1. Glaucoma pathophysiology (Optic nerve head)
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Glaucoma pathophysiology (Optic nerve head)

2. Anatomy and Histology Optic nerve head optic nerve의 distal portion
directly susceptible to elevated intraocular pressure
extends ant. from retinal surface to the myelinated portion of optic n. that begins just behind the sclera & post. to laminar cribrosa
composed of the nerve fibers that originate the ganglion cell layer of the retina
At the surface of nerve head, axons bend acutely to exit globe through fenestrated scleral canal, called lamina cribrosa

3. Anatomy and Histology Optic nerve head Optic nerve head의 직경 :
- 평균 1.88 mm vertically, 1.77mm horizontally
Disc area : 0.68mm2 ~ 4.42 mm2 (average 2.42 mm2)
Cup area has stronger correlation with the disc area than rim area → correction for disc size may be more important for cup area than rim area
Another study showed a positive correlation for between the optic disc size and the thickness of the peripapillary RNFL

4. Division of Optic Nerve Head
(A) Surface nerve fiber area
: predominantly nerve fiber
(B) Prelaminar region
: nerve axon, astrocyte
(C) Laminar cribrosa region
: scleral connective tissue,
elastic fiber
Astrocyte separate, line fenestrae
Fascicles of neurons leave these openings
Optic n head는 4가지 구역으로 나뉜다.
B- astroganglial tissue 의양이 많아짐.
D- oligodendrocyte 로 온 myelin들이 많아짐.
(D) Retrolaminar region
: decrease in astrocyte
acquisition of myelin

5. Vasculature-Arterial supply
Posterior ciliary artery(PCA) circulation
: optic nerve head 의 main source of blood supply
except the nerve fiber layer(by retinal circulation)
central retinal artery의 arteriolar branch
Surface nerve fiber layer
short posterior ciliary artery-form the circle of Zinn-Haller
Minimally peripapillary choroid
Prelaminar /
laminar region
both ciliary and retinal circulation
Retrolaminar region
The nerve fiber layer, which is supplied by the retinal circulation
Zinn-haller : perineural, circular arterial anastomosis at the scleral level

6. Vasculature Capillaries Venous drainage
Derived from both retinal & ciliary circulations
tight junction, abundunt pericytes,
nonfenestrated endothelium
→ resemble the features of retinal capillaries
Not leak fluorescein → Nerve-blood barrier
Nerve blood barrier: no fluorescein leak
Venous drainage
Almost through the central retinal vein
Although though the choroidal system
( retinociliary or cilio-optic vein )

7. Astrogilal support Astrocyte
provide a continuous layer between the nerve fibers & blood vss. in the optic nerve head
Joined by “gap junctions” which resemble tight junctions but have minute gaps
Thick-bodied astrocyte :prelarminar ~ laminar region의 axon
Thin-bodied astrocyte : NFL의 axon

8. Astrogilal support Supportive structure of ONH
provides covering for portions of optic nerve head
Internal limiting membrane of Elschnig (a)
: separates the nerve head from the vitreous
Central meniscus of Kuhnt (c)
: central portion of internal limiting membrane
Muller cells
: major element of intermediary tissue of Kuhnt (d)
(separate nerve from retina)
Major role : remodeling of the extracellular matrix of the optic nerve head & synthesizing GF & cellualar mediators

9. Connective tissue support
Lamina cribrosa
not simply a porous region of the sclera, a specialized extracellular matrix
(fenestrated sheets of connective tissue & elastic fibers lined by astrocytes)
astrocytes respond to elevated IOP in glaucoma, leading to axonal loss and
RGC degeneration at the level of laminar cribrosa
Hyaluronate
- found surrounding the myelin sheaths in the retrolaminar nerve
- maintenance of the of the ECM
- Decreases with age and is further reduced in COAG
, possibly increasing susceptibility to elevated IOP

10. Connective tissue support
Lamina cribrosa
Significantly thinner in glaucomatous eyes
Analysis of pores in lamina cribrosa
: Physiologic cupping – nearly round pores
COAG – compressed pores
Regional differences
LC 의 cell of glaucomatous eyes – express more profibrotic gene
sup. & inf.
nasal & temporal.
larger size of pore
thinner connective tissue & glial cell support
types I-VI collagens, laminin, and fibronectin

11. Connective tissue support
Lamina cribrosa
about 10% of axons exit more peripherally, where the lamina cribrosa is
more curvilinear, which may influence the regional susceptibility for
glaucomatous optic nerve fiber loss
Proteoglycans : role in the organization of other extracellular matrix
components and in the hydration and rigidity of tissue
composed of types I-VI collagens, laminin, fibronectin
Abnormalities of this extracellular matrix in the lamina cribrosa may
influence optic nerve function and its susceptibility to glaucomatous
damage caused by elevated IOP.
types I-VI collagens, laminin, and fibronectin

12. Connective tissue support
Nerve sheath
extend between choroid and optic nerve tissue, especially temporally
Optic n. – surrounded by meningeal sheath (pia, arachnoid, dura)
types I-VI collagens, laminin, and fibronectin
Arching above & below the fovea of fibers temporal to optc n. head
Fibers from central retinae, papillomacular, nasal fibers take direct path to n.head.

