Angle Closure Glaucoma

Definition & Overview

• Primary — occurs in anatomically predisposed eyes
• Secondary — caused by another ocular or systemic factor

Classification (Spectrum)

Pathophysiology

1. Aqueous is produced by the ciliary body and normally flows from the posterior chamber → through the pupil → into the anterior chamber → exits via the trabecular meshwork into Schlemm's canal.
2. When the posterior iris surface contacts the anterior lens surface, a pressure differential builds between the posterior and anterior chambers.
3. This bows the peripheral iris forward (iris bombé), narrowing and eventually closing the trabecular meshwork angle.
4. IOP rises rapidly — from a normal 10–20 mmHg to 50–80+ mmHg.
5. When IOP exceeds the corneal pump's capacity, corneal epithelial oedema develops → blurred vision and halos.

• Plateau iris configuration — anteriorly rotated ciliary processes hold the peripheral iris in a forward position; not relieved by iridotomy alone
• Phacomorphic closure — swollen or anteriorly subluxated lens

Risk Factors

Precipitating Factors for Acute Attack

• Pharmacological mydriasis (atropine, antihistamines, TCAs, cold/flu remedies, motion sickness patches)
• Sympathomimetics (epinephrine, pseudoephedrine, intranasal cocaine)
• Nebulized bronchodilators (albuterol + ipratropium) in ICU patients
• Topiramate and other sulfa derivatives (cause ciliary body effusion)
• Dim illumination / watching TV in a dark room
• Semi-prone position (e.g. reading)
• Acute emotional stress

Clinical Features

Symptoms

• Acute: sudden severe periocular/orbital pain, markedly decreased vision, nausea and vomiting (may simulate acute abdomen), headache
• Subacute/intermittent: blurring ("smoke-filled room") and haloes around lights from transient corneal oedema

Signs

• Visual acuity typically 6/60 to hand movements
• IOP 50–80 mmHg (rock-hard globe)
• Hazy/steamy cornea (corneal epithelial oedema)
• Circumcorneal (ciliary) injection with violaceous hue
• Fixed, mid-dilated, vertically oval pupil — classic and pathognomonic
• Shallow anterior chamber with aqueous flare
• Fellow eye typically shows an occludable angle

After Resolution (Resolved APAC)

• Early: folds in Descemet's membrane, low IOP (ciliary body shutdown)
• Late: glaukomflecken (white foci of anterior lens necrosis), iris atrophy with spiral pattern, posterior synechiae, irregular pupil

Diagnosis

Differential Diagnosis of Acute IOP Elevation

• Acute APAC
• Lens-induced angle closure (swollen/subluxated lens)
• Malignant glaucoma (aqueous misdirection) — especially post-operatively
• Secondary angle closure (neovascular, inflammatory)
• Hypertensive uveitis / herpetic trabeculitis / Posner-Schlossman syndrome
• Scleritis with angle involvement

Treatment

Immediate (Acute Attack)

⚠️ Pilocarpine is no longer recommended acutely — at very high IOP, the ischaemic iris sphincter is unresponsive; cholinergic agents can paradoxically shallow the anterior chamber and worsen closure. — Tintinalli's, 10e

Definitive Treatment

• Bilateral PI is standard (the fellow eye has an occludable angle)
• Does not help plateau iris — laser peripheral iridoplasty or lens extraction needed in those cases

Prophylaxis for PACS

Summary Flowchart

Acute red eye + severe pain + fixed mid-dilated pupil + cloudy cornea
                        ↓
           Measure IOP (≥40–50 mmHg) → APAC
                        ↓
    Supine position + Acetazolamide + Timolol + Apraclonidine
                        ↓
         If IOP not ↓ in 1 hr → IV Mannitol
                        ↓
   Urgent ophthalmology consult → Peripheral laser iridotomy
                        ↓
     Prophylactic PI to fellow eye

Primary Open-Angle Glaucoma (POAG)

Definition

• Retinal nerve fibre layer (RNFL) thinning
• Glaucomatous optic nerve damage
• Characteristic visual field (VF) loss as damage progresses
• Open anterior chamber angle on gonioscopy (distinguishing it from angle-closure)
• Absence of secondary causes

Epidemiology

• The most prevalent glaucoma type in European and African populations
• Prevalence >70 years: ~6% in White, ~16% in Black, ~3% in Asian populations
• Affects both genders equally
• Responsible for the second leading cause of blindness worldwide

Risk Factors

Diabetes mellitus is often cited clinically but longitudinal studies show no independent increased risk — an association seen in clinic-based studies reflects selection bias.

