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Glaucoma - Complete MBBS Guide

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1. DEFINITION

• Kanski's: "Glaucoma is the term used to describe a group of conditions that have in common a chronic progressive optic neuropathy that results in characteristic morphological changes at the optic nerve head and in the retinal nerve fibre layer."
• Goal of treatment: to slow progression throughout a patient's lifetime, maintaining visual function and quality of life.

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2. AQUEOUS HUMOR DYNAMICS (Pathophysiology Foundation)

1. Trabecular (conventional) pathway (~85%): Posterior chamber → pupil → anterior chamber → trabecular meshwork (TM) → Schlemm's canal → episcleral veins. This is the pressure-dependent route.
2. Uveoscleral (unconventional) pathway (~15%): Through ciliary muscle bundles to supraciliary/suprachoroidal space. Pressure-independent; enhanced by prostaglandins.

• Increased production (rare)
• Decreased trabecular outflow (most common)
• Raised episcleral venous pressure (e.g., Sturge-Weber, AV fistula)

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3. CLASSIFICATION

Full Classification:

GLAUCOMA
├── Primary
│   ├── Primary Open-Angle Glaucoma (POAG)
│   │   └── Normal Tension Glaucoma (NTG) - subset
│   ├── Primary Angle-Closure Glaucoma (PACG)
│   └── Primary Congenital Glaucoma
└── Secondary
    ├── Open-angle: Pigmentary, Pseudoexfoliation, Steroid-induced, Traumatic
    └── Angle-closure: Neovascular, Phacolytic, Phacomorphic, Lens-induced

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4. PRIMARY OPEN-ANGLE GLAUCOMA (POAG)

Epidemiology

• Prevalence in >70 years: ~6% in White, ~16% in Black, ~3% in Asian populations
• Affects both genders equally
• Most prevalent form globally (60-70% of all glaucoma cases)

Risk Factors

Pathogenesis

1. Mechanical theory: Elevated IOP causes physical distortion of the lamina cribrosa, compressing and damaging RGC axons as they pass through
2. Vascular theory: Reduced ocular perfusion pressure → ischaemia of the optic nerve head (explains NTG)

Clinical Features

Visual Field Defects (in order of progression)

1. Enlarged blind spot (earliest, but non-specific)
2. Paracentral scotomas - small depressions, often superonasally
3. Nasal step - difference in sensitivity above and below horizontal midline in nasal field; bounded by horizontal raphe
4. Arcuate (Bjerrum) scotoma - arcs from blind spot to nasal horizontal meridian (superior or inferior arcade follows nerve fibre bundle pattern)
5. Ring scotoma - when superior and inferior arcuates connect
6. Temporal wedge - less common, similar implications
7. Advanced loss - only temporal island + central island remaining
8. Tubular vision (end stage) - only central 5-10° preserved
9. Total blindness

Investigations

Diagnosis

• Open anterior chamber angle on gonioscopy
• Characteristic optic disc/RNFL changes
• Characteristic visual field defects (when present)
• Absence of secondary cause

Treatment of POAG

• Selective Laser Trabeculoplasty (SLT): Can be used as first-line (LiGHT trial: non-inferior to drops). 532 nm frequency-doubled Nd:YAG laser targets pigmented TM cells. 80 laser spots over 360°. Repeatable. 25-30% IOP reduction.
• Argon Laser Trabeculoplasty (ALT): Older modality, not repeatable.

• Trabeculectomy (guarded filtration surgery): Creates a fistula between anterior chamber and subconjunctival space. MMC (mitomycin C) or 5-FU used to prevent scarring. Gold standard surgical procedure.
• Glaucoma Drainage Devices (GDD/Tube shunts): Ahmed, Baerveldt, Molteno devices - for complex cases/failed trabeculectomy.
• Minimally Invasive Glaucoma Surgery (MIGS): iStent, Hydrus, OMNI - less risk but less IOP reduction. Best combined with cataract surgery.
• Cyclodestructive procedures: Diode laser cyclodiode ablation - reduces AH production by destroying ciliary body. Reserved for end-stage/blind painful eyes.

