ophthalmology residency program

1. Ocular physiology
Dr.mohammed muneer

2. agenda
1. Lacrimal appartus
2. Tear film
3. Eyelids
4. Aqueous humour and Iop
5. vitreous

3. Lacrimal gland
• The lacrimal gland is comprised of acini that drain into progressively larger tubules or ducts that
coalesce into one or more excretory ducts
• In cross- section an acinus contains a ring of pyramidal-shaped acinar cells that are joined at the
junction of the apical and lateral membranes by tight junctions. The tight junctions polarize the
cells and ensure unidirectional secretion of electrolytes, water, and protein
• The lacrimal gland also contains a small population of lymphocytes, plasma cells, mast cells, and
macrophages. The plasma cells express immunoglobulins, especially IgA.

4. Lacrimal gland innervation
• The lacrimal branch of the trigeminal nerves carries sensory
stimuli from the lacrimal gland and forms the afferent innervation
of the gland.
• The efferent innervation of the gland consists of
• parasympathetic ( predominate )
• sympathetic nerves.

5. • Parasympathetic nerves release the neurotransmitters Ach and VIP
that activate receptors on the myoepithelial, acinar, and duct
cells.
• Sympathetic nerves release the neurotransmitters norepinephrine
and neuropeptide Y (NPY). Norepinephrine activates α1D-
adrenergic and β-adrenergic receptors located on acinar cells.

6. Excretory system
• Puncta
• Canaliculae
• Lacrimal sac
• Nasolacrimal duct

7. TEAR FILM
• The tear film overlays the ocular surface
• the tear film is the first refractive surface of the eye
• For mucous and aqueous layers, secretion is regulated by neural reflexes.
Sensory nerves in cornea and conjunctiva are activated by mechanical, chemical, and
thermal stimuli that in turn activate the efferent parasympathetic and sympathetic nerves,
which innervate the lacrimal gland and the conjunctival goblet cells, and cause mucous and fluid
secretion.
• For the lipid layer, the blink itself regulates release of pre-secreted meibomian gland lipids
stored in the meibomian gland duct
• Tear secretion is balanced by drainage and evaporation.
Drainage of tears can be regulated by neural reflexes from the ocular surface that cause
vasodilation and vasoconstriction of the cavernous sinus blood supply of the drainage duct
• Evaporation depends on the amount of time the tear film is exposed between blinks and
temperature, humidity, and wind speed.

8. Tear production
• Basic secretion
to keep the cornea moist and nourished
to lubricate the eye and keep it clear of dust
• Reflex secretion
to wash out any irritant that come incontact with the eye
Can occur with bright light
Hot and pepper stimuli to tongue and mouth.

9. 1. Parasympathetic and sympathetic nerves release their neurotransmitters, which
interact with specic G-protein–linked receptors in the lacrimal glands, cornea, and
conjunctiva;
2. these receptors then activate their respective signaling pathways. There are 2 main
signaling pathways:
i. Ca2+/protein kinase C–dependent pathway
ii. cyclic adenosine monophosphate (cAMP)–dependent pathway.
In most tissues, the Ca2+/protein kinase C–dependent pathway is activated by
acetylcholine and, except in the main lacrimal gland, by norepinephrine.
Acetylcholine, released from parasympathetic nerves, activates muscarinic
receptors;
norepinephrine, released from sympathetic nerves, activates α1-adrenergic
receptors.
 Stimulation of muscarinic and α1-adrenergic receptors activates a guanine nucleotide-
binding protein (G protein) which then turns on phospholipase C.

10.  Phospholipase C breaks down a membrane lipid—phosphatidylinositol
4,5,- bisphosphate—into inositol 1,4,5-trisphosphate (IP3) and
diacylglycerol. IP3 releases intracellular Ca2+.
The depletion of Ca2+ from intracellular stores causes the influx of
extracellular Ca2+ to refill these stores.
Ca2+ (either by itself or by activating Ca2+-calmodulin–dependent
protein kinases) stimulates protein and/or electrolyte and water secretion.
 The increase in diacylglycerol activates protein kinase C, a family of 11
isozymes that stimulate protein and/or electrolyte and water secretion.

