Vitreous

Published on 20/03/2015 by admin

Filed under Pathology

Last modified 22/04/2025

Print this page

This article have been viewed 3548 times

Vitreous

Normal Anatomy

I. The transparent vitreous body, or hyaloid (Fig. 12.1), is one of the most delicate connective tissues in the body.

A. It occupies the posterior or largest compartment of the eye (~80% of the eye’s volume), filling the globe between the internal limiting membrane of the neural retina and the posterior lens capsule.

B. The structure is composed of a framework of extremely delicate, embryonic-like collagen filaments closely associated with a large quantity of water-binding hyaluronic acid.

Fig. 12.1 Normal vitreous. A, The vitreous compartment is completely filled by the vitreous body. The major components of the vitreous are hyaluronic acid and delicate collagenous filaments. B, On the left is a vitreous body stained with colloidal iron so that it appears blue. On the right, the tissue was first treated with hyaluronidase and no staining occurred, indicating that the blue-staining material on the left is hyaluronic acid. C, The other major components—the collagenous, delicate vitreous filaments (f)—are demonstrated by this electron micrograph of a shadow-cast preparation. The neural retina (r) occupies the diagonal lower left side and the filaments the diagonal upper right side. D, A ciliary-body melanoma has elevated the ora serrata region (o) so that it is clearly seen. Note that the attachment site (a) of the vitreous base appears as two white lines, one easily seen just anterior to the ora serrata and the other less easily seen just posterior to the ora serrata. This is the strongest attachment site of the vitreous body. The next strongest attachment site surrounds the optic nerve head, followed by a ring in the clivus of the anatomic fovea centralls (i, iris). (A, Armed Forces Institute of Pathology Neg. 57–1284. B and C, modified from Fine BS, Yanoff M: Ocular Histology: A Text and Atlas, 2nd edn. © Elsevier 1979.)

II. Embryology

A. Embryologically, the developing avascular secondary vitreous surrounds and compresses the vascularized primary vitreous into a tube or canal that extends from the optic disc to the back of the lens, forming the hyaloid canal (canal of Cloquet).

B. The hyaloid vessel, which atrophies and disappears before birth, passes through the canal.

C. Persisting remnants of the primary vitreous or hyaloid vessel produce congenital anomalies (see later), the most common being retention of tissue fragments on the back of the lens (Mittendorf’s dot; Fig. 12.2), retention of tissue on the nasal optic disc (Bergmeister’s papilla), and persistent primary vitreous (see Chapter 18).

Fig. 12.2 Mittendorf’s dot. A, Slit-lamp appearance of tiny white Mittendorf’s dot (m) at back of lens. B, Microscopic appearance of hyaloid vessel (h) as it approaches the posterior capsule (u, posterior umbilication of lens considered to be an artifactitious finding often seen in infants).

Congenital Anomalies

Persistent Primary Vitreous

I. Remnants of the primitive hyaloid vascular system, either anterior or posterior, may persist, or the entire hyaloid vessel from the optic disc to the back of the lens may remain.

Hyaloid vessel remnants are observed in more than 90% of infants of less than 36 weeks’ gestation and in more than 95% of infants weighing less than 5 pounds (2.275 kg) at birth.

A. Anterior remnants (see Fig. 12.2; see also Fig. 9.3)

1. The lenticular portion of the hyaloid artery may hang free in the vitreous from its lens attachment site.

2. Mittendorf’s dot is an opacity just below and nasal to the lens posterior pole at the lenticular attachment site of the hyaloid artery.

B. Posterior remnants (Fig. 12.3)

1. Vascular loops from the optic disc may remain within Cloquet’s canal.

2. Bergmeister’s papilla is the glial remnant of the hyaloid system at the optic disc. The papilla, which usually occupies the nasal portion of the optic disc, may appear as a solid mass of whitish tissue; as a delicate, ragged strand; or as a well-defined membrane stretching over the disc.

3. Congenital cysts, which are usually pearly gray, wrinkled, and translucent, are the cystic remains of the hyaloid system.

They usually float freely but may be attached to the optic disc or suspended by a pedicle. Some have been shown histologically to consist of gliotic retinal or vascular remnants, whereas others resemble pigment epithelial cells (i.e., choristoma of the primary hyaloid system).

