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Primary Open Angle Glaucoma

Disease Details

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Description: Primary open-angle glaucoma is a chronic eye disorder characterized by progressive optic nerve damage and vision loss due to increased intraocular pressure.
Type: Primary open-angle glaucoma is typically considered to have a complex inheritance pattern, where multiple genes and environmental factors contribute to the risk. While it can run in families, it does not follow a straightforward Mendelian inheritance pattern. Several genes, such as MYOC and OPTN, have been associated with the condition, and mutations in these genes can increase the risk of developing primary open-angle glaucoma.
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: Onset of primary open-angle glaucoma (POAG) is typically gradual and often occurs in adults over the age of 40. The condition is chronic and progressive, developing over many years without noticeable symptoms in the early stages. By the time vision problems are detected, significant irreversible damage to the optic nerve may have already occurred.
Prevalence: The prevalence of primary open-angle glaucoma (POAG) varies by age and ethnicity. Globally, it is estimated to affect approximately 2-3% of the population over the age of 40. For specific groups, prevalence rates can be higher, with African descent populations experiencing a 4-5% prevalence rate for those over 40, and as high as 10% in those over 80.
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: Primary open-angle glaucoma (POAG) is a chronic eye condition that can lead to irreversible vision loss if not managed properly. However, it is not considered intractable. With appropriate treatment, such as medications, laser therapy, or surgery, the progression of the disease can be slowed or halted, thereby preserving vision. Regular monitoring and adherence to treatment are crucial for effective management of POAG.
Disease Severity: Primary open-angle glaucoma (POAG) is a chronic condition that can lead to permanent vision loss if not properly managed.

- **Disease Severity**: The severity of POAG can vary significantly among patients. It typically progresses slowly and may initially be asymptomatic, which makes early detection challenging. As the disease advances, patients may experience a gradual loss of peripheral vision, which can progress to central vision loss if left untreated. Effective management and treatment are crucial to slowing disease progression.

- **Nan**: No applicable information for "nan" in the context of primary open-angle glaucoma.
Healthcare Professionals: Disease Ontology ID - DOID:1070
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: Primary open-angle glaucoma (POAG) is not inherited in a simple Mendelian fashion, so there is no "carrier status" as there might be for single-gene recessive disorders. Instead, POAG is a complex disease influenced by multiple genetic and environmental factors. Individuals with a family history of glaucoma are at higher risk, but there's no specific carrier state.
Mechanism: Primary open-angle glaucoma (POAG) primarily involves the gradual increase in intraocular pressure (IOP) due to improper drainage of aqueous humor through the trabecular meshwork, leading to optic nerve damage.

Molecular mechanisms include:
1. **Trabecular Meshwork Dysfunction**: Disruption in the extracellular matrix and cytoskeletal organization of the trabecular meshwork, impaired cellular function may lead to reduced aqueous humor outflow.
2. **Oxidative Stress**: Increased oxidative stress can damage trabecular meshwork cells and optic nerve cells, exacerbating disease progression.
3. **Genetic Factors**: Mutations in genes such as MYOC (myocilin), OPTN (optineurin), and TBK1 (TANK-binding kinase 1) have been linked to altered protein function contributing to POAG.
4. **Neurodegenerative Pathways**: Dysregulation of neurotrophic factors, glutamate toxicity, and mitochondrial dysfunction can lead to the death of retinal ganglion cells.
5. **Immune Response**: Abnormal immune responses and chronic inflammation may play a role in optic nerve damage.

These mechanisms collectively contribute to the characteristic optic neuropathy observed in POAG.
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 primary open-angle glaucoma (POAG), compassionate use treatments, off-label, or experimental options can sometimes be considered, typically under strict regulatory guidance and often in clinical trial settings. Here are a few such options:

1. **Rho-Kinase Inhibitors:** Primarily developed for lowering intraocular pressure (IOP), some newer drugs in this category like netarsudil are being explored in a broader context for glaucoma.

2. **Neuroprotective Agents:** While IOP-lowering is the mainstay, experimental treatments such as brimonidine (an alpha-2 adrenergic agonist) are being studied for their potential neuroprotective effects.

3. **Cannabinoids:** There is ongoing research into the use of cannabinoids (like THC and CBD) for glaucoma. However, this is still highly experimental and controversial due to mixed efficacy and potential side effects.

4. **Gene Therapy:** Another experimental approach involves gene therapy to improve aqueous outflow or protect retinal cells from degenerating.

5. **Sustained-Release Drug Delivery Systems:** Various sustained-release formulations, such as bimatoprost implants, are under investigation to provide long-term IOP control with fewer side effects.

