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Optic Nerve Head (ONH) Evaluation

1. Normal ONH Anatomy

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2. The ISNT Rule

Inferior > Superior > Nasal > Temporal

• Sensitivity for glaucoma: 81%, but low specificity (32%)
• Eyes without glaucoma often do not respect this rule
• A 2026 meta-analysis (PMID: 41212675) is the most recent evidence on ISNT rule diagnostic accuracy

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3. Cup/Disc (C/D) Ratio

• Vertical C/D ratio is preferred over horizontal
• Only 2% of the population has a C/D ratio >0.7
• Asymmetry ≥0.2 between eyes raises suspicion for glaucoma — but always exclude a genuine difference in disc size first
• Small discs → small cups (may be normal); Large discs → large cups (may also be normal)

💡 Tip: Any cupping in a small disc may be pathological; a large disc with a large cup may be entirely healthy.

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4. Optic Disc Size

• Measured by vertical diameter; normal median: 1.5–1.7 mm (white population)
• Large discs may be more susceptible to IOP-induced lamina cribrosa displacement (relevant in normal tension glaucoma, NTG)
• Disc size varies by racial group — largest in those of African descent
• Measured clinically using a slit beam + correction factor (Table 11.3 in Kanski)

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5. Glaucomatous Changes at the ONH

Structural signs of glaucomatous damage:

Classic glaucomatous subtypes (Fig. 11.9):

• Focal ischaemic — inferior notch
• Myopic — temporal crescent + inferior NRR loss
• Sclerotic — superior shelving, inferior notching
• Concentrically enlarged — deep, uniform cup enlargement

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6. Peripapillary Atrophy (PPA)

• Alpha zone (outer): Superficial RPE changes; larger/more common in glaucomatous eyes
• Beta zone (inner): Chorioretinal atrophy; larger, more common in glaucoma; risk factor for progression; its location predicts the orientation of visual field loss

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7. Retinal Nerve Fibre Layer (RNFL)

• Arcuate fibres (superotemporal and inferotemporal) are most vulnerable to glaucomatous damage
• Papillomacular bundle fibres are most resistant
• RNFL defects (wedge-shaped or diffuse) precede detectable disc and visual field changes
• Assessed using:
  • Red-free (green) light on slit lamp / fundus photography
  • OCT (optical coherence tomography)
  • Scanning laser polarimetry

⚠️ RNFL defects are not specific to glaucoma — they can occur in neurological disease and in apparently normal individuals.

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Key Images

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Recent Evidence Update

• PMID 41212675 (Eur J Ophthalmol, 2026): Systematic review/meta-analysis on ISNT rule — most current evidence on its diagnostic accuracy for glaucoma
• PMID 39392516 (Int Ophthalmol, 2024): Comprehensive review of ONH/RNFL imaging modalities in high myopia with glaucoma

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Trabeculectomy

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Indications

1. Failure of conservative (medical) therapy to achieve adequate IOP control
2. Progressive deterioration despite seemingly adequate IOP control (including poor adherence)
3. Primary therapy in advanced disease requiring very low target pressure — early surgery may give superior long-term outcomes, particularly in younger patients
4. Patient preference — desire to be free of chronic medication

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Surgical Technique (Classical Procedure)

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Ex-Press Mini-Shunt

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Antimetabolites in Filtration Surgery

Risk Factors for Surgical Failure:

• Previous failed trabeculectomy or MIGS
• Previous conjunctival or cataract surgery
• Secondary glaucoma (inflammatory, neovascular, post-traumatic)
• Black race, age <65 years
• Topical medication >3 years (especially sympathomimetics)

5-Fluorouracil (5-FU)

• Inhibits fibroblast proliferation by retarding DNA synthesis
• Intraoperative: sponge soaked in 50 mg/ml applied under Tenon flap for 5 minutes
• Postoperative: subconjunctival injection of 25–50 mg/ml solution
• Complications: persistent corneal epithelial defects, bleb leakage

Mitomycin C (MMC)

• Alkylating agent — more potent than 5-FU
• Typical: 0.2 mg/ml for 2 minutes intraoperatively; up to 0.4 mg/ml for high-risk patients
• Sponges placed away from the limbus to improve bleb profile
• Risk: cystic thin-walled bleb → chronic hypotony, late bleb leak, endophthalmitis

Bevacizumab (anti-VEGF)

• More effective than placebo, but increases risk of bleb encapsulation
• Not superior to MMC alone; combining with MMC shows no benefit