Genetics

• MYOC gene → myocilin protein (expressed in trabecular meshwork)
• OPTN gene → optineurin

Pathophysiology

Clinical Features

Symptoms

• Usually asymptomatic until late — the insidious, painless onset is the hallmark
• Peripheral field loss goes unnoticed until advanced
• Late symptoms: difficulty reading, loss of contrast sensitivity, glare
• Central vision and acuity are preserved until end-stage

Optic Disc Signs

• Increased cup-to-disc (C:D) ratio — concentric enlargement of the cup; C:D >0.6 or asymmetry >0.2 is suspicious
• Neuroretinal rim notching — most common inferiorly (ISNT rule: normal rim is thickest Inferior > Superior > Nasal > Temporal)
• RNFL defects — wedge-shaped defects in the peripapillary NFL
• Disc haemorrhages (Drance haemorrhages) — small splinter bleeds at the disc margin; a marker of active progression
• Bayonetting / nasal displacement of vessels — vessels appear to dive into the disc and re-emerge

Gonioscopy

• Open angle — no peripheral anterior synechiae (PAS); this is the key finding distinguishing POAG from PACG

Visual Field Defects

• Early: MD > −6 dB
• Moderate: −6 to −12 dB
• Severe: < −12 dB

1. Glaucoma Hemifield Test (GHT) outside normal limits on ≥2 consecutive tests, OR
2. Cluster of ≥3 non-edge points depressed at P<5%, with at least 1 at P<1%, on ≥2 tests, OR
3. Corrected PSD (pattern standard deviation) <5% of normal on ≥2 consecutive fields

Investigations

Atypical features warranting further workup: optic pallor > cupping, VF defects respecting the vertical midline or hemianopic, decreased VA/colour vision disproportionate to cupping → consider neurological cause; MRI brain/orbits with gadolinium.

Treatment

Goal

Step 1 — Medical Therapy (First-Line)

• Timolol 0.25–0.5%, levobunolol — once or twice daily
• Avoid in: asthma, COPD, heart block, bradyarrhythmia, CHF, depression, myasthenia gravis
• Systemic effects: bronchospasm, bradycardia, hypotension, reduced libido, CNS depression

• Brimonidine 0.1–0.2% — b.i.d. to t.i.d.
• Contraindicated with MAOIs (hypertensive crisis); avoid in children <5 (CNS/cardiorespiratory depression)
• Apraclonidine 0.5–1%: short-term only (tachyphylaxis, high allergy rate)

• Dorzolamide 2% or brinzolamide 1% — b.i.d. to t.i.d.
• Systemic CAIs (acetazolamide, methazolamide) reserved for refractory/urgent cases; monitor electrolytes; rare aplastic anaemia, Stevens-Johnson syndrome

• Netarsudil 0.02% — once daily; newer class; increases trabecular outflow

Step 2 — Laser Trabeculoplasty

Step 3 — Surgery

Follow-Up

• After starting new medication: review in 4–8 weeks
• If satisfactory response: reassess every 3–6 months
• If inadequate response: switch or add a second agent (wait 5 min between drops to prevent washout)
• Progressive disease despite good IOP: consider poor adherence; assess drop technique
• Serial optic disc photos + OCT RNFL + HVF at every significant visit

Normal-Tension Glaucoma (NTG)

Comparison: POAG vs Angle-Closure Glaucoma

Optic Nerve Head (ONH) Evaluation — Techniques

Overview

1. Clinical Examination

Direct & Indirect Ophthalmoscopy

Slit-Lamp Biomicroscopy with Fundus Lens

2. Normal ONH Parameters

Cup-to-Disc (C:D) Ratio

• Vertical C:D is used (more sensitive than horizontal)
• C:D >0.7 in only 2% of the normal population
• Inter-eye asymmetry ≥0.2 in ~5% of normals but ~25% of glaucoma patients
• Key principle: large discs have large physiological cups — a C:D of 0.8 in a large disc may be normal; any cup in a small disc may be abnormal

Neuroretinal Rim (NRR) — The ISNT Rule

• Sensitivity for glaucoma: 81%; specificity: 32% (not specific — many normal eyes violate ISNT)
• Glaucoma characteristically causes rim notching first inferiorly, then superiorly

Optic Disc Size

• Normal median vertical diameter: 1.5–1.7 mm (White populations)
• Largest mean disc size in persons of African descent
• Large discs are more vulnerable to glaucomatous damage (thinner lamina cribrosa, especially in NTG)

Disc Hemorrhages (Drance Hemorrhages)

• Small, splinter-shaped hemorrhages at the disc margin, usually inferotemporal
• Marker of active RNFL loss and glaucoma progression
• More common in NTG than POAG

3. Optic Disc Photography

Stereo Disc Photography

• Historically the reference standard for disc imaging and documentation
• Images acquired by slightly repositioning the camera between shots (manually or with a stereo separator)
• Allows direct serial comparison at follow-up
• Limitation: subjective interpretation, no automated quantification

Fundus Camera (2D)

