Introduction to Optic Nerve and Glaucoma

What characteristics of the ONH do we eveluate?

• Disc margin

• Elevation

• Color of NRR

• Inner cup margin (C/D ratio)

• Integrity of NRR

• Peripapillary region

• Nerve fiber layer

What optic neuropathies are glaucomatous?

• Primary open angle (includes NTG)

• Primary angle closure

• Secondary open angle

• Secondary angle closure

• Congenital

• Syndromes

What optic neuropathies are non-glaucomatous?

• Papilledema

• Ischemic optic neuropathy

• Diabetic papillopathy

• Optic neuritis

• Traumatic optic neuropathy

• Toxic optic neuropathy

• Optic disc drusen

• Compressive

All glaucomatous optic neuropathy results in what?

Cupping

Does glaucomatous optic neuropathy have pallor?

Rarely (only in advanced stage cupping and only sometimes)

Does glaucomatous optic neuropathy have elevation?

No (never)

Does glaucomatous optic neuropathy have sweeling?

No (never)

Odd looking nerve that may or may not have normal function

Anomalous (non-glaucomatous)

Nerve that has a blurred disc margin from edema

Swollen (non-glaucomatous)

Nerve that has nerve tissue (NRR) that looks pale, yellow, not pink

Pallor (non-glaucomatous)

ONH that looks normal (function NOT normal)

Normal (non-glaucomatous)

All optic neuropathies demonstrate what (depending on the stage of disease)?

Some reduced function of the ON

• Decreased VA

• Decreased CV

• Decreased contrast sensitivity

• VF defect

• APD (if unilateral or asymmetric)

A patients with glaucomatous optic neuropathy usually asymptomatic or symptomatic?

Asymptomatic

A patients with non-glaucomatous optic neuropathy usually asymptomatic or symptomatic?

Symptomatic

What might a patient with glaucomatous optic neuropathy complain about?

Usually asymptomatic, but may c/o blur or decreased vision in advanced stage disease

What might a patient with non-glaucomatous optic neuropathy complain about?

Decreased vision (VA may be normal or abnormal)

Do patients with non-glaucomatous optic neuropathy have a VF defect?

Yes

Do patients with glaucomatous optic neuropathy have a VF defect?

Depends on the stage

Do patients with glaucomatous optic neuropathy have a APD?

Only if asymmetric

Do patients with non-glaucomatous optic neuropathy have a APD?

If unilateral (many are)

"A _____ in which an optic neuropathy develops that is manifested by the death of ganglion cell axons, which results in excavation of the optic nerve head."

"This damage causes characteristic nerve fiber bundle defects which lead to visual field loss and other abnormalities of visual function."

Family of diseases

"A family of diseases in which an optic neuropathy develops that is manifested by the _____, which results in excavation of the optic nerve head."

"This damage causes characteristic nerve fiber bundle defects which lead to visual field loss and other abnormalities of visual function."

Death of ganglion cell axons

"A family of diseases in which an optic neuropathy develops that is manifested by the death of ganglion cell axons, which results in _____."

"This damage causes characteristic nerve fiber bundle defects which lead to visual field loss and other abnormalities of visual function."

Excavation of the optic nerve head

"A family of diseases in which an optic neuropathy develops that is manifested by the death of ganglion cell axons, which results in excavation of the optic nerve head."

"This damage causes _____ which lead to visual field loss and other abnormalities of visual function."

Characteristic nerve fiber bundle defects

"A family of diseases in which an optic neuropathy develops that is manifested by the death of ganglion cell axons, which results in excavation of the optic nerve head."

"This damage causes characteristic nerve fiber bundle defects which lead to _____ and other abnormalities of visual function."

Visual field loss

Glaucoma is primarily a disease of the what?

