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Neovascular Glaucoma

Disease Details

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Description: Neovascular glaucoma is a severe form of glaucoma characterized by the growth of new, abnormal blood vessels on the iris and the trabecular meshwork, leading to increased intraocular pressure and vision loss.
Type: Neovascular glaucoma is not classified primarily by genetic type or transmission. It is a secondary glaucoma that occurs due to the formation of abnormal new blood vessels in the eye, often related to underlying conditions like diabetes, retinal vein occlusion, or other ischemic ocular diseases.
Signs And Symptoms: Open angle glaucoma usually presents with no symptoms early in the course of the disease. However, it may gradually progress to involve difficulties with vision. It usually involves deficits in the peripheral vision followed by central vision loss as the disease progresses, but less commonly it may present as central vision loss or patchy areas of vision loss. On an eye examination, optic nerve changes are seen indicating damage to the optic nerve head (increased cup-to-disc ratio on fundoscopic examination).Acute angle closure glaucoma, a medical emergency due to the risk of impending permanent vision loss, is characterized by sudden ocular pain, seeing halos around lights, red eye, very high intraocular pressure, nausea and vomiting, and suddenly decreased vision. Acute angle closure glaucoma may further present with corneal edema, engorged conjunctival vessels and a fixed and dilated pupil on examination.Opaque specks may occur in the lens in glaucoma, known as glaukomflecken. The word is German, meaning "glaucoma-specks".
Prognosis: In open-angle glaucoma, the typical progression from normal vision to complete blindness takes about 25 years to 70 years without treatment, depending on the method of estimation used. The intraocular pressure can also have an effect, with higher pressures reducing the time until blindness.
Onset: Neovascular glaucoma typically has an onset associated with conditions that lead to poor blood flow to the eye, such as diabetic retinopathy, central retinal vein occlusion, or other ischemic retinal diseases. It can also occur after ocular surgeries or trauma. The neovascularization process results in the growth of new, abnormal blood vessels in the eye, particularly on the iris and over the ocular drainage system, leading to increased intraocular pressure. The onset can be acute or gradual, depending on the underlying condition causing the neovascularization.
Prevalence: Neovascular glaucoma is relatively rare. It typically occurs as a complication of other conditions, such as diabetic retinopathy or central retinal vein occlusion. Exact prevalence rates are not well-defined but it is considered uncommon compared to primary open-angle or angle-closure glaucoma.
Epidemiology: As of 2010, there were 44.7 million people in the world with open angle glaucoma. The same year, there were 2.8 million people in the United States with open angle glaucoma. By 2020, the prevalence is projected to increase to 58.6 million worldwide and 3.4 million in the United States.Both internationally and in the United States, glaucoma is the second-leading cause of blindness. Globally, cataracts are a more common cause. Glaucoma is also the leading cause of blindness in African Americans, who have higher rates of primary open-angle glaucoma. Bilateral vision loss can negatively affect mobility and interfere with driving.A meta-analysis published in 2009 found that people with primary open angle glaucoma do not have increased mortality rates, or increased risk of cardiovascular death.
Intractability: Neovascular glaucoma is considered intractable in many cases because it is challenging to manage and often does not respond well to conventional treatments. It is a secondary glaucoma characterized by the growth of abnormal new blood vessels on the iris and over the eye's drainage channels, leading to increased intraocular pressure. Treatment typically involves a combination of addressing the underlying cause, medications to lower intraocular pressure, laser therapy, and sometimes surgical interventions. Despite these measures, managing the disease effectively can be difficult, and long-term outcomes may be poor.
Disease Severity: Neovascular glaucoma is a severe and potentially sight-threatening condition. It often results from an underlying systemic or ocular disorder, such as proliferative diabetic retinopathy or central retinal vein occlusion. The disease is characterized by the growth of new, abnormal blood vessels on the iris and the anterior chamber angle, which can obstruct the outflow of aqueous humor, leading to increased intraocular pressure. Without appropriate and timely treatment, neovascular glaucoma can lead to significant vision loss or blindness.
