The vitreous body is a transparent tissue without blood vessels, so bleeding from adjacent tissues spreads into the vitreous gel, causing vitreous hemorrhage. Vitreous hemorrhage is a condition in which bleeding into the vitreous cavity enters the gel through a tear in the vitreous membrane. It also includes the spread of preretinal hemorrhage (between the internal limiting membrane and the nerve fiber layer, or between the internal limiting membrane and the posterior vitreous membrane) into the vitreous cavity.
The incidence of spontaneous vitreous hemorrhage is reported to be approximately 7 per 100,000 population per year, and 4.8 per 10,000 in Taiwan, varying by population characteristics, geography, and other factors. It often presents with rapid, painless, significant vision loss, making it a common condition encountered not only by ophthalmologists but also in emergency departments. The most common cause is proliferative diabetic retinopathy, followed by posterior vitreous detachment and ocular trauma. 12)
ICD-10 code: H43.1
It is estimated to occur in about 7 per 100,000 population per year, and is a relatively common cause of sudden vision loss in ophthalmology. The incidence varies depending on the underlying cause and patient background.
Sudden painless vision loss and blurred vision are the main complaints.
Slit-lamp examination identifies red blood cells in the anterior vitreous, the presence of pigment epithelial cells, and inflammatory cells in the anterior chamber or vitreous. Over time, as hemolysis progresses, the remaining cells become whitish. If the hemorrhage is small, the red color may not be prominent, and differentiation from uveitis may be necessary.
Vitreous hemorrhage becomes white over months (organization), so white does not necessarily indicate inflammation. Also, the distribution is often uneven, with dense sedimentation inferiorly and thinner superiorly where the retina may be visible.
Usually, vitreous hemorrhage itself is painless. Sudden painless vision loss or floaters are typical symptoms. If caused by trauma, pain from the injury may be present.
The frequency of causes of vitreous hemorrhage varies depending on the characteristics of the study population. In unilateral vitreous hemorrhage of unknown cause, common causes include rupture of neovascularization due to retinal vein occlusion, posterior vitreous detachment, retinal tear, and retinal detachment.
The three most common causes account for 59–88.5% of all cases.
Proliferative Diabetic Retinopathy
Rupture of neovascularization: Retinal ischemia leads to production of angiogenic factors such as VEGF, causing proliferation of fragile new blood vessels. Normal eye movements, acute posterior vitreous detachment, and fibrovascular contraction trigger bleeding.
Frequency: The most common of the three major causes. Poorly controlled diabetes is a high risk factor.
Posterior Vitreous Detachment
Retinal vessel rupture: Vitreous hemorrhage occurs in about 8% of patients with posterior vitreous detachment (PVD).
Complicated retinal tear: 70–95% of vitreous hemorrhages associated with acute posterior vitreous detachment involve a retinal tear or break. There is a direct correlation between the amount of bleeding and the likelihood of a retinal tear. 4)
Ocular Trauma
Closed and open globe injuries: Blunt trauma compresses the globe and causes retinal vessel rupture. In open globe injuries, bleeding can occur through the full thickness of the eye.
Age characteristics: Vitreous hemorrhage in individuals under 40 years of age is often associated with a history of trauma.
Children show a different distribution of causes compared to adults. Main causes include Coats disease, retinopathy of prematurity, ocular trauma (including shaken baby syndrome), blood disorders (leukemia, thrombocytopenia), and retinoblastoma. In bilateral vitreous hemorrhage in infants, shaken baby syndrome due to abuse should be considered.
Vitreous hemorrhage is a clinical finding, so identifying the underlying cause is important. If the bleeding is mild and the fundus can be observed, identifying the cause is relatively easy.
Diabetes, hypertension, sickle cell disease, trauma, and past retinal diseases or ophthalmic surgeries are important clues for diagnosis. The presence of systemic diseases such as hypertension or diabetes, and the condition of the fellow eye, may help infer the cause of bleeding.
When the fundus is completely obscured by vitreous hemorrhage, B-mode ultrasonography is essential. Use B-mode to assess the extent and severity of hemorrhage and to check for posterior vitreous detachment. In vitreous hemorrhage due to age-related macular degeneration, subretinal hemorrhage may be present, so pay attention to the retinal reflection near the macula.
