Glaucoma

 

 Glaucoma

Glaucoma, the second leading cause of permanent blindness in the United States, predominantly affects older adults. Glaucoma is not a single disease process but a group of disorders characterized by a progressive optic nerve neuropathy resulting in a characteristic appearance of the optic disc and a specific pattern of an irreversible visual field defect that are associated frequently but not invariably with raised IOP. 

It encompasses four main types: primary open-angle and angle-closure, secondary open and angle-closure glaucoma. Primary open-angle glaucoma (POAG) is the most prevalent type in the US. Glaucoma is characterized by the gradual loss of retinal ganglion cells and optic nerve fibers, resulting in a distinct appearance of the optic nerve head and progressive vision impairment, notably peripheral vision loss.

POAG often presents without symptoms until advanced stages, highlighting the importance of regular eye exams for early detection. Conversely, acute angle-closure glaucoma can manifest suddenly with rapid vision decline, accompanied by symptoms like eye pain, headache, nausea, and vomiting. Secondary glaucoma typically stems from prior eye injury or disease, leading to elevated intraocular pressure and subsequent optic nerve damage. Additionally, normal or low-tension glaucoma showcases similar visual loss patterns to POAG but with normal intraocular pressure readings.

Although congenital, infantile, and juvenile variants exist, the aforementioned types primarily affect individuals over 40. While increased intraocular pressure is a common correlation, its direct causative role remains unproven. Genetic factors may contribute, as indicated by higher concordance rates in monozygotic twins. However, environmental influences also play a role.

Despite the lack of a cure or prevention, glaucoma progression can be managed to prevent further vision loss through medication, glaucoma laser treatment, or surgical interventions.

Primary Open-Angle Glaucoma (POAG)

  Etiology: Exact cause unknown; clear correlation with elevated eye pressures in most cases.

  Pathophysiology:

•  Slow, painless optic nerve damage attributed to ineffective drainage system in the eye
•  The decreased outflow facility primarily starts at the inner wall of Schlemm’s canal.
•  Gradual elevation of intraocular pressure (IOP) leads to characteristic optic nerve damage.
•  Possible mechanism: Increased IOP causes decreased blood flow to optic nerve fibers, resulting in ischemic damage.

  Clinical Presentation:

• The most common type.Asymptomatic until advanced stages
•  Slow loss of peripheral vision.
•  Eventually progresses to central vision loss if untreated.
• Optic disc changes and increased cup-to-disc ratio (>0.5) are observed.

Subsets of Open-Angle Glaucoma

  Juvenile Open-Angle Glaucoma:

•    Affects individuals aged 5-35.
•    Uncommon; presents later due to gradual elevation of IOP.
•    Eye pressures typically >30 mm Hg.
•    Similar pathophysiology to POAG but in younger patients.

  Low-Tension/Normal-Tension Glaucoma:

• Characteristic optic disc cupping and peripheral visual-field loss.
• Consistently low IOP (<21 mm Hg).
• Theories: Abnormally pressure-sensitive optic nerve or intermittent ischemic change.
• Higher prevalence of vasospastic disorders; possible vascular autoregulatory defect involvement such as migraines, Raynaud phenomenon, autoimmune diseases, ischemic vascular diseases, and coagulopathies seen in these patients, which may suggest a vascular autoregulatory defect playing a role in the pathogenesis of the disease.
• Unique features: Greater frequency of nerve fiber layer hemorrhages; thinner neuroretinal rim inferiorly and inferotemporal.
• Visual field defects: Focal, deeper, closer to fixation.

Angle-Closure Glaucoma

• Etiology: Abrupt blockage of the eye's drainage system.

Pathophysiology:

• Age-related thickening of lens leading to relative pupillary block.
• Anteriorly displaced iris and anatomical variations facilitate blockage.
• Pupillary block is the underlying cause in >90% of cases.
• Sudden pupil dilation or anteriorly displaced iris blocks drainage, causing rapid intraocular pressure increase.

  Clinical Presentation:

• Presents with sudden severe ocular pain, redness, blurry vision, and nausea.
• Medical emergency; rapid vision loss due to retinal vascular occlusion, ischemic optic neuropathy, or optic nerve damage.
• High intraocular pressure (typically 30-50 mm Hg).
• Pupillary dilation triggers attacks.
• Physical exam shows unresponsive mid-dilated pupil and firm eyeball.
• Represents about 10% of glaucoma cases.

