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OP7.4 | Secondary Glaucoma: Cause Framework — SDL Guide

Learning Objectives

• Classify secondary glaucoma by mechanism: open-angle (pre-trabecular, trabecular, post-trabecular) and closed-angle (with/without pupil block)
• Identify the major named secondary glaucomas and their underlying causes
• Distinguish phacomorphic (closed-angle) from phacolytic (open-angle) glaucoma by mechanism and gonioscopy
• Recognise the clinical clues pointing to specific secondary glaucoma causes (Krukenberg spindle, PXF material, rubeosis iridis, angle recession)
• Describe the two-pronged management approach: IOP reduction plus treatment of the underlying cause
• State why steroid-induced glaucoma is clinically important and how it is managed

INSTRUCTIONS

Secondary glaucoma is a heterogeneous group of conditions unified by a single theme: intraocular pressure is elevated because an identifiable underlying disease or factor is physically obstructing aqueous outflow. The skill in secondary glaucoma is detective work — finding the cause from the history, slit-lamp signs, and gonioscopy. This module uses a mechanistic framework (the HOW: open-angle vs closed-angle, and WHERE within each) as the intellectual scaffold, then maps the major named glaucomas onto it. This approach is more durable than rote memorisation of a list, because once you understand the mechanism, the clinical presentation and treatment follow logically.

References

• AK Khurana — Comprehensive Ophthalmology, 7th edition, Chapter: Glaucoma (textbook)
• Parsons' Diseases of the Eye, 23rd edition, Chapter: Glaucoma (textbook)

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Version 2.0 | NMC CBUC 2024

Secondary Glaucoma: Clinical Clues and the Why

The clinical hallmark of any secondary glaucoma is that the elevated IOP has an identifiable underlying cause — it is not a primary failure of the drainage system but a consequence of another ocular or systemic disease, or a drug, or a physical event. This is both the defining feature and the clinical opportunity: identify the cause, and you may be able to treat it at source rather than merely controlling the IOP symptomatically. In primary glaucomas (POAG, PACG), no reversible underlying cause exists and treatment is lifelong IOP reduction. In secondary glaucomas, by contrast, removing the cause may resolve the glaucoma entirely: stopping the offending steroid can normalise IOP within weeks in steroid-induced glaucoma; extracting the swollen lens in phacomorphic glaucoma opens the angle immediately; administering anti-VEGF in neovascular glaucoma causes rubeosis to regress within days. This therapeutic reversibility makes secondary glaucoma both diagnostically important and clinically rewarding — but only if the clinician has the pattern-recognition skills to identify the underlying cause at the first encounter rather than treating elevated IOP blindly.

The clinical approach to secondary glaucoma always starts with history and context:
- Medical history: diabetes (neovascular glaucoma), inflammatory conditions (uveitic glaucoma), steroid use (steroid-induced), trauma (angle recession)
- Drug history: any topical, periocular, or systemic steroid; mydriatics; certain antihypertensives
- Ocular history: previous uveitis, previous retinal vein occlusion, previous vitreous haemorrhage, previous ocular surgery
- Family history: less prominent than in primary glaucomas, but some secondary types have genetic predispositions (pseudoexfoliation has genetic associations with LOXL1 gene)

The secondary glaucoma patient almost always has additional ocular signs that point to the underlying cause — signs that are absent in primary glaucoma. The slit-lamp and gonioscopy are your diagnostic tools: they will reveal the Krukenberg spindle of pigmentary glaucoma, the white PXF material on the anterior lens capsule and pupil margin in pseudoexfoliation, the new blood vessels on the iris (rubeosis iridis) in neovascular glaucoma, the angle recession of traumatic glaucoma, or the hypermature swollen lens of lens-induced glaucoma. This pattern-recognition approach — 'what does the slit-lamp show me that is NOT present in a normal eye?' — is the key clinical skill.

