blood glucose levels. The high blood glucose then damages the capillaries in the retina, and areas of retina then lose their blood supply and then become 'ischaemic'. 
Then a second process occurs: the ischaemic retina produces chemicals such as vascular endothelial growth factor (VEGF) which then causes the capillaries in nearby areas of retina to leak fluid (retinal oedema) or grow abnormally (new blood vessels).
Types of retinopathy
Background or early non-proliferative (R1)
The damaged capillaries become visible as small red dots, called microaneurysms, on the retinal surface. Also, tiny retinal haemorrhages are visible as red blots (dots and blots). In addition, there may be whitish exudates on the retinal surface; these contain lipids from the leaky vessels. 
The retinal screening service examines the retinal photographs of nearly all diabetic patients in the UK, and terms this degree of retinopathy 'R1'.
Maculopathy (M1)
In older patients the retinopathy progresses first to damage the centre of the retina, termed the macula, with microaneurysms, haemorrhages, and exudates. 
Later oedema (leakage in the macula) develops; the retina becomes waterlogged like a sponge, termed diabetic macular oedema (DMO). The leaky fluid is similar to blood serum, ie. blood without the red cells. 
The oedema is seen easily with an optical coherence tomography (OCT) scan as thickened retina: the OCT is a camera that produces a three-dimensional picture of the retina. It is mainly this macular disease that causes loss of sight. This degree of retinopathy is termed M1.
Proliferative retinopathy (R3) 
In younger patients the proliferation occurs before the maculopathy. Here the VEGF stimulates the capillaries to start growing, meaning new capillaries grow on the surface of the retina, and forward into the vitreous. These new blood vessels are best seen with retinal photography, but they can be seen by ophthalmoscopy with a very bright ophthalmoscope and a green filter. This is called R3.
Pre-proliferative, also termed non-proliferative (R2) 
This is the stage before proliferation with blot haemorrhages or capillary abnormalities (IRMA, intraretinal microvascular abnormalities). There may be a few haemorrhages (early none-proliferative), or a lot (severe none-proliferative).
Retinal and other complications 
Vitreous haemorrhages are caused when the tiny new blood vessels burst and the blood leaks into the vitreous. Initially they are usually temporary and the blood often clears by itself, but after repeated bleeding the blood takes longer to clear. If there is continued bleeding, retinal/vitreous scar tissue may develop. Blood vessels may grow on the iris and cause rubeotic glaucoma. 
Treatment of retinopathy
Good diabetic control is needed, including lowering glucose levels, blood pressure, and cholesterol, is essential long term, and this will prevent the retinal capillary damage. 
A laser is a very bright focused pulse of light. The patient sits in a darkened room, with anaesthetic drops in the eye, a contact lens is placed on the eye, and pulses of laser are focused onto the retina. The laser is not usually painful, but it can be if a lot is needed.
These are injections of an anti-VEGF drug into the eye, in a clean room in an outpatient clinic. Repeated treatment is usually needed, guided by the retinal thickness on the OCT examination four weeks after the injection. As the treatment has only just been introduced in the UK, we are learning how to use it.
Sometimes the injection is a little painful. There is a one in 1,000 risk of a very serious infection in the eye (endophthalmitis) after each injection, and patients are warned if they get cloudy vision one to five days after the injection, they must attend an eye emergency clinic within 30 minutes.
Treatment of different types of retinopathy
Background retinopathy/early non-proliferative
No treatment is needed to the eye. All patients not attending the eye clinic need yearly retinal examination with photographs, carried out by the UK retinopathy screening program.
Treatment of macular oedema
This needs to be treated early otherwise the leakage increases. Gentle laser may reduce the oedema after one to two years. However, anti-VEGF injections help reduce the oedema dramatically in most patients, and they have only been approved by the National Institute of Health and Care Excellence (NICE) for general use in the last year.
If the leakage is untreated, then there will be permanent damage to retinal cells, which cannot be repaired and causes reduced sight. Anti-VEGF injections only reduce leakage and do not repair this damage.
We know that if we start anti-VEGFs early, we can maintain good sight in the long term, which we cannot not achieve with laser, or if treatment is started late. NICE recommends that we have to wait until 400 microns of retinal thickness occurs before anti-VEGF treatment is started, and earlier treatment may be more effective.