11. • The cAMP-dependent pathway is activated by VIP and norepinephrine.
VIP, released from parasympathetic nerves, interacts with VIP receptors;
norepinephrine, released from sympathetic nerves, activates β-adrenergic
receptors.
• Stimulation of VIP or β-adrenergic receptors activates G protein Gsα subtypes,
which in turn stimulate adenylyl cyclase.
• Activation of adenylyl cyclase produces cAMP from ATP.
• cAMP activates cAMP-dependent protein kinases to stimulate protein and/or
electrolyte and water secretion.
The action of cAMP is terminated when it is broken down by cAMP-dependent
phosphodiesterases.

12. • Another mechanism for stimulating tear secretion (in addition to nerves) is peptide and
steroid hormones.
• Peptide hormones, including α-melanocyte-stimulating hormone and adrenocorticotropic
hormone (ACTH), stimulate protein secretion from the main lacrimal gland.
These hormones activate the cAMP-dependent pathway described for VIP and β-
adrenergic receptors.
• The steroid hormones, specically the androgens, stimulate secretion of sIgA from the
main lacrimal gland and lipid secretion from the meibomian glands.
Androgens diffuse into the nucleus and bind to receptors, which are members of the
steroid/thyroid hormone/retinoic acid family of transcription factors.
The monomeric-activated androgen-receptor complex then associates with the response
elements in the regulating region of the target gene (eg, for sIgA secretion, the target is
the secretory component gene).
• This association promotes dimerization of 2 androgen-receptor complexes, a process that
then activates gene transcription and eventually protein synthesis.

13. • Eyelid movement is important in tear-film renewal, distribution, turnover, and drainage.
As the eyelids close in a complete blink, the superior and inferior fornices are
compressed by the force of the preseptal muscles, and the eyelids move toward each
other, with the upper eyelid moving over the longer distance and exerting force on the
globe. This force clears the anterior surface of debris and any insoluble mucin and
expresses secretions from meibomian glands.
The lower eyelid moves horizontally in a nasal direction and pushes tear fluid and
debris toward the superior and inferior puncta.
When the eyelids are opened, the tear film is redistributed. The upper eyelid pulls
the aqueous phase of the tear film by capillary action. The lipid layer spreads as fast as
the eyelids move, so that no area of the tear film is left uncovered by lipid.
The lipid layer increases tear-film thickness and stabilizes the tear film. Polar
lipids, present in the meibomian secretions, concentrate at the lipid–water interface and
enhance the stability of the lipid layer.

14. FORMATION OF PREOCULAR TEAR FILM
• Wettability of a surface- determined by the tendency of liquids to spread
on it.
• Cornea is a hydrophobic surface
conjunctiva forms a thin layer of mucus , On this, aqueous component
spreads spontaneously.
• Then finally, superficial lipid layer spreads contributing to its stability &
retarding evaporation between blinks.

15. DISPLACEMENT PHENONMENON
• Surface of cornea is covered by a film possessing certain stability,
compressibility & elasticity, which is unaffected by gravity.
• Displacement phenomenon
(ie particles in the tear film move up or down the cornea as an integral whole,
all particles on the surface including those lying far away from margin of the
lid)
is possible due to thin monomolecular layer on the surface of cornea.

16. EVAPORATION FROM TEAR FILM
• Retardation of evaporation of water is because of lipid layer made
of cholesterol esters & wax
• evaporation is about 10% of production rate, which accounts to
abt 0.12microlt/min
( tear production rate is 1.2 microlt/min)

17. DRYING AND BREAK UP OF TEAR FILM
• TEAR FILM BREAK UP…
• Precorneal tear film has a short lived stability.
• If blinking is prevented for 15-40 sec, tear film ruptures & dry spots appear on
cornea
• HOLLY & LEMPS MECHANISM OF TEAR FILM BREAK UP..
1. 1st – film thins uniformly by evaporation
2. Aft a critical thickness, lipid molecules begin to be attracted by mucin layer.
3. When mucin layer on epithelium is sufficiently contaminated by lipid migrating down
from top surface of the film, mucin becomes hydrophobic & tear film ruptures
4. Blinking can repair the rupture by restoring thick aqueous layer.
5. Dry spot is localised non-wetting, more on temporal quadrant

18. Elimination of tears
• Drainage of lacrimal fluid from lacus lacrimalis into naso lacrimal
duct
• Lacrimal pump mechanism… constituted by fibres of preseptal
portion of orbicularis