Presentation modes vary:
- Acute: sudden very high IOP, pain, red eye (phacomorphic, neovascular, uveitic)
- Subacute/chronic: gradually rising IOP without acute symptoms (steroid-induced, pseudoexfoliation, pigmentary, angle recession — the same silent presentation as POAG)
- Discovered incidentally: elevated IOP noted on routine check-up (steroid-induced especially)

Pathophysiological Framework: How the IOP Rises

Rather than memorising a list of secondary glaucomas, understanding them through a mechanistic scaffold is more efficient and more durable. The framework has two branches — OPEN-ANGLE and CLOSED-ANGLE — each with sub-levels indicating WHERE in the outflow pathway the obstruction occurs. This scaffold works because the anatomy of aqueous drainage is fixed: fluid must pass through the trabecular meshwork, then Schlemm's canal, then the episcleral venous system. Any secondary glaucoma impairs drainage at one of these anatomical stations, and the gonioscopic appearance (open or closed angle) immediately narrows which branch applies. An open angle on gonioscopy means aqueous can reach the trabecular meshwork but cannot pass through it or beyond it — the obstruction is at or downstream of the meshwork. A closed angle means the peripheral iris has physically occluded the trabecular meshwork before aqueous can even reach it — the obstruction is at the entrance to the drainage system. This single gonioscopic finding — open vs closed — is therefore not merely descriptive; it is the first and most powerful branch point in determining both mechanism and treatment in any case of secondary glaucoma.

BRANCH A: OPEN-ANGLE SECONDARY GLAUCOMAS
The iridocorneal angle is open on gonioscopy, but the aqueous cannot drain normally because of an obstruction at or downstream of the trabecular meshwork.

A1. Pre-trabecular (a membrane or tissue covers the trabecular meshwork):
- Neovascular glaucoma (early): a fibrovascular membrane (driven by VEGF from ischaemic retina) grows over the trabecular meshwork, physically covering the drainage surface. As the membrane contracts, the angle closes (becomes closed-angle NVG — see Branch B).
- Epithelial ingrowth: epithelium grows into the anterior chamber post-surgery, covering the angle.

A2. Trabecular (obstruction within the trabecular meshwork itself):
- Pseudoexfoliation glaucoma: fibrillar extracellular material (PXF material) deposits within the trabecular beams, clogging outflow. This is the COMMONEST secondary open-angle glaucoma worldwide.
- Pigmentary glaucoma: pigment granules (from the iris pigment epithelium, mechanically rubbed off by the iris against the zonules in a concave iris configuration) deposit in the trabecular beams, obstructing them. The Krukenberg spindle (vertical pigment stripe on the corneal endothelium) is the pathognomonic slit-lamp sign.
- Phacolytic glaucoma: liquefied lens protein from a hypermature cataract leaks through the intact lens capsule; macrophages (attempting to clear the protein) and the protein itself clog the trabecular meshwork.
- Ghost cell glaucoma: degenerated, rigid, khaki-coloured red blood cells (ghost cells) from a vitreous haemorrhage enter the anterior chamber and clog the trabecular meshwork.
- Steroid-induced glaucoma: steroids reduce the phagocytic activity of trabecular endothelial cells, allowing extracellular matrix accumulation and increasing outflow resistance.
- Angle-recession glaucoma: traumatic tear in the ciliary body face (between the longitudinal and circular muscle bundles) — the angle appears widened and irregular on gonioscopy; the injured TM develops progressive fibrosis and outflow failure years later.
- Uveitic glaucoma (open-angle component): trabeculitis (direct inflammation of the trabecular meshwork) or steroid therapy given for the uveitis raises IOP.

A3. Post-trabecular (increased episcleral venous pressure backs up outflow):
- Sturge-Weber syndrome: episcleral haemangioma raises episcleral venous pressure → increased outflow resistance → elevated IOP. Associated with facial port-wine naevus (V1/V2 distribution) and choroidal haemangioma.
- Carotid-cavernous sinus fistula: arterialised blood in cavernous sinus raises episcleral venous pressure.

BRANCH B: CLOSED-ANGLE SECONDARY GLAUCOMAS
The peripheral iris is in contact with the trabecular meshwork, obstructing outflow by physical apposition.