Optic nerve (blindness results from nerve damage)

Glaucoma with an anatomically normal, open angle as viewed with gonioscopy

Open angle (POAG or NTG)

Glaucoma with an anatomically narrow or closed angle as viewed with gonioscopy (< or equal to ½ TM visible x 180 degrees or more)

Closed angle (PAC or AAC)

Increased IOP and glaucomatous changes which are the direct result of some other ocular or systemic abnormality

Secondary glaucoma (open or closed angle forms)

Elevated IOP and glaucomatous disc damage due to abnormal development of the eye

Developmental glaucoma

Glaucomatous damage to the ONH AND/OR glaucomatous VF defects WITH elevated IOP (>21) AND gonioscopically open angle in a patient 40+

Primary open angle glaucoma

Glaucomatous damage to the ONH AND/OR glaucomatous VF defects WITHOUT elevated IOP (<22) AND gonioscopically open angle in a patient 40+

Normal tension glaucoma (Low tension glaucoma)

What is the cutoff IOP for NTG/POAG?

21 mmHg

• 21 or lower = NTG

• 22 or higher = POAG

Is ocular HTN a form of glaucoma?

No (but patients are at risk of developing it)

IOP repeatedly over 21 mmHg AND no glaucomatous damage changes to the optic nerve AND no glaucomatous changes to the VF

Ocular hypertension

Patient with some findings suspicious for glaucoma without definitive damage

Glaucoma suspect

How do you discriminate between a low and high risk glaucoma suspect?

Discriminated based on number of risk factors (3 or more = high)

What is suspicious of glaucoma?

• Abnormal VF changes

• Abnormal RNFL/GCL on OCT

• Suspicious of NRR thinning or excavation

• Strong FH (1 or more 1st degree relatives)

• Elevated IOP (especially with a thin cornea)

Any combination of these may raise suspicion of glaucoma but in “glaucoma suspects” there is NO definitive structure-function correlation

A larger C/D ratio in an otherwise healthy looking ONH

Physiological cupping

Glaucomatous damage to the ONH AND/OR glaucomatous VF defects WITH elevated IOP (>21) resulting from closed (or partially closed) anterior chamber angle

Primary angle closure glaucoma

Normal IOP AND no glaucomatous changes to the ONH or RNFL AND a critically narrow anterior chamber angle

Primary angle closure suspect (aka anatomically narrow angle)

• Note: not a form of glaucoma

How do we define critically narrow angles?

Based on gonioscopy view

• When the most posterior structure visible is ½ TM (ATM) or less over 180 degrees or more

When should we do gonioscopy?

Performed on all glaucoma patients and suspects

What type of gonioscopy is preferred?

4 mirror (allows for indentation/compression of the cornea to differentiate degree and type of angle closure)

Is POAG/NTG unilateral or bilateral?

Bilateral (often asymmetric)

Is POAG/NTG chronic or acute?

Chronic

Is POAG/NTG stable or progressive?

Progressive (usually slowly)

Is vision loss in glaucoma perminant?

Yes

Do we usually see structural or functional loss first in glaucoma?

Structural (RNFL injury observed up to 6 years before VF defects)

Eyes with mild VF loss are associated with what % ganglion cell axon loss?

10-50

By the time VF loss is considered abnormal by typical clinical criteria, what % of RGCs have been lost?

25-35

What is the prevalence (%) of OAG (POAG + NTG) in the US population 40+ years?

~2

What % of people with OAG are not diagnosed

~50

What % of all glaucoma patients have NTG (<22)?

30-50

What % of Americans 40+ have OHTN?

4-10%

What is the #1 cause of vision loss in African Americans?

Glaucoma

What is the #2 cause of blindness worldwide?

Glaucoma

Are more people blind from OAG or angle-closure glaucoma?

Angle closure (even though it’s less common)

Which is more common OAG or angle-closure glaucoma?

Open-angle glaucoma

An event, condition, or characteristic that plays an essential role in producing an occurrence of the disease

A risk factor

What are the ocular risk factors of glaucoma?

• IOP

• Pachymetry (CCT)

• Corneal hysteresis

• Optic nerve

• Myopia

• Low OPP

What are the non-ocular risk factors of glaucoma?

• Age

• Race

• Family history

• Diabetes

• HTN (over treatment)

• Obstructive sleep apnea

• Low OPP

Is age a strong risk factor for glaucoma?

Yes (very strong)

• Dramatic increase in prevalence with age

What is the prevalence (%) of glaucoma in patients over 75?

4.7% (1 in 20)

What race(s) are at greater risk of developing POAG?

Black and Hispanic

What race(s) are at greater risk of developing acute angle closure glaucoma?

