Glaucoma

Overview

Definition

• Glaucoma is an optic neuropathy Neuropathy Leprosy that results in a characteristic atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation of the optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions head with corresponding progressive visual field Visual Field The Visual Pathway and Related Disorders defects.
• Often associated with elevated intraocular pressure Intraocular Pressure The pressure of the fluids in the eye. Ophthalmic Exam (IOP), but can occur in normal IOP (normal: 8–21 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg)

Epidemiology

• Glaucoma: 2nd-leading cause of permanent blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity worldwide (after cataract Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). Neurofibromatosis Type 2) 
• Typically occurs after age 40
• Primary open-angle glaucoma: most common type in the United States
• Angle-closure glaucoma: more common in Asian population

Physiology

• Aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy
  • Clear fluid produced by the ciliary body Ciliary body A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. Eye: Anatomy
  • Functions:
    • Preserves intraocular pressure Intraocular Pressure The pressure of the fluids in the eye. Ophthalmic Exam
    • Supplies nutrients and oxygen to cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy and lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy
    • Removes waste products from the same structures
  • Drainage: fluid from ciliary body Ciliary body A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. Eye: Anatomy → posterior chamber Posterior chamber Eye: Anatomy → through the pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities → anterior chamber Anterior chamber The space in the eye, filled with aqueous humor, bounded anteriorly by the cornea and a small portion of the sclera and posteriorly by a small portion of the ciliary body, the iris, and that part of the crystalline lens which presents through the pupil. Eye: Anatomy (angle of cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy and iris) → 90% to trabecular meshwork → canal of Schlemm → episcleral veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology (venous circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment)
• Intraocular pressure Intraocular Pressure The pressure of the fluids in the eye. Ophthalmic Exam
  • Determined by the aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy formation and outflow
  • Autonomic nervous system Autonomic nervous system The ANS is a component of the peripheral nervous system that uses both afferent (sensory) and efferent (effector) neurons, which control the functioning of the internal organs and involuntary processes via connections with the CNS. The ANS consists of the sympathetic and parasympathetic nervous systems. Autonomic Nervous System: Anatomy effects on IOP:
    • Parasympathetic system Parasympathetic system The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system. Autonomic Nervous System: Anatomy: ↓ IOP
      • Ciliary muscle contraction → increased pore size of trabecular meshwork → promotes fluid drainage and decreased pressure
      • Pupillary sphincter muscle contraction ( miosis Miosis Pupil: Physiology and Abnormalities) → opens trabecular meshwork → promotes fluid drainage and decreased pressure
    • Sympathetic system Sympathetic system The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body’s response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. Autonomic Nervous System: Anatomy: ↑ IOP
      • Ciliary muscles Ciliary Muscles Pupil: Physiology and Abnormalities relaxation → decreased pore size of meshwork → increased intraocular pressure Increased intraocular pressure An ocular disease, occurring in many forms, having as its primary characteristics an unstable or a sustained increase in the intraocular pressure which the eye cannot withstand without damage to its structure or impairment of its function. The consequences of the increased pressure may be manifested in a variety of symptoms, depending upon type and severity, such as excavation of the optic disk, hardness of the eyeball, corneal anesthesia, reduced visual acuity, seeing of colored halos around lights, disturbed dark adaptation, visual field defects, and headaches. Osmotic Diuretics
      • Pupillary dilator muscle contraction (mydriasis) → blocks trabecular meshwork → increased pressure

Types of glaucoma

• Primary open-angle glaucoma (POAG): 
  • Overproduction or decreased outflow of aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy
  • More common than angle-closure glaucoma
• Primary angle-closure glaucoma (PACG): 
  • Physical blockage of aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy outflow due to anatomic predisposition 
• Both types have secondary forms (caused by other eye conditions, trauma, medications).
• Subsets:
  • Juvenile open-angle glaucoma:
    • Affects younger population
    • Less common and presents as gradual increase in IOP
  • Normal-tension or low-tension glaucoma:
    • Characteristic optic disc Optic disc The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. Eye: Anatomy cupping and peripheral visual field Visual Field The Visual Pathway and Related Disorders defect
    • IOP is normal.

