- ICD-9 379.23
- ICD-10 H43.1
Vitreous Hemorrhage is a relatively common cause of acute vision loss, having an incidence of approximately 7 cases per 100,000, 4.8 per 10000 in Taiwan, and may vary according to population characteristic, geography, and other factors. It is therefore frequently encountered by ophthalmologists and Emergency Room professionals alike due to its often rapid onset which causes painless, but substantial vision loss. Although the diagnosis of vitreous hemorrhage is often straightforward to make on funduscopic examination or ultrasonography, further investigation may be required to determine the underlying etiology.
The frequency of the etiologies of vitreous hemorrhage is variable according to the characteristics of the study population.
The three most common causes include
- proliferative diabetic retinopathy (PDR),
- posterior vitreous detachment (PVD) with or without retinal tear, and
- ocular trauma, which account for 59-88.5% of all cases.
Less common causes of vitreous hemorrhage include
- retinal vein occlusion,
- retinal vasculitis,
- proliferative sickle cell retinopathy,
- retinal arterial macroanuerysm,
- subarachnoid hemorrhage (Terson syndrome),
- Valsalva retiniopathy
- other disorders including X-linked retinochisis, retinopathy of prematurity, familial exudative vitreoretinopathy, intermediate uveitis,
- Blood dyscrasias/coagulation disorders, and
- neovascular age-related macular degeneration (See Differential Diagnosis, below).
The population at risk for vitreous hemorrhage will have the demographic and clinical characteristics according to its causes. For example, poorly controlled diabetics with end-organ damage such as proliferative diabetic retinopathy are at high risk. People younger than 40 with vitreous hemorrhage often have a history of recent ocular trauma whereas older, non-diabetic populations with vitreous hemorrhage often suffered an acute PVD and/or retinal tear.
Although anticoagulants and antiplatelet agents do not likely cause spontaneous vitreous hemorrhage, they may enhance bleeding from pathology. Notably, however, the Early Treatment of Diabetic Retinopathy Study did not show increased risk of vitreous hemorrhage among aspirin users. Patients with systemic coagulation disorders and blood dyscrasias such as leukemia and thrombocytopenia may have an increased risk of vitreous hemorrhage, but these cases are rare.
Extravasation of blood into the vitreous cavity is generally caused by two basic mechanisms:
- Rupture of normal vessels through mechanical force:
- Closed globe injury from blunt trauma: Compression of the globe in an anterior-posterior direction causes the equator of the globe to bulge in a coronal plane. Especially in a young patient with formed vitreous and strong adherence of the vitreous to the retina, this bulging in the coronal plane causes inward-directed traction exerted by the vitreous on the retina. The fact that the vitreous base, an area of especially strong vitreous attachment, is near the equator contributes to the tractional force the vitreous exerts on the retina in this area. This inward-directed tractional force on the retina by the vitreous can cause a retinal dialysis, but it can also result in retinal tears and vitreous hemorrhage as retinal vessels may be ruptured. Blunt trauma may also rupture blood vessels associated with the iris and ciliary body, causing hyphema and spillover hemorrhage into vitreous.
- Open globe injury: Blunt or sharp trauma causing a full-thickness defect in the eyewall may cause hemorrhage in all layers of the eye, including vitreous hemorrhage.
- Shaken baby syndrome: The trauma associated with shaken baby syndrome may cause hemorrhage in all ocular layers, including vitreous hemorrhage. It has been suggested that vitreous hemorrhage in this context may portend a worse prognosis.
- Acute PVD: Vitreous hemorrhage in the setting of acute PVD is associated with a retinal tear or break in 70-95% of cases and should invoke an exhaustive search for retinal breaks.
- Terson syndrome: Terson syndrome is a rare cause of vitreous hemorrhage associated with subarachnoid hemorrhage. The vitreous hemorrhage is not a direct extension of subarachnoid hemorrhage into the eye via the optic nerve sheath. Rather, increased intracranial pressure causes increased pressure in retinal venules, causing them to rupture. Sub-internal limiting membrane (sub-ILM) hemorrhage is noted and intraoperatively a break may be noted in the ILM through which the blood is thought to reach the vitreus gel from the sub-ILM cavity.