13. PATHOPHYSIOLOGY Mechanical theory Vs. Vascular theory
In 1968, the role of axoplasmic flow in glaucomatous optic atrophy was introduced,
which support for the mechanical theory
Glial Alteration
Vascular Alteration
Lamina Cribrosa alteration
- alterations in the lamina may actually be a primary event in
the pathogenesis of glaucomatous optic atrophy
- backward bowing : produce a pressure gradient along the axoplasm of exiting
optic nerve axons, compromise the circulation and and cause compression of the
axons.
- ECM of the lamina cribrosa may play an important role in the progression of
glaucomatous damage
그이전, controversy

14. PATHOPHYSIOLOGY Axonal Alterations
The actual cause of early optic nerve head cupping in glaucoma appears to be the loss of axonal tissue
chronic IOP elevation : posterior and lateral displacement of the lamina cribrosa,
which compresses the axons and disrupts axoplasmic flow
in the early stages of glaucoma, selective loss of the larger ganglion cells in
both the mid-periphery and fovea
- suggested that psychophysical testing should be aimed at these cells
RGCs in glaucoma die by apoptosis
Secondary degeneration
- experimental injury of RGCs, causing loss of neighboring RGCs
exposed to chronic IOP elevation suggest that the
damage is associated with a posterior and lateral displacement of the lamina cribrosa, which compresses
the axons and disrupts axoplasmic flow
Secondary degeneration - experimental injury of RGCs, causing loss of
neighboring RGCs as an indirect effect of the injury and death of transected RGCs.

15. PATHOPHYSIOLOGY Blood flow
elevation of IOP : flow in the lamina cribrosa is reduced only with extreme pressure
(autoregulation)
Blood-flow measurements in the optic nerve head of human eyes demonstrate
autoregulatory compensation to reduced perfusion pressure secondary to elevated IOP
however, glaucomatous eyes show reduced flow velocity in the nerve head
Eyes with glaucoma also appear to have more diurnal fluctuation
of optic nerve blood flow
Age may influence the vascular responses to IOP
- major retinal vessels at the disc border increased in response to IOP reduction in
patients with COAG who were 55 years or younger
Molecules such as endothelin and nitric oxide are being investigated for their possible role in the normal and altered autoregulatory responses
그이전, controversy

16. PATHOPHYSIOLOGY Fluoroescein Angiography Normal pattern
1) first phase (an initial filling, or preretinal arterial)
- represent filling of the prelaminar and lamina cribrosa regions by the
posterior ciliary arteries
2) peak fluorescence ( or retinal arteriovenous phase)
- filling of the dense capillary plexus on the nerve head surface from
retinal arterioles
3) late phase
- connective tissue of the lamina cribrosa
types I-VI collagens, laminin, and fibronectin

17. PATHOPHYSIOLOGY Fluoroescein Angiography
Effect of Artificially Elevated IOP
- general delay in the entire ocular circulation in response to an elevation of IOP
- increases in fluorescein-filling defect areas correlate with glaucomatous progression
In low-tension glaucoma
- retinal arteriovenous passage times are prolonged
(increased resistance in the central retinal and posterior ciliary arteries.)
types I-VI collagens, laminin, and fibronectin

18. PATHOPHYSIOLOGY Axoplasmic Flow
The flow of axoplasm : orthograde (from retina to lateral geniculate body)
retrograde (lateral geniculate body to retina)
Obstruction to axoplasmic flow may be involved in the pathogenesis of
glaucomatous optic atrophy : primarily? whether mechanical or vascular factors
Ischemia may be the predominant factor : glaucomas at the lower end of IOP scale
More direct mechanical effect of the pressure : with higher IOP
(observed differences in glaucomatous visual field defects)
types I-VI collagens, laminin, and fibronectin

19. Morphology of the Normal Optic Nerve and Head
1. General feature
Vertical oval
Central portion of disc
: depression, the cup & area of pallor (absence of axon)
Neural rim
tissue between the cup & disc margins
location of bulk of the axon
normally orange-red color
because of the associated capillaries

20. Morphology of the Normal Optic Nerve and Head
2. Physiology of Neural Rim
Cup/Disc ratio (C/D)
: the only indirect measure of the amount of neural tissue in the
optic nerve head
: may be misleading
larger diameter of nerve head may be associated with thinner neural rim width and larger cup size, despite a stable number of axon.
The larger disc have larger neural rim area.
Inf.> Sup.>Nasal>Temporal
????????????