Fig. 12.3 Posterior remnants. Posterior remnants may be mild, as in this Bergmeister’s papilla located on the nasal optic disc (A), or extreme, as in this posterior hyperplastic vitreous (B), which extends from the optic disc to the back of the lens (C). D, The enucleated eye shows posterior remnants of the hyaloid system over the nasal portion of the optic nerve head (b, Bergmeister’s papilla). E, Histologic section shows a Bergmeister’s papilla (b) in the form of a glial remnant of the hyaloid system.

Persistent Hyperplastic Primary Vitreous (Persistent Fetal Vasculature)

I. Anterior (see Chapter 18)

II. Posterior (congenital retinal septum; ablatio falciformis congenita)

A. Posterior persistent hyperplastic primary vitreous (PHPV; see Fig. 12.3) is most often unilateral and present at birth. Poor vision and strabismus are the most common presenting complaints.

B. Posterior PHPV consists of vitreous membranes extending from the disc usually toward the equatorial zone, posterior radial retinal fold (usually in the area of the vitreous membrane), disturbances of macular function, and neural retinal detachment.

Inflammation

Acute

See Chapter 3.

Chronic

See Chapters 3 and 4.

Vitreous Adhesions

Post Nonsurgical and Surgical Trauma

I. Vitreocorneal adhesions may cause corneal “touch” syndrome (see Fig. 5.5).

A. Corneal touch syndrome occurs when formed vitreous touches the endothelium of the posterior surface of the cornea, usually after a complicated cataract extraction, especially in the era of intracapsular cataract extraction.

B. The cornea becomes thickened and edematous in the region of touch.

II. Iridovitreal adhesions may lead to total posterior synechiae (seclusion of pupil) with resultant iris bombé, or they may form a membrane across the pupil (occlusion of pupil), or both.

III. Cyclovitreal adhesions may lead to a cyclitic membrane and subsequent neural retinal detachment.

IV. Vitreoretinal adhesions may lead to the macular vitreous traction syndrome (cystoid macular edema; Irvine–Gass syndrome; see Chapter 5) or to wrinkling of the internal limiting membrane, namely “cellophane” retina (see Figs. 11.43–11.45).

Traction of the vitreous on normal paravascular vitreoretinal attachment sites in an eye with a posterior vitreous detachment can cause neural retinal tears. Neural retinal tears tend to occur in clusters between the equator and the posterior border of the vitreous base.

V. White-without-pressure most likely is related to vitreoretinal adhesions. The areas of white-without-pressure may be migratory.

Postinflammation

See Chapters 3 and 4.

Idiopathic

Idiopathic vitreous adhesions may follow partial vitreoretinal separation (posterior vitreous detachment).

Vitreous Opacities

Hyaloid Vessel Remnants

Muscae volitantes are minute remnants of the hyaloid vascular system or detachments of small folds of poorly differentiated retinal tissue, usually present in the anterior vitreous.

Muscae volitantes also is a historical, obsolete term for acquired vitreous floaters.

Acquired Vitreous Strands and Floaters

I. Collapse and condensation of vitreous sheets with aging, especially in myopes, frequently cause the formation of strands and floaters.

II. Separation of the vitreous attachment to the optic disc after posterior vitreoretinal separation may cause a complete or incomplete ringlike floater (vitreous “peephole”; see subsection on vitreous detachment, later).

III. Symptomatic degenerative vitreous floaters may have a negative impact on the quality of life.

Inflammatory Cells

I. “Snowball” opacities (microabscesses) may occur with mycotic infections (especially with the mold fungi).

II. Whitish masses (“white balls”) may be seen inferiorly with vitreitis (e.g., sarcoidosis).

Macrophages and small T lymphocytes are the major cell types found in vitreous opacity samples diagnosed as inflammation.

III. Numerous vitreous opacities, foamy “Whipple” macrophages, may be found in persons with Whipple’s disease (Fig. 12.4).

A. Whipple’s disease is a disorder of men, usually older than 35 years of age.

1. The detection of the causative agent, Tropheryma whippelii, by polymerase chain reaction allows confirmation of the clinical diagnosis.

2. The gram-positive bacteria, Arthrobacter species, phylogenetically related to T. whippelii, may also be causative agents.

B. Arthritis, fever, serous effusions, cough, lymphadenopathy, and malaise may occur for several years preceding the intestinal malabsorption, steatorrhea, and cachexia.

