Glaucoma

Slide 1 · Glaucoma

Anterior-segment outflow disorders and optic-nerve injury

Mechanisms • Morphology • Clinicopathologic reasoning

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Trace aqueous humor from production to trabecular outflow.

Distinguish open-angle from angle-closure mechanisms and primary from secondary causes.

Explain selected secondary glaucomas through outflow resistance, venous pressure, or physical angle obstruction.

Relate chronic pressure-associated injury to the retina, optic nerve, and visual field.

Slide 3 · Glaucoma: A structural–functional disease

The name encompasses disease processes with characteristic optic-nerve cupping and visual-field changes.

Elevated intraocular pressure is usually associated, but is not indispensable.

The clinically important endpoint is optic-neural injury, not pressure elevation alone.

Slide 4 · Two linked expressions of glaucomatous injury

Outflow / pressure

Raised intraocular pressure is common, but not universal.

Neural structure

Characteristic optic-nerve cup and retinal axonal loss.

Visual function

Corresponding alteration of the visual field.

Slide 5 · Intraocular pressure and glaucoma are not identical

Normal-tension glaucoma

Characteristic cupping and visual-field change

IOP may remain within a normal range

Neural susceptibility cannot be inferred from IOP alone

Pressure elevation without glaucoma

Some eyes remain without characteristic cupping

Visual fields may be preserved on long follow-up

Elevated IOP is a risk context, not a complete definition

Slide 6 · Neuronal susceptibility is heterogeneous

IOP exposure

Ocular tissues experience intraocular pressure.

Susceptibility

Different axons / eyes are not equally vulnerable.

Outcome

Similar IOP does not guarantee the same nerve damage.

Slide 7 · Anterior-segment compartments

The anterior chamber lies between cornea and iris.

The posterior chamber lies behind the iris, in front of the lens.

These chambers communicate through the pupil.

Ciliary body

Cornea

Lens

Iris

Anterior chamber

Posterior chamber

Pupil

Trabecular outflow

Slide 8 · Ciliary body: Origin of aqueous humor

Aqueous humor forms at the ciliary body, specifically its pars plicata.

Newly produced fluid enters the posterior chamber.

Ongoing production matters when the pupil or angle becomes obstructed.

Ciliary body

Cornea

Lens

Iris

Anterior chamber

Posterior chamber

Pupil

Trabecular outflow

Slide 9 · Normal aqueous-humor circulation

Ciliary body

Aqueous humor production

Posterior chamber

Fluid behind the iris

Pupil

Passage to the front

Anterior chamber

Fluid approaches outflow angle

Slide 10 · The drainage angle is peripheral

The major drainage site is at the corneal periphery.

The anterior surface of the iris meets the corneal periphery at the angle.

Access to the trabecular meshwork determines whether the angle is functionally open.

Ciliary body

Cornea

Lens

Iris

Anterior chamber

Posterior chamber

Pupil

Trabecular outflow

Slide 11 · Trabecular outflow route

Anterior chamber

Fluid arrives at iridocorneal angle

Trabecular meshwork

Principal resistance / egress site

Schlemm canal

Main collector named by Robbins

Slide 12 · Major and minor routes of outflow

Trabecular pathway

Accounts for most aqueous-humor drainage

At the anterior chamber angle

Leads into Schlemm canal

Alternative pathways

Uveoscleral outflow also occurs

A minor route involving the iris

Not the central mechanism of its glaucoma classification

Slide 13 · Why outflow impairment can raise pressure

Production continues

Ciliary body supplies aqueous humor

Egress impaired

Resistance increases or route is occluded

Pressure effect

IOP may become elevated

Slide 14 · Two classification axes in glaucoma

Angle configuration

Primary process

Secondary process

Open angle

Primary open-angle glaucoma

Pseudoexfoliation; debris; raised venous pressure

Closed / obstructed angle

Primary angle-closure glaucoma

Neovascular membrane; mass effect; synechiae

Slide 15 · Open angle and angle closure: Decisive distinction

Open-angle mechanism

Trabecular meshwork physically accessible

Increased resistance to outflow

Angle may appear structurally unobstructed

Angle-closure mechanism

Peripheral iris impedes angle outflow

Apposition or adhesions can obstruct meshwork

Anatomical interference dominates

Slide 16 · Open angle: Access is preserved

An open-angle eye retains physical access to trabecular meshwork.

