Vitreous Hemorrhage

Brian A Phillpotts, MD, MD

Brian A Phillpotts, MD, MD is a member of the following medical societies: American Academy of
Ophthalmology, American Diabetes Association, American Medical Association, National Medical
Association
Updated: May 04, 2015

Vitreous hemorrhage is the extravasation of blood into one of the several potential spaces formed within
and around the vitreous body. This condition may result directly from retinal tears or neovascularization of
the retina, or it may be related to bleeding from preexisting blood vessels in these structures.
The vitreous body is bounded posterolaterally by the internal limiting membrane of the retina,
anterolaterally by the nonpigmented epithelium of the ciliary body, and anteriorly by the lens zonular fibers
and posterior lens capsule. The retrolental space of Erggelet and the canal of Petit are potential spaces.
These 2 spaces are located between the anterior hyaloid membrane, the posterior lens capsule, and the
orbiculoposterocapsular portion of the zonular fibers. The hyaloideocapsular ligament separates them from
each other.
The Cloquet canal and the bursa premacularis are fluid-filled spaces within the formed vitreous into which
blood can enter during vitreous hemorrhage. The aqueous-filled space anterior to the formed vitreous is
called the canal of Hannover. This space is located between the orbiculoanterocapsular and
posterocapsular portions of the zonular fibers.
Historically, anatomists do not consider it a part of vitreous humor; however, hemorrhage into this space is
considered functionally as vitreous hemorrhage. The same is true for bleeding into the retrohyaloid or
subhyaloid spaces and for subinternal limiting membrane hemorrhage.
On April 20, 1970, the first pars plana vitrectomy for the treatment of nonclearing vitreous hemorrhage was
performed by Machemer.[1] Prior to pars plana vitrectomy, the removal of nonclearing vitreous hemorrhage
was attempted by excising vitreous gel through the pupillary aperture using cellulose sponges and scissors
via a corneoscleral incision, which was coined "open-sky" vitrectomy by Kasner.[2] The procedure was
frequently unsuccessful, and patients often had a permanent reduction in vision.

Pathophysiology
The vitreous has 3 strong attachment areas with the retina. The strongest attachment straddles the most
anterior area of the retina (ora serrata) where a 4-mm circular band forms the vitreous base. Traction at the
vitreous base usually is transmitted to the adjacent peripheral retina. The next strong attachment of the
vitreous is at the circular zone around the optic nerve head. This zone becomes progressively weakened
with increasing age, and it becomes easily separated with posterior vitreous detachment.
In the adult, the vitreous body volume is approximately 4 mL, which is 80% of the globe. The content of the
vitreous is 99% water, and the remaining 1% mostly is composed of collagen and hyaluronic acid.
Additionally, there are a few other soluble components such as ions, proteins, and trace cells. These
components account for the gelatinous but clear nature of the vitreous.
The vitreous is avascular and inelastic. Pathological mechanisms of vitreous hemorrhage can include
hemorrhage from diseased retina, traumatic insult, and/or spread of hemorrhage into the retina and
vitreous from any other intraocular sources.
Given the history and physical findings, it also may be reasonable to consider extraocular etiologies such
as leukemia. Usually, coagulation disorders or anticoagulant therapy does not cause vitreous hemorrhage;
however, bleeding from abnormal new vessels or rupture of normal retinal vessels from direct or indirect
trauma frequently is associated with vitreous hemorrhage. Bleeding from neovascular and fragile vessels in
proliferative diabetic retinopathy, proliferative sickle cell retinopathy, ischemic retinopathy secondary to
retinal vein occlusion, and retinopathy of prematurity are among the most common pathological causes of
vitreous hemorrhage.
The most common pathogenesis of bleeding in this group of disorders is believed to be retinal ischemia
causing the release of angiogenic vasoactive factors, most notably vascular endothelial growth factor
(VEGF), basic fibroblast growth factors (bFGF), and insulin-like growth factor (IGF). The second most
frequent pathological mechanism for vitreous hemorrhage is tearing of the retinal vessels caused by either
a break in the retina or detachment of the posterior vitreous, while the cortical vitreous is adherent to the

