Key Features
- •
Optically clear.
- •
May modulate growth of the eye.
- •
Maintains media transparency.
- •
Serves as a reservoir for antioxidants.
- •
Plays a role in oxygen physiology of the eye.
- •
Separates from the retina during aging, in most cases resulting in innocuous posterior vitreous detachment (PVD).
- •
Anomalous PVD is a unifying concept in various vitreoretinopathies, including vitreo-maculopathies and rhegmatogenous retinal detachment.
Associated Features
- •
PVD is a common cause of vitreous floaters and may degrade contrast sensitivity function, known as Vision Degrading Myodesopsia.
- •
Some surgeons advocate vitrectomy for symptomatic vitreous floaters to normalize contrast sensitivity function.
- •
PVD and vitrectomy increase oxygen levels contributing to cataractogenesis.
- •
Anomalous PVD is the inciting event in diseases of the vitreous–macular interface via vitreomacular traction and vitreoschisis and contributes to proliferative diabetic retinopathy, macular edema in diabetes and vein occlusions, and possibly exudative age-related macular degeneration.
Introduction
Although vitreous is the largest structure within the eye, constituting 80% of the ocular volume, investigators of vitreous anatomy are hampered by two fundamental difficulties:
- •
Attempts to characterize vitreous morphology are efforts to visualize a tissue that is invisible “by design” ( Fig. 6.4.1 ).
Fig. 6.4.1
Vitreous Obtained at Autopsy on a 9-Month-Old Child.
The sclera, choroid, and retina were dissected off the transparent vitreous, which remained attached to the anterior segment. A band of gray tissue could be seen posterior to the ora serrata. This was a neural retina that was firmly adherent to the vitreous base and could not be dissected. The vitreous was almost entirely gel (because of the young age of the donor) and thus was solid and maintained its shape, although situated on a surgical towel exposed to room air.
(Courtesy The New England Eye Bank, Boston, MA.)
- •
The various techniques that were previously employed to study vitreous structure were flawed by artifacts induced by tissue fixatives, which caused precipitation of hyaluronan, formerly called hyaluronic acid.
The development of slit-lamp biomicroscopy by Gullstrand in 1911 was expected to enable clinical investigation of vitreous structure without the introduction of these artifacts. Nonetheless, a widely varied set of descriptions resulted. This phenomenon even persists in more modern investigations. Consider that in the 1970s, Eisner described “membranelles” and Worst described “cisterns”; in the 1980s, Sebag and Balazs identified “fibers”; and in the 1990s, Japanese investigators described “pockets” in the posterior vitreous, although the largest one is very likely the same as Worst’s bursa premacularis. What has been largely agreed upon is the molecular composition of vitreous.
Molecular Morphology
Supramolecular Organization
Vitreous is composed of a dilute meshwork of collagen fibrils ( Fig. 6.4.2 ) interspersed with extensive arrays of hyaluronan molecules. The collagen fibrils provide a solid structure that is “inflated” by the hydrophilic hyaluronan. Rheological observations also suggest the existence of an important interaction between hyaluronan and collagen. Balazs hypothesized that the hydroxylysine amino acids of collagen mediate polysaccharide binding to the collagen chain through O -glycosidic linkages. These polar amino acids are present in clusters along the collagen molecule, consistent with proteoglycans attachment to collagen in a periodic pattern.
Hyaluronan–collagen interaction in the vitreous body may be mediated by a third molecule. In cartilage, “link glycoproteins” have been identified that interact with proteoglycans and hyaluronan. Supramolecular complexes of these glycoproteins are believed to occupy interfibrillar spaces. Bishop has elegantly described the potential roles of type IX collagen chondroitin sulfate chains, hyaluronan, and opticin in the short-range spacing of collagen fibrils and how these mechanisms might break down in aging and disease.