Outflow may nevertheless meet elevated resistance.

“Open” does not imply normal pressure regulation.

Ciliary body

Cornea

Lens

Iris

Anterior chamber

Posterior chamber

Pupil

Trabecular outflow

Angle accessible; Egress is resistant

Slide 17 · Angle closure: The iris blocks access

Peripheral iris position or adhesion can obstruct trabecular outflow.

Anatomical obstruction may cause a marked elevation in intraocular pressure.

Pupillary block and contracting membranes are distinct routes to closure.

Ciliary body

Cornea

Lens

Iris

Anterior chamber

Posterior chamber

Trabecular outflow

Peripheral iris obstructs the angle

Slide 18 · Primary versus secondary is a separate question

Type

Source-based organizing concept

Example

Primary

Disease form without a separately identified precipitating ocular disorder

Primary open-angle glaucoma

Secondary

A recognizable process alters outflow or venous drainage

Pseudoexfoliation glaucoma

Secondary

External mechanical obstruction of the angle

Neovascular glaucoma

Slide 19 · Primary open-angle glaucoma

This as the most common form of glaucoma.

The drainage angle remains anatomically open.

Relatively few obvious structural changes are apparent in the angle.

Impaired outflow is attributed to increased resistance.

Slide 20 · Primary open-angle glaucoma: Mechanistic inference

Angle open

No physical exclusion of trabecular access

Outflow resistance

Egress through open angle is hindered

Pressure association

IOP is usually increased

Axonal vulnerability

Optic-nerve injury develops in susceptible eyes

Slide 21 · Primary open-angle glaucoma: Etiologic uncertainty

The proximate cause of increased resistance remains uncertain in the Robbins account.

Genetic factors are suspected contributors.

An anatomically patent angle must not be misinterpreted as normal outflow function.

Slide 22 · Genetic association is not a complete mechanism

Genome-wide association studies implicating 40 genes in open-angle glaucoma.

Association does not identify a single causal lesion that accounts for all cases.

Avoid converting the gene-association count into a deterministic diagnostic test.

Slide 23 · Secondary open-angle glaucoma: Shared endpoint

Abnormal process

Fibrils, particles, or venous pressure change

Outflow compromised

Resistance or downstream drainage pressure rises

Angle stays open

Trabecular meshwork remains physically accessible

IOP may rise

Secondary open-angle glaucoma results

Slide 24 · Pseudoexfoliation: Fibrillar accumulation

Robbins calls pseudoexfoliation the most common secondary open-angle glaucoma.

Fibrillar material of varying composition is deposited through the anterior segment.

The deposit-associated outflow abnormality occurs despite an open angle.

Slide 25 · Pseudoexfoliation extends beyond the ocular angle

In the eye

Fibrillar deposits throughout anterior segment

Deposits associated with secondary open-angle glaucoma

Local accumulation interferes with aqueous drainage

Extraocular distribution

Connective tissue around blood vessels

Other visceral organs may contain deposits

Liver, kidney, and gallbladder

Slide 26 · Debris can obstruct an anatomically open meshwork

Physical openness of the angle does not prevent particles reaching the meshwork.

Obstructing material may derive from lens, blood, iris epithelium, or tumor.

The identity of the debris defines clinically meaningful secondary subtypes.

