Ocular Disease Ii - Glaucoma

Front 1

Definition: Glaucoma

Back 1

Group of disorders characterized by progressive structural/functional damage to the eye, particularly the ONH. IOP may be statistically normal at all times!

Front 2

Becker-Schafer Definition of Glaucoma

Back 2

That IOP which produces damage to the optic nerve is glacumomatous. Glaucoma is not an IOP, it is a disorder characterized by damaging intraocular pressure in some patients

Front 3

Definition: Low Tension Glaucoma
aka: Normal tension Glaucoma
(form of POAG)

Back 3

ONH damage consistent with glaucoma in presence of consistently "normal" IOP

Front 4

Definition: Ocular Hypertension

Back 4

Elevated IOP no accompanied by clinically apparent ocular damage characteristic of glaucoma

Front 5

What __% of ocular hypertensives develop glaucoma over a 10 year period?

Back 5

4-10%

Front 6

What ___% of ocular hypertensives per year develop glaucoma over time?

Back 6

.5 - 1 %

Front 7

OHTS: Conclusion?

Back 7

Untreated: 9.5% developed ONH or VF damage over 5 years
Treated: 4.4% of ocular hypertensives developed glaucoma over 5 years

Front 8

True of False? Risk of glaucoma increases with IOP

Back 8

True: at IOP > 21 the risk of glaucomatous VF loss is 5-6x greater than IOP < 21

Front 9

Definition: Angle Closure Glaucoma

Back 9

Glaucoma caused by clinically evident obstruction of aqueous flow TO the TM

Front 10

True or false? Pupillary Block (obstruction of flow thru the lens-iris diaphragm) is the least common cause of angle closure

Back 10

False - Pupillary Block is the most common cause of angle closure glaucoma

Front 11

Open Angle Glaucoma

Back 11

aqueous flow does get thru the lens-iris diaphragm and TO the TM but not THRU the TM

Front 12

True or False: POAG is the 2nd leading cause of blindness in the U.S.?

Back 12

False: 3rd (after cataract and ARMD)

Front 13

T or F? <75% of glaucoma-caused blindness in the U.S. is due to POAG

Back 13

False: > 75%

Front 14

T or F? Angle Closure Glaucoma is much less common but can quickly damage the ONH and cause blindness in 2-3 days if untxed

Back 14

True. High IOPs can be reached in and can be as quick as 1 day

Front 15

T or F? POAG accounts for ~70% of all adult glaucoma cases in the US

Back 15

True

Front 16

T or F? Only 20-30% of U.S. population have an angle narrow enough to possibly close (grade 1 or 2)

Back 16

False: 2-6%. ACG is uncommon in the U.S. Only about 5% of these actually go on to close = PACG

Front 17

T or F? < 10% of all glaucomas in the US are PACG

Back 17

True

Front 18

List two common sx of congenital/infantile glaucoma

Back 18

Photophobia (cornea becomes edematous which causes glare) and lacrimation

Front 19

List 6 common signs of congenital/infantile glaucoma

Back 19

Eye rubbing, Megalacornea, Buphthalmos, Hobbs striae (breaks in descmets), Elevated IOP and Large cups (reversible)

Front 20

Adult onset glaucoma is classified by three ways... list them

Back 20

1. By etiology
2. By anatomy of filtration angle
3. Mixed

Front 21

Is Primary or Secondary glaucoma the result from a clinically evident systemic or ocular disorder causing obstruction of flow to the TM or increased resistance to outflow?

Back 21

Secondary. Primary is NOT the result of a clinically evident systemic or ocular disorder

Front 22

Can Primary glaucoma be bilateral, inherited, open angle and angle closure

Back 22

Yes, all of these are characteristics of Primary Glaucoma

Front 23

OAG and ACG are differentiated by what technique?

Back 23

Gonioscopy

Front 24

Define OAG

Back 24

aqueous flow to the TM is NOT blocked by an anomaly. Accounts for the vast majority of glaucoma. Aqueous outflow obstruction is not clinically evident - the obstruction is within the TM

Front 25

T or F? Secondary OAG accounts for most OAG

Back 25

False. Primary OAG does

Front 26

Define ACG

Back 26

Aqueous flow to TM IS blocked, usually obstruction is either at the pupil (PUPILLARY BLOCK), at the angle (ANGLE CLOSURE) or both. Only occurs in anatomically at risk eyes - narrow angles = Primary ACG or obstruction due to a condition = Secondary ACG