Secondary Causes of Angle-Closure Glaucoma

  Marfan’s Syndrome:

•    Lens subluxation displaces into the pupil or anterior chamber, causing the acute pupillary block.

  Plateau Iris:

•    Elongated or anteriorly positioned ciliary processes push iris edges forward, leading to chronic angle closure.

  Iridocorneal Endothelial Syndrome:

• Irregular corneal endothelium migrates onto trabecular meshwork and peripheral iris, creating contraction and high peripheral anterior synechiae, closing angle.

  Neovascularization:

• Fibrovascular membrane formation flattens the iris, and displaces it anteriorly, causing total synechial closure of angle.

  Post-ophthalmic Surgery:

•  Ciliary body edema, scleral buckle placement, fibrin deposition, gas, or silicone oil induce angle-closure.

Secondary Open-Angle Glaucoma:

 Causes:

• Injury, eye disease, rarely eye surgery causing increased intraocular pressure and optic nerve damage.

  Mechanisms:

• Laser surgery: Can cause pigment release, inflammatory cells, debris, and mechanical deformation, leading to trabecular meshwork blockage and increased intraocular pressure.
• Neovascularization: diseases can physically block outflow tracts, contributing to secondary open-angle glaucoma.
• Pseudoexfoliative type: Flaky material peels off the outer lens capsule, clogging the trabecular meshwork.
• Pigmentary type: Pigment granules from the back of the iris break off, clogging the trabecular meshwork, particularly in myopic eyes.
• Steroids Induced Glaucoma: Steroids increase outflow resistance by upregulating glucocorticoid receptors in the trabecular meshwork and accumulating glycosaminoglycans, suppressing phagocytic activity.
• Carotid-Cavernous Fistula: Abnormal communication between cavernous sinus and carotid artery leads to elevated episcleral venous pressure, dilation of retinal veins, and optic disc swelling, damaging optic nerve fibers.
• Glaucomatocyclitic Crisis: Recurrent acute attacks of increased intraocular pressure can cause glaucomatous damage to the optic nerve over time, even if they resolve without treatment.

Epidemiology:

Global Epidemiology of Glaucoma

• Approximately 60 million people worldwide suffer from optic neuropathy due to glaucoma.
• Open-angle glaucoma is most prevalent in the African population.
• African descent individuals are up to 15 times more likely to experience blindness from open-angle glaucoma compared to other population groups.
• Angle-closure glaucoma is most prevalent in the Inuit population.
•  Women are affected at a higher rate than men, especially in populations of Asian descent, which generally have shallower anterior chambers.
• Normal-tension glaucoma is most prevalent in Japanese populations

Risk Factors:

• Age is a significant risk factor for the continual loss of retinal ganglion cells in all types of glaucoma.

Other risk factors include:

• Family history of glaucoma in primary relatives (parents, siblings, children).
• Medical conditions such as diabetes, high blood pressure, and heart disease.
• Eye trauma, anatomical differences (e.g., thinner corneas), history of retinal detachment, eye tumors, or inflammation.
• Prolonged corticosteroid use.

Pathophysiology:

Optic Nerve and Visual Transmission:

• The optic nerve is a bundle of over 1 million nerve fibers responsible for transmitting visual signals from the retina to the brain's visual processing centers in the occipital lobe.
• Glaucoma causes damage primarily to the retinal nerve fiber layer, disrupting the transmission of visual signals and resulting in progressive vision loss.

Aqueous Humor Dynamics:

• Aqueous humor is a clear fluid produced by the non-pigmented epithelial cells of the ciliary body processes.
• It provides nutrients to the avascular tissues of the anterior segment and helps maintain intraocular pressure.
•  Aqueous humor has a circadian pattern of production, with fluctuations throughout the day.

Aqueous Humor and Drainage:

• Aqueous humor, the fluid within the anterior chamber of the eye, is crucial for maintaining intraocular pressure and nourishing ocular structures.
• Produced by non-pigmented epithelial cells of the ciliary body processes, aqueous humor circulates through a drainage system: It exits through the trabecular meshwork, Schlemm’s canal, episcleral venous system, and larger orbital venous system into systemic circulation.
• Trabecular meshwork, composed of multiple layers of connective tissue and the endothelium of Schlemm’s canal, acts as a one-way valve for aqueous drainage.