• Non-stereoscopic single photographs; widely used for screening and baseline documentation
• Colour photographs document NRR colour, pallor, haemorrhages, peripapillary atrophy (PPA)

4. Optical Coherence Tomography (OCT)

OCT RNFL Analysis

• A circular scan (3.46 mm diameter) is placed around the optic disc
• RNFL thickness is measured in microns at each clock position
• Displayed as a TSNIT plot (Temporal–Superior–Nasal–Inferior–Temporal) with a double-hump pattern in normal eyes
• Compared to a normative age-matched database; results colour-coded:
  • Green = within normal limits (p>5%)
  • Yellow = borderline (p<5%)
  • Red = below normal limits (p<1%)

OCT Optic Disc Analysis (Neuroretinal Rim)

• Measures rim area, disc area, C:D ratio, and rim width objectively
• BMO-MRW (Bruch's Membrane Opening — Minimum Rim Width): newer, more accurate parameter; measures the shortest distance from the BMO edge to the inner limiting membrane

OCT Ganglion Cell Complex (GCC) / Macular OCT

• Measures ganglion cell layer (GCL) + inner plexiform layer (IPL) thickness in the macular region
• Detects early glaucomatous damage — especially useful when the disc appearance is ambiguous or the optic disc is large/small
• Perifoveal GCL thinning corresponds to early superior/inferior arcuate VF defects

Serial OCT for Progression

• Event-based analysis: flags significant change from baseline
• Trend-based analysis: calculates rate of RNFL thinning (μm/year)

Key principle: RNFL thinning on OCT precedes both optic disc changes and visual field loss on standard automated perimetry. OCT can detect structural damage years before functional loss becomes measurable.

5. Heidelberg Retinal Tomograph (HRT) — Confocal Scanning Laser Ophthalmoscopy (cSLO)

• Uses a confocal laser (670 nm diode) to acquire a series of images at different focal depths, building a 3D topographic map of the ONH surface
• Key parameters: rim area, cup area, cup volume, rim volume, mean RNFL thickness, cup shape measure
• Moorfields Regression Analysis (MRA): compares rim area to disc area against a normative database for each of 6 sectors — classified as within normal limits, borderline, or outside normal limits
• Glaucoma Probability Score (GPS): alternative analysis without requiring a manual disc margin contour
• Serial exams enable topographic change analysis (TCA) — automatically identifies areas of significant surface depression

6. Scanning Laser Polarimetry (GDx)

• Uses polarized laser light to measure birefringence of RNFL — the parallel arrangement of microtubules in RGC axons retards polarized light in proportion to NFL thickness
• Output: TSNIT average, superior average, inferior average, Nerve Fiber Indicator (NFI) (0–100; NFI >30 = glaucoma likely)
• Variable Corneal Compensation (VCC) and Enhanced Corneal Compensation (ECC) correct for corneal birefringence artefacts

7. Anterior Segment OCT (AS-OCT)

• Evaluates the filtration angle structure non-invasively
• Measures Angle Opening Distance (AOD500) — distance between the iris and trabecular meshwork at 500 μm from the scleral spur
• Measures Trabecular-Iris Surface Area (TISA) — cross-sectional area of the angle recess
• Particularly useful for angle-closure assessment, screening, and post-iridotomy evaluation
• Limitation: cannot image structures behind the iris (ciliary body, lens zonules)

8. Ultrasound Biomicroscopy (UBM)

• High-frequency ultrasound (35–50 MHz) providing up to 25 μm axial / 50 μm lateral resolution
• Unique ability to visualise structures posterior to the iris — ciliary body, posterior chamber, lens zonules, ciliary processes
• Essential for diagnosing:
  • Plateau iris configuration
  • Ciliary body cysts/tumours
  • Malignant glaucoma (aqueous misdirection — showing forward rotation of the ciliary body)
  • Angle recession
• Requires immersion in saline or coupling gel; patient must be supine

9. Pattern ERG (pERG)

• Measures electrical activity of macular retinal ganglion cells in response to a pattern-reversal stimulus
• Waveform components: N35 (35 ms negative), P50 (50 ms positive), N95 (95 ms negative) — N95 is reduced in glaucoma (reflects RGC dysfunction)
• Objective, non-invasive measure that can detect functional RGC loss before structural changes on OCT in some cases
• Not a substitute for clinical examination or imaging; useful for monitoring subtle optic neuropathy

10. Corneal Pachymetry

• Measures central corneal thickness (CCT)
• Not an ONH technique per se, but essential for interpreting IOP — applanation tonometry (Goldmann) assumes a CCT of ~540 μm
  • Thin corneas (e.g. <520 μm): IOP underestimated → true IOP is higher
  • Thick corneas (e.g. >600 μm): IOP overestimated → true IOP is lower
• CCT is also an independent risk factor for glaucoma progression (thinner CCT = higher risk), beyond just its effect on IOP measurement

Summary Comparison Table