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2. Physiology of
Aqueous Humour
&
IOP Regulation
Dr. Akash Keshav Chaurewar
Under the Guidance of
Dr. Shubha Ghonsikar Ma’m

3. OUTLINE
• INTRODUCTION TO AQUEOUS
• COMPOSITION OF AQUEOUS
• FUNCTIONS OF AQUEOUS
• FORMATION OF AQUEOUS
• OUTFLOW OF AQUEOUS
• IOP REGULATION

4. INTRODUCTION
TO
AQUEOUS

5. INTRODUCTION TO AQUEOUS
• Aqueous is Clear , Colorless fluid that fills the anterior and posterior chambers of eye.
• Volume = 0.31ml
• Anterior Chamber 0.25ml
• Posterior Chamber 0.06ml
• Refractive Index = 1.333
• PH = 7.2
• Hyperosmotic
• Rate of Formation = 2-3 microL/min

6. INTRODUCTION TO AQUEOUS…
• Previously thought to be stagnant until 1921 that Siedel proved aqueous indeed
circulating.
• Thermal current in Aqueous humour- due to warmer Iris and cooler Cornea,
rises near Iris and Descends near cornea.
(Clinical Imp.- Keratic Precipitates and Kruckenberg Spindles)

7. Keratic Precipitates Kruckenberg Spindles

8. COMPOSITION
OF
AQUEOUS

9. COMPOSITION OF AQUEOUS
• Difficult to obtain aqueous humour sample, particularly posterior
chamber sample.
• Accordingly, most of our knowledge about composition is based on
animal studies.

10. AQUEOUS
COMPOSITION
Water
99.9 %
Other
0.1%
proteins Glucose Electrolytes
Na+ , Cl- , HCO-
3
Ascorbic ACID
Lactate &
Pyruvate

11. Proteins
• Non-pigmented ciliary epithelium and
capillaries of iris are not permeable to
proteins
• Concentration of protein in aqueous humour
is 0.02% whereas in plasma 7 %
• Smaller proteins(albumin) are present in
higher concentration than larger proteins
(IgM,IgA,IgD)

12. Glucose
• Concentration is relatively Low.
• Most of it is lost to vitreous or taken up by
Lens and Cornea.

13. ELECTROLYTES
• Most of the sodium enters the eye by active
transport and aqueous sodium
concentration is not closely linked to plasma
sodium concentration.
• Chloride is actively transported and depends
on pH and concentration of sodium.
• Bicarbonates are actively transported either
primarily or linked with sodium.

14. ASCORBIC
ACID
• Actively transported into the eye against the
large concentration gradient.
• Protects the eye from oxidative damage
from ultraviolet induced free radicles.

15. LACTATE &
PYRUVATE
• Concentration of both are relatively high.
• Presumably due to glycolytic activity by
avascular tissue such as Lens and Cornea.

16. FUNCTIONS
OF
AQUEOUS

17. FUNCTIONS OF AQUEOUS
• Nutrition to cells of Cornea, Lens and Iris (Oxygen, Glucose, Amino Acids).
• Removes toxic metabolic product(Lactate, CO2) from Cornea, Lens and Iris.
• Provides optically clear media for vision.
• Inflates the globe and maintains the Intra-Ocular Pressure and shape of eyeball.
• Protects against Ultraviolet-induced oxidative damage (High Ascorbic Acid levels).
• Facilitates Cellular and Humoral responses of eye to inflammation and infection.

18. CIRCULATION
OF
AQUEOUS

20. FORMATION
OF
AQUEOUS

21. ANATOMY
OF
CILIARY BODY

23. Composed Of
• Epithelium
• Vessels
• Muscles

24. BLOOD SUPPLY
OF CILIARY
BODY

25. ULTRA-STRUCTURE
OF
CILIARY PROCESS
3
1
2
1. CAPILLARIES
3. STROMA
2. EPITHELIUM

26. Blood-aqueous
barrier
Transport
Across
Blood-
Aqueous
Barrier
Behind
NPCE (Ciliary
channel)
Ciliary Stroma
Ciliary Capillaries
(Connexin 43)
Ultra-
Filtratio
n
(Water
soluble)
Diffusion
(Lipid
soluble)
Active
Secretion
(Large)

27. ULTRAFILTRATION
• Ultrafiltration is process
by which a fluid and its
solutes crosses
semipermeable
membrane under
pressure gradient.

