Retinopathy Hemoglobinopathies

What is Retinopathy Hemoglobinopathies?

Hemoglobinopathy refers to certain genetic disorders related to abnormal or insufficient production of hemoglobin in the blood. Hemoglobin is vital for transporting oxygen around our bodies. Examples of hemoglobinopathies include diseases like sickle cell disease, which is caused by abnormal hemoglobin, and thalassemia, which causes inadequate hemoglobin production.

Sickle cell disease was first discovered by James Herrick when he noticed unusual cell shapes in the blood of a West Indian patient. By 1930, Cook had found that sickle cell disease could also impact the eyes, identifying it was the cause of retinal bleeding in a patient who passed away from a type of stroke known as a subarachnoid hemorrhage.

Thalassemia was first identified in 1925 by a Detroit doctor who observed severe anemia, stunted growth, and premature mortality in Italian children. Eyes can also be impacted by thalassemia for various reasons; either due to the disease itself, from an overload of iron caused by blood transfusions, or from the medicine desferrioxamine used to manage iron overload.

What Causes Retinopathy Hemoglobinopathies?

Sickle cell disease is a condition that results from a small genetic change. Normally, part of our red blood cells contains a protein called beta globin. In sickle cell disease, a single change at one point of the beta globin protein causes a different molecule, called valine, to replace the usual one, glutamic acid. This leads to the production of a different type of hemoglobin, called HbS or sickle hemoglobin.

Sickle cell disease is associated with a constant destruction of red blood cells, leading to a condition called chronic hemolytic anemia. It can come in different forms, such as the HbSS form where a person has two copies of the altered gene, or the HbSC form and HbS beta-thalassemia form where there’s a combination of the Hemoglobin S gene and another gene (HbC or beta-thalassemia). While individuals with the HbSS type are more likely to experience complications throughout the body, those with the HbSC type are more likely to develop eye issues (sickle cell retinopathy) and risk losing their vision.

Beta thalassemia, on the other hand, is a condition where there’s not enough beta globin chains produced or the chains are completely absent. This is due to mutations called beta plus or beta. If a person has two copies of a beta mutation, this results in beta thalassemia major. Alpha thalassemia is another related condition, caused by the absence of an alpha-globin chain.

Risk Factors and Frequency for Retinopathy Hemoglobinopathies

The World Health Organization (WHO) states that around 7% of people worldwide carry hemoglobinopathies, a group of blood disorders. Every year, between 300,000 to 400,000 babies are born with a severe form of these conditions. Proliferative sickle cell retinopathy, which can seriously harm vision, is a complication of sickle cell disease. It affects approximately 0.5% of patients with HbSS disease and about 2.5% of HbSC disease. Eye complications in beta-