What Is Glaucoma?
A progressive optic neuropathy — not simply a disease of raised intraocular pressure.
Watch the Lecture
Start here before reading the notes →Definition
Glaucoma is a group of optic neuropathies characterised by progressive loss of retinal ganglion cells and their axons. [1,2,8]
The Pressure Paradox
Glaucoma is often associated with raised intraocular pressure. But pressure alone does not define the disease.
- High IOP is not sufficient: an eye may have elevated pressure without established glaucomatous optic neuropathy.
- High IOP is not necessary: glaucoma may occur even when untreated IOP measurements remain within the conventional population range. [1–5]
What Is Damaged?
Glaucoma affects retinal ganglion cells and their axons. Progressive neural loss becomes visible structurally at the retinal nerve fibre layer and optic nerve head, and functionally on visual field testing.
Why Does Damage Occur?
Glaucomatous damage develops through interacting mechanisms in a susceptible optic nerve. These are useful ways to understand the disease, not completely separate causes.
Mechanical stress
Retinal ganglion cell axons pass through the lamina cribrosa at the optic nerve head. Pressure-related stress may deform the lamina, distort its pores, and stretch, compress, or bend the axons. This may impair axoplasmic transport.
Vascular vulnerability
The optic nerve head needs stable perfusion. Reduced ocular perfusion pressure, impaired autoregulation, vascular dysregulation, or repeated fluctuation in blood flow may increase vulnerability to injury.
Cellular and neurodegenerative stress
Mitochondrial dysfunction, oxidative stress, and persistent glial activation may reduce retinal ganglion cell survival. Cytokines, disturbed glutamate handling, and related mediators may add to neural injury.
Structural and Functional Expression
Glaucoma becomes clinically visible through structural change and functional change. These are closely related, but they may not become abnormal at exactly the same stage.
Structural evidence
Progressive loss of retinal ganglion cell axons affects the retinal nerve fibre layer and optic nerve head.
- Optic nerve head examination
- RNFL assessment
- Retinal imaging and OCT
Functional evidence
As neural loss progresses, visual function may be affected and characteristic visual field defects may become detectable.
- Visual field testing
- Reproducible defects
- Change over time
Glaucoma as an Umbrella Term
Glaucoma is not one single disease. It is an umbrella term for disorders that can ultimately produce progressive glaucomatous optic neuropathy.
Classification by cause
No identifiable associated ocular or systemic cause explains the glaucoma.
An identifiable associated process is present, such as inflammation, trauma, lens-related disease, pigment dispersion, pseudoexfoliation, neovascularisation, or medication exposure.
Classification by angle and mechanism
The anterior chamber angle remains open on gonioscopic examination.
The angle is narrow or closed, altering access to the trabecular meshwork and the mechanism of pressure elevation.
Role of IOP
Intraocular pressure is one of the most important measurements in glaucoma. It is also the major modifiable risk factor for glaucoma development and progression.
The conventional IOP reference range is approximately 10–21 mmHg. This upper limit arose from the statistical distribution of IOP measurements in a reference population.
It tells us what is uncommon in that population. It does not represent a biological dividing line between a safe optic nerve and an unsafe optic nerve. [10]
IOP is
- A major modifiable risk factor
- Important for risk assessment
- Important for monitoring
- Relevant to treatment planning
IOP is not
- A diagnosis of glaucoma
- Proof of optic nerve damage
- A substitute for structural assessment
- A substitute for functional assessment
Clinical Categories
Look for three things in every patient: elevated IOP, glaucomatous damage, and whether IOP remains within the conventional population range.
Ocular hypertension
IOP is elevated, but there is no detectable glaucomatous optic nerve damage and no corresponding glaucomatous visual field loss.
Glaucoma with elevated IOP
Characteristic glaucomatous optic neuropathy is present and the IOP is elevated.
Normal-tension glaucoma
Characteristic glaucomatous optic neuropathy and corresponding functional loss are present even though untreated IOP measurements remain within the conventional population range.
What Do OHTS and EMGT Teach?
Two landmark trials help place IOP in its proper clinical context.
Ocular Hypertension Treatment Study
Participants had elevated IOP without glaucomatous damage at baseline. In the trial population, the five-year cumulative incidence of primary open-angle glaucoma was lower with pressure-lowering treatment than with observation.
Early Manifest Glaucoma Trial
In patients with established early open-angle glaucoma, lowering IOP delayed progression. Benefit was seen in eyes with both normal and elevated baseline IOP.
