Vitreous humor

• Sanket Parajuli

Development of VITREOUS

• Related to the dev of the hyaloid art

• At 4 WOG mesodermal cells invade the cavity of the developing optic cup through the patent optic fissure

• These cells differentiate into the hyaloid artery (& branches),the vasa hyaloidae propria, which occupy most of the space between the lens and the neural retina

• 4-5th WOG retrolental space becomes filled with the primary vitreous, which consists of fibrillar material, mesenchymal cells and vascular channels.

THE SECONDARY VITREOUS

Sec by neuroectoderm of OC• At first it occupies the narrow space

between the retina and the posterior (outer) limit of the primary vitreous

• The secondary vitreous, which is

avascular, consists of a more compact network of type II collagen fibrils

• It fills….1ary vit /primitive …..reduced…cloquets canal

THE TERTIARY VITREOUS

• At 12 WOG frm neuroectoderm in ciliary region

• This development of the tertiary vitreous constitutes the embryonic 'zone of origin' of vitreous base, and is known as the marginal bundle of Drualt

• The zonular apparatus of the lens will ultimately develop anterior to these collagen fibrils

FINAL ORGANIZATION OF VITREOUS

• 5th mnth:: The pupillary membrane and the posterior vascular capsule on the anterior and posterior surfaces of the lens regresses

• 7th Mnth :: Blood flow in the hyaloid artery ceases and the vessel is almost completely atrophied by birth

• Remnants may persist at the posterior lens capsule as Mittendorf's dots and at the optic disc as the area of Martegiani

• Finally the hyalocytes phagocytose debris and then come to occupy a position in the cortex of the vitreous where they begin to synthesize hyaluronic acid.

BERGMEISTER'S papillae

• Bergmeister's papilla is formed by focal proliferation of glial cells at the optic nerve head by 9 weeks of gestation

• The base of the cells are spread along the internal limiting membrane and the apex extends into the vitreous

• Subsequent focal necrosis and tissue remodeling are responsible for its atrophy.

• However, Bergmeister's papilla can remain, together with remnants of the hyaloid artery, on the optic disc with no apparent harmful visual effects.

GROSS anatomy of vitreous humour

transparent colourless gel of a consistency somewhat firmer than egg white

fills posterior 4/5th of the globe

in contact with the retina behind, and the ciliary body, zonule and lens, in front

roughly spherical, but is flattened anteriorly

exhibits a cup-shaped anterior depression, the patellar fossa which accommodates the lens

Vitreous is separated from lens by the capillary space of Berger

Divided into 3 parts:

• Hyaloid layer / membrane• Cortical vitreous• Central or core vitreous

Hyaloid layer/ membrane:

• Not a true membrane but the outermost surface layer or a condensation of vitreous body

Further divided into:1. Anterior hyaloid membrane2. Posterior hyaloid membrane

Anterior hyaloid membrane:• Covers the vitreous body anteriorly starting from a point

anteriorly from ora seratta

• Lies in contact with pars plana ciliary processes zonules & posterior lens capsule

• Attached to posterior lens capsule by ligamentum hyaloideo capsulare of Wieger

• Central area within the ring contains a potential space—retrolental space of berger/patellar fossa

• From midpoint of bergers space the anterior hyaloid ligament turns backwards to from anterior portion of cloquet’s canal

Other connections of anterior hyaloid membrane:

• Hyalociliary zonules: fibers extend from anterior hyaloid membrane to valley between ciliary processes

• Coronay ligaments: fibers extend from anterior hyaloid membrane to inner face of posterior third of ciliary processes circumferentially

• Median ligament: at the level of midzone of pars plana

Posterior hyaloid membrane:

• Extends back from the vitreous base till optic disc

• Lies in contact with the internal limiting membrane of the retina and is clinically indistinguishable

Cortical vitreous:

• It refers to entire peripheral zone-100-200 µm in width of main vitreous mass

• Consists of relatively condensed fibrillary vitreous

• Consists of a delicate meshwork of type 2 collagen fibers interspread with the sodium hyaluroante, mucopolysaccharide molecule -- elasticity and tensile strength

