Diabetic Retinopathy is a potentially blinding complication of diabetes that damages the eye's retina. The retina is a thin membrane located in the inside of the eye, adhered to the wall of the eye like "wallpaper" and that acts like the film of a camera, capturing the image that will be transmitted to the brain through the optic nerve. The macula is the central area of the retina. We use the macula to see details, colours, read small print and discriminate faces, between others. Diabetic Retinopathy can affect half of all patients diagnosed with diabetes.

Diabetic Retinopathy occurs when Diabetes Mellitus damages the blood vessels in the retina impairing its oxygenation and nutrition.

Some patients with Diabetic Retinopathy develop a condition called Macular Oedema, which occurs when the damaged blood vessels leak fluid onto the macula. The leaked fluid makes the macula swell and this in turn blurs the central vision.

As the Diabetic Retinopathy progresses, it enters its advanced or proliferative stage where new and abnormal blood vessels grow along the retina and use the gel-like vitreous that fills the inside of the eye as scaffolding.

There are two different types of Diabetic Retinopathy:

Non-proliferative Diabetic Retinopathy (NPDR)

Non-proliferative diabetic retinopathy is the early stage of diabetic retinopathy. In this stage, tiny blood vessels in the retina outside the macula leak blood and fluid.

People with non-proliferative diabetic retinopathy may experience no visual symptoms. However, those who do experience problems are those who develop macular oedema or macular ischaemia.

Macular ischaemia occurs when small blood vessels that nourish the macula close off leading to cell death with irreversible blur or loss of central vision.

Proliferative Diabetic Retinopathy (PDR)

Proliferative diabetic retinopathy is the more severe stage of the disease when abnormal blood vessels grow along the retina or optic nerve head. In PDR much of the circulation of the retina closes down and abnormal blood vessels grow into the retina in an attempt to compensate for the reduced blood flow. These abnormal vessels unfortunately do not adequately compensate the reduced blood flow, are often fragile and may bleed. Scar tissue usually develops along these new vessels. When the scar tissue contracts it can cause the retina to pull away from the wall of the eye – causing Retinal Detachment or Vitreous Haemorrhage (bleeding into the jelly of the eye).

As abnormal blood vessels can grow in any part of the retina, both central and peripheral vision can be affected by Proliferative Retinopathy.

As a result of Vitreous Haemorrhage, vision can become markedly reduced as the retina is being blocked. Blood can generally clear up over several months. Vitreous haemorrhage is generally removed surgically if it has not cleared within 3 to 6 months. The surgery to remove a vitreous haemorrhage is called Vitrectomy. During this surgery, the vitreous gel, blood and scar tissue can be removed from the eye and replaced with a clear solution. Mr Stanga will carry out this surgery if necessary.

Laser photocoagulation, intravitreal Kenalog® (steroid: Triamcinolone) and surgery, independently form each other or in combination, are the NHS standard treatments for Proliferative Diabetic Retinopathy and/or Macular Oedema.

Refractory Macular Oedema affects vision but does not respond adequately to the usual treatment methods. Without effective treatment, vision loss could progress and become permanent.

A molecule, called Vascular Endothelial Growth Factor (VEGF), tends to be released in eyes that have ischaemia. VEGF is thought to stimulate the growth of abnormal, leaking blood vessels that grow on the retina leading to either PDR and/or Macular Oedema.

Pan-retinal photocoagulation aims at ablating or burning and therefore destroying the areas of ischaemic retina which induce the formation of VEGF.

Mr Stanga photocoagulates using the new OptiMedica PASCAL® Pattern Scan Laser Photocoagulator system.

The PASCAL® laser uses a semi-automated pattern generation method. As many as 25 spots can be delivered in 0.5 sec. This new system significantly reducing both treatment time and patient discomfort. The PASCAL® laser may allow for more rapid, precise, and safe treatment. One thousand burns can be carried out within an average time of four minutes and generally more confortably for the patient than when using standard single spot argon lasers. Laser photocoagulation remains the most widely used primary treatment for PDR and macular oedema for the time being.

Mr Stanga is currently indicating either Lucentis® or Avastin® as anti-VEGF drugs.

It is possible that the pre-operative intraocular injection of anti-VEGF drugs can reduce the risk of intraoperative bleeding during surgery while attempting to severe abnormal new vessels or scar tissue, any intraocular bleed in the immediate post-operative period as well as reducing any pre-existing macular oedema.
 
If, after extensive discussion with Mr Stanga, it is decided that preoperative anti-VEGF is the best way forward for you then Mr Stanga will inject intraocularly an anti-VEGF drug (either Lucentis® or Avastin®) 1 week prior to the surgery to the eye where a vitrectomy has been. See AMD section for more details on anti-VEGF drugs.

