Glaucoma
Glaucoma is the leading cause of irreversible blindness worldwide, and irreversible is the word that organises everything about it. Cataract blindness waits patiently for surgery. Glaucomatous blindness does not wait and cannot be undone.
The subject is usually taught as a set of pressure numbers and drug names, which is why it feels arbitrary. It becomes coherent once two ideas are separated: what the disease actually is, and where the pressure comes from.
1. An Optic Neuropathy, Not a Pressure
Glaucoma is a progressive optic neuropathy with characteristic structural damage to the optic nerve head and corresponding visual field loss. Intraocular pressure appears nowhere in that definition.
Pressure matters for one reason only: it is the sole risk factor that can be modified. Age, family history, ethnicity, myopia and corneal thickness cannot be changed, and pressure can.
Two consequences follow, and both are examined.
A normal pressure does not exclude glaucoma. Normal tension glaucoma is common, and roughly half of people with glaucoma have a pressure within the statistically normal range at any single measurement.
A raised pressure does not establish it either. Ocular hypertension means raised pressure with a normal disc and normal field, and most such patients never convert.
The diagnosis is therefore made at the optic disc and in the visual field, and the pressure is what is treated.
2. The Aqueous Pathway and Where It Blocks
Aqueous humour is produced by the ciliary epithelium into the posterior chamber, passes forward through the pupil into the anterior chamber, and leaves mainly through the trabecular meshwork into Schlemm canal and then into the episcleral veins. A secondary uveoscleral route drains a smaller proportion.
The organising tool is that glaucoma is an obstruction somewhere on that path, and the whole subject is locating it.
| Site of obstruction | Mechanism | Example |
|---|---|---|
| At the pupil | Pupillary block | Primary angle closure |
| At the angle | Physically closed by iris | Angle closure, neovascular |
| At the trabecular meshwork | Open angle but increased resistance | Primary open angle, steroid-induced, pseudoexfoliation |
| Beyond the eye | Raised episcleral venous pressure | Carotid-cavernous fistula, Sturge-Weber |
Gonioscopy is the instrument that answers the question, and it is the single most important examination in glaucoma because it determines treatment. An open angle is treated by lowering production or improving outflow; a closed angle is treated by opening it.
Gonioscopy requires a mirrored contact lens because the angle cannot be seen directly. Light from it undergoes total internal reflection at the corneal surface, so the lens is needed to overcome that and bring the image out.
Measuring the pressure
Goldmann applanation tonometry is the standard, and it works on the Imbert-Fick principle, that the pressure inside a sphere equals the force needed to flatten its surface divided by the flattened area.
The instrument flattens a fixed area of cornea, chosen so that corneal rigidity and the surface tension of the tear film cancel each other out at that diameter, and measures the force required.
The assumption is a cornea of average thickness, which is why a thin cornea reads falsely low and a thick one falsely high, and why oedematous or scarred corneas make the reading unreliable.
Schiotz indentation tonometry measures how far a weighted plunger sinks into the cornea, and it therefore depends on scleral rigidity as well as pressure. In a highly myopic eye with a distensible sclera it under-reads.
Pressure varies through the day, typically peaking in the early morning, so a single normal reading in an afternoon clinic does not establish that pressure is controlled. Diurnal measurement is used when the disc is deteriorating despite apparently acceptable readings.
3. Reading the Optic Disc
The optic disc consists of a central cup and a surrounding neuroretinal rim made of the axons themselves. Glaucoma destroys axons, so the rim thins and the cup enlarges.
Cup-to-disc ratio alone is a poor sign, because a large disc has a large cup normally. What matters is the rim.
The ISNT rule states that in a normal disc the rim is thickest inferiorly, then superiorly, then nasally, then temporally. Violation of that order suggests glaucoma even when the cup-disc ratio looks acceptable.
Three further findings carry weight. Focal notching of the rim, usually at the inferotemporal or superotemporal pole, is highly specific. A disc haemorrhage at the rim margin indicates active progression. Asymmetry of cupping between the two eyes is significant because discs are normally symmetrical.
Retinal nerve fibre layer thinning, now measured objectively by optical coherence tomography, frequently precedes detectable field loss.
4. The Visual Field
Glaucomatous field loss follows the anatomy of the nerve fibre layer, which is why its patterns are so characteristic.
