Neovascular Glaucoma

What is Neovascular Glaucoma?

Neovascular glaucoma (NVG) is a type of secondary glaucoma where new blood vessels form on the iris and in the front chamber of the eye. This condition usually results in poor vision. The new blood vessels form because of low oxygen supply to the back part of the eye, which can be due to various eye and body health conditions. The most usual causes are advanced diabetes-related retinal disease, blockage of the central retinal vein, and reduced blood flow to the eyes, known as ocular ischemic syndrome.

The term ‘neovascular glaucoma’ was first used in 1906 by Coats when he noticed new vessels on the iris of a patient with a blocked retinal vein. Other names for NVG include hemorrhagic glaucoma, thrombotic glaucoma, and congestive glaucoma, and they all refer to the formation of new vessels, increased eye pressure, and growth of connective tissue in the front part of the eye.

NVG is generally resistant to treatment and can significantly affect a person’s vision. The number of NVG cases is increasing, likely due to more people getting diabetes and other diseases that obstruct blood flow in the retina, which include diabetic retinopathy, retinal vein blockage, and ocular ischemic syndrome. Therefore, it’s crucial for all eye specialists to know how to assess and manage NVG well.

What Causes Neovascular Glaucoma?

Neovascular glaucoma, or NVG, is a condition caused by reduced blood flow to the retina or eye. This reduction in blood flow then leads to the formation of new vessels over the iris and the part of the eye called the anterior chamber. There are various reasons why this can happen, and these are divided into different categories:

1. Diseases that limit blood flow to the retina: This includes conditions like diabetic retinopathy; blockages in the central retinal vein or artery and their branches; retinal detachment; retinopathy of prematurity; sickle cell retinopathy and others.
2. Disruptions in blood flow caused by things like cancer treatment or tumors: This includes exposure to radiation (such as photo-radiation, external beam radiation, charged particle radiation like proton and helium ion, and a type of treatment known as plaque brachytherapy) as well as tumors like choroidal, iris, and ciliary body melanoma and retinoblastoma.
3. Conditions that make the blood too thick: Myeloproliferative disorders, which are a group of conditions that make the blood more viscous, are one example.
4. Inflammatory diseases: These include conditions like chronic uveitis and iridocyclitis, Behcet disease, Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia, endophthalmitis, panophthalmitis, Crohn disease, and giant cell arteritis.
5. Eye traumas and certain surgical procedures: This includes carotid endarterectomy, pars plana vitrectomy, cataract extraction, Nd:YAG Capsulotomy, and laser pupiloplasty.
6. Conditions outside the vascular structure: This category includes conditions like ocular ischemic syndrome and obstructions in the carotid artery, as well as a condition known as carotid-cavernous fistula.

While there are many causes, three conditions are responsible for most NVG cases: diabetic retinopathy, ischemic central retinal vein occlusion (CRVO), and ocular ischemic syndrome, forming 33%, 33%, and 13% respectively. In patients with an ischemic CRVO, up to 60% can develop NVG within a few weeks to 2 years after the onset of CRVO. Additionally, eyes with non-ischemic CRVO also have a risk of converting to ischemic CRVO over time.

When it comes to diabetic retinopathy, between 1% and 17% of eyes with this condition could develop NVG. This likelihood especially increases for proliferative diabetic retinopathy. Ocular ischemic syndrome typically affects one eye, but can affect both eyes in 20% of cases. This condition can cause the formation of new vessels both in the anterior and posterior segments of the eye, and is often associated with severe carotid artery occlusion and diabetic retinopathy.

Risk Factors and Frequency for Neovascular Glaucoma

Neovascular glaucoma (NVG) impacts different populations in various ways. Based on numerous studies carried out in different locations, the rate at which people get NVG can vary noticeably. It’s estimated that out of the total cases of glaucoma, around 5.8% are NVG in China. In Singapore’s Indian population, this drops to 0.12%, and in West Bengal, India, NVG prevalence is even lower at 0.01%.

In secondary glaucoma patients, NVG affects 9 to 17.4% of them as per hospital studies. Additionally, between 40 to 45% of eyes with a condition called ischemic CRVO are likely to develop NVG. Furthermore, it is estimated that around 3,800 patients with ischemic CRVO develop NVG each year.

Among patients with another eye condition – proliferative diabetic retinopathy – 65% of the eyes develop NVI. For these patients who have NVG in one eye, there’s a 33% chance to develop NVG in the other eye as well. In cases of OIS, another eye disease, 68% of patients’ eyes can develop NVG, with a higher risk in those having more advanced carotid stenosis. The Diabetes Control Complications Trial reported that 24% of the standard treatment group developed NVG over nine years, in contrast to only 8% in the intensive treatment group.