6. **New Surgical Techniques:** Minimally invasive glaucoma surgeries (MIGS) like the use of micro-stents are also part of ongoing clinical trials to assess their effectiveness and safety over the long term.

Patients interested in these treatments usually participate in clinical trials or special access programs and should consult with their ophthalmologist to discuss potential benefits and risks.
Lifestyle Recommendations: For managing primary open-angle glaucoma, consider these lifestyle recommendations:

1. **Regular Eye Exams**: Schedule comprehensive eye exams as recommended by your healthcare provider to monitor eye pressure and optic nerve health.

2. **Medication Adherence**: Use prescribed eye drops or medications consistently to reduce intraocular pressure.

3. **Physical Activity**: Engage in regular physical exercise, like walking or jogging, which can help lower eye pressure. Avoid exercises that involve inverted positions or heavy lifting.

4. **Healthy Diet**: Eat a balanced diet rich in antioxidants, vitamins, and minerals, particularly those beneficial for eye health, such as leafy greens and fish high in omega-3 fatty acids.

5. **Hydration**: Drink fluids in small amounts frequently rather than large quantities at once to avoid spikes in eye pressure.

6. **Protect Your Eyes**: Wear protective eyewear to prevent injuries that could exacerbate the condition.

7. **Smoking and Alcohol**: Avoid smoking and limit alcohol consumption as they can adversely affect overall eye health.

8. **Stress Management**: Practice stress-reduction techniques such as meditation or yoga, which can help lower eye pressure.

9. **Elevate Head During Sleep**: Use pillows to elevate your head slightly during sleep, which may help reduce intraocular pressure.

10. **Limit Caffeine**: Reduce caffeine intake, as it can cause short-term spikes in eye pressure.

Discuss these recommendations with your healthcare provider to tailor them to your specific condition and overall health.
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 primary open-angle glaucoma (POAG), some repurposable drugs that have shown potential include:

1. **Statins**: Commonly used for lowering cholesterol, statins have been studied for their potential neuroprotective effects in glaucoma.

2. **Brimonidine**: Originally an alpha-2 adrenergic agonist used for lowering intraocular pressure, it also has potential neuroprotective properties.

3. **Dorzolamide**: Typically used to reduce intraocular pressure, this carbonic anhydrase inhibitor may have additional neuroprotective benefits.

4. **Timolol**: A non-selective beta-blocker used for reducing intraocular pressure which might have repurposable benefits in glaucoma therapy.

These drugs are considered based on their potential to target different aspects of the disease, such as neuroprotection, vascular flow improvement, and reduction of intraocular pressure. However, the effectiveness and safety of these repurposed drugs for POAG need further validation through clinical trials.
Metabolites: In primary open-angle glaucoma (POAG), the metabolic profile can be altered. Some studies have identified changes in various metabolites, including amino acids, lipids, and glucose metabolism. Elevated levels of homocysteine and alterations in lipid profiles, particularly cholesterol and triglycerides, have been observed in patients with POAG. These metabolites may play a role in the pathophysiology of the disease, potentially influencing intraocular pressure and optic nerve health. Further research is necessary to fully understand the metabolic changes associated with POAG and their implications for diagnosis and treatment.
Nutraceuticals: The role of nutraceuticals in primary open-angle glaucoma (POAG) is an area of active research. Some potential nutraceuticals that may have beneficial effects for POAG patients include:

1. **Antioxidants**: Nutrients like vitamins C and E, along with compounds such as flavonoids found in fruits and vegetables, may help reduce oxidative stress in the eye.
2. **Omega-3 Fatty Acids**: Found in fish oil, these may improve ocular blood flow and have neuroprotective effects.
3. **Ginkgo Biloba**: Some studies suggest that Ginkgo Biloba extract may improve blood flow to the optic nerve.
4. **Coenzyme Q10**: This antioxidant may support mitochondrial function and prevent optic nerve damage.
5. **Polyphenols**: Compounds like resveratrol, found in red wine and berries, have been shown to have neuroprotective properties.

It's important for patients to consult with their healthcare provider before starting any nutraceutical regimen, as these supplements can interact with other medications and may not be suitable for everyone.
Peptides: Peptide-based therapies for primary open-angle glaucoma (POAG) are being explored for their potential neuroprotective and intraocular pressure-lowering effects. Some peptides may help protect retinal ganglion cells from degeneration or reduce intraocular pressure by targeting specific pathways involved in aqueous humor dynamics.

Nanotechnology in POAG treatment involves the use of nanoparticles for drug delivery, enabling targeted and sustained release of therapeutic agents. Nanocarriers can improve the bioavailability and efficacy of drugs with potentially fewer side effects, thereby enhancing treatment outcomes for POAG.