Angle Closure Glaucoma
Disease Details
Family Health Simplified
- Description
- Angle-closure glaucoma is a type of glaucoma where the drainage angle of the eye becomes blocked, leading to a rapid increase in intraocular pressure.
- Type
- Angle-closure glaucoma, also known as acute or narrow-angle glaucoma, is typically classified as a primary glaucoma when it occurs without an underlying cause. It can inherit in a familiar pattern, often suggesting multifactorial inheritance involving multiple genes and environmental factors. However, specific patterns of simple Mendelian inheritance are not typically associated with this condition.
- 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
- Angle-closure glaucoma typically has a sudden onset. The abrupt increase in intraocular pressure can cause rapid vision changes, severe eye pain, headache, nausea, and even vomiting. It is considered a medical emergency and requires prompt treatment to prevent permanent vision loss.
- Prevalence
- Angle-closure glaucoma is less common than open-angle glaucoma. Its prevalence varies by ethnicity and age. In general, the prevalence is estimated to be about 0.6% to 1.2% in Asian populations, where it is more frequent. It is less common in Caucasian and African populations, with rates typically below 0.5%. The risk increases with age and is more common in women than in men.
- 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
- Angle-closure glaucoma can be challenging to manage, particularly if it is not diagnosed early. However, it is not considered intractable. With timely diagnosis and appropriate treatment—such as medications to lower intraocular pressure, laser therapy, or surgical interventions—the condition can often be managed effectively to prevent vision loss. Early detection and ongoing eye care are critical for the best outcomes.
- Disease Severity
- Angle-closure glaucoma is a severe form of glaucoma where the drainage angle of the eye becomes blocked, leading to rapid increases in intraocular pressure. If not treated promptly, it can result in permanent vision loss. This condition is considered a medical emergency that requires immediate attention.
- Healthcare Professionals
- Disease Ontology ID - DOID:13550
- Pathophysiology
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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
- Angle-closure glaucoma, also known as acute glaucoma or narrow-angle glaucoma, is not typically described in terms of carrier status because it is not a condition inherited in a simple recessive or dominant genetic pattern. It is an eye condition that results from the iris being too close to the drainage angle in the eye, which can suddenly block the flow of aqueous humor and increase intraocular pressure. This is more common in people with certain anatomical predispositions, such as a shallow anterior chamber or a smaller-than-average eye. Various factors, including genetics, age, and ethnicity, can contribute to the risk, but there is no carrier state as there might be for single-gene recessive disorders.
- Mechanism
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**Mechanism:**
Angle-closure glaucoma is caused by a blockage or closure of the eye's drainage angle, where the iris and cornea meet. This blockage prevents aqueous humor from flowing out of the eye, leading to a rapid increase in intraocular pressure (IOP). The condition can manifest suddenly (acute angle-closure glaucoma) or gradually (chronic angle-closure glaucoma).
**Molecular Mechanisms:**
1. **Genetic Factors:** Specific genetic mutations have been linked to angle-closure glaucoma. Variants in genes like *PITX2*, *FOXC1*, and others involved in anterior segment development can predispose individuals to the condition.
2. **Collagen and Extracellular Matrix (ECM) Remodeling:** Abnormalities in collagen and ECM proteins can affect the structure of the trabecular meshwork and Schlemm's canal, contributing to impaired aqueous humor outflow.
3. **Cell Signaling Pathways:** Dysregulation of signaling pathways, including those involving transforming growth factor-beta (TGF-β) and matrix metalloproteinases (MMPs), can lead to altered trabecular meshwork cellularity and function.
4. **Inflammatory Mediators:** Increased levels of inflammatory cytokines have been observed in angle-closure glaucoma, suggesting that local inflammation may play a role in trabecular meshwork dysfunction and angle closure.
These molecular mechanisms collectively contribute to the pathophysiology of angle-closure glaucoma by affecting the structural and functional integrity of the eye's drainage system. - Treatment
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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
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For angle-closure glaucoma, compassionate use treatments and off-label or experimental options are considered when conventional treatments are ineffective or unsuitable. These may include:
1. **Compassionate Use Treatments**:
- **Cyclodestructive procedures**: Such as cyclophotocoagulation, which uses a laser to reduce the production of aqueous humor and lower intraocular pressure.
2. **Off-label or Experimental Treatments**:
- **Micropulse Laser Therapy (MPTLT)**: A newer laser technique that delivers short, repetitive energy pulses to minimize damage to surrounding tissues.