19. On eyelid closing 3 events occur concomitantly
• 1.Contraction of pretarsal fibres of orbicularis, compresses ampulla & shortens
canaliculi- this movement propels tear fluid present in ampulla& horizontal
part of canaliculi towards lacrimal sac.
• 2. Contraction of preseptal fibres of orbicularis pulls lac fascia & lateral wall
of lac sac laterally, hence opening normally closed lac sac- produces relative
negative pressure & draws tears from canaliculi into sac.
• 3. With the increasing tension on the lacrimal fascia (which opens the sac),
inferior portion closes more tightly, preventing aspiration of air from nose.

20. • When eyelids open,
tone of orbicularis muscle decreases & following events occur
concomitantly…
1. Relaxation of pretarsal fibers of orbicularis– canuliculi to expand
& reopen. Expansion of canaliculi & ampulla draws in lac fluid
through puncti from lac lake.
2. Relaxation of portion of preseptal fibres (horners muscle) allows
lac sac to collapse. This collapse of lac sac expels fluid
downwards into nasolacrimal duct.

21. drainage of lacrimal fluid from naso lacrimal
duct into nasal cavity
• Once fluid enters upper end of nld, influence of eyelid movements
on its further downward flow ends.
• Factors which influence flow of tears along nld are-
1. Gravity in downward movement.
2. Air current movement within the nose- induce negative pr within
nld & thus draws fluid down the potential lumen of duct into
nose.

24. EYELIDS

25. Functions of the Eyelid
1. Reconstitution of the tear film.
2. Maintain the integrity of the corneal surface.
3. Maintain the proper position of the globe within the orbital
contents.
4. Regulate the amount of light allowed to enter the eye.
5. Provide protection from airborne particles.
6. Coverage of the eye during sleep.

26. EYELID MOVEMENT

27. Lid opening
Upper lid
elevators
Levator
palpebrae m
Frontalis m Muller m
•Lower lid
retractors
Lid closure
Orbicularis
oculi m

28. •Lower lid retractors
• NO true counterpart of the levator is present, and therefore, the
opening movement depends upon several factors:
• 1. Traction exerted by the attachment of the inferior rectus to
the inferior tarsus.
• 2. Inferior palpebral muscle (identical to Muller’s muscle in the
upper lid).

29. blinking
voluntary
Winking
involuntary
Reflex spontaneous

30. BELL’S PHENOMENON
• It is a highly coordinated reflex between the facial and oculomotor nuclei,
whereby on closure of the eyelids, the eyeball is rotated upward and
outward.
• This is a protective mechanism
• Bell’s phenomenon is NOT present in 10% of otherwise healthy persons.

31. Aqueous and Vitreous Humors

32. ANTERIOR CHAMBER
• The anterior chamber is bounded
• anteriorly by the corneal endothelium.
• peripherally by the trabecular meshwork, a portion of the ciliary body, and the
iris root.
• posteriorly by the anterior iris surface and the pupillary area of the anterior
lens.

33. ANTERIOR CHAMBER ANGLE STRUCTURES
• Scleral Spur
The posterior portion of the scleral spur is the attachment site for the
tendon of the longitudinal ciliary muscle fibers, whereas many of the trabecular
meshwork sheets attach to the spur’s anterior aspect
• Trabecular Meshwork
has a triangular shape, with its apex at the termination of Descemet’s
membrane (Schwalbe’s line) and its base at the scleral spur. The inner face
borders the anterior chamber, and the outer side lies against corneal stroma,
sclera, and Schlemm’s canal

34. Canal of Schlemm
• The external wall of the canal lies against the limbal sclera, and the internal
wall lies against the juxtacanalicular connective tissue and the scleral spur
• The lumen is lined with endothelial cells, many of which are joined by zonula
occludens.The endothelial cells have an incomplete basement membrane.
• The continuous endothelial lining with cells joined by tight junctions make
the canal similar to blood vessels
• the discontinuous basement membrane make it similar to lymph channels.
• The tight junctions of the inner wall restrict flow into the canal between the
lateral walls of the cells. Pores and pinocytic vesicles in the cell membrane
may be an avenue for passage of aqueous humor

35. Juxtacanalicular Connective Tissue
• The region separating the endothelial cell lining of the canal from
the trabecular meshwork is called the juxta- canalicular
• The cells of this region have processes occasionally joined by
adhering and gap junctions. The cells also form similar
connections with the endothelium of the inner wall of Schlemm’s
canal.

