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Glaucoma

Disease Details

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Description: Glaucoma is a group of eye conditions that damage the optic nerve, often due to abnormally high pressure in the eye, which can lead to vision loss or blindness if untreated.
Type: Glaucoma primarily comes in two types: open-angle and angle-closure. The genetic transmission of glaucoma can vary depending on the specific form and subtype, but broadly speaking, it can be inherited in an autosomal dominant or autosomal recessive manner. Specific genes, such as MYOC (myocilin) for primary open-angle glaucoma, and others like OPTN (optineurin) and WDR36, have been implicated. Genetic predisposition combined with environmental factors also plays a role in the development of the disease.
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: Glaucoma is a group of eye conditions that damage the optic nerve, often due to high intraocular pressure. The onset of glaucoma can be gradual and asymptomatic, making early detection challenging. Regular eye exams are crucial, especially for those at higher risk, such as individuals over 60, those with a family history, or people of African, Asian, or Hispanic descent.
Prevalence: The prevalence of glaucoma varies by age, ethnicity, and geographic region. Globally, it is estimated that over 76 million people were affected by glaucoma in 2020, with a projected increase to approximately 111.8 million by 2040. The risk of developing glaucoma increases with age, and it is more common among certain ethnic groups such as African Americans, who are at higher risk of open-angle glaucoma, and East Asians, who are more prone to angle-closure glaucoma. Early detection and treatment are crucial to prevent vision loss associated with this condition.
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: Glaucoma is a chronic eye condition that typically involves increased intraocular pressure, leading to optic nerve damage. While it is not curable, it is not considered intractable because effective treatments exist that can manage the condition and slow its progression. These treatments include medications (such as eye drops), laser therapy, and surgical procedures. Early detection and consistent management are crucial to preserving vision.
Disease Severity: The severity of glaucoma can vary widely and depends on factors such as the type of glaucoma, the stage at which it is diagnosed, and how well it responds to treatment. It can range from mild, where there is minimal damage to the optic nerve and slight vision loss, to severe, where there is significant optic nerve damage and major vision impairment. In the worst cases, untreated glaucoma can lead to blindness. Regular monitoring and appropriate treatment are crucial in managing the progression of the disease.
Healthcare Professionals: Disease Ontology ID - DOID:1686
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: Glaucoma is not typically characterized by a carrier status because it is not a single-gene inherited condition. Instead, it is often a complex disease influenced by multiple genetic and environmental factors. Some specific types of glaucoma can have a hereditary component, but carrier status in the traditional sense, often used in single-gene recessive disorders, is not applicable here.
Mechanism: Glaucoma is a group of eye conditions that damage the optic nerve, often associated with elevated intraocular pressure. Here are the mechanisms and molecular mechanisms involved in glaucoma:

**Mechanisms:**
1. **Elevated Intraocular Pressure (IOP):** Most forms of glaucoma are linked to increased IOP, which exerts pressure on the optic nerve. The elevated pressure can result from impaired drainage of aqueous humor through the trabecular meshwork and Schlemm's canal.
2. **Optic Nerve Damage:** The increased pressure can lead to progressive damage to the optic nerve fibers, which results in visual field loss and, if untreated, can lead to blindness.
3. **Loss of Retinal Ganglion Cells (RGCs):** Damage to the optic nerve fibers results in the loss of retinal ganglion cells, which are crucial for transmitting visual information from the retina to the brain.

**Molecular Mechanisms:**
1. **Mechanical Stress:** Elevated IOP causes mechanical stress on the optic nerve head, leading to axonal injury and impairment of retrograde axonal transport. This disrupts the delivery of essential neurotrophic factors to RGCs.
2. **Ischemia and Hypoxia:** High IOP can compress blood vessels supplying the optic nerve, leading to ischemic conditions and insufficient oxygen (hypoxia), contributing to RGC death.
3. **Neuroinflammation:** Damage to the optic nerve triggers a neuroinflammatory response, characterized by the activation of glial cells, release of pro-inflammatory cytokines, and recruitment of immune cells. This inflammation exacerbates neurodegeneration.
4. **Oxidative Stress:** Elevated IOP and impaired blood flow can increase the production of reactive oxygen species (ROS), leading to oxidative stress and subsequent damage to cellular components, including lipids, proteins, and DNA.
5. **Apoptosis:** Stress signals from mechanical and ischemic damage activate apoptotic pathways, particularly via the intrinsic (mitochondrial) and extrinsic (death receptor) pathways. Key molecules involved include cytochrome c, caspases, and Bax/Bcl-2 proteins, leading to programmed cell death of RGCs.
6. **Genetic Factors:** Mutations in genes such as MYOC (myocilin), OPTN (optineurin), and CYP1B1 are linked to glaucoma. These genetic mutations can affect aqueous humor outflow, optic nerve health, and susceptibility to damage.

