Glaucoma (Adult)

1. Overview

Glaucoma is a group of progressive optic neuropathies characterised by structural damage to the optic nerve head and retinal nerve fiber layer, typically associated with characteristic patterns of visual field loss. It represents the leading cause of irreversible blindness worldwide, affecting over 76 million people globally and projected to impact 111.8 million by 2040. [1,2]

The condition is fundamentally a disease of retinal ganglion cell death and axonal loss, most commonly (but not exclusively) associated with elevated intraocular pressure (IOP). The hallmark pathological finding is progressive excavation ("cupping") of the optic disc, where the cup-to-disc ratio increases as nerve fibers are lost from the neuroretinal rim.

Glaucoma is termed the "silent thief of sight" because most forms are asymptomatic until advanced stages, when irreversible visual loss has already occurred. Early detection through screening and lifetime monitoring are critical, as treatment can slow or halt progression but cannot reverse existing damage. [3]

Key Clinical Message: Glaucoma is a chronic, progressive condition requiring lifelong monitoring and treatment adherence. The goal of all interventions is to lower IOP to a level that prevents further optic nerve damage, thereby preserving functional vision and quality of life.

2. Classification of Glaucoma

Glaucoma is classified by multiple schemas based on anatomical, aetiological, and temporal factors:

By Anatomy (Angle Status)

Open Angle Glaucoma:

• The iridocorneal angle (drainage angle) is anatomically open on gonioscopy
• Aqueous outflow resistance occurs at the level of the trabecular meshwork or distal structures
• Accounts for ~90% of glaucoma cases in Western populations
• Typically chronic and asymptomatic

Angle Closure Glaucoma:

• The peripheral iris obstructs the trabecular meshwork, impeding aqueous drainage
• Can be acute (medical emergency) or chronic
• More common in Asian and Inuit populations
• Accounts for ~50% of glaucoma blindness globally despite lower prevalence [4]

By Aetiology

Primary Glaucoma:

• No identifiable underlying ocular or systemic cause
• Includes: Primary Open Angle Glaucoma (POAG), Primary Angle Closure Glaucoma (PACG), Normal Tension Glaucoma (NTG)

Secondary Glaucoma:

• Identifiable cause related to other ocular or systemic conditions
• Includes: Neovascular, pseudoexfoliative, pigment dispersion, traumatic, uveitic, steroid-induced, lens-related

Congenital/Developmental Glaucoma:

• Present from birth or early childhood
• Due to developmental abnormalities of the drainage angle
• Not covered in this adult-focused topic

By Temporal Course

• Acute: Rapid IOP elevation (e.g., acute angle closure)
• Chronic: Gradual progression over years (e.g., POAG)
• Intermittent: Episodic IOP elevations (e.g., intermittent angle closure)

3. Epidemiology

Global Burden

Primary Open Angle Glaucoma (POAG)

• Prevalence: 2-3% of population > 40 years; increases to 10-15% in those > 80 years [5]
• Age: Prevalence doubles with each decade after age 40
• Sex: Slightly higher in males (1.4:1 ratio)
• Ethnicity:
  • Highest in individuals of African descent (4-8% prevalence, 3-4x higher than Europeans) [6]
  • Earlier onset and more aggressive course in African ancestry
  • Intermediate rates in Hispanic populations
  • Lowest in European populations

Primary Angle Closure Glaucoma (PACG)

• Prevalence: 0.5-1% in Western populations; 1-4% in Asian populations [7]
• Age: Prevalence increases with age, peak incidence 55-65 years
• Sex: Female predominance (2-3:1 ratio due to smaller anterior segment dimensions)
• Ethnicity:
  • Highest in East Asian (Chinese, Vietnamese, Mongolian) and Inuit populations
  • Accounts for ~90% of glaucoma blindness in Asia [4]
  • Much lower rates in European and African populations

Normal Tension Glaucoma (NTG)

• Accounts for ~30-40% of open angle glaucoma in Western populations
• Up to 90% of open angle glaucoma in Japan [8]
• More common in females
• Associated with systemic vascular conditions

Risk Factors

Non-Modifiable:

• Age: Single greatest risk factor (exponential increase after 40)
• Family History: First-degree relative increases risk 4-9 fold [9]
• Ethnicity: As described above
• Genetics: Multiple genes identified (MYOC, OPTN, TBK1, CAV1/CAV2)

Modifiable/Associated:

• Elevated IOP: Most important modifiable risk factor (relative risk 10-20 for IOP > 26 mmHg) [10]
• Myopia: High myopia (>-6D) increases POAG risk 2-3 fold [11]
• Hyperopia: Shallow anterior chamber predisposes to angle closure
• Central corneal thickness: Thin cornea (less than 500 μm) associated with higher risk [12]
• Diabetes mellitus: ~1.5x increased risk of POAG
• Hypertension: Controversial association with POAG; low perfusion pressure increases risk
• Systemic vasospasm: Migraine, Raynaud's associated with NTG
• Steroid use: Topical/systemic corticosteroids can cause IOP elevation
• Obstructive sleep apnoea: Emerging risk factor for glaucoma progression

4. Aetiology & Pathophysiology

Aqueous Humour Dynamics

Understanding glaucoma requires understanding aqueous production, flow, and drainage:

Production:

• Secreted by ciliary body epithelium (posterior chamber)
• Rate: ~2-3 μL/min (~2.5 mL/day)
• Active secretion (accounts for ~80%) and ultrafiltration
• Circadian variation (higher during day, lower at night)

Flow Pathway:

1. Posterior chamber (behind iris)
2. Through pupil
3. Anterior chamber (between cornea and iris)
4. Drainage via two routes

Drainage:

• Conventional (Trabecular) Pathway (~75-90%):

  • Aqueous crosses trabecular meshwork → Schlemm's canal → Collector channels → Episcleral veins
  • Primary site of outflow resistance in POAG
  • Pressure-dependent drainage

• Unconventional (Uveoscleral) Pathway (~10-25%):

  • Aqueous flows through ciliary muscle bundles → suprachoroidal space → absorbed by uveal vessels
  • Target of prostaglandin analogue medications
  • Pressure-independent drainage

IOP Regulation:

The modified Goldmann equation describes IOP:

IOP = (F/C) + Pv

Where:

• F = Aqueous production rate
• C = Outflow facility (ease of drainage)
• Pv = Episcleral venous pressure

Normal IOP: 10-21 mmHg (mean ~16 mmHg)

Glaucoma is almost always a disorder of increased outflow resistance (decreased C), not increased production.

Pathophysiology of Primary Open Angle Glaucoma (POAG)

Trabecular Meshwork Dysfunction:

• Progressive reduction in outflow facility
• Mechanisms include:
  • Trabecular meshwork cell loss and dysfunction
  • Accumulation of extracellular material
  • Decreased matrix metalloproteinase activity
  • Oxidative stress and cellular senescence
  • Transforming growth factor-β (TGF-β) signaling abnormalities

Optic Nerve Head Damage: The optic nerve head (ONH) is the primary site of injury. Multiple mechanisms contribute:

1. Mechanical Stress Theory:

   • Elevated IOP causes mechanical deformation of the lamina cribrosa (connective tissue sieve through which ganglion cell axons exit)
   • Backward bowing of lamina compresses and damages axons
   • Disrupts axonal transport of neurotrophic factors from brain to retinal ganglion cells

2. Vascular Theory:

   • Reduced blood flow to ONH
   • Mechanisms: Direct compression of vessels, impaired autoregulation, reduced perfusion pressure
   • Ischaemia leads to ganglion cell death
   • Particularly relevant in NTG

3. Excitotoxicity:

   • Glutamate accumulation in retina
   • Overstimulation of NMDA receptors
   • Calcium-mediated cell death

4. Neuroinflammation and Glial Activation:

   • Microglial activation
   • Astrocyte reactivity
   • Complement activation
   • Contributes to progressive neurodegeneration