- Hemorrhage from pathologic structures:
- Rupture of retinal neovascularization: Retinal ischemia caused by conditions such as diabetic retinopathy, retinal vein occlusion, sickle cell retinopathy, and retinopathy of prematurity promote the growth of new vessels (neovascularization) via the elaboration of angiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and insulinlike growth factor. The neovascular vessels grow into the vitreous and are fragile. Normal eye movements, acute PVD, and fibrovascular contraction of the neovascularization can all cause these vessels to bleed.
- Retinal macroaneurysms and acutely occluded retinal venules in retinal vein occlusion may rupture, causing vitreous hemorrhage.
- Choroidal tumors, or choroidal neovascularization secondary to conditions such as age-related macular degeneration can cause "break-through" bleeding, through the retina and into the vitreous.
Hemorrhage into the vitreous body results in rapid clot formation and clears at a rate of approximately 1% per day . Erythrocytes exit through the trabecular meshwork, undergo hemolysis, phagocytosis, or persist within the vitreous for many months. The cellular response to erythrocytes in the vitreous is unusual because there is no early polymorphonuclear cell response and the ensuing inflammatory response is instead more similar to a "low-turnover" granuloma. The muted inflammatory response in the immunologically privileged eye serves to mitigate ocular tissue damage and promote clarity of the visual axis.
Primary prevention should be directed at controlling risk factors for systemic vascular disease such as diabetes, hypertension, and smoking. Frequent dilated fundus exams can reveal advanced retinopathy in high risk populations and provide the opportunity for therapeutic intervention. Proper eye protection should be worn during activities likely to cause eye trauma (e.g. hammering or grinding metal, using firearms, playing sports with high-speed balls such as racquetball).
Evidence of vitreous hemorrhage is often seen on physical exam and inferred through history. Systemic past medical and ocular history can help lead to diagnosis.
Sudden, painless visual loss or haze is a common presentation. Patients may describe a red hue to their vision. Patients may describe new onset floaters, shadows, or "cobwebs". Symptoms may be worse in the morning if blood settles on the macula during the night. History of diabetes, hypertension, sickle cell disease, trauma, previous retinal conditions or ocular surgery may help lead to the diagnosis.
Visual acuity is variable based on the location, size, and degree of vitreous hemorrhage. In severe cases, patients may have dramatically reduced visual acuity and/or visual field defects. Slit lamp examination usually reveals red blood cells in the anterior vitreous. Presence of iris rubeosis and intraocular pressure should be noted. Gonioscopy should be used to detect neovascularization of the angle. Dilated fundus exam may reveal hemorrhage diffusely spread throughout the vitreous cavity, or the blood may conform to the anatomy of the vitreous. For example, hemorrhage in the subhyaloid space may result in a scaphoid (boat-shaped) hemorrhage. Occasionally, a detached posterior hyaloid face will have blood adherent to its posterior surface. If vitreous hemorrhage is associated with acute PVD, retinal tear or detachment should be ruled out using scleral depression. It is important to thoroughly examine the fellow eye, as it will often reveal clues as to the etiology. In chronic vitreous hemorrhage, the red blood cells become dehemoglobinized and the hemorrhage takes on a khaki color or even yellow or white color.
If the vitreous hemorrhage obscures a complete view to the retina, B-scan ultrasonography can detect vitreous hemorrhage, PVD, retinal tears, retinal detachment, tractional membranes, intraocular tumors, and foreign bodies. Fluorescein angiography may be useful in the setting of mild to moderate vitreous hemorrhage to help identify neovascularization. If an open globe injury is suspected, orbital CT scan is indicated to characterize the orbital bony structures, assess the integrity of posterior the eyewall (though clinically its presence is denoted by hypotony and other features), and rule out intraocular foreign body. Blood pressure should also be checked. If familial exudative vitreoretinopathy is suspected, examination of family members is helpful.
Laboratory testing is used according to clinical suspicion to diagnose diabetes, sickle cell disease, leukemia, thrombocytopenia, and other hematologic abnormalities.
