Aqueous humor dynamics, epidemiology

1. AQUEOUS HUMOR
DYNAMICS,
EPIDEMIOLOGY AND
PATHOLOGICAL BASIS
Bipin Bista
2nd year Resident
National medical College
& Teaching Hospital
Ophthalmology

2. ANATOMICAL OVERVIEW
Ciliary body – site of
aqueous humour dynamics
Trabecular meshwork –
principal site of aqueous
humour outflow.
Scleral sulcus – indentation
which has sharp posterior
margin scleral spur & a
sloping anterior wall that
extends to the peripheral
cornea.
 TM bridges the sulcus and
converts it into tube,
Schlemm canal.
 Schwalbe line : Ridge
created by meshwork

3. CILIARY BODY
It attaches to scleral spur and makes potential space , supraciliary
space between itself and the sclera.
Ciliary body has the shape of a rt. Triangle, and the ciliary processes
which occupy the innermost anterior most portion of this structure :
Pars Plicata.
Ciliary processes consist of 70-80 radial ridges.
Posterior portion of CB, has a flatter surface and joins choroid at the
ora serrata.

4. BIOLOGY OF AQUEOUS
HUMOR INFLOW
1. Production
2. Resistance of aqueous flow
3. Episcleral venous pressure.

5. CELLULAR ORGANISATION
OF THE CILIARY BODY AND
THE CILIARY PROCESSES
1. Ciliary body muscle
2. Ciliary body vessels
3. Ciliary processes

6. CILIARY BODY MUSCLE
Longitudinal and circular fibers.
Attach the ciliary body to the limbus at the scleral spur. Portion of
muscle runs posteriorly to insert into the suprachoroidal lamina.
Circular fibers occupy the anterior and inner portions of the ciliary
body and run parallel to the limbus.

7. VESSELS
Collateral circulation.
Episcleral circle : anterior ciliary arteries and episcleral plexus
anastomose.
Intramuscular circle : ACA with PCA in the ciliary muscle.
Major arterial circle : Iris root anterior to Intramuscular circle.

8. CILIARY PROCESSES
1. Capillaries : occupy the center,
2. Stroma : capillaries, composed of MPS,proteins, and plasma
solutes, Collagen Type III fibrils.
3. Epithelium
Pigmented : melanin granules.
Non pigmented : Glycoproteins , faces aq. Humor.
Zonula occludens in NPE : effective barrier to intermediate and high
molecular wt. substance.

9. AUTONOMIC INNERVATION
Sympathetic and Parasympathetic.
Sympathetic : Superior cervical ganglion gets distributed to ciliary
vessels, as epithelium is not innervated, catecholamine later diffuse
to adrenergic receptors on the epithelium.
Parasympathetic : E-W Nucleus to innervate ciliary muscles.
Acetylcholine stimulates cholinergic receptors. Ciliary contraction
thus leads to reduction in resistance to conventional aqueous humor
outflow.

10. MOLECULAR MECHANISM
Anterior portion of ciliary epithelium has increased basal and lateral
interdigitations, mitochondria and RER ; numerous fenestrations;
thinner layer of stroma and increase in cell organelle and gap
junctions between pigmented and non-pigmented epithelia.
Aqueous humor is derived from plasma within capillary network of
ciliary processes.
Temperature gradient also makes a conventional flow.

11. MOLECULAR MECHANISM
Processes involved :
1. Diffusion : lipid soluble subs. are transported through lipid
portions of membrane proportional to concentration gradient
across the membrane.
2. Ultrafiltration : water and water soluble subs. flow through
‘micropores’ in the protein of cell membrane in response to
osmotic gradient.
3. Secretion : charged particles are transported by active transport
whereas proteins are transported in the membrane with expense of
Adenosine Triphosphate (ATP) hydrolysis.

12. BASIC PHYSIOLOGIC
PROCESS
1. Accumulation of Plasma Reservoir : pass easily through stroma and
between epithelial cells before accumulating behind the tight
junctions of the non-pigmented epithelium. This movement takes
place by diffusion and ultrafiltration.
2. Transport across Blood-Aqueous Barrier : active secretion takes
place between cations, anions, and other substances across blood-
aqueous barrier formed by the tight junctions between the non-
pigmented epithelium.
Aqueous humor secretion is mediated by transferring Nacl from
Ciliary body stroma by 3 steps :
>Uptake of Nacl from Stroma to Pigment Epithelium by Electroneutral
transporters.
>By passage of Nacl from pigmented to non-pigmented cells through
gap junctions

13. BASIC PHYSIOLOGIC
PROCESS
3) Osmotic Flow : This
phenomenon across the ciliary
epithelium supports the
movement of other plasma
constituents.
Na+ is the driving cationic force
for this flow.

