Open-angle Glaucoma
Disease Details
Family Health Simplified
- Description
- Open-angle glaucoma is a chronic eye condition characterized by progressive damage to the optic nerve, often associated with increased intraocular pressure, leading to gradual vision loss.
- Type
- Open-angle glaucoma is primarily inherited in an autosomal dominant manner.
- 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
- Open-angle glaucoma typically has an insidious onset, meaning it develops slowly over time without noticeable symptoms in the early stages. As it progresses, individuals may experience gradual loss of peripheral vision, which can advance to central vision loss if untreated. Regular eye exams are crucial for early detection.
- Prevalence
- Open-angle glaucoma is the most common form of glaucoma, affecting approximately 1-2% of people over the age of 40 worldwide. The prevalence increases with age, particularly affecting populations over 60 years old, and can vary by demographic factors such as ethnicity, with higher rates observed among African American and Hispanic populations.
- 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
- Open-angle glaucoma is often considered intractable in that it cannot be cured; however, it can be managed effectively with ongoing treatment. Treatments include medications, laser therapy, and sometimes surgery to reduce intraocular pressure and prevent further vision loss. Early detection and consistent management are crucial for preserving vision.
- Disease Severity
- Open-angle glaucoma is a chronic condition where the eye's drainage canals become clogged over time, leading to increased intraocular pressure (IOP). This pressure can damage the optic nerve, resulting in gradual vision loss. Early stages often have no noticeable symptoms, so regular eye exams are critical for early detection. Left untreated, it can ultimately lead to blindness.
- Healthcare Professionals
- Disease Ontology ID - DOID:1067
- 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
- Open-angle glaucoma is an eye condition characterized by gradual damage to the optic nerve, often associated with increased intraocular pressure. It does not have a "carrier status" as it is not a condition that is passed down in a simple recessive or dominant genetic pattern like some other genetic disorders. Instead, it results from a combination of genetic and environmental factors. Multiple genes may contribute to the risk, and having a family history of the condition can increase the likelihood of developing it.
- Mechanism
-
Open-angle glaucoma is a chronic eye condition characterized primarily by an increase in intraocular pressure (IOP) that can lead to optic nerve damage and vision loss. The mechanisms and molecular aspects involved in its pathogenesis include:
### Mechanism
1. **Intraocular Pressure:** Increased IOP is a significant risk factor. It results from impaired drainage of aqueous humor through the trabecular meshwork and Schlemm’s canal.
2. **Optic Nerve Damage:** The elevated IOP exerts pressure on the optic nerve, leading to progressive nerve fiber loss and corresponding visual field defects.
### Molecular Mechanisms
1. **Extracellular Matrix (ECM) Remodeling:** Dysfunction in the ECM of the trabecular meshwork affects aqueous humor outflow. Key molecules involved are matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).
2. **Oxidative Stress:** Increased production of reactive oxygen species (ROS) can damage the trabecular meshwork and optic nerve cells.
3. **Genetic Factors:** Mutations and polymorphisms in genes such as MYOC (myocilin), OPTN (optineurin), and CYP1B1 have been associated with the disease.
4. **Inflammation:** Upregulation of inflammatory cytokines and immune cell infiltration might contribute to trabecular meshwork dysfunction and optic nerve damage.
5. **Cell Signaling Pathways:** Dysregulation of pathways such as Wnt, TGF-β (Transforming Growth Factor-beta), and NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) can affect cellular homeostasis in the trabecular meshwork and optic nerve.
Understanding these mechanisms is crucial for developing targeted therapies for open-angle 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
-
For open-angle glaucoma, several off-label or experimental treatments are being explored:
1. **Rho Kinase Inhibitors (e.g., Netarsudil)**: Although approved for lowering intraocular pressure, their broader therapeutic potentials are still under investigation.
2. **Cannabinoids**: Research is ongoing to determine their efficacy in reducing intraocular pressure, though they are not yet approved for this use.