21. Morphology of the Normal Optic Nerve and Head
2. Physiology of Neural Rim
Gray crescent
- variation of the normal anatomy
- mistaking the gray crescent for a peripapillary pigmented crescent

22. Morphology of the Normal Optic Nerve and Head
3. Physiologic peripapillary retina
Retinal nerve fiber layer
: 정상적으로 striation이 관찰됨.
Peripapillary pigmentary variations
1. cup
2. neuroretinal rim
3. scleral lip  thin, even, white rim
4. zone beta (chorioscleral crescent)
RPE retraction from the disc margin
: larger zone beta area-to-disc area ratio
associated with an increased risk of the
development of glaucomatous damage
in Pt. with OHT
5. zone alpha
 malposition of the embryonic fold with a double layer or irregularity of RPE
which represents a retraction of retinal pigment
epithelium from the disc margin
often associated with a thinning or absence of choroid next to the disc,
with exposure of the sclera

23. Physiologic Cup Differential diagnosis Symmetry of cup size
Configuration of the cup and neural rim
Appearance of the peripapillary pigmentation and RNFL
Progressive cup enlargement
 highly suggestive of glaucoma
Vertical CDR>>Horizontal CDR
 suspicious glaucomatous change

24. Glaucomatous optic atrophy
* Generalized
large cup
Asymmetric cups
Progressive enlargement of cup
* Focal Rim notching Vertical elongation of cup Splinter Hm. Regional pallor NFL loss
* Other
Exposed lamina cribrosa
Nasal displacement of vessels
Baring of circumlinear vessels
Peripapillary crescent
Arteriolar narrowing

25. Glaucomatous optic atrophy
Disc pattern
Vascular sign
Peripapillary change

26. Glaucomatous optic atrophy
Disc pattern
- Focal atrophy : inferotemporal rim > superotemporal > temporal > nasal (notching)
- Concentric atrophy : less commonly
(cf. temporal unfolding : begins temporally and then progresses circumferentially
toward poles)
- Deepening of the cup : produce vascular overpassing, LDS
- Pallor cup discrepancy : enlargement of the cup may progress ahead of that of
the area of pallor
- Advanced glaucomatous cupping
Saucerization : in which diffuse, shallow cupping extends to the disc margins with
retention of a central pale cup

27. Neuroretinal rim shape
In myopic eye, and disc with age related open angle glaucoma : tends to be shallow, especially temporally
Other type : thinning can be localized, notch or a pit at the disc rim
Slop of wall : steepest at nasally, shallowest temporally
cupping : reversible at young children and infants (elastic capacity), less dramatic in older patient

28. Glaucomatous optic atrophy
Vascular sign
Optic disc hemorrhage
: common feature of glaucomatous damage
Normal tension glaucoma
Inferior quadrant
Preceding RNFL defect, neural rim notch,
glaucomatous VF defect
Tortuosity of retinal vessels
: advanced glaucomatous optic atrophy

29. Glaucomatous optic atrophy
Vascular sign
overpass cupping
baring of the circumlinear vessel
: vessel that pass circumferentially the temporal aspect of the cup
Bared – pass the exposed depths of the cup

30. Glaucomatous optic atrophy
Peripapillary change
Nerve fiber bundle defect : most useful parameter in the early detection of glaucomatous damage
Peripapillary pigment disturbance : glaucomatous optic atrophy , myopia, aging change
Variation in the diameter of retinal arterioles
: Diffuse narrowing of retinal vessel (not specific)
Glaucoma 뿐아니라 다양한 optic atrophy, 연령증가에 ㄸㅏ 라발생하게 된다.

31. Subtypes of glaucoma by optic nerve head appearance
Glaucoma types
Age
& sex
Optic disc size and shape
Optic cupping
Disc hm or rim notching
RNFL defect
VF changes
PPCA changes
IOP
Associated systemic anomalies
High myope
<50, M>F
Large
Concentric sallow, sloping
Thin sup&inf rims N
Dens, focal (sup=inf)
marked
Normal-high -
Focal normal pressure
(focal ischemic)
>60, F>M
Normal
Deep & steep
Frequent disc hm & polar rim loss Y
Dens, focal, near fixation sup>inf +-
Migrain, peripheral vasospasm
Age-related atrophic POAG
>60
Saucerized, shallow, concentric and
‘moth-eaten’
Relative defect with diffuse loss
Frequent; associated with tessellated fundus
Ischemic heart disease+- systemic Hypertension
Juvenile OAG
10~40YRS
POAG
(generalized enlargement)
>40
Diffuse and round;concentric and symmetric
Rare disc hm & rare focal rim notch
Diffuse
High
Subtypes of glaucoma by optic nerve head appearance

32. REFERENCE Shields Textbook of Glaucoma, 6th edition
Becher-Shaffer`s Diagnosis and Therapy of the Glaucomas, 8th edition

33. THANK YOU