Front 27

Define Mixed glaucoma

Back 27

Both angle closure and open angle glaucoma in the same eye. Ex. a POAG pt experiencing an angle closure is not uncommon. Periodic gonio on all glaucoma suspects

Front 28

Name the two mechanisms of Aqueous production

Back 28

1. Ultrafiltration = 20% of production
2. Active Secretion = 75-80% (from non-pigmented ciliary epithelium)

Front 29

T or F? Ultrafiltration is a pressure-dependent mechanism

Back 29

True. If IOP increases --> ultrafiltration is reduced (homeostatic). If perfusion thru capillaries in the ciliary processes decreases, then ultrafiltration decreases

Front 30

List 3 classes of glaucoma meds that INCREASE TM outflow

Back 30

1. Miotics (Pilocarpine, Carbachol)
2. Non-specific adrenergic agonists (Epi and Propine)
3. Prostaglandins and prostamides (Lumigan)

Front 31

List 3 classes of glaucoma meds that INCREASE Uveoscleral outflow

Back 31

1. Prostaglandin analogs (Xalatan, Travatan) and prostamides (Lumigan)
2. Non-specific adrenergic agonists (Epi and Propine)
3. Alpha-2 agonists (Alphagan, Iopidine)

Front 32

List 3 classes that Reduce Ultrafiltration --> decreases aqueous production

Back 32

1. Beta Blockers
2. Alpha-2 adrenergic agonists (Iopidine, Alphagan)
3. Osmotics

Front 33

List the class that reduces active secretion (hint: think about the enzyme required for active secretion)

Back 33

Carbonic anhydrase inhibitors (Azopt, Trusopt, Diamox, Neptazane)

Front 34

Review the Glaucoma meds and their mechanism of action pg. A11-12

Back 34

Review

Front 35

Describe the method for max overall effect of a glaucoma med

Back 35

For best additivity, combine two meds that have different mechanisms of action. Ex. One that works on aqueous production and the other on increasing outflow

Front 36

What happens in the early stages of inflammation (ant. uveitis) on IOP?

Back 36

Early uveitis or iritis decreases IOP due to decreased aqueous production of the ciliary processes; increases WBC, Fibrin in aqueous

Front 37

What about in later stages of inflammation? (Later iritis)

Back 37

WBC, fibrin and protein can clog TM outflow path causing increased IOP

Front 38

Name two mechanisms of Primary Angle Closure Glaucoma (breakdown the name into steps)

Back 38

1. Pupillary Block - most common. Lens-iris diaphragm is tightest when pupil is mid-dilated - increases pressure of PC and bows iris forward (Iris Bombe)
2. Plateau Iris - narrow angle approach - as pupil dilates it bunches into the narrow angle. Laser PI will be ineffective

Front 39

T or F? Almost all elevated IOP/glaucoma is due to an over production of aqueous

Back 39

False. Almost all due to OUTFLOW problem
- TM is major site of obstruction in POAG (specifically the Juxtacanalicular TM)

Front 40

T or F? Uveoscleral outflow does not depend on the pressure of the episcleral venous plexus

Back 40

True. Not pressure dependent (unlike TM outflow)

Front 41

List the 6 components of the Filtration angle and related physiology

Back 41

1. Uveal Trabeculum: Adjacent to AC - Large openings = little resistance to outflow
2. Corneo-scleral Trabeculum: from schwalbes ring to SS and CB - Smaller holes decreasing in size away from AC
3. Intratrabecular space: MPS (GAGs) = substance filling space between trabecular sheets. MPS secreted by trabecular endo.
4. Juxtacanalicular: Immediately adjacent to Schlemms. Endo cells different than other areas. Site of greatest resistance
5. Schlemm's: Lined by endo cells w/ TJ. Aqueous transported by vacuoles (pressure dependent)
6. Episcleral Plexus: 30-35 channels dumping into intrascleral veins then into episcleral plexus. 1:1 pressure change in plexus.

Front 42

List a few factors that cause an increase in Episcleral venous plexus pressure (inturn raises IOP)

Back 42

Sturge-Weber, Valsalva, enthusiastic gonio, carotid cavernous fistula, etc..

