Table of contents

Principles of Glaucoma

Glaucoma is defined as: progressive optic neuropathy with characteristic changes in the optic disc and corresponding loss of visual fields (VF). It is the second leading cause of blindness worldwide.

It is the final common pathway for several conditions associated with raised intraocular pressure (IOP). It can be considered as an umbrella term for these conditions

Aqueous humour (AQH)

Glaucoma is caused by a disorder in the normal flow of aqueous humour. It is important to understand aqueous humour in detail.

Chambers of the eye. The green is the posterior chamber and is where aqueous humour is first secreted. By Holly Fischer, CC BY 3.0.

Physiology

Aqueous humour supplies nutrients to the cornea and lens

It flows from the posterior chamber to the anterior chamber via the pupil.
It fills the anterior chamber at 0.25mL (larger than the posterior chamber)
It is composed of 99% water and has a lower glucose and protein concentration than plasma.

Production and secretion

Aqueous humour is formed by the non-pigmented inner epithelium of the ciliary processes at the pars plicata

The inner non-pigmented epithelium is continuous with the neural retina
Most secretion occurs by active transport which is under sympathetic control:
- Stimulation of beta-2 receptors increase secretion
- Stimulation of alpha-2 receptors decreases secretion

The ciliary body also has an outer pigmented epithelium that is posteriorly continuous with RPE

Drainage

AQH travels from the posterior chamber to the anterior chamber via the pupil (the hole in the iris centre). There are 2 main pathways for AQH to drain from the eye:

Trabecular path (90%)

Also known as the conventional route
AQH flows through the trabecular meshwork → Schlemm's canal → episcleral veins
Contraction of ciliary muscle increases trabecular outflow

Uveoscleral path

AQH passes directly outward through ciliary muscle → suprachoroidal space → choroidal veins → vortex veins

Trabecular Meshwork (TM)

Normal aqueous flow, through Trabecular Meshwork. By Tun Soe.

The TM is a band of cellular sheets which form a sieve-like structure. It is triangular in cross-section and is found at the anterior chamber angle

Blocked Aqueous Flow due to Damaged Trabecular Meshwork. By Tun Soe.

It consists of 3 parts:

Innermost → uveal meshwork with large holes
Middle → corneoscleral meshwork with smaller holes
Outermost → juxtacanalicular meshwork connects TM to Schlemm canal

The juxtacanalicular meshwork contains the narrowest spaces and confers the largest resistance to normal AQH outflow via the conventional route

Scleral Spur

A fibrous projection from the sclera.

Longitudinal ciliary muscles insert onto its posterior surface.
It is an important landmark in gonioscopy.

Anterior Chamber (AC) Angle

Extends from Schwalbe's line (termination of Descemet's membrane of the cornea) to the TM, scleral spur and ciliary body.
Clinically significant because the closure of the angle will impede AQH outflow via the conventional route.

Angle-closure → AQH outflow blocked → AQH buildup → increased IOP → optic neuropathy → visual field defects → angle-closure glaucoma

Assessment of Glaucoma

Diagnosis is based on the 'glaucoma triad': raised IOP, abnormal disc, and visual field defects. The latter 2 signs are most important.

Intraocular Pressure

Goldmann tonometry is the gold standard method of measuring intraocular pressure

Normal range is 11-21 mmHg
Diurnal variation of up to 5 mmHg is normal. Peaks in the morning
Supine positioning leads to higher IOP than sitting
IOP measurement is affected by corneal thickness, astigmatism and the axial length of the eyeball.

You do not need raised IOP to diagnose glaucoma!

Optic Disc Changes

A healthy optic disc By Ske, CC BY-SA 3.0

An optic disc in advanced glaucoma. Note the increased cut-to-disc ratio and asymmetrical thinning of the neuroretinal rim. By Snoop, CC BY-SA 3.0

Glaucomatous diseases processes invariably damage the optic nerve, evidence of this damage can be seen in the optic disc during fundoscopy

The neuroretinal rim is the border of the optic disc and contains the retinal neuronal cells. The centre of the disc is the cup and contains the central retinal vessels
Neuroretinal rim thickness follows the ISNT rule of thickness: inferior (thickest), superior, nasal and temporal (thinnest).
In glaucoma, the neuroretinal rim becomes thinner so that it no longer follows the order of the ISN’T rule. This is called cupping of the disc.
A normal cup-to-disc ratio is around 0.3
In glaucoma, the cup-to-disc ratio is increased
Nasal vessel displacement and haemorrhages at the disc are also signs of glaucomatous change

Decreased nerve fibre layer (NFL) thickness readings on OCT would make one suspicious for optic nerve damage.

Visual Fields

Relatively specific glaucomatous field defects By Broadway DC, CC BY 2.0.

Perimetry is the measurement of visual field defects

The best test for monitoring glaucoma is Humphrey 24-2 perimetry
Glaucomatous visual field defects occur as a result of damage to the retinal nerve fibres

Gonioscopy

Gonioscopy is a method of visualizing the anterior chamber angle, it is important in identifying angle-closure glaucoma. Peripheral anterior synechiae might be found in angle closure, this is the iris bowing forward and closing off the angle.