Aqueous Humor Drainage Pathways:

Aqueous humor exits the eye through two main pathways:

• The conventional outflow pathway: It is the main outlet for aqueous from the anterior chamber. Approximately 70 to 80% of the total aqueous is drained out through this route.
• A pressure-dependent system involving the trabecular meshwork, Schlemm's canal, and episcleral venous system.
• The uveoscleral outflow pathway: A pressure-independent pathway allowing fluid to egress through the ciliary muscle and iris root into the supraciliary and suprachoroidal space.

 

Pressure Regulation and Glaucomatous Damage:

•  Elevated intraocular pressure (IOP) is a major risk factor for glaucomatous optic nerve damage.
• Prolonged elevation of IOP leads to the death and atrophy of retinal ganglion cells and their axons, resulting in characteristic optic nerve cupping on fundoscopic examination.

Normal Intraocular Pressure (IOP):

•  Normal IOP is considered to be approximately 16 +/- 3 mm Hg, but it fluctuates throughout the day due to various physiological factors.
• Factors influencing IOP fluctuations include heart rate, respiration, exercise, fluid status, systemic medications, time of day, alcohol consumption, patient position, and topical medications.

Screening and Diagnosis:

• Pressure readings above 21 mm Hg are considered above normal physiologic eye pressure and raise concerns for potential glaucomatous nerve damage.
• However, elevated screening pressure alone is not diagnostic of glaucoma, as transient spikes in pressure may go undetected during routine screening.
  

Evaluation for Glaucoma:

Evaluation for glaucoma involves a combination of tests to assess various aspects of eye health and function. These tests include:

1. Fundoscopic Examination: Examination of the optic nerve head and surrounding structures for signs of damage or characteristic changes associated with glaucoma.

2. Visual Field Testing: Assessing the peripheral vision to detect any visual field defects, which can be indicative of glaucoma progression.

3. Tonometry: Measurement of intraocular pressure (IOP), as elevated IOP is a significant risk factor for glaucoma.

4. Optical Coherence Tomography (OCT): Imaging technique used to assess the thickness of the retinal nerve fiber layer, providing detailed information about structural changes associated with glaucoma.

5. Gonioscopy: Examination of the drainage angle of the eye to assess the risk of angle-closure glaucoma.

Other helpful tests may include:

1. Visual Acuity: Assessing the clarity of vision to determine if glaucoma is affecting visual function.
2. Pachymetry: Measurement of corneal thickness, as thin corneas may be associated with an increased risk of glaucoma.
3. Retinal Scans: Imaging techniques to monitor progressive changes in the retinal nerve fiber layer, providing additional information for glaucoma management.

Diagnosis and Staging:

Glaucoma diagnosis is based on characteristic clinical findings of progressive optic neuropathy or visual field defects observed during the evaluation tests mentioned above. It's important to note that there isn't a single definitive test for diagnosing glaucoma. Healthcare providers need to recognize characteristic optic nerve appearance, assess risk factors, and integrate results from various tests to establish an accurate diagnosis and stage the severity of glaucoma.

Recommendations for Screening:

The American Academy of Ophthalmology recommends routine comprehensive eye examinations for individuals with risk factors for glaucoma. The frequency of these examinations should be determined on an individual basis, considering factors such as age, race, family history, and other relevant risk factors.

This comprehensive approach to evaluation and diagnosis allows healthcare providers to effectively manage and monitor glaucoma, thereby preserving vision and improving patient outcomes.

Treatment and Management of Glaucoma:

Glaucoma management focuses on preventing further vision loss, as there is currently no treatment to reverse existing damage. Treatment plans are tailored to the specific type and severity of glaucoma.

1. Open-Angle Glaucoma:

1. Medications: Initial management typically involves eye drops to lower intraocular pressure (IOP). These include prostaglandin analogs, beta-blockers, carbonic anhydrase inhibitors, alpha-2 agonists, miotic agents, rho-kinase inhibitors, and nitric-oxide donating medications.
2. Laser Trabeculoplasty: This procedure may be used as a primary treatment option to improve drainage of aqueous humor and lower IOP.
3. Surgical Options: If medication and laser treatments are ineffective, surgical interventions like trabeculectomy (creating a new drainage channel), inserting drainage valves or tubes, or laser treatment to reduce aqueous production may be considered.
4. Minimally Invasive Glaucoma Surgery (MIGS): An evolving option for mild-moderate glaucoma, MIGS has a favorable safety profile compared to traditional surgeries and can effectively reduce IOP levels.