36. AQUEOUS HUMOR
• Clear
• colorless fluid that fills the anterior and posterior chambers of the
eye.

37. Physiological properties
• Volume 0.2ml ant chamber
0.06 ml post chamber
• Refractive index 1.333
• PH 7.2
• Hyper osmotic
• Rate of formation 1.5 to 4.5 µl/min

38. Composition
• Water constitutes 99.9% of Normal Aqueous
• Proteins (5-16mg/100ml) concentration in Aqueous is less than 1% of its plasma
concentration
• Glucose – 75% of the plasma concentration.
• Electrolytes: –
Na+ similar in plasma and aqueous
Bicarbonate ion Concentration in PC & in AC
Cl ion concentration than plasma
phosphate concentration than plasma
• Ascorbic acid concentration is very high in aqueous.
• Various components of the coagulation and anticoagulation pathways may be present
in human aqueous humor.

39. FUNCTIONS
• the aqueous humor has several important functions:
1. It provides nutrients (eg, glucose and amino acids) to support the function
of tissues of the anterior segment, such as the avascular lens, cornea, and
trabecular meshwork.
2. It removes metabolic waste products (eg, lactic acid, pyruvic acid) from
these tissues.
3. It helps maintain appropriate intraocular pressure (IOP).
4. Because the aqueous humor is devoid of blood cells and of more than 99% of
the plasma proteins, it provides an optically clear medium for the
transmission of light along the visual path.

40. The aqueous humor formation
• The aqueous humor is secreted by the ciliary epithelium at a flow rate of 2–3 μL/min.
• The ciliary epithelium is a bilayer of polarized epithelial cells lining the surface of the
ciliary body; the 2 cell layers are the
1. NPE, which faces the aqueous humor through the cells’ basal plasma membrane,
2. the PE, which faces the stroma, also through the cells’ basal plasma membrane.
• Therefore, the apical plasma membranes of NPE and PE cells appose each other,
establishing cell-to-cell communication through numerous gap junctions.
• Of the 2 cell layers forming the ciliary epithelium, the NPE cells are those that
establish the blood–aqueous barrier by the presence of tight junctions proximal to the
apical plasma membrane, thereby preventing the free passage of plasma proteins and
other macromolecules from the stroma into the posterior chamber.
• In contrast, the PE cell layer is considered a leaky epithelium because it allows solutes
to move through the intercellular space between the PE cells

41. AQUEOUS HUMOR
• Three physiologic processes contribute to the formation and chemical
composition of the aqueous humor:
• diffusion, 10%
• ultrafiltration 20%
• active secretion 70%

42. 1- Difusion
• lipid-soluble substances are transported through the lipid portions
of the cell membrane proportional to a concentration gradient
across the membrane

43. 2- ultra filtration
• water and water-soluble substances, limited by size and charge,
flow through theoretical micropores in the cell membrane in
response to an osmotic gradient or hydrostatic pressure
• influenced by
1. intraocular pressure,
2. blood pressure in the ciliary capillaries,
3. plasma oncotic pressure

44. • Diffusion and ultrafiltration are both passive mechanisms, with
lipid- and water-soluble substances from the capillary core
traversing the stroma and passing between pigmented epithelial
cells and limited by the tight junctions of the non-pigmented
epithelial cells

45. 3- active secretion
• water-soluble substances of larger size or greater charge are actively
transported across the cell membrane, requiring the expenditure of
energy;
• Na-K ATPase and glycolytic enzymes are present in nonpigmented epithelial
cells.
• Active transport is decreased by hypoxia, hypothermia, and any inhibitor of
active metabolism.
• Active transport accounts for the majority of aqueous production.
• MEDIATED BY GLOBULAR PROTEINS IN MEMBRANE

46. • Active secretion is essentially pressure-insensitive at near-
physiologic IOP. However, the ultrafiltration component of aqueous
humor formation is sensitive to changes in IOP, decreasing with
increasing IOP.
• This phenomenon is quantifiable and is termed facility of inflow,
or pseudofacility, the latter because a pressure-induced decrease
in inflow will appear as an increase in outflow when techniques
such as tonography and constant-pressure perfusion are used to
measure outflow facility.