C. Ocular findings, in addition to vitreous opacities, include inflammations and ophthalmoplegia.

D. Foamy macrophages containing periodic acid–Schiff (PAS)-positive cytoplasm may be found in intestinal and rectal mucosa, mesenteric and extra-abdominal lymphatic tissue, heart, lungs, liver, adrenals, spleen, serous membranes, neural retina, and vitreous.

1. In addition, intracellular and extracellular rod-shaped bacillary bodies and serpiginous membranes are found by electron microscopic examination of macrophages.

2. It is now assumed that the characteristic macrophages derive their PAS-positivity from ingested rod-shaped bacilli (Tropheryma whippelii) and also from their residue in autophagic vacuoles of the macrophages.

Fig. 12.4 Whipple’s disease. A, Inner retinal layers infiltrated by macrophages that exhibit pale blue cytoplasm and eccentric or paracentral small nuclei. Few macrophages are seen along internal limiting membrane (ILM). Epiretinal membrane has caused ILM to wrinkle. B, Decreased magnification shows neural retinal nerve fiber layer adjacent to macula containing myriad intensely PAS-positive macrophages. Outer and inner nuclear layers are relatively spared. C, Electron microscopy shows macrophage with serpiginous stacks of membranous structures intermixed with degenerating rod-shaped bacteria, both of which are encased in phagocytic vacuoles. D, Another macrophage shows almost equal admixture of membranous structures and degenerating bacteria. Inset depicts rod-shaped organism in longitudinal section and in cross-section. (From Font RL et al.: Arch Ophthalmol 96:1431, 1978. © American Medical Association. All rights reserved.)

Red Blood Cells

I. Red blood cells in the vitreous compartment (see Figs. 12.11 and 12.12) are most often caused by neural retinal tears but may have other causes. Red blood cells may be subvitreal (between vitreous body and internal limiting membrane of the neural retina) or intravitreal (within the vitreous body).

II. Hypoxia of the vitreous body may be demonstrated when blood enters it in a patient who has sickle-cell trait or disease.

A. Sickling and hemolysis of the erythrocytes increase toward the central vitreous, the most hypoxic area.

B. On histologic examination of a vitreous specimen or an enucleated globe, occasionally the diagnosis of sickle-cell trait or disease is made in a person not known previously to be so affected.

Iridescent Particles

I. Asteroid hyalosis (Benson’s disease; Figs. 12.5 and 12.6) consists of complex lipids embedded in an amorphous matrix containing mainly calcium and phosphorus and attached to the vitreous framework.

A. Diabetes mellitus is a major risk factor; other risk factors include systemic hypertension, atherosclerotic vascular disease, and hyperopia.

B. Asteroid hyalosis has the following clinical properties:

1. Asteroid bodies remain attached to collagenous framework and move only when the framework oscillates. They are seen as gold balls when viewed with side illumination (e.g., with the ophthalmoscope) and appear white with direct illumination (e.g., with the slit lamp).

2. The condition is usually unilateral and most common in the seventh and eighth decades of life. It is infrequently associated with neural retinal detachment.

Asteroid hyalosis may be a risk factor for the development of calcification of silicone lens implants.

C. Histologically, asteroid bodies consist of an amorphous matrix that is both PAS-positive and acid mucopolysaccharide-positive and contains birefringent, small crystals when viewed with polarized light. Electron microscopically, the bodies are composed of finely laminated ribbons of complex lipids, especially phospholipids, lying in a homogeneous background and intertwined with filaments of vitreous framework.

Fig. 12.5 Asteroid hyalosis. A, The fundus reflex shows tiny gold-colored balls in the anterior vitreous. B, The enucleated globe shows multiple tiny white spherules suspended throughout the vitreous body. Histologic section shows that the spherules stain positively with the acid mucopolysaccharide stain (C) and are birefringent to polarized light (D).

Fig. 12.6 Asteroid hyalosis. A, Scanning electron micrograph of asteroid bodies intertwined with vitreous collagen. B, Center and edge of single asteroid body show core of dense interlacing ribbons surrounded by rim (right side) of delicate strands. (A, Courtesy of Dr. RC Eagle, Jr.; B, courtesy of Dr. BW Streeten.)

