Glaucoma

Introduction

Glaucoma is an eye condition which causes damage to the optic nerve. The official definition is “a group of progressive optic neuropathies characterised by slow, progressive degeneration of retinal ganglion cells and their axons”.¹

There are different forms of glaucoma and together they are a leading cause of worldwide blindness.² If glaucoma is undetected, untreated or under-treated, it may lead to a loss of visual function which presents as loss of peripheral vision. Patients may be unaware of this in the early stages. Glaucoma results in characteristic changes in the appearance of the optic nerve head and retinal nerve fibre layer & patterns of visual loss. It can affect one eye or both eyes.

Raised pressure inside the eye (intraocular pressure (IOP) is a major risk factor for development of glaucoma.³ Reducing IOP reduces the rate of progression of glaucoma.^4-6 Currently IOP is the only modifiable risk factor and the mainstay of treatment is to lower IOP. Without adequate treatment, glaucoma can progress to visual disability and eventual blindness.⁷

There are different ways to categorise glaucoma and they all complement each other. The European Glaucoma Society (EGS) classification is based on the mechanism of IOP outflow obstruction.

• Open Angle
  • Primary: Primary Open Angle Glaucoma (POAG); POAG suspect, and Ocular Hypertension
  • Secondary: Result of ocular disease, Pseudoexfoliation, Pigment Dispersion Syndrome, Neovascular, result of ocular trauma, iatrogenic, extraocular disease
• Angle closure
  • Primary: Includes Primary Angle Closure (PAC), Primary Angle Closure Glaucoma (PACG), Acute Angle Closure (AAC)
  • Secondary: with pupil block, without pupil block I(anterior pulling; posterior pushing)
• Developmental
  • Primary Congenital (birth to 2 years)
  • Late onset childhood or early juvenile
  • Secondary Childhood

In the USA, glaucoma classification typically follows guidelines established by professional organizations such as the American Academy of Ophthalmology (AAO) and the American Glaucoma Society (AGS). These guidelines provide a framework for categorizing glaucoma based on various factors, including the underlying cause, clinical findings, and disease progression. Here is an overview of the general approach to glaucoma classification:

• Primary Open-Angle Glaucoma (POAG)
• Angle-Closure Glaucoma
  • Further classified as acute angle-closure glaucoma (sudden onset) or chronic angle-closure glaucoma (gradual onset).
• Secondary Glaucoma
• Congenital Glaucoma
• Normal-Tension Glaucoma (NTG)
• Classification Based on Disease Severity
  • Common classification systems include the AAO Preferred Practice Pattern guidelines⁸ and the Hodapp-Parrish-Anderson Criteria.⁹

Classification may also consider risk factors for disease progression, such as age, ethnicity, family history, central corneal thickness, and presence of other ocular or systemic conditions.

Overall, glaucoma classification in the USA aims to provide a standardized framework for diagnosing and managing different types and stages of glaucoma, allowing for personalized treatment plans and improved patient outcomes.

Worldwide the global prevalence of POAG is around 3% and of primary angle closure glaucoma (PACG) is around 0.5%.¹⁰

Anatomy of the Eye

The aqueous humour is clear fluid present in the anterior chamber of the eye. It has important functions:

• Contributes to the rigidity and shape of the globe of the eye and maintains IOP
• Adds to ocular refracting power and optical clarity of the eye
• Provides nutrition to the avascular cornea and lens
• Removes metabolic waste-products via onward drainage
• Helps in defense against infection and inflammation
• Has a protective effect against harmful ultraviolet radiation

The aqueous humour is responsible for the maintenance of the IOP which is the only modifiable risk factor for glaucoma and the progression.¹⁶

Aqueous humour is produced by the ciliary epithelium of the ciliary body in the posterior chamber. Aqueous flows through posterior chamber and into the anterior chamber. Aqueous then exits the eye via two pathways:

• Trabecular meshwork/canal of Schlemm
• Uveoscleral pathway

The production of the aqueous humour varies during the day. It is highest in the morning, and lowest during the night. The outflow is adjusted throughout the day to account for this. A balance of aqueous inflow and outflow is essential for maintaining ‘normal’ IOP.¹⁹

Trabecular Outflow Pathway or Conventional Route

Most of the aqueous humour drains via the trabecular meshwork at the irido-corneal angle. This is an open pore structure which absorbs the aqueous humour. The Canal of Schlemm collects the aqueous and it leaves the eye via the epi-scleral venous network. This pathway accounts for 70-95% of the drainage.²⁰ It is sensitive to IOP changes, and the outflow rate depends on the IOP of the eye.

