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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Ophthalmology

The Biology of "SOS" Signals: Root Causes of NVG

At a Glance

Neovascular glaucoma (NVG) is a secondary condition caused when the eye is starved of oxygen (ischemia). In response, the eye releases a protein called VEGF to grow new blood vessels, but these abnormal vessels block the eye's drainage system. Common causes include advanced diabetes and eye strokes.

Neovascular glaucoma (NVG) is never a “primary” disease. It is always a complication of another condition that has starved the eye of oxygen [1][2]. To treat the pressure in your eye effectively, your medical team must also identify and manage the root cause of the oxygen shortage, a state known as ischemia [3][4].

The Biological “SOS” Signal: VEGF

When the retina (the light-sensitive layer at the back of the eye) does not get enough oxygen-rich blood, it releases a protein called VEGF (Vascular Endothelial Growth Factor) [5][6].

Think of VEGF as a biological “SOS” signal. Its job is to tell the body to grow new blood vessels to bring in more oxygen [7]. Unfortunately, these new vessels (neovascularization) are weak, leaky, and grow in the wrong places, such as over the eye’s drainage system [6][4]. This creates a “secondary” glaucoma because the pressure rise is a result of this abnormal growth [8].

The Three Most Common Root Causes

Most cases of NVG can be traced back to one of three conditions that disrupt the eye’s blood supply:

1. Proliferative Diabetic Retinopathy (PDR)

In advanced diabetes, high blood sugar damages the tiny blood vessels in the retina over many years [9]. Eventually, these vessels close off entirely. The resulting lack of oxygen triggers a massive release of VEGF, leading to the growth of abnormal vessels [3][10]. Managing your blood sugar (HbA1c) is a critical part of stabilizing this condition [9][3].

2. Central Retinal Vein Occlusion (CRVO)

This is often called an “eye stroke.” It occurs when the main vein that carries blood away from the retina becomes blocked [3]. Blood backs up, oxygen levels drop, and the retina becomes severely ischemic. This condition is sometimes called “90-day glaucoma” because the severe pressure spike of NVG typically develops about three months after the initial blockage in the vein occurs [3][11].

3. Ocular Ischemic Syndrome (OIS)

Unlike the other two, OIS is caused by a problem outside the eye—usually a severe blockage in the carotid arteries in the neck [12][13]. Because less blood can reach the eye, the entire organ becomes starved for oxygen [14]. In these cases, doctors may need to check the blood flow in your neck to address the source of the problem [15][16].

Differentiating NVG from Similar Conditions

Because the treatment for NVG is so specific, your doctor must ensure it isn’t another condition that can look similar:

  • Fuchs Heterochromic Iridocyclitis (FHI): This is a long-term inflammation that can cause fine vessels to appear on the iris. However, these vessels are different from NVG because they don’t usually leak or form the scarring membranes that block the drain [8].
  • ICE Syndrome (Iridocorneal Endothelial Syndrome): This is a rare condition where the “skin” cells of the cornea grow over the eye’s drain. While it also causes high pressure and scarring, it is caused by abnormal cell growth, not a lack of oxygen or VEGF [17].

By identifying the specific cause of your ischemia, your doctor can tailor a treatment plan that addresses both the high eye pressure and the underlying biological “SOS” signal [5][18].

Common questions in this guide

What causes neovascular glaucoma?
Neovascular glaucoma is a complication of an underlying condition that starves the eye of oxygen. The most common root causes include advanced diabetic retinopathy, a central retinal vein occlusion (sometimes called an eye stroke), or a severe blockage in the carotid arteries.
What is VEGF and why is it important in NVG?
VEGF is a protein that acts as an 'SOS' signal when the retina doesn't receive enough oxygen. It prompts the body to grow new blood vessels to bring in more oxygen, but these new vessels are abnormal, leaky, and grow over the eye's drainage system, causing a severe spike in eye pressure.
Why is neovascular glaucoma sometimes called 90-day glaucoma?
This term is often used when the condition develops after a central retinal vein occlusion (CRVO). It's called '90-day glaucoma' because the severe spike in eye pressure typically occurs about three months after the initial blockage in the retinal vein.
How does diabetes lead to neovascular glaucoma?
In advanced diabetes, prolonged high blood sugar damages the tiny blood vessels in the retina, causing them to close off entirely. This severe lack of oxygen triggers the massive release of VEGF, which leads to the growth of abnormal blood vessels that block the eye's drainage system.
Why does my eye doctor want to check the arteries in my neck?
If your doctor suspects Ocular Ischemic Syndrome (OIS), they may check the carotid arteries in your neck. Because these arteries supply blood to the head, a severe blockage in the neck can restrict blood flow to the eye, starving it of oxygen and triggering neovascular glaucoma.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my exam, which underlying condition (like PDR, CRVO, or OIS) triggered the ischemia in my eye?
  2. 2.Do I need a carotid ultrasound to check for blockages in my neck that might be affecting my eye's blood flow?
  3. 3.What is my HbA1c level, and how does my blood sugar control impact the success of my eye treatments?
  4. 4.How do you distinguish the blood vessels you see in my eye from other conditions like Fuchs or ICE syndrome?
  5. 5.What stage of NVG am I in—is the drainage angle still open, or has it started to scar?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (18)
  1. 1

    Expression of platelet-derived growth factor-C in aqueous humor of patients with neovascular glaucoma and its correlation with vascular endothelial growth factor.