II. Synchysis scintillans (cholesterolosis; see Figs. 5.39 and 5.40) consists of degenerative material not attached to the vitreous framework.

When vitreous gains access to the anterior chamber (e.g., in aphakia), a synchysis scintillans of the anterior chamber results.

A. Synchysis scintillans has the following clinical properties:

1. It is golden in color both to retroillumination and to direct view.

2. Usually it is unilateral and most common in men in their fourth or fifth decade.

3. It frequently follows an intravitreal (within vitreous body) hemorrhage.

4. The material settles inferiorly when the eye is immobile.

5. When in the anterior chamber, it disappears (melts) on the application of heat (e.g., as with a sun lamp).

B. Histologically, clefts represent the sites of dissolved-out cholesterol crystals within the vitreous body.

Retinal Fragments

A free-floating operculum is the nonattached or separated neural retinal tissue derived from a neural retinal hole.

Traumatic Avulsion of Vitreous Base

The condition is rare and usually caused by trauma or shrinkage of vitreal fibrous membranes (Fig. 12.7).

Fig. 12.7 Avulsion of vitreous base. The vitreous base is seen to be partially avulsed (a). The patient had blunt injury to this eye (o, ora serrata; t, traumatic chorloretinal atrophy; r, retina).

Vitreous Detachment

I. Anterior

A. Hyaloideocapsular separation occurs in approximately 0.1% of the population.

B. It has a greater incidence in phakic eyes that contain a neural retinal detachment.

II. Posterior (Figs. 12.8 and 12.9)

A. The condition is present in approximately 65% of people older than 65 years of age and in more than 50% of people between 50 and 65 years of age. Posterior vitreous detachment (PVD) often develops in the fellow eye within two years of development in the first year.

B. Partial PVD is less common than the complete form, but late complications such as retinal tears are more likely to occur than with complete PVD. Shafer’s sign or “tobacco dust” is vitreous pigment secondary to PVD, retinal hole formation or retinal detachment.

C. The most common cause of PVD is senescence; other causes include high myopia, diabetes mellitus, ocular inflammation, and aphakia.

D. The most important complication of PVD, aside from the creation of floaters, is neural retinal tears. If a neural retinal detachment is to occur, it usually ensues at the time of the PVD; it is rare as a late event.

E. Syneresis (i.e., one or more areas of central degeneration and liquefaction of the vitreous body) may occur with or without PVD.

F. Histologically, the vitreous filaments are collapsed anteriorly so as to form a condensed posterior vitreous layer (“membrane”). The new subvitreal space posteriorly contains a watery fluid but lacks collagenous filaments.

Fig. 12.8 Posterior vitreous detachment. A, Gross eye shows the vitreous completely detached posteriorly from the neural retina but still attached to the optic nerve head. B, Histologic section of eye shown in A demonstrates fibrous connection (f) of vitreous to the edges of the optic nerve but posteriorly detached elsewhere (r, retina).

Fig. 12.9 Posterior vitreous detachment (PVD). A, Clinical appearance of PVD consists here of a circle viewed against a background of the fundus reflex (“vitreous peephole”). B, Here, PVD appears solid. PVD may appear to patient as a circle (doughnut) or, if broken, as J- or C-shaped, or solid opacity. C, Gross specimen shows complete detachment posteriorly of vitreous from neural retina and optic nerve. D, Gross specimen of another eye shows the previous attachment site of the vitreous to the optic nerve now floating freely in the central vitreous compartment as a round fibrous band. E, PVD noted at 3:30 o’clock of the lens as round, white ring in gross specimen.

Proteinaceous Deposits

I. Proteinaceous deposits may form diffuse dust-like or cloud-like opacities.

II. They are analogous to plasmoid aqueous and occur chiefly with cyclitis, chorioretinitis, or trauma.

Amyloid

I. Primary familial amyloidosis (AL amyloidosis; Fig. 12.10; see also Chapter 7)

A. Primary familial amyloidosis has immunoglobulin light-chain immunoglobulin fragments that are designated as amyloid AL (the same type of amyloid that is found in myeloma-associated amyloid).

B. Vitreous opacities, frequently in the form of bilateral, sheetlike vitreous veils, are seen along with a retinal perivasculitis. Amyloid may reach the vitreous directly from affected retinal blood vessels.