47. STEPS OF AQUEOUS FORMATION
Formation of Stromal
pole
Active transport of
stromal filterate
PASSIVE TRANSPORT
ACROSS NON
PIGMENTED CILIARY
EPITHELIUM

48. Formation of Stromal pole
Substances
pass cap. Of
C.P.
Across stroma
Behind tight
junction of
NPE

49. • Active transport across non pigmented epithelium result in
osmotic and electical gradient
• Sodium is primarily responsible for movement of water into
posterior chamber and its secretion is major factor in formation of
aqueous

50. ACTIVE TRANSPORT OF STROMAL FILTRATES
• The tight junction between non pigmented epithelial cells creat
part of blood aqueous barrier
• Substances actively transported are
• 1)NA
• 2)chloride
• 3)potassium
• 3)ascorbic acid
• 4)amino acid n bicarbonate

51. Control of aqueous formation
 ADRENERGIC INNERVATION
• ciliary epithelium does not show nerve supply , but vessels have
nerve supply
• majority of receptors in ciliary body are α2 & β2 receptors
• stimulation of α 2 receptor lower aqueous humour production
through inhibition of adenylate cyclase
• stimulation of β 2 receptor leads to increase in production by
stimulation of adenylate cyclase
• α 2 AGONIST LIKE CLONIDINE AND β2 ANTAGONIST LIKE TIMOLOL
DECREASES AQUEOUS PRODUCTION

52. Blood–aqueous Barrier
• The blood–aqueous barrier is a functional concept, rather than a discrete
structure, invoked to explain the degree to which various solutes are relatively
restricted in travel from the ocular vasculature into the aqueous humor.
• The capillaries of the ciliary processes and choroid are fenestrated, but the
interdigitating surfaces of the retinal pigment epithelia and the ciliary process
non-pigmented epithelia respectively are joined to each other by tight junctions
(zonulae occludens) and constitute an effective barrier to intermediate- and
high-molecular-weight substances , such as proteins.
• The endothelia of the inner wall of Schlemm's canal are similarly joined,
preventing retrograde movement of solutes and fluid from the canal lumen into
the TM and anterior chamber.
• Tight junctions are also present in the iridial vascular endothelium as well as
between the iris epithelia.

53. • For present purposes, one may say that the blood–aqueous barrier
comprises the tight junctions of the ciliary process non-pigmented
epithelium, the inner wall endothelium of Schlemm's canal, and
the iris vasculature, and the outward-directed active transport
systems of the ciliary processes.
• A more universal concept of the blood–aqueous barrier must deal
with the movement of smaller molecules, lipid-soluble substances,
and water into the eye

54. • With disease-, drug, or trauma-induced breakdown of the blood–aqueous
barrier , plasma components enter the aqueous humor.
• Net fluid movement from blood to aqueous increases, but so does its IOP
dependence (pseudofacility).
• Total facility, as measured by IOP-altering techniques cannot distinguish
pseudofacility from total outflow facility (Ctot) and therefore erroneously
record the pseudofacility component as increased Ctot (hence the term,
―pseudofacility‖) and therefore underestimate the extent to which the
outflow pathways have been compromised by the insult

56. Intraocular pressure
• IOP is the pressure exerted by the intraocular contents on the
coats of the eyeball.
• Normal IOP : 12-21 mm of Hg (mean 16 ± 2.5 mm of Hg)
• IOP is essentially maintained by the dynamic equilibrium between
formation and outflow of aqueous humour.

57. Factors affecting IOP
a) Local factors
1. Rate of aqueous formation
2. Resistance to aqueous outflow
3. Increased episcleral venous pressure
4. Dilation of pupil

58. b) General factors
1. Hereditary
2. Age
3. Sex
4. Diurnal variation
5. Postural variation
6. Seasonal variation
7. Blood pressure
8. Osmotic pressure of blood
9. Effects of Drugs
10. Effects of general anesthesia
11. Systemic hyperthermia
12. Refractive error
13. Mechanical pressure on globe

59. Iop measuring
1. Manometry
2. Tonometry
I. Indentation or Impression tonometry
II. Applanation tonometry

60. FACTORS EXERTING SHORT-TERM INFLUENCE ON
IOP
• Diurnal
• Postural Variation
• Exertional Influences
• Lid and Eye Movement
• Intraocular Conditions
• Systemic Conditions
• Environmental Conditions
• General Anesthesia
• Foods and Drugs

