www.diabeticretinopathy.org.uk

Proliferative Retinopathy

David Kinshuck

 

What is proliferative retinopathy?

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Enlarge  side view: in proliferative retinopathy 'new blood vessels' grow on the surface of the retina and can bleed.

 

In this condition very small blood vessels grow from the surface of the retina.

The retina is the film at the back of your eye , and the tiny blood vessels are capillaries. These growing blood vessels are very delicate and bleed easily. Without laser treatment, the bleeding causes scar tissue that starts to shrink and pull the retina off, and the eye becomes blind. Laser treatment prevents blindness, but often some vision is lost.

If you have had diabetes for years your retinae may develop this condition. As the retina is damaged by diabetes, the diseased retina releases special growth chemicals. These chemicals make tiny blood vessels grow: these are called 'new blood vessels'.
See Animation, case with obvious new vessels,   photo , photo

 

Some details

new vessles grow in proliferative retinopathy

Enlarge New blood vessels growing on the retinal surface and slightly in front of the surface.

The new vessel growth in diabetes only occurs in the retina, nowhere else in the body. When a retina becomes damaged by a higher than normal sugar, over many years, it seems to release special growth hormones.

VEGF is one of the main growth hormones; VEGF stands for Vascular Endothelial Cell Growth Factor. It seems to be manufactured and released by 'sick' retinal capillaries, and in turn makes other capillaries grow. This seems to be an exaggeration of one of the body's normal responses.... the retina becomes starved of nutrients, and then the retina makes chemicals that make new blood vessels grow to deliver more nutrients.  There are other growth factors and processes involved.

 

Description of events in proliferative retinopathy

 

the mechanism of proliferative retinopathy (start at top) with laser treatment

diabetes for years
^
retinal damage
^
retina releases growth chemicals
^
'new vessels' grow
^
anti-VEGF or laser
^
oxygen and nutrient flow to retina improves
^
new vessels close up
^
more diabetes damage to retina
^
more new vessels grow
^
more anti-VEGF or laser
^
new vessels close up
^
and so on until eventually they stop growing

 

The treatment: anti-VEGF injections, good diabetic control, and not smoking, and laser.

 

Laser Treatment

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Enlarge Laser burns for proliferative retinopathy. 500-1000 burns in a typical session

Laser is the only treatment if anti-VEGF injections are not available.

The tiny laser burns allow more oxygen and nutrients to reach the retina, and this improves the retinal circulation. The retina then stops making the growth substances, and the 'new vessels' close up as a result. NEJM 11

Deterioration may be rapid if the control of your diabetes suddenly improves: see rapid progression.

Laser was the main way of treating this condition. With laser the new vessels will usually stop growing, although sometimes several laser sessions are needed.

The new vessels do usually close up, but may start growing again 4-8 months later, and requiring more laser. 2-3000 or so light laser shots are applied at each session to each eye(see Laser Treatment), but in the average insulin-dependant person about 5 sessions may be needed. See photos. After laser, regular examination is needed. This patient has persistent retinopathy, but an angiogram showed there were no new vessels. (HbA1c 75mmol/l [9%]) (Case 39).

 

Anti-VEGF injections

Recent reports indicate these should be used in most cases Retina17. DCRnet S    Patients should be told they are not funded by the NHS if there is no macular oedema, but results are better than laser.

The anti-VEGF injections should be started as soon as possible. Patients with more aggressive disease may also need laser. They will reduce the proliferation without causing retinal scarring or epiretinal membrane formation. There were reports that traction increases, but this is not the case, only the condition causes the traction: they can be safely given if there is traction,  Bressler, Seminar, 2017 DRCRnet 16 . New results indicate that treatment with anti-VEGF injections without much laser may produce the best visual outcome, as laser tends to cause retina scarring   Clarity study 2017.

Each one anti-VEGF injection   will have temporary effect, and monthly treatment may be needed, especially for a while. Retina 14 Oph 15Jama 15.   At least 5/each eye injections are generally needed he first year, but fewer are needed after that. At present, NICE guidelines only recommend anti-VEGF injections if there is more than 400µ macular oedema, although some hospitals are able to offer Avastin treatment which is very effective.

Most diabetic retinopathy specialists considers this guideline inappropriate, as anti-VEGF injections are highly effective. IJO 16

 

 

Severe proliferative retinopathy

sever retinopathy needs 6000 or more laser burns

Enlarge Extensive laser is needed for some people with proliferative retinopathy

If you have the severest type of proliferative retinopathy, a lot of Anti-VEGF injections and/or laser will be needed over the years. As a result, r side vision and night vision may be badly affected.
In 2016 with Anti-VEGF injections we are likely to get much better results than we did previously, and none smokers detected early (unless control is very poor indeed) should be expected to keep good vision. Many patients with type 1 diabetes may benefit from an insulin pump, and these may be necessary to achieve the best results.