Signs and Symptoms of Neovascular Glaucoma

Neovascular glaucoma (NVG) is caused by many factors, and when seeking treatment, patients should discuss their medical history in detail. Patients suffering from diabetes need to share information about their blood sugar control, and if they have other conditions like high blood pressure, high cholesterol, anemia, kidney disease, and heart disease.

Patients with Central Retinal Vein Occlusion (CRVO) should share about anything that could cause blood clots. Conditions like diabetes, high blood pressure, high cholesterol, and too many red blood cells can cause these clots. Other factors can include genetic conditions that cause blood clotting, smoking, contraceptive pills, and pregnancy. Glaucoma can also contribute to this problem. Patients with Ocular Ischemic Syndrome (OIS) might have had strokes or mini-strokes in the past, and these patients need a thorough neurological evaluation.

Patients who have had eye surgery, such as vitrectomy, glaucoma drainage surgery, and cataract surgery, should share if they had any problems during the surgery. Issues like a torn posterior capsule and loss of vitreous fluid are related to a higher rate of NVG in patients with proliferative diabetic retinopathy (PDR). Patients without a lens inside their eyes (aphakia), are at higher risk of NVG than those with artificial lenses (pseudophakia). Repeat retinal detachment and surgeries to fix the retina are risk factors for NVG, too.

Patients from regions or belonging to ethnic groups with high rates of sickle cell disease and similar disorders need to be tested for sickle cell anemia. They should share if they have had blood transfusions or painful limbs.

Children should share if they were a low-birth-weight baby, premature, a twin, had an infection soon after birth, or needed excess oxygen. All of these increase the likelihood of developing abnormal blood vessels in the retina (retinopathy of prematurity or ROP), and can result in NVG. They need to be tested for eye cancer (retinoblastoma), especially if a family member has had it. They should be checked for conditions like persistent hyperplastic primary vitreous (PHPV) or Coat disease.

Patients with a past history of uveitis need to share information about the frequency and duration of instances when their eyes were red and painful. It’s also important to discuss any history of tumors in the eye like choroidal melanoma, retinoblastoma, iris melanoma, and ciliary body melanoma, as well as any eye or adjacent area radiation therapy they might have undergone.

Usually, an eye with NVG is chronically red and painful. However, in young patients with a good reserve of cells lining the inner surface of cornea (endothelium), the redness and pain might not be as severe. Initial symptoms in some could be sensitivity to light and blurry vision.

The pressure inside an eye with NVG is typically high, often over 50 mm Hg. Swelling in the cornea might or might not be present. The prominent signs of NVG during examination of the front part of the eye are new blood vessels on the iris and the angle of the eye. These new blood vessels can be seen earliest after a fluorescence dye test that reveals leakage of dye. They usually form at the edge of the pupil. Sometimes these new vessels can arise from a certain procedure done for glaucoma. These can be differentiated from normal blood vessels emanating from the ciliary body seen over the iris. New abnormal vessels in the eye’s drainage angle is a sign that can be observed during a glaucoma test.

NVG can be divided into four stages. The first is the pre-rubeotic stage, where the new blood vessels are not notable in an exam, but can be seen during a fluorescence dye test due to leakage from the pupil’s edge. The second stage involves visible new blood vessels on the iris or the angle of the eye. The third stage happens when the fibrous and vascular membrane covers the front part of the eye obstructing the flow of aqueous humor (eye fluid). The fourth stage is when this membrane over the angle of the eye contracts, causing the angle to close.

Testing for Neovascular Glaucoma

The process of diagnosing neovascular glaucoma (NVG) involves both eye-specific and body-wide tests.

Eye-specific tests include:

1. Slit-lamp biomicroscopy: This test helps spot new blood vessels and other signs of NVG on the surface of the iris — the part of the eye that gives it its color. It can also identify certain changes and build up of blood cells in the eye.

2. Gonioscopy: Through this test, doctors examine the angles of your eye’s anterior chamber, mainly where the cornea and iris meet, under different lighting conditions. The goal is to spot any new blood vessels that may have developed because of NVG.

3. Fundus Fluorescein Angiography (FFA): This dye-based test can detect areas of new blood vessel formation and spots where the capillaries (tiny blood vessels) aren’t functioning correctly in the back of the eye.

4. Optical coherence tomography angiography (OCTA): Like FFA, OCTA is also used to spot new vessels and non-working capillaries. This imaging test, however, doesn’t involve any dye and can also be used over time to monitor the progress of NVG.

