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Glaucoma - MBBS Ophthalmology Notes

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1. Definition

• Characteristic morphological changes at the optic nerve head (ONH) and retinal nerve fibre layer (RNFL)
• Progressive retinal ganglion cell death
• Visual field loss
• Intraocular pressure (IOP) is the key modifiable risk factor

Goal of treatment: Slow disease progression to maintain visual function and quality of life throughout the patient's lifetime.

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2. Normal IOP

• Normal range: 10-21 mmHg (statistically defined)
• Measured by Goldmann applanation tonometry (gold standard)
• Ocular hypertension (OHT): IOP >21 mmHg without glaucomatous damage
• Normal-tension glaucoma (NTG): Glaucomatous damage despite IOP ≤21 mmHg

Note: Corneal thickness (CCT) affects IOP readings - thick corneas give falsely high readings, thin corneas give falsely low readings.

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3. Classification

Glaucoma
├── Primary
│   ├── Primary Open-Angle Glaucoma (POAG) ← most common
│   ├── Normal-Tension Glaucoma (NTG)
│   ├── Primary Angle-Closure Glaucoma (PACG)
│   └── Primary Congenital/Developmental Glaucoma
└── Secondary
    ├── Pseudoexfoliation glaucoma (commonest secondary OAG)
    ├── Pigmentary glaucoma
    ├── Neovascular glaucoma
    ├── Inflammatory (uveitic) glaucoma
    ├── Traumatic glaucoma
    ├── Phacolytic / Phacomorphic glaucoma
    └── Steroid-induced glaucoma

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4. Aqueous Humour Dynamics (Pathophysiology)

• Aqueous is produced by the ciliary body (epithelium) via active secretion and ultrafiltration
• Drains via two routes:
  • Conventional (trabecular): Trabecular meshwork → Canal of Schlemm → episcleral veins (~80-90%)
  • Uveoscleral: Across ciliary muscle into supraciliary/suprachoroidal space (~10-20%)
• Most drugs work by reducing production or increasing outflow
• In open-angle glaucoma: trabecular meshwork resistance is increased
• In angle-closure glaucoma: the peripheral iris physically blocks the trabecular meshwork

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5. PRIMARY OPEN-ANGLE GLAUCOMA (POAG)

Definition

• Open anterior chamber angle on gonioscopy
• RNFL thinning and glaucomatous disc changes
• Characteristic visual field loss
• No signs of secondary glaucoma

Epidemiology

• Most common form in White and African populations
• Prevalence: ~6% in White people >70 years; ~16% in Black people >70 years
• Affects both genders equally
• 2nd leading cause of blindness worldwide (up to 50% undiagnosed)

Risk Factors

Genetics

• MYOC gene mutation (myocilin, found in trabecular meshwork)
• OPTN gene mutation (optineurin) - also in NTG

• 127 associated loci in the human genome (Nature Communications, 2021)

Clinical Features

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6. Optic Disc Changes in Glaucoma

Key Terms

• Cup-to-disc (C:D) ratio: Normal <0.5; >0.7 is suspicious; asymmetry >0.2 is significant
• Neuroretinal rim (NRR): The neural tissue between disc edge and cup edge. Follows ISNT rule normally (Inferior > Superior > Nasal > Temporal)
• Pathological cupping: Irreversible decrease in nerve fibres, glia, and blood vessels

Signs of Glaucomatous Disc Damage

1. Increased C:D ratio / enlarging cup (always significant if documented)
2. NRR thinning or notching - especially inferotemporal and superotemporal
3. Disc haemorrhages - small, flame-shaped, most common inferotemporal; marker of progression (more common in NTG)
4. Bayonetting of vessels - vessels appear to disappear at cup edge then reappear
5. Baring of circumlinear vessels
6. Nasal shift of vessels
7. RNFL defects - visible as dark wedge-shaped streaks on red-free photography