• It’s the metabolic center of vitreous body and contains vitreous cells-the hyalocytes (found in cortical vitreous except in retrolental part)

• Glial cells and fibroblasts are also present in the cortex

Hyalocytes:

• Vitreous cortex—metabolic center of vitreous—due to presence of hyalocytes

• Capable of synthesizing hyaluronic acid

• Hyalocytes are spindle shaped/ oval

• Are 10-15 µm in diameter

• Contain lobulated nucleus a well developed golgi complex SER and RER and PAS positive granules

• Posterior hyalocytes are however flat and spindle shaped whereas anterior hyalocytes are larger rounder and at times star shaped

• @ rest they produce matrix GAGs however they become phagocytic in response to inducing stimuli and inflammation

Medullary vitreous:• Major portion of vitreous body

• Structure similar to cortex but it has less fibrillary structure & essentially cell free

• Homogenous but exhibit wavy lines of watered silk appearance in slit lamp

• Running down the center of vitreous body from the optic disc to posterior pole of lens is the hyaloid canal(cloquet’s canal)

• It represents the remnant of primary vitreous and down this canal runs the hyaloid artery of the vitreous

• The canal is 1-2 mm in width and its walls are formed by vitreous condensation rather than true membrane

• Vitreous tracts:

RETROLENTAL TRACT inserted into a circular area on the lens capsule, near to the hyaloideocapsular ligament, and extends posteriorly into the central vitreous

CORONARY TRACT passes backwards into the central vitreous from a circular zone overlying the posterior third of the ciliary processes (the coronary ligament)

MEDIAN TRACT Inserted into a circular zone at the anterior margin of the vitreous base, about the middle of the pars plana, which is termed the median ligament. The tract extends backwards as a faint veil into the central vitreous

PRERETINAL TRACT Inserted at the ora serrata Is more strongly reflecting than the preceding two

Topographic subdivisions of vitreous:

• Vitreous Can be divided into 3 zones by 2 optically disctinct tracts :retrolental and preretinal tract into::

1. Retrolental zone: • bounded anteriorly by patellar fossa of lens and

circumferentially by retrolental tract

2. Intermediate zone:• lies between retrolental tract and pre retinal tract • contains coronary and median tract

3. Preretinal zone : between retina and preretinal tract

Attachments :

• Strong attachment of vitreous in several parts:

1. Vitreous base2. Margin of optic disc3. Macula4. Along the retinal vessels5. Behind the lens---along hyaloid fossa

Vitreous base: is a 3 dimensional zone

• 4mm wide zone where vitreous is firmly attached to region of ora serrata• 2mm of pars plana anteriorly and 2 mm region of

retina posterior to ora serrata temporally and 3 mm nasally

In some vitreous base may have posterior extensions of firm attachment which may act as points of high vitreoretinal traction and may produce tears

• In the vitreous base collagen fibers from cortical vitreous gets inserted into internal limiting membrane of retina and pars plana of ciliary body @ right angles to their surface

(in posterior part the insertion is parallel to ILL)

Firm attachment of vitreous base::

a) Anterior to ora the attachment consists of complex interdigitations of collagen with non pigmented ciliary epithelium

b) Posterior to ora-- the ILL shows focal ruptures—through it vitreous fibers are attached to retinal glial cells

Composition of vitreous

• Approximately 99% water

• 0.15% macromolecules: collagen, hyaluronan (hyaluronic acid), and soluble proteins

• LMW:: sugars, AA, Ascorbic acid

• Hyaluronidase and MMP are also present

Collagen :Vitreous collagen fibrils are composed of 3 different collagen types:Type 2 (major component of the fibrils)—90%Type 9 (located on surface of fibril)---10%Type 5/11At present 19 types of collagen are known

• More collagen are in the cortex than in central vitreous

• Collagen fibrils of vitreous are loosely attached to the inner limiting lamina of retina

Fibroblasts:

• These cells constitute < 10% of total vitreous cell population

Hyaluronan:

• HMW polysaccharide (GAG) that has a repeating unit of glucuronic acid and N acetyl glycosamine linked with a beta 1,3 glycoxidic acid

