Inflammations
As a relatively acellular and completely avascular structure, the vitreous is not an active participant in inflammatory disorders. It does become involved secondarily in inflammatory conditions of adjacent tissues, however. The term vitritis is used to denote the presence of benign or malignant white blood cells in the vitreous. Vitreous inflammation associated with infectious agents, particularly bacteria and fungi, is clinically referred to as infectious endophthalmitis. Bacterial endophthalmitis is characterized by neutrophilic infiltration of the vitreous (Fig 10-2). This infiltration leads to liquefaction of the vitreous, with subsequent posterior vitreous detachment. Severe inflammation may be accompanied by formation of fibrocellular membranes, which typically form in the retrolental space and may exert traction on the peripheral retina. The vitreous infiltrate in noninfectious uveitis is typically composed of chronic inflammatory cells, including T and B lymphocytes, macrophages, and histiocytes. See also BCSC Section 9, Intraocular Inflammation and Uveitis.
Degenerations
Syneresis and Aging
Syneresis of the vitreous is defined as liquefaction of the gel. Syneresis of the central vitreous is an almost universal consequence of aging. It also occurs as a consequence of vitreous inflammation and hemorrhage and in the setting of pathologic myopia. The prominent lamellae and strands that develop in aging and following inflammation or hemorrhage are the result of abnormally aggregated collagenous vitreous fibers around syneretic areas (Fig 10-3). Syneresis is one of the contributing factors leading to vitreous detachment.
Posterior Vitreous Detachment
Posterior vitreous detachment (PVD) occurs when a dehiscence in the vitreous cortex allows fluid from a syneretic cavity to gain access to the potential subhyaloid space, causing the remaining cortex to be stripped from the ILM (Fig 10-4). As fluid drains out of the syneretic cavities under the newly formed posterior hyaloid, the vitreous body collapses anteriorly, remaining attached only at its base. Vitreous detachment generally occurs rapidly over the course of a few hours to days.
A weakening of the adherence of the cortical vitreous to the ILM with age also plays a role in PVDs. The reported incidence of PVD is up to 65% at age 65 and is increased by intraocular inflammation, aphakia or pseudophakia, trauma, and vitreoretinal disease. PVD is important in the pathogenesis of many conditions, including retinal tears and detachment, vitreous hemorrhage, and macular hole formation. See BCSC Section 12, Retina and Vitreous, for additional discussion.
Rhegmatogenous Retinal Detachment and Proliferative Vitreoretinopathy
Retinal tears form from vitreous traction on the retina during or after PVD or secondary to ocular trauma. Tears are most likely to occur at sites of greatest vitreoretinal adhesion, such as the vitreous base (Fig 10-5) or the margin of lattice degeneration. The histopathology of retinal tears reveals that the vitreous is adherent to the retina along the flap of the tear. In the area of retina separated from the underlying retinal pigment epithelium (RPE), there is loss of photoreceptors.
Retinal detachment occurs when vitreous traction and fluid currents resulting from eye
movements combine to overcome the forces maintaining retinal adhesion to the RPE. The principal histopathologic findings in retinal detachment consist of the following:
degeneration of the outer segments of the photoreceptors eventual loss of photoreceptor cells
migration of Müller cells
proliferation and migration of RPE cells
Small cystic spaces develop in the detached retina, and in chronic detachment, these cysts may coalesce into large macrocysts (Fig 10-6).
With rhegmatogenous retinal detachment, cellular membranes may form on either surface (anterior or posterior) of the retina (Fig 10-7). Clinically, this process is referred to as proliferative vitreoretinopathy (PVR). PVR membranes form as a result of proliferation of RPE cells and other cellular elements, including glial cells (Müller cells, fibrous astrocytes), macrophages, fibroblasts, myofibroblasts, and possibly hyalocytes. The cell biology of PVR is complex and involves the interaction of various growth factors, integrins, and cellular proliferation. Studies have shown a significant association between clinical grades of PVR and the expression levels of specific cytokines and/or growth factors in the vitreous fluid.
Harada C, Mitamura Y, Harada T. The role of cytokines and trophic factors in epiretinal membranes: involvement of signal transduction in glial cells. Prog Retin Eye Res. 2006;25(2):149–164. Epub 2005 Dec 27.
Macular Holes
Idiopathic macular holes most likely form as the result of degenerative changes in the vitreous. Optical coherence tomography (OCT) has greatly advanced our understanding of the anatomical features of full-thickness macular holes and early macular hole formation. These studies are most consistent with a focal anteroposterior traction mechanism, but some inconsistencies in clinical cases suggest a role for degeneration of the inner retinal layers. Localized perifoveal vitreous detachment (an early stage of age-related PVD) appears to be the primary pathogenetic event in idiopathic macular hole formation (Fig 10-8). Detachment of the posterior hyaloid from the pericentral retina exerts anterior traction on the foveola and localizes the dynamic vitreous traction associated with ocular rotations into the perifoveolar region.
OCT has clarified the pathoanatomy of early macular hole stages, beginning with a foveal pseudocyst (stage 1a), typically followed by disruption of the outer retina (stage 1b), before progressing to a full-thickness dehiscence (stage 2). Histologically, full-thickness macular holes are similar to holes in other locations. A full-thickness retinal defect with rounded tissue margins (stage 3) is accompanied by loss of the photoreceptor outer segments in adjacent retina that is separated from the RPE by subretinal fluid (Fig 10-8C). An epiretinal membrane composed of Müller cells, fibrous astrocytes, and fibroblasts with myoblastic differentiation is often present on the surface of the retina adjacent to the macular hole. Cystoid macular edema in the parafoveal retina adjacent to the full-thickness macular hole is relatively common. Following surgical repair of macular holes, closer apposition of the remaining photoreceptors and variable glial scarring close the macular defect. See BCSC Section 12, Retina and Vitreous, for further discussion.
Gass JD. Reappraisal of biomicroscopic classification of stages of development of a macular hole. Am J Ophthalmol. 1995;119(6):752–759.
Smiddy WE, Flynn HW Jr. Pathogenesis of macular holes and therapeutic implications. Am J Ophthalmol. 2004;137(3):525–537.
Hemorrhage
A constellation of pathologic features may develop in the vitreous following vitreous hemorrhage. After 3–10 days, red blood cell clots undergo fibrinolysis and red blood cells may diffuse throughout the vitreous cavity. At this time, breakdown of the red blood cells also occurs. Loss of hemoglobin from the red blood cells produces ghost cells (see Chapter 7, Fig 7-10) and hemoglobin spherules (Fig 10-9). Obstruction of the trabecular meshwork by these cells may lead to ghost cell glaucoma. See also BCSC Section 10, Glaucoma.
The process of red blood cell dissolution attracts macrophages, which phagocytose the effete red blood cells. The hemoglobin is broken down to hemosiderin and then removed from the eye. In massive hemorrhages, cholesterol crystals caused by the breakdown of red blood cell membranes may be present, often surrounded by a foreign body giant cell reaction. Cholesterol appears clinically as refractile intravitreal crystals (synchesis scintillans). Syneresis of the vitreous and PVD are common after vitreous hemorrhage.
Asteroid Hyalosis
Asteroid hyalosis is a condition with a spectacular clinical appearance (see Fig 16-8 in BCSC Section 12, Retina and Vitreous) but little clinical significance. Histologically, asteroid bodies are rounded structures measuring 10–100 nm that stain positively with alcian blue and positively with stains for neutral fats, phospholipids, and calcium (Fig 10-10). The bodies stain metachromatically and exhibit birefringence. Occasionally, asteroid bodies will be surrounded by a foreign body giant cell, but the condition is not generally associated with vitreous inflammation.
The exact mechanism of formation of asteroid bodies is not known; however, element mapping by electron spectroscopic imaging has revealed a homogeneous distribution of calcium, phosphorus, and oxygen. The electron energy loss spectra of these elements show details similar to those found for hydroxyapatite. Immunofluorescence microscopy has revealed the presence of chondroitin-6- sulfate at the periphery of asteroid bodies; and carbohydrates specific for hyaluronic acid were observed by lectin-gold labeling to be part of the inner matrix of asteroid bodies. Thus, asteroid bodies exhibit structural and elemental similarity to hydroxyapatite, and proteoglycans and their glycosaminoglycan side chains appear to play a role in regulating the biomineralization process.
Winkler J, Lünsdorf H. Ultrastructure and composition of asteroid bodies. Invest Ophthalmol Vis Sci. 2001;42(5):902–907.
Vitreous Amyloidosis
The term amyloidosis refers to a group of diseases that lead to extracellular deposition of amyloid. Amyloid is composed of various proteins that have a characteristic ultrastructural appearance of nonbranching fibrils with variable length and a diameter of 75–100 Å (Fig 10-11). The proteins forming amyloid also have in common the ability to form a tertiary structure characterized as a β- pleated sheet, which then enables the proteins to bind Congo red stain and show birefringence in polarized light (Fig 10-12).
Amyloid may be derived from various types of protein, and the protein of origin is characteristic for different forms of amyloidosis. Amyloid deposits occur in the vitreous when the protein forming the amyloid is transthyretin, previously known as prealbumin. Multiple genetic mutations have been described that result in various amino acid substitutions in the transthyretin protein. The most common mutations were originally described in familial amyloid polyneuropathy (FAP) types I and II. Systemic manifestations in patients with FAP include vitreous opacities and perivascular infiltrates (Fig 10-13), peripheral neuropathy, cardiomyopathy, and carpal tunnel syndrome.