Anatomy and Physiology of the Vitreous

1. Introduction / Overview

2. Embryology

• The hyaloid artery supplies the primary vitreous during fetal life; it regresses during gestation, leaving behind the hyaloid canal (Canal of Cloquet) - a potential space running from the optic disc to the posterior pole of the lens capsule.
• If regression of the hyaloid system is incomplete: persistent hyperplastic primary vitreous (PHPV).

3. Gross Anatomy / Structure

Shape and Dimensions

• Volume: ~4 mL
• Roughly spherical posteriorly, with an anterior patellar fossa (a concavity that accommodates the posterior surface of the lens)
• Separated from the lens by the hyaloidocapsular ligament (ligament of Wieger/Egger's ring) - a 9 mm annular attachment

Zones (from outside in)

1. Vitreous cortex (peripheral gel) - densest collagen concentration; in contact with the ILM of retina
2. Vitreous base - 3-4 mm wide zone straddling the ora serrata (2 mm anterior, 2 mm posterior); site of strongest vitreoretinal adhesion; persists even after PVD
3. Central vitreous - less dense, more liquid (fluid vitreous or vitreous humor)
4. Hyaloid canal (Cloquet's canal) - runs centrally from the optic disc to the posterior lens capsule

Boundaries

• Anteriorly: Posterior lens capsule, zonular fibers, pars plana
• Posteriorly: Retinal ILM
• Anterolateral: Ciliary body

4. Composition

5. Sites of Vitreoretinal Adhesion

• Vitreous base (strongest - persists after PVD)
• Optic disc margins (fairly strong)

• Perifoveal region (fairly weak)
• Along major retinal vessels (weak)
• Posterior lens capsule (Egger's ring)

6. Functions (Physiology)

7. Age-Related Changes (Clinically Important)

1. Synchysis - Progressive liquefaction of gel due to dissociation of collagen-HA network; fluid-filled lacunae form
2. Syneresis - Collapse and condensation of residual gel
3. Posterior Vitreous Detachment (PVD) - Separation of the posterior vitreous cortex (posterior hyaloid membrane) from the ILM posterior to the vitreous base
   • Incidence: <10% under age 50; ~65% over age 70
   • Can present with floaters (Weiss ring at disc), photopsia
   • Complicated PVD may cause retinal tears (at sites of abnormal adhesion) leading to rhegmatogenous retinal detachment

8. Clinical Correlates

ANATOMY OF THE VITREOUS HUMOR

(Comprehensive Long Answer)

SECTION 1 — INTRODUCTION AND OVERVIEW

Key Facts at a Glance

SECTION 2 — EMBRYOLOGICAL DEVELOPMENT

Stage 1 — Primary Vitreous (Vascular vitreous, Weeks 4-8)

• Formed from mesenchyme that invades the interior of the optic cup through the embryonic choroid fissure
• The invading mesenchyme forms the hyaloid vascular system: the hyaloid artery (a branch of the ophthalmic artery), hyaloid vein, and a vascular plexiform network - the vasa hyaloidea propria and tunica vasculosa lentis - which supply the developing lens
• In addition, the mesenchyme forms a delicate fibrillar network between the lens and retina; the interstitial spaces of this network later fill with a transparent gelatinous substance to form the vitreous body
• The primary vitreous = the fibrovascular mass occupying the center of the optic cup in early fetal life

Stage 2 — Secondary Vitreous (Avascular, Weeks 9 onward)

• The secondary vitreous is produced by the retinal neuroectoderm (inner layer of optic cup) and ciliary body
• It forms the bulk of the adult vitreous - avascular, transparent, and gel-like
• The primary vitreous is progressively compressed into the central axis by the expanding secondary vitreous, where it persists as the hyaloid canal (Cloquet's canal)
• The hyaloid vessels within the primary vitreous regress and obliterate during fetal life (by the 8th-9th month of gestation), leaving behind the Cloquet's canal as a patent but fluid-filled remnant

Stage 3 — Tertiary Vitreous (Zonular fibers)

• These are formed from the non-pigmented ciliary epithelium
• Strictly, these become the zonules of Zinn (suspensory ligaments of the lens), not true vitreous
• They form the connection between the ciliary body and the lens equator

Clinical Consequences of Abnormal Development

SECTION 3 — GROSS ANATOMY / STRUCTURE

3.1 Shape and Position

• The vitreous body is roughly spherical in the posterior two-thirds of its extent
• Anteriorly it has a concave anterior face - the patellar fossa (fossa patellaris) - which accommodates the posterior convexity of the lens
• It is entirely enclosed within the vitreous chamber, which has a capacity of approximately 4 mL

3.2 Subdivisions / Zones (from periphery to center)

• The outermost 100-300 microns of vitreous adjacent to the retina and pars plana
• Has the highest density of collagen fibrils oriented parallel to the surface of the retina
• Divided into:
  • Anterior cortex - adjacent to the ciliary body, pars plana, and posterior lens
  • Posterior cortex - adjacent to the retina; delineated by the posterior hyaloid membrane (PHM)
• The posterior hyaloid membrane separates vitreous from the preretinal space; it is NOT a true membrane but a condensation of peripheral cortical gel
• The anterior hyaloid membrane is similarly a condensation facing the posterior lens and ciliary body