5. OCTA of iris: This is simply the application of OCTA to detect new blood vessels in the iris.

6. B-scan ultrasound: In certain situations, an ultrasound of the back of your eye might be conducted. This test can identify a variety of issues, including any internal bleeding, growths, or a detached retina.

Whole-body (systemic) tests are conducted to identify any body-wide diseases that could be contributing to NVG. These might include:

1. Blood pressure tests, since hypertension can link to NVG,
2. Blood sugar levels and HbA1c test for diabetes, another potential player in NVG,
3. Tests for high levels of fat (lipids) in your blood,
4. A test to check the blood flow in your neck (carotid Doppler and magnetic resonance angiography),
5. Tests to diagnose inflammation in the eye, Tuberculosis, and Sarcoidosis,
6. Various blood tests to check for blood disorders. These tests can also help diagnose inflammation and measure the thickness of the blood.

Treatment Options for Neovascular Glaucoma

Managing NVG (Neovascular Glaucoma) relies on several principles, such as:

• Identifying and addressing the root causes contributing to retinal damage, such as diabetes or blocked carotid arteries.
• Treating retinal damage with techniques such as all-over laser treatment or injections of medications that block blood vessel growth in the eye.
• Keeping eye pressure in check with medications or surgeries.
• Using eye drops that contain corticosteroids to control inflammation.
• Using eye drops that widen (dilate) the pupil, such as atropine drops.

It’s important to identify and manage the root causes of the patient’s NVG to prevent damage to the retina (back of the eye), especially in patients who currently only have NVG in one eye. It may be necessary to involve other healthcare professionals, such as physicians to manage uncontrolled diabetes or hypertension, vascular surgeons to address severely blocked carotid arteries, or hematologists for any blood abnormalities.

If the cause of NVG is an inflammatory condition of the eye, such as uveitis, or an internal eye tumor, these will also need to be addressed as part of managing NVG.

Retinal damage due to NVG is typically treated using laser treatment or injections of medications that halt the growth of new blood vessels into the eye. These treatments might not have an immediate effect, but they can have a long-lasting impact on the progression of NVG. Sometimes, both treatments are given together. Unfortunately, certain conditions, such as high eye pressure and certain types of cataracts, can make these treatments more difficult, and other interventions might be required, such as injections of medications that reduce eye pressure or improve the clarity of the cornea (the eye’s clear front surface).

In terms of managing eye pressure, various medications could be used, such as eye drops that reduce the amount of fluid in the eye or pills that lower eye pressure. If these do not work, surgery may be required. A common treatment option is the placement of a drainage device to improve eye fluid outflow and lower eye pressure, but it is not always successful, and other treatments may be necessary.

In addition to managing pressure, it’s also important to control inflammation in the eye with corticosteroid eye drops. Eye drops that dilate the pupil can help with discomfort due to involuntary muscle contractions.

However, in those with NVG who have no light perception and are not in pain, no treatment may be necessary. But if these eyes eventually become painful, treatment to lower eye pressure, eye drops that dilate the pupil, and possibly a type of surgery to decrease fluid production in the eye could be required.

What else can Neovascular Glaucoma be?

Diagnosing NVG or Neovascular Glaucoma can be challenging as a lot of other eye diseases have similar symptoms. Some of these include:

• Acute angle-closure glaucoma: This mimics NVG symptoms, characterized by corneal swelling, inflammation in the front part of the eye, and slight bulging of the iris blood vessels associated with increased eye pressure. Diagnosing this involves examining the other eye and noting a shallow chamber at the front of the eye and blocked ‘gonia’ or angle. An examination of the back of the eye or ‘fundus’ can be difficult due to the cornea’s haziness. To confirm it isn’t NVG, a detailed fundus examination or angiography must be done.
• Acute or chronic uveitis: Just like NVG, these eye conditions include symptoms like protein deposits lining the inside layer of the cornea and bulging blood vessels that are easily distinguishable from the new and delicate vessels typical of NVG.
• Post-operative cases of eye surgeries that involve the front part of the eye: Post-surgical eyes might show swollen blood vessels of the iris, though these veins are different from the newly formed vessels of NVG.
• Posterior segment ocular tumors: If present, these tumors can make the iris blood vessels appear engorged. Timely diagnosis can be done using fundus examination, ultrasound scans, gonioscopy, and MRI scans.
• Carotid-cavernous fistula: A condition where a connection is formed between the carotid artery and the cavernous sinus, might show new blood vessel formation on the iris. It can be diagnosed using gonioscopy that detects blood in the Schlemm’s canal and using radiographs of the brain and eye sockets.
• Ocular ischemic syndrome: This condition, associated with either normal or low eye pressure, presents with new blood vessel formation in the anterior segment of the eye. A special type of ultrasound test or MRI scans can assist in identifying blocked arteries.
• Anterior segment dysgenesis, particularly severe iris thinning: Diagnosing this involves checking for iris thinning and misplacement of the pupil. Other conditions like pseudoexfoliation syndrome and Fuchs heterochromic iridocyclitis can also present similar symptoms and could lead to increased eye pressure.