Fresh vitreous hemorrhage shows clumped or feathery echoes with mobility. Posterior vitreous detachment is seen as a membrane echo. Continuity with the optic disc is a key point for differentiating from retinal detachment. When hemorrhage aggregates on the posterior vitreous membrane, it may be difficult to distinguish from detached retina.
The sensitivity of B-mode ultrasonography for detecting retinal tears in fundus-obscuring vitreous hemorrhage associated with PVD is reported to be 44–100%. 10) Since false negatives can occur with ultrasound alone, detailed fundus examination after resolution of hemorrhage is important.
The main conditions requiring differentiation from vitreous hemorrhage are listed below.
The following shows the main uses of each test.
| Test | Main purpose | Indication |
|---|---|---|
| B-mode ultrasound | Rule out retinal detachment, confirm posterior vitreous detachment | When fundus view is obscured |
| FA | Identify neovascularization | Mild to moderate hemorrhage |
| ERG | Assess retinal function | Unknown cause or suspected retinal disease |
| Orbital CT | Confirm intraocular foreign body | Trauma cases |
B-mode ultrasonography is essential. It helps differentiate from retinal detachment by assessing vitreous echoes due to hemorrhage, presence of posterior vitreous detachment, and continuity with the optic disc. Even if the fundus is completely opaque, indirect ophthalmoscopy with scleral depression may allow visualization of the peripheral retina.
The basic principle is to treat the underlying cause as quickly as possible.
If the hemorrhage is mild, observation is continued while waiting for spontaneous absorption. Blood clears at a rate of approximately 1% per day.
If neovascularization (e.g., proliferative diabetic retinopathy, retinal vein occlusion) is the cause and the view is adequate, PRP is performed to regress new vessels and reduce the risk of further bleeding. Randomized controlled trials have shown that panretinal photocoagulation reduces the risk of severe vision loss in proliferative diabetic retinopathy by more than 50%. 8)
When the view for PRP is inadequate, anti-VEGF injections are used to regress neovascularization in proliferative retinopathy. For vitreous hemorrhage due to age-related macular degeneration, intravitreal anti-VEGF injection is usually indicated.
In a randomized controlled trial for vitreous hemorrhage associated with proliferative diabetic retinopathy, comparing intravitreal ranibizumab with saline injection, no difference in vitrectomy rates at 16 weeks was observed. Data from DRCR.net Protocol S comparing PRP and intravitreal ranibizumab for proliferative diabetic retinopathy showed similar rates of vitreous hemorrhage at 5 years (approximately 50%). 5)
Because delayed treatment can lead to permanent retinal damage or neovascular glaucoma due to ischemia, it is necessary to carefully consider whether to continue conservative observation or perform surgical treatment. If retinal detachment is present on B-scan, early surgery should be performed to achieve retinal reattachment.
Vitrectomy is indicated in the following cases: 5)
In proliferative retinopathy associated with diabetes, if new vitreous hemorrhage does not resolve within one month, many surgeons perform vitrectomy. However, in known patients with proliferative diabetic retinopathy and a history of PRP, a longer observation period (3–6 months) may be reasonable. Intraoperative endolaser (endophotocoagulation) or preoperative anti-VEGF agents may be considered.
Initial results from DRCR.net Protocol AB compared an initial aflibercept treatment group (100 patients) with an initial vitrectomy plus laser treatment group (105 patients) in patients with vitreous hemorrhage due to proliferative diabetic retinopathy. At 24 weeks, there was no statistical difference in mean visual acuity scores, but the surgery group had faster visual recovery, and about one-third of the aflibercept group required vitrectomy during follow-up (8% in the surgery group). 5)
Red blood cells disappear at a rate of about 1% per day, and complete absorption may take several months. For mild cases, natural absorption is awaited with observation, but if absorption does not occur or if retinal detachment is present, vitrectomy is indicated.
It depends on the underlying disease and the extent of hemorrhage. If retinal detachment is present, early surgery is performed. In proliferative diabetic retinopathy, vitrectomy is considered if new vitreous hemorrhage does not resolve within one month. In patients with a history of PRP, an observation period of 3 to 6 months may be appropriate. For severe vitreous hemorrhage in type 1 diabetes, earlier vitrectomy is advantageous for visual recovery. 9) Vitrectomy is also indicated for vitreous hemorrhage where panretinal photocoagulation cannot be completed. 6)
The vitreous is a transparent tissue without blood vessels, so bleeding from adjacent tissues into the vitreous gel causes vitreous hemorrhage. Leakage of blood into the vitreous cavity is caused by two main mechanisms.