• A 3-4 mm wide collar-shaped zone straddling the ora serrata - approximately 2 mm anterior (onto the pars plana) and 2 mm posterior (onto the peripheral retina) to the ora
• Represents the site of strongest vitreoretinal adhesion in the entire eye
• The cortical vitreous here is firmly anchored to the ILM of the pars plana epithelium and peripheral retina by interdigitation and adhesion molecules (fibronectin, laminin, collagen)
• Persists permanently - the vitreous base does NOT detach even in complete PVD
• Following PVD, the posterior hyaloid face remains attached at the vitreous base
• Blunt trauma can avulse the vitreous base, tearing the pars plana epithelium anteriorly and the retina posteriorly

• Less dense than the cortex
• Traversed by the Cloquet's canal (see below)
• In aging eyes, this is the first region to liquefy (form liquid vitreous or lacunae)

• An S-shaped, optically empty potential space/tunnel running through the center of the vitreous
• Extends from the optic disc posteriorly to the posterior pole of the lens capsule anteriorly
• Approximately 1-3 mm wide near the optic disc, wider anteriorly
• Is the remnant of the primary hyaloid vascular system
• Not always visible on examination; may be seen on OCT or slit lamp in young patients

3.3 Boundaries and Relations

3.4 Hyaloidocapsular Ligament (Ligament of Wieger / Egger's Ring)

• A circular zone of attachment between the anterior vitreous face and the posterior lens capsule
• Annular in shape, ~8-9 mm in diameter
• Represents the junction of the anterior hyaloid membrane with the posterior lens capsule
• It is strongest in young individuals and weakens with age
• When intact, it forms an anatomical barrier preventing the free passage of fluid between vitreous and posterior chamber

SECTION 4 — MICROSCOPIC ANATOMY / HISTOLOGY

4.1 Overall Histological Appearance

4.2 Components

Water (99%)

• Vitreous is 99% water - one of the most hydrated biological tissues in the body
• This water is bound to and organized by the macromolecular framework (primarily hyaluronic acid)

Collagen Fibrils (structural scaffold)

• The main structural element; form a three-dimensional fibrillar network
• Predominantly type II collagen (as in cartilage); also types V, IX, and XI
• Collagen fibrils are very thin (~10 nm diameter), heterotypic, and arranged in a specific pattern:
  • In the cortex: fibrils run parallel to the retinal surface - a basket-weave pattern
  • In the vitreous base: densely packed, oriented perpendicular to the basal lamina
  • In the central vitreous: randomly arranged, sparsely distributed
• Collagen provides the tensile strength and structural framework

Hyaluronic Acid / Hyaluronan (HA)

• A non-sulfated glycosaminoglycan (GAG) - a polymer of repeating disaccharide units of glucuronic acid and N-acetylglucosamine
• Present at a concentration of about 0.1-0.4 mg/mL; higher in cortex than center
• HA molecules are extremely large (molecular weight 1-4 million Da) and highly hydrophilic
• They form an expanded random coil occupying a large hydrodynamic domain, filling the spaces between collagen fibrils with bound water
• Interaction between collagen fibrils and HA maintains the gel state of the vitreous - collagen provides the structural frame, HA provides hydration and viscosity
• With age: HA dissociates from collagen → vitreous liquefaction (synchysis)

Other Macromolecules

• Opticin (vitrican): a leucine-rich proteoglycan; acts as an anti-angiogenic factor and is important in maintaining vitreoretinal adhesion
• Versican: a large chondroitin sulfate proteoglycan
• Fibronectin and laminin: glycoproteins at the vitreoretinal interface; mediate cell adhesion and vitreoretinal adhesion
• Ascorbic acid: present at high concentrations; acts as an antioxidant protecting against UV-induced reactive oxygen species (ROS)
• Glucose, amino acids, and inorganic salts: similar ionic composition to plasma

4.3 Cellular Components

• Location: cortical vitreous, predominantly at the posterior cortex, within 100 microns of the ILM
• Shape: rounded or oval with short processes
• Number: approximately 1.0 × 10⁵ cells total
• Origin: mesodermal/monocytic lineage (related to macrophages)
• Ultrastructure: abundant rough endoplasmic reticulum (rER) and Golgi apparatus (indicating high secretory activity)
• Function: primary source of HA and collagen synthesis within the vitreous; also capable of phagocytosis
• On H&E: difficult to visualize due to sparse number and pale cytoplasm
• In pathology: hyalocytes can transform into myofibroblasts and contribute to proliferative vitreomacular disease (e.g., epiretinal membrane)

• Rare; found at the periphery of the vitreous body near the pars plana
• Contribute to collagen synthesis