As these conditions have similar presentations, it’s important for an accurate diagnosis to be differentiated clinically.

What to expect with Neovascular Glaucoma

The outcome of Neovascular glaucoma (NVG) is uncertain and hinges on quick prevention or treatment of retinal ischemia – a condition where the retina does not get enough oxygen supply. Controlling the intraocular pressure (IOP) – the pressure within the eye – is another crucial factor for the visual outcome. Elevated IOP often resists medical treatment.

The success of a surgical procedure called trabeculectomy does not have a high success rate in NVG because of inflammation and hyphema – a condition where blood collects inside the front part of the eye. However, previously administered procedures such as intravitreal bevacizumab injections, pan-retinal photocoagulation of the retina with various medications have shown an increased success rate.

It is important to note that IOP control with a particular medicine called MMC fluctuates between 62% and 82% after a year, then drops sharply over the following years. On the other hand, success in controlling IOP has been higher in eyes treated with a surgical tool called GDD.

Both valved and non-valved GDDs, used to relieve pressure inside the eye effectively control IOP in patients with NVG. Combining an injection of anti-VEGF agents – a group of medicines that restrict the growth of new blood vessels and GDD may result in better vision retention and IOP control than using GDD alone. Early surgery with GDD may be more beneficial than initial trabeculectomy in NVG patients. It’s also worth mentioning that research did not show any difference in the failure rate of NVG treated with GDD, regardless of the cause of NVG.

Possible Complications When Diagnosed with Neovascular Glaucoma

Neovascular glaucoma (NVG) complications can be split into two categories: those caused by the disease itself, and those resulting from the treatment methods. Disease-related complications could include corneal damage due to long-term increased eye pressure, ectropion uvea, where a fibrous membrane develops over the iris’ surface due to contraction, and vision loss, either due to lack of blood supply to the retina or damage to the optic nerves caused by glaucoma.

The most frequently seen complication from surgical management to control eye pressure is hyphema, which is the presence of blood inside the anterior part of the eye, seen in a varying range of patients. Other possible complications from surgery may include a fluid-filled detachment of the choroid membrane in the eye, or bleeding behind this area.

While it is rare, there can also be complications like inflammation of a vein (phlebitis), leakage from a drainage bleb, and infection inside the eye (endophthalmitis) following an eye procedure called a trabeculectomy, regardless of the surgery’s purpose. In surgeries involving the use of glaucoma drainage devices, there could be complications such as tearing of the thin outer layer of the eye covering the device, blockage of the tube, and corneal damage due to contact with the tube tip.

The complications specifically tied to a treatment known as transscleral cyclophotocoagulation (TSCPC) may include shrinkage of the eyeball (phthisis) and thinning of the outer layer of the eyeball (sclera). All surgical treatments, especially TSCPC, carry the risk of a rare, potentially devastating eye condition called sympathetic ophthalmia.

Common complications:

• Corneal damage
• Ectropion uvea
• Vision Loss
• Hyphema
• Choroidal detachment
• Suprachoroidal hemorrhage
• Phlebitis
• Bleb leak
• Endophthalmitis
• Conjunctival erosion (in surgeries involving glaucoma drainage devices)
• Tube block (in surgeries involving glaucoma drainage devices)
• Corneal endothelial defects (in surgeries involving glaucoma drainage devices)
• Phthisis (especially in TSCPC surgeries)
• Scleral thinning (especially in TSCPC surgeries)
• Sympathetic ophthalmia (especially in TSCPC surgeries)

Preventing Neovascular Glaucoma

Neovascular glaucoma (NVG) is a type of eye condition that can be challenging to treat and often results in poor control of eye pressure and vision loss. When someone with this condition waits too long to seek help from an eye specialist, it can lead to even worse vision problems.

People at risk, including those with diabetes, high blood pressure, high cholesterol, blood vessel diseases in the neck, or eye tumors, should be aware of NVG symptoms. Experts highly recommend they seek immediate treatment from an eye health professional. In addition, the primary eye doctors caring for these patients should quickly direct them to a specialized eye care center for treatment, which might include glaucoma drainage device surgeries or special eye injections.

Patients with NVG must stick to the follow-up plan closely, as it often involves multiple medical visits. Patients should be prepared for the fact that controlling eye pressure and improving vision might be challenging, despite all efforts.