5. Loss of Neurotrophic Support:

   • Reduced brain-derived neurotrophic factor (BDNF)
   • Impaired retrograde transport from lateral geniculate nucleus

Pattern of Damage:

• Retinal ganglion cells die preferentially in characteristic patterns
• Early loss: Inferior and superior arcuate nerve fibers
• Creates arcuate scotomas in visual field
• Nasal fibers affected earlier than temporal
• Central 5-10° of vision typically spared until late stages

Structural Changes:

• Optic Disc Cupping: Progressive excavation of the cup
  • "Normal cup-to-disc ratio (CDR): less than 0.5"
  • "Glaucomatous: CDR > 0.6 or asymmetry > 0.2 between eyes"
• Neuroretinal Rim Thinning: Loss follows ISNT rule (Inferior > Superior > Nasal > Temporal rim thickness in normal eyes; reversed in glaucoma)
• Nerve Fiber Layer Loss: Visible as wedge-shaped defects
• Parapapillary Atrophy: Zones of retinal pigment epithelium loss adjacent to disc

Pathophysiology of Primary Angle Closure Glaucoma (PACG)

Anatomical Predisposition:

• Short axial length: Hyperopic eyes have crowded anterior segments
• Shallow anterior chamber: less than 2.5 mm depth increases risk
• Thick lens: Increases with age due to continued lens growth
• Small corneal diameter: Associated with crowded angles
• Anteriorly positioned ciliary body: Narrows angle
• Plateau iris configuration: Anteriorly positioned iris root

Mechanisms of Angle Closure:

1. Pupillary Block (Most common, ~75% of cases):

   • Iris in mid-dilation blocks aqueous flow through pupil
   • Pressure builds in posterior chamber
   • Peripheral iris bows forward (iris bombé), occluding trabecular meshwork
   • Precipitated by:
     • Dim lighting (physiologic mydriasis)
     • Anticholinergic medications (pharmacologic mydriasis)
     • Emotional stress
     • Prone positioning
     • Reading in dim light

2. Plateau Iris Configuration:

   • Anatomically narrow angle despite normal anterior chamber depth
   • Anteriorly positioned ciliary body pushes peripheral iris forward
   • Angle may close even without pupillary block

3. Phacomorphic Mechanism:

   • Intumescent (swollen) lens in advanced cataract
   • Anterior displacement of lens-iris diaphragm
   • Shallow anterior chamber

4. Lens-Related Mechanisms:

   • With age, lens enlarges and moves anteriorly
   • Progressive narrowing of angle
   • Chronic angle closure may be asymptomatic

Acute Angle Closure Crisis:

• Sudden complete obstruction of trabecular meshwork
• IOP rises rapidly to 40-80 mmHg (normal 10-21 mmHg)
• Corneal endothelial oedema (causes haloes, blurred vision)
• Iris ischaemia (causes fixed mid-dilated pupil)
• Ciliary body ischaemia and inflammation (causes severe pain, red eye)
• Optic nerve ischaemia (can cause permanent vision loss within hours)

Chronic Angle Closure:

• Progressive iridotrabecular contact
• Peripheral anterior synechiae (PAS) formation (permanent adhesions)
• Trabecular meshwork damage
• Gradual IOP elevation similar to POAG

Pathophysiology of Normal Tension Glaucoma (NTG)

NTG is characterized by glaucomatous optic neuropathy with IOP consistently ≤21 mmHg.

Proposed Mechanisms:

1. Vascular Insufficiency (Primary theory):

   • Reduced ocular perfusion pressure
   • Systemic hypotension (especially nocturnal dips)
   • Vasospasm (migraine, Raynaud's phenomenon)
   • Impaired autoregulation of ONH blood flow
   • Endothelial dysfunction

2. Structural Weakness:

   • Inherently weak or abnormal lamina cribrosa
   • Susceptible to damage at "normal" IOP levels
   • Genetic predisposition

3. Other Factors:

   • Nocturnal hypotension
   • Sleep apnoea
   • High myopia
   • Optic disc haemorrhages (marker of instability)

Pathophysiology of Secondary Glaucomas

Neovascular Glaucoma (NVG):

• Ischaemic retinal diseases (diabetes, central retinal vein occlusion) produce VEGF
• Abnormal vessels grow on iris (rubeosis iridis) and angle
• Fibrovascular membrane contracts, causing synechial angle closure
• Very high IOP, poor visual prognosis

Pseudoexfoliative Glaucoma (PXG):

• Pseudoexfoliation syndrome: Deposition of abnormal fibrillar material
• Material flakes off lens capsule, deposits in trabecular meshwork
• Causes trabecular obstruction and dysfunction
• Often higher IOP, more aggressive than POAG

Pigmentary Glaucoma (PG):

• Iris pigment liberated and deposited in trabecular meshwork
• Common mechanism: Reverse pupillary block (posterior iris bowing)
• Iris rubs against lens zonules (especially with blinking, exercise)
• Pigment showers block outflow
• Typical patient: Myopic young males

Uveitic Glaucoma:

• Multiple mechanisms: Inflammatory trabecular obstruction, synechiae, steroid-induced
• Treatment addresses both inflammation and IOP

Steroid-Induced Glaucoma:

• Corticosteroids increase trabecular meshwork resistance
• Genetic predisposition (some individuals very sensitive)
• Can occur with topical, periocular, systemic, or inhaled steroids
• Usually reversible with steroid cessation

5. Clinical Presentation

Primary Open Angle Glaucoma (POAG)

Natural History: POAG is insidious and asymptomatic until late stages.

Stages of Progression:

1. Ocular Hypertension Phase (IOP > 21 mmHg, no detectable damage):

   • Completely asymptomatic
   • Normal optic disc and visual fields
   • ~10% per year convert to glaucoma [13]

2. Early Glaucoma (mild optic nerve/VF damage):

   • Asymptomatic (binocular vision compensates)
   • Small paracentral or arcuate scotomas on perimetry
   • Subtle disc changes: CDR 0.6-0.7, localized rim thinning

3. Moderate Glaucoma:

   • Still often asymptomatic
   • Larger arcuate scotomas (Bjerrum's area)
   • Nasal step defects
   • CDR > 0.7, obvious rim loss

4. Advanced Glaucoma:

   • Noticeable visual symptoms: Peripheral vision loss, "tunnel vision"
   • Difficulty with mobility, driving, reading
   • Extensive visual field loss (only central island or temporal field remaining)
   • CDR > 0.8-0.9, severe cupping

5. End-Stage:

   • Central vision lost
   • Blind or perception of light only
   • Total disc cupping (CDR ~1.0)

Symptoms (When Present):

• Peripheral visual field loss (late)
• Difficulty with stairs, curbs, obstacles
• Difficulty reading (loss of sequential letters)
• Difficulty with mobility in unfamiliar environments
• Reduced quality of life

Signs:

• Elevated IOP: Mean ~24-26 mmHg (but may be normal in NTG)

• Optic Disc Changes:

  • Increased cup-to-disc ratio (vertical CDR > 0.6)
  • Asymmetry between eyes (> 0.2 difference suspicious)
  • "Violation of ISNT rule (normal: Inferior rim > Superior > Nasal > Temporal)"
  • Focal notching of neuroretinal rim
  • Disc haemorrhages (Drance haemorrhages – splinter haemorrhages at disc margin)
  • Peripapillary atrophy (β-zone)
  • Laminar dot sign (visible pores in lamina cribrosa)

• Retinal Nerve Fiber Layer (RNFL) Defects:

  • Wedge-shaped or slit defects
  • Best seen with red-free (green) light

• Gonioscopy: Open angles (Grade 3-4 by Shaffer classification)

• Visual Field Defects:

  • Isolated scotomas
  • Nasal step (respects horizontal midline)
  • Arcuate scotoma (Bjerrum scotoma – arcs from blind spot)
  • Ring scotoma (advanced)
  • Temporal island (end-stage)

Typical Patient Profile:

• Age > 50 years
• African or Hispanic ethnicity (higher risk)
• Family history of glaucoma
• High myopia
• Incidental finding on routine optometry exam or screening

Primary Angle Closure Glaucoma (PACG)

Acute Angle Closure (AAC) – MEDICAL EMERGENCY

Symptoms:

• Severe ocular pain: Often described as "worst pain ever experienced"
• Headache: Ipsilateral or frontal
• Blurred vision: Marked reduction (corneal oedema)
• Haloes around lights: Rainbow-colored rings (pathognomonic – due to corneal oedema)
• Nausea and vomiting: Vagal response to severe pain; can mimic GI or neurological emergency
• Photophobia
• Red eye

Signs:

• Very high IOP: 40-80 mmHg (palpably rock-hard eye)
• Corneal oedema: Hazy, steamy appearance
• Shallow anterior chamber: Compare to fellow eye
• Mid-dilated, fixed pupil: Oval shape, non-reactive to light (iris ischaemia)
• Conjunctival injection: Ciliary flush (circumcorneal redness)
• Anterior chamber cells and flare: Inflammatory response
• Closed angle on gonioscopy: No trabecular meshwork visible

Precipitating Factors:

• Dim lighting (pupil dilation)
• Emotional stress
• Anticholinergic medications (antihistamines, antidepressants, antiparkinsonian drugs)
• Topical mydriatics (tropicamide, cyclopentolate)
• Prone positioning
• Watching movies/theatre in dark

Fellow Eye:

• 40-80% risk of AAC in fellow eye without prophylaxis [14]
• Fellow eye examination shows narrow angles, shallow AC

Typical Patient Profile:

• Female > 60 years
• Asian, Inuit, or Hispanic ethnicity
• Hyperopia (small eyes)
• Presenting after watching TV/movie in dark room

Chronic Angle Closure (CAC)

Symptoms:

• Often asymptomatic
• Intermittent symptoms (subacute angle closure):
  • Transient blurred vision
  • Mild haloes
  • Mild ocular discomfort
  • Self-limiting episodes

Signs:

• Moderately elevated IOP (typically 25-35 mmHg)
• Narrow angles with variable degree of closure on gonioscopy
• Peripheral anterior synechiae (PAS) – permanent adhesions
• Glaucomatous optic neuropathy (similar to POAG)
• Visual field defects

Normal Tension Glaucoma (NTG)

Clinical Features:

• Identical to POAG except IOP consistently ≤21 mmHg
• Often more localized, deeper disc cupping
• More frequent disc haemorrhages
• Greater propensity for central visual field involvement
• Association with migraine, Raynaud's, cold extremities

Symptoms:

• Asymptomatic until advanced
• May notice central scotomas earlier than POAG

Secondary Glaucomas – Selected Entities

Neovascular Glaucoma

Symptoms:

• Severe pain (often out of proportion to findings)
• Profound vision loss
• Red eye

Signs:

• Rubeosis iridis (abnormal vessels on iris, visible at pupil margin)
• Very high IOP (> 40 mmHg)
• Hyphema (blood in anterior chamber) may be present
• Evidence of underlying cause: Diabetic retinopathy, CRVO

Pseudoexfoliative Glaucoma

Symptoms:

• Usually asymptomatic

Signs:

• White flaky material on lens capsule (visible with dilated exam)
• Material on corneal endothelium, iris, angle structures
• IOP often > 30 mmHg (higher than typical POAG)
• More aggressive course

Pigment Dispersion Syndrome / Pigmentary Glaucoma

Symptoms:

• May have transient blurred vision or haloes after exercise (pigment shower)
• Usually asymptomatic

Signs:

• Krukenberg spindle (vertical line of pigment on corneal endothelium)
• Dense trabecular meshwork pigmentation (360°)
• Radial iris transillumination defects (mid-peripheral)
• IOP elevation after exercise/pupil dilation

Typical Patient:

• Myopic male in 20s-40s

6. Differential Diagnosis

When evaluating suspected glaucoma, consider:

Mimics of POAG

Mimics of Acute Angle Closure

Causes of Secondary Glaucoma to Exclude

• Neovascular: Check for diabetes, retinal vein occlusion, ocular ischaemic syndrome
• Uveitic: Anterior chamber cells/flare, keratic precipitates, synechiae
• Lens-induced: Phacomorphic (intumescent cataract), phacolytic (hypermature cataract)
• Traumatic: History of blunt trauma, angle recession on gonioscopy, hyphema
• Steroid-induced: History of steroid use (topical, systemic, inhaled)
• Pseudoexfoliation: White material on lens
• Pigment dispersion: Krukenberg spindle, iris transillumination defects

7. Investigations

Glaucoma diagnosis requires assessment of:

1. Intraocular pressure
2. Optic nerve structure
3. Visual function
4. Anterior chamber angle anatomy

First-Line Investigations

1. Tonometry (IOP Measurement)

Goldmann Applanation Tonometry (GAT):

• Gold standard
• Measures force required to flatten (applanate) a fixed area of cornea
• Normal: 10-21 mmHg (mean ~16 mmHg)
• Considerations:
  • Diurnal variation (IOP typically highest in morning)
  • "Central corneal thickness affects reading:"
    • Thick cornea (> 545 μm) → Overestimation of IOP
    • Thin cornea (less than 500 μm) → Underestimation of IOP

Alternative Methods:

• Perkins tonometry (portable applanation)
• Icare rebound tonometry (no anaesthetic needed)
• Non-contact (air-puff) tonometry (screening)

Interpretation:

• IOP > 21 mmHg: Abnormal (but 30% of glaucoma patients have "normal" IOP)
• IOP > 24 mmHg: High suspicion for glaucoma
• IOP > 30 mmHg: Strong indicator, treatment usually indicated
• IOP asymmetry > 3 mmHg between eyes: Suspicious

Diurnal IOP Testing:

• Multiple measurements throughout the day
• Identifies peak IOP and fluctuation
• Fluctuation > 10 mmHg is risk factor for progression

2. Ophthalmoscopy / Fundoscopy (Optic Disc Assessment)

Direct Ophthalmoscopy:

• Initial screening
• Limited view of disc

Slit Lamp Biomicroscopy with 78D/90D Lens:

• Standard examination
• Stereoscopic view of disc

Key Findings:

• Cup-to-Disc Ratio (CDR):

  • "Normal: less than 0.5 (cup occupies less than half of disc diameter)"
  • "Suspicious: 0.6-0.7"
  • "Glaucomatous: > 0.7"
  • "Inter-eye asymmetry: > 0.2 difference suspicious"

• Neuroretinal Rim:

  • "Normal: Follows ISNT rule (Inferior thickest > Superior > Nasal > Temporal)"
  • "Glaucoma: Rim thinning, focal notching, violation of ISNT"

• Disc Haemorrhages:

  • Splinter haemorrhages at disc margin (Drance haemorrhages)
  • Indicate active damage, increased risk of progression

• Peripapillary Atrophy:

  • β-zone (adjacent to disc): Associated with glaucoma progression
  • α-zone (peripheral): Less specific

• Nerve Fiber Layer Defects:

  • Wedge or slit defects
  • Best seen with red-free (green) filter

3. Perimetry (Visual Field Testing)

Automated Static Perimetry:

• Standard: Humphrey Visual Field Analyser or Octopus
• Common Protocols:
  • 24-2 or 30-2 SITA (Swedish Interactive Threshold Algorithm)
  • Central 24° or 30° of vision tested
  • 54 or 76 test points

Output Indices:

• Mean Deviation (MD): Average difference from age-matched normal

  • "Normal: 0 dB"
  • "Mild glaucoma: -3 to -6 dB"
  • "Moderate: -6 to -12 dB"
  • "Severe: < -12 dB"

• Pattern Standard Deviation (PSD): Irregularity of field

  • Elevated in localized defects (glaucoma)

• Visual Field Index (VFI): Percentage of normal visual function (100% = normal)

Glaucomatous Visual Field Defects:

• Paracentral scotomas
• Nasal step (respects horizontal midline)
• Arcuate (Bjerrum) scotoma (arcs from blind spot superiorly or inferiorly)
• Temporal wedge
• Advanced: Ring scotoma, temporal island
• Respects vertical midline (neurologic lesions cross midline)

Reliability Indices:

• Fixation losses less than 20%
• False positives less than 15%
• False negatives less than 33%

Limitations:

• Requires patient cooperation and alertness
• Learning effect (first 1-2 tests may be unreliable)
• Not suitable for severe cognitive impairment

4. Gonioscopy (Angle Assessment)

Technique:

• Goldman 3-mirror or 4-mirror lens
• Direct visualization of iridocorneal angle

Grading Systems:

Shaffer Grading:

• Grade 4 (35-45°): Wide open
• Grade 3 (25-35°): Open
• Grade 2 (20°): Moderately narrow (20% risk of closure)
• Grade 1 (10°): Extremely narrow (high risk of closure)
• Grade 0 (0°): Closed (iris against trabecular meshwork)

Visible Structures (from anterior to posterior):

• Schwalbe's line (termination of cornea)
• Trabecular meshwork (pigmented band)
• Scleral spur
• Ciliary body band
• Iris root

Findings:

• POAG: All structures visible (open angle), often heavily pigmented trabecular meshwork
• PACG: Structures not visible (closed), peripheral anterior synechiae (PAS)
• Angle recession: Post-traumatic, widened ciliary body band
• Neovascularization: Vessels crossing scleral spur

Dynamic Gonioscopy:

• Indentation gonioscopy to differentiate appositional (reversible) from synechial (permanent) closure

Second-Line / Specialist Investigations

5. Optical Coherence Tomography (OCT)

OCT of Optic Nerve Head and RNFL:

• Non-invasive imaging
• Quantifies RNFL thickness and optic nerve parameters
• Comparison to normative database

Parameters:

• RNFL Thickness: Measures nerve fiber layer around disc

  • "Average thickness: ~90-100 μm"
  • "Color-coded: Green (normal), yellow (borderline), red (abnormal)"
  • Superior and inferior quadrants most important

• Rim Area: Quantifies neuroretinal rim

• Cup/Disc Parameters: Automated CDR measurements

Advantages:

• Objective, reproducible
• Detects early structural changes before visual field loss
• Useful for monitoring progression

Limitations:

• Cannot distinguish glaucoma from other optic neuropathies
• Artifacts from media opacities
• Limited in very advanced disease (floor effect)

6. OCT Angiography (OCTA)

• Emerging technology
• Evaluates microvascular perfusion of optic disc and macula
• Reduced vessel density associated with glaucoma
• Research tool becoming clinical application

7. Anterior Segment OCT (AS-OCT)

• High-resolution imaging of anterior chamber
• Measures anterior chamber depth, angle width, iris configuration
• Useful in angle closure assessment
• Can visualize angle structures without contact (unlike gonioscopy)

8. Ultrasound Biomicroscopy (UBM)

• High-frequency ultrasound of anterior segment
• Visualizes ciliary body, iris, lens, and angle
• Useful for:
  • Plateau iris diagnosis
  • Anterior segment tumors
  • Lens position abnormalities

9. Pachymetry (Corneal Thickness)

• Central corneal thickness (CCT) measurement
• Normal: 540-560 μm
• Thin cornea (less than 500 μm):
  • Underestimates true IOP
  • Independent risk factor for glaucoma progression [12]
• Thick cornea (> 580 μm):
  • Overestimates IOP
  • May explain ocular hypertension without damage

10. Blood Tests (Selected Cases)

Not routine, but consider in:

• NTG: FBC, ESR, lipid profile, glucose, thrombophilia screen (if young or suggestive history)
• Suspected GCA: ESR, CRP (temporal arteritis can cause acute optic nerve damage mimicking glaucoma)
• Systemic associations: HbA1c (diabetes), autoimmune markers (uveitic glaucoma)

11. Neuroimaging (Selected Cases)

MRI Brain and Orbits:

• If atypical features suggesting non-glaucomatous optic neuropathy:
  • Bitemporal hemianopia (chiasmal compression)
  • Decreased visual acuity out of proportion to field loss
  • Rapid progression
  • Young patient
  • Optic disc pallor without cupping

8. Classification / Staging

Glaucoma Severity Staging

Based on visual field loss (Hodapp-Anderson-Parrish Classification):

Advanced Glaucoma Intervention Study (AGIS) Score

• Score 0-20 based on number and depth of defects
• Used in research and clinical trials
• Higher score = more severe disease

Glaucoma Staging System (GSS)

5 stages based on visual field and structural damage:

• Stage 0: Ocular hypertension or suspect
• Stage 1: Early damage
• Stage 2: Moderate damage
• Stage 3: Advanced damage
• Stage 4: Severe damage
• Stage 5: End-stage (blindness)

Angle Closure Spectrum (PACS, PAC, PACG)

Primary Angle Closure Suspect (PACS):

• Narrow angles (≥180° iridotrabecular contact on gonioscopy)
• Normal IOP
• No PAS, no optic nerve damage

Primary Angle Closure (PAC):

• Iridotrabecular contact PLUS
• Elevated IOP and/or PAS
• NO optic nerve damage or visual field loss

Primary Angle Closure Glaucoma (PACG):

• Iridotrabecular contact PLUS
• Glaucomatous optic neuropathy and/or visual field loss

9. Management

Fundamental Principle: The ONLY proven treatment for glaucoma is lowering IOP. All interventions aim to reduce IOP to a level that prevents further optic nerve damage.

Target IOP:

• Individualized based on:
  • Severity of disease (more advanced = lower target)
  • Rate of progression
  • Life expectancy
  • Baseline IOP
• General targets:
  • "Early glaucoma: 25-30% reduction from baseline"
  • "Moderate glaucoma: 30-40% reduction"
  • "Advanced glaucoma: 40-50% reduction or IOP less than 12-14 mmHg"
  • "NTG: Target often less than 12 mmHg"

Treatment Modalities:

1. Medical (topical medications)
2. Laser therapy
3. Surgical (incisional surgery)

Management of Primary Open Angle Glaucoma (POAG)

Medical Management

First-Line: Prostaglandin Analogues (PGA)

Most effective class for IOP reduction.

Mechanism: Increase aqueous drainage via uveoscleral pathway by prostaglandin F2α receptor agonism.

Key Points:

• Most potent single-agent IOP reduction
• Once-daily dosing improves compliance
• Permanent iris color change (hazel/green to brown) in 10-20%; inform patients
• Eyelash changes (length, thickness, number) – cosmetically desirable but warn patients
• Contraindications: Active uveitis, herpetic keratitis, pregnancy (Category C), cystoid macular oedema
• Generally well-tolerated systemically (minimal absorption)

Second-Line: Beta-Blockers (β-adrenergic antagonists)

Mechanism: Block β2-adrenergic receptors on ciliary epithelium → Reduce aqueous production.

Key Points:

• Contraindications: Asthma, COPD, bradycardia, heart block, heart failure – CRITICAL exam point
• Systemic absorption significant despite topical use
• Check pulse before prescribing; monitor for bradycardia
• Tachyphylaxis (loss of efficacy) over time
• Combination products common (e.g., timolol + dorzolamide, timolol + latanoprost)

Third-Line: Carbonic Anhydrase Inhibitors (CAI)

Topical:

Systemic:

Mechanism: Inhibit carbonic anhydrase in ciliary epithelium → Reduced aqueous secretion.

Key Points:

• Topical CAI useful as adjunctive therapy
• Systemic CAI (acetazolamide) reserved for acute situations or refractory cases
• Contraindications (systemic): Sulfa allergy, severe renal impairment, hepatic impairment, hypokalemia
• Check electrolytes (K+) with prolonged systemic use

Fourth-Line: Alpha-2 Adrenergic Agonists

Mechanism: α2-agonists act on ciliary body (reduce production) and uveoscleral pathway (increase drainage).