When intracranial pressure rises rapidly due to idiopathic intracranial hypertension (IIH) or subarachnoid hemorrhage, the CSF pressure within the optic nerve sheath compresses the central retinal vein and choroidal-retinal anastomotic vessels. This leads to venous stasis, and blood cannot drain through the anastomotic channels, causing rupture and severe hemorrhage that breaks through the internal limiting membrane into the vitreous.
Vosoughi & Micieli (2022) reported a case of idiopathic intracranial hypertension in a 32-year-old obese woman (BMI 54.9 kg/m²) who presented with flashes and floaters without headache, pulsatile tinnitus, or transient visual disturbances, and exhibited vitreous hemorrhage and papilledema. Lumbar puncture opening pressure was 34 cmH₂O. Treatment with acetazolamide 500 mg twice daily led to improvement of papilledema at 3 months and complete resolution of vitreous hemorrhage and visual recovery at 6 months. 3)
Hanai et al. (2022) reported a case of a 12-year-old boy with unilateral dilated petrous apex cyst (PAC) and contralateral vitreous hemorrhage secondary to elevated intracranial pressure. Lumbar puncture opening pressure was 250 mmH₂O. Administration of acetazolamide 250 mg twice daily resulted in gradual resolution of vitreous hemorrhage and papilledema. 1)
Blood released into the vitreous cavity rapidly forms a clot and clears at a rate of approximately 1% per day. Red blood cells are eliminated through the trabecular meshwork, undergo hemolysis and phagocytosis, or remain in the vitreous for several months. The immune response within the vitreous is unique, resembling a low-turnover granuloma, with no initial polymorphonuclear cell reaction. This suppressed inflammatory response reduces damage to ocular tissues and helps maintain transparency of the visual axis.
The Diabetic Retinopathy Vitrectomy Study (DRVS) was a landmark trial that first demonstrated the efficacy of early vitrectomy for severe vitreous hemorrhage in type 1 diabetes. At the 2-year analysis, the early vitrectomy group showed significantly better visual recovery compared to the observation group. 9) This study, along with advances in small-incision vitrectomy techniques, formed the basis for current vitrectomy indications.
Tan et al. (2010) conducted a randomized controlled trial comparing early vitrectomy and observation for vitreous hemorrhage associated with retinal tears. Although there was no significant difference in final visual acuity, the incidence of retinal detachment was significantly lower in the early surgery group compared to the observation group. 11) This evidence supports early active intervention in vitreous hemorrhage suspected to be due to retinal tears.
Matsuo & Noda (2022) reported a case of a 60-year-old ophthalmologist with no abnormalities on annual checkups who experienced recurrent vitreous hemorrhage approximately 2.5 months after the second and third doses of the COVID-19 mRNA vaccine (BNT162b2, Pfizer-BioNTech). After each vaccination, a tendency for diastolic blood pressure to increase by 10–20 mmHg over a period of 2–3 months was observed, which was temporally associated with the recurrence of vitreous hemorrhage. Although this is a single case report and insufficient to prove causation, checking vaccination history is recommended in patients with recurrent vitreous hemorrhage and elevated blood pressure after COVID-19 vaccination. 2)
DRCR.net Protocol AB is a randomized controlled trial comparing anti-VEGF monotherapy versus vitrectomy plus laser therapy for vitreous hemorrhage due to proliferative diabetic retinopathy. Data on long-term visual prognosis and conversion rate to surgery are expected to accumulate in the future.
Since vitreous hemorrhage involves various underlying diseases, the prognosis depends on the cause. In general, if macular function is preserved, the visual prognosis is good.
In cases complicated by retinal detachment, whether preoperatively or postoperatively, there is a risk of progression to proliferative vitreoretinopathy and poor prognosis. Caution is required, especially when tractional changes become chronic or when surgery is delayed, as the risk of proliferative vitreoretinopathy increases.
If the underlying disease is appropriately managed, the risk of rebleeding can be reduced. In diabetic retinopathy, regression of neovascularization through panretinal photocoagulation and anti-VEGF therapy is important for preventing rebleeding.