- Posterior vitreous detachment with or without retinal tear, with or without rhegmatogenous retinal detachment
- With neovascularization
- Proliferative diabetic retinopathy
- Retinal vein occlusion
- Hypertensive retinopathy
- Sickle retinopathy
- Radiation retinopathy
- Retinopathy of prematurity
- Familial exudative vitreoretinopathy
- Nonperfusion from retinal vasculitis (e.g. sarcoidosis)
- Without neovascularization
- Retinal vein occlusion
- Familial retinal arteriolar tortuosity
- With neovascularization
- Choroidal neovascularization secondary to:
- Age-related macular degeneration
- Peripheral exudative hemorrhagic chorioretinopathy
- Pathologic myopia
- Inflammatory/infectious choroidopathies (e.g. sarcoidosis, punctate inner choroidopathy, presumed ocular histoplasmosis syndrome, etc)
- Choroidal tumors (e.g. uveal melanoma)
- Choroidal neovascularization secondary to:
- Shaken baby syndrome
- Closed globe injury
- Open globe injury
- Avulsion of prepapillary loop
- Valsalva maneuver
- Blood disorders (thrombocytopenia, leukemia, hemoglobinopathies, etc.)
- Terson syndrome
- Inflammatory/infectious conditions causing vitritis mimicking chronic vitreous hemorrhage (multifocal choroiditis with panuveitis, endophthalmitis, etc)
- Primary central nervous system lymphoma masquerading as chronic vitreous hemorrhage
Treat the underlying etiology as soon as possible.
If the retina can be adequately visualized and the etiology of the vitreous hemorrhage can be determined, treatment of the underlying cause may be attempted, if needed.
If the retina can be adequately visualized and the etiology of the vitreous hemorrhage can be determined, but the vitreous hemorrhage does not permit safe treatment of the underlying etiology, pars plana vitrectomy is indicated. A short period of cautious observation for vitreous clearing may be reasonable. For example, occasionally a retinal tear associated with vitreous hemorrhage can be seen with a bright indirect ophthalmoscope, but adequate uptake of laser spots to the posterior margin of the break cannot be achieved. Red laser may be tried in such cases as it has better penetration. Cryotherapy can be considered in these cases, but the dual risk of cryotherapy and vitreous hemorrhage potentially leading to proliferative vitreoretinopathy should be considered compared to the risk of pars plana vitrectomy with endolaser.
If the retina cannot be adequately visualized in 360 degrees and the etiology of the vitreous hemorrhage is unknown, prompt pars plana vitrectomy is indicated. Again, a short period of cautious observation for vitreous clearing may be reasonable. For example, in a case of a superior retinal tear with dense vitreous hemorrhage, adequate treatment of the superior retinal tear may be achieved. However, undetected inferior retinal breaks may be present. Between office visits, retinal detachment may progress underneath vitreous hemorrhage without a change in the patient’s symptoms. Therefore, if the view is not clearing briskly, pars plana vitrectomy is indicated. Neovascularization of the iris or angle in the setting of new dense vitreous hemorrhage would prompt earlier surgical intervention.
Diabetics frequently present with vitreous hemorrhage, and in general the same principles apply as outlined above. Of note, new vitreous hemorrhage in diabetics cannot always be assumed to be secondary to diabetic retinopathy if there is an inadequate view; diabetics are susceptible to retinal tears and detachments like the general population. The severity of the fellow eye may give a clue as to the etiology of the vitreous hemorrhage, but asymmetric levels of retinopathy are relatively common. In any case, diabetic patients with proliferative diabetic retinopathy, new vitreous hemorrhage prohibiting adequate panretinal photocoagulation, and no history of panretinal photocoagulation benefit from pars plana vitrectomy with intra-operative panretinal photocoagulation or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection. In this scenario, if the vitreous hemorrhage does not clear in about one month, many surgeons will perform pars plana vitrectomy. However, in the case of an established patient with known proliferative diabetic retinopathy and known panretinal photocoagulation, a new or recurrent vitreous hemorrhage is far more likely to be secondary to diabetes than a retinal tear. Longer periods of observation (3 to 6 months) before considering pars plana vitrectomy may be reasonable in these situations.
As always, individual situations, patient wishes, and surgeon judgment are paramount.
Patients are instructed to minimize strenuous activity, as an increase in blood pressure may disrupt the newly formed clot and cause new active bleeding. Patients are also instructed to keep their head of bed elevated to allow settling of the blood, improving their vision and permitting more complete fundoscopic examination. Bilateral patching and bedrest may facilitate settling of blood. However, the patches must be removed immediately before examination or treatment, as normal eye movements quickly disperse the hemorrhage again. For this reason and its inconvenience to patients, bilateral patching is infrequently attempted.
Neovascularization from proliferative retinopathy, associated with diabetes or otherwise, is often treated with panretinal photocoagulation if the view is adequate. This will cause regression of neovascularization and help reduce the risk of further hemorrhage.