Key Points:

• Brimonidine useful adjunct
• High rate of ocular allergy limits long-term use
• Apraclonidine used for acute IOP control, prophylaxis around laser procedures
• Possible neuroprotective effects (under investigation)

Fifth-Line: Cholinergic Agonists (Miotics)

Mechanism: Muscarinic receptor agonism → Ciliary muscle contraction → Opens trabecular meshwork.

Key Points:

• Largely fallen out of favor due to side effects and dosing frequency
• Still used in angle closure (constricts pupil, pulls iris peripherally)
• Very uncomfortable for younger patients (accommodative spasm)
• Caution in retinal disease (theoretical increased RD risk)

Combination Drops: To reduce drop burden and improve compliance:

• Cosopt (dorzolamide + timolol)
• Ganfort (bimatoprost + timolol)
• Xalacom (latanoprost + timolol)
• Simbrinza (brinzolamide + brimonidine)

Treatment Approach:

1. Start with prostaglandin analogue (latanoprost)
2. If inadequate IOP reduction, add second agent (usually beta-blocker or CAI)
3. If still inadequate, add third agent or consider laser/surgery
4. Maximum medical therapy = 3-4 topical agents

Monitoring:

• IOP checks every 3-6 months once stable
• Visual fields annually (more frequent if progression)
• Optic disc exam every 6-12 months
• OCT annually

Laser Therapy

Selective Laser Trabeculoplasty (SLT)

Mechanism:

• 532 nm Nd:YAG laser applied to trabecular meshwork
• Selective targeting of pigmented trabecular cells (spares adjacent tissue)
• Stimulates biological response: Cytokine release, macrophage recruitment, extracellular matrix remodeling
• Improves aqueous outflow facility

Efficacy:

• IOP reduction: 20-30% from baseline (6-8 mmHg) [15]
• Success rate: ~75-80% at 1 year
• Effect may diminish over time (median duration 3-4 years)
• Can be repeated

Indications:

• First-line alternative to medications (NICE 2022 recommends offering SLT as first-line) [16]
• Adjunct to medical therapy
• Poor compliance with medications
• Intolerance to medications

Procedure:

• Outpatient
• Topical anaesthesia
• 50-100 laser spots applied over 180-360° of trabecular meshwork
• Duration: 5-10 minutes

Advantages:

• Non-invasive
• No systemic side effects
• No compliance issues
• Cost-effective over time
• Repeatable

Disadvantages:

• Transient IOP spike (treat with prophylactic apraclonidine or close monitoring)
• Inflammation (treat with topical steroids for 3-5 days)
• Unpredictable response (some patients non-responders)
• Effect wears off over time

Evidence:

• LiGHT Trial (2019): SLT first-line superior to medications in terms of IOP control, quality of life, and cost-effectiveness over 3 years [15]

Argon Laser Trabeculoplasty (ALT):

• Older technique (non-selective)
• Less commonly used now (SLT preferred)
• Higher energy, more collateral damage
• Cannot repeat as effectively

Surgical Management

Reserved for:

• Inadequate IOP control on maximum tolerated medical therapy
• Intolerance to medications
• Poor compliance
• Advanced disease requiring very low target IOP
• Patient preference (especially in developing world where medication access limited)

1. Trabeculectomy

Gold Standard glaucoma surgery.

Principle:

• Create new drainage pathway for aqueous from anterior chamber to subconjunctival space
• Forms filtering "bleb" under conjunctiva

Procedure:

• Partial-thickness scleral flap created
• Sclerectomy (remove piece of trabecular meshwork and inner scleral tissue)
• Peripheral iridectomy (prevent iris blocking internal ostium)
• Scleral flap loosely sutured (allows aqueous egress)
• Conjunctiva closed

Antimetabolites:

• Mitomycin C (MMC) or 5-fluorouracil (5-FU) applied intraoperatively
• Inhibit fibroblast proliferation
• Prevent bleb scarring and failure
• Increase success but also increase complication risk

Efficacy:

• Success (IOP less than 21 mmHg): ~80-90% at 1 year, ~60-70% at 5 years [17]
• Mean IOP reduction: 40-50% (often to low-mid teens mmHg)

Complications:

• Early:

  • Hypotony (IOP too low) – 10-15%
  • Shallow/flat anterior chamber
  • Choroidal effusion/haemorrhage (less than 5%, sight-threatening)
  • Hyphema
  • Wound leak

• Late:

  • Bleb failure (scarring) – 20-30% over 5 years
  • Bleb-related infection (blebitis, endophthalmitis) – 1-2% lifetime risk
  • Cataract progression (50% over 5 years)
  • Hypotony maculopathy
  • Late suprachoroidal haemorrhage

Success Factors:

• Use of antimetabolites (especially MMC)
• Younger age associated with more scarring (worse outcome)
• Previous ocular surgery reduces success
• Afro-Caribbean ethnicity (more aggressive scarring)

Follow-up:

• Intensive initially (weekly, then decreasing frequency)
• Bleb needling with 5-FU may be needed if early scarring
• Lifelong monitoring for bleb-related infections

2. Tube Shunt Surgery (Glaucoma Drainage Devices)

Examples: Ahmed valve, Baerveldt implant, Molteno implant.

Principle:

• Silicone tube inserted into anterior chamber
• Drains aqueous to equatorial plate under conjunctiva
• Forms bleb around plate

Indications:

• Failed trabeculectomy
• High-risk cases (neovascular glaucoma, uveitic glaucoma, previous conjunctival scarring)
• Preferred over trabeculectomy in some scenarios

Valved vs. Non-Valved:

• Valved (Ahmed): Pressure-sensitive valve limits flow; lower early hypotony risk
• Non-Valved (Baerveldt): No valve; higher flow, better long-term IOP control but higher hypotony risk initially

Efficacy:

• Similar to trabeculectomy (~60-70% success at 5 years)
• Tube Versus Trabeculectomy (TVT) Study: Similar IOP control, different complication profiles [18]

Complications:

• Early hypotony (especially non-valved)
• Tube malposition/erosion
• Corneal endothelial damage (if tube touches cornea)
• Diplopia (restrictive strabismus from plate)
• Infection
• Late failure

3. Minimally Invasive Glaucoma Surgery (MIGS)

Emerging class of procedures with better safety profile but more modest IOP reduction.

Examples:

• iStent/iStent inject: Trabecular micro-bypass stent (inserts into Schlemm's canal)
• Hydrus Microstent: Schlemm's canal scaffold
• Trabectome: Ab interno trabeculotomy (removal of trabecular meshwork from inside eye)
• Kahook Dual Blade (KDB): Goniotomy/trabeculotomy
• XEN Gel Stent: Subconjunctival micro-stent
• PreserFlo MicroShunt: Subconjunctival drainage device

Indications:

• Mild to moderate POAG
• Often combined with cataract surgery
• Patients desiring reduced medication burden

Efficacy:

• IOP reduction: 15-25% (modest, less than trabeculectomy)
• Many patients still require medications
• Success depends on specific procedure

Advantages:

• Excellent safety profile
• Faster recovery
• Ab interno approach (no conjunctival dissection for most)
• Preserves conjunctiva for future filtering surgery

Disadvantages:

• Limited IOP reduction (not suitable for advanced disease or high IOP)
• Long-term data still emerging
• Expensive devices
• Not all effective in all glaucoma types

4. Cyclodestructive Procedures

Principle: Destroy ciliary body to reduce aqueous production.

Methods:

• Transscleral diode laser cyclophotocoagulation
• Endoscopic cyclophotocoagulation (ECP)
• Cyclocryotherapy (rarely used now)

Indications:

• Refractory glaucoma (failed multiple surgeries)
• Poor visual potential (usually less than 6/60)
• Neovascular glaucoma
• End-stage painful glaucoma

Efficacy:

• Variable IOP reduction
• May need repeated treatments
• Risk of hypotony, phthisis (shrunken, non-functional eye)

Complications:

• Pain, inflammation
• Hypotony
• Vision loss
• Phthisis bulbi
• Sympathetic ophthalmia (rare)

Management of Acute Angle Closure Glaucoma (AAC)

Acute angle closure is an OPHTHALMIC EMERGENCY. Irreversible vision loss can occur within hours.