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5. NORMAL TENSION GLAUCOMA (NTG)

• IOP consistently ≤21 mmHg but glaucomatous disc and field damage present
• ~30-40% of POAG patients have NTG
• Pathogenesis: Vascular insufficiency (vasospasm, nocturnal hypotension, sleep apnoea, autoimmune) predominates over mechanical
• Disc haemorrhages more frequent; more localised, deeper scotomas closer to fixation
• Associations: Flammer syndrome, obstructive sleep apnoea, autoimmune diseases
• Treatment: Same drugs as POAG (aim lower target IOP); treat systemic vascular risk factors; CCBs (nifedipine) in selected patients

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6. PRIMARY ANGLE-CLOSURE GLAUCOMA (PACG)

Overview

• "Angle closure" = occlusion of TM by peripheral iris (iridotrabecular contact, ITC)
• PACG may cause up to half of all glaucoma globally and is particularly prevalent in Asia (East and South)
• Progresses rapidly, more likely to cause visual loss than POAG

Anatomical Predisposition

• Shallow anterior chamber
• Short axial length (hypermetropia)
• Anterior lens position (increases with age as lens thickens)
• Small corneal diameter
• Thick peripheral iris

Mechanisms (from anterior to posterior)

Gonioscopy - Shaffer Grading System

• Slit beam at limbus, compare anterior chamber depth to peripheral corneal thickness
• Ratio <1/4 → narrow angle → formal gonioscopy needed

PACG Spectrum (Terminology)

ACUTE ANGLE-CLOSURE ATTACK (Clinical Emergency)

• Mydriasis: dim lighting, anticholinergics (e.g., atropine, antihistamines, TCAs), sympathomimetics, motion sickness patches
• Topiramate (causes anterior rotation of ciliary body - unusual mechanism)
• Prone position (reading)
• Emotional stress

• Sudden severe unilateral eye pain
• Blurred vision with coloured halos around lights (corneal oedema causing diffraction)
• Frontal headache, nausea, vomiting (may mimic acute abdomen/migraine)
• Photophobia

• Ciliary/circumcorneal congestion (perilimbal injection)
• Corneal oedema (steamy, hazy cornea)
• Shallow anterior chamber (Oblique illumination test / van Herick)
• Mid-dilated, fixed, oval (vertically oval) pupil - key sign
• High IOP (often 40-80 mmHg)
• Corneal endothelial oedema (Haab's striae in congenital)
• Optic disc congestion

Management of Acute Attack

1. Topical medications (instill with 3-5 min interval):
   • Apraclonidine 0.5-1% (α2-agonist)
   • Timolol 0.5% (β-blocker)
   • Prednisolone 1% or dexamethasone 0.1% (reduce inflammation)
2. Pilocarpine 2%: 1 drop to affected eye, repeat after 30 min; 1% to fellow eye. Note: Do NOT repeat if IOP >40 mmHg (ischaemia renders iris sphincter unresponsive)
3. Analgesia + antiemetic
4. Systemic hyperosmotic agents (if topical insufficient):
   • Mannitol 20%: 1-2 g/kg IV over 1 hour
   • Oral glycerol 50%: 1 g/kg
   • Oral isosorbide: 1-1.5 g/kg
   • These raise serum osmolality → draw fluid from vitreous → reduce IOP
5. Oral/IV acetazolamide 250-500 mg (CAI - reduces AH production)

• Corneal indentation (force aqueous posteriorly to open angle)
• 50% topical glycerol to clear corneal oedema before laser
• Paracentesis (rapid IOP reduction, small risk)
• Early laser iridotomy/iridoplasty once cornea clears

• Laser peripheral iridotomy (LPI): Creates a full-thickness hole in peripheral iris → equalizes pressure between posterior and anterior chambers → relieves pupillary block → angle opens. Bilateral (fellow eye prophylactically). Gold standard.
• Lens extraction (phacoemulsification): Particularly if significant phacomorphic component; increasingly favoured (EAGLE trial showed superior outcomes over LPI alone)
• Trabeculectomy: If persistent IOP elevation despite patent iridotomy

• Continue pilocarpine 2% QDS; topical steroid for inflammation
• Repeat gonioscopy to confirm angle is open
• Low threshold for cataract surgery

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7. PRIMARY CONGENITAL GLAUCOMA (PCG)

• Autosomal recessive (CYP1B1 gene mutation most common)
• Due to trabeculodysgenesis (maldevelopment of angle structures)
• Presents from birth to age 3 (most within first year)

Classic Triad:

1. Epiphora (watering, photophobia)
2. Blepharospasm (squinting in light)
3. Corneal cloudiness (oedema)

Signs:

• Buphthalmos (ox eye): enlarged globe, due to scleral stretching in infants (sclera is distensible)
• Haab's striae: breaks in Descemet's membrane, horizontal or concentric, from distension
• Elevated IOP
• Deep, large cup

Treatment:

• Medical treatment is inadequate alone as a long-term measure
• Goniotomy (internal incision of angle, requires clear cornea) or Trabeculotomy (external approach): first-line surgical options
• Trabeculectomy + MMC: if above fail
• GDD: best for long-term IOP control if surgery fails

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8. SECONDARY GLAUCOMAS

8a. Pseudoexfoliation (PXF) Glaucoma

• Deposition of grey-white fibrillar material on anterior segment structures (lens surface, TM, zonules)
• Leads to TM blockage and reduced outflow
• Associated with zonular weakness → cataract surgery complications (phacodonesis)
• Most common identifiable cause of secondary OAG worldwide
• More aggressive than POAG; responds less well to medications

8b. Pigment Dispersion Syndrome / Pigmentary Glaucoma

• Reversed pupillary block: concave iris bows backwards, rubbing against zonular packets → pigment dispersed into AH → deposited on TM → obstructs outflow
• Classic triad: Krukenberg spindle (vertical fusiform pigment on corneal endothelium), Sampaolesi line (TM pigment band), Spoke-wheel iris TID (transillumination defects)
• Young, myopic males
• Exercise/dilation can precipitate acute IOP spikes
• Treatment: pilocarpine (re-deepens AC, moves iris forward), laser iridotomy for reverse pupillary block

8c. Neovascular Glaucoma (NVG)

• New vessels grow on iris (rubeosis iridis) and angle
• Fibrovascular membrane contracts → PAS → closed angle
• Causes: central retinal vein occlusion (most common), diabetic retinopathy, CRAO, carotid occlusive disease ("hypoxic ocular syndrome")
• Treatment: anti-VEGF injections, panretinal photocoagulation (PRP), + surgical IOP control

8d. Steroid-Induced Glaucoma

• Topical > systemic > inhaled > nasal steroids
• Mechanism: Steroids increase TM resistance by accumulation of extracellular material (fibronectin, proteoglycans) and inhibition of phagocytosis in TM
• Steroid responder: Defined as IOP rise of ≥6-10 mmHg with steroids
• POAG patients and their relatives are particularly susceptible
• Management: Discontinue steroid; use IOP-lowering drops; may need surgery

8e. Phacolytic Glaucoma

• Hypermature cataract releases lens proteins through intact capsule
• Macrophages engulf proteins → engorged cells block TM
• Open-angle mechanism; severe inflammation
• Treatment: Urgent cataract extraction

8f. Phacomorphic Glaucoma

• Swollen/intumescent cataract pushes iris-lens diaphragm forward → angle closure
• Angle-closure mechanism
• Treatment: medical IOP reduction followed by urgent cataract extraction; iridotomy may help temporarily

8g. Traumatic Glaucoma

• Angle recession (from blunt trauma): rupture of ciliary body face → RGC damage, TM fibrosis over years
• Hyphaema → blood blocks TM
• Ghost cell glaucoma: degenerated RBCs from old vitreous haemorrhage block TM
• Lens dislocation → pupillary block
• Long-term monitoring needed after blunt ocular trauma

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9. PHARMACOLOGY OF GLAUCOMA DRUGS (Detailed)

• Latanoprost + Timolol (Xalacom)
• Dorzolamide + Timolol (Cosopt)
• Brimonidine + Timolol (Combigan)
• Bimatoprost + Timolol (Ganfort)

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10. GLAUCOMA SURGERY

Trabeculectomy

• Creates a guarded fistula under a scleral flap allowing AH to drain into subconjunctival space (bleb)
• Antifibrotics: 5-fluorouracil (5-FU) or Mitomycin C (MMC) applied to bleb area to inhibit fibroblast proliferation and prevent bleb scarring
• Complications: Hypotony, bleb leak, blebitis/endophthalmitis, choroidal effusion/haemorrhage, cataract progression, failure

Glaucoma Drainage Devices (GDD)

• Ahmed (FP7/S2), Baerveldt, Molteno
• Tube in anterior chamber → plate sutured to episclera posteriorly
• Used for: failed trabeculectomy, neovascular glaucoma, post-vitreoretinal surgery

MIGS (Minimally Invasive Glaucoma Surgery)