Open-angle Glaucoma

Risk factors

• Advanced age
• Family history Family History Adult Health Maintenance of glaucoma
• African American race
• Other conditions: hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, elevated IOP

Etiology

• Primary open-angle glaucoma due to idiopathic Idiopathic Dermatomyositis overproduction or decreased drainage of aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy
• Secondary causes: uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea, trauma, steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, and retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome

Clinical presentation

• Initially, asymptomatic (even with elevated IOP)
• Incidental finding on comprehensive eye examination
• As chronic disease progresses: gradual loss of bilateral peripheral vision Vision Ophthalmic Exam → loss of central vision Vision Ophthalmic Exam (late manifestation)
• Blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity, if left untreated

Diagnosis

• Diagnostic triad:
  1. Optic disc Optic disc The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. Eye: Anatomy changes
  2. Visual field Visual Field The Visual Pathway and Related Disorders changes 
  3. Elevated IOP
• Fundus Fundus The superior portion of the body of the stomach above the level of the cardiac notch. Stomach: Anatomy examination:
  • “Cupping”: hollowed-out appearance of optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions
  • Increased cup-to-disc ratio (cup diameter > 50% of vertical disc diameter)
• Visual field testing Visual Field Testing Ophthalmic Exam: automated perimetry Perimetry Ophthalmic Exam
• Intraocular pressure Intraocular Pressure The pressure of the fluids in the eye. Ophthalmic Exam:
  • Elevated IOP (> 21 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg): glaucoma suspect; refer to ophthalmology
  • IOP > 40 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg: emergency referral
  • Affected by corneal thickness and diurnal variation Diurnal Variation Fever
  • Goldmann applanation tonometry: measures IOP but affected by corneal thickness (↑ thickness, false ↑ in pressure) 
  • Pachymetry: measures corneal thickness; helps in accuracy of IOP reading
  • Pneumotonometry/air-puff tonometry:
    • Non-contact
    • Uses air to flatten cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy
• Gonioscopy: 
  • Allows ophthalmologist to visualize angle between cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy and iris
  • “Open” angle: 20–45 degrees
• Optical coherence Coherence A view of the world and the individual’s environment as comprehensible, manageable, and meaningful, claiming that the way people view their life has a positive influence on their health. Neurological Examination tomography:
  • Non-contact
  • Provides digital cross-sectional imaging of optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions, retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy, and anterior chamber Anterior chamber The space in the eye, filled with aqueous humor, bounded anteriorly by the cornea and a small portion of the sclera and posteriorly by a small portion of the ciliary body, the iris, and that part of the crystalline lens which presents through the pupil. Eye: Anatomy