28. ULTRAFILTRATION…
• Blood flows through ciliary process = 150ml/min
• 4% of plasma filtered out from fenestration through capillary wall into interstitial
space.
• Rate of protein leakage is relatively low. However ciliary epithelium is even less
permeable to colloids into posterior chamber.
• Interstitial space colloid concentration 75% of plasma which favors the movement
of water into stroma but retards the movement into posterior chamber

29. ULTRAFILTRATION…
• Few studies postulates that ultrafiltration is main process for formation of
majority of aqueous humour
But
1. It is unlikely that hydrostatic pressure difference between ciliary capillaries and
posterior chamber can overcome the large oncotic pressure differential.
2. Does not explain why active ion transport inhibitors such as ouabain capable of
reducing aqueous humour formation by 70 to 80%.
3. Ultrafiltration moves fluid from capillaries to ciliary stroma but alone is
insufficient to account for volume of fluid moved to posterior chamber.

30. DIFFUSION
• Diffusion is movement of a substance
across a membrane along its
concentration gradient.

31. DIFFUSION
• During passage from Posterior Chamber to Schelmm’s canal , aqueous is in
contact with iris , lens , cornea where diffusion takes place
• As a result , Anterior chamber aqueous resembles plasma more closely than
posterior chamber .
• Aqueous provides oxygen and nutrient with surrounding tissues and removes
metabolic waste by diffusion.

32. ACTIVE SECRETION
• Energy dependent process that selectively moves substance against its
concentration gradient across cell membrane.
• It is postulated that majority of aqueous humour formation depends on ions
being actively secreted into intercellular clefts of non-pigmented ciliary
epithelium beyond tight junctions.
• Performed by Non-pigmented epithelial cells which secretes aqueous 1/3rd of its
Intracellular volume per min.

33. Uptake of NaCl
from Stroma
Passage from
PCE to NPCE via
Gap Junctions
Into post.
Chamber via
NaK-ATPase & Cl-
Channel

34. Blood Aqueous Barrier
• Barrier to movement of substance from plasma to aqueous humour
in posterior chamber
• However tight junctions connecting apical portion of adjacent non-
pigmented epithelium often implicated as actual site of barrier.

36. FACTORS AFFECTING AQUEOUS HUMOUR
FORMATION
• Aueous humour formation averages 2-3 microL/min during daytime in
normal humans.
• Rate of formation is not static but varies and affected by many factors

37. FACTORS AFFECTING AQUEOUS HUMOUR
FORMATION…
1. Diurnal Variations
• Maximum pressure in morning hours and minimum in late nights
• During sleep, rate of formation is approx. ½ the rate upon first
awakening.
• Reduction is result of decreased stimulation of ciliary epithelium
by circulating catecholamines

38. FACTORS AFFECTING AQUEOUS HUMOUR
FORMATION…
2. AGE/SEX
• Male=Female
• Reduction in formation of aqueous after age 60years, decline =
3.2%per decade and overall, 25% in lifetime
• Decrease could be due to ageing of ciliary epithelium.

39. FACTORS AFFECTING AQUEOUS HUMOUR
FORMATION…
3. BLOOD FLOW TO CILIARY BODY
• Modest reduction in ciliary body blood flow , doesn’t have much
effect.
• Only transient effect is seen.
• However profound vasoconstriction does diminish rate of aqueous
flow.

40. FACTORS AFFECTING AQUEOUS HUMOUR
FORMATION…
4. NEURAL CONTROL
• CNS mechanism do influence aqueous secretory rates, but mechanism
is unclear.
• Stimulation of cervical sympathetic chain decreases aqueous
production.
• Sympathetic system may be involved in circadian rhythm of aqueous
production.
• However, U/L Horner’s syndrome does not affect aqueous formation
rate.