• Occasional macrophages in the peripheral vitreous
• Phagocytic function

SECTION 5 — SITES OF VITREORETINAL ADHESION

5.1 Physiological (Normal) Adhesion Sites

5.2 Pathological (Abnormal) Adhesion Sites

• Lattice degeneration (focal vitreoretinal adhesion at edges of lattice)
• Cystic retinal tufts
• Retinal pigment clumps
• Vitreous base anomalies (posterior extensions)
• "White with pressure" and "white without pressure" zones
• Preretinal new vessels (proliferative diabetic retinopathy, etc.)
• Vitreomacular traction syndrome

SECTION 6 — BLOOD-RETINAL BARRIER AND THE VITREOUS

SECTION 7 — AGE-RELATED CHANGES IN THE VITREOUS

7.1 Synchysis (Liquefaction)

• Biochemical mechanism: dissociation of the collagen-HA complex - HA separates from the collagen fibril scaffold and diffuses away, taking its bound water with it
• This causes localized dissolution of the gel structure
• Fluid-filled lacunae (optically empty spaces) form within the gel, initially in the central vitreous
• By age 80: approximately 50% of the vitreous is liquid
• Promoted by: aging, myopia, inflammation, trauma

7.2 Syneresis (Shrinkage/Condensation)

• As liquefaction progresses, the remaining gel collapses and condenses into fibrils/strands
• These condensed fibrils form visible floaters - opacities that cast shadows on the retina
• The condensed fibrils may aggregate as asteroid bodies (calcium-lipid deposits) or synchysis scintillans (cholesterol crystals)

7.3 Posterior Vitreous Detachment (PVD)

1. Synchysis creates liquid vitreous in the central cavity
2. A dehiscence (defect) forms in the cortical gel or PHM, usually in the premacular region
3. Liquid vitreous accesses the preretinal space (between PHM and ILM) through the defect
4. Progressive peeling of the PHM from the retina proceeds from the posterior pole forward - the last attachment released is at the optic disc margin
5. On release from the disc: the circular glial ring of Elschnig (normally adherent to disc) detaches as a Weiss ring - visible as a ring-like floater

• < 10% of individuals under 50 years
• ~65% of individuals over 70 years

• Retinal tear (at sites of abnormal vitreoretinal adhesion) → rhegmatogenous RD
• Vitreous hemorrhage (from avulsed vessel)
• Vitreomacular traction syndrome
• Macular hole formation

SECTION 8 — PHYSIOLOGY (FUNCTIONS OF THE VITREOUS)

SECTION 9 — CLINICAL ANATOMY (SURGICAL CONSIDERATIONS)

Pars Plana — The Surgical Window

• The pars plana (posterior 4 mm of ciliary body) is the standard entry site for vitreoretinal surgery and intravitreal injections
• Optimal entry: 4 mm from limbus in phakic eyes; 3.5 mm from limbus in pseudophakic eyes
• Entry through the pars plana traverses: conjunctiva → Tenon's capsule → sclera → ciliary body epithelium → vitreous base

Intravitreal Injections

• Vitreous can be accessed for drug delivery (anti-VEGF agents, steroids, antibiotics)
• Vitreous volume, its avascular nature, and slow drug clearance make it ideal for sustained drug delivery

Vitreous Substitutes (used after vitrectomy)

SECTION 10 — CLINICAL CONDITIONS PRIMARILY INVOLVING THE VITREOUS

SECTION 11 — SUMMARY TABLE

Sources

• Kanski's Clinical Ophthalmology: A Systematic Approach, 10th ed.
• Junqueira's Basic Histology: Text and Atlas, 17th ed.
• Histology: A Text and Atlas with Correlated Cell and Molecular Biology, 8th ed.
• Langman's Medical Embryology, 14th ed.
• Robbins & Cotran Pathologic Basis of Disease, 10th ed.
• *Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th ed.*This is a fully sourced, 6-page-equivalent comprehensive answer covering every aspect of vitreous anatomy. Here is what each section covers:

1. Introduction - overview, key facts table
2. Embryology - 3 stages of vitreous development, hyaloid system, Cloquet's canal, clinical anomalies (PFV, Mittendorf dot, Bergmeister's papilla)
3. Gross Anatomy - shape, subdivisions (cortex, vitreous base, central vitreous, Cloquet's canal), boundaries, Egger's ring with measurements
4. Microscopic Anatomy / Histology - water, collagen (types II, V, IX, XI), hyaluronic acid biochemistry, other proteoglycans (opticin, versican), fibronectin/laminin; hyalocytes (location, origin, ultrastructure, function), fibroblasts, macrophages
5. Sites of Vitreoretinal Adhesion - physiological (vitreous base strongest, optic disc, perifoveal, vessels) and pathological (lattice, tufts, etc.)
6. Blood-Retinal Barrier - inner and outer components, convective flow
7. Age-Related Changes - synchysis, syneresis, PVD (mechanism, epidemiology, Weiss ring, complications)
8. Physiology / Functions - 9 functions in table format
9. Clinical Anatomy / Surgical - pars plana entry, intravitreal injections, vitreous substitutes table
10. Clinical Conditions - 10 key conditions with anatomical basis
11. Summary Table - exam-ready revision