2. Normal-Tension Glaucoma:

1. Medications: Similar to open-angle glaucoma, medications are used to lower IOP. These may include prostaglandin analogs, alpha-2 agonists, carbonic anhydrase inhibitors, and miotics.
2. Treatment of Underlying Conditions: Addressing any underlying medical conditions that may contribute to glaucoma is important.
3. Surgical Interventions: If medical management fails, laser trabeculoplasty or filtration surgery may be considered to prevent vision loss.

3. Angle-Closure Glaucoma:

1. Emergency Treatment: Angle-closure glaucoma requires immediate attention due to the risk of optic nerve damage or retinal vascular occlusion. Medications to reduce eye pressure are administered, followed by a laser procedure called laser peripheral iridotomy.
2. Laser Peripheral Iridotomy: This procedure creates a small hole in the iris to relieve pressure and open the drainage angle.
3. Follow-Up: After the acute crisis, patients should undergo follow-up gonioscopy to ensure the angle has reopened, and prophylactic measures may be considered for the contralateral eye.

4. Secondary Glaucoma:

• Treatment of Underlying Cause: Secondary glaucoma is managed by addressing the underlying condition that contributes to elevated intraocular pressure. This may include medications to lower IOP, depending on the cause.

Regular follow-up appointments and monitoring are essential to track disease progression and adjust treatment plans accordingly. Collaboration between patients and healthcare providers is crucial in managing glaucoma effectively and preserving vision.

Differential Diagnosis in Glaucoma: In diagnosing primary open-angle glaucoma (POAG), it's crucial to rule out other disease processes that can cause optic neuropathy. Additionally, in acute angle-closure glaucoma (AACG), various conditions with similar presentations must be considered. Here's an overview of the potential differentials: 1. Primary Open-Angle Glaucoma (POAG):

1. Ischemic Optic Neuropathy: Previous episodes of ischemic optic neuropathy can mimic the visual field loss seen in POAG.
2. Optic Atrophy: Optic nerve atrophy may present with similar visual field defects and pseudo-cupping of the optic nerve.
3. Compressive Non-Glaucomatous Optic Neuropathy: Conditions causing compression of the optic nerve, such as tumors or orbital masses, can lead to similar visual field defects.
   

2. Acute Angle-Closure Glaucoma (AACG):

• Iritis: Inflammation of the iris can cause symptoms similar to AACG, including ocular pain and redness.

• Traumatic Hyphema: Hemorrhage into the anterior chamber after trauma can lead to elevated intraocular pressure and mimic AACG symptoms.

• Conjunctivitis: Although typically less severe, conjunctivitis can present with ocular pain, redness, and blurred vision.

• Migraine and Cluster Headache: Headache disorders may present with ocular symptoms resembling AACG.

• Corneal Abrasion, Ulcer, or Infectious Keratitis: Corneal conditions can cause severe eye pain and redness.

• Periorbital Infections: Infections around the eye can manifest with similar symptoms to AACG.

Prognosis of Glaucoma:

Glaucoma is a serious condition that, if left untreated, can lead to permanent vision loss. The risk of optic nerve damage increases with higher intraocular pressure (IOP). However, with appropriate treatment, the prognosis is generally good for most patients. Maintaining low intraocular pressures can prevent further visual field loss and halt the progression of the disease

Complications:

Complications of glaucoma include visual field loss, which can eventually progress to complete blindness, with some individuals experiencing no light perception in the affected eye.

Patient Education:

Regular eye exams, including checking the intraocular pressure of both eyes and a fundoscopic exam with careful attention to the optic nerve, are crucial for early detection of glaucoma suspects. Further testing may be necessary to confirm the diagnosis in high-risk individuals.

Patients should be educated about the causes, risk factors, and treatment options for glaucoma. Patients need to understand that glaucoma often causes slow, progressive vision loss that may not be noticeable until a significant portion of the visual field is affected. Therefore, regular eye exams are highly recommended to identify high-risk patients and prevent irreversible vision loss.

By emphasizing the importance of regular eye exams and early detection, patients can take proactive steps to manage their condition effectively and preserve their vision.

REFERENCE:

Dietze J, Blair K, Havens SJ. Glaucoma. [Updated 2022 Jun 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.https://www.ncbi.nlm.nih.gov/books/NBK538217/

https://www.researchgate.net/publication/370818317_Molecular_genetics_of_primary_open-angle_glaucoma?_tp=eyJjb250ZXh0Ijp7ImZpcnN0UGFnZSI6Il9kaXJlY3QiLCJwYWdlIjoiX2RpcmVjdCJ9fQ