14. GENERAL CHARACTERISTICS
OF AQUEOUS HUMORSlightly hypertonic
Acidic
Marked excess of Ascorbate
Marked deficit of protein
Slight excess of chlorine , Lactic acid
Slight deficit of Sodium, Bicarbonate, Carbondioxide and Glucose
AA
Sodium Hyaluronate
Norepinephrine
Coagulation properties
Tissue plasminogen activator.
Latent collagenase activity.

15. MOLECULAR MECHANISM OF
AQUEOUS HUMOR OUTFLOW
RESISTANCE
Perfusion studies
Morphology changes
Extracellular matrix
Glucocorticoid mechanisms
Cellular and cytoskeletal mechanisms

16. PERFUSION STUDIES
Trabecular meshwork is a three dimensional set of crossing collagen
fibrils, which responds to displacement in Schlemm canal.
TM tension causes increased outflow d/t widening of schlemm canal
and increase in canal inner wall porosity.
Trabeculectomy eliminates only half the measured aqueous flow
resistance.

17. MORPHOLOGY CHANGES
Change in shape : wedge (long) to rhomboidal.
Trabecular beams thickens, trabecular denuding d/t decrease in
endothelial cellularity.
Decrease in giant vacuoles and cell count in schlemm canal.
Significant increase in electron dense plaques that adhere to the
sheaths of the elastic fibers and their connections to the inner wall
endothelium. (COAG)
Subendothelial schlemm canal will have increase in fine fibrillar
material. (steroid IG)

18. EXTRACELLULAR MATRIX
Fibrillar and non-fibrillar collagens, elastin-containing microfibrils,
matricellular and structural organizing proteins, GAG, PAG.
Fibrinolysis is favoured as a protective mechanism against
obstruction from fibrin and platelets.
TPA may also influence resistance by altering the glycoprotein
content.

19. GLUCOCORTICOID
MECHANISMS
Inhibits the synthesis of endogenous prostaglandins which are
supposed to increase IOP in high doses but reduce ocular tension in
moderate to low concentrations.
Glucocorticoid may influence the outflow facility by a direct effect on
the ECM metabolism and the cytoskeleton.

20. CELLULAR AND
CYTOSKELETAL
MECHANISMS
Trabecular endothelial cells have potentiality to phagocytize and
degrade foreign bodies.
Decreased functioning of TM is due to progressive accumulation of
damaged proteins with age due to oxidative stress and to decline in
cellular proteolytic machineries.
Sulfhydryl groups as well as glutathione peroxidase catalyses reaction
between glutathione and hydrogen peroxidase, thereby detoxifying
the latter and presumably protecting the meshwork from its harmful
effects

21. EPIDEMIOLOGY OF
GLAUCOMA

22. 67 million persons are affected by glaucoma, of whom 10% or 6.6
million are estimated to be blind.
Leading cause of irreversible blindness worldwide
Second to cataract for the leading cause of worldwide blindness.
Normal tension glaucoma is far more common than expected.
Prevalence of COAG is higher among Blacks than in Whites.
COAG accounts 85 to 90% in whereas Angle closure is higher in some
Asian populations(Mongolia)
Incidence in COAG in Blacks increases at an earlier age than in Whites
in fourth and fifth decades.

23. NATURAL HISTORY OF
GLAUCOMA
Three phases
1. Latency phase
2. Detectable pre-clinical phase
3. Clinical phase

24. ETIOLOGY
Disturbance in the delicate balance of vascular, connective tissue,
mechanical, and neural component that keep the optic nerve healthy
and functioning.

25. DETECTION THRESHOLD
Point at which glaucomatous optic nerve damage can be accurately
detected by diagnostic testing.
Visual field can be considerable before this stage, as 40% of axons
can be lost before white-on-white Humphrey perimetry will show an
abnormality.
For careful observation, Stereoscopic Disc Photography of Optic Nerve
can be done for earlier diagnosis and earlier detection of progression.

26. RISK FACTORS
Demographic Risk Factors
Race : Black Africans and their
descendants, Hispanics, White,
Chinese and Asian Indians
Age : Increases significantly with
age. Highest prevalence above the
age of 80.
Gender : No consistent association.
Family history : Two to fourfold
increased risk of having glaucoma to
themselves. Counselling is
important. Association of two genes
: myocilin and optineurin

27. OCULAR RISK FACTORS FOR
POAG
INTRAOCULAR PRESSURE
Important role .
In patient with asymmetric IOP, visual field analysis is more severe in
the eye with greater IOP. Proper IOP lowering has decreased the rate
of visual field loss.
Despite these facts, large degree of people with and without glaucoma
makes it a poor screening tool.