• iStent/iStent inject: Titanium stent through TM into Schlemm's canal
• Hydrus Microstent: Scaffold within Schlemm's canal
• OMNI: Viscodilation + trabeculotomy
• XEN Gel Stent: Gelatin stent from AC to subconjunctival space
• Lower risk profile than trabeculectomy; best combined with phaco; moderate IOP reduction

Cyclodestructive Procedures

• Diode laser cyclophotocoagulation (CPC): Transscleral delivery; damages ciliary processes → ↓ AH production
• Reserved for refractory/end-stage/blind painful eyes
• Risks: Phthisis bulbi, hypotony, pain

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11. OCULAR HYPERTENSION (OHT)

• IOP consistently >21 mmHg with normal optic disc, normal visual fields, and open angles
• NOT the same as glaucoma; only ~9.5% convert to POAG over 5 years (OHTS study)
• Treatment reduces conversion to 4.4% (OHTS)
• Treat if: IOP ≥30 mmHg (>40% 5-year risk), or high-risk profile (thin CCT, large C/D ratio, older age, Black ethnicity)
• Monitoring acceptable for lower-risk individuals

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12. OPTIC NERVE HEAD IMAGING (OCT)

• RNFL thickness map (TSNIT: Temporal-Superior-Nasal-Inferior-Temporal pattern)
• Loss typically starts inferiorly and superiorly (corresponding to superior/inferior arcuate field defects)
• Ganglion Cell Layer (GCL) analysis: Macula GCL thinning mirrors RNFL loss
• Serial OCT critical for progression analysis
• OCT detects structural damage earlier than visual field loss (structural precedes functional)

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13. GLAUCOMA IN PHACOMATOSES

• Sturge-Weber syndrome: Glaucoma in ~30% ipsilateral to facial haemangioma; 60% develop before age 2 (buphthalmos). Mechanism: trabeculodysgenesis (early) + raised episcleral venous pressure from AV communication (late). Goniotomy/trabeculotomy for early-onset; GDD for others. High risk of choroidal effusion/haemorrhage during filtration surgery.
• Neurofibromatosis type 1: Rare; when present, usually unilateral and congenital. Association with plexiform neurofibroma of upper eyelid. Mechanisms: angle anomaly, ectropion uveae.

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14. QUICK REVISION TABLE: POAG vs PACG

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15. EXAM HIGH-YIELD POINTS

1. Normal IOP: 10-21 mmHg; Goldmann applanation is the gold standard tonometer
2. POAG is chronic and painless; asymptomatic until late - "sneak thief of sight"
3. Visual field defect starts peripherally in POAG (ring scotoma, then tunnel vision); in NTG, defects are closer to fixation
4. Prostaglandin analogues are first-line medical therapy for POAG
5. Acute angle closure is an emergency: mid-dilated fixed oval pupil + rocky hard eye + corneal oedema
6. Pilocarpine is contraindicated when IOP >40 mmHg in acute attack (ischaemic iris fails to respond)
7. Laser peripheral iridotomy is the definitive treatment for pupillary block angle closure
8. Congenital glaucoma triad: epiphora + photophobia/blepharospasm + corneal cloudiness; buphthalmos is pathognomonic
9. ISNT rule: Normal NRR is Inferior > Superior > Nasal > Temporal; violation = glaucoma
10. Neovascular glaucoma: Think ischaemic conditions - CRVO, PDR, carotid occlusion
11. Steroid-induced glaucoma: Any route of steroid administration; especially risky in POAG patients
12. Acetazolamide: Most common side effect is paraesthesias (tingling of hands/feet)
13. Timolol: Contraindicated in asthma (bronchospasm), heart block
14. SLT is repeatable (unlike ALT); can be used as primary therapy (LiGHT trial)
15. Trabeculectomy + MMC: Gold standard surgery; bleb complications are major concern
16. NTG diagnosis requires: IOP always ≤21 mmHg + glaucomatous damage + exclude other causes (pituitary tumour compressing optic chiasm, etc.)
17. C/D ratio >0.7 or asymmetry >0.2 warrants full glaucoma workup
18. Brimonidine is absolutely contraindicated in infants (<2 years) - causes CNS depression and apnoea
19. OCT shows structural damage before visual field loss - structural-functional correlation
20. EAGLE trial: Lens extraction superior to laser iridotomy as initial treatment for PAC/PACG

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