Slide 27 · Phacolytic glaucoma: Proteinaceous obstruction

Lens dissolution

High-molecular-weight lens proteins appear

Aqueous compartment

Proteins are available to drainage pathway

Trabecular clogging

Outflow resistance rises with open angle

Slide 28 · Ghost-cell glaucoma: Post-traumatic cellular debris

Eye trauma

Blood-derived cells enter relevant ocular spaces

Cell aging

Senescent red cells / “ghost cells” persist

Trabecular obstruction

Particles clog meshwork in open angle

Slide 29 · Pigmentary glaucoma: Iris epithelial granules

Iris epithelium

Pigment granules become available

Aqueous stream

Particles approach trabecular angle

Open-angle clogging

Outflow resistance increases

Slide 30 · Melanomalytic glaucoma: Tumor-derived material

Necrotic tumor

Tumor material breaks down

Debris reaches angle

Particulate load rises

Meshwork impairment

Open-angle secondary pressure elevation

Slide 31 · Particle-associated open-angle subtypes

Named form

Obstructing material

Source context

Phacolytic

High-molecular-weight lens proteins

Dissolving lens

Ghost-cell

Senescent red blood cells

After trauma

Pigmentary

Iris epithelial pigment granules

Pigment dissemination

Melanomalytic

Necrotic tumor material

Tumor breakdown

Slide 32 · High episcleral venous pressure: A different route

The trabecular angle may remain anatomically open.

Higher pressure in venous drainage at the eye surface impedes effective aqueous egress.

This secondary route differs from plugging the trabecular meshwork with particles.

Slide 33 · Sturge–Weber syndrome: Vascular link

Surface ocular vessels

Vascular malformations associated with syndrome

Venous pressure

Episcleral venous pressure becomes elevated

Aqueous drainage

Open-angle glaucoma can result

Slide 34 · Carotid–cavernous fistula: Arterialized veins

Spontaneous or traumatic fistula

Arterial blood enters abnormal venous route

Episcleral veins

Arterialization increases venous pressure

Open-angle consequence

Impaired aqueous drainage can elevate IOP

Slide 35 · Open-angle secondary mechanisms compared

Mechanism

Representative cause

Impaired step

Fibrillar deposits

Pseudoexfoliation

Trabecular outflow

Particle obstruction

Lens / red cells / pigment / tumor

Trabecular meshwork

Venous back-pressure

Sturge–Weber; carotid–cavernous fistula

Downstream venous drainage

Slide 36 · Primary angle closure: Anatomical predisposition

A shallow anterior chamber favors primary angle closure.

Frequent association with hyperopia.

The peripheral iris can obstruct the outflow angle when pressure and spatial relations change.

Slide 37 · Pupillary block begins at iris–lens apposition

The pupillary iris margin comes transiently against the anterior lens surface.

Aqueous flow through the pupil is impeded.

Production behind the iris does not stop when the pupil blocks.

Ciliary body

Cornea

Lens

Iris

Anterior chamber

Posterior chamber

Trabecular outflow

Peripheral iris obstructs the angle

Slide 38 · Pupillary block creates a posterior pressure gradient

Iris–lens apposition

Pupil passage becomes blocked

Aqueous production

Ciliary body continues supplying fluid

Posterior chamber

Pressure behind iris rises relative to anterior side

Slide 39 · Iris bombé: Pressure bows the iris forward

Accumulated posterior-chamber pressure pushes the peripheral iris anteriorly.

Forward bowing is termed iris bombé.

This change brings the iris into contact with trabecular outflow structures.

Ciliary body

Cornea

Lens

Iris

Anterior chamber

Posterior chamber

Trabecular outflow

Peripheral iris obstructs the angle

Slide 40 · Primary angle closure: Full causal sequence

Shallow chamber

Predisposition to crowding

Pupillary block

Posterior aqueous passage restricted

Iris bombé

Peripheral iris bows toward the angle

Angle occlusion

Outflow obstruction and IOP elevation

Slide 41 · Two different obstructions in primary angle closure

At the pupil

Iris margin contacts anterior lens

Posterior-to-anterior flow is blocked

Posterior chamber pressure accumulates

At the angle

Bowed iris meets peripheral trabecular region

Aqueous egress is directly obstructed

Intraocular pressure can rise markedly

Slide 42 · Why elevated pressure can injure the lens

The crystalline lens is avascular.

Lens epithelium depends on aqueous humor for nutrition.

Unremitting elevation of pressure can damage the epithelium and produce minute anterior subcapsular opacities.

Slide 43 · Anterior subcapsular lens changes after angle closure

Unremitting high IOP

Sustained pressure stress

Lens epithelium

Aqueous-dependent epithelial tissue is damaged

Slit-lamp finding

Small anterior subcapsular opacities

Slide 44 · Corneal edema despite normal endothelial cell number

Persistently elevated IOP can produce corneal edema.