Treatment of severe non-proliferative and proliferative retinopathy
Laser of the peripheral retina is very effective, and this has to be given on repeated occasions. Often the new blood vessels grow until all the peripheral retina is lasered, requiring 6-10 laser sessions. If laser is delayed, vitreous haemorrhages occur (see complications). Anti-VEGF's reduce new vessel growth dramatically for a few weeks, whereas laser works long-term. Currently patients are receiving less laser and lighter laser and more anti-VEGF injections than previously used.
Retinal Surgery
Surgery to remove the blood may be needed if there is a dense vitreous haemorrhage and it does not naturally clear. The surgery includes removing the vitreous (vitrectomy) and replacing it with a salt solution. Retinal detachments may need surgical repair.
Legacy effect
We know that high glucose levels one year may cause retinal damage even 30 years later. This may explain why some patients with perfect diabetic control still develop retinopathy; they may have had high glucose levels years previously, sometimes undetected. However, generally after three years of good diabetic control the retinopathy progression rate slows considerably.
There is also a genetic contribution, as we know that not everyone with poor diabetic control will develop retinopathy. Similarly, patients with a strong family history of heart disease will develop more severe retinopathy.
Sudden decrease in HbA1c
A sudden improvement in control (HbA1c drop of 3% [33mmol/l]) often leads to a temporary rapid increase in progression of retinopathy; laser or anti-VEGF treatment may be needed. Nevertheless, a low HbA1c is essential for good vision, so despite this temporary deterioration, a low HbA1c will be very helpful.
Sight in diabetic retinopathy
Good vision depends mainly on the health of the macula. If there is macula oedema or scarring, central vision will be reduced and the patient will find it difficult to see small print and see faces and drive. Damage to the fovea will limit detailed vision.
There may be very aggressive retinopathy, with many new vessels for instance, yet if the macula has no oedema sight will be good: this is why retinal photographic screening is so important.
If there is a vitreous haemorrhage, a minor haemorrhage is seen as black veils moving in front of the eye, but with a dense haemorrhage everything is dark and obscured. If the retina is detached the patient may become blind.
Cataracts are also common. The lens becomes cloudy, causing misty or very misty vision. Cataract surgery is usually straightforward.
Laser burns enlarge after many years, and this can reduce sight when heavy laser was given in the past (lighter laser is used now). This can reduce central vision or cause lots of glare. 
People with 6/18 vision or worse cannot legally drive. Patients with macular oedema can drive if their vision is good (at least 6/12 and preferably better).
Occasionally patients who have needed a lot of laser may lose side vision may not be able to drive at all, or may be safe just to drive only during daylight. Sunlight causes glare, and although cataract surgery may help, glare from retinal damage does stop some patients driving, especially at night.
A vitreous haemorrhage may make driving unsafe until it clears. People can legally drive with only one good eye, but if the sight is lost in one eye one day, perhaps from a haemorrhage, a time of adjustment is needed. It is not safe or legal for a patient who has had their first vitreous haemorrhage one day to drive the next - they have to get used to the reduced sight first.
Other diabetic complications
Patients with retinopathy may have neuropathy, reduced kidney function, hypertension, impotence, amputations, or reduced cognitive function, and good diabetic control can prevent most of these problems.
We really need to act at all levels, preventing diabetes, detecting diabetes early, detecting retinopathy in diabetes patients, controlling diabetes glucose and blood pressure levels, and starting anti-VEGF treatment and laser early. So first we need to keep thin and exercise to prevent diabetes in the first place. Next, we need to screen non-diabetics in order to detect diabetes early before diabetic complications develop (two to three-yearly HbA1c checks). 
Once people have diabetes, they need low HbA1c and blood pressure levels and yearly retinal photographic screening for retinopathy. This is effective detecting retinopathy needing treatment, but currently eye clinics do not have enough capacity for all the patients who need it.
The Future
We know diabetic retinopathy can be prevented, and yet people continue to lose sight from the condition, so priority should be given to prevent diabetes itself. Yet we are all becoming more overweight, so until our society addresses this, diabetes will increase.
In Iceland, sight loss from retinopathy has been prevented by good organisation of the health service, so we know we can prevent most patients from losing sight. We need much more effective treatment for diabetes, such as easier ways for patients to test blood glucose levels and deliver insulin. Finally, we need to use the best treatment: anti-VEGF injections help, and eye clinics need more capacity, and a long-acting anti-VEGF drug is needed.
1. The Royal College of Ophthalmologists. Diabetic Retinopathy Guidelines. London: RCO; 2012.