Many investigators believed that hyaluronan-collagen interaction occurs on a “physicochemical” rather than a “chemical” level. Reversible complexes of an electrostatic nature between solubilized collagen and various glycosaminoglycans could, indeed, form because electrostatic binding between the negatively charged hyaluronan and the positively charged collagen likely occurs in vitreous.
Supramolecular Organization
Vitreous is composed of a dilute meshwork of collagen fibrils ( Fig. 6.4.2 ) interspersed with extensive arrays of hyaluronan molecules. The collagen fibrils provide a solid structure that is “inflated” by the hydrophilic hyaluronan. Rheological observations also suggest the existence of an important interaction between hyaluronan and collagen. Balazs hypothesized that the hydroxylysine amino acids of collagen mediate polysaccharide binding to the collagen chain through O -glycosidic linkages. These polar amino acids are present in clusters along the collagen molecule, consistent with proteoglycans attachment to collagen in a periodic pattern.
Hyaluronan–collagen interaction in the vitreous body may be mediated by a third molecule. In cartilage, “link glycoproteins” have been identified that interact with proteoglycans and hyaluronan. Supramolecular complexes of these glycoproteins are believed to occupy interfibrillar spaces. Bishop has elegantly described the potential roles of type IX collagen chondroitin sulfate chains, hyaluronan, and opticin in the short-range spacing of collagen fibrils and how these mechanisms might break down in aging and disease.
Many investigators believed that hyaluronan-collagen interaction occurs on a “physicochemical” rather than a “chemical” level. Reversible complexes of an electrostatic nature between solubilized collagen and various glycosaminoglycans could, indeed, form because electrostatic binding between the negatively charged hyaluronan and the positively charged collagen likely occurs in vitreous.
Vitreous Anatomy
Macroscopic Morphology
In an emmetropic adult human eye, vitreous is approximately 16.5 mm in axial length with a depression anteriorly just behind the lens (patellar fossa). The hyloideocapsular ligament of Weiger is the annular region (1–2 mm in width and 8–9 mm in diameter), where vitreous is attached to the posterior aspect of the lens. Erggelet’s or Berger’s space is at the center of the hyaloid capsular ligament. The canal of Cloquet arises from this space and courses posteriorly through the central vitreous ( Fig. 6.4.3 ), which is the former site of the hyaloid artery in the embryonic vitreous. The former lumen of the artery is an area devoid of collagen fibrils and surrounded by multifenestrated sheaths that were previously the basal laminae of the hyaloid artery wall. Posteriorly, Cloquet’s canal opens into a funnel-shaped region anterior to the optic disc, known as the area of Martegiani.
Within the adult human vitreous there are parallel nonbranching fibers that course in an anteroposterior direction ( Fig. 6.4.4 ), arising from the vitreous base, where they insert anterior and posterior to the ora serrata. The connections between the peripheral anterior vitreous fibers and the retina underlie the pathophysiology of retinal tears because of the strong adhesion in this location. The peripheral vitreous fibers are circumferential with the vitreous cortex, whereas the central fibers “undulate” parallel to Cloquet’s canal. Ultrastructural studies have demonstrated that collagen, organized in bundles of parallel fibrils, is the only microscopic structure corresponding to these fibers. It is hypothesized that visible vitreous fibers form when hyaluronan molecules no longer separate the microscopic collagen fibrils, which results in the aggregation of collagen fibrils into bundles from which hyaluronan molecules are excluded. The areas adjacent to these large fibers have a low density of collagen fibrils and a relatively high concentration of hyaluronan molecules. Composed primarily of “liquid vitreous,” these areas scatter very little incident light and, when prominent, constitute the “lacunae” seen with aging ( Fig. 6.4.5 ).
Microscopic Morphology
The vitreous cortex is the peripheral “shell” of the vitreous body that courses forward and inward from the anterior vitreous base (anterior vitreous cortex) and posteriorly from the posterior border of the vitreous base, (posterior vitreous cortex). The posterior vitreous cortex is 100–110 mm thick and consists of densely packed collagen fibrils. Although no direct connections exist between the posterior vitreous and the retina, the posterior vitreous cortex is adherent to the inner limiting membrane (ILM) of the retina, which is, in part, the basal lamina of retinal Müller cells. Adhesion between the posterior vitreous cortex and the ILM probably results from the action of various extracellular matrix molecules.