Glaucoma Suspect
A glaucoma suspect is a patient in whom glaucoma is possible, but not yet established.
Why might glaucoma be suspected?
- Elevated IOP
- Suspicious optic nerve appearance
- Suspicious RNFL finding
- Suspicious visual field finding
- More than one suspicious feature together
What is the purpose of assessment?
- Establish a reliable baseline
- Assess IOP, angle, optic nerve, structure, and function
- Identify the likely glaucoma mechanism
- Follow over time for consistent change
Diagnosis: Clinical Synthesis
Glaucoma is not diagnosed from one isolated result. It is recognised by bringing multiple domains together in the correct clinical context.
Pressure
What is the IOP level and pattern?
Angle
Is the angle open, narrow, closed, or abnormal?
Structure
Is there characteristic optic nerve head or RNFL damage?
Function
Is there corresponding visual field loss?
Time
Is there evidence of consistent change over time?
High-Yield Clinical Pearls
Keep these points clear before moving into glaucoma evaluation and management.
- Glaucoma is a group of progressive optic neuropathies.
- Retinal ganglion cell loss and axonal injury are central to glaucomatous damage.
- High IOP is neither necessary nor sufficient for glaucoma.
- IOP is a major modifiable risk factor, but it is not the diagnosis.
- The lamina cribrosa is a key site of pressure-related axonal injury.
- Mechanical, vascular, mitochondrial, oxidative, glial, and inflammatory mechanisms may interact.
- Structural and functional evidence must be interpreted together.
- Primary/secondary and open-angle/angle-closure are complementary classification axes.
- Ocular hypertension is a risk state, not established glaucoma.
- A glaucoma suspect has possible, but not yet established, glaucoma.
- The long-term aim is to preserve visual function and quality of life over the patient’s lifetime. [1,2,5–7]
One-Minute Revision Summary
Read this once before leaving the lecture.
References
- 1. Pazos M, Traverso CE, Viswanathan A, et al; European Glaucoma Society. European Glaucoma Society – Terminology and guidelines for glaucoma, 6th Edition. Br J Ophthalmol. 2025;109(Suppl 1):1-212. doi:10.1136/bjophthalmol-2025-egsguidelines.
- 2. Gedde SJ, Bowden EC, Challa P, Vinod K, Kolomeyer NN, Chopra V, Budenz DL; American Academy of Ophthalmology Preferred Practice Pattern Glaucoma Committee. Primary Open-Angle Glaucoma Preferred Practice Pattern®. Ophthalmology. 2026;133(4):P1-P103. doi:10.1016/j.ophtha.2025.12.029.
- 3. Gedde SJ, Kolomeyer NN, Challa P, Chopra V, Vinod K, Bowden EC, Budenz DL; American Academy of Ophthalmology Preferred Practice Pattern Glaucoma Committee. Primary Open-Angle Glaucoma Suspect Preferred Practice Pattern®. Ophthalmology. 2026;133(4):P104-P152. doi:10.1016/j.ophtha.2025.12.028.
- 4. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, et al; Ocular Hypertension Treatment Study Group. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701-713. doi:10.1001/archopht.120.6.701.
- 5. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M; Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-1279. doi:10.1001/archopht.120.10.1268.
- 6. Leske MC, Heijl A, Hussein M, Bengtsson B, Hyman L, Komaroff E; Early Manifest Glaucoma Trial Group. Factors for glaucoma progression and the effect of treatment: the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2003;121(1):48-56. doi:10.1001/archopht.121.1.48.
- 7. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014;311(18):1901-1911. doi:10.1001/jama.2014.3192.
-
8.
Allingham RR, Damji KF, Freedman S, Moroi SE, Rhee DJ, Shields MB, editors. Shields’ Textbook of Glaucoma. 7th ed. Philadelphia: Wolters Kluwer; 2021.
- 9. Fernández-Albarral JA, Ramírez AI, de Hoz R, Matamoros JA, Salobrar-García E, Elvira-Hurtado L, et al. Glaucoma: from pathogenic mechanisms to retinal glial cell response to damage. Front Cell Neurosci. 2024;18:1354569. doi:10.3389/fncel.2024.1354569.
- 10. Hollows FC, Graham PA. Intra-ocular pressure, glaucoma, and glaucoma suspects in a defined population. Br J Ophthalmol. 1966;50(10):570-586. doi:10.1136/bjo.50.10.570.
Click a reference to open its source. ↳ Useful when you want to read beyond the lecture.