B1. With pupil block (aqueous trapped in posterior chamber → iris bombe → angle closure):
- Uveitic glaucoma (closed-angle): posterior synechiae (adhesions between iris and anterior lens capsule) form in anterior uveitis → pupil margin becomes adherent to the lens → seclusio pupillae (360-degree posterior synechiae) → complete pupil block → iris bombe → closed-angle glaucoma.
- Subluxation of lens: if the lens subluxes forward, it may occlude the pupil → pupil block.

B2. Without pupil block (iris pushed or pulled into angle without pupil block):
- Phacomorphic glaucoma: a swollen, intumescent mature cataract physically pushes the iris-lens diaphragm anteriorly, mechanically closing the angle. The angle is closed but there is no pupil block — confirmed by the lens occupying most of the posterior chamber. Treatment: phacoemulsification (lens removal).
- Neovascular glaucoma (late/contracted): the fibrovascular membrane that initially covered the angle (pre-trabecular, open-angle) contracts, dragging the peripheral iris over the trabecular meshwork and closing the angle.
- Malignant glaucoma (aqueous misdirection): aqueous secreted into the vitreous rather than the anterior chamber; lens and iris pushed forward; can occur after intraocular surgery. A notoriously difficult management problem.

Classification of Secondary Glaucoma by Outflow Obstruction Mechanism

Key Investigations for Secondary Glaucoma

The investigation of secondary glaucoma is guided by the principle that the slit-lamp and gonioscopy will usually reveal the underlying cause if examined systematically. The standard glaucoma work-up (tonometry, optic disc assessment, perimetry, OCT) applies to all cases; the cause-specific investigations are layered on top. The key insight is that secondary glaucoma patients almost always have additional anterior segment signs that are absent in primary glaucoma — signs that point directly to the underlying aetiology. The examining clinician's task is therefore not simply to measure IOP and assess the optic nerve (as in POAG), but to read the entire anterior segment as a diagnostic text: the corneal endothelium, the anterior chamber depth and clarity, the iris surface and pupil margin, the anterior lens capsule, and the angle on gonioscopy each carry specific diagnostic information. Missing these signs — focusing only on IOP and the disc — leads to the dangerous error of treating secondary glaucoma as if it were POAG, missing the reversible underlying cause, and committing the patient to lifelong IOP therapy when the correct intervention is entirely different.

Slit-lamp examination — look for cause-specific signs:
- Corneal endothelium (Koeppe illumination): vertical brown pigment stripe = Krukenberg spindle (pigmentary glaucoma); keratic precipitates (KPs) = uveitis; sclerotic scatter of cornea
- Anterior chamber: cells and flare (uveitis); white fluffy material (phacolytic — macrophages visible); pseudopodial anterior chamber depth (very shallow = phacomorphic)
- Iris: rubeosis iridis (fine blood vessels on iris surface, especially at the pupil margin = neovascular glaucoma); ectropion uvea (late NVG from membrane traction); heterochromia; posterior synechiae; PXF material at pupil margin
- Lens: white fluffy flocculent material on anterior lens capsule = PXF material (pseudoexfoliation); nuclear sclerosis + white flocculent material leaking = phacolytic; swollen, intumescent lens = phacomorphic; anteriorly subluxed lens = pupil block
- Vitreous: khaki/hazel-coloured cells in anterior vitreous or anterior chamber = ghost cells (vitreous haemorrhage history)

Gonioscopy — the MOST IMPORTANT investigation:
- Open angle: POAG or open-angle secondary — then look for specific angle signs:
- Dense trabecular meshwork pigmentation: pigmentary glaucoma (heavy band) or PXF (irregular deposits)
- Angle recession (widening, grey/white ciliary body band): traumatic glaucoma
- New vessels in angle (first at Schwalbe's line/iris root): neovascular glaucoma
- PXF material on trabecular surface
- Closed angle with PAS: chronic angle closure, NVG (contracted), uveitic glaucoma
- Closed angle with lens contact: phacomorphic

Additional targeted investigations:
- B-scan ultrasound: lens position, vitreous haemorrhage, retinal detachment
- Fluorescein angiogram / fundus photography: PDR, CRVO — causes of NVG
- Blood glucose, HbA1c: underlying diabetes
- TORCH screen / ACE / ANA: uveitis work-up