A hole in the prepapillary vitreous cortex can sometimes be visualized clinically when the posterior vitreous is detached from the retina ( Fig. 6.4.6 ). If peripapillary tissue is torn away during PVD and remains attached to the vitreous cortex about the prepapillary hole, it is referred to as Weiss’ ring. Vitreous can extrude through the prepapillary hole in the vitreous cortex but does so to a lesser extent than through the premacular vitreous cortex, where, occasionally, vitreomacular adhesion and axial traction can cause vitreomacular traction syndrome. Tangential vitreomacular traction is implicated in the pathogenesis of macular holes and macular pucker, often with vitreoschisis (see below).
Embedded within the posterior vitreous cortex are hyalocytes. These mononuclear phaocytes are spread widely apart in a single layer situated 20–50 µm from the ILM of the retina. The highest density of hyalocytes is in the vitreous base, followed next by the posterior pole, with the lowest density at the equator. Hyalocytes are oval or spindle shaped, 10–15 µm in diameter, and contain a lobulated nucleus, a well-developed Golgi complex, smooth and rough endoplasmic reticula, many large lysosomal granules (periodic acid–Schiff positive), and phagosomes ( Fig. 6.4.7 ). Balazs pointed out that hyalocytes are located in the region of highest hyaluronan concentration and suggested that these cells are responsible for hyaluronan synthesis. Hyalocyte capacity to synthesize collagen was first demonstrated by Newsome et al. Similar to chondrocyte metabolism in the joint, hyalocytes may synthesize vitreous collagen at some, but not all, times during life. The phagocytic capacity of hyalocytes is consistent with the presence of pinocytic vesicles and phagosomes and the presence of surface receptors that bind immunoglobulin G and complement. It is intriguing to consider that hyalocytes are among the first cells to be exposed to any migratory or mitogenic stimuli during various disease states, particularly proliferative vitreoretinopathy. These cells may, therefore, be important in the pathophysiology of proliferative disorders at the vitreous–retinal interface, including macular pucker.
The vitreo–retinal interface is not only important as the site of many tractional and proliferative vitreoretinal disorders but also impacts therapeutics. Pharmacologic vitreolysis of vitreoretinal adhesion as well as drug delivery to the macula and transretinal gene therapies via viral vectors that must traverse this interface are influenced by the underlying anatomy and biochemistry of the vitreous–retinal interface. The basal laminae surrounding the vitreous body are composed of type IV collagen closely associated with glycoproteins.
At the pars plana, the basal lamina has a true lamina densa. The basal lamina posterior to the ora serrata is the ILM of the retina. The layer immediately adjacent to the Müller cell is a lamina rara, which is 0.03–0.06 mm thick. The lamina densa is thinnest at the fovea (0.01–0.02 mm) and disc (0.07–0.1 mm). It is thicker elsewhere in the posterior pole (0.5–3.2 mm) than at the equator or vitreous base. The anterior surface (vitreous side) of the ILM is normally smooth, whereas the posterior aspect is irregular, filling the spaces created by the irregular subjacent nerve fiber layer. This feature is most marked at the posterior pole, whereas in the periphery both the anterior and posterior aspects of the ILM are smooth. The significance of this topographical variation is not known. At the rim of the optic disc the ILM ceases, although the basal lamina continues as the “inner limiting membrane of Elschnig.” This membrane is 50 microns thick and is believed to be the basal lamina of the astroglia in the papilla. At the central-most portion of the optic disc, the membrane thins to 20 microns, follows the irregularities of the underlying cells of the optic nerve head, and is composed only of glycosaminoglycans with no collagen. This structure is known as the central meniscus of Kuhnt. The thinness and chemical composition of these membranes may account for, among other phenomena, the frequency with which abnormal cell proliferation arises from or near the optic disc in proliferative diabetic retinopathy and macular pucker.