Morphological Patterns of Glaucomatous Damage

• Focal ischaemic discs: Localized notching superiorly/inferiorly; early threat to fixation
• Myopic disc with glaucoma: Tilted disc, temporal crescent; common in young males
• Sclerotic discs: Shallow saucerized cup; older patients; associated with vascular disease
• Concentrically enlarging discs: Uniform NRR thinning; very high IOP at presentation

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7. Visual Field Defects in Glaucoma

Progression of Field Loss (in order)

1. Increased variability - earliest, before visible scotomas
2. Paracentral scotomas - small depressions, often superonasal; more common in NTG
3. Nasal step - difference in sensitivity above/below horizontal midline in nasal field (bounded by horizontal raphe)
4. Temporal wedge - less common
5. Arcuate (Bjerrum) scotoma - coalescence of paracentral scotomas, arcing from blind spot around fixation (10-20° from fixation)
6. Ring scotoma - superior + inferior arcuate scotomas joining
7. End-stage: Small central island + temporal island; central vision last to go

Staging (Mean Deviation on SAP)

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

Investigations

• Standard Automated Perimetry (SAP): Humphrey field analyser; 24-2 pattern routinely used for glaucoma
• Frequency Doubling Technology (FDT): Detects early defects
• Gonioscopy: Assesses angle (essential for classification)
• OCT (Optical Coherence Tomography): Measures RNFL thickness and disc parameters - detects changes before visual field loss
• CCT (Central Corneal Thickness): Affects IOP measurement interpretation

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8. PRIMARY ANGLE-CLOSURE GLAUCOMA (PACG)

Epidemiology

• Responsible for up to 50% of glaucoma globally
• Particularly common in Asian populations (Far Eastern, Indian)
• Progresses rapidly; more likely to cause visual loss than POAG

Risk Factors

Mechanisms of Angle Closure

• Failure of aqueous flow through pupil → pressure differential between anterior and posterior chambers → anterior bowing of iris → closes angle
• Treated by peripheral iridotomy (equalizes chamber pressures)

• Plateau iris syndrome
• Thick peripheral iris roll
• Lens-related (phacomorphic)
• Ciliary body/choroidal effusion (e.g., topiramate)

Classification of Angle Closure

• Primary angle closure suspect (PACS): ITC in ≥180°, no peripheral anterior synechiae (PAS), no optic nerve damage
• Primary angle closure (PAC): ITC in ≥180° + PAS or elevated IOP, no optic nerve damage
• Primary angle closure glaucoma (PACG): PAC + glaucomatous optic neuropathy

Gonioscopy - Shaffer Grading

ACUTE PRIMARY ANGLE CLOSURE (APAC) - Emergency!

Precipitating Factors

• Darkened room (mydriasis)
• Pharmacological mydriasis (antimuscarinics, adrenergic agonists)
• Emotional stress
• Drugs: topiramate, anticholinergics in inhalers/cold remedies

Symptoms

• Severe unilateral painful red eye
• Blurring of vision ("smoke-filled room" appearance)
• Halos around lights (due to corneal epithelial oedema)
• Headache, nausea, vomiting, abdominal pain (can mimic acute abdomen!)

Signs

• VA: usually 6/60 to hand movements
• IOP: very high, 50-80 mmHg
• Circumcorneal (ciliary) injection - violaceous
• Corneal epithelial oedema (hazy cornea)
• Shallow anterior chamber
• Aqueous flare
• Mid-dilated, vertically oval, non-reactive pupil (classic sign)
• Fellow eye shows occludable angle

Late Signs (Resolved APAC)

• Glaukomflecken: White foci of lens opacity (anterior subcapsular) due to ischaemic necrosis - pathognomonic of previous acute attack
• Iris atrophy with spiral configuration
• Irregular pupil (synechiae)
• Optic atrophy (combined pallor + cupping)