61. Diurnal Variation
• IOP shows cyclic fluctuations throughout the day.
• Ranges from approximately 3 mm Hg to 6 mm Hg.
• Higher lOP is associated with greater fluctuation, and a diurnal
fluctuation of greater than 10 mm Hg is suggestive of glaucoma.
• The peak IOP is in the morning hours
• Primary clinical value of measuring diurnal IOP variation is to avoid the
risk of missing a pressure elevation with single readings.

62. Vitreous
• The vitreous body makes up approximately 80% of the volume of the eye
• the largest single structure of the eye.
• In the anterior segment of the eye, it is delineated by and adjoins the ciliary body,
the zonules, and the lens.
• In the posterior segment of the eye, the vitreous body is delineated by and adjoins
the retina.
• The vitreous body is a specialized connective tissue whose postembryologic
functions include
1. serving as a transparent gel occupying the major volume of the globe
2. acting as a conduit for nutrients and other solutes to and from the lens

63. Anatomy of the mature vitreous body
• It has an almost spherical appearance, except for the anterior part, which is
concave.
• it is not completely homogeneous.
• The outermost part of the vitreous, called the cortex, is divided into an anterior
cortex and a posterior cortex
• The cortex is also called the anterior and the posterior hyaloid.
• The cortex consists of densely packed collagen fibrils.
• The vitreous base is a three-dimensional zone.
• It extends approximately from 2 mm anterior to the ora serrate to 3 mm
posterior to the ora serrata, and it is several millimeters thick. The collagen
fibrils are especially densely packed in this region.

64. Vitreous
Medullary
vit
Hyaloid
layer or m
Ant limiting
mm
Post limiting
mm
Cortical vit

65. Vitreous
spaces
3 zones
Retrolental
zone
Intermediate
zone
Preretinal
zone
2 optical
distinct
tracts
Tractus
retrolentalis
T.
preretinalis

67. Composition
• The vitreous contains approximately 98% water and 0.15% macromolecules,
including collagen, hyaluronan, and soluble proteins.
• The remainder of the solid matter consists of ions and low-molecular- weight
solutes.
• several noncollagenous structural proteins and glycoproteins have been
identified in the vitreous; these components include versican, link protein,
bulin-1, nidogen-1, bronectin, and 2 novel glycoproteins—opticin and VIT1.
• The human vitreous also contains hyaluronidase and at least 1 matrix
metalloproteinase (MMP-2, or gelatinase), suggesting that turnover of vitreous
structural macromolecules can occur.

68. Collagen
• Vitreous collagen brils are composed of 3 dierent collagen types:
•
• 1. Type II, which forms the major component of the fibrils
• 2. Type IX, which is located on the surface of the fibril
• 3. Type V/XI, which has an unconfirmed location that may allow
its amino terminus to project from the surface of the fibril

69. • At present, 19 types of collagen are known, and the genes for several more
have been identified.
• The vitreous collagens are closely related to the collagens of hyaline cartilage.
• The collagen fibrils of the vitreous are only loosely attached to the internal
limiting membrane (ILM) of the retina; however, at the vitreous base, the fibrils
are firmly anchored to the peripheral retina and pars plana, as well as to the
margins of the optic disc.

70. Hyaluronan
• Is a polysaccharide (glycosaminoglycan) that has a repeating unit of glucuronic
acid and N-acetylglucosamine.
• Nontoxic, noninflammatory, and nonimmunogenic.
• At physiologic pH, hyaluronan is a weak polyanion because of the ionization of
the carboxyl groups present in each glucuronic acid residue.
• In free solution, hyaluronan occupies an extremely large volume relative to its
weight and probably uses all of the space in the vitreous except for that
occupied by the collagen fibrils.
• Hyaluronan molecules of the vitreous may undergo lateral interactions with
each other, and such interactions may be stabilized by noncollagenous proteins.