retinal vessels. In addition, patients with sickle cell retinopathy may show a salmon-patch hemorrhage
caused by blowout in the vessel wall following abrupt occlusion in the arterioles by aggregated sickled red
blood cells.
Other less common pathological mechanisms of vitreous hemorrhage include subretinal bleeding with
secondary extension into the vitreous cavity.
Age-related macular degeneration and choroidal melanoma are the two leading causes of vitreous
hemorrhage secondary to breakthrough bleeding. Terson syndrome is subarachnoid hemorrhage
associated with vitreous bleeding caused by rupture of retinal venules and/or capillaries as a result of a
sudden increase in intracranial pressure (which is transmitted to the retinal vasculature via the optic nerve).
Reports have shown that about 33% of patients with subarachnoid hemorrhage may have associated
intraocular hemorrhage, and approximately 6% of patients have vitreous hemorrhage. In Terson syndrome,
branches of the central retinal vein or the central retinal vein itself is the most common source of intraocular
bleeding. Terson syndrome occurs mostly in younger individuals (age 30-50 y).

Epidemiology
Frequency
United States
The prevalence of vitreous hemorrhage tends to parallel the frequency of the causative disease. In general,
the cause-prevalence of vitreous hemorrhage depends on the study population, mean age of the patients,
and geographical region where the study is conducted. In adults, proliferative diabetic retinopathy is the
most frequent cause of vitreous hemorrhage, 31.5-54% in the United States, 6% in London, and 19.1% in
Sweden.
The other causes of vitreous hemorrhage include the following:

Retinal tear (11.4-44%)

Posterior vitreous detachment with retinal vascular tear (3.7-11.7%)
Rhegmatogenous retinal detachment (7-10%)
Proliferative sickle cell retinopathy (0.2-5.9%)
Macroaneurysm (0.6-7.4%)
Age-related macular degeneration (0.6-4.3%)
Terson syndrome (0.5-1%)
Trauma (12-18.8%)
Retinal neovascularization as a result of branch or central retinal vein occlusion (3.5-16%)
Rare causes of vitreous hemorrhage account for about 6.4-18% of vitreous hemorrhage. In several studies,
2-7.6% of the hemorrhage could not be attributed to a specific cause.
The leading cause of vitreous hemorrhage in young people is trauma.
Congenital retinoschisis and pars planitis also may cause vitreous hemorrhage in both children and adults.

Mortality/Morbidity
The complications of vitreous hemorrhage include hemosiderosis bulbi with photoreceptor toxicity,
glaucoma, severe floaters, and myopic shift in infants.
In hemosiderosis bulbi, iron (Fe3+) is released during hemoglobin breakdown. This occurs intracellularly in
macrophages with subsequent storage as ferritin or hemosiderin. Alternatively, the catabolism of
hemoglobin can take place extracellularly and the released iron binds to vitreous proteins with iron-binding
capacity, such as lactoferrin and transferrin. The vitreous contains 13 times more iron-binding proteins
relative to the serum, with a physiological saturation of the total iron-binding capacity of about 35%. Given
the slow clearance of blood in the vitreous, the persistence of intact red blood cells and the slow hemolysis
in the vitreous, the amount of iron released from hemoglobin is a relatively small fraction of that available at
any given time.
The exact mechanism of postvitreous hemorrhage retinal damage has not been completely elucidated. It
currently is believed that this damage may be caused by direct or indirect toxicity of iron. For example, iron
enters cell wall membranes via secondary lysosomes with the liberation of contained enzymes causing

indirect damage. Iron also has been implicated in the release of mitogenic growth factor from macrophages
following phagocytosis of blood from vitreous hemorrhage.
Overall, patients with long-standing vitreous hemorrhage and relatively normal retina tend to have good
visual acuity. The vitreous hemorrhage-induced glaucoma is secondary to the blockade of the trabecular
meshwork by formed ghost cells due to long-standing blood cells in the vitreous. Ghost cells are small,
khaki-colored, spherical, more rigid cells, which develop from long-standing red blood cells in the vitreous
where there is a relatively low oxygen tension. In hemolytic glaucoma, the trabecular meshwork is blocked
by red blood cell debris, free hemoglobin, and hemoglobin-laden macrophages. In hemosiderotic
glaucoma, the iron derived from vitreous hemorrhage binds to the trabecular meshwork
mucopolysaccharide causing endothelial cell damage with possible complications of sclerosis and
obliteration of the intertrabecular spaces. This form of glaucoma often presents after years of recurrent
vitreous hemorrhage.
Myopic shift and amblyopia have been reported to follow long-standing vitreous hemorrhage in infants,
especially in those younger than 2 years.
In high myopic persons, the risk of retinal tears, detachment, and associated vitreous hemorrhage is
increased.
In general, iron-related toxicity may become clinically apparent in instances of significant long-standing
vitreous hemorrhage, often with histopathologic signs of hemosiderosis.