Emergency Management

• Acetazolamide 500 mg IV (if IOP >50 mmHg) or orally if <50 mmHg
  • CI: sulfonamide allergy, topiramate-induced attack
• Timolol 0.5% topically (reduces aqueous production)
• Apraclonidine 0.5%/1% topically (reduces aqueous, increases outflow)
• Pilocarpine 2% 1 drop to affected eye, repeat after 30 min; then 1% to fellow eye
  • Do NOT repeat if IOP remains >40 mmHg (ischaemia impairs iris sphincter; risk of anterior shift)
• Prednisolone 1% / Dexamethasone 0.1% topically (reduce inflammation)
• Wait 3-5 min between each topical drop
• Analgesia + antiemetic as needed

• IV Mannitol 20%, 1-2 g/kg over 1 hour (osmotic agent)
• OR Oral glycerol 50% / isosorbide 1-1.5 g/kg
• Central corneal indentation to force aqueous into angle

• Nd:YAG laser peripheral iridotomy (LPI) - treatment of choice once cornea clears
• Both eyes treated (fellow eye prophylactically)
• If LPI fails or not possible: surgical peripheral iridectomy, lens extraction, trabeculectomy

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9. NORMAL-TENSION GLAUCOMA (NTG)

• IOP consistently ≤21 mmHg on diurnal testing
• Glaucomatous optic nerve damage + visual field loss
• Open angle on gonioscopy
• No secondary cause

Key Differences from POAG

Pathogenesis

• Vascular insufficiency to the optic nerve head (local or systemic)
• Structural optic nerve vulnerability (low lamina cribrosa stiffness)
• Autoimmune factors
• Low CCT giving falsely low IOP readings
• Nocturnal IOP spikes
• Nocturnal hypotension (BP dip >20%)

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10. SECONDARY GLAUCOMAS

Pseudoexfoliation Glaucoma (PXG) - Commonest Secondary OAG

• Pseudoexfoliative material (grey-white fibrillary substance) deposited on lens capsule, zonules, iris, trabeculum
• LOXL1 gene mutation on chromosome 15
• Incidence of glaucoma at PXS diagnosis: 15-30%; cumulative risk of requiring treatment: ~60% at 5 years
• Progresses more rapidly than POAG; more likely to cause significant visual loss
• Signs: "Bull's-eye" pattern on anterior lens capsule, pigment on zonules, heavy trabecular pigmentation
• Associated with zonular weakness (risk of lens subluxation during cataract surgery)

Pigmentary Glaucoma (PG)

• Pigment liberated from iris pigment epithelium → deposited in trabecular meshwork → obstruction
• Mechanism: Posterior bowing of iris → iridozonular contact → pigment shedding (reverse pupillary block)
• Typically: Young, myopic White males
• Signs:
  • Krukenberg spindle: Vertical pigment deposit on corneal endothelium
  • Radial spoke-like iris transillumination defects (midperipheral)
  • Deep anterior chamber
  • Heavy trabecular meshwork pigmentation (all 4 quadrants)
• IOP may spike after exercise
• Treatment: similar to POAG; laser trabeculoplasty often effective; laser iridotomy flattens iris concavity

Neovascular Glaucoma (NVG)

• New blood vessels (rubeosis iridis) on iris/angle → fibrovascular membrane → angle closure
• Causes: Proliferative diabetic retinopathy, central retinal vein occlusion, ocular ischaemic syndrome
• Treat underlying cause first (panretinal photocoagulation, anti-VEGF)
• Medical treatment usually inadequate; glaucoma drainage devices often required

Steroid-Induced Glaucoma

• Topical > periocular > systemic steroids
• Mechanism: Increased trabecular meshwork resistance
• Steroid responders: IOP rises 10+ mmHg; ~5% of general population
• Occurs 2-6 weeks after starting steroids; reversible on stopping
• Risk: pre-existing POAG, family history, young age, high myopia, diabetes