The vitreous body is most firmly attached at the vitreous base, disc, and macula and over retinal blood vessels. The posterior aspect (retinal side) of the ILM demonstrates irregular thickening farther posteriorly from the ora serrata. So-called attachment plaques between the Müller cells and the ILM have been described in the basal and equatorial regions of the fundus but not in the posterior pole, except for the fovea. It has been hypothesized that these develop in response to vitreous traction on the retina. The thick ILM in the posterior pole dampens the effects of this traction, except at the fovea, where the ILM is thin. The thinness of the ILM and the purported presence of attachment plaques at the central macula could explain the predisposition of this region to changes induced by traction. An unusual vitreous–retinal interface overlies retinal blood vessels. Physiologically, this may provide a shock-absorbing function to dampen arteriolar pulsations. However, pathologically, this arrangement could also account for the proliferative and hemorrhagic events that are associated with vitreous traction on retinal blood vessels.
Macroscopic Morphology
In an emmetropic adult human eye, vitreous is approximately 16.5 mm in axial length with a depression anteriorly just behind the lens (patellar fossa). The hyloideocapsular ligament of Weiger is the annular region (1–2 mm in width and 8–9 mm in diameter), where vitreous is attached to the posterior aspect of the lens. Erggelet’s or Berger’s space is at the center of the hyaloid capsular ligament. The canal of Cloquet arises from this space and courses posteriorly through the central vitreous ( Fig. 6.4.3 ), which is the former site of the hyaloid artery in the embryonic vitreous. The former lumen of the artery is an area devoid of collagen fibrils and surrounded by multifenestrated sheaths that were previously the basal laminae of the hyaloid artery wall. Posteriorly, Cloquet’s canal opens into a funnel-shaped region anterior to the optic disc, known as the area of Martegiani.
Within the adult human vitreous there are parallel nonbranching fibers that course in an anteroposterior direction ( Fig. 6.4.4 ), arising from the vitreous base, where they insert anterior and posterior to the ora serrata. The connections between the peripheral anterior vitreous fibers and the retina underlie the pathophysiology of retinal tears because of the strong adhesion in this location. The peripheral vitreous fibers are circumferential with the vitreous cortex, whereas the central fibers “undulate” parallel to Cloquet’s canal. Ultrastructural studies have demonstrated that collagen, organized in bundles of parallel fibrils, is the only microscopic structure corresponding to these fibers. It is hypothesized that visible vitreous fibers form when hyaluronan molecules no longer separate the microscopic collagen fibrils, which results in the aggregation of collagen fibrils into bundles from which hyaluronan molecules are excluded. The areas adjacent to these large fibers have a low density of collagen fibrils and a relatively high concentration of hyaluronan molecules. Composed primarily of “liquid vitreous,” these areas scatter very little incident light and, when prominent, constitute the “lacunae” seen with aging ( Fig. 6.4.5 ).
Microscopic Morphology
The vitreous cortex is the peripheral “shell” of the vitreous body that courses forward and inward from the anterior vitreous base (anterior vitreous cortex) and posteriorly from the posterior border of the vitreous base, (posterior vitreous cortex). The posterior vitreous cortex is 100–110 mm thick and consists of densely packed collagen fibrils. Although no direct connections exist between the posterior vitreous and the retina, the posterior vitreous cortex is adherent to the inner limiting membrane (ILM) of the retina, which is, in part, the basal lamina of retinal Müller cells. Adhesion between the posterior vitreous cortex and the ILM probably results from the action of various extracellular matrix molecules.