41. FACTORS AFFECTING AQUEOUS HUMOUR
FORMATION…
5. HORMONAL EFFECT
• Circulating corticosteroids have significant effect.
• Increased ADH ---- Increase active secretion of Na+ across ciliary
epithelium --- Increased Aqueous production.
• Brubaker and co-workers –
melatonin/progesterone/desmopressin-No effect

42. FACTORS AFFECTING AQUEOUS HUMOUR
FORMATION…
6. Intracellular regulators
• cAMP plays important role in intracellular secretory process
of ciliary body
• cGMP is second messenger for regulation of aqueous
secretion

43. FACTORS AFFECTING AQUEOUS HUMOUR
FORMATION…
7. Hypothermia/Acidosis/ Diabetes Mellitus/ Retinal
Detachment/Choroidal detachment/ Cyclodialysis----Decreases
8. Hyperthermia/Alkalosis---Increases

44. FACTORS AFFECTING AQUEOUS HUMOUR
FORMATION…
DRUGS
Decreases Aqueous
Secretion
Beta 2 Blockers
Timolol
Levobunolol
Carteolol
Betaxolol
Alpha Agonist
Brimonidine
Apraclonidine
CA Inhibitor
Acetazolamide
Brinzolamide
Dorzolamide

45. AQUEOUS HUMOUR
OUTFLOW

46. AQUEOUS
OUTFLOW
CONVENTIONAL
TRABECULAR
MESHWORK
83-96%
NON-
CONVENTIONAL
UVEO-SCLERAL
5-15%
UVEO-VORTEX
(minimal)

47. TRABECULAR MESHWORK OUTFLOW
• TM is interposed
between anterior
chamber and
schelmm’s canal.

48. TRABECULAR MESHWORK OUTFLOW
UVEAL
• Adjacent to AC
• From root of iris to
Schwalbe’s line
• 70microM in diameter
• Randomly oriented
interconnecting bands
• Only few layers thick

49. TRABECULAR MESHWORK OUTFLOW
CORNEO
SCLERAL
• From Schwalbe’s line to
Scleral spur
• 8-14 flattened
perforated parallel
sheets
• 35microM in diameter
• Longitudinal muscle
fibres inserts on
posterior portion

50. TRABECULAR MESHWORK OUTFLOW
JUXTA-
CANALICULAR
• Lines
endothelium of
Schlemm’s canal
• 7microM in
Diameter(Highest
Resistance)

51. Schlemm’s Canal
• Circumferential vascular channel in perilimbal area
• Total circumference = 36mm
• Surrounded by sclera, TM and scleral spur
• Lumen is 50 microM at posterior base and 5-10 microM
at apex But it changes with IOP. Large at low IOP and
small at high IOP

53. Biomechanical Pump
Model
• Powered by transient
increase in IOP caused
by
As pressure increases ,
fluid is forced into one
way collector valves.
Cardiac Cycle
blinking and eye
movements

54. Theory of
Vacuolation
3
1
2
5
4

55. Collector
Channels
Deep scleral
plexus
Intra Scleral
venous plexus
Aqueous
Veins of Asher
Episcleral
Veins
DIRECT
4-6

56. Episcleral Veins
Anterior ciliary
vein
Superior
ophthalmic vein
Cavernous
Sinus
DIRECT
4-6

57. UVEO-
SCLERAL
OUTFLOW

58. UVEO-
VORTEX
OUTFLOW

59. Factors affecting Aqueous outflow
1. AGE – Decreases with age
2. Hormones
• Corticosteroids- Decreases
• Progesterone- Increases
• Thyroxin- Increases

60. Factors affecting outflow..
3. Drugs Increases
Aqueous
Outflow
Trabecular
Outflow increase
Miotics (Pilocarpine)
RHO kinase Inhibitor (Netarsudil)
Uveoscleral
outflow increase
PG Analogues
Latanoprost,Travoprost,Bimatoprost

61. Factors affecting outflow..
3. Drugs
Decreases
• Parasympatholytic
• Ganglionic Blocking
Agents
• Substance P

62. IOP REGULATION

63. IOP REGULATION
• Too high intra ocular pressure is universally accepted as one of the
most important risk factor for optic nerve damage
• Therefore, study of those elements that contribute to intra-ocular
pressure maintenance becomes necessary to understand
pathophysiology of disease.