Management

• Goals:
  • Prevent progression of optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions changes
  • Prevent visual field Visual Field The Visual Pathway and Related Disorders deterioration
• Pharmacologic therapy (topical agents):
  • Prostaglandin F2α agonists (preferred initial therapy)
    • Increase drainage of aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy
    • Once- to twice-daily dosing
    • No systemic side effects
    • Side effects: eye irritation, hyperemia, lengthened lashes
    • Latanoprost Latanoprost A prostaglandin f analog used to treat ocular hypertension in patients with glaucoma. Eicosanoids, bimatoprost, tafluprost
  • β-blockers
    • Decrease aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy production 
    • Once–twice daily dosing
    • More affordable than prostaglandin agonists
    • Contraindicated in pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis (can ↑ airway obstruction Airway obstruction Airway obstruction is a partial or complete blockage of the airways that impedes airflow. An airway obstruction can be classified as upper, central, or lower depending on location. Lower airway obstruction (LAO) is usually a manifestation of chronic disease, such as asthma or chronic obstructive pulmonary disease (COPD). Airway Obstruction) or heart disease (worsens bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias, heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR); ↑ heart block, hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension)
    • Timolol Timolol A beta-adrenergic antagonist that is similar in action to propranolol; the levo-isomer is more active. Timolol has been proposed as an anti-hypertensive, anti-arrhythmic, anti-angina, and anti-glaucoma agent. It is also used in the treatment of migraine disorders and tremor. Class 2 Antiarrhythmic Drugs (Beta Blockers) (non-selective), betaxolol Betaxolol A cardioselective beta-1-adrenergic antagonist with no partial agonist activity. Class 2 Antiarrhythmic Drugs (Beta Blockers)
  • α-adrenergic agonists
    • Dual effect: increase outflow and decrease production of aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy
    • Side effects: allergic conjunctivitis Allergic Conjunctivitis Conjunctivitis, hyperemia
    • Also with systemic effects: hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension; caution in cardiovascular disease
    • Brimonidine Brimonidine Rosacea, apraclonidine
  • Carbonic anhydrase Carbonic anhydrase A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of carbon dioxide from the tissues to the lung. Carbonic Anhydrase Inhibitors inhibitors
    • Decrease in aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy production
    • Not as effective in reducing IOP
    • Dorzolamide
  • Cholinergic agonists
    • Increase aqueous outflow
    • Rarely used
    • Side effects: fixed, small pupils
    • Pilocarpine Pilocarpine A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. Cholinomimetic Drugs
  • Rho-kinase inhibitor
    • Increase aqueous outflow
    • New medication: netarsudil
• Laser therapy:
  • Laser trabeculoplasty
    • Increases outflow of aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy through trabecular network
    • Can be first-line therapy or an option in failed medical therapy or medication intolerance
  • Diode laser cyclophotocoagulation (DLCP)
    • Ablation of ciliary process
    • For refractory glaucoma
• Surgical treatment (trabeculectomy):
  • Trabeculectomy
    • Creates a bleb in sclera Sclera The white, opaque, fibrous, outer tunic of the eyeball, covering it entirely excepting the segment covered anteriorly by the cornea. It is essentially avascular but contains apertures for vessels, lymphatics, and nerves. Eye: Anatomy to allow drainage of the aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy
    • Primary treatment for advanced glaucoma (severe visual field Visual Field The Visual Pathway and Related Disorders loss)
    • Risks of cataracts, scarring Scarring Inflammation, hypotony
  • Minimally invasive glaucoma surgery (MIGS)
    • Conjunctiva-sparing surgery

Angle-closure Glaucoma

Risk factors

• Female
• Age > 60 years
• Hyperopia Hyperopia Refractive Errors
• Family history Family History Adult Health Maintenance of angle-closure glaucoma
• Pseudoexfoliation
• Asians (Southeast Asians, Chinese) and Inuit

Etiology

• Results from blockage of aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy outflow from posterior chamber Posterior chamber Eye: Anatomy to the anterior chamber Anterior chamber The space in the eye, filled with aqueous humor, bounded anteriorly by the cornea and a small portion of the sclera and posteriorly by a small portion of the ciliary body, the iris, and that part of the crystalline lens which presents through the pupil. Eye: Anatomy
• Anatomic predisposition:
  • Shallow anterior chamber Anterior chamber The space in the eye, filled with aqueous humor, bounded anteriorly by the cornea and a small portion of the sclera and posteriorly by a small portion of the ciliary body, the iris, and that part of the crystalline lens which presents through the pupil. Eye: Anatomy
  • Lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy size
  • Anterior location of the iris-lens diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm: Anatomy
  • Narrow entrance to the anterior chamber Anterior chamber The space in the eye, filled with aqueous humor, bounded anteriorly by the cornea and a small portion of the sclera and posteriorly by a small portion of the ciliary body, the iris, and that part of the crystalline lens which presents through the pupil. Eye: Anatomy angle
• Lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy is located forward, in contact with the iris, slowing aqueous drainage → pupillary block (fluid no longer flows normally through the pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities)
• Aqueous fluid accumulates → ↑ IOP → compression Compression Blunt Chest Trauma of optic disc Optic disc The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. Eye: Anatomy
• Secondary causes: medication ( topiramate Topiramate A sulfamate-substituted fructose analog that was originally identified as a hypoglycemic agent. It is used for the treatment of epilepsy and migraine disorders, and may also promote weight loss. Second-Generation Anticonvulsant Drugs), trauma or surgery, tumor Tumor Inflammation, lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy subluxation Subluxation Radial Head Subluxation (Nursemaid’s Elbow) in Marfan’s syndrome