A hole in the prepapillary vitreous cortex can sometimes be visualized clinically when the posterior vitreous is detached from the retina ( Fig. 6.4.6 ). If peripapillary tissue is torn away during PVD and remains attached to the vitreous cortex about the prepapillary hole, it is referred to as Weiss’ ring. Vitreous can extrude through the prepapillary hole in the vitreous cortex but does so to a lesser extent than through the premacular vitreous cortex, where, occasionally, vitreomacular adhesion and axial traction can cause vitreomacular traction syndrome. Tangential vitreomacular traction is implicated in the pathogenesis of macular holes and macular pucker, often with vitreoschisis (see below).
Embedded within the posterior vitreous cortex are hyalocytes. These mononuclear phaocytes are spread widely apart in a single layer situated 20–50 µm from the ILM of the retina. The highest density of hyalocytes is in the vitreous base, followed next by the posterior pole, with the lowest density at the equator. Hyalocytes are oval or spindle shaped, 10–15 µm in diameter, and contain a lobulated nucleus, a well-developed Golgi complex, smooth and rough endoplasmic reticula, many large lysosomal granules (periodic acid–Schiff positive), and phagosomes ( Fig. 6.4.7 ). Balazs pointed out that hyalocytes are located in the region of highest hyaluronan concentration and suggested that these cells are responsible for hyaluronan synthesis. Hyalocyte capacity to synthesize collagen was first demonstrated by Newsome et al. Similar to chondrocyte metabolism in the joint, hyalocytes may synthesize vitreous collagen at some, but not all, times during life. The phagocytic capacity of hyalocytes is consistent with the presence of pinocytic vesicles and phagosomes and the presence of surface receptors that bind immunoglobulin G and complement. It is intriguing to consider that hyalocytes are among the first cells to be exposed to any migratory or mitogenic stimuli during various disease states, particularly proliferative vitreoretinopathy. These cells may, therefore, be important in the pathophysiology of proliferative disorders at the vitreous–retinal interface, including macular pucker.
The vitreo–retinal interface is not only important as the site of many tractional and proliferative vitreoretinal disorders but also impacts therapeutics. Pharmacologic vitreolysis of vitreoretinal adhesion as well as drug delivery to the macula and transretinal gene therapies via viral vectors that must traverse this interface are influenced by the underlying anatomy and biochemistry of the vitreous–retinal interface. The basal laminae surrounding the vitreous body are composed of type IV collagen closely associated with glycoproteins.
At the pars plana, the basal lamina has a true lamina densa. The basal lamina posterior to the ora serrata is the ILM of the retina. The layer immediately adjacent to the Müller cell is a lamina rara, which is 0.03–0.06 mm thick. The lamina densa is thinnest at the fovea (0.01–0.02 mm) and disc (0.07–0.1 mm). It is thicker elsewhere in the posterior pole (0.5–3.2 mm) than at the equator or vitreous base. The anterior surface (vitreous side) of the ILM is normally smooth, whereas the posterior aspect is irregular, filling the spaces created by the irregular subjacent nerve fiber layer. This feature is most marked at the posterior pole, whereas in the periphery both the anterior and posterior aspects of the ILM are smooth. The significance of this topographical variation is not known. At the rim of the optic disc the ILM ceases, although the basal lamina continues as the “inner limiting membrane of Elschnig.” This membrane is 50 microns thick and is believed to be the basal lamina of the astroglia in the papilla. At the central-most portion of the optic disc, the membrane thins to 20 microns, follows the irregularities of the underlying cells of the optic nerve head, and is composed only of glycosaminoglycans with no collagen. This structure is known as the central meniscus of Kuhnt. The thinness and chemical composition of these membranes may account for, among other phenomena, the frequency with which abnormal cell proliferation arises from or near the optic disc in proliferative diabetic retinopathy and macular pucker.