Intravitreal injection of anti-VEGF agents may be used to cause regression of neovascularization in proliferative retinopathies, particularly if there is no view to perform panretinal photocoagulation. Bhavsar et al. compared the use of ranibizumab with saline injected intravitreally for patients with proliferative diabetic retinopathy-associated vitreous hemorrhage in a randomized trial, and found that there seemed to be no difference in vitrectomy rates at 16 weeks between the two groups. Of note, the recent Protocol S data from the Diabetic Retinopathy Clinical Research Network (DRCR.net) compared the use of panretinal photocoagulation versus intravitreal ranibizumab for proliferative diabetic retinopathy; at five years, the rates of vitreous hemorrhage were similar (nearly 50%) in both groups. Additionally, there is anecdotal evidence that anti-VEGF injection may worsen tractional retinal detachment as neovascular membranes contract, so the the potential risks and benefits should be considered in this setting. Recently, the initial results from Protocol AB from the Diabetic Retinopathy Clinical Research Retina Network evaluated 100 patients with vitreous hemorrhage from proliferative diabetic retinopathy initially treated with aflibercept vs. 105 patients with vitreous hemorrhage initially treated with pars plana vitrectomy with laser photocoagulation. At 24 weeks, there was no statistically difference in the primary outcome of mean visual acuity letter score between the vitrectomy and aflibercept cohorts, although the vitrectomy group showed a faster visual recovery. Approximately one-third of patients in the aflibercept cohort required vitrectomy during follow-up compared with 8% of the patients in the vitrectomy/laser cohort.
Many surgeons use pre-operative anti-VEGF agents 1 to 7 days before pars plana vitrectomy for vitreous hemorrhage in diabetics, as regression of neovascular membranes reduces intra- and post-operative bleeding and dissection of tissue may become easier. Several small studies support this belief, although other small studies refute it. There is concern, however, that these patients frequently fail their pre-anesthesia testing and that their surgery may be cancelled after the anti-VEGF agent has been given, potentially exacerbating tractional retinal detachment. For this reason, many surgeons wait until the patient is medically cleared for surgery before giving the anti-VEGF agent.
Intravitreal injection of an anti-VEGF agent is usually indicated when the cause of vitreous hemorrhage is neovascular age-related macular degeneration.
The Early Treatment of Diabetic Retinopathy Study showed that aspirin did not increase risk of vitreous hemorrhage, and no anticoagulant has been definitively shown to increase risk of vitreous hemorrhage. One report showed that patients taking aspirin, clopidogrel, or warfarin who develop an acute PVD are more likely to develop a vitreous hemorrhage, although the difference was small. Most clinicians do not recommend discontinuation of anticoagulation with the goal of resolving a vitreous hemorrhage, especially when the anticoagulation is medically indicated.
Medical follow up
Patients with systemic causes of vitreous hemorrhage are followed closely by an internist or endocrinologist in addition to close ophthalmology follow up.
Pars plana vitrectomy is indicated for vitreous hemorrhage accompanied by retinal detachment or break seen on B-scan, nonclearing vitreous hemorrhage, many cases of intraocular foreign body, vitreous hemorrhage with iris neovascularization or associated with hemolytic or ghost-cell glaucoma. Pars plana vitrectomy is also indicated in cases of dense vitreous hemorrhage of unknown etiology. In these cases, pars plana vitrectomy can be both diagnostic and therapeutic. Depending on the etiology of vitreous hemorrhage, endolaser may also be placed intraoperatively.
Some surgeons will also perform a concurrent air-fluid exchange after the vitrectomy or may even inject intravitreal anti-VEGF at the conclusion of case, but there is no substantial evidence that this prevents post-operative recurrent vitreous hemorrhage, a frustrating occurrence seen in some patients, especially diabetic patients.
In cases of open globe injury with vitreous hemorrhage but without intraocular foreign body, most surgeons close the eyewall first and address the vitreous hemorrhage as a second stage procedure.
Surgical follow up
Frequency of follow up is specific to the surgical indication.
The prognosis is variable according to the etiology, status of optic nerve, and macular involvement. For example, patients with vitreous hemorrhage secondary to proliferative diabetic retinopathy or age-related macular degeneration will have a more guarded prognosis compared to those with vitreous hemorrhage resulting from posterior vitreous detachment. Thus, it is important to counsel the patient pre-operatively that prognosis might be guarded, especially since a thorough assessment is precluded while the vitreous hemorrhage is present.
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