Healthcare Professionals: Disease Ontology ID - DOID:1687
Pathophysiology: The main effect of glaucoma is damage to the optic nerve. Eventually, this damage leads to vision loss, which can deteriorate with time. The underlying cause of open-angle glaucoma remains unclear. Several theories exist on its exact etiology. However, the major risk factor for most glaucomas and the focus of treatment is increased intraocular pressure. Intraocular pressure is a function of production of liquid aqueous humor by the ciliary processes of the eye, and its drainage through the trabecular meshwork. Aqueous humor flows from the ciliary processes into the posterior chamber, bounded posteriorly by the lens and the zonules of Zinn, and anteriorly by the iris. It then flows through the pupil of the iris into the anterior chamber, bounded posteriorly by the iris and anteriorly by the cornea.
From here, the trabecular meshwork drains aqueous humor via the scleral venous sinus (Schlemm's canal) into scleral plexuses and general blood circulation.In open/wide-angle glaucoma, flow is reduced through the trabecular meshwork, due to the degeneration and obstruction of the trabecular meshwork, whose original function is to absorb the aqueous humor. Loss of aqueous humor absorption leads to increased resistance and thus a chronic, painless buildup of pressure in the eye.In primary angle closure glaucoma, the iridocorneal angle is narrowed or completely closed obstructing the flow of aqueous humor to the trabecular meshwork for drainage. This is usually due to the forward displacement of the iris against the cornea, resulting in angle closure. This accumulation of aqueous humor causes an acute increase in pressure and damage to the optic nerve.The pathophysiology of glaucoma is not well understood. There are several theories regarding the mechanism of the damage to the optic nerve in glaucoma. The biomechanical theory hypothesizes that the retinal ganglion cell axons (which form the optic nerve head and the retinal nerve fiber layer) are particularly susceptible to mechanical damage from increases in the intraocular pressure as they pass through pores at the lamina cribrosa. Thus increases in intraocular pressure would cause nerve damage as seen in glaucoma. The vascular theory hypothesizes that a decreased blood supply to the retinal ganglions cells leads to nerve damage. This decrease in blood supply may be due to increasing intraocular pressures, and may also be due to systemic hypotension, vasospasm or atherosclerosis. This is supported by evidence that those with low blood pressure, particularly low diastolic blood pressure, are at an increased risk of glaucoma.The primary neurodegeneration theory hypothesizes that a primary neurodegenerative process may be responsible for degeneration at the optic nerve head in glaucoma. This would be consistent with a possible mechanism of normal tension glaucoma (those with open-angle glaucoma with normal eye pressures) and is supported by evidence showing a correlation of glaucoma with Alzheimer's dementia and other causes of cognitive decline.
Both experimental and clinical studies implicate that oxidative stress plays a role in the pathogenesis of open-angle glaucoma as well as in Alzheimer's disease.Degeneration of axons of the retinal ganglion cells (the optic nerve) is a hallmark of glaucoma. The inconsistent relationship of glaucomatous optic neuropathy with increased intraocular pressure has provoked hypotheses and studies on anatomic structure, eye development, nerve compression trauma, optic nerve blood flow, excitatory neurotransmitter, trophic factor, retinal ganglion cell or axon degeneration, glial support cell, immune system, aging mechanisms of neuron loss, and severing of the nerve fibers at the scleral edge.
Carrier Status: Neovascular glaucoma is not associated with a carrier status because it is not an inherited condition. It typically develops secondary to other diseases, such as diabetic retinopathy or central retinal vein occlusion, which lead to abnormal blood vessel growth that blocks drainage in the eye, causing increased intraocular pressure and optic nerve damage.
Mechanism: Neovascular glaucoma is a type of secondary glaucoma characterized by the growth of abnormal new blood vessels on the iris and in the drainage angle of the eye, leading to increased intraocular pressure (IOP) and optic nerve damage.