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Complications

1. Shallow Anterior Chamber

2. Failure of Filtration

• Flat, avascular bleb
• Vascularized bleb — episcleral fibrosis
• Encapsulated bleb (Tenon cyst) — localized, dome-shaped, fluid-filled, engorged vessels

• Extrascleral: Subconjunctival/episcleral fibrosis; bleb encapsulation
• Scleral: Over-tight flap suturing; scleral bed scarring
• Intraocular: Sclerostomy blockage (vitreous, blood, uveal tissue, membranes)

3. Bleb-Associated Infection

• Conjunctival swab (do NOT aspirate from within bleb)
• Topical broad-spectrum antibiotics hourly (e.g. ofloxacin + cephalosporin)
• Oral co-amoxiclav 500/125 mg TDS + ciprofloxacin 750 mg BD for ≥5 days (or azithromycin 500 mg/day)
• Steroids only after definite antibiotic response

4. Late Bleb Leakage

• Positive Seidel test confirms aqueous leak through bleb
• Risks: thin-walled or MMC blebs
• Management: pressure dressing, bandage contact lens, surgical revision, or bleb needling with 5-FU

5. Bleb Dysaesthesia

• Discomfort from a large or anteriorly placed bleb contacting the lid
• Reduced by placing incisions at 12 o'clock

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Recent Evidence

• PMID 39394492 (Graefe's, 2025): Meta-analysis — PreserFlo MicroShunt vs. trabeculectomy: comparable IOP reduction with a different complication profile
• PMID 39670502 (Dtsch Arztebl Int, 2025): MIGS vs. trabeculectomy — trabeculectomy remains the gold standard for advanced glaucoma

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Technique of Trabeculectomy

Numerous modifications are in use. The classical procedure is described below.

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Principle

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Step-by-Step Surgical Technique

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Step 1 — Preoperative Preparation

• Pupil constriction: Pilocarpine 2% instilled preoperatively
  • Deepens anterior chamber, protects the lens, and tents the iris away from the sclerostomy

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Step 2 — Bridle Suture

• Inserted at superior cornea or superior rectus muscle
• Rotates the eye downward to expose the superior limbus

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Step 3 — Conjunctival Flap

• Both include the conjunctiva + Tenon capsule
• Fashioned superiorly at 12 o'clock (reduces risk of bleb dysaesthesia compared to off-centre incisions)

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Step 4 — Episcleral Preparation

• Episcleral tissue cleared
• Major vessels cauterized to minimize intraoperative bleeding

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Step 5 — Lamellar Scleral Flap (Trapdoor)

• Incisions made through ~50% of scleral thickness
• Creates a trapdoor/lamellar flap — shapes available:
  • Rectangular 3 × 3–4 mm (most common)
  • Trapezoidal
  • Triangular
• Flap dissected anteriorly until clear cornea is reached

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Step 6 — Paracentesis

• Made in temporal peripheral clear cornea
• Allows AC reformation and IOP testing at any point during surgery
• Also used postoperatively for laser suture lysis or AC reformation if needed

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Step 7 — Anterior Chamber Entry & Sclerectomy

• AC entered along most of the width of the trapdoor base
• Block of deep sclera excised — typically using a Kelly punch (creates the internal sclerostomy/fistula)

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Step 8 — Peripheral Iridectomy

• Created to prevent iris prolapse into / blockage of the internal sclerostomy
• Some surgeons omit this step in pseudophakic eyes — but a small risk of iris prolapse remains if omitted
• Performed with Vannas scissors and fine forceps

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Step 9 — Scleral Flap Suturing

• Posterior corners sutured first
• Suturing strategy determines the key postoperative IOP balance:

Releasable and lysable sutures are the modern preferred approach — they allow tight intraoperative closure (safe early phase) with controlled flow titration in the postoperative period.

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Step 10 — Fistula Patency Test

• BSS injected through the paracentesis to deepen the AC and confirm the fistula is patent
• IOP is assessed and bleb formation observed

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Step 11 — Conjunctival Closure

• Conjunctiva/Tenon capsule flap sutured (10-0 nylon or absorbable suture)
• Paracentesis irrigation repeated to produce a bleb
• Bleb inspected for leakage (Seidel test if needed)

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Step 12 — Postoperative Medications

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Variant: Ex-Press Mini-Shunt

• Scleral flap created identically to standard technique
• No Kelly punch sclerectomy — instead, a needle is used to enter the AC
• No peripheral iridectomy required
• Lower rates of hypotony and hyphaema compared to standard trabeculectomy
• IOP control is equivalent to standard trabeculectomy
• Not suitable for primary angle-closure glaucoma without concurrent/prior cataract surgery