This may occur despite an otherwise healthy complement of endothelial cells.

Corneal edema in this setting need not indicate primary endothelial dystrophy.

Slide 45 · From pressure elevation to bullous keratopathy

Sustained high IOP

Persistent anterior-segment pressure injury

Corneal edema

Fluid-related loss of transparency

Bullous keratopathy

Severe edematous epithelial consequence

Slide 46 · Secondary angle closure: A membrane can move the iris

Abnormal membranes may form on the iris surface.

Contractile components pull peripheral iris over the meshwork.

The angle becomes physically obstructed even without the primary pupillary-block mechanism.

Slide 47 · Chronic retinal ischemia creates a proangiogenic signal

Retinal ischemia

Chronic retinal hypoperfusion context

Proangiogenic response

VEGF and other factors are upregulated

Aqueous humor

VEGF can act on anterior-segment tissues

Slide 48 · Neovascular glaucoma: Membrane formation

VEGF signal

Aqueous contains proangiogenic factors

Iris response

Thin fibrovascular membranes grow over iris

Clinical appearance

Membranes may be initially transparent

Slide 49 · Myofibroblasts turn neovascularization into closure

Fibrovascular membrane

Abnormal membrane invests iris surface

Myofibroblasts

Contractile elements tighten membrane

Iris displacement

Iris is drawn toward the angle

Synechial obstruction

Trabecular egress is occluded

Slide 50 · Neovascular glaucoma: Traction closes the angle

Membranes change iris surface architecture and may smooth normal crypts.

Myofibroblast contraction favors peripheral anterior synechiae.

Synechial closure blocks aqueous outflow.

Ciliary body

Cornea

Lens

Iris

Anterior chamber

Posterior chamber

Trabecular outflow

Peripheral iris obstructs the angle

Slide 51 · Neovascular glaucoma: Integrated mechanism

Retinal ischemia

VEGF rises in the aqueous

Iris neovascular membrane

Fibrovascular proliferation appears

Membrane contraction

Myofibroblasts pull iris periphery

Closed angle

Outflow obstruction raises IOP

Slide 52 · Necrotic retinoblastoma can drive iris neovascularization

Necrotic tumors, particularly retinoblastoma, as causes of iris neovascularization.

The resulting membrane can participate in secondary angle closure.

Tumor-driven neovascular closure is distinct from tumor debris clogging an open angle.

Slide 53 · Ciliary-body tumor: Direct mechanical angle closure

Ciliary-body mass

Expanding lesion behind iris

Iris displacement

Mass physically presses iris forward

Trabecular closure

Aqueous-humor egress is blocked

Slide 54 · Inflammatory synechiae can also obstruct outflow

Anterior inflammation

Inflammatory exudate in chamber

Adhesion formation

Iris adheres to angle structures

Anterior synechiae

Trabecular access and egress are hindered

Pressure effect

Secondary glaucoma may result

Slide 55 · Secondary angle closure: Compare causal pathways

Pathway

Initiating abnormality

Mechanism of closure

Neovascular

Retinal ischemia / tumor-driven neovessels

Contracting iris fibrovascular membrane

Mass effect

Ciliary-body tumor

Iris mechanically pressed against meshwork

Inflammatory

Anterior-segment exudate

Anterior synechiae block angle

Slide 56 · Retinal ganglion cell depletion in glaucoma

Long-standing disease features loss of retinal ganglion cells.

The retinal nerve fiber layer becomes thinner as ganglion-cell axons are lost.

These structural changes link anterior-segment mechanisms to optic neuropathy.

Schematic — not a histologic image

Normal

Nerve fiber layer

Ganglion cell layer

Inner plexiform

Long-standing glaucoma

Nerve fiber layer

Ganglion cell layer

Inner plexiform

Loss of ganglion cells accompanies thinning of their nerve fibers.

Slide 57 · Optic-nerve cupping is a structural hallmark

Advanced glaucomatous disease shows an enlarged optic-nerve cup.