**Mechanism:**
The primary mechanism involves the formation of new, abnormal blood vessels in response to ischemia or insufficient blood supply. These vessels can obstruct the trabecular meshwork, which is responsible for draining aqueous humor from the eye. The obstruction leads to impaired outflow of the aqueous humor, resulting in elevated intraocular pressure (IOP) and subsequent optic nerve damage.

**Molecular Mechanisms:**
1. **Vascular Endothelial Growth Factor (VEGF):** One of the key molecular drivers of neovascularization is VEGF. Hypoxia or ischemia conditions stimulate the upregulation of VEGF, which promotes the growth of new blood vessels. This is often seen in conditions like diabetic retinopathy or central retinal vein occlusion.

2. **Hypoxia-Inducible Factor (HIF):** Hypoxia conditions in the retina trigger the stabilization and activation of HIF, a transcription factor that enhances the expression of VEGF and other angiogenic factors.

3. **Inflammatory Cytokines and Chemokines:** Inflammation can contribute to the neovascular response. Molecules like interleukins and tumor necrosis factor-alpha (TNF-α) can promote angiogenesis and perpetuate the pathological process.

4. **Matrix Metalloproteinases (MMPs):** These enzymes degrade the extracellular matrix, facilitating the migration and proliferation of endothelial cells involved in new vessel formation.

5. **Integrins and Adhesion Molecules:** These molecules help in the attachment of new blood vessels to the extracellular matrix, thereby supporting neovascular growth.

Understanding these mechanisms provides insight into potential targets for therapeutic intervention aimed at inhibiting neovascularization and managing neovascular glaucoma.
Treatment: The modern goal of glaucoma management is to decrease the intraocular pressure (IOP), thus slowing the progression of glaucoma and preserving the quality of life for patients, with minimal side-effects. This requires appropriate diagnostic techniques and follow-up examinations, and judicious selection of treatments for the individual patient. Although IOP is only one of the major risk factors for glaucoma, lowering it via various pharmaceuticals and/or surgical techniques is currently the mainstay of glaucoma treatment.
The IOP should be reduced to a target level at which the disease progression is controlled protecting the visual field and improving life quality. The target level is set individually depending on multiple factors including the pretreatment IOP, the severity and rate of the disease progression, and the side effects of the medications. In general, the target IOP is equal or lower than 18mmHg in mild, 15mmHg in moderate and 12mmHg in severe stage glaucoma. After setting the target IOP, regular follow-up should be done assessing the IOP and the disease progression.
Vascular flow and neurodegenerative theories of glaucomatous optic neuropathy have prompted studies on various neuroprotective therapeutic strategies, including nutritional compounds, some of which may be regarded by clinicians as safe for use now, while others are on trial. Mental stress is also considered as consequence and cause of vision loss which means that stress management training, autogenic training and other techniques to cope with stress can be helpful.
Compassionate Use Treatment: Neovascular glaucoma is a severe form of glaucoma associated with the growth of new, abnormal blood vessels in the eye. Compassionate use treatment and off-label or experimental treatments for neovascular glaucoma can include the following options:

1. **Anti-VEGF Therapy**: Drugs like bevacizumab (Avastin), ranibizumab (Lucentis), and aflibercept (Eylea) are used off-label to inhibit vascular endothelial growth factor (VEGF) and reduce neovascularization. These injections are commonly used in various retinal diseases and have shown promise in treating neovascular glaucoma.

2. **Cyclodestructive Procedures**: Cyclophotocoagulation (CPC) using a laser to target and reduce the ciliary body's fluid production can be considered. This treatment is often used when other methods fail.

3. **Surgical Interventions**: Experimental surgical approaches, including the use of new glaucoma drainage devices or modifications to existing devices, can be pursued if conventional surgeries are unsuccessful.

4. **Steroid Injections**: Intravitreal steroid injections, such as triamcinolone, can be utilized off-label to reduce inflammation and secondary neovascularization, although they carry risks of elevated intraocular pressure.

5. **Gene Therapy**: Research is ongoing in the area of gene therapy, which aims to address the underlying genetic causes of neovascular glaucoma. Though still largely experimental, it holds potential for future treatments.

Compassionate use treatments are typically reserved for cases where standard therapies have failed, and the disease is progressing. Always consult with a healthcare professional to discuss the potential benefits and risks associated with these treatments.
Lifestyle Recommendations: For individuals with neovascular glaucoma, lifestyle recommendations include:

1. **Regular Eye Exams**: Schedule frequent check-ups with an ophthalmologist to monitor the condition and manage intraocular pressure.
2. **Medication Adherence**: Strictly adhere to prescribed medications, including eye drops to manage eye pressure and other treatments to control underlying conditions like diabetes.
3. **Healthy Diet**: Follow a balanced diet rich in fruits, vegetables, and omega-3 fatty acids to support overall eye health.
4. **Blood Sugar Control**: For diabetic patients, maintain tight control of blood sugar levels to prevent worsening of the condition.
5. **Exercise**: Engage in regular, moderate exercise to improve blood circulation, but avoid straining activities that could increase intraocular pressure.
6. **Avoid Smoking**: Quit smoking as it can exacerbate vascular problems and negatively impact eye health.
7. **Limit Caffeine**: Reduce caffeine intake since it can transiently raise eye pressure.
8. **Wear Protective Eyewear**: Use protective glasses in environments where eye injuries are a risk.
9. **Elevate Head During Sleep**: Use pillows to keep the head elevated when sleeping to help lower eye pressure.