Race
The demographics of vitreous hemorrhage correspond to the incidence of the underlying disease with
which it is associated.
In blacks, diabetes and sickle cell disease tend to be the most common.
In elderly whites with vitreous hemorrhage, retinal vascular tears and neovascularization caused by
proliferative diabetic retinopathy and branch retinal vein occlusion are more common. In the same
population, macular degeneration and breakthrough bleeding into the vitreous are not infrequent.

Sex
Corresponds to the incidence of the underlying disease with which it is associated

Age
Corresponds to the incidence of the underlying disease with which it is associated

Clinical Presentation
History
Patients with vitreous hemorrhage often present with a complaint of visual haze, floaters, cloudy vision or
smoke signals, photophobia, and perception of shadows and cobwebs.
Small vitreous hemorrhage often is perceived as new multiple floaters, moderate vitreous hemorrhage is
perceived as dark streaks, and dense vitreous hemorrhage tends to significantly decrease vision even to
light perception.
Usually, no pain is associated with vitreous hemorrhage. Exceptions may include cases of neovascular
glaucoma, severe acute ocular hypertension secondary to ghost-cell glaucoma, or trauma.
Ophthalmoscopic examination reveals blood within the vitreous gel and/or the anterohyaloid or retrohyaloid
spaces.

Physical

Vitreous hemorrhage within the Berger space tends to settle and form a crescent-shaped pool overlying the
hyaloideocapsular ligament.
In the Cloquet canal, vitreous hemorrhage tends to delineate its inferior border and that within the
retrohyaloid space caused by vitreous detachment may accumulate as a meniscus at the inferior
vitreoretinal boundary, boat-shaped hemorrhage.
Similarly, vitreous hemorrhage within the space between the internal limiting and the nerve fiber layer may
resemble that within the retrohyaloid space, except that the blood does not shift with change in the head
position as may be the case with subhyaloid hemorrhage.
Note that subinternal limiting membrane hemorrhage usually implies an intraretinal source of bleeding,
whereas subhyaloid hemorrhage usually implies a source of bleeding anterior to the retina.
Vitreous hemorrhage due to Terson syndrome, anemia, Valsalva retinopathy, shaken baby syndrome, and
retinal macroaneurysm rarely breaks through the internal limiting membrane or into the subretinal space.
Vitreous hemorrhage due to diabetic retinopathy and branch retinal vein occlusion starts anterior to the
internal limiting membrane and bleeds into the vitreous.
The hemorrhage tends to progress through a distinct change in color from red to pink to orange to yellow
white. In subinternal limiting membrane hemorrhage, especially in sickle cell retinopathy, iridescent spots
may develop with resolution of these hemorrhages. Iridescent spots are refractile, copper-colored granules
representing hemosiderin-laden macrophages subjacent to the internal limiting membrane. These spots are
unusual in hemorrhages anterior to the internal limiting membrane as in diabetic retinopathy or branch
retinal vein occlusion.
Because of the presence of focal attachment between the internal limiting membrane and the retina at the
central fovea area and peripheral to the posterior pole, subinternal limiting membrane hemorrhage tends
to spare the central fovea. Some attachment of the vitreous at the fovea may exist, which may explain why
some preretinal hemorrhages spare the fovea.
On the other hand, bleeding into the vitreous body shows no definite border. In massive vitreous
hemorrhages, a mild afferent pupillary defect may be observed.
Detailed history and physical examination are very important. History of any ocular or systemic diseases
(particularly those mentioned above) as being associated with vitreous hemorrhage, including trauma,
should be elicited.
Complete eye examination should be performed, including slit lamp examination (with gonioscopy to
determine angle and iris neovascularization), intraocular pressure, and dilated fundus examination of both
eyes with indirect ophthalmoscopy.
Scleral depression may be performed in some instances of spontaneous vitreous hemorrhage if a view of
the peripheral retina is possible. In general, scleral depression is not recommended until 3-4 weeks after
traumatic, vitreous hemorrhage. Scleral depression may detect a flap retinal tear.
In the absence of a view of the retina, B-scan ultrasonography is used to ascertain the presence of retinal
detachment, retinal tear, intraocular foreign body, or intraocular tumor.
In some cases, the cause of vitreous hemorrhage may be ascertained by a fluorescein angiogram, if the
clarity of the media allows.

