PROLIFERATIVE DIABETIC RETINOPATHY
Proliferative diabetic retinopathy (PDR) refers
to a severe stage of diabetic eye disease in which new blood vessels
proliferate on the surface of the retina. Most patients with PDR have
had background diabetic retinopathy
for at least a few years prior to developing the proliferative form of
the disease. The diagnosis of PDR requires the presence of new
proliferating blood vessels (neovascularization) arising from the retina
or optic disc and growing on the retinal surface or into the vitreous
cavity. This diagnosis is made primarily by examination of the retina
and sometimes by fluorescein angiography.
The photograph on the left shows a tuft of
neovascularization (arrowhead) extending from the optic nerve head into
the vitreous cavity. These new vessels take on a frond-like
configuration as they grow, similar in appearance to a sea fan. The
photograph on the right is a fluorescein angiogram of a different
patient showing a frond of vessels (arrowhead) extending from the disc.
Neovascularization leaks fluorescein dye (white in this photograph),
giving it a fluffy appearance.
The most likely cause for the
neovascularization in PDR is ischemia (decreased blood supply) of the
retina. In diabetes, multiple small patches of the retina lose their
blood supply because of closure of retinal capillaries. As these patches
of the retina are deprived of oxygen and nutrients, they probably
produce a chemical signal: a vessel-producing or vasoproliferative
factor. This factor diffuses into the vitreous cavity, and stimulates
growth of new vessels throughout the retina and on the iris. A growth
factor has been isolated from the vitreous of diabetic patients that can
produce this neovascular response in otherwise normal animal eyes. These
stimulating factors may be opposed by other growth factors that inhibit
new vessel growth. However, when enough segments of the retina have been
deprived of their blood supply and are producing vasoproliferative
factors, the balance is tipped toward new vessel formation.
The rate of growth of these new vessels can be
quite variable. Some patients have rapid growth over a few weeks, while
other show little or no change in the new vessels over months or years.
This variability may have to do with the balance between proliferative
and inhibitory growth factors in the eye.
If allowed to progress unchecked,
neovascularization tends to go through a "life cycle" of
growth, fibrosis, and regression. Over time, the fronds of tiny, fine
new vessels gradually become larger and more mature. Cells called
fibroblasts grow along with the new vessels. The fibroblasts lay down
collagen fibers, producing a fibrovascular complex. Eventually, the
newer vessels tend to regress, leaving behind the fibrous tissue and the
larger, more mature vessels.
COMPLICATIONS OF PROLIFERATIVE DIABETIC
RETINOPATHY
This neovascular response in a retina that
needs more blood supply may sound like a positive effect. However, the
new blood vessels are not necessarily in the same location as the
ischemic part of the retina. Also, the new vessels tend to be very
fragile and may bleed, filling the eye with blood. When these vitreous
hemorrhages occur, patients notice black or red "strings" or
"cobwebs" in the vision. As the blood disperses through the
vitreous cavity, the vision becomes blurred or dim. If enough bleeding
occurs, the vision is seriously impaired.
The eye is able to clean this blood out of the
vitreous cavity as long as there is not too much blood. Some of the red
blood cells diffuse forward into the anterior portion of the eye and are
removed through the normal drainage apparatus, the trabecular meshwork.
White blood cells probably also travel into the vitreous, ingest old red
blood cells, and carry them away. Both of these processes are slow, and
the speed at which the blood is removed can be quite variable from
patient to patient. A small amount of blood in the vitreous can
sometimes be removed in a few weeks, whereas larger hemorrhages may take
months or years to clear. In cases of dense blood or multiple recurrent
hemorrhages, the vision may not return because of residual inflammatory
debris and dead cells that cannot be removed. Vitreous hemorrhage is a
concern not only because of the poor vision, but also because of the
poor visibility into the eye. With the eye full of blood, it is
difficult or impossible for the ophthalmologist to tell if the
proliferating vessels are continuing to grow and if they are damaging
the retina with traction or scarring.
One of the most feared complications of
diabetic eye disease is traction retinal detachment. As mentioned above,
the new vessels tend to lay down fibrous scar tissue as they grow and
then regress. Like any scar, this fibrous tissue contracts or shrinks as
it matures. If the neovascularization is on the surface of the retina,
the contraction of the fibrous scar may produce some distortion of the
retina. Vessels that grow out into the vitreous cavity develop adhesions
between the fibrovascular complex and the collagen fibers that make up
the vitreous gel. When the vitreous separates away from the retina (a
normal aging change) or when the fibrous scar contracts, the scar tissue
pulls on the retina, producing traction that can distort or detach the
retina. These traction detachments can be limited and have little effect
on the vision, or they may be extensive and cause complete blindness.