If the blood vessels continue to grow despite Anti-VEGF injections or laser they may bleed, causing haemorrhages such as this subhyaloid haemorrhage.

More bleeding causes vitreous haemorrhages. These is make it difficult seeing..like looking through cobwebs.

A fluorescein angiogram will detect the areas of non-perfusion, but these can be estimated clinically. An angiogram is therefore seldom required prior to laser for proliferative retinopathy see. In any respect, the laser treatment does not have to be precisely applied in any particular section of retina.  See also and here if maculopathy is present as well as proliferation...new drugs are being used.

 

Diabetes is not forgiving

Good control of your diabetes is important if you want to keep your sight. Unfortunately retinopathy can still affect people who have tried really hard to control their diabetes. Doctors treating people with retinopathy know that their patients have tried really hard, but the condition can be really vicious. There are some genetic factors that make it more likely for some people to get proliferative changes than those that don't, but as we cannot get new genes we have to make the most of what we have.

We now believe that if you can reach these targets below, and do not smoke, the conditions has every chance of stabilising and you will need much less laser than you would have otherwise. Conversely we know that if someone's diabetes diabetes is very badly controlled, the eye disease can be very severe indeed.  Renal failure is a risk factor Retina16.

 

Targets

Controlling the diabetes is critically important in the long term. see

 

Without anti-VEGF or laser

Without anti-VEGF or laser 10% of patients lose vision each year (see & ETDRS).

graph of visual result with/without laser

Laser may not keep all sight, but unless's your diabetes has been very badly controlled or the laser was started very late, it will keep most of your sight (see). The benefits of  laser last all your life.

 

Photos

disc new vessels...proliferative retinopathy

before laser  enlarge

disc new vessels...proliferative retinopathy

before laser  enlarge

 

 

 

 

 

 

 

 

disc new vessels have regressedafter laser  enlarge

disc new vessels have regressed  after laser  enlarge

 

see case 3 to for a similar case

 

This patient presented late, and his new vessels remain despite laser, indirect laser, and IVT.  Vision on presentation was 6/60 & 6/9, and has deteriorated to 6/60 & 6/36 despite treatment. He is awaiting his first dose of Avastin. enlarge  

laser burns for proliferative retinopathy

  the laser burns   enlarge

laser burns for proliferative retinopathy

the laser burns  enlarge

 

 

Anti-VEGF: Avastin, Lucentis, Eyelea and steroid implants

Anti-VEGF: Avastin, Lucentis, Eyelea injections into the eye can be very helpful, but effects may be temporary. Anti-VEGF drugs block the effect of VEGF, and stop the new vessels growth for a while. Repeated injections may be needed, and laser is strongly recommended in addition (initial anti-VEGF treatment helps Retina15).

Even without laser, new vessels disappear in a few days, but unless there is adequate laser they always seem to reappear. Even with laser, they may reappear. Nevertheless, Avastin should prove extremely helpful. Few Primary Care Trusts will fund treatment in the UK. We had a few patients funded and could see the effects, but now funding has been withdrawn.

In this paper complete laser was given, but the new vessels continued to grow. The Avastin was then given after the laser was completed. Given in this way the Avastin was effective if given every 3 months.
Anti-VEGFs are not considered safe alone...laser must be given also, but nearly all retinopathy experts would like to have access to Anti-VEGFs for certain stages of proliferative retinopathy, particularly reducing the new vessel growth whilst waiting for the laser and good diabetic control to take effect (see 2010).

Iluvien, a steroid implant , will also prevent or help to resolve proliferation.

 

When stable can be discharged

After 3 years of no laser or new vessel growth, and if there are no/very few retinal haemorrhages, patients can be discharged from the clinic. Photographic monitoring is best restarted, in a screening program. Such patients also need to be checked for glaucoma (at their optometrists, yearly checks), and many will develop cataracts.

When lots of laser has been needed and the retinopathy stabilises, so there are no haemorrhages/exudates/oedema, the condition is stable, termed 'burnt out'.

On the other hand, when lots of anti-VEGF treatment has been given and the haemorrhages etc disappear, the condition may reactivate unless the diabetic control has improved a lot. Such patients need to be monitored regularly, and in the UK this will usually be in the diabetic retinopathy screening program with regular photographs.

burnt out diabetic retinopathy

Right eye (top) enlarge.                                        Left eye( bottom)

Lots of laser, few haemorrhages or exudates. OCT shows slight retinal atrophy but no oedema. The retinopathy is nearly stable, and unless the diabetic control is poor, is unlikely to change. Cataracts may develop, and rarely glaucoma: optometry checks /diabetic screening service review) are needed yearly. There is one haemorrhage at the left fovea. Vision 6/12 both eyes.

See Eye 14   

Abbreviations