Gonioscopic view of the anterior chamber angle. 1. Schwalbe's line, 2. Trabecular meshwork (TM), 3. Scleral spur, 4. Ciliary body, 5. Iris. By Snoop, CC BY-SA 3.0

Gonioscopy allows the visualisation of the anterior chamber angle. By Mick lucas, CC BY-SA 3.0.

Order of structures seen on gonioscopy from superficial to deep

Posterior corneal surface
Schwalbe’s line
Non-pigmented trabecular meshwork
Pigmented trabecular meshwork
Scleral spur
Ciliary body
Iris
Pupil

Medical treatment

Glaucoma drugs are commonly tested in the exam. You should be aware of their mechanisms of action and side effects.

Medical treatment can on average lower IOP by 20-30% (5-7mm Hg)

Prescribing

Order of use:

Latanoprost
Timolol
Brinzolamide
Brimonidine

Except in pregnancy/paediatrics:

No eye drops are licensed for children or pregnant women. Use brimonidine in first the trimester and switch to timolol in 3rd

Compliance is almost always an issue when you prescribe more than 2 drops over time.

Drug class	Mechanism of Action	Side Effects	Contraindications
Prostaglandin agonists (e.g Latanoprost)	Analogues of PGF2Alpha → increase uveoscleral outflow	Iris pigmentation Lash lengthening Hyperaemia Uveitis Macular oedema	Avoid in uveitis as it worsens inflammation
Beta-Blockers (e.g Timolol)	Block adrenergic cAMP → reduces aqueous production Betaxolol is a selective beta 1 blocker Carteolol is a competitive intrinsic agonist which has intrinsic sympathomimetic properties. This means that it doesn’t cause as many side effects	Bradycardia Worsens asthma	Lung and heart conditions Breastfeeding
Alpha 2 agonists	Decrease aqueous production and increase uveoscleral outflow A2 selective (brimonidine) A1 + A2 (apraclonidine)	Dry mouth Dry eyes	A2 selective blockers are lipophilic, and can cross the blood brain barrier, resulting in respiratory depression in the young
Cholinergic agonists (e.g Pilocarpine)	Muscarine agonism leads to ciliary contraction, opening the trabecular meshwork → Increases trabecular outflow Also causes miosis which relieves pupil block, where the the pupil has fallen down and is obstructing the flow of aqueous	Polyuria Diarrhea Lacrimation Sweating salivation	Cholinergic medications are not used in secondary angle closure because contraction of the ciliary body can cause it to rotate forward, making the anterior chamber even shallower
Carbonic anhydrase inhibitors (e.g Brinzolamide (any -lamide))	Inhibit anhydrase isoenzyme II → reduce aqueous production Oral (acetazolamide) is more effective because it also blocks isoenzyme IV	Hypokalemia Metabolic acidosis	Sulfonamide sensitivity Renal/liver failure

Order of use: Prostaglandins > Beta-blockers > Alpha 2 agonists > Cholinergics > Carbonic anhydrase inhibitors

The major distribution of beta receptors is: 1 heart, 2 lungs, 3 adipose

Trabeculectomy

Blebitis. By Rakesh Ahuja, MD, CC BY-SA 2.5.

Performed in chronic glaucoma where medications have failed to control IOP.

The creation of a fistula from the anterior chamber to the sub-tenon space - creating a bleb (elevation of the conjunctiva where the aqueous gathers)
Antimetabolites can be used adjunctively to slow the healing process and prevent bleb failure
- 5-FU: pyrimidine analogue which inhibits fibroblasts by blocking DNA synthesis
- Mitomycin C: alkylating agent which inhibits fibroblasts
  
  Conventional Trabeculectom

Laser surgery

Procedure	Indication	Laser
Peripheral iridoplasty - contraction burns of the peripheral iris pull it away from the angle	Temporising measure in acute angle-closure	Argon (455-529nm)
Peripheral iridotomy - creates a hole in the peripheral iris to allow aqueous flow through a closed-angle	Definitive treatment in acute angle-closure	ND: YAG (1064nm)
Selective laser trabeculoplasty (SLT) - laser applied to the trabecular meshwork to facilitate drainage	Used in open-angle glaucoma where medical treatment is not tolerated	Frequency-doubled Q-switched ND: YAG (532nm)

Selective laser has replaced argon laser in trabeculoplasty

Iatrogenic Glaucoma

Raised IOP is not uncommon in the post-surgical patient. Cataract and vitreoretinal surgeries are the most associated and will be discussed in this section.

Post-Vitreoretinal Surgery

Intraocular gasses can raise the IOP due to gas expansion
- Usually, short-term acetazolamide is enough to control IOP but consider the half-life of the gas
Scleral buckling can cause secondary angle-closure can occur due to ciliary body swelling but this usually resolves spontaneously
Silicone oil blocks the trabecular meshwork
- Usually resolves spontaneously
- Try cyclodestruction if it persists
Vitrectomy via ghost cell glaucoma (discussed further in the secondary open-angle glaucoma chapter)

Post-Cataract Surgery

Usually due to retained viscoelastic, retained fragments or inflammation.