Causes
See Pathophysiology.

Vitreous Hemorrhage Differential Diagnoses

Diagnostic Considerations

ARMD, Exudative
Branch Retinal Artery Occlusion
Branch Retinal Vein Occlusion
Central Retinal Vein Occlusion
Diabetic Background Retinopathy
Diabetic Proliferative Retinopathy
Diabetic Retinopathy
Eales Disease
Leukemias
Macroaneurysm
Melanoma, Choroidal
Melanoma, Ciliary Body
Melanoma, Iris
Neovascular Membranes, Subretinal
Neovascularization, Choroidal
Ocular Ischemic Syndrome
Ocular Manifestations of Syphilis
Presumed Ocular Histoplasmosis Syndrome
Retinitis Pigmentosa
Retinoblastoma
Retinopathy of Prematurity
Sarcoidosis
Uveitis, Intermediate

Workup
Laboratory Studies
Consider ordering laboratory studies as per the suspected underlying etiology and its corresponding
differential diagnosis. See Differentials.

Imaging Studies
Consider ordering imaging studies as per the suspected underlying etiology and its corresponding
differential diagnosis.
With CT scan and/or MRI, exclude globe perforation, intraocular foreign body, avulsed optic nerve,
intraocular tumor, displaced scleral buckle, and intraocular lens materials. See Differentials.

Ocular B-scan ultrasonography is used when the media is opacified enough to preclude a complete and
clear (including view of the ora serrata) funduscopic examination.

Treatment & Management

Medical Care
Treatment is directed at the underlying cause, if known.
On rare occasions, such as unreliable/noncompliant patients with vitreous hemorrhage complicated with
severe hyphema, patients may be admitted to the hospital for close observation. Otherwise, most patients
are monitored closely on an outpatient basis with emphasis on cooperation with treatment instructions.
Bed rest with the head of the bed elevated 30-45 with occasional bilateral patching to allow the blood to
settle inferiorly, allowing a view of the superior peripheral fundus
Avoid drugs such as aspirin and other anticlotting agents when necessary.

Surgical Care
The goal is to treat the underlying cause as quickly as possible. For example, retinal breaks are closed by
laser photocoagulation or cryotherapy (unlike cryotherapy, laser photocoagulation can close the
compromised vessel in addition to the retinal tear); detached retinas are reattached with surgery; and
proliferative retinal vascular diseases are treated with laser photocoagulation or cryotherapy (when there is
no view of the retina).
Indications for surgical removal of the vitreous blood include the following:

Vitreous hemorrhage associated with detached retina

Long-standing vitreous hemorrhage with duration greater than 2-3 months (Vitrectomy for isolated
vitreous hemorrhage (eg, without retinal detachment) may be performed before 2-3 months in patients
with juvenile-onset diabetes, patients with bilateral vitreous hemorrhage, children in the amblyogenic age
range, and/or when retinal traction is suspected.) [4]
Vitreous hemorrhage associated with rubeosis
Vitreous hemorrhage associated with hemolytic or ghost-cell glaucoma

Consultations
Consultations depend on the suspected underlying etiology and most likely differential diagnoses. See
Differentials.
Retinal specialist

Medication Summary
Medical therapy depends on the suspected underlying etiology and the most likely differential diagnosis.
See Differentials. Avoid drugs such as aspirin and other anticlotting agents when necessary.

Follow-up
Further Outpatient Care
Initially, patients with vitreous hemorrhage are monitored daily for 2-5 days to rule out retinal tear or
detachment, then every 1-2 weeks for spontaneous clearing. However, in the event that the dense vitreous

hemorrhage persists without known underlying cause, a B-scan ultrasonography should be serially
performed.

Inpatient & Outpatient Medications

Medications depend on the suspected underlying etiology and most likely differential diagnoses. See
Differentials.

Deterrence/Prevention
A study by Smith and Steel has shown a certain amount of evidence to support that using antivascular
endothelial growth factor preoperatively in diabetic vitrectomy can lower the occurrence of early
postoperative vitreous cavity hemorrhage.[5]

Prognosis
Prognosis depends on the suspected underlying etiology and most likely differential diagnoses. See
Differentials.