Axons from the nasal retina run straight to the disc, while those from the temporal retina arch above and below the macula, respecting the horizontal raphe. Damage to an arcuate bundle therefore produces an arcuate scotoma that respects the horizontal midline, and a nasal step is the visible edge of that respect.
The paradox that explains late presentation is that central acuity is preserved until very late. The patient reads the chart perfectly while losing the periphery, and because the two eyes overlap and the brain fills in, they notice nothing.
By the time a patient reports visual difficulty, a substantial proportion of axons have already gone, and none of them return.
5. Primary Open Angle Glaucoma
This is chronic, bilateral though often asymmetric, painless, and asymptomatic until advanced.
Risk factors are raised intraocular pressure, increasing age, family history, African ancestry, myopia, diabetes and thin central corneal thickness.
Corneal thickness matters twice over. A thin cornea causes applanation tonometry to underestimate the true pressure, and it is also an independent risk factor for conversion in its own right, which was one of the most useful findings of the Ocular Hypertension Treatment Study.
Normal tension glaucoma is the same disease occurring at statistically normal pressures, and it still responds to pressure lowering, which is the strongest argument that pressure is a continuum rather than a threshold. Vascular dysregulation, migraine, Raynaud phenomenon and nocturnal hypotension are associated.
Treatment is aimed at a target pressure, meaning the level at which that particular nerve appears to stop deteriorating, set lower for more advanced damage.
Deciding whom to treat
Not every raised pressure is treated, and the decision is a judgement rather than a threshold.
Treatment is favoured by a higher pressure, a thinner cornea, a suspicious disc, a positive family history, younger age with more years at risk, and established disease in the fellow eye.
The counterweight is that treatment is lifelong, drops have side effects and cost, and most ocular hypertensives never convert. Treating everyone with a pressure above 21 would commit a large number of people to unnecessary therapy.
6. Medical Therapy
| Class | Mechanism | Caution |
|---|---|---|
| Prostaglandin analogues | Increase uveoscleral outflow | Iris and periocular pigmentation, lash growth, uveitis |
| Beta blockers | Reduce aqueous production | Asthma, bradycardia, heart block |
| Alpha-2 agonists | Reduce production and increase uveoscleral outflow | Contraindicated in infants |
| Carbonic anhydrase inhibitors | Reduce production | Sulphonamide sensitivity, systemic acidosis with oral use |
| Cholinergics | Contract ciliary muscle, open the meshwork | Miosis, brow ache, accommodative spasm |
| Rho kinase inhibitors | Increase trabecular outflow | Conjunctival hyperaemia |
Prostaglandin analogues are the usual first choice because they are given once daily, are the most effective single agent, and have no systemic contraindications of significance.
Brimonidine is contraindicated in infants and young children, because it crosses the immature blood-brain barrier and causes central nervous system depression and apnoea. This is examined regularly.
Topical beta blockers cause systemic effects, and a patient with asthma can bronchospasm from eye drops, which is why punctal occlusion after instillation is taught.
7. Laser and Surgery
Selective laser trabeculoplasty applies short low-energy pulses to pigmented trabecular cells, triggering a biological remodelling response that improves outflow without thermal damage.
The LiGHT trial changed where it sits in the treatment pathway. At six years, 69.8 percent of eyes treated with laser first remained at target pressure with no drops at all. Disease progression was less frequent in the laser arm than in the drops arm, 19.6 percent against 26.8 percent, and far fewer eyes required trabeculectomy, 13 against 32.
Selective laser trabeculoplasty is now recommended as first-line treatment for open angle glaucoma and ocular hypertension in NICE guidance and is listed as a first-line option in European and American guidelines. This is a genuine change from the drops-first teaching in most revision material.
Trabeculectomy creates a guarded fistula from the anterior chamber to a subconjunctival bleb. Its failure mode is scarring of that bleb, which is why antimetabolites such as mitomycin C are used, and why the operation works less well in young patients who heal vigorously.
Glaucoma drainage devices divert aqueous to a plate placed posteriorly, and minimally invasive procedures target the trabecular meshwork or the suprachoroidal space with a better safety profile but more modest pressure reduction.
8. Primary Angle Closure Disease
Angle closure matters disproportionately in India and across Asia, and it causes blindness out of proportion to its prevalence because each episode does more damage.