Front 43

T or F? Most ACG is primary AND most primary ACG is the result of pupillary block

Back 43

True. Most ACG has no apparent cause thus it's primary

Front 44

T or F? The narrow angle can be detected with SLE only

Back 44

False. Gonioscopy is needed

Front 45

Which condition has a anatomically narrow angle, often little or no pupillary block and dilation crowds the iris root into the angle causing ACG

Back 45

Plateau Iris

Front 46

List 6 risk factors for PACG due to pupillary block

Back 46

1. Age: increased with age due to increased thickness of lens
2. Race: Increased rate in Eskimos, chinese, vietnamese
3. Sex: Females tend to have shallower ACs
4. FHx: 3.5-6x greater risk in first degree relatives of patients with PACG
5. RE: Hyperopes have a smaller globe = smaller AC
6. Cortical Cataracts: lens thickened

Front 47

T or F? Pupillary block is often times caused by the doctor during dilation

Back 47

False. It is very infrequently Iatrogenic. Most causes are spontaneous

Front 48

T or F? Must inform patient if they are anatomically at risk for ACG

Back 48

True. Should also further evaluate with gonio or prophylactic laser PI to minimize risk

Front 49

Describe the mechanism to differentiate Primary angle closure glaucoma

Back 49

Gonioscopy. If angle closes in the presence of PI --> this suggests that pupillary block is NOT playing a major role - plateau iris is.

Front 50

Describe the treatment of ACG secondary to pupillary block

Back 50

Control IOP - to minimize damage
-Use Meds (know the list)
Clear cornea if edemous- NaCl solution
Pull iris root out of angle (miosis) - allows for shot at PI - use 2% pilo q15 min for total of 4 doses
May use corneal indentation to force fluid into TM to open angle - indent for 30s followed by 30s of rest. several times for 15 min
Laser PI- produces alternative path
Provocative Dilation test - plateau iris component

Front 51

Describe the treatment for PACG secondary to plateau iris

Back 51

Control IOP
Pull iris out of angle
LPI
Provocative test (dilate)
Gonioplasty/iridoplasty if positive provocative test

Front 52

Acute IOP increases cause what symptoms of corneal edema

Back 52

Halos and glare

Front 53

At what level of IOP is pilo non-effective due to an ischemic sphincter muscle

Back 53

> 45-50 mmHg

Front 54

What is Lens-glaukomflecken?

Back 54

Lens-induced epithelial necrosis due to acute increase in IOP. Appears as Ant. Subcapsular gray-white opacities

Front 55

T of F? Optic nerve fibers are affected in about 3 days and Disc edema occurs in about 4-5 days of acute IOP increase. Also Axon dropout in 6-7 days and Cupping 1-2 weeks

Back 55

False. ON - 1 day
Disc Edema 3-4 days
Axon dropout 5-7 days
Cupping 1-2 months

Front 56

When could vision loss and blindness occur in an episode of acute IOP spike?

Back 56

Vision loss within 24 hours and blindness within 2-3 days

Front 57

List 6 signs of an old acute ACG

Back 57

1. Pupil not round due to segmental sphincter paralysis
2. Iris atrophy
3. Glaucomflecken
4. Peripheral anterior synchiae
5. Posterior synechiae or pigment on ant. lens capsule
6. Iridotomy near 12 o clock

Front 58

Chronically elevated IOP (symptoms unlikely)
1. Cornea
2. Iris
3. Lens
4. Choroid
5. Sclera
6. ON

Back 58

1. Generally no effect. Possible edema
2. Iris atrophy (unlikely)
3. cataract (unlikely)
4. Choriocapillaris atrophy?
5. in young, staphyloma, generally posterior
6. most devastating and damaging from increased IOP

Front 59

RNFL normal anatomy: Where are the ganglion cell bodies located?

Back 59

Ganglion cell layer of retina

Front 60

List the 3 major nerve bundles of the RNFL

Back 60

1. Papillomacular bundle: 80-90% of the fibers
2. Arcuate bundles
3. Nasal radial fibers

Front 61

Describe the papillomacular bundle fibers

Back 61

From macula to temporal ONH. Small, compact bundles with alot of overlap. Damage hard to detect on VF. Hard to see clinically cause of size. Make up most fibers of ON but occupy little space in the ONH

Front 62

Describe the Arcuate Fibers

Back 62

Do not cross horiontal raphe temporal to the macula. Large diameter fiber bundles. Less overlap so damage seen quickly in VF. All temporal retina innervated by arcuate - nasal step

Front 63

Describe Nasal Radial Fibers

Back 63

From nasal fundus to nasal side of ONH. Temporal wedge of the VF. Affected later in glaucoma thus a temporal island is often left.

Front 64

Where are the axons from the periphery located in the RNFL?

Back 64

They are the deepest axons. They also enter more peripherally of the ONH

Front 65

What part of the VF is affected first in glaucoma and why?