Uveoscleral Outflow Pathway or Alternative/Unconventional Pathway

This pathway is less well understood. It is thought that approximately 5-30% of aqueous humour leaves the eye via this route. The aqueous enters the ciliary body and passes through it and leaves the eye via veins in the ciliary muscle and drains into the vortex veins. The uveoscleral pathway is not pressure dependent so mostly remains consistent.²⁰

Optic Nerve Head

The optic nerve head (ONH) is the second cranial nerve (CN II). It passes all visual information form the eye to the brain. It is the only visible part of the central nervous system. As well as allowing the exit of the retinal ganglion cell axons the optic nerve also allows entry and exit of the retinal blood vessels.²¹ The retinal ganglion cells are neurons that receive signals from the photoreceptors in the retina. They process the signals and transmit them in axons through the optic nerve to the brain.¹⁶ There are 1.2 million individual neurons in the optic nerve. Over time this number decreases with age and this has been estimated to be around 6000 axons per year.

Glaucoma causes damage and death of the retinal ganglion cells at an increased rate. This can lead to progressive impairment of the visual field.¹⁶ In glaucoma examination of the optic nerve often reveals characteristic features of glaucomatous optic neuropathy and is an important diagnostic sign.

The features of glaucoma differ depending on the type. The most common can help to distinguish glaucomatous optic neuropathy from other optic neuropathies. The most common features seen in glaucomatous optic neuropathies are:

• Abnormalities of neuroretinal rim
• Abnormalities of peripapillary retinal nerve fibre layer
• Increasing disc excavation (cupping)
• Retinal nerve fibre layer (RNFL) haemorrhages at the disc margin

Causes for Glaucoma

The causes for glaucoma are complex and mostly still under investigation via genetics and testing for treatments.¹⁴ Theories of glaucoma pathogenesis:

1. Mechanical – The mechanical theory for the cause of glaucoma focuses on the role of IOP. Increased resistance to the outflow of aqueous humour results in an increase in IOP. This leads to mechanical stress and damages the ganglion cells.
2. Vascular – The vascular theory is based on poor ocular blood flow (perfusive neuropathy). It is thought there is insufficient blood flow to the eye which can be due to raised IOP or low blood pressure. This causes mild hypoxia (reduced availability of tissue oxygen) and /or ischaemia (reduced tissue nutrients).
3. Immune related – This theory suggested that glaucoma may arise from an autoimmune response in the patient. It is thought that mechanical stress leads to the release of neurotoxic factors which then result in ganglion cell death.

Clinical Evaluation

Risk Factors

There are different risk factors for the different types of glaucoma.

Risk factors for POAG:

• Older age. Population studies have shown that POAG increases in prevalence with advancing age.^{16, 22}
• Ocular risk factors
  • Elevated IOP²²
  • Optic nerve head changes
  • Thin central corneal thickness (CCT)
  • Corneal biomechanics
  • Myopia^{16, 22}
• Non-caucasian ethnicity. Population studies have shown that POAG increases in prevalence with ethnicity.^{23, 24} Glaucoma is the most common cause of blindness amongst Afro-Caribbean ethnicity.¹⁴
• Family history of glaucoma. Glaucoma has an estimated heritability of 70%.¹¹ A first degree relative has a 22% risk in their lifetime of developing glaucoma in comparison to 2.3% for non-relatives.^14,22
• Vascular risk factors including hypertension and diabetes.²²
• Drug induced. This is mainly steroid, (systemic or topical) but can also include drugs such as antihistamines, Parkinson’s medications, botulinum toxin, topiramate, tricyclic antidepressants¹⁴ which are commonly prescribed to patients.

Risk Factors for NTG:

• Glaucoma with low IOPs
• More common in women with vascular dysregulation²⁵
  • Migraine
  • Raynaud’s syndrome
• Older age
• Presence of RNFL haemorrhages at the optic disc
• Thinner central corneal thickness (CCT)

Risk Factors for OHT:

This includes conversion to POAG and is based on the Ocular Hypertension Treatment Study (OHTS)²⁶ and the European Glaucoma Prevention Study (EGPS):²⁷

• Older age
• Higher IOP
• Higher pattern standard deviation in visual fields
• Thinner CCT

Risk Factors for PAC:²⁵

• Increasing age
• Hypermetropia
• Female gender
• Ethnicity
• Diabetes
• Shorter axial length
• Shallow central anterior chamber (AC)
• Large, more anterior lens

To detect and monitor glaucoma, depending on local guidance, it is usual for the clinician to conduct some or all of the following in the examination:⁸

• Full patient history
• Visual acuity
• Pupil examination
• Slit lamp examination
• IOP measurement
• Gonioscopy
• Optic nerve head examination
• Fundus examination
• Central corneal thickness measurement
• Visual field examination
• ONH, RNFL and macular imaging