3. **Neuroprotective Agents (e.g., Memantine)**: Originally approved for Alzheimer's disease, these agents are being studied for their potential to protect optic nerve cells in glaucoma patients.
4. **Gene Therapy**: Experimental treatments involving gene modification to increase fluid outflow from the eye are in early stages of research.
5. **Stem Cell Therapy**: Investigations are ongoing to evaluate if stem cells can regenerate damaged optic nerve cells or improve fluid drainage in the eye.
These treatments are not yet standard care and are generally available only through clinical trials or special programs. - Lifestyle Recommendations
-
Lifestyle recommendations for managing open-angle glaucoma include:
1. **Regular Eye Exams**: Schedule routine eye check-ups to monitor intraocular pressure and optic nerve health.
2. **Medication Adherence**: Consistently use prescribed eye drops or medications to control eye pressure.
3. **Healthy Diet**: Consume a diet rich in leafy greens, fruits, and omega-3 fatty acids to support eye health.
4. **Exercise Regularly**: Engage in moderate physical activity like walking or swimming to lower intraocular pressure.
5. **Manage Blood Pressure**: Keep blood pressure within a healthy range to avoid additional eye pressure and damage.
6. **Avoid Smoking**: Quit smoking to improve vascular health and reduce the risk of ocular damage.
7. **Protect Eyes from UV Rays**: Wear sunglasses to reduce exposure to harmful ultraviolet light.
8. **Limit Caffeine**: Reduce caffeine intake, as excessive consumption can elevate intraocular pressure.
9. **Stay Hydrated**: Drink plenty of water throughout the day to maintain overall fluid balance.
10. **Mind Your Head Position**: Avoid positions that keep your head upside down for extended periods. - 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 open-angle glaucoma, there are several drugs that have been explored for repurposing. These include:
1. **Brimonidine**: Originally developed to treat hypertension, brimonidine has found a role in reducing intraocular pressure in glaucoma patients.
2. **Rho-kinase inhibitors (e.g., Netarsudil)**: These were initially investigated for cardiovascular conditions but have shown efficacy in reducing intraocular pressure by increasing aqueous humor outflow.
3. **Statins (e.g., Simvastatin)**: Commonly used for lowering cholesterol, statins have been studied for their potential neuroprotective effects in glaucoma.
4. **Cannabinoids**: Though primarily known for their use in pain management and as antiemetics, cannabinoids have been investigated for their intraocular pressure-lowering effects.
Further research is ongoing to fully understand the efficacy and safety of these repurposed drugs for the treatment of open-angle glaucoma. - Metabolites
-
Open-angle glaucoma is associated with several metabolic changes, primarily involving the dysregulation of metabolites that affect eye pressure and optic nerve health. Key metabolites and pathways include:
1. **Amino Acids**: Alterations in the levels of certain amino acids, such as glutamate, have been observed, which may contribute to neurotoxicity.
2. **Lipids**: Changes in lipid metabolism, including cholesterol and sphingolipids, can impact the trabecular meshwork and intraocular pressure.
3. **Antioxidants**: Levels of antioxidants like glutathione are often decreased, leading to increased oxidative stress and damage to ocular tissues.
Research in metabolomics continues to uncover more about the specific metabolites involved, offering potential pathways for new treatments and diagnostics. - Nutraceuticals
- For open-angle glaucoma, nutraceuticals like omega-3 fatty acids, antioxidants (e.g., vitamins C and E), and ginkgo biloba may have potential benefits in supporting eye health, although their effectiveness specifically for glaucoma is not well-established. Research into their role is ongoing and not universally endorsed by the medical community. Always consult with a healthcare provider before starting any new supplements for glaucoma management.
- Peptides
- For open-angle glaucoma, peptides and nanotechnology have emerged as potential areas of therapeutic development. Peptides may play a role in regulating intraocular pressure by influencing cellular mechanisms and signaling pathways. Nanotechnology, on the other hand, can enhance drug delivery systems, allowing for controlled release and targeted treatment, potentially improving the efficacy and reducing side effects of existing medications.