28. OCULAR NERVE
PARAMETERS
Cup disc , rim area, narrowest rim width do a poor job of identifying
glaucomatous patients.
Confocal scanning laser microscopy with the HRT II (Heidelberg
retinal tomograph) and SD OCT (Spectral Domain OCT) are able to
differentiate normal and Glaucomatous eyes with sensitivity and
specificity exceeding 70% and 80 to 90% respectively .

29. HRT

30. NERVE FIBER LAYER
Characteristic : Thinning of the nerve fiber layer (NFL) as a result of
ganglion cell death. Gives us the clue but not the reliable
distinguishing factor .
Measured by Optical coherent topography(OCT) and scanning laser
polarimetry(GDx).

32. MYOPIA
Two to four folds higher association for Myopes to have POAG.
Higher with higher degrees of Myopia.
Longer axial lengths and flatter corneas were also associated.

33. PERIPAPILLARY ATROPHY
Set to be found in more than half of glaucomatous patients than in
comparison to Ocular hypertensives.

34. CENTRAL CORNEAL
THICKNESS
Independent risk factors for progression to glaucoma
Yet a conflicting evidence whether thin cornea is a risk factor

35. SYSTEMIC RISK
FACTORS FOR POAG

36. DIABETES MELLITUS
Appears to be higher in diabetic due to important confounder of the
association between diabetes and glaucoma because persons with
diabetes appears to have slightly higher IOP.

37. HYPERTENSION
Higher systolic and higher diastolic are associated with increased IOP.
Insufficient perfusion of the optic nerve may contribute to glaucoma .
Significant increase in the rate of POAG has been found for diastolic
perfusion pressure under 50 with greater than six folds odds if below
30.

38. RISK FACTORS FOR
PACG

39. DEMOGRAPHIC RISK
FACTORS
RACE
Higher Eskimos and East Asians in comparisons to black and whites.
Chinese residents have higher susceptibility than Indians nearly more
than half preponderance.

40. GENDER
Not significant.
Female are more prone for getting attacks of AAC in different variety
of ethnic groups.

41. FAMILY HISTORY
Increased risk in family members with patient of PACG.

42. OCULAR RISK
FACTORS FOR PACG

43. ANTERIOR CHAMBER DEPTH
PACG is associated with eyes with depth 0.3-1.0 mm shallower than
normal eyes .
This may partially account for gender, age, and racial distribution of
AAC and PACG.

44. LIMBAL ANTERIOR CHAMBER
DEPTH
Van Herick method
Narrower anterior chamber angles as well as smaller angle opening
distances in AAC.

45. AXIAL LENGTH
Axial length 0.5-1.0 mm shorter than normal.
Hyperopia greater than 2 D had thrice more preponderance than
myopes .

46. LENS THICKNESS
Lens 0.2 – 0.6 mm thicker than controls .
Thickness increases with age : important explanation for progressive
shallowing of anterior chamber and increased prevalence of PACG.

47. RADIUS OF CORNEAL
CURVATURE
Smaller radius leads to more crowded chamber which is associated
with higher risk of angle closure.

48. MECHANISMS OF
GLAUCOMA

49. PATHOLOGY
Three major theories regarding glaucoma :
1. Mechanical
2. Vascular
3. Biochemical

50. MECHANICAL
Trabecular meshwork
Cytoskeletal changes
Extracellular matrix

51. Increased
IOP
Increased
pressure on
bulbar wall
Caving of
lamina
Axonal
damage
Glaucomatous
optic
neuropathy

52. VASCULAR THEORY
Optic nerve head is dependent on the following factors :
• Resistance to blood flow, Blood pressure, IOP, Blood Viscosity.
Blood flow = Perfusion pressure/Resistance to flow.
Perfusion pressure = Mean arterial BP – IOP.
Mean arterial BP = Diastolic BP + 1/3 (Systolic BP – Diastolic BP)
Deficient auto regulatory mechanisms leads to ischemia & contribute
to development of glaucomatous patients.
Endothelin-1
Migraine and peripheral vascular abnormality.

54. BIOCHEMICAL THEORY
Excitotoxic – glutamate and aspartate which leads to neural excitation
in their normal state and cell toxicity when they are excess.
Apoptic cell death of RGCs , hypoxic conditions of retinal cells are
known to release Glutamate.
Entry of extracellular Ca++ and Na + into the neurons, finally leading
to apoptosis and cell death.
Excess production of NO by astrocytes and microglia in Optic Nerve
Head.
These highly reactive free radicals are capable of causing massive
destruction of cell components and macromolecules leading to
apoptosis.

55. THANK YOU FOR
YOUR ATTENTION
Refrence from:
1.Glaucoma – Shield
Textbook of Glaucoma
2.Recent advances –
Curbside Consultation in
Glaucoma : Steven J. Gedde
3.Myron yanoff and jay s
duker4th edition