These lifestyle modifications can complement medical and surgical treatments to help manage neovascular glaucoma effectively.
Medication: There are several pressure-lowering medication groups that could be used in lowering the IOP, usually eyedrops. The choice of medication usually depends on the dose, duration and the side effects of each medication. However, in general, prostaglandin analogues are the first-line treatment for glaucoma.Prostaglandin analogues, such as latanoprost, bimatoprost and travoprost, reduce the IOP by increasing the aqueous fluid outflow through the draining angle. It is usually prescribed once daily at night. The systemic side effects of this class are minimal. However, they can cause local side effects including redness of the conjunctiva, change in the iris color and eyelash elongation.There are several other classes of medications that could be used as a second-line in case of treatment failure or presence of contraindications to prostaglandin analogues. These include:

Topical beta-adrenergic receptor antagonists, such as timolol, levobunolol, and betaxolol, decrease aqueous humor production by the epithelium of the ciliary body.
Alpha2-adrenergic agonists, such as brimonidine and apraclonidine, work by a dual mechanism, decreasing aqueous humor production and increasing uveoscleral outflow.
Less-selective alpha agonists, such as epinephrine, decrease aqueous humor production through vasoconstriction of ciliary body blood vessels, useful only in open-angle glaucoma. Epinephrine's mydriatic effect, however, renders it unsuitable for closed-angle glaucoma due to further narrowing of the uveoscleral outflow (i.e. further closure of trabecular meshwork, which is responsible for absorption of aqueous humor).
Miotic agents (parasympathomimetics), such as pilocarpine, work by contraction of the ciliary muscle, opening the trabecular meshwork and allowing increased outflow of the aqueous humour. Echothiophate, an acetylcholinesterase inhibitor, is used in chronic glaucoma.
Carbonic anhydrase inhibitors, such as dorzolamide, brinzolamide, and acetazolamide, lower secretion of aqueous humor by inhibiting carbonic anhydrase in the ciliary body.Each of these medicines may have local and systemic side effects. Wiping the eye with an absorbent pad after the administration of eye drops may result in fewer adverse effects. Initially, glaucoma drops may reasonably be started in either one or in both eyes.The possible neuroprotective effects of various topical and systemic medications are also being investigated.
Repurposable Drugs: For neovascular glaucoma, repurposable drugs could include anti-VEGF (vascular endothelial growth factor) agents such as bevacizumab (Avastin) and ranibizumab (Lucentis). These drugs are primarily used in treating age-related macular degeneration and other retinal diseases but can also be injected into the eye to inhibit the abnormal blood vessel growth that characterizes neovascular glaucoma.
Metabolites: Neovascular glaucoma does not have specific metabolites directly linked to its pathophysiology. This condition is characterized by the abnormal growth of new blood vessels on the iris and over the eye's drainage channels, leading to increased intraocular pressure. It is often associated with underlying diseases such as diabetes mellitus, central retinal vein occlusion, or other conditions that cause retinal ischemia. These underlying conditions may have altered metabolic profiles, but no unique metabolites are specifically identified for neovascular glaucoma itself.
Nutraceuticals: Nutraceuticals for neovascular glaucoma have limited evidence supporting their efficacy. Currently, there are no nutraceuticals specifically approved for treating this condition. Neovascular glaucoma is often managed through medications to lower intraocular pressure, and treatments addressing the underlying vascular issue.

Nanotechnology (i.e., "nan") offers promising research avenues for medical treatment, including drug delivery systems for glaucoma. Nanoparticles can potentially enhance the delivery of medications directly to the eye, improving outcomes by increasing bioavailability and reducing side effects. However, more research is needed to implement these technologies effectively for neovascular glaucoma.
Peptides: Neovascular glaucoma is a type of secondary glaucoma characterized by the growth of abnormal new blood vessels on the iris and over the eye's drainage channels. This condition can lead to increased intraocular pressure and subsequent damage to the optic nerve, potentially resulting in vision loss. The most common underlying conditions include diabetic retinopathy and central retinal vein occlusion.

Regarding peptides and nanotechnology (nan), research into these areas is ongoing. Peptides, such as anti-VEGF (vascular endothelial growth factor) agents, are being studied and used to inhibit the growth of new blood vessels, which can help manage the progression of neovascularization.

Nanotechnology offers the potential for targeted drug delivery systems. Nanocarriers can be designed to deliver therapeutic agents directly to the eye, potentially improving the efficacy of treatments and reducing side effects. Current research is investigating various nanoparticle formulations to optimize the delivery of anti-glaucoma medications and peptides for more effective management of neovascular glaucoma.