The nonfamilial form of primary amyloidosis is a rare condition that even more rarely can cause vitreous opacity.

C. Ecchymosis of lids, proptosis, ocular palsies, internal ophthalmoplegia, and neuroparalytic keratitis result from amyloid deposition in the lids and orbital connective tissues, muscles, nerves, and ganglia.

D. Glaucoma may be caused by amyloid deposition in the aqueous outflow areas.

E. Systemic amyloid deposition is widespread.

F. Histologically, a pale eosinophilic material is found in the vitreous that binds iodine and Congo red, demonstrates birefringence and dichroism (see later), shows metachromasia with metachromatic dyes such as toluidine blue and crystal violet, shows fluorescence after exposure to thioflavin-T, and has a filamentous ultrastructure.

Birefringence is the change in refractive indices with respect to light polarized in different directions through a substance. Dichroism is the property of a substance absorbing light polarized in a certain direction. When light is polarized at right angles to this direction, it is transmitted to a greater extent. In contrast to birefringence, dichroism can be specific for a particular substance. Dichroism can be observed in a microscope with the use of either a polarizer or an analyzer, but not both, because the dichroic substance itself (e.g., amyloid) serves as polarizer or analyzer, depending on the optical arrangement. Amyloid is dichroic only to green light.

1. The deposited amyloid filaments found in tissues are portions of immunoglobulin light chains. Filaments of amyloid are difficult to differentiate from normal vitreous filaments.

2. The walls of retinal and choroidal blood vessels may be thickened by the amyloid material.

Fig. 12.10 Amyloidosis. A, Prominent diffuse vitreous opacities present in each eye. Diagnostic vitrectomy was performed. Histologic section of vitreous biopsy shows Congo red-positivity (B) and birefringence with polarized light (C). D, Electron micrograph shows fibrillar material with the individual fibers measuring 7–10 nm in diameter and having a faintly banded pattern. (Case presented by Dr. DJ Wilson to the meeting of the Verhoeff Society, 1994.)

II. Familial amyloidotic polyneuropathy (FAP)

A. FAP is a hereditary form of systemic amyloidosis that involves vitreous (types I and II) and peripheral nerves. FAP, first described in an Indian pedigree with Swiss origins, also has been described in Portuguese, Swedish, and Japanese kindreds.

1. In both FAP types I and II, the responsible protein is mutant transthyretin, designated amyloid AF.

In the majority of patients, the valin-30 of transthyretin is replaced by methionine.

2. Type I FAP includes vitreous amyloidosis and an autonomic and peripheral neuropathy, most often affecting the lower extremities.

3. Type II FAP includes vitreous amyloidosis and peripheral neuropathy, most often affecting the upper extremities first, along with a cardiomyopathy and sometimes a carpal tunnel syndrome.

4. Patients with types III and IV FAP do not acquire vitreous opacities, but they do develop peripheral neuropathy, nephropathy, and peptic ulcers.

a. In type III FAP, mutant apolipoprotein A1 is the responsible precursor protein.

b. In type IV FAP (also called Meretoja syndrome), mutant gelsolin is the responsible protein deposited.

Familial Exudative Vitreoretinopathy

I. Familial exudative vitreoretinopathy (FEVR) is characterized by organized membranes in all quadrants of the vitreous.

A. Vitreoretinal traction results from the pull of the membranes.

B. Snowflake-like opacities are present in the vitreous body.

C. The vitreous is usually detached posteriorly.

II. Frequently encountered are peripheral neural retinal exudates, localized neural retinal detachment often forming a broad fold temporally from the disc, and peripheral neural retinal neovascularization with recurrent vitreous hemorrhages.

Results of fluorescein angiography suggest a primary abnormality in the peripheral retinal circulation as the cause of the entity.

III. Slowly progressive ocular changes may ultimately lead to a condition that mimics certain aspects of retinopathy of prematurity, Coats’ disease, and peripheral uveitis.

IV. FEVR is genetically heterogeneous: X-linked, autosomal-dominant (most common), and autosomal-recessive types have been described.

At least three corresponding genes (FZD4, LRP5, and NDP) in four loci (EVR1-i) have been identified.