Immediate Management (Emergency Department / Acute Setting)

Goals:

1. Lower IOP rapidly
2. Relieve pupil block
3. Clear corneal oedema (to allow laser treatment)
4. Prevent fellow eye involvement

Step 1: Initial Assessment

• Measure IOP (often 40-80 mmHg)
• Assess vision (often markedly reduced)
• Examine fellow eye (narrow angle, at risk)

Step 2: Medical Therapy to Lower IOP

All of the following should be initiated immediately:

1. Systemic Carbonic Anhydrase Inhibitor:

   • Acetazolamide 500 mg IV (or 500 mg PO if IV not available)
   • Most effective agent for rapid IOP reduction
   • Contraindications: Sulfa allergy, severe renal failure

2. Topical Beta-Blocker:

   • Timolol 0.5% one drop
   • Contraindications: Asthma, COPD, bradycardia, heart block

3. Topical Alpha-Agonist:

   • Apraclonidine 1% or Brimonidine 0.2% one drop

4. Topical Steroid:

   • Prednisolone acetate 1% one drop
   • Reduce inflammation

5. Hyperosmotic Agent (if IOP very high > 50 mmHg and not responding):

   • IV Mannitol 20% 1-2 g/kg over 30-45 minutes
   • Creates osmotic gradient, draws fluid from eye
   • Contraindications: Heart failure, renal failure
   • Foley catheter (causes diuresis)

Step 3: Miotic Agent (AFTER IOP starts to lower)

6. Pilocarpine 1-2%:
   • Do NOT give initially (if IOP very high and iris ischaemic, pupil won't constrict)
   • Give AFTER IOP less than 40 mmHg (usually 30-60 minutes after above treatments)
   • Constricts pupil → Pulls peripheral iris away from angle
   • One drop every 15 minutes × 2, then every 6 hours

Step 4: Analgesia and Antiemetics

• Severe pain common
• Analgesia: Paracetamol, NSAIDs, opioids if needed
• Antiemetics: Ondansetron, metoclopramide (vomiting common)

Step 5: Urgent Ophthalmology Referral

• Same-day assessment
• Arrange laser iridotomy once IOP controlled and cornea clear

Response:

• IOP typically falls within 1-2 hours
• Symptoms improve as IOP lowers
• Corneal oedema clears (allows visualization for laser)

Definitive Management: Laser Peripheral Iridotomy (LPI)

Timing: Within 24-48 hours of presentation (once IOP controlled and cornea clear).

Principle:

• Create hole in peripheral iris
• Equalizes pressure between posterior and anterior chambers
• Eliminates pupillary block
• Allows iris to fall back, opening the angle

Procedure:

• Outpatient, sitting at slit lamp
• Topical anaesthesia
• Nd:YAG laser (1064 nm) or Argon laser
• 1-2 small holes created in peripheral iris (usually superiorly, hidden under eyelid)
• Takes 5-10 minutes

Post-procedure:

• Topical steroid (prednisolone 1%) four times daily for 5-7 days
• Check IOP 1 hour post-procedure (transient spike possible)
• Recheck gonioscopy to confirm angle opened

Success:

• 95% successful in relieving pupillary block

• Prevents future acute attacks in that eye

Prophylactic LPI in Fellow Eye:

• ESSENTIAL: 40-80% risk of AAC in fellow eye within 5 years if untreated [14]
• Perform prophylactic LPI in fellow eye within days to weeks

Complications of LPI:

• Transient IOP spike (treat with apraclonidine)
• Bleeding (transient)
• Localized lens opacity (if laser hits lens)
• Diplopia/glare (if iridotomy large and not covered by lid)
• Closure of iridotomy (5-10%; may need repeat)

Surgical Management if Laser Fails

Laser Iridoplasty (Gonioplasty):

• Argon laser applied to peripheral iris
• Contracts iris stroma, pulls iris peripherally
• Useful in plateau iris or if LPI insufficient

Surgical Iridectomy:

• Rarely needed
• If LPI not possible (very hazy cornea) or fails

Lens Extraction (Phacoemulsification):

• Definitive treatment
• Removes lens (often cataractous in elderly)
• Deepens anterior chamber
• Highly effective
• Increasingly used as primary or early intervention

Management of Chronic Angle Closure Glaucoma (CACG)

• LPI: Eliminates pupillary block component
• Medical therapy: As for POAG (to lower IOP)
• Lens extraction: Very effective (removes phacomorphic component)
• Trabeculectomy or tube: If synechial damage extensive and IOP not controlled

Management of Normal Tension Glaucoma (NTG)

Target IOP: 30% reduction from baseline (even though baseline "normal"), typically targeting less than 12 mmHg.

Medical Therapy:

• Same agents as POAG
• Prostaglandin analogues first-line

Systemic Considerations:

• Treat systemic vascular risk factors (hypertension, diabetes, hyperlipidemia)
• Avoid nocturnal hypotension
• Evaluate for sleep apnoea (CPAP if present)
• Evaluate for vasospasm (migraine treatment)
• Consider 24-hour BP monitoring

Neuroprotection:

• Theoretical interest but no proven agents currently
• Research ongoing (brimonidine, memantine, citicoline)

Imaging:

• Rule out other optic neuropathies (MRI if atypical features)

Management of Secondary Glaucomas

Neovascular Glaucoma

Urgent Treatment:

• Lower IOP: Maximum medical therapy (acetazolamide, topical agents)
• Panretinal photocoagulation (PRP): Laser to ischaemic retina (reduces VEGF drive)
• Anti-VEGF injection: Intravitreal bevacizumab or ranibizumab (causes rapid regression of new vessels)
• Surgery: Tube shunt preferred over trabeculectomy (better success in neovascular cases)

Poor Prognosis: Often severe vision loss, difficult to control.

Pseudoexfoliative Glaucoma

• Treat as POAG but expect higher IOP, more aggressive
• Often requires multiple medications or surgery
• Increased risk of complications during cataract surgery (weak zonules)

Pigmentary Glaucoma

• Treat as POAG
• Laser iridotomy controversial (may reduce reverse pupillary block, but evidence mixed)
• Advise avoiding activities that cause pigment liberation (vigorous exercise, eye rubbing)

Uveitic Glaucoma

• Treat underlying inflammation first (topical/systemic steroids, immunosuppression)
• Lower IOP (avoid prostaglandins if active inflammation)
• Surgery difficult (high failure rate due to scarring)

Steroid-Induced Glaucoma

• Stop or reduce steroid if possible
• Switch to less IOP-elevating steroid (fluorometholone instead of prednisolone)
• Treat elevated IOP as POAG
• Usually reversible with steroid cessation

10. Complications

Complications of Glaucoma Itself

Complications of Medical Therapy

Covered above in medication tables. Key points:

• Beta-blockers: Systemic cardiovascular and respiratory effects
• Prostaglandins: Iris pigmentation, periocular changes
• Acetazolamide: Electrolyte disturbances, renal stones

Complications of Surgical Therapy

Covered above in surgical sections. Key points:

• Trabeculectomy: Hypotony, bleb leak, infection (blebitis/endophthalmitis), cataract
• Tube shunts: Tube malposition, corneal decompensation, diplopia
• Laser: IOP spike, inflammation (usually transient and manageable)

11. Prognosis

Natural History (Untreated)

• POAG: Slow progression over 10-20 years from onset to blindness
• AAC: Rapid vision loss within hours to days if untreated
• NTG: Often slower progression than high-pressure glaucoma but still progresses

With Treatment

• POAG: Most patients retain useful vision throughout life if diagnosed early and treated adequately