    Li Y, Hu D, Lv P, et al.

    European journal of ophthalmology 2020; (30(3)):500-505 doi:10.1177/1120672119832785.

    PMID: 30803266
  2. 2

    Neovascular glaucoma - A review.

    Senthil S, Dada T, Das T, et al.

    Indian journal of ophthalmology 2021; (69(3)):525-534 doi:10.4103/ijo.IJO_1591_20.

    PMID: 33595466
  3. 3

    Posterior Vitreous Detachment and Risk of Neovascular Glaucoma in Eyes with Prior Retinal Vascular Occlusions.

    Palmer LD, Peterson JD, Evans JK, et al.

    Ophthalmology and therapy 2024; (13(11)):3013-3024 doi:10.1007/s40123-024-01039-1.

    PMID: 39342534
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    Widefield swept-source optical coherence tomography angiography metrics associated with neovascular glaucoma in patients with proliferative diabetic retinopathy.

    Lu ES, Cui Y, Le R, et al.

    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 2024; (262(4)):1111-1120 doi:10.1007/s00417-023-06290-z.

    PMID: 37962666
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    Molecular and Cellular Mechanisms Involved in the Pathophysiology of Retinal Vascular Disease-Interplay Between Inflammation and Oxidative Stress.

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    International journal of molecular sciences 2024; (25(21)) doi:10.3390/ijms252111850.

    PMID: 39519401
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    Neovascularization of the Iris/Angle in Primary Angle Closure Glaucoma: A Distinct Entity!

    Angmo D, Warjri GB, Verma S, et al.

    Journal of current glaucoma practice 2025; (19(4)):229-233 doi:10.5005/jp-journals-10078-1499.

    PMID: 41523172
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    Prethreshold retinopathy of prematurity: VEGF inhibition without VEGF inhibitors.

    Gaynon MW, Wong RJ, Stevenson DK, Sunshine P

    Journal of perinatology : official journal of the California Perinatal Association 2018; (38(10)):1295-1300 doi:10.1038/s41372-018-0177-9.

    PMID: 30046180
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    Etiology, pathogenesis, and diagnosis of neovascular glaucoma.

    Călugăru D, Călugăru M

    International journal of ophthalmology 2022; (15(6)):1005-1010 doi:10.18240/ijo.2022.06.20.

    PMID: 35814894
  9. 9

    Frequency and Risk Factors for Neovascular Glaucoma After Vitrectomy in Eyes with Diabetic Retinopathy: An Observational Study.

    Liang X, Zhang Y, Li YP, et al.

    Diabetes therapy : research, treatment and education of diabetes and related disorders 2019; (10(5)):1801-1809 doi:10.1007/s13300-019-0644-0.

    PMID: 31321746
  10. 10

    Association between stress hyperglycemia ratio and neovascular glaucoma in patients with proliferative diabetic retinopathy.

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    BMC ophthalmology 2025; (25(1)):163 doi:10.1186/s12886-025-03982-4.

    PMID: 40170000
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    Central retinal thickness changes and risk of neovascular glaucoma after intravitreal bevacizumab injection in patients with central retinal vein occlusion.

    Lee YH, Kim YC

    Scientific reports 2022; (12(1)):2051 doi:10.1038/s41598-022-06121-x.

    PMID: 35136171
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    Optical Coherence Tomography Angiography Before and After Bevacizumab Injection in Ocular Ischemic Syndrome.

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    Retina (Philadelphia, Pa.) 2018; (38(3)):e23-e25 doi:10.1097/IAE.0000000000001981.

    PMID: 29206756
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    Angiogenic and Inflammatory Vitreous Biomarkers Associated With Increasing Levels of Retinal Ischemia.

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    Investigative ophthalmology & visual science 2015; (56(11)):6523-30 doi:10.1167/iovs.15-16793.

    PMID: 26447988
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    Clinical Features of Ocular Ischemic Syndrome and Risk Factors for Neovascular Glaucoma.

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    Korean journal of ophthalmology : KJO 2017; (31(4)):343-350 doi:10.3341/kjo.2016.0067.

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    Carotid revascularization and circle of Willis in ocular ischemic syndrome: association with neovascular glaucoma and visual prognosis.

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    Journal of neurointerventional surgery 2025; doi:10.1136/jnis-2024-022959.

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    Carotid Endarterectomy for Ocular Ischemic Syndrome: A Case Report and Review of the Literature.

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    [A case of atypical iris corneal endothelial syndrome].

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    Neovascular Glaucoma from Ocular Ischemic Syndrome Treated with Serial Monthly Intravitreal Bevacizumab and Panretinal Photocoagulation: A Case Report.

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This page explains the biological causes of neovascular glaucoma for educational purposes only. Always consult your ophthalmologist for an accurate diagnosis, monitoring, and treatment plan for your specific eye condition.

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