Phacolytic Glaucoma

• Hypermature cataract leaks lens proteins → obstruct trabecular meshwork
• Presents with acute pain, red eye, high IOP
• Treatment: urgent cataract extraction

Phacomorphic Glaucoma

• Intumescent (swelling) lens pushes iris forward → angle closure
• Treatment: lens extraction

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11. CONGENITAL/DEVELOPMENTAL GLAUCOMA

Primary Congenital Glaucoma (PCG)

• Autosomal recessive; mutations in CYP1B1 gene
• Trabeculodysgenesis (maldevelopment of trabecular meshwork)
• Presents in first 3 years of life

Classic Triad

1. Epiphora (excessive tearing)
2. Photophobia
3. Blepharospasm

Signs

• Buphthalmos ("ox eye"): Enlarged globe due to raised IOP stretching the infant's elastic sclera
• Haab's striae: Horizontal breaks in Descemet membrane (horizontal corneal striae)
• Corneal clouding/oedema
• Increased corneal diameter (>11 mm in newborn, >12 mm in first year = suspicious)
• Increased C:D ratio
• High IOP

Treatment

• Goniotomy: Incision of trabecular meshwork under direct vision (if cornea clear)
• Trabeculotomy: External approach to Schlemm's canal
• Combined trabeculotomy-trabeculectomy
• Glaucoma drainage devices for refractory cases

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12. MEDICAL TREATMENT OF GLAUCOMA

Drug Classes

Principles of Medical Management

1. Start with a single drug (usually prostaglandin analogue or beta-blocker)
2. Review in 4-8 weeks; assess target IOP achieved
3. If inadequate response: switch drug or add a second agent
4. If two drugs used: wait 5 min between instillation to prevent washout
5. Target IOP: Start at <18 mmHg (based on AGIS study); individualise
6. If progression despite target IOP: lower target, consider surgery

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13. LASER TREATMENT

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14. SURGICAL TREATMENT

Trabeculectomy (Filtering Surgery)

• Gold standard surgical procedure for glaucoma
• Creates a guarded fistula between the anterior chamber and subconjunctival space (bleb)
• Adjunctive antimetabolites: Mitomycin-C (MMC) or 5-Fluorouracil (5-FU) to prevent scarring
• Complications: Bleb failure (scarring), hypotony, infection (blebitis, endophthalmitis), cataract

Glaucoma Drainage Devices (Tubes)

• Baerveldt, Ahmed, Molteno implants
• Used when trabeculectomy has failed or is high-risk (e.g., neovascular glaucoma, uveitic glaucoma, aniridia)

Minimally Invasive Glaucoma Surgery (MIGS)

• iStent, Kahook blade goniotomy, Trabectome
• Lower risk than trabeculectomy; used in mild-moderate glaucoma (often combined with cataract surgery)
• Lower IOP reduction compared to trabeculectomy

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15. QUICK REVISION: Key Mnemonics & Differentiators

POAG vs PACG

Classic Exam Points

• Glaukomflecken = pathognomonic of previous acute angle closure
• Haab's striae = pathognomonic of congenital glaucoma
• Krukenberg spindle = pigmentary glaucoma
• "Bull's-eye" anterior lens capsule = pseudoexfoliation
• ISNT rule normally (NRR: Inferior > Superior > Nasal > Temporal)
• Cupping >0.7 or asymmetry >0.2 = suspicious
• Second leading cause of blindness worldwide; first is cataract
• Normal IOP: 10-21 mmHg; measured by Goldmann applanation
• Acetazolamide is CI in sulfonamide allergy and topiramate-induced APAC
• Pilocarpine NOT effective when IOP >40 mmHg (sphincter ischaemia)
• NTG is associated with migraine, Raynaud's, nocturnal hypotension, more common in Japanese
• Prostaglandins = 1st line; once daily dosing; given at night
• Primary congenital glaucoma: autosomal recessive, CYP1B1 mutation, treatment = surgery (goniotomy/trabeculotomy)

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