How does vitreous degeneration and collagen aggregation lead to posterior vitreous detachment?
Executive summary
Posterior vitreous detachment (PVD) results when the aged vitreous gel liquefies and its collagen framework aggregates and collapses, weakening the molecular “glue” that tethers the posterior vitreous cortex to the retina and allowing the cortex to separate from the retinal surface [1][2]. The same processes that create symptomatic floaters — synchysis (liquefaction) and syneresis (collagen aggregation) — therefore both signal and mechanically drive the stages that culminate in PVD [3][4].
1. The gel in the back of the eye: composition and attachments
The vitreous is a transparent hydrogel of ~98% water built on a scaffold of type II (and other) collagen fibrils enmeshed with hyaluronic acid and proteoglycans; its posterior surface (the posterior vitreous cortex) adheres to the retina via an extracellular-matrix “glue” including laminin, fibronectin and other molecules at the internal limiting lamina (ILL) [1][5][6].
2. Two ageing processes: synchysis (liquefaction) and syneresis (fibril aggregation)
Age-related degeneration begins with synchysis—formation of liquid pockets as hyaluronan depolymerizes and dissociates from collagen—followed or concurrent with syneresis, in which collagen fibrils condense, fuse or fragment into visible thick bundles that scatter light as floaters (myodesopsia) [1][7][4].
3. How collagen aggregation destabilizes the gel architecture
When collagen fibrils lose their normal surface coatings (for example loss of type IX collagen) they fuse or fragment and redistribute unevenly, concentrating fibers in some regions and leaving lacunae in others; this redistribution produces both local collapse of the gel and an increase in vitreous mobility that predisposes to posterior collapse of the cortex [8][7][9].
4. From weakened glue to mechanical separation at the vitreoretinal interface
Liquefaction creates subvitreal fluid pockets while fibrillar aggregation and biochemical changes in extracellular-matrix components reduce adhesion at the vitreoretinal interface; together, reduced adhesive strength plus increased mobility and vitreous shrinkage permit progressive dehiscence of the posterior cortex, which clinically manifests as staged PVD and, in complete separation, a Weiss ring over the optic nerve [10][6][11].
5. Modifiers, risks and clinical significance
Not everyone with extensive liquefaction develops complete PVD; factors that accelerate or alter the process include myopia, intraocular surgery, inflammation, trauma, hereditary collagen disorders, oxidative damage and enzymatic remodeling that degrades matrix components — all of which can increase the chance of anomalous PVD, retinal tears, or retinal detachment [12][13][10][2]. The clinical urgency stems from the momentary vitreoretinal traction during detachment: flashes, a sudden increase in floaters, and a small but real risk of retinal breaks that ophthalmologists screen for after symptomatic PVD [1][11].
6. Mechanistic gaps, alternative models, and therapeutic implications
Although broad consensus links liquefaction plus collagen aggregation to PVD, the precise molecular sequence—whether fibril fusion, fragmentation, loss of hyaluronan, oxidative modification, or matrix-enzyme activation is dominant—remains debated in the literature and may vary by patient; this uncertainty matters because pharmacologic vitreolysis (e.g., ocriplasmin and experimental reagents) must target both liquefaction and vitreoretinal adhesion without retinal toxicity, creating a translational incentive for industry-funded research into enzymes and collagen-targeting agents [7][14][5][13].
7. Bottom line: a mechanical and biochemical duet driving PVD
Posterior vitreous detachment is best understood as a duet of biochemical degeneration and mechanical rearrangement — hyaluronan depolymerization and oxidative or enzymatic changes create liquid pockets while collagen fibrils aggregate and condense, producing gel collapse and weakening adhesion so the posterior vitreous cortex can separate from the retinal surface; clinical risk depends on where adhesions persist and on patient-specific modifiers [1][3][8][2].