  • "Progression to blindness: ~5-10% of patients despite treatment"
  • "Unilateral blindness: ~15-20%"
  • "Risk factors for progression: Advanced disease at diagnosis, poor IOP control, high baseline IOP, thin corneas, older age"

• AAC: Excellent prognosis if treated promptly (within 24-48 hours)

  • "If delay > 1 week: Permanent vision loss likely"
  • "Fellow eye: Prophylactic LPI almost always prevents AAC"

• NTG: Variable progression

  • Lower IOP still beneficial
  • 30% reduction in IOP reduces progression risk

Prognostic Factors

Worse Prognosis:

• Advanced disease at presentation
• Poor IOP control
• High IOP fluctuation
• Older age
• Thin central corneal thickness
• Cardiovascular disease (especially in NTG)
• Disc haemorrhages
• Afro-Caribbean ethnicity (more aggressive disease)

Better Prognosis:

• Early detection
• Good IOP control (to target)
• Good treatment adherence
• Regular monitoring

Life Expectancy Considerations

• Glaucoma is a lifelong disease
• Treatment decisions should consider:
  • Patient's age and life expectancy
  • Rate of progression
  • Current functional vision
  • Quality of life impact
• In very elderly or those with limited life expectancy and early disease, observation may be appropriate

12. Prevention & Screening

Primary Prevention

No proven strategies to prevent glaucoma onset, but modifiable risk factors:

• Control diabetes
• Maintain cardiovascular health
• Avoid unnecessary corticosteroid use
• Protect eyes from trauma

Secondary Prevention (Early Detection)

Screening Recommendations:

United Kingdom (NICE):

• No national screening program
• Opportunistic case finding through optometry
• Free NHS eye tests for high-risk groups:
  • Age ≥60 years
  • Age ≥40 years if Afro-Caribbean or family history
  • Diabetics

American Academy of Ophthalmology (AAO):

• Comprehensive eye exam:
  • "Age 40: Baseline exam"
  • "Age 40-54: Every 2-4 years"
  • "Age 55-64: Every 1-3 years"
  • "Age ≥65: Every 1-2 years"
• More frequent if high risk

High-Risk Groups (more frequent screening):

• First-degree relative with glaucoma
• Afro-Caribbean, Asian (especially East Asian for angle closure)
• High myopia
• Diabetes
• Previous eye injury
• Long-term steroid use

Screening Tests:

• Tonometry (IOP)
• Optic disc examination (fundoscopy)
• If abnormal → Refer for gonioscopy, visual fields, OCT

Tertiary Prevention (Prevent Progression)

• Early diagnosis and treatment
• Adherence to medications
• Regular monitoring (IOP, visual fields, disc imaging)
• Patient education

13. Key Guidelines

NICE Guideline NG81: Glaucoma (2017, updated 2022) [16]

Key Recommendations:

1. Offer SLT as first-line treatment for POAG and ocular hypertension (alongside or instead of eye drops)
2. If medications used, start with prostaglandin analogue
3. Refer those with angle closure or suspected angle closure same-day to ophthalmologist
4. Offer information about support organizations (e.g., Glaucoma UK)

European Glaucoma Society (EGS) Guidelines (2020)

• Comprehensive guidelines on diagnosis and management
• Emphasize individualized target IOP
• Detailed imaging and perimetry protocols

American Academy of Ophthalmology (AAO) Preferred Practice Patterns

• POAG (2020)
• Primary Angle Closure (2021)
• Evidence-based recommendations on diagnosis, treatment, monitoring

Royal College of Ophthalmologists (RCOphth) Guidelines

• Commissioning guidance for glaucoma services (UK)
• Standards for monitoring intervals

14. Exam-Focused Sections

Common Exam Questions (FRCOphth, MRCP, Medical Finals)

MRCP/Medical Students:

1. "A 65-year-old Afro-Caribbean man is found to have an IOP of 26 mmHg in his right eye on routine optometry visit. What is your initial management?"
2. "An 80-year-old lady presents with severe right-sided headache, vomiting, and blurred vision. On examination, she has a red right eye with a hazy cornea and a fixed, dilated pupil. What is the most likely diagnosis and immediate management?"
3. "What are the contraindications to timolol eye drops?"
4. "A patient on latanoprost for glaucoma reports that his eyes have changed color. What do you tell him?"
5. "What is the mechanism of action of prostaglandin analogues in glaucoma?"

FRCOphth/Specialist:

1. "Describe the aqueous drainage pathways and how they are affected in POAG vs PACG."
2. "A patient has a CDR of 0.7, IOP of 18 mmHg, and arcuate scotoma on visual field. How do you establish the diagnosis of glaucoma?"
3. "What are the indications for trabeculectomy, and what are the major complications?"
4. "Compare and contrast SLT and ALT."
5. "Describe the classification of the angle closure spectrum (PACS, PAC, PACG)."
6. "A patient with advanced POAG on maximum medical therapy has an IOP of 22 mmHg but continues to progress. What is your management?"
7. "What is the role of OCT in glaucoma diagnosis and monitoring?"
8. "Describe the LiGHT trial and its implications for glaucoma management."

Viva Points

Opening Statement: "Glaucoma is a group of progressive optic neuropathies characterized by retinal ganglion cell death and optic nerve head damage, typically associated with elevated intraocular pressure. It is the leading cause of irreversible blindness worldwide, affecting over 76 million people. The two main types are primary open angle glaucoma, which is chronic and asymptomatic, and acute angle closure glaucoma, which is a sight-threatening emergency."

Key Facts for Viva:

1. Prevalence: 2-3% of population > 40 years; projected 111.8 million by 2040 globally [1,2]
2. Risk Factors: Age, family history (4-9x risk), Afro-Caribbean ethnicity (POAG), Asian ethnicity (PACG), high myopia
3. Pathophysiology: Increased outflow resistance at trabecular meshwork (POAG) or physical angle closure (PACG)
4. Diagnosis: Triad of elevated IOP, optic disc cupping, and characteristic visual field defects
5. First-line treatment (POAG): Prostaglandin analogue (latanoprost) OR selective laser trabeculoplasty (SLT) – NICE 2022 [16]
6. AAC emergency management: IV acetazolamide 500 mg, topical timolol + apraclonidine + steroid, then pilocarpine once IOP lowering, followed by YAG laser iridotomy within 24-48 hours
7. Evidence: LiGHT Trial (2019) showed SLT superior to medications as first-line [15]

Classic Exam Traps to Mention:

• Beta-blockers contraindicated in asthma/COPD (systemic absorption)
• Prostaglandins cause permanent iris color change (inform patients)
• Prophylactic LPI in fellow eye essential after AAC (40-80% risk)
• Never dilate a patient with narrow angles (can precipitate AAC)
• 30% of glaucoma patients have "normal" IOP (normal tension glaucoma)
• Glaucoma damage is irreversible (treatment prevents further loss only)

Common Mistakes (That Fail Candidates)

❌ Mistakes:

1. Not recognizing acute angle closure as an emergency – Must initiate treatment immediately, not "refer to ophthalmology clinic"
2. Prescribing timolol to an asthmatic – Classic exam fail
3. Missing the need for prophylactic treatment of the fellow eye in AAC
4. Thinking glaucoma treatment can restore vision – Treatment only prevents further loss
5. Not appreciating that normal IOP doesn't exclude glaucoma – 30% have normal-tension glaucoma
6. Dilating pupils in a patient with shallow anterior chambers – Can precipitate angle closure
7. Forgetting to check central corneal thickness – Affects IOP measurement accuracy
8. Not knowing NICE now recommends SLT as first-line option – Updated 2022
9. Stating that all glaucoma patients have high IOP – NTG exists
10. Missing red flags in history – Severe pain + haloes + vomiting = AAC until proven otherwise

Model Answers

Q: A 70-year-old Chinese lady presents to ED with severe right eye pain, headache, vomiting, and seeing haloes around lights for 3 hours. Describe your approach.

