Primary Open Angle Glaucoma

Introduction

General Glaucoma Features:
- Lamina cribrosa thins immensely, displacing posteriorly. Along with this, GCL undergoes apoptotic degeneration, leading to anterograde degeneration, distorting and thinning the RG cell axons in the LC.
- Thinning and atrophy of the RG cell axons of the LGN target relay neurons, disrupts axon transports.
- Atrophy causes the rim to disappear, and the cup to enlarge.

Epidemiology:
- Globally in adults aged 50 or older
- 3.6M are blind (2nd leading cause of blindness)
- 4.1M are moderate/severe vision impairment (4th leading cause)

IOP Pathophysiology
- The true pathophysiology of glaucoma is not fully understood
- Aqueous provides oxygen and nutrients to avascular structures of the eye, such as the lens and endothelium. Resistance naturally causes increased IOP.
- The increased IOP can exert mechanical stress or strain on the posterior structures of the eye, directly affecting the retinal ganglion cells
- The lamina cribrosa is 1/3 of the thickness of the sclera, and is thus the weakest point in the wall of the pressurized eye, it is most susceptible straining.
- Believed that elevated IOP impairs axoplasmic flow and transport of essential neurotrophic factors. Normal axoplasmic flow allows transport of essential neurotrophic factors from the brain to the RGC in the retina by the axons.

Blood Flow
- It has also been shown that blood flow to the ONH and retina are greatly reduced in Px with glaucoma.
- Due to the GCL's high energy damage, it becomes very susceptible to metabolic stress
- Ischaemia or irregular blood flow can damage GCL by starvation of oxygen

Reactive Gliosis:
- Astrocyte become reactive, which make RGC more susceptible to biomechanical stress
- Can end up causing excitotoxicity, and damage lamina cribrosa structure
- Excitotoxicity occurs with excessive stimulation of neurotransmitter such as glutamate

Upregulation of autophagy:
- Normal process of self-degradation of unwanted or dysfunctional cell components is increased in response to stress

Genetics:
- Family Hx of glaucoma increases the risk of glaucoma by 10x
- Primary congenital glaucoma --> CYP1B1 or LTBP2
- Developmental glaucoma --> PITX2, PAX6, FOXC1
- Early onset glaucoma (<35y) --> MYOC
- Typically there are many genetic variants which cannot be localised to a single mutation

POAG Epidemiology:
- Global prevalence of 2.3%, mainly affecting people >=40 years
- Has regional variation, more commonly in Africa and South America
- Is the age related glaucoma

Dead Giveaways

Basic Diagnostic Criteria:

For primary open angle glaucoma to be present, there must be elevated IOP with no identifiable cause or simply the lack of IOP manifestation, with optic nerve damage that does not include swelling such as from papilloedema.
Elevated IOP is typically measured using the applanation tonometry, is the gold standard. Applies force over a small area of 3.06mm^2
Corneal thickness plays a major role. Normative: 545um +/- 35um. If it is thin, it can underestimate true IOP.

Glaucomatous Disc Features:

Enlargement of the optic disc cup. Larger discs are more likely to have cupping
CDR asymmetry >0.2 between eyes
NRR thinning/notching
- Thin focal narrowing or notching of the NRR typically in the superior or inferior poles of the ONH
- ISNT rule is not obeyed in 80% of patients
Presence of optic disc haemorrhage, or Drance Haemorrhage
RNFL layer thinning
- Often adjacent RNFL thinning which can be visible as reduced reflectivity or a defined wedge defect, particularly in the superior and inferior bundles. This is more typical towards the temporal side, especially inferotemporal.
Blood vessels at the optic disc.
- Nasalisation of central ONH vessels, making the vessels emerging at the disk margin making a sharp bend.
Peripapillary atrophy
- Zone-beta PPA. Represents loss of RPE and choriocapillaris

Associated Diagnostic Hexad:

Neuroretinal rim narrowing and notching
1. Forms a notch shape
2. Can be inferonasal or superotemporal in aspect
Disc Size and Cupping
1. Optic cupping is best quantified by a progressively increasing CDR
2. Additionally, there is typically a larger CDR in one eye
RNFL defects
1. RNFL thinning may be seen, more evidently in red-free
2. This is also emphasised in the inferotemporal usually
Optic Disc Haemorrhage (Drance)
1. Presents within the RNFL, typically within 1DD of the disc. Is classically supero or inferotemporal. Is self-limiting
2. Can also be associated with retinal vascular disease, diabetes, hypotension
3. Drance haemorrhage follows shape of RNFL
OCT RNFL-A and GC-A
1. RNFL is typically thinner around the infero and superotemporal areas of the optic disc
2. NRR thinning marked by RPE-Bruch's complex termination being very close to cup.
3. Infero and superotemporal loss
Perimetry
1. Visual field defects occur along the RNFL
2. Cans tart as nasal steps, arcuate or paracentral defect
  1. Nasal steps must have at least 1 point that is at the edge, and only in the nasal, and is contiguous with other points
  2. Nasal or paracentral start, progress to arcuate
3. It then develops to affect the full hemifield, both hemifields, and may or may not spare the central until the end.
4. Gold standard currently for glaucoma testing is the 24-2 standard/faster Humphrey VF
5. Anderson and Patella's Criteria:
  1. For a VF defect to be present, there must be a cluster of 3 contiguous points in a single hemifield on PSD of P<5%, with one point being P<1%
6. Thank you Professor Madigan

diagnostic features

Normal IOP:

15-21 mmHg +/- 3mmHg

Family Hx Risk:

Family history increases risk of glaucoma up to 10x

POAG Historical Risk Factors:

High
- Age
- Family Hx
Moderate
- Myopia
- Sleep Apnoea
- Vasospastic disorder, Raynaud's syndrome, migraine
Low
- Diabetes
- Hyper/hypotension

Gonioscopy:

The normal structures of the angle. This is open angle. Pigmentation is usually moderate