The optic nerve is also atrophic.

The conjunction of cupping and atrophy as characteristic.

Schematic — not a histologic image

Usual configuration

Advanced glaucoma

Glaucomatous cupping coexists with optic-nerve atrophy.

Slide 58 · Optical coherence tomography and disease morphology

Retinal ganglion cells

Loss of neuronal cell bodies

Retinal nerve fiber layer

Thinning of axons

OCT assessment

Thickness can be measured structurally

Slide 59 · Elevated IOP has age-dependent ocular consequences

Infants and children

Globe may enlarge: Buphthalmos

Corneal enlargement: Megalocornea

Immature tissues respond to elevated IOP with enlargement

Adult-sized eye

Prolonged elevation may thin sclera locally

Ectatic sclera can be lined by uveal tissue

Result may be termed staphyloma

Slide 60 · Case: Open angle with lens-derived material

CLINICOPATHOLOGIC VIGNETTE

An eye retains an open iridocorneal angle, but dissolving lens material releases abundant high-molecular-weight proteins into aqueous humor.

Which named secondary mechanism is most consistent with this description?

Interpretation: Phacolytic glaucoma — lens proteins can clog an otherwise accessible trabecular meshwork.

Slide 61 · Case: Shallow chamber with iris bombé

CLINICOPATHOLOGIC VIGNETTE

An eye with a shallow anterior chamber develops transient iris–lens apposition. Continued aqueous production bows the iris forward against the angle.

What sequence explains the pressure increase?

Interpretation: Pupillary block → posterior-chamber pressure increase → iris bombé → trabecular angle closure.

Slide 62 · Case: Retinal ischemia followed by angle obstruction

CLINICOPATHOLOGIC VIGNETTE

Chronic retinal ischemia is followed by fine fibrovascular membranes over the iris surface. The membranes contract and draw the iris peripherally.

Which category and mechanism best explain the obstruction?

Interpretation: Secondary angle-closure glaucoma caused by neovascular membrane contraction and peripheral anterior synechiae.

Slide 63 · Case: High pressure without glaucomatous cupping

CLINICOPATHOLOGIC VIGNETTE

An eye has had elevated intraocular pressure on repeated evaluations, but characteristic optic-nerve cupping and visual-field loss have not appeared during prolonged follow-up.

Why should the terms pressure elevation and glaucoma not be conflated?

Interpretation: There is variable neural susceptibility; A high IOP does not by itself demonstrate glaucomatous optic neuropathy.

Slide 64 · Mechanistic classification: High-yield synthesis

Finding

Most directly supported interpretation

Common trap

Angle open, resistant outflow

Open-angle glaucoma

Assuming “open” means normal flow

Shallow chamber; iris bombé

Primary angle-closure mechanism

Confusing pupil block with meshwork obstruction

Fibrovascular iris membrane

Secondary neovascular angle closure

Assuming all angle closures require pupil block

Cupping and nerve-fiber loss

Glaucomatous neural injury

Using IOP alone as the disease definition

Slide 65 · The complete clinicopathologic chain

Source of outflow defect

Trabecular resistance, angle closure, or venous pressure

Physiologic change

Aqueous drainage becomes insufficient

Pressure association

IOP often rises; Not obligatory for glaucoma

Neural end-organ effect

Ganglion-cell and axonal injury; Cupping / field change

Slide 66 · Core distinctions to retain

Glaucoma is defined by characteristic optic-neural and visual-field change; Pressure is strongly related but not synonymous.

Open-angle disease reflects resistance despite access; Angle closure reflects physical iris obstruction.

Secondary open-angle mechanisms include fibrils, cells / proteins / pigment / tumor debris, and high episcleral venous pressure.

Angle closure may follow pupillary block, fibrovascular traction, tumor mass effect, or inflammation.

Slide 67 · Selected primary reading and scope

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th edition (2026).

Primary teaching basis: the glaucoma section on aqueous dynamics, mechanisms, and major disease categories.

Adjacent section context: anterior-segment inflammation and glaucomatous optic-nerve damage.

Original diagrams in this deck are explanatory schematics, not reproductions of textbook figures.