Primary Angle Closure Glaucoma and Nanophthalmos

Pathophysiology and Mechanisms of Primary Pupillary Block Angle Closure

• Definition and Core Mechanism: Primary pupillary block is the most common form of angle closure glaucoma. It occurs when the iris moves forward and lies over the trabecular meshwork, blocking the drainage of aqueous humor. This obstruction causes an elevation in intraocular pressure (IOP).
• Relative Seal Formation: The process begins with a relative seal forming between the posterior iris and the anterior lens surface. This seal traps aqueous humor in the posterior chamber, behind the iris.
• Iris Bomb: The trapped aqueous humor creates a pressure gradient that drives the peripheral iris forward toward the cornea. This forward bowing is known as "iris bombé," which physically covers the trabecular meshwork.
• Contemporary Research and Uncertainties: While the pupillary block model is the standard, research by Harry Quigley and colleagues suggests alternate mechanisms.
  • Iris Volume: Most irises lose volume during pupil dilation; however, eyes prone to angle closure may fail to lose this volume, contributing to angle crowding.
  • Choroidal Thickness: Variations in choroidal thickness may also play a role in the mechanism of closure.

Comparison with Primary Open Angle Glaucoma (POAG)

• The Kitchen Sink Analogy:
  • POAG: In open angle glaucoma, the "sink drain" (trabecular meshwork) appears normal upon visual inspection. The resistance to fluid outflow is located deep within the drainage structures.
  • Angle Closure: This is analogous to having a "stopper in the sink." The trabecular meshwork is visibly covered by the iris, creating a mechanical obstruction.

Epidemiology and Demographic Risk Factors

• Racial and Ethnic Prevalence:
  • Asian Populations: There is a high prevalence in individuals of Asian derivation. Notably, $91\%$ of bilateral blindness in China is attributed to angle closure glaucoma.
  • Inuit and Eskimo Populations: These groups in the U.S. have a very high prevalence of angle closure, as they are ethnically closely related to Asian populations.
  • African Heritage: Acute angle closure is relatively uncommon in this group, but chronic angle closure is more frequent.
• Gender: Women are at a substantially increased risk compared to men.
• Family History: A positive family history of angle closure significantly increases individual risk.
• Anatomical Risk Factors (Ocular Biometry):
  • Hyperopia: Patients are typically hyperopic (farsighted) with shorter axial lengths.
  • Crowded Anatomy: Often characterized by a shallow anterior chamber and a small, "crowded" eye.
  • Aging: Risk increases with age because the lens naturally thickens and the pupil becomes smaller (miotic) over time, both of which exacerbate the pupillary block.

Precipitants and Triggers for Acute Attacks

• Mydriasis (Pupillary Dilation): Factors that cause the iris to dilate can precipitate an attack:
  • Dim Illumination: E.g., sitting in a dark movie theater.
  • Emotional Stress: High stress levels can induce sympathetic dilation.
  • Pharmacological Agents: Medications with warning labels for glaucoma usually refer to angle closure risk. This includes many over-the-counter cold medicines and sleep aids.
• The "Mid-Dilation" Danger Zone: Attacks do not typically occur during full dilation but rather when the iris is slowly constricted back from a dilated state (the "mid-dilated" position).
  • Clinical Caveat: A normal IOP reading during a dilated clinic exam does not guarantee safety; the attack may occur as the patient's pupil comes down while driving home.
• Strong Cholinergic Agents: High-percentage pilocarpine or medicines like echothiophate can move the lens-iris diaphragm forward, potentially inducing angle closure.

Clinical Forms and Presentations

• Acute Angle Closure:
  • Characterized by sudden, severe ocular pain and headaches.
  • Visual Symptoms: Blurred vision and the appearance of colored halos around lights.
  • Systemic Symptoms: Severe distress can lead to nausea and vomiting, which is sometimes misdiagnosed as a gastrointestinal (GI) problem.
• Intermittent (Subacute) Angle Closure:
  • Patients experience transient episodes of pain, headache, or blurred vision that may resolve spontaneously.
  • Case Example: A radiologist (working in the dark) suffered years of intractable headaches. Despite CT, MRI, and lumbar puncture (LP) tests, the cause was only found via gonioscopy (critically narrow angles). A laser iridotomy provided complete resolution for over $9$ years.
• Chronic Angle Closure:
  • Asymptomatic in early stages, similar to POAG.
  • Causes gradual decrease in peripheral and night vision, eventually leading to central vision loss.
  • Differentiated from POAG via gonioscopy, which reveals narrow angles and peripheral anterior synechiae (PAS).

