3. Risk factors and diagnosis

Diagnosing glaucoma: Key factors during eye examinations

• Patient risk factors: age, race, refractive error, systemic disease

• Anterior chamber angle (ACA)

• IOP (and central corneal thickness [CCT])

• Optic nerve head (ONH) appearance

• Retinal nerve fibre layer (RNFL)

• Visual field (VF)

• Interocular symmetry: IOP, ONH, VF

• Changes over time

• Marriage between ONH and VF (correlation of structure and function)

Glaucoma progression as a continuum

• Glaucoma progression described as a continuum from asymptomatic to symptomatic, with detectable structural changes preceding functional loss and potential progression to blindness

• Stages and relationships:

  • ASYMPTOMATIC DISEASE with detectable RNFL change

  • UNDETECTABLE DISEASE with neuronal apoptosis but undetectable RNFL change

  • Retinal nerve fiber layer change (undetectable) before VF changes

  • Short wavelength automated perimetry indicates VF changes before standard automated VF tests

  • Functional impairment progresses from detectable VF changes to moderate and severe VF loss

  • Final stage: Blindness

  

Epidemiological factors

• Age:

  • POAG is age-related with increasing incidence after 60

• Race:

  • Higher POAG prevalence in black Americans

  • Lower POAG prevalence in Asians (though higher prevalence of ACG in Asians)

• Family history:

  • first-degree relatives confer markedly higher risk (up to 4–10× greater likelihood

  • 2× if a parent

  • 4× if a sibling

Systemic disease

• Diabetes and systemic hypertension are important conditions to consider

• Diabetics or hypertensives with untreated or uncontrolled glaucoma exhibit ONH damage sooner and faster

• Glaucoma occurs more frequently in diabetics than in non-diabetics (possible ischemic contribution)

Other factors

• Refractive status:

  • Myopia increases risk for POAG

  • Hyperopia increases risk for PACG

• Medication use:

  • Topical steroids

  • Topical decongestants (slight risk of mydriasis and PACG in susceptible individuals)

• History of eye trauma or surgery

• Cataract surgery status: aphakia or pseudophakia

  • especially in young patients (congenital)

What raises suspicion?

• Positive family history

• Disc appearance:

  • cup-to-disc ratio (CD) ≥ 0.7

  • CD asymmetry ≥ 0.2

• IOP characteristics:

  • raised IOP (> 22 mmHg)

  • IOP asymmetry > 5 mmHg

  • diurnal variation > 6 mmHg

• Anterior chamber angle status: shallow angle (Van Herick grading)

• Reduced central corneal thickness (CCT)

Clinical workup

• Case history

• Refraction and best corrected visual acuity

• Optic nerve head appearance: stereoscopic view; photography for documentation over time

• RNFL assessment: red-free filters (ophthalmoscopy, photography, OCT, etc.)

• IOP assessment: serial/phase tensions (diurnal sampling if possible)

• Computerised perimetry (threshold visual fields)

• Pachymetry (CCT)

• Anterior chamber/corneal assessment plus gonioscopy

• Always correlate visual fields with disc and RNFL appearance

Intraocular pressure (IOP)

• Mean IOP in adult population: $16 \, \pm \, 2.5\text{ mmHg}$

• Upper limit of “normal”: $21\text{ mmHg}$

• Many glaucoma patients have IOP < 21 mmHg

• Framingham study: $33\%-50\%$ of glaucoma patients have IOP < 21 mmHg on a single reading

IOP – diurnal variations

• IOP typically highest in the morning (around 6–7 AM) and lowest in the late evening (around 6–7 PM)

• Average diurnal variation: $\approx 4\text{ mmHg}$

• Ocular hypertensives: diurnal variation around $7-8\text{ mmHg}$

• POAG: higher diurnal curve, range $10-12\text{ mmHg}$

• Low-tension or normotensive glaucomas may also have IOP spikes

• Suspicion if: IOP asymmetry > $5\text{ mmHg}$ or diurnal variation > $6\text{ mmHg}$

• Always note time of day and instrument used when measuring IOP

IOP and VF/ONH correlations (simplified)

• IOP < 21 with Normal VF and Normal ONH

• IOP > 21 with Normal VF and Normal ONH

• IOP > 21 with Abnormal VF and Abnormal ONH

• IOP < 21 with Abnormal VF and Abnormal ONH

Corrections for CCT and IOP

• Thicker than average cornea = overestimate of IOP

• Thinner than average cornea = underestimate of IOP

• IOP correction factor for CCT: 0.5 mmHg per 10 µm

  • No correction factors have been validated

• New tonometric techniques thought to give more accurate IOP reading closer to the true IOP (based on internal algorithms/design).