If you are having anti-VEGF treatment, please inform Mr Stanga if you are pregnant as we don’t yet know whether these drugs are safe for an unborn baby. If necessary, we can draw a blood specimen from your arm vein to determine if you are pregnant.

It is sometimes necessary to carry out investigations both initially and at regular intervals. The most commonly requested tests are fundus fluorescein angiography (FFA) and Optical Coherence Tomography (OCT).

During FFA a dye injected into a vein in the patient's arm and flash photographs are obtained through dilated pupils. FFA provides a detailed view of the macular blood vessels.

OCT is a non-contact test that is analogous to ultrasound but uses near-infrared light instead of sound to images the macula by means of cross-sectional images similar to a histopathological microscope section. OCT can be very useful to determine the presence or absence of fluid, objectively determine the retinal thickness and response to treatment.

Lucentis® has been used in approximately 3000 patients for the treatment of age-related macular degeneration. Studies in approximately 1300 patients have so far shown that Lucentis® is effective and well tolerated.

Intravitreal injection of Avastin® has been shown to induce regression of diabetic retinal as well as iris neovascularisation (NV).  A retrospective review conducted in the United States of America of consecutive patients receiving intravitreal Avastin® for PDR at two clinical practices (26 patients) showed no significant ocular or systemic side effects. All patients demonstrated reduction or absence of angiographic leakage of NV following injection, sometimes within 1 day. The NV also appeared to involute in most patients with a dramatic reduction in the calibre of perfused blood vessels. In some patients, a subtle reduction in leakage of iris or retinal NV was observed in the fellow or uninjected eye. This short-term study demonstrated proof of principle that intravitreal Avastin® can cause at least short term regression of retinal and iris NV secondary to PDR.

POSSIBLE BENEFITS OF AVASTIN® AND LUCENTIS® AND “OFF-LABEL” STATUS OF AVASTIN®

Avastin® was not initially developed to treat PDR.  Based upon the results of clinical trials that demonstrated its safety and effectiveness, Avastin® was approved by the Food and Drug Administration (FDA) in the United States of America (USA) for the treatment of metastatic colorectal cancer.  As a condition of approval, the manufacturer produced a “label” explaining the indications, risks, and benefits.  The label explains that Avastin® works by blocking a substance known as VEGF.  Blocking or inhibiting VEGF helps prevent further growth of the blood vessels that the cancer needs to continue growing. 

Once a device or medication is approved by the FDA, physicians in the USA may use it “off-label” for other purposes if they are well-informed about the product, base its use on firm scientific method and sound medical evidence, and maintain records of its use and effects.  Ophthalmologists are using Avastin® “off-label” to treat Age-related Macular Degeneration (AMD) and similar conditions since research indicates that VEGF is one of the causes for the growth of the abnormal vessels that cause these conditions.  Some patients treated with Avastin® had less fluid and more normal-appearing maculas, and their vision improved.  Avastin® is also used, therefore, to treat macular oedema, or swelling of the macula secondary to conditions other than AMD. 

Recently, a medication similar in function and designed for intravitreal administration Lucentis®, was approved by the FDA in the USA for the treatment of AMD and is currently licensed in the United Kingdom (UK) for the treatment of AMD via intravitreal injections. Please note that Lucentis® was not initially developed to treat PDR nor Diabetic Macular Oedema.

The goal of treatment is to prevent further loss of vision. After the pupil is dilated and the eye is numbed with anaesthesia, the medication is injected into the vitreous, or jelly-like substance in the middle of the eye.

Click here for more information on Diabetic Retinopathy

COMPLICATIONS FROM THE MEDICATION AND INJECTION

Complications when Avastin® is given to patients with cancer

When Avastin® is given to patients with metastatic colorectal cancer, some patients experienced serious and sometimes life-threatening complications, such as gastrointestinal perforations or wound healing complications, hemorrhage, arterial thromboembolic events (such as stroke or heart attack), hypertension, proteinuria, and congestive heart failure. 

Patients who experienced these complications not only had metastatic colon cancer, but were also given 400 times the dose you will be given, at more frequent intervals, and in a way (through an intravenous infusion) that spread the drug throughout their bodies.

Complications following Lucentis®

The prescribing information for intravitreal Lucentis® contains a warning about arterial thromboembolic events:  “Although there was a low rate (<4%) of arterial thromboembolic events observed in the LUCENTIS clinical trials, there is a theoretical risk of arterial thromboembolic events following intravitreal use of inhibitors of VEGF.