Autosomal-Dominant Vitreoretinochoroidopathy (ADVIRC; Peripheral Annular Pigmentary Dystrophy of the Retina)

I. ADVIRC clinically shows a stationary or slowly progressive, circumferential (360°), bilateral and symmetric involvement of a coarse, peripheral hyperpigmentation and hypopigmentation of the fundus; a relatively discrete posterior border occurs in the region of the equator.

A. The retinopathy is associated with fibrillar condensation of the vitreous and superficial and deep, yellowish-white, punctate opacities in the fundus.

B. Other ocular findings include retinal vascular attenuation, transudation, and neovascularization; cystoid macular edema; choroidal atrophy; and cataract formation.

II. Histologically, disorganization of the peripheral neural retina occurs with focally atrophic retinal pigment epithelium (RPE).

A. Altered RPE cells surround retinal vessels and line the internal limiting membrane.

B. The equatorial neural retina shows an unusual multifocal loss of photoreceptors.

C. An extensive epiretinal membrane consists of condensed vitreous, cellular debris, and layers of Müller cells.

Autosomal-Dominant Neovascular Inflammatory Vitreoretinopathy (ADNIV)

I. ADNIV clinically resembles ADVIRC, except that in the initial stage it shows a characteristic selective reduction of the electroretinogram b-wave amplitude; in addition, the pigmentary changes are less distinctive in ADNIV than in ADVIRC.

II. Cystoid macular edema, vitreous hemorrhage, tractional neural retinal detachment, and neovascular glaucoma can cause a profound loss of vision.

Erosive Vitreoretinopathy

I. Erosive vitreoretinopathy is characterized by pronounced vitreous abnormalities, complicated neural retinal detachments, and a progressive pigmentary retinopathy.

A. The condition is inherited in an autosomal-dominant pattern. Mutations that cause erosive vitreoretinopathy (and also Wagner’s disease) are linked to markers on the long arm of chromosome 5 (5q13–14).

B. Clinically, nyctalopia, progressive visual field loss, marked vitreous syneresis, progressive atrophy of the RPE, and combined traction–rhegmatogenous neural retinal detachments are seen.

1. Previously normal-appearing RPE seems to thin or erode (hence the term erosive) in younger patients, allowing increased visualization of choroidal vessels. Advanced cases show equatorial areas apparently devoid of RPE.

2. Electroretinography demonstrates diffuse rod–cone dysfunction.

High myopia, epiphyseal dysplasia, orofacial anomalies, and systemic manifestations characteristic of other vitreoretinopathies are absent.

C. No histologic studies are available.

Knobloch Syndrome

I. Knobloch syndrome is characterized by high myopia, vitreoretinal degeneration, retinal detachment, and a localized defect in the occipital region of the skull.

A. It is inherited as an autosomal recessive disease.

B. A mutation occurs in the COL1A1 gene, which encodes collagen XVII and its normal product endostatin, an inhibitor of angiogenesis.

II. Endostatin is absent from the serum.

III. Persistent hyperplastic primary vitreous may be present.

Vitreous Hemorrhage

Definitions

I. Subvitreal hemorrhage (Fig. 12.11)—blood is present between the internal limiting membrane of the neural retina and the posterior “face” of the vitreous and takes weeks to months to clear. This type of hemorrhage is commonly seen in diabetic patients.

Fig. 12.11 Vitreous hemorrhage. A, Histologic section shows blood present between the internal limiting membrane (ILM) of the neural retina and the posterior “face” of the vitreous (takes weeks to months to clear). B, Blood is present in the vitreous body (takes many months to years to clear). C, Fundus appearance of hemorrhage completely within the neural retina between the ILM and the nerve fiber layer (intraretinal submembranous hemorrhage) (r, retinal hemorrhage; s, sub-ILM intraretinal hemorrhage). D, Histologic section shows blood present between the ILM and the nerve fiber layer completely within the neural retina (intraretinal submembranous hemorrhage) (i, internal surface of retina; s, sub-ILM intraretinal hemorrhage).

II. Intravitreal hemorrhage (Fig. 12.12; see Fig. 12.11)—blood is present in the vitreous body and takes many months to years to clear.