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Summary of Key Technical Decisions

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Formation of Aqueous Humour

Site of Production

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Mechanisms of Formation

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1. Ultrafiltration (Passive)

• Blood within the fenestrated capillaries of the ciliary processes exerts hydrostatic pressure
• A high-protein filtrate is driven by this pressure gradient out of the capillaries into the stroma of the ciliary processes
• This is a passive, pressure-dependent process — it does not require energy

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2. Active Secretion (Primary mechanism)

• From the ciliary stromal filtrate, active transport of solutes (ions) occurs across the dual-layered ciliary epithelium:
  • Outer pigmented epithelium (PE) — faces the stroma
  • Inner non-pigmented epithelium (NPE) — faces the posterior chamber
• Key transporters involved:
  • Na⁺/K⁺-ATPase — pumps sodium into the posterior chamber, driving osmotic water flow
  • Carbonic anhydrase — generates bicarbonate ions, contributing to the osmotic gradient
  • Aquaporins — water channels facilitating passive water movement

This is the predominant mechanism of aqueous formation and the target of most IOP-lowering drugs.

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3. Diffusion (Passive)

• The osmotic gradient established by active ion transport facilitates passive flow of water into the posterior chamber
• Some additional plasma components diffuse across the epithelium along concentration gradients

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Summary of Mechanisms

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Neural Regulation

This is the pharmacological basis for:

• Beta-blockers (e.g. timolol) — block β₂ receptors → reduce production
• Alpha-2 agonists (e.g. brimonidine) — stimulate α₂ receptors → reduce production
• Carbonic anhydrase inhibitors (e.g. dorzolamide, acetazolamide) — inhibit enzyme → reduce active secretion

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Diurnal Variation

• Aqueous production follows a diurnal pattern — it is lower at night
• This contributes to normal diurnal IOP fluctuation (IOP tends to be higher in the morning)

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Flow of Aqueous After Formation

1. Posterior chamber (formed here by ciliary processes)
2. → Through the pupil
3. → Anterior chamber
4. → Exits via:

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IOP Homeostasis

IOP is determined by the rate of aqueous production versus the resistance to outflow at the trabecular meshwork and episcleral venous pressure.

• Normal upper limit: 21 mmHg (applanation tonometry)
• Production rate: ~2–3 µL/min

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Clinical Relevance

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Minimally Invasive Glaucoma Surgery (MIGS)

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Indications

• Mild to moderate glaucoma with slow visual field loss and modest target IOP (aiming for 15–17 mmHg)
• Combined with phacoemulsification + IOL to reduce dependence on topical medications
• Not suitable for advanced glaucoma requiring very low target pressures

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Classification by Mechanism

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Group 1 — Schlemm Canal Surgery (No Bleb)

A. Trabecular Excision (Ab Interno)

B. Trabecular Bypass Stents

C. Canaloplasty

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Group 2 — Subconjunctival Drainage (Bleb-Forming)

• Mitomycin C 0.02% (0.1 ml) is usually injected subconjunctivally adjacent to the implant to reduce bleb fibrosis
• Bleb needling is often required postoperatively
• Shares complications with trabeculectomy: overfiltration, bleb-related infection, encapsulation
• Additional risk of stent malposition and erosion

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Group 3 — Supraciliary/Uveoscleral Drainage (No Bleb)

• No bleb formed
• No antimetabolite required
• Small risk of late corneal endothelial cell loss

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Also Related: Non-Penetrating Glaucoma Surgery

• AC is never entered → avoids hypotony and its sequelae
• IOP reduction generally less than trabeculectomy
• Main indication: POAG (primary open-angle glaucoma)
• Preferred when advanced disease makes hypotony-related visual loss a concern

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Complications Summary

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Results

⚠️ Results of MIGS combined with cataract surgery are biased — phacoemulsification itself independently reduces IOP by ~15%.

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Recent Evidence

• PMID 38853535 (Clin Exp Ophthalmol, 2024): Systematic review/meta-analysis — angle-based MIGS in normal tension glaucoma shows meaningful IOP reduction
• PMID 40439165 (Turk J Ophthalmol, 2025): Review of ab interno goniotomy/goniectomy techniques
• PMID 39670502 (Dtsch Arztebl Int, 2025): Meta-analysis confirms trabeculectomy remains gold standard for advanced glaucoma; MIGS has better safety profile for mild-moderate disease

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