The anatomy is a crowded anterior segment: a short axial length, therefore a hypermetropic eye, with a relatively large and anteriorly positioned lens that thickens with age, and a shallow anterior chamber.
The mechanism is pupillary block. Aqueous passing from posterior to anterior chamber must squeeze between iris and lens, and where those surfaces are closely apposed, resistance rises. Pressure builds behind the iris, bowing its periphery forward against the trabecular meshwork.
Closure is favoured at mid-dilation, because that is when the iris is both maximally in contact with the lens and maximally slack peripherally, which is why attacks occur in dim light, during stress, and after pupil-dilating drugs.
The condition is a spectrum: suspect, meaning a narrow angle only; primary angle closure, meaning angle closure with raised pressure or peripheral anterior synechiae; and primary angle closure glaucoma, once the optic nerve is damaged.
The acute attack
Acute angle closure presents with severe pain, a red eye, blurred vision with haloes, and often nausea and vomiting severe enough that patients are admitted under general medicine.
Signs are a hazy cornea from oedema, a shallow anterior chamber, a mid-dilated fixed oval pupil, ciliary injection and pressure often between 50 and 80 mmHg.
Management lowers pressure first with intravenous acetazolamide, topical beta blocker, alpha agonist and steroid, and hyperosmotic agents where needed.
Pilocarpine does not work at very high pressure, because the iris sphincter is ischaemic and cannot contract, so it is given once the pressure has begun to fall.
Laser peripheral iridotomy is the definitive treatment, creating an alternative route for aqueous that bypasses the pupil. It must also be performed prophylactically on the fellow eye, which carries a high risk of an attack of its own.
When iridotomy does not work
Two mechanisms close an angle without pupillary block, and both are recognised by the iridotomy having failed.
Plateau iris arises from anteriorly positioned ciliary processes that hold the peripheral iris forward against the meshwork. The central chamber depth looks normal, so the eye does not appear at risk, and treatment is laser iridoplasty rather than iridotomy.
Malignant glaucoma, also called aqueous misdirection, is the dangerous one. Aqueous is diverted posteriorly into the vitreous cavity instead of forward, pushing the whole lens-iris diaphragm ahead of it.
The recognition point is that the anterior chamber is shallow both centrally and peripherally, and the pressure rises despite a patent iridotomy. Adding a miotic makes it worse, and cycloplegics are used instead, which reverses the usual reflex.
9. Secondary Glaucomas
| Type | Mechanism | Recognising feature |
|---|---|---|
| Neovascular | New vessels and fibrovascular membrane close the angle | Ischaemic retina from diabetes or vein occlusion, rubeosis iridis |
| Steroid-induced | Increased trabecular resistance | Any route of steroid, including inhaled and skin preparations |
| Pseudoexfoliation | Fibrillar material clogs the meshwork | Flaky deposits on lens and pupil margin, Sampaolesi line |
| Pigment dispersion | Iris pigment released and deposited in the meshwork | Young myopic men, Krukenberg spindle, iris transillumination |
| Uveitic | Inflammatory cells, synechiae or steroid response | Pressure may rise or fall depending on ciliary function |
Neovascular glaucoma is the one to fear, because the underlying disease is retinal ischaemia and the angle is being permanently closed by contracting fibrovascular tissue. Treatment must address the ischaemia with panretinal photocoagulation and anti-VEGF agents, not only the pressure.
Roughly a third of the population are steroid responders, and the response can follow inhaled steroid for asthma or steroid cream applied to the eyelids, which is why the drug history must be specific rather than general.
Pseudoexfoliation carries a surgical warning as well as a pressure one, since the same material weakens the zonules, making cataract surgery in these eyes more likely to be complicated by zonular dialysis.
10. Childhood Glaucoma
Primary congenital glaucoma results from maldevelopment of the angle, and the infant eye responds differently from the adult eye because its coats are elastic.
The classical triad is epiphora, photophobia and blepharospasm, and it is frequently mistaken for a blocked tear duct.
Raised pressure stretches the globe, producing buphthalmos, and stretching Descemet membrane produces horizontal breaks called Haab striae. Corneal enlargement and clouding follow.