• Present in all vertebrate connective tissues and is non toxic non inflammatory and non immunogenic

• Synthesized primarily by hyalocytes

• 3 forms of hyaluronan sunthetase are known

• Hyaluronan concentration is maximum at posterior cortical layer near retina and lowest in anterior portion behind the lens

• At physiologic PH hyaluronan is a weak poly anion because of the ionization of carboxyl groups present in each glucuronic acid residue

• In free solution it occupies an extremely large volume relative to its weight and probably occupies all of space in vitreous except for the space occupied by the collagen fibrils

• It has ability to absorb water due to electrostatic repulsion between negative charged coils

Soluble proteins:

• Low protein concentration in vitreous

• High concentration in cortical vitreous similar to hyaluronic acid

• Serum albumin is the major soluble vitreous protein

• The concentration of the serum protein in the vitreous depends on the integrity of the retinal vasculature and the degree of any intraocular inflammation

• Sodium: its concentration in vitreous is same as that of other intraocular and extracellular fluids

• Potassium: its concentration in the anterior vitreous is greater because of the active transport of potassium from the ciliary body

• Bicarbonate levels in posterior vitreous is lower due to active metabolism of surrounding ocular tissue

• Glucose: its concentration is lower in posterior vitreous because of its uptake and usages by the metabolically active retinal tissue. content is half of that of AH

• Ascorbic acid: its concentration is higher in vitreous mainly due to active transport by ciliary epithelium from the blood

• Amino acids: less than in aqueous or plasma

• Calcium: content of vitreous humor is equal to that of AH

• Lactic acid: high in posterior vitreous due to high retinal metabolism

• Lipids : accounts for 7% of the wet weight:Palmitate: 25%Stearate: 18%Oleate: 23%Arachidonate: 17%

Physiochemical properties:

• Weight=4gms• Refractive index= 1.33

• Plasticity== due to 3D network of randomly distributed collagen which are electrostatically neutral and are not crosslinked—allow vitreous to expand

• Elasticity==due to hyaluronic acid entangled among collagen fibers……..sponge like polymer coils of hyaluronic acid precipitate extreme volume changes with change in physiochemical environment

• Gel stability==combination of hyaluronic acid and collagen…form stable gel system…resist disorganizing forces(this mechanism aka frictional interaction)

Vitreous expansion and contraction:

• Vitreous contain positively charged Na, K & other molecules that neutralize the negatively charged H acid

• If these are replaced by positively charged macromolecules--the coils of H acid cross links and gel system contract

• If positively charge molecules are removed and not replaced--- the sodium ions remaining do not shield the negative charges on the H acid molecules

• H acid coils repel reach other—vitreous expand

The exclude volume concept:

• Explains why macromolecules, other cells or proteins do not penetrate vitreous

• The collagen are thicker and more numerous• H acid themselves are spheroidal particles• H acid + collagen occupy most volume—thus others excluded

Blood vitreous barriers:

Consists of 3 components:

• Tight junctional complexes at the level of retinal vascular endothelium, pigment epithelium of retina and non pigmented epithelium of ciliary body. It inhibits passage of HMW constituents

• Basal lamina of vitreoretinal junction: It physically blocks the passage of large molecules

• Vitreous cortex: physiochemical characteristic of hyaluronic acid in cortical vitreous effectively blocks or retards movement of cells macromolecules and cations.

DISEASES OF THE VITREOUS

Posterior vitreous detachment:• Separation of cortical vitreous gel from the

internal limiting membrane as far as posterior border of vitreous base ---the separation does not extend into vitreous base owing to strong attachment of vitreous and retina at that zone

• PVD is sudden event—during which—liquefied vitreous from the center of vitreous body passes through a hole in posterior vitreous cortex and dissects the residual cortical gel from the inner limiting lamina

• Residual vitreous gel collapses anteriorly within vitreous cavity (synersis)

Heriditary hyaloideoretinopathies with optically empty vitreous:

Stickler/Wagner syndrome:• AD• Premature vitreous collapse and cause retinal

detachment• Mutations in type 2 procollagen chains• Ocular abnormalities: Myopia, OAG and

cataract• Facial abnormalities: Midfacial flattening and

Pierre-Robin malformation (micrognathia, cleft palate and glossoptosis)

VITREOUS OPACITIES

Vitreous is a transparent structure – any non-transparent structure present in it will form an opacity and cause symptoms of FLOATERS

MUSCAE VOLITANTES

• physiologic opacities

• residues primitive hyaloid vasculature

• perceived as fine dots and filaments, which drift in and out of the field against bright background

PERSISTENT HYPERPLASTIC PRIMARY VITREOUS

• failure of the primary vitreous structure to regress

• U/L in 90%

Anterior PHPV: hyaloid artery remain as white vascularised fibrous membrane behind the lens• Associated with leukocoria, microphthalmos, shallow AC and long ciliary

processes• Dehiscence of posterior lens capsule can cause swelling of lens and thus

secondary angle closure

Posterior PHPV: may be isolated or in association with anterior PHPV• Microphthalmic eyes but AC normal, lens clear• A stalk of tissue runs along the apex of a retinal fold (usually in

inferior quadrant) and runs along circumferentially toward anterior retina

AMYLOID DEGENERATION

is a localized or systemic condition in which there is extracellular deposition of a fibrillary protein

vitreous opacities may be unilateral or bilateral and are initially perivascular

Later they involve the anterior vitreous and take on a characteristic sheet-like (‘glass wool’) appearance

The opacities may become attached to the posterior lens by thick footplates

Dense opacification resulting in significant visual impairment may require vitrectomy

ASTEROID HYALOSIS

• small, white rounded bodies suspended in the vitreous gel• formed due to accumulation of calcium containing

lipids• unilateral, asymptomatic condition usually seen in

old patients with healthy vitreous • move with the vitreous during eye movements• but do not sediment inferiorly when the eye is

immobile• genetic relationship between this condition, diabetes

and hypercholesterolemia

SYNCHYSIS SCINTILLANS

• vitreous is laden with small white angular and crystalline bodies with formed of cholesterol

• seen in damaged eyes that suffered trauma, vitreous hemorrhage or inflammatory disease in the past

• vitreous is liquid and crystals sink in the bottom and stirred up with every movement

• Occsaionally AC is also invloved

• “beautiful shower of golden rain” on ophthalmoscopy

VITREOUS HEMORRHAGE

• usually occurs from the retinal vessels

• May present as pre-retinal (sub-hyaloid) or an intragel haemorrhage

• Intragel hemorrhage may involve anterior, middle, posterior or the whole vitreous body

Vitrectomy:

• Anterior• Core• Subtotal/total

Vitreous substitutes:

• Air• Expansile gasesPerchloroethanePerfluoropropane• Silicon oil

References:

• American academy of ophthalmology• Kanski’s• Wolff’s anatomy of eye and orbit• Internet sources

VITREOUS LIQUEFACTION

• most common degenerative change in vitreous• Vitreous--progressive liquefaction with age• There’s decrease in gel volume and increase in

liquid volume• Begins in central vitreous • on Slit lamp -- absence of normal fibrillar

structure and visible pockets of liquefaction • appearance of coarse aggregate material which

moves freely in the free vitreous

Exact cause unknown –thought to be due to alteration in hyaluronic acid collagen interaction

Myopia is associated with liquefaction

with age –there’s weakening of adhesion between vitreoretinal interface(between cortical vitreous gel and inner limiting lamina)---+ liquefaction of vitreous---these combined processes can lead to PVD

Liquefaction of vitreous starts as early as 2 years in a zone above posterior pole and produces a space k/a premacular bursa or precortical vitreous pocket

• Enzymatic and non enzymatic cross linking of collagen fibers free radical damage and decrease in network density of collagen fibrils lead to destabilization of vitreous gel—vitreous gel start to shrink---portions of retina under traction---retinal tears / holes

• The tractional force when spread over a large area—not sufficient to produce holes –instead distort retina or cause tractional elevation of retina—vitreomacular traction syndrome where patient develops blurring+metamorphopsia