Central corneal thickness (CCT) and glaucoma

• A thinner CCT is a risk factor for the development of glaucoma

• In POAG: thinner CCT associated with larger CD ratio and more advanced visual field loss

• Reasons for association:

  • Delayed diagnosis due to IOP underestimation with applanation tonometry in thin corneas

  • Potential intrinsic susceptibility: thinner CCT may reflect thinner lamina cribrosa (limited evidence)

Studies of “normal” healthy eyes (baseline references)

• Framingham study: average CD ratio $0.25 \pm 0.17$

• Jonas (1988, n=475 normals): horizontal (H) $0.39 \pm 0.28$; vertical (V) $0.34 \pm 0.25$

• Direct ophthalmoscopy: average CD ≈ $0.2$

• Stereoscopic view: average CD ≈ $0.4$

• Prevalence in normal populations:

  • 86% have CD ratio < 0.4

  • 7% have CD ratios ≥ 0.5

  • CD asymmetry > 0.2 present in only ~6% of normals

• Conclusion: “Normal” ONH definitions rely on cup-to-disc metrics and symmetry thresholds

When to get suspicious?

• General rule: CD ≥ $0.7$ or CD asymmetry ≥ $0.2$ warrants closer evaluation

• A funny-looking disc or asymmetric CD/disc appearance warrants VF, OCT, and IOP monitoring

Pathological optic nerve head changes

• Evidence of neural rim thinning and cell loss

• Cupping patterns:

  • Concentric enlargement: cup enlarges in all directions

  • Focal enlargement (polar notch): cup elongated vertically compared to disc; inferior-temporal notching (avocado sign)

  • Laminar dot sign: lamina cribrosa becomes spotty and visible

  • Bean pot cup: end-stage with deep excavation and almost no neural rim left

Progression of glaucomatous cupping (illustrative sequence)

• Focal enlargement (polar notch): cup is more vertically elongated than the disc, infero-temporal notching (avocado sign)

ISNT rule and neural rim tissue configuration

• ISNT: Inferior – Superior – Nasal – Temporal

• In glaucoma, rim tissue is often lost from inferior or superior poles

• Result: nasal or temporal rims appear thicker than inferior or superior rims

• Some healthy eyes do not follow ISNT; some glaucoma eyes do follow ISNT

End stage cupping

• Cupped-out optic nerve head appearance in advanced disease

Pathological optic nerve head changes – vascular aspects

• Disc pallor: neural rim tissue appears greyish; reduced capillaries

• Baring of circumlinear vessels: vessels follow cup edge and are left behind as the cup enlarges

  

• Splinter/Drance/Flame haemorrhages: within or at 1 disc diameter (1 DD) of the disc; common near the disc

• Peripapillary atrophy: halo of pale retina around disc; RPE atrophy due to vascular deficiency

Optic disc haemorrhage (Drance/splinter haemorrhage)

• Small flame-shaped haemorrhage, usually superficial NFL

• Located on or adjacent to the disc (within 1 DD); most commonly inferotemporally

• Resolves in 1–3 months; recurrences are common

• More frequent in normotensives than in high-tension glaucoma

• Indicator of early or progressive nerve damage, especially if recurrent

• May precede ONH or VF defects

• Easily missed; a deliberate search improves detection

• Glaucoma patients with Drance haemorrhage are ~4× more likely to have VF progression than those without

Peripapillary atrophy and zones

• Peripapillary atrophy: halo of pale retina surrounding disc; RPE atrophy due to vascular deficiency

• Beta zone atrophy: RPE loss with choriocapillaris loss (more common in glaucoma)

• Alpha zone atrophy: pigmentation changes (more common in normal eyes)