Treatment is surgical, not medical. Goniotomy or trabeculotomy addresses the abnormal angle directly, and drops are used only as a temporary measure while awaiting surgery.
11. The Indian Burden
Estimates place around 11.2 million Indians aged 40 and over with glaucoma, of whom roughly 6.5 million have primary open angle glaucoma and 2.5 million primary angle closure glaucoma, while some 27.6 million have primary angle closure disease of some form.
Angle closure causes disproportionately more blindness than its numbers suggest, with blindness affecting about twice as many angle closure as open angle patients.
The public health difficulty is that glaucoma fails the usual criteria for population screening. It is asymptomatic, no single test is both sensitive and specific, pressure measurement alone misses half of cases, and disc assessment requires a trained examiner.
The practical consequence is opportunistic case finding: examining the discs of everyone attending for another reason, and screening first-degree relatives of known patients, whose risk is several times that of the general population.
12. Worked Examples
Example 1. A 62-year-old hypermetrope presents with severe eye pain, vomiting and haloes. The cornea is hazy, the anterior chamber shallow, and the pupil mid-dilated and fixed. Pressure is 62 mmHg. Why is pilocarpine ineffective now?
Because the iris sphincter is ischaemic. At pressures above roughly 40 to 50 mmHg, perfusion of the sphincter fails and the muscle cannot contract, so a cholinergic agonist has no target. Pressure is lowered first with intravenous acetazolamide and topical agents, and pilocarpine is added once the pressure falls. Laser peripheral iridotomy is definitive, and the fellow eye must also be treated.
Example 2. A patient with a cup-disc ratio of 0.5 has a rim that is thinnest inferiorly. Is this normal?
No. The ISNT rule states that the normal rim is thickest inferiorly, then superiorly, then nasally, then temporally. A rim thinnest inferiorly violates that order and suggests glaucomatous damage, despite a cup-disc ratio that looks unremarkable. This is why rim configuration is more informative than the ratio, which merely reflects disc size in many normal eyes.
Example 3. A 55-year-old with pressures of 26 mmHg, a healthy disc and a normal field is found to have a central corneal thickness of 490 micrometres. What is the significance?
Two things. A thin cornea causes applanation tonometry to underestimate true pressure, so the real pressure is higher than measured. Independently of that, thin central corneal thickness was shown by the Ocular Hypertension Treatment Study to be a strong predictor of conversion from ocular hypertension to glaucoma in its own right. This patient therefore warrants treatment rather than observation.
Example 4. A 68-year-old with proliferative diabetic retinopathy has a pressure of 48 mmHg, new vessels on the iris and a closed angle. Why is pressure lowering alone inadequate?
Because the driver is retinal ischaemia. Ischaemic retina releases vascular endothelial growth factor, which diffuses forward and induces a fibrovascular membrane on the iris and across the angle. That membrane contracts and closes the angle permanently, so any pressure gained is temporary while the stimulus persists. Panretinal photocoagulation and anti-VEGF treatment address the ischaemia, and only then does pressure control become durable.
Summary
Glaucoma is an optic neuropathy, not a pressure, and pressure is treated because it is the only modifiable risk factor.
Normal pressure does not exclude it and raised pressure does not establish it.
Locate the obstruction on the aqueous pathway, and gonioscopy is the instrument that does it.
Judge the disc by the rim, not the cup, using the ISNT rule, notching, disc haemorrhage and asymmetry.
Field loss is arcuate and respects the horizontal midline, and central acuity survives until late, which is why patients present late.
Thin corneas both underestimate pressure and independently predict conversion.
Prostaglandins are the usual first drug; brimonidine is contraindicated in infants; beta blockers can cause bronchospasm from eye drops.
The LiGHT trial made selective laser trabeculoplasty a first-line treatment, with 69.8 percent of laser-treated eyes drop-free at six years and fewer progressing.
Angle closure is pupillary block in a crowded hypermetropic eye, worst at mid-dilation, and iridotomy is definitive in both eyes.
Pilocarpine fails at very high pressure because the iris sphincter is ischaemic.
Neovascular glaucoma requires treating the ischaemia, not just the pressure.
Childhood glaucoma presents with epiphora, photophobia and blepharospasm and is treated surgically.
India has some 11.2 million people with glaucoma, and angle closure blinds about twice as many as open angle disease.