64. Contributors to IOP
1. Aqueous formation(F)
2. Facility of outflow(C)
3. Episcleral venous pressure(Pv)
These are related to each other by Goldmann Equation:
Po= F/C + Pv

65. FACTORS AFFECTING IOP
FACTORS
EXERTING LONG
TERM INFLUENCE
ON IOP
FACTORS
EXERTING SHORT
TERM INFLUENCE
ON IOP

66. FACTORS EXERTING LONG TERM INFLUENCE ON
IOP
1. AGE
• IOP increases with age
• Children have lower pressure than normal population
2. GENDER
• Between 20-40 years IOP is equal in Males and Females
• In older age group IOP is more in women

67. FACTORS EXERTING LONG TERM INFLUENCE ON
IOP
3. RACE
• Blacks have higher IOP than Whites.
4. Genetics
• Some induvial may be genetically predisposed to higher IOPs.
• Higher in individuals who have relatives with open angle
glaucoma.

68. FACTORS EXERTING SHORT TERM INFLUENCE
ON IOP
1. DIURNAL
• IOP shows cyclic fluctuations throughout the day
• Ranges from 3-6 mm Of Mercury
• Higher IOP associated with greater fluctuations and diurnal
fluctuation of greater than 10mm Of Mercury is suggestive of
glaucoma

69. FACTORS EXERTING SHORT TERM INFLUENCE
ON IOP…
2. Postural
• IOP increases when changing posture-- Sitting < Supine < Prone
• Posture has greater influence on eyes with glaucoma.
• Patients with systemic hypertension have greater IOP increase
after 15min in supine.

70. FACTORS EXERTING SHORT TERM INFLUENCE
ON IOP…
3. Exercise
• Depends on nature of exercise performed.
• Running / Bicycling – Lowers IOP
• Straining as associated with Valsalva, playing wind instrument—
Elevates the IOP

71. FACTORS EXERTING SHORT TERM INFLUENCE
ON IOP…
4. Ocular Conditions
• Blinking raises IOP by 10 mm Of Mercury, while hard squeezing up
to 90 mm Of Mercury
• Myopes have higher IOP (IOP corelates with axial length)
• Inflammation decreases IOP unless aqueous humor outflow
affected more than inflow
• Surgery decreases IOP unless aqueous humor outflow affected
more than inflow

72. FACTORS EXERTING SHORT TERM INFLUENCE
ON IOP…
5. Systemic Conditions
• Systemic Hypertension – Increases IOP
• Obesity– Increases IOP
• Hyperthyroidism – Decreases IOP
• Hypothyroidism – Increases IOP
• Diabetic patients have higher IOP

73. FACTORS EXERTING SHORT TERM INFLUENCE
ON IOP…
6. Environmental Conditions
• Higher IOP in winter months
(attributed to change in number of hours of light and alteration of
atmospheric pressure)
• Reduced gravity causes sudden marked increase in IOP.

74. FACTORS EXERTING
SHORT TERM
INFLUENCE ON IOP…
7. Food and Drugs

75. FACTORS AFFECTING AQUEOUS HUMOUR
FORMATION…
Anti-Glaucoma Drugs
Decreases Aqueous
Secretion
Beta 2 Blockers
Timolol
Levobunolol
Carteolol
Betaxolol
Alpha Agonist
Brimonidine
Apraclonidine
CA Inhibitor
Acetazolamide
Brinzolamide
Dorzolamide
Increases Aqueous
Outflow
Trabecular Outflow
increase
Miotics (Pilocarpine)
RHO kinase Inhibitor
(Netarsudil)
Uveoscleral outflow
increase
PG Analogues
Latanoprost
Travoprost
Bimatoprost

76. REFERENCES
• BECKER-SHAFFER'S DIAGNOSIS AND THERAPY OF
THE GLAUCOMAS
• ANATOMY AND PHYSIOLOGY OF EYE- A.K.
KHURANA

78. Mentors
• Dr. Archana Vare
Professor & HOD
Dept. Of Ophthalmology
GMC Aurangabad
• Dr. Shubha Ghonsikar
Professor(Academic)
Department Of Ophthalmology
GMC Aurangabad.
Special Thanks to all other faculty, Senior Residents , Colleagues who help in in understanding
the topic in simple way.