The vitreous body is most firmly attached at the vitreous base, disc, and macula and over retinal blood vessels. The posterior aspect (retinal side) of the ILM demonstrates irregular thickening farther posteriorly from the ora serrata. So-called attachment plaques between the Müller cells and the ILM have been described in the basal and equatorial regions of the fundus but not in the posterior pole, except for the fovea. It has been hypothesized that these develop in response to vitreous traction on the retina. The thick ILM in the posterior pole dampens the effects of this traction, except at the fovea, where the ILM is thin. The thinness of the ILM and the purported presence of attachment plaques at the central macula could explain the predisposition of this region to changes induced by traction. An unusual vitreous–retinal interface overlies retinal blood vessels. Physiologically, this may provide a shock-absorbing function to dampen arteriolar pulsations. However, pathologically, this arrangement could also account for the proliferative and hemorrhagic events that are associated with vitreous traction on retinal blood vessels.
Age-Related Changes
Embryology and Postnatal Development
Early in embryogenesis, the vitreous is filled with blood vessels, called the vasa hyaloidea propria. It is not known what stimulates regression of this hyaloid vascular system, but recent studies have identified significant changes in the proteome of the human embryo that may underlie the process of vascular regression. Teleologically, this seems necessary not only to induce regression of the vascular primary vitreous but also to inhibit subsequent cell migration and proliferation and thereby minimize light scatter and achieve transparency. Identifying the phenomena inherent in this transformation may reveal how to control pathological neovascularization in the eye and elsewhere. Recent studies have characterized the proteomic profile of embryonic human vitreous during hyaloid vessel regression in an attempt to identify the factors that might create and maintain a clear vitreous. These studies found that there is upregulation of certain pathways with concurrent downregulation of others. These findings may, thus, have relevance to developing new therapeutic strategies to induce the regression of pathological neovascularization in ocular and systemic diseases, such as metastatic carcinoma.
Developmental Anomalies
Persistent fetal vasculature (PFV) syndrome is an uncommon developmental anomaly in which the hyaloid vasculature of the primary vitreous fails to involute. This condition was initially described in detail by Reese in his 1955 Jackson Memorial Lecture, where he named it persistent hyperplastic primary vitreous . The subject was revisited by Goldberg in his 1997 Jackson Memorial Lecture, where he coined the term PFV.
There is a spectrum of PFV severity, ranging from pupillary strands and a Mittendorf’s dot to a dense retrolenticular membrane and/or retinal detachment. Anterior PFV consists of retrolenticular fibrovascular tissue that attaches to the ciliary processes and draws them centrally, inducing cataract formation, shallowing of the anterior chamber, and angle-closure glaucoma. Iris vessel engorgement and recurrent intraocular hemorrhage can result in phthisis bulbi, although the prognosis with surgery is often fair. Posterior PFV consists of a prominent vitreous fibrovascular stalk that emanates from the optic nerve and courses anteriorly. Preretinal membranes at the base of the stalk are common, often with tractional retinal folds and traction retinal detachment. The prognosis for posterior PFV is poor, suggesting that pharmacotherapy may be the only solution for this form of PFV. In this regard, it has recently been proposed that insufficient levels of vitreous endostatin may be important in the pathogenesis of PFV, consistent with the aforementioned proteomic studies.
Improper vitreous biosynthesis during embryogenesis underlies a variety of developmental abnormalities. Normal vitreous biosynthesis requires normal retinal development because at least some of the vitreous structural components are synthesized by retinal Müller cells. A clear gel, typical of normal “secondary vitreous,” appears only over developed retina. Thus in various developmental anomalies, such as retinopathy of prematurity (ROP), familial exudative vitreoretinopathy, and related entities, vitreous that overlies undeveloped retina in the peripheral fundus is a viscous liquid but not a gel. The extent of this finding depends, at least in ROP, on the gestational age at birth because the younger the individual, the more undeveloped is the peripheral retina, especially temporally. In other truly congenital conditions, there are inborn errors of collagen metabolism that have now been elucidated. In Stickler’s syndrome, defects in specific genes have been associated with particular phenotypes, thus enabling the classification of patients with Stickler’s syndrome into four subgroups. Patients in the subgroups with vitreous abnormalities are found to have defects in the genes coding for type II procollagen and type V/XI procollagen.
Ongoing synthesis of both collagen and hyaluronan occurs during development to adulthood, and hyaluronan stabilizes the collagen network.
Aging of the Vitreous Body
Substantial rheological, biochemical, and structural alterations occur in vitreous during aging. After age 45–50 years, there is a significant decrease in the gel volume and an increase in the liquid volume of human vitreous. These findings were confirmed qualitatively in postmortem studies of dissected human vitreous, and liquefaction was observed to begin in the central vitreous. Vitreous liquefaction actually begins much earlier than detectable by clinical examination or ultrasonography. Postmortem studies have found evidence of liquid vitreous at age 4 years and have observed that by the time the human eye reaches its adult size (ages 16–18 years) approximately 20% of the total vitreous volume consists of liquid vitreous. In these studies of fresh, unfixed postmortem human eyes, it was observed that after age 40 years, there is a steady increase in liquid vitreous, simultaneous with a decrease in gel volume. By age 80–90 years, more than half the vitreous body is liquid. The finding that the central vitreous is where fibers are first observed is consistent with the concept that breakdown of the normal hyaluronan-collagen association results in simultaneous vitreous liquefaction and aggregation of collagen fibrils into bundles of parallel fibrils, seen as large fibers (see Fig. 6.4.4 ). In the posterior vitreous, such age-related changes often form large pockets of liquid vitreous, recognized clinically as lacunae, or pockets.
The mechanism of vitreous liquefaction is not well understood. Gel vitreous can be liquefied in vivo through the removal of collagen by exogenous enzymatic destruction of the collagen network. It has also been shown that the injection of chondroitinase can induce liquefaction and “disinsertion” of the vitreous. Ocriplasmin is another agent that can induce vitreous liquefaction. Because of its ability to also induce dehiscence at the vitreous–retinal interface, this agent received approval for pharmacological vitreolysis
Endogenous vitreous liquefaction may be the result of changes in the minor glycosaminoglycans and chondroitin sulfate profile of vitreous. Another possible mechanism is a change in the conformation of hyaluronan molecules with aggregation or cross-linking of collagen molecules. Singlet oxygen can induce conformational changes in the tertiary structure of hyaluronan molecules. Free radicals generated by metabolic and photosensitized reactions could alter hyaluronan and/or collagen structure and trigger a dissociation of collagen and hyaluronan molecules, which ultimately results in liquefaction. This is plausible because the cumulative effects of a lifetime of daily exposure to light may influence the structure and interaction of collagen and hyaluronan molecules by the proposed free radical mechanism(s).
Biochemical studies support the rheological observations. Total vitreous collagen content does not change after age 20–30 years. However, in studies of a large series of normal human eyes obtained at autopsy, the collagen concentration in the gel vitreous at age 70–90 years (approximately 0.1 mg/mL) was twofold greater than at age 15–20 years (approximately 0.05 mg/mL). Because the total collagen content does not change, this finding most likely reflects the decrease in the volume of gel vitreous that occurs with aging and consequent increase in the concentration of the collagen that remains in the gel. The collagen fibrils in aging vitreous gel become packed into bundles of parallel fibrils, likely with cross-links between them. In patients with diabetes, abnormal collagen cross-links have been identified in the vitreous body, a phenomenon that has been described for other extracellular matrices in patients with diabetes. These findings are consistent with the existence of a diabetic vitreopathy, independent of diabetic retinopathy. The structural effect of these biochemical and rheological changes consists of a transition from a clear vitreous in youth ( Fig. 6.4.8 ), to a fibrous structure in the adult (see Fig. 6.4.4 ), which results from aggregation of collagen fibrils. In patients with diabetes, this occurs earlier in life because of nonenzymatic glycation of vitreous collagen. In old age, advanced liquefaction (synchisis; see Fig. 6.4.5 ) ultimately leads to collapse (syneresis) of the vitreous and posterior vitreous detachment (PVD).