Back 65

Central field is because axons from the central retina enter the ONH closest to the cup. As cup enlarges, these fibers are affected first.

Front 66

Descibe the visualization of RNFL

Back 66

Reflect light - red free reflected more. Thicker bundles reflect more light. Glial cells separate fibers = striations. Astrocytes allow redfree light to pass thru to RPE where it is absorbed. Most evident Superior and Inferiorly

Front 67

How many axons are in the ON?

Back 67

1 - 1.3 million bundles- bundles surrounded by astrocytes

Front 68

List the regions of the ONH

Back 68

1. Surface nerve fiber layer
2. Prelaminar region
3. Laminar region
4. Retro-laminar region

Front 69

T or F? Cup size increase is due mostly to axon loss --> loss of rim tissue

Back 69

True. Cup itself is filled with Glial cells - outside of the cup is axons.

Front 70

What is the correlation of cupping and RNFL changes to VF changes in early and late glaucoma?

Back 70

Early: structural damage might be evident with NO VF loss
Late: changes in VF are often not accompanied by observable ONH/RNFL change

Front 71

In the laminar region, Why is the size of the scleral canal important clinically?

Back 71

A small scleral canal = small diameter of ONH = small cup. Direct relationship

Front 72

Which region does the myelin sheath (oligodendrocytes) start (less astroglia)?

Back 72

Retro-Laminar region

Front 73

List 4 major theories and some characteristics of ON damage

Back 73

1. Vascular: Imbalance b/w IOP and perfusion pressure in capillaries of laminar region causes hypoperfusion --> ischemia --> ON damage
2. Mechanical: Elevated IOP causes mechanical damage to axons --> not due to direct pressure on axons but changes in lamina cribosa (shearing pressure)
3. Combo of both vascular and mechanical --> Individual variation
4. Axoplasmic: likely that both ischemia (lowered perfusion) and mechanical factors can reduce axoplasmic flow

Front 74

List 3 major problems with the mechanical theory

Back 74

1. Low tension glaucoma
2. Ocular hypertension
3. Vascular disease relationship to glaucoma

Front 75

List the 4 stages in the pathogenesis of glaucoma

Back 75

Stage 1: Primary event - primary factors such as mechanica, vascular, genetic
Stage 2: Damaging stimulus - Molecular changes in and around the ganglion cells
Stage 3: Apoptosis of ganglion cells - preprogrammed death (not by necrosis)
Stage 4: Ganglion cells are dead

Front 76

What is the main excitatory NT in the CNS under normal physiological conditions?

Back 76

Glutamate. High [] levels are toxic to ganglion cells. Ischemia can cause glutamate release from ganglion cells

Front 77

What is BDNF?

Back 77

Neurotrophin = brain derived neurotrophic factor. Produced by LGN and move by retrograde axoplasmic flow to ganglion cells. Necessary for cell viability

Front 78

T of F? Axon loss occurs very early in natural history of glaucoma, before evident structural changes but not before VF loss

Back 78

False. Axon loss comes before structural changes and long before VF Loss. Therefore you will need substantial axon loss before recognizable VF loss on SAP

Front 79

___% axon loss before recognizable VF defect on Goldmann perimeter

Back 79

40-50%

Front 80

___% axon loss before detectable VF loss on white-on-white threshold perimetry

Back 80

30-40%. 20% ganglion cell loss corresponds to ~5 dB of VF loss on SAP

Front 81

Explain why there is such extensive axon loss before VF loss is detected

Back 81

Because of the redundancy of axon bundles. Overlapping of the visual fields allows for significant bundle loss before any changes can be detected.

Front 82

T of F? Pallor precedes cupping (loss of axons) in glaucoma

Back 82

False. Cupping precedes pallor. Highly specific to glaucomatous optic neuropathy compared to other optic neuropathies

Front 83

Which pattern of structural damage is characterized by general cup enlargement, general RNFL dropout, late onset VF loss and a B-Y color defect?

Back 83

Diffuse axon loss. May cause up to 50% axon loss before detection possible.

Front 84

Describe some characteristics of Focal axon loss

Back 84

1. Poles of ONH - arcuate by far most common (large diameter axons). Temporal = least
common.
2. Notch in sup/inf rim
3. Slit defects in arcuate RNFL
4. Localized VF defects: Nasal steps, paracentral scotomas
5. More quickly detected than diffuse
6. Tend to occur more in elderly patients with normal or slightly elevated IOP.

Front 85

T or F? Most often a combination of diffuse and focal axon loss develops

Back 85

TRUE!