Case Study: Acute Presentation

• Patient Profile: A $49$-year-old white male with a $4$-day history of intermittent right-sided headache and pain.
• Presentation: Acute loss of vision, constant pain, severe headache, and nausea.
• Exam Findings:
  • Mid-dilated, fixed pupil.
  • "Steamy" or cloudy cornea (corneal edema).
  • Injected (red) eye.
  • Visual acuity: Count fingers (CF).
  • Intraocular Pressure: $50\,mmHg$.
• Differential Diagnosis Strategy:
  • Question 1: Refractive Error: If the patient is highly myopic (e.g., $-4.00\,D$), pupillary block is highly unlikely.
  • Question 2: Contralateral Angle: If the fellow eye has a wide-open angle, the diagnosis of primary pupillary block is questionable.

Physical Signs and Sequelae of High IOP

• Immediate Signs:
  • IOP often reaches $60\,mmHg$ or higher.
  • Iris bombé and peripheral anterior chamber narrowing.
• Post-Attack Sequelae:
  • Iris Atrophy: Patchy loss of iris tissue or "spiraling" of iris fibers (fibers appear twisted rather than radial).
  • Glaucomflecken: Sub-epithelial lens deposits/opacities caused by aqueous stasis and high pressure.
  • Berlin Tears: Tears in the iris.
  • Synechiae: Permanent adhesions between the iris and the trabecular meshwork (PAS).
  • Optic Nerve Changes: Disc hyperemia during the attack, followed by pallor and cupping.

Management and Treatment Strategies

• Emergency Medical Management:
  • Topical Drops: Multiple agents used to lower IOP.
  • Systemic Medications: Acetazolamide (carbonic anhydrase inhibitor) or hyperosmotic agents like Mannitol.
  • Pilocarpine: Use only once IOP is sufficiently lowered; high pressure can paralyze the sphincter muscle, making the drop ineffective initially.
• Mechanical Maneuvers:
  • Corneal Indentation: Pushing on the cornea (e.g., with a Zeiss or Posner-Sussman lens) to drive aqueous into the peripheral angle and push the iris back mechanically can break an acute attack.
• Laser and Surgical Procedures:
  • Laser Peripheral Iridotomy (LPI): Creating a hole in the iris to allow aqueous flow and let the iris settle back. Preferred placement is often temporal.
  • Iridoplasty: Used if the cornea is too cloudy for LPI; it pulls the iris out of the angle.
  • Surgical Iridectomy: Rarely performed; reserved for patients who cannot cooperate with laser (e.g., mentally challenged).
  • Goniosynechialysis: Manual stripping of the iris from the angle with a spatula; usually done during cataract surgery for synechiae less than one year old.

Clinical Precautions and Prophylaxis

• The Fellow Eye: There is a high risk of the untreated fellow eye developing angle closure. Prophylactic LPI is strongly recommended, especially since the stress of an attack in one eye can trigger an attack in the other via sympathetic stimulation.
• Monitoring: Even after LPI, the angle may remain relatively narrow. Serial gonioscopy is required.
• Mixed Mechanism Glaucoma: Occurs when IOP remains elevated despite a patent LPI and open angles. Causes include narrow angles developing into POAG or lens enlargement over time.
• Patient Counseling: If an angle is narrow enough to warn a patient about dark theaters or cold meds, the clinician should simply perform the iridotomy to remove the risk.

Nanophthalmos

• Description: A rare condition featuring a very small but structurally organized eye.
• Biometry: Axial length is typically less than $20\,mm$.
• Anatomical Abnormalities:
  • Very thick and impermeable sclera.
  • Large lens relative to the small eye size.
• Clinical Risks:
  • Angle closure occurs at an early age.
  • Choroidal Effusion: High risk during surgery because fluid cannot easily escape through the thick sclera.
• Treatment Limitations: Avoid intraocular surgery if possible. Use LPI or iridoplasty. If surgery is mandatory, "scleral windows" (sclerotomies) are performed to drain suprachoroidal fluid.