Proliferative Retinopathy

• what is proliferative retinopathy
• some details
• description of events
• laser
• severe proliferative retinopathy
• early vitrectomy in severe proliferative retinopathy
• diabetes is not forgiving
• targets for diabetic control
• Without laser
• photos
• See Animation.
• Avastin
• When stable can be discharged

What is proliferative retinopathy

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

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.

Drugs are being tried out that block VEGF and stop it working, and are starting to be used. Ophthalmologists are not yet sure how to use these new drugs.

 

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 ^ laser burns ^ oxygen and nutrient flow to retina improves ^ new vessels close up ^ more diabetes damage to retina ^ more new vessels grow ^ more laser needed ^ new vessels close up ^ and so on until eventually they stop growing

 

Laser Treatment

We believe laser works as 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 is 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 9%) (Case 39).

Avastin injections into the eye can be very helpful, but effects may be temporary.

 

Severe proliferative retinopathy

If you have the severest type of proliferative retinopathy, a lot of laser is needed over the years. As a result, your side vision and night vision may be badly affected.
Often the best result that can be achieved in 2007 is maintaining good (perhaps not perfect) central vision, enabling you to work, watch TV, and read.

If the blood vessels continue to grow despite 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.

 

Early vitrectomy in severe proliferative retinopathy

There are many reports that early vitrectomy can help patients with severe or very active proliferative retinopathy (cases presented EASDec 2010 and many previous years). Most growth factors are released from the retina, and are reduced by laser and anti-vegf treatment, but the growth factors are released into the vitreous. The vitreous acts like a back of growth factors, and so if the retina is lasered but the new vessels remain, then this is probably because of vitreal growth factors, and if the vitreous is removed the neovascularisation will regress. The same may apply to macular oedema...if this remains despite lots of laser (in patients who have had extensive laser for proliferative retinopathy), early vitrectomy may be helpful. There are many case reports supporting this, but not large studies.

Nevertheless, very few experts recommend early vitrectomy, but perhaps we should. This is probably because of the uncertain outcome of vitrectomy (see).

 

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.

 

Targets

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

 

Without laser

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

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

before laser   enlarge	before laser   enlarge

after laser   enlarge	after laser   enlarge
see this case; also, see case 3 to zoom in a similar case

the laser burns    enlarge	the laser burns enlarge

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  

 

Avastin

Avastin injections into the eye can be very helpful, but effects may be temporary. Avastin is an anti-VEGF drug. By blocking the effect of VEGF, Avastin stops the new vessels growing for a while. Repeated injections may be needed, and laser is strongly recommended in a

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.
Avastin is not considered safe alone...laser must be given also, but nearly all retinopathy experts would like to have access to Avastin 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).

 

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.