Vitreous Haemorrhage

Vitreous haemorrhage happens when blood leaks into the eye. If severe, it can lead to serious loss of vision or blindness. The pharmaceutical industry is beginning to understand how this happens and is working towards new treatment options for it.

What is vitreous haemorrhage? Top

Vitreous haemorrhage is the leaking of blood into one of the several potential spaces formed within and around the vitreous body of the eye, which may then obscure a patient’s vision. The vitreous humour is a clear, gel-like substance that comprises the back of the eye and prevents light from directly reaching the retina. A mild vitreous haemorrhage may result in a patient being able to see only a few dark spots, while a severe event may block out all vision, only permitting perception of light.

The volume of the vitreous body of an adult person is approximately 4 ml, which is 80 per cent of the eyeball. The content of the vitreous body is 99 per cent water; the remaining 1 per cent is mostly composed of collagen and the carbohydrate molecule hyaluronic acid. Additionally, there are 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 does not contain any blood vessels and is inelastic. The outer limits of the vitreous body are not defined by a membrane, but instead are condensations of fibrils that form attachments at the peripheral retinal border and posterior ciliary body, posterior lens capsule and around the optic nerve.

Depending on the severity of the bleeding, it may take several months or significantly longer for the body to reabsorb the blood and for the patient to regain vision. In addition to obstructing the patient's vision, a vitreous haemorrhage often prevents physicians from exploring the back of the eye to diagnose or treat the cause of the haemorrhage. If extensive or repeated bleeding occurs, fibrous tissue or scarring can form on the retina, which can lead to a detachment of the retina and permanent vision loss or blindness.

Who does vitreous haemorrhage affect? Top

The prevalence of vitreous haemorrhage tends to parallel the frequency of the causative diseases which depend on the study population, mean age of patients, and geographical region. In adults, proliferative diabetic retinopathy is the most frequent cause. The leading cause of vitreous haemorrhage in young people is trauma. The incidence of spontaneous vitreous haemorrhage is approximately 7 cases per 100,000 population. Approximately 35,000 cases of spontaneous vitreous haemorrhage occur in the European Union each year.

Most often vitreous haemorrhage is associated with diabetic retinopathy (about 60 per cent of all cases), with a traumatic insult of the eye (about 15 per cent) or with other factors (about 25 per cent), such as a hypertensive episode or bleeding into the brain (subarachnoid haemorrhage).

Underlying diseases such as leukaemia may also lead to blood leaking into the eye. Pathological mechanisms of vitreous haemorrhage also include haemorrhage from a diseased retina, or blood leaking into the retina and vitreous body from any other intraocular sources. Here, the pathogenesis of bleeding is believed to be retinal ischemia causing the release of growth factors, most notably vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and insulinlike growth factor 1 (IGF-1).

Scheme of the human eye

Present treatments: Top

Today, treatment options for patients with a vitreous haemorrhage are rather limited. Currently, there is no medication. Most retinal specialists initially recommend a watchful waiting period, during which no medical treatment is provided in the hope that the blood leaking will clear on its own. The risks may include continued bleeding and, if caused by diabetic retinopathy, disease progression during the time it takes for the blood to clear on its own, if at all.

An alternative to watchful waiting is a surgical procedure called vitrectomy, in which the vitreous humour and haemorrhage are surgically removed and replaced with a fluid. Small instruments are inserted into the eye and the vitreous gel is cut and suctioned out. After removal of the vitreous gel, the surgeon may treat the retina with a laser (photocoagulation), cut or remove fibrous or scar tissue from the retina, or repair tears or holes in the retina. At the end of the surgery, a balanced salt solution or silicone oil or a gas (perfluropropane) is injected into the eye to replace the vitreous gel and restore normal pressure in the eye. There are some risks associated with this approach, including both cataract formation and possible loss of vision associated with retinal detachment. These risks contribute to the limited use of vitrectomy as an initial treatment option.

Experimental non-surgical treatment options involve improvement of natural repair mechanisms in order to accelerate clot-resolving, liquefaction, and removal of protein debris by white blood cells. For example, there are clinical reports on Rh-positive patients in whom vitreous haemorrhage did not resolve over a long time period. It appears that they were successfully treated with intravitreal injection of human anti-Rh-immunoglobulin, a product normally used to prevent sensitization in Rh-negative mothers after delivery of a Rh-positive baby. In cases where watchful waiting did not result in the clearing of the eye and surgical procedures were contraindicated, patients with a Rh-positive blood group underwent intravitreal injection treatment with specific human immunoglobulin. Antibodies directed against the Rhesus factor were apparently effective in breaking down Rh-positive red blood cells in the vitreous.

What’s in the development pipeline? Top

In 2004, the first medicine under development for the treatment of vitreous haemorrhage has completed its programme of Phase 3 clinical trials. The preparation contains a highly purified form of ovine hyaluronidase for intravitreal injection. At the moment, it is under review by the US authorities for the treatment of vitreous haemorrhage.

Hyaluronidase is a naturally occurring enzyme that digests certain forms of carbohydrate molecules called proteoglycans, which serve as connective tissues in various parts of the body, including the eye. When injected into the vitreous humour, the compound breaks down the proteoglycan matrix, causing the vitreous humour to liquefy. It is further believed that this also results in the separation of the vitreous humour from the retina.

The longer-term future Top

Treatment of vitreous haemorrhage is still an unmet medical need. As its prevalence tends to parallel the frequency of underlying diseases such as diabetes, future research will be looking into factors which have been implicated as strong promoters of proliferative diabetic retinopathy. Main targets will be growth hormone and IGF-1. The prevalence of vitreous haemorrhage may be further reduced by better management of other underlying diseases, such as hypertensive episodes and leukaemia.

There are first clinical results on the reduction of bleeding and preservation of visual acuity by treatment with a long-acting somatostatin analogue in diabetic patients at an advanced stage of proliferative diabetic retinopathy. After three years of treatment, the incidence of vitreous haemorrhages and the need for vitreo-retinal surgery was significantly lower in the treated patients compared to the group receiving placebo.