Clinical presentation

• Acute angle-closure glaucoma:
  • Medical emergency!
  • More rapid ↑ in IOP: more symptoms
  • Often occurs in evening; lower light levels cause pupillary dilation (mydriasis)
  • Symptoms:
    • Severe eye pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
    • Photophobia Photophobia Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. Migraine Headache
    • Blurred vision Blurred Vision Retinal Detachment
    • Halos around bright lights
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Signs:
    • Red-eye with a “steamy cornea”
    • Pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities mid-dilated and non-reactive to light
    • Absence of accommodation Accommodation Refractive Errors and light reflex
• Chronic closed angle-closure glaucoma:
  • Less severe and may be asymptomatic
  • Due to partial angle blockage or gradual angle closure: slow ↑ in IOP
  • Symptom: gradual loss of peripheral vision Vision Ophthalmic Exam then decrease in central vision Vision Ophthalmic Exam

Diagnosis

• IOP:
  • Diagnostic in acute angle-closure glaucoma (no imaging needed) 
  • Tonometry can show 60–80 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg pressure in an acute attack.
• Undilated fundus Fundus The superior portion of the body of the stomach above the level of the cardiac notch. Stomach: Anatomy examination:
  • Pupillary dilation will exacerbate condition.
  • Cupping of optic disc Optic disc The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. Eye: Anatomy
  • Scattered opacities on anterior lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy
• Gonioscopy:
  • Ophthalmologist able to view the angle
  • Use of special lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy with slit lamp Slit Lamp A microscope with a light source that can be projected into a linear beam. It allows cross-sectional viewing of the aqueous humor; conjuncteiva; cornea; eyelids; iris; and lens of the eye. Ophthalmic Exam
• Anterior segment optical coherence Coherence A view of the world and the individual’s environment as comprehensible, manageable, and meaningful, claiming that the way people view their life has a positive influence on their health. Neurological Examination tomography:
  • High-definition imaging showing details of anterior chamber Anterior chamber The space in the eye, filled with aqueous humor, bounded anteriorly by the cornea and a small portion of the sclera and posteriorly by a small portion of the ciliary body, the iris, and that part of the crystalline lens which presents through the pupil. Eye: Anatomy
  • Non-contact
  • Mechanism of angle closure can be discerned from findings.
• Ultrasound biomicroscopy
  • Ultrasound of anterior chamber Anterior chamber The space in the eye, filled with aqueous humor, bounded anteriorly by the cornea and a small portion of the sclera and posteriorly by a small portion of the ciliary body, the iris, and that part of the crystalline lens which presents through the pupil. Eye: Anatomy, showing angle
  • Not widely available