Visual fields in glaucoma

• Within normal limits vs. severe glaucomatous loss

• Disc appearance married to visual field defect: structure–function relationship

Glaucomatous defects (types and testing)

• Earliest defects: generalized depression and nerve fibre bundle defects

• Paracentral island scotomas: small, isolated, 5–15° from fixation; higher incidence in the superior field

  • Relative (reduction in sensitivity) or absolute (total loss of sensitivity) scotomas along the course of the arcuate nerve fibre path

• Arcuate scotoma (Bjerrum scotoma): islands scotomas enlarge/coalesce along nerve fibre paths

  • respects the horizontal midline

    

• Nasal step: sensitivity difference across horizontal raphe; may be central or peripheral; often with island scotomas

  • may take form of a depression or scotoma

  • may occur in isolation

• Visual field testing in glaucoma (automated perimetry): designed to detect these defects; consider the Glaucoma Hemifield Test (GHT)

  • Emphasis on respect of horizontal midline; focal arcuate patterns are common

Paracentral island scotomas

• Located along arcuate fibre paths; 5–15° from fixation

• Predominantly found in the superior field in studies

Arcuate scotoma (Bjerrum pattern)

• Island scotomas may enlarge and coalesce into an arcuate pattern following the fibre pathways

Nasal step

• A sensitivity difference across the horizontal raphe; can appear as a depression or scotoma

• May occur within central isopters (about 30°) or more peripherally

• Often associated with island scotomas

Consider 10-2 VF in early and late stage; Central 24-2 Threshold Test

Mimic glaucoma VF loss (different etiologies that can resemble glaucoma VF loss)

• Arcuate NFL bundle loss can be mimicked by:

  • Optic disc pit

  • Optic nerve head drusen

  • Optic nerve coloboma

  • Branch retinal vascular occlusions

Normal vs damaged optic nerve head (DIFFERENTIATORS)

• ONH coloboma example: structural anomaly that can affect interpretation of RNFL and VF

Retinal nerve fibre layer defects (RNFL)

• RNFL defects are among the earliest signs of glaucomatous damage in POAG

• RNFL loss can precede VF loss and ONH damage

• Normal RNFL appearance features:

  • fine white striations in the anterior retina

  • white haze over underlying areas

  • brighter closer to the ONH

RNFL thickness maps and deviation maps

• RNFL Thickness Map and RNFL Thickness Deviation maps are used to visualize thinning relative to normative data

  

Detecting glaucoma before development of VF defect

• 35% of eyes had abnormal average RNFL thickness 4 years before development of visual field loss

• 19% of eyes had abnormal results 8 years before field loss

Clinical take-home messages

• Evaluate ONH cupping and search for neural tissue loss and disc haemorrhages

• Always search for RNFL defects in patients suspected of having glaucoma

• Use dilated, stereoscopic observation for a thorough ONH assessment

• Measure IOP in everyone (when possible)

• Maintain a high degree of suspicion: symmetry of IOP, discs, and VF between eyes

RANZCO pathway for glaucoma management

Initial diagnosis and risk classification (RANZCO framework)

• Early disc abnormality with some VF MD < 6 dB indicates Early glaucoma risk

• Moderate glaucoma: VF MD 6–12 dB with field loss not within central 10°

• Advanced glaucoma: VF MD > 12 dB with potential central involvement

• Unstable: IOP not within target or fluctuating > 3 mmHg; disc changes/haemorrhage; VF changes; intolerance to treatment

• Acute: angle-closure, uveitis, neovascular, or secondary glaucoma with high IOP (e.g., PXF/PDS-induced)

OHT asymmetry/asymmetric OHT and NICE management framework (OHT/Asymmetric OHT vs LTG vs normal)

• Asymmetric OHT (funny disc) and LTG vs Normal:

  • Management strategies depend on risk assessment

  • Low risk: A–D management by Optometrist

  • Low risk with risk factor: Co-management

  • Low risk with E category (e.g., additional risk factors): Co-management

  • High risk: Co-management (referral and closer follow-up)

• The pathway emphasizes collaboration between ophthalmologists and optometrists for timely diagnosis and management of glaucoma and suspects