71. Biochemical Changes With Aging and
Disease

72. 1. Vitreous Liquefaction and Posterior Vitreous
Detachment
• by the age of 80–90 years, more than half of the vitreous is liquid. which leads to early posterior
vitreous detachment (PVD).
• The process of vitreous liquefaction has, as a crucial component, the breakdown of the thin (12–15
nm) collagen fibrils into smaller fragments; implicated in this process is less “shielding” of type II
collagen due to the age-related exponential loss of type IX collagen.
• Some proteolytic enzymes, such as plasminogen, may have elevated vitreous concentrations with
increasing age.
• The fragments aggregate into thick fibers, or fibrillar opacities, which are visible with low-power,
slit-lamp microscopy.
• As liquefaction proceeds, the collagen fibrils become condensed into the residual gel phase and
are absent from (or in low concentration in) the liquid phase. In terms of hyaluronan
concentration or molecular weight, there are no differences between the gel and liquid phases.
• With increasing age, there is a weakening of adhesion between the cortical vitreous gel and the
ILM. These combined processes eventually result in PVD in approximately 50% of the population.

73. • PVD is a separation of the cortical vitreous gel from the ILM as far anteriorly as
the posterior border of the vitreous base;
• the separation does not extend into the vitreous base owing to the unbreakable
adhesion between the vitreous and retina in that zone.
• As the residual vitreous gel collapses anteriorly within the vitreous cavity,
retinal tears sometimes occur at areas where the retina is more strongly
attached to the vitreous than the surrounding retina can withstand, which
subsequently can result in rhegmatogenous retinal detachment.
• A PVD can protect against proliferative diabetic retinopathy by denying a
scafold for fibrovascular proliferation emanating from the disc and the retina.

74. • A PVD can be achieved surgically during macular hole surgery.
• it is now clinically recognized that in many eyes thought to have a PVD,
collagen fibrils are still extensively attached to the ILM; and even after
production of an acute PVD during vitreous surgery, some collagen fibrils
typically remain adherent to the ILM.
• Removal of the ILM itself is now more frequently the goal in limiting the extent
of traction maculopathy.

75. Myopia
• When the axial length of the globe is greater than 26 mm, both collagen and
hyaluronan concentrations are approximately 20%–30% lower than their
concentrations in emmetropic eyes.

76. Vitreous as an Inhibitor of Angiogenesis
• This inhibitory activity is decreased in diabetic vitreoretinopathy.
• However, the molecular basis of the phenomenon remains poorly understood.
• Known inhibitors of angiogenesis, such as thrombospondin 1 and pigment
epithelium–derived factor, are present within the mammalian vitreous and may
inhibit angiogenesis in normal eyes.
• In contrast, vascular endothelial growth factor (VEGF), a promoter of
angiogenesis, is markedly elevated in the vitreous of patients with proliferative
diabetic vitreoretinopathy, in which the vitreous also acts as a scafold for
retinal neovascularization.

77. Physiologic Changes After Vitrectomy
• Both the normal vitreous and the vitreous cavity after vitrectomy are 99%
water.
• the viscosity decreases between 300- and 2000-fold.
• growth factors and other compounds such as antibiotics transfer between the
posterior and anterior segments more easily, but they are also cleared more
quickly from the eye
• oxygen movement is more rapid, and the normal oxygen gradient between the
well-oxygenated anterior segment and the posterior segment flattens
signicantly, with greatly increased oxygen tension at the retina. It has been
proposed that increased oxygen tension at the posterior pole of the lens may
be part of postvitrectomy cataractogenesis.

78. Injury With Hemorrhage and Inflammation
• If blood penetrates the vitreous cortex, platelets come into contact with
vitreous collagen, aggregate, and initiate clot formation.
• The clot in turn stimulates a phagocytic inflammatory reaction, and the
vitreous becomes liquefied in the area of a hemorrhage.

79. Involvement of Vitreous in Macular Hole
Formation
• macular holes sometimes originate from traction generated by attachment
of the vitreous specically to the fovea, with the subsequent generation of
additional tangential tractional force along the ILM, causing hole
enlargement.

80. Enzymatic Vitreolysis
• Enzymes that have been proposed for injection into the vitreous cavity include
hyaluronidase, plasmin, dispase, and chondroitinase.
• Ocriplasmin, which cleaves bronectin and laminin, however, was able to induce
a PVD (compared with placebo) and demonstrated eficacy in nonsurgical
management of vitreomacular traction and macular holes.

81. THANKS ALO FOR YOUR
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