Asian and native Alaskan

Why do we not rely on IOP measurements to scream for glaucoma?

Subjects whose IOP was <21mmHg were three times more likely to be undetected than those who had higher IOP

Why do we not rely solely on the race or ethnicity of a patient as a risk factor?

OHTS found that if you control for corneal thickness and cup size, black race is NOT a risk factor

In the US black American are at what greater risk than white Americans?

4-5x

How does lifetime absolute risk change with individuals having relatives with glaucoma?

Lifetime absolute risk at 80 is 10x higher

How does family history change your risk of glaucoma?

The more relatives of closer relation, the higher risk

Mutations to what two genes cause early onset familial NTG with AD inheritance?

Optineurin (OPTN) and Tank binding protein 1 (TBK1)

Mutations to what gene causes JOAG with dominant inheritance?

Myocilin (MYOC)

Mutations to Optineurin (OPTN) can cause what type of glaucoma?

Normal tension glaucoma

Mutations to Tank binding protein 1 (TBK1) can cause what type of glaucoma?

Normal tension glaucoma

Mutations to Myocilin (MYOC) can cause what type of glaucoma?

JOAG

Is FH a significant risk factor?

Yes (the more family members of closer relation with glaucoma, the greater the risk to the individual)

Assessment of risk for a condition (ex glaucoma) by combining the risk from hundreds to thousands of genetic variants

• Provides an overall genetic risk relative to the population studied

Polygenic Risk Score (PRS)

Is diabetes mellitus a serious risk factor of glaucoma?

No, a MODEST risk factor (1.35x increased risk)

Is systemic HTN a serious risk factor for glaucoma?

Somewhat controversial

• No association in several studies

• High BP “protective” in others

• Low BP effects OPP

  • Low OPP is a risk factor

  • Over-treatment of the HTN can be an issue

Is obstructive sleep apnea a serious risk for glaucoma?

Yes (patients with OSA have a 40% greater risk of glaucoma)

How does having obstructive sleep apnea (OSA) increase your risk of glaucoma?

• Repetitive hypoxic episodes may damage RGC axons

• Increased IOP at night

What is the strongest correlation to glaucoma?

IOP

T/F: Most patients with IOP >21mmHg will go on to develop glaucoma

False (but IOP is still the strongest correlation to glaucoma)

What optic disc parameters can indicate glaucoma?

• Asymmetry is an important feature

• A large C/D ratio may pose greater risk, but no single cutoff can be made

Is myopia a serious risk factor for glaucoma?

Depends on the amount, glaucoma risk increases with increasing myopia

• Consider low myopia a modest RF

• For myopia >6D, the risk is more significant, and that risk grows with greater and greater myopia

For each 1D increase in myopia, how does glaucoma risk change?

For each 1D increase in myopia, glaucoma risk increases by ~20%

• But, the relationship is not linear

  • Risk accelerates at 6D

  • Further accelerates at 8D

How does pachymetry (CCT) alter the risk of glaucoma?

Thinner corneas increase the risk of developing POAG in patients with OHTN

• Thinner CCT suggests a higher true GAT, on average

Why are thinner corneas a risk factor for glaucoma in patients with OHTN?

Increased risk may be related to an anatomic weakness in the ONH or laminar region

A biomechanical property displayed by viscoelastic tissues (ex. cornea)

Corneal hysteresis

Geometrical attribute of the cornea (thickness)

Pachymetry

Is corneal hysteresis a serious risk factor for glaucoma?

Yes (independently and strongly associated with glaucoma)

What CH puts you at a higher risk for glaucoma?

<9

What CH puts you at a lower risk for glaucoma?

>12

The difference between arterial BP and IOP

OPP

Regulated to maintain constant blood flow to the optic nerve

OPP

Is OPP a serious RF for glaucoma?

Yes, low OPP is a risk for both the development and progression

Estimates a patient’s overall risk for onset and progression of disease based on multiple rather than a single factor

Global risk assessment

What pieces of information does the PHTS risk calculator take into consideration?

1. Age

2. Untreated IOP

3. CCT

4. Vertical cup to disc ratio

5. Pattern standard deviation (Humphrey or Octopus VF)