Management

• Acute angle-closure glaucoma
  • Refer immediately to ophthalmology
  • Empiric treatment can be started when IOP significantly elevated (> 40 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg) with:
    • 0.5% timolol Timolol A beta-adrenergic antagonist that is similar in action to propranolol; the levo-isomer is more active. Timolol has been proposed as an anti-hypertensive, anti-arrhythmic, anti-angina, and anti-glaucoma agent. It is also used in the treatment of migraine disorders and tremor. Class 2 Antiarrhythmic Drugs (Beta Blockers) (1 drop)
    • 1% apraclonidine (1 drop)
    • 2% pilocarpine Pilocarpine A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. Cholinomimetic Drugs (1 drop)
    • Systemic medications: ( carbonic anhydrase Carbonic anhydrase A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of carbon dioxide from the tissues to the lung. Carbonic Anhydrase Inhibitors inhibitor: acetazolamide Acetazolamide One of the carbonic anhydrase inhibitors that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. Carbonic Anhydrase Inhibitors 500 mg PO or IV; alternative: mannitol Mannitol A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. Osmotic Diuretics IV once angle-closure confirmed; not in diabetics)
    • Same eye drops after ½–1 hour (if IOP still elevated)
  • Laser peripheral iridotomy
    • Definitive management after acute episode subsides
    • Relieves pupillary block by allowing aqueous flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure in a different route
    • Surgical iridotomy: option if laser iridotomy not possible 
• Chronic angle-closure glaucoma
  • Laser peripheral iridotomy
  • Avoid anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs agents and decongestants while awaiting surgery

Differential Diagnosis

The differential diagnoses of glaucoma include the following conditions:

• Cataracts: a decrease in vision Vision Ophthalmic Exam due to clouding of the lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy, which presents as painless, often bilateral blurry vision Vision Ophthalmic Exam and glare problems. Cataracts are the leading cause of blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity worldwide. Although the condition can occur at any age, most cases affect those > 60 years.
• Ischemic optic neuropathy Ischemic optic neuropathy Ischemic injury to the optic nerve which usually affects the optic disk and less frequently the retrobulbar portion of the nerve. The injury results from occlusion of arterial blood supply which may result from temporal arteritis; atherosclerosis; collagen diseases; embolism; diabetes mellitus; and other conditions. The disease primarily occurs in the sixth decade or later and presents with the sudden onset of painless and usually severe monocular visual loss. Anterior ischemic optic neuropathy also features optic disk edema with microhemorrhages. The optic disk appears normal in posterior ischemic optic neuropathy. Giant Cell Arteritis (ION): loss of vision Vision Ophthalmic Exam secondary to reduced blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure causing optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions damage. The condition commonly occurs after age 50 and can be arteritic (due to giant cell arteritis Giant Cell Arteritis Giant cell arteritis (GCA), also known as temporal arteritis, is a type of large-vessel vasculitis that predominantly affects the aorta and its major branches, with a predilection for the branches of the carotid (including the temporal artery). Giant cell arteritis is defined by inflammatory leukocytes in the vessel walls leading to reactive damage, ischemia, and necrosis. Giant Cell Arteritis) or nonarteritic (other causes). Nonarteritic ION is more frequent and presents as an acute, painless visual loss (monocular) associated with altitudinal visual field Visual Field The Visual Pathway and Related Disorders defect. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship often have vascular risk factors such as diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus and hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension.
• Conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the conjunctiva Conjunctiva The mucous membrane that covers the posterior surface of the eyelids and the anterior pericorneal surface of the eyeball. Eye: Anatomy, the outer lining of the eye. Etiology can be infectious or non-infectious. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with redness Redness Inflammation and discharge on one or both eyes Both Eyes Refractive Errors. Bacterial conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis often has purulent discharge Purulent Discharge Dacryocystitis, whereas viral causes have watery discharge.
• Uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the uvea Uvea The pigmented vascular coat of the eyeball, consisting of the choroid; ciliary body; and iris, which are continuous with each other. Eye: Anatomy or the middle layer of the eye. Uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea can be caused by infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (herpes, syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis) or can be related to systemic inflammatory disease (inflammatory bowel disease, rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis). The condition can present with red-eye with pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (anterior uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea) or without pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (intermediate and posterior uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea). Symptoms can include visual floaters Floaters Chorioretinitis.