Model Answer:

"This presentation is highly suggestive of acute angle closure glaucoma, which is an ophthalmic emergency requiring immediate treatment to prevent irreversible vision loss.

Initial Assessment: I would perform a rapid examination including visual acuity, pupil reactions, and IOP measurement. I would expect to find a very high IOP (typically 40-80 mmHg), a red eye with a hazy cornea, a mid-dilated fixed pupil, and a shallow anterior chamber. I would also examine the fellow eye, which is likely to have a narrow angle and be at risk of the same problem.

Immediate Management: My goals are to rapidly lower the IOP and relieve the pupillary block. I would initiate:

1. Systemic treatment: IV or oral acetazolamide 500 mg
2. Topical treatment: Timolol 0.5%, apraclonidine 1%, and prednisolone 1% drops
3. Once the IOP begins to fall (below 40 mmHg), I would add pilocarpine 2% to constrict the pupil
4. Analgesia and antiemetics for symptom relief

Definitive Treatment: I would arrange urgent same-day ophthalmology review. Once the IOP is controlled and the cornea clears, the definitive treatment is laser peripheral iridotomy (LPI) to create a hole in the iris, which relieves the pupillary block and prevents future attacks.

Fellow Eye: Crucially, the fellow eye has a 40-80% risk of acute angle closure within 5 years, so prophylactic LPI must be performed on the fellow eye as well.

Follow-up: After LPI, the patient would need regular monitoring to ensure the angles remain open and to detect any chronic glaucomatous damage that may have occurred."

---

Q: What are the causes of a painful red eye with reduced vision?

Model Answer:

"The key differential diagnoses for a painful red eye with reduced vision include:

1. Acute Angle Closure Glaucoma: Very high IOP, haloes, fixed mid-dilated pupil, rock-hard eye
2. Anterior Uveitis: Miotic (small) pupil, photophobia, keratic precipitates, normal or low IOP
3. Scleritis: Deep boring pain, scleral injection, tenderness, normal pupil
4. Corneal Ulcer/Keratitis: History of trauma or contact lens, fluorescein uptake, infiltrate
5. Endophthalmitis: Severe inflammation, hypopyon, recent surgery or trauma

The IOP, pupil size, and specific examination findings help differentiate these conditions. A fixed mid-dilated pupil and rock-hard eye point strongly toward acute angle closure."

---

15. Patient Explanation

What is Glaucoma?

"Glaucoma is an eye condition where the nerve at the back of your eye (the optic nerve) becomes damaged, usually because of high pressure inside the eye. Think of your eye like a football – it needs a certain amount of pressure to keep its shape. Fluid is constantly being made inside your eye and draining away. In glaucoma, the drainage system gets blocked, so pressure builds up. This pressure damages the nerve, which causes permanent loss of vision, usually starting from the sides and working inward."

Can My Vision Be Restored?

"Unfortunately, no. The damage to the optic nerve is permanent, and we cannot restore vision that has been lost. However, we can prevent further damage by lowering the pressure in your eye with eye drops, laser treatment, or surgery. This is why it's so important to use your treatment every day, even if you feel fine. Glaucoma is often called the 'silent thief of sight' because you don't notice the vision loss until it's quite advanced."

Will I Go Blind?

"Most people with glaucoma do NOT go completely blind, especially if it's caught early and treated properly. With modern treatments and regular monitoring, the vast majority of patients keep useful vision for their entire lives. The key is using your drops every day and attending all your appointments so we can check that the treatment is working and adjust it if needed."

Why Do I Need Treatment If I Can See Fine?

"This is a very common question. Glaucoma usually affects your peripheral (side) vision first, and your brain is very good at filling in the gaps, so you don't notice it. By the time you notice vision loss, a lot of permanent damage has already occurred. We can see this damage early using special tests and scans, long before you'd notice it yourself. That's why treatment is so important even when you feel your vision is fine – we're preventing future loss."

What Happens If I Miss My Drops?

"Missing drops occasionally isn't ideal but won't cause disaster. However, if you frequently miss your drops, the pressure can rise again and cause more damage. Glaucoma treatment only works if you use it. Think of it like taking blood pressure tablets – missing them doesn't cause immediate harm, but over time, it increases your risk of serious problems. If you're struggling with the drops (stinging, difficulty remembering, cost), please tell me – there are often solutions."

16. References

1. Tham YC, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081-2090. doi:10.1016/j.ophtha.2014.05.013

2. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262-267. doi:10.1136/bjo.2005.081224

3. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014;311(18):1901-1911. doi:10.1001/jama.2014.3192

4. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 2002;86(2):238-242. doi:10.1136/bjo.86.2.238

5. Friedman DS, Wolfs RC, O'Colmain BJ, et al. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol. 2004;122(4):532-538. doi:10.1001/archopht.122.4.532

6. Tielsch JM, Sommer A, Katz J, et al. Racial variations in the prevalence of primary open-angle glaucoma. The Baltimore Eye Survey. JAMA. 1991;266(3):369-374.

7. Cheng JW, Zong Y, Zeng YY, Wei RL. The prevalence of primary angle closure glaucoma in adult Asians: a systematic review and meta-analysis. PLoS One. 2014;9(7):e103222. doi:10.1371/journal.pone.0103222

8. Kim CS, Seong GJ, Lee NH, et al. Prevalence of primary open-angle glaucoma in central South Korea the Namil study. Ophthalmology. 2011;118(6):1024-1030. doi:10.1016/j.ophtha.2010.10.016

9. Wolfs RC, Klaver CC, Ramrattan RS, et al. Genetic risk of primary open-angle glaucoma. Population-based familial aggregation study. Arch Ophthalmol. 1998;116(12):1640-1645. doi:10.1001/archopht.116.12.1640

10. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701-713. doi:10.1001/archopht.120.6.701

11. Marcus MW, de Vries MM, Montolio FG, Jansonius NM. Myopia as a risk factor for open-angle glaucoma: a systematic review and meta-analysis. Ophthalmology. 2011;118(10):1989-1994.e2. doi:10.1016/j.ophtha.2011.03.012

12. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):714-720. doi:10.1001/archopht.120.6.714

13. European Glaucoma Prevention Study (EGPS) Group. Predictive factors for open-angle glaucoma among patients with ocular hypertension in the European Glaucoma Prevention Study. Ophthalmology. 2007;114(1):3-9. doi:10.1016/j.ophtha.2006.05.075

14. Lowe RF. Acute angle-closure glaucoma: the second eye: an analysis of 200 cases. Br J Ophthalmol. 1962;46(11):641-650. doi:10.1136/bjo.46.11.641

15. Gazzard G, Konstantakopoulou E, Garway-Heath D, et al. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet. 2019;393(10180):1505-1516. doi:10.1016/S0140-6736(18)32213-X

16. National Institute for Health and Care Excellence. Glaucoma: diagnosis and management. NICE guideline [NG81]. Published January 2017, updated November 2022. Available at: https://www.nice.org.uk/guidance/ng81

17. Gedde SJ, Herndon LW, Brandt JD, et al. Postoperative complications in the Tube Versus Trabeculectomy (TVT) study during five years of follow-up. Am J Ophthalmol. 2012;153(5):804-814.e1. doi:10.1016/j.ajo.2011.10.024

18. Gedde SJ, Schiffman JC, Feuer WJ, et al. Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up. Am J Ophthalmol. 2012;153(5):789-803.e2. doi:10.1016/j.ajo.2011.10.026

19. Peters D, Bengtsson B, Heijl A. Lifetime risk of blindness in open-angle glaucoma. Am J Ophthalmol. 2013;156(4):724-730. doi:10.1016/j.ajo.2013.05.027

20. Lamoureux EL, Chong E, Wang JJ, et al. Visual impairment, causes of vision loss, and falls: the Singapore Malay Eye Study. Invest Ophthalmol Vis Sci. 2008;49(2):528-533. doi:10.1167/iovs.07-1036