Genentech, the company that manufactures bot Avastin® and Lucentis®, has advised ophthalmologists “of a higher incidence in one LUCENTIS study of strokes in the 0.5-mg dose group compared with the 0.3-mg dose group (1.2% versus 0.3%, respectively; P=0.02).”

One study showed that patients who have had a stroke are at greater risk of having one again. The causal relationship between Lucentis and strokes is unclear, and patients with AMD are already at risk for stroke.

It must be noted that whenever a medication is used in a large number of patients, a small number of coincidental life-threatening problems may occur that may have no relationship to the treatment. 

Risk when Avastin® or Lucentis® is given to treat patients with eye conditions

Ophthalmologists believe that the risk of these complications for patients with eye conditions is low.  Patients receiving Avastin® for eye conditions are healthier than the cancer patients, and receive a significantly small dose, delivered only to the cavity of their eye.  While there are no randomised controlled trials about the use of Avastin® in the eye that prove it is safe and effective, Lucentis®, a similar drug, was recently licensed for AMD. One study of patients who received Avastin® through an intravenous infusion reported only a mild elevation in blood pressure.  Another study of patients treated like you will be with intravitreal Avastin® (that is, Avastin® injected into the eye) did not have these elevations or the other serious problems seen in the patients with cancer. 

However, the benefits and risks of intravitreal Avastin® or Lucentis® for eye conditions are not yet fully known.  In addition, whenever a medication is used in a large number of patients, a small number of coincidental life-threatening problems may occur that have no relationship to the treatment.  For example, patients with diabetes are already at increased risk for heart attacks and strokes.  If one of these patients being treated with Avastin® or Lucentis® suffers a heart attack or stroke, it may be caused by the diabetes and not the Avastin® or Lucentis® treatment.

There is the risk that Avastin® or Lucentis® reduce even further the blood supply in eyes suffering from conditions where the blood supply is already compromised, such as diabetic retinopathy or central or branch retinal vein occlusion.

Known risks of intravitreal eye injections

Your condition may not get better or may become worse.  Any or all of these complications may cause decreased vision and/or have a possibility of causing blindness.  Additional procedures may be needed to treat these complications.  During the follow up visits or phone calls, you will be checked for possible side effects and the results will be discussed with you.

Possible complications and side effects of the procedure and administration of Avastin® include but are not limited to retinal detachment, cataract formation (clouding of the lens of the eye), glaucoma (increased pressure in the eye), hypotony (reduced pressure in the eye), damage to the retina or cornea (structures of the eye), and bleeding.  There is also the possibility of an infection inside the eye infection (endophthalmitis).  You will receive eye drops with instructions on when to use them to reduce the possibility of this occurring.  Any of these rare complications may lead to severe, permanent loss of vision or blindness and in extreme cases, even loss of the eyeball. You may require to be admitted into hospital for treatment that could include, between others, further injections into the eye or surgery. The prognosis in such event is usually guarded.

Patients receiving an injection of Avastin® or Lucentis® may experience less severe side effects related to the pre-injection preparation procedure (eyelid speculum, anaesthetic drops, dilating drops, antibiotic drops, povidone-iodine drops and the injection of the anaesthetic).  These side effects may include eye pain, subconjunctival haemorrhage (bloodshot eye), vitreous floaters, irregularity or swelling of the cornea, inflammation of the eye, and visual disturbances.

PATIENT RESPONSIBILITIES
You must immediately contact Mr Stanga or his team if any of the following signs of infection or other complications develop: pain, blurry or decreased vision, sensitivity to light, redness of the eye (compared to immediately after the injection), or discharge from the eye. You should not rub my eyes or swim for three days after each injection. Please keep all post-injection appointments or scheduled telephone calls so that Mr Stanga or his team can check for complications.  

Although the likelihood of serious complications affecting other organs of your body is low, you should immediately contact your GP doctor or go to the Accidents and Emergency Room if you experience abdominal pain associated with constipation and vomiting, abnormal bleeding, chest pain, severe headache, slurred speech, or weakness on one side of the body.

As informed by Mr Stanga and his team, symptoms of stroke include sudden changes in vision; sudden numbness or weakness of the face, arm, or leg, especially on one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble walking, dizziness, loss of balance or co-ordination; sudden, severe headache with no known cause.

Please notify Mr Stanga or his team about any of these problems.
           
Please read the section Vitrectomy and posturing if undergoing this type of surgery.

Please remember that each patient is different and the information here provided is only a general guide. If you require further advice or information please contact Mr Stanga or a member of his team.