Once the central part of the retina has detached, the chance of getting
good vision back is low, even is the retina can be successfully
re-attached. For this reason, the emphasis in diabetic eye care should
be on prevention and early treatment whenever possible.
TREATMENT OF PROLIFERATIVE DIABETIC RETINOPATHY
When neovascularization is seen on
ophthalmologic exam, laser treatment should be considered. Cases in
which only very small tufts of new vessels are seen can be watched
closely without treatment, since the new vessels may not continue to
grow. However, most patients with new vessels should undergo a laser
treatment known as panretinal photocoagulation (PRP). PRP involves
extensive treatment with an argon or diode laser to the peripheral and
middle portions of the retina. The central or macular region is not
treated, since this would likely cause serious loss of vision. This PRP
is usually done in the office without anesthesia, although some patients
have pain and require an anesthetic injection near the eye for pain
relief. The initial treatment usually consists of approximately
1500-2000 spots of laser per eye. This is done in two or more sessions,
since it can be dangerous to the eye to give more than 1000 spots in a
single session. The vision is usually poor immediately after the
treatment, but recovers to the pre-treatment level within a few hours.
![[Photograph of PDR and laser
scars]](prpscar.jpeg)
This is a color
photograph of an eye with proliferative diabetic retinopathy and laser
scars. There is a large frond of neovascularization (large arrowhead)
extending from the optic nerve head. Multiple laser scars (small
arrowhead) can be seen throughout the retina, except for in the macular
region. (The laser scars in this patient are closer to the center of the
retina than usual).
Panretinal photocoagulation probably works by
reducing the level of vasoproliferative factors produced by the ischemic
retina. This is thought to be accomplished by two mechanisms. First,
laser treatment destroys small patches of ischemic retina, reducing the
oxygen demand of the retina and reducing the production of
vasoproliferative growth factors. Second, the laser thins the pigmented
tissue under the retina, allowing more oxygen to diffuse in from the
vessels under the retina. Microelectrode studies have shown higher
levels of oxygen in the vitreous directly over a laser scar than in the
vitreous over adjacent untreated retina. By increasing oxygen supply and
decreasing demand, the stimulus for new vessels is reduced, and the
neovascularization tends to shrivel up and go away. The larger, more
mature vessels do not always regress, and the fibrous scar tissue
persists despite the laser treatment, so early detection and treatment
are advantageous.
Laser treatment of neovascularization is a
titration effect; there seems to be a threshold above which new vessels
will form and below which new vessels will regress. For any individual
patient, this means that careful observation is necessary. If the
vessels do not regress with the initial treatment, further treatment is
needed. If the vessels regress, but then begin to grow again after
months or years, more treatment is indicated.
Although PRP is helpful in causing regression
of neovascularization, it will not destroy scar tissue that has formed,
and it cannot be done through dense vitreous hemorrhage. A surgical
procedure known as a vitrectomy can be performed to remove blood and
debris from the vitreous cavity and to re-attach the retina in cases of
traction detachment. In a vitrectomy, three small (1 mm) incisions are
made into the eye. Through one of these incisions, an infusion cannula
is placed and sutured into place. This allows constant infusion of
saline solution to keep the eye inflated at the proper pressure. A
fiberoptic light source is inserted through one incision, and a
suction/cutter device through another. The suction/cutter has a small
port with a rotating or sliding blade inside. Vitreous gel and blood are
sucked into the port, cut off by the blade, and removed from the eye.
The surgeon watches through a contact lens on the eye, looking through a
microscope. After the blood and vitreous are removed, any additional
treatment needed can be performed, including laser treatment, cautery of
bleeding sites, and removal of scar tissue.
Vitrectomy is a very useful procedure, but it
does have potential risks and complications. There is a 5% risk of
retinal tears or detachments caused by the procedure itself, which may
necessitate further surgery. There is a 10%-40% risk of visually
significant cataract in patients who have not already had cataract
surgery. Also, in diabetics, there is a 20-30% risk of recurrent
bleeding in the eye in the first few days following the surgery. This
recurrent bleeding tends to clear more quickly then the initial
hemorrhage, and usually does not require further surgery, but does slow
the return of vision. For these reasons, vitrectomy is used only when
the potential risks are outweighed by the benefits expected. In cases
with relatively mild hemorrhage, patients are often better off waiting
for the blood to clear on its own, despite the inconvenience of
decreased vision for several months. In cases where the blood has not
cleared spontaneously in 4-6 months, or where waiting would be dangerous
due to retinal detachment or untreated progressing neovascularization,
early surgery is indicated.
The Country Hills Eye Center Home Page
Dr. Scott C. Richards Main Page
For information regarding the
Country Hills Eye Center phyician
specializing in retinal and diabetic eye diseases
www.countryhillseyecenter.eyemd.org
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