Understanding these mechanisms and molecular pathways is crucial for developing targeted therapies to prevent or mitigate optic nerve damage in 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: Compassionate use and off-label or experimental treatments for glaucoma are generally considered when standard therapies are insufficient or unsuitable.

**Compassionate Use Treatment:**
1. **Gene Therapy:** Research is ongoing into gene therapies that could potentially protect or regenerate optic nerve cells.
2. **Stem Cell Therapy:** Experimental treatments using stem cells aim to repair or replace damaged optic nerve tissues.

**Off-Label Treatments:**
1. **Memantine:** Originally used for Alzheimer's disease, it is being investigated for its neuroprotective properties to prevent optic nerve damage.
2. **Pharmacological Neuroprotection:** Specific drugs, such as brimonidine, may be used off-label for their potential neuroprotective effects to preserve vision.

**Experimental Treatments:**
1. **Rho Kinase Inhibitors:** These are currently being explored for their ability to enhance aqueous humor outflow and reduce intraocular pressure (IOP).
2. **Cannabinoids:** Some studies are examining the efficacy of cannabinoids in lowering IOP, though results have been mixed and further research is warranted.
3. **Neurotrophic Factors:** These include molecules like brain-derived neurotrophic factor (BDNF) aimed at supporting retinal ganglion cells.

Patients should consult with their healthcare providers to discuss the potential risks and benefits of these treatments.
Lifestyle Recommendations: ### Lifestyle Recommendations for Glaucoma:

1. **Regular Eye Exams**: Timely screenings help in early detection and management.
2. **Medication Adherence**: Follow prescribed treatments meticulously.
3. **Healthy Diet**: Incorporate leafy greens, citrus fruits, and fish high in omega-3 fatty acids.
4. **Exercise**: Engage in regular physical activity like walking or swimming, which may help lower eye pressure.
5. **Hydration**: Drink fluids evenly throughout the day to avoid sudden spikes in eye pressure.
6. **Eye Protection**: Wear protective eyewear to prevent injuries that can exacerbate glaucoma.
7. **Limit Caffeine**: Excessive caffeine can increase intraocular pressure.
8. **Stress Management**: Practice relaxation techniques such as meditation or yoga.
9. **Avoid Smoking**: Smoking can worsen glaucoma and overall eye health.
10. **Elevate Head During Sleep**: Use a wedge pillow to keep your head elevated, lowering eye pressure during sleep.

These tips can support management and slow the progression of glaucoma.
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: No known repurposable drugs are approved specifically for glaucoma treatment. Glaucoma management primarily includes medications like prostaglandin analogs, beta blockers, alpha agonists, and carbonic anhydrase inhibitors. It's essential to consult with a healthcare provider for a treatment plan suitable for the individual's condition.
Metabolites: Glaucoma is a group of eye conditions that damage the optic nerve, often due to elevated intraocular pressure. Metabolites associated with glaucoma include certain amino acids, lipids, and oxidative stress markers. For instance, disruptions in metabolites like glutamate, glycine, and various fatty acids have been observed in patients with glaucoma.

Nanotechnology offers potential in glaucoma treatment and diagnosis. Nanoparticles can be used for targeted drug delivery to achieve controlled release and higher bioavailability. Additionally, nanoparticle-based imaging agents can enhance early diagnosis by improving the visualization of ocular tissues at a molecular level.
Nutraceuticals: For glaucoma, nutritional supplements and nutraceuticals that have been studied for their potential benefits include antioxidants like vitamins C and E, omega-3 fatty acids, and ginkgo biloba extract, which may help protect retinal cells and optic nerves. However, while some studies suggest potential benefits, the evidence is not conclusive, and these should not replace standard medical treatments.

Nanotechnology approaches, specifically nanoparticles, are being explored for glaucoma treatment to improve drug delivery to the eye. This includes nanoscale eye drops and implants that enhance the penetration and extended release of medications, potentially improving treatment effectiveness and patient compliance.

Always consult healthcare providers for personalized advice and treatments.
Peptides: In the context of glaucoma, peptides can be involved in the development of new therapeutic strategies. Peptides may be designed to target specific pathways that regulate intraocular pressure or protect retinal ganglion cells.

Nanotechnology, particularly using nanoparticles, offers potential for improving glaucoma treatment by enabling targeted drug delivery, enhancing drug stability, and allowing for sustained release of medications, potentially increasing the effectiveness and reducing the side effects of glaucoma therapies.