- **Endoscopic Cyclophotocoagulation (ECP)**: An internal laser procedure. Though primarily used for open-angle glaucoma, it’s being explored for angle-closure cases.
- **Gene therapy and novel pharmacologic agents**: These are under investigation in clinical trials and aim to correct underlying genetic defects or introduce new drug mechanisms.
Patients considering these treatments should discuss the potential benefits and risks with their healthcare provider to ensure all avenues are thoroughly evaluated. - Lifestyle Recommendations
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Here are some lifestyle recommendations for managing angle-closure glaucoma:
1. **Regular Eye Check-ups**: Frequent visits to an eye specialist can help monitor the condition and detect any changes early.
2. **Medication Adherence**: Ensure you take prescribed medications as directed to control eye pressure.
3. **Limit Caffeine**: High caffeine intake can increase intraocular pressure, so moderate your consumption.
4. **Hydrate Properly**: Drink fluids regularly but avoid consuming large amounts in a short time to prevent sudden eye pressure increases.
5. **Exercise**: Engage in regular, moderate exercise to improve overall health and potentially lower intraocular pressure.
6. **Avoid Certain Activities**: Activities such as reading in dim light, watching TV in a dark room, or extensive time in low-light conditions can strain the eyes.
7. **Head Elevation**: Sleep with your head slightly elevated to help reduce eye pressure.
8. **Manage Stress**: Practices like yoga, meditation, or deep-breathing exercises can help manage stress, potentially benefiting your eye health.
Always consult with your healthcare provider for personalized guidance. - Medication
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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
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Angle-closure glaucoma is a type of glaucoma where the flow of aqueous humor is blocked, causing a rapid increase in intraocular pressure. Elevated intraocular pressure can damage the optic nerve, leading to vision loss.
### Repurposable Drugs:
1. **Acetazolamide (Diamox):** Primarily a diuretic, acetazolamide is used to reduce intraocular pressure by decreasing the production of aqueous humor in the eye.
2. **Pilocarpine:** This is traditionally an anti-glaucoma medication that can induce miosis and help in opening the trabecular meshwork to improve aqueous outflow.
3. **Timolol:** A beta-blocker commonly used for hypertension, it can also reduce intraocular pressure by decreasing the production of aqueous humor.
### NAN:
The term "nan" typically stands for "not a number," but in the context of diseases and treatments, it could correspond to various applications of nanotechnology:
- **Nanoparticles for Drug Delivery:** Nanoparticles can be designed to deliver anti-glaucoma medications (like timolol or acetazolamide) more effectively with controlled release mechanisms.
- **Nanostructured Implants:** Implants using nanostructures can potentially assist in maintaining intraocular pressure by providing new pathways for aqueous humor drainage.
- **Nanomedicine for Diagnosis:** Advanced imaging techniques using nanotechnology can provide detailed images of eye structures, potentially aiding in the early diagnosis and management of angle-closure glaucoma.
Repurposing existing drugs and leveraging nanotechnology can provide new avenues for the treatment and management of angle-closure glaucoma. - Metabolites
- In angle-closure glaucoma, the buildup of aqueous humor due to blocked drainage can lead to elevated intraocular pressure. This pressure can result in the accumulation of certain metabolites such as lactate and reactive oxygen species. Elevated levels of these metabolites can contribute to optic nerve damage and vision loss associated with the disease.
- Nutraceuticals
- Currently, there is limited evidence to support the use of nutraceuticals specifically for the treatment or prevention of angle-closure glaucoma. Nutraceuticals are products derived from food sources that offer health benefits beyond basic nutrition. While general eye health may benefit from a well-balanced diet rich in antioxidants, vitamins, and minerals, these are not substitutes for the medical and surgical interventions commonly required for angle-closure glaucoma. It's essential for individuals with this condition to follow their healthcare provider’s recommendations and to seek immediate medical attention if symptoms such as sudden vision loss or severe eye pain occur.
- Peptides
- In angle-closure glaucoma, "peptides" and "nan" (short for nanotechnology) do not have widely recognized direct roles in standard treatment or management. Angle-closure glaucoma typically requires immediate medical attention to reduce intraocular pressure via medications, laser therapy, or surgical procedures. Peptides and nanotechnology might be subjects of future research, potentially providing new therapeutic avenues, but they are not currently standard clinical interventions for this condition.