Fig. 12.12 Vitreous hemorrhage. A, A hemorrhage is seen in the vitreous body (b, blood in vitreous compartment; i, iris with superior-sector iridectomy). B, In this vitrectomy specimen of an intravitreal hemorrhage from a 67-year-old black man, the red blood cells were noted to have a sickle configuration; a diagnosis of sickle-cell trait was made. The diagnosis had not been made previously. C, Another vitrectomy specimen shows red blood cells (r) and pigment-containing macrophages (p). D, A special stain for iron (Perl’s stain) shows that the pigment in some of the macrophages stains positively (blue), signifying hemosiderin; the pigment in other macrophages does not stain and presumably represents melanin or hemoglobin not yet oxidized to hemosiderin. (A, Courtesy of Dr. SH Sinclair; B–D, courtesy of Dr. RC Eagle, Jr.)

III. Subhyaloid hemorrhage—this is identical to subvitreal hemorrhage, but use of the term clinically may be confusing.

Sometimes the term subhyaloid hemorrhage is used clinically to describe an intraretinal submembranous hemorrhage (i.e., a hemorrhage located mainly between the nerve fiber layer and the internal limiting membrane of the neural retina; see (Figs. 12.12 and 11.42D).

Causes

I. Causes include blood dyscrasias; choroidal hemorrhage with extension; diabetic retinopathy; Eales’ disease; hypertensive retinopathy; juvenile retinoschisis; malignant melanoma; metastatic intraocular tumors; neural retinal neovascularization from any cause; neural retinal tears; retinal angiomas; retinoblastoma; subneural retinal neovascularization; Terson’s syndrome; sickle-cell retinopathy; subarachnoid hemorrhage; trauma; uveitis; and vitreoretinal separation.

II. Terson’s syndrome

A. Terson’s syndrome consists of hemorrhage into the vitreous compartment associated with intracranial, subarachnoid, or subdural hemorrhage. Vitreous hemorrhage develops in approximately 16% or 17% of patients in whom spontaneous subarachnoid hemorrhage occurs.

B. Vitreous hemorrhage frequently obscures visualization of the fundus.

1. When visualization of the neural retina is possible, multiple preneural, intraneural (usually subinternal limiting membrane), and subneural retinal hemorrhages are often seen.

2. Other findings include epiretinal membranes, proliferative vitreoretinopathy, pigmentary macular changes, and perimacular neural retinal folds similar to the folds seen in the battered-baby (shaken-baby) syndrome.

Complications

I. Organization

A. Membranes may lie on the internal surface of the neural retina (i.e., epiretinal) and cause a cellophane retina or fixed retinal folds (see Figs. 11.43–11.45).

B. Many of the delicate epiretinal (on the retinal surface) and preretinal (elevated from the retinal surface) membranes, especially those of the macular and paravascular regions, are believed to form from inward migration and proliferation of the various small glial cells normally present in the nerve fiber and ganglion cell layers.

1. Other cells, such as RPE cells, fibrocytes, and myofibroblasts, can also be found.

2. As the membranes shrink or contract, fixed folds of the retina develop (see Chapter 11).

C. When fibrous RPE or glial membranous proliferations on the internal or external surface of the neural retina are associated with vitreous retraction, a neural retinal detachment and new neural retinal holes may result.

D. When the membranous process is extensive and associated with a total neural retinal detachment, it is called proliferative vitreoretinopathy (PVR); the older terminologies were massive vitreous retraction and massive periretinal proliferation.

1. PVR may follow perforating trauma, neural retinal detachment, and surgical manipulation.

2. Although PVR most often develops posteriorly and equatorially, it may also occur anteriorly, where it results in anterior dragging of the peripheral neural retina.

3. PVR probably represents a tissue-reparative process and can be thought of as nonvascular granulation tissue.

4. The provariant of p53 codon 72 polymorphism may be a significant risk factor for PVR development.

Some evidence suggests that fibronectin may mediate the initial events in epiretinal membrane formation and that vitronectin may modulate the adhesion mechanisms in established membranes. Transforming growth factor-β₂ levels are increased in eyes that have intravitreal fibrosis associated with PVR, and the levels appear to correlate with the severity of PVR.

E. Histologically, glial, fibrous, or RPE membranes, or any combination, are seen on the internal, external, or both surfaces of the retina.

1. T lymphocytes and macrophages may be present in the membranes.

2. The membrane stroma or matrix is composed primarily of types I, II, and III collagen, accompanied focally by types IV and V collagen, laminin, and heparan sulfate.

II. Hemolytic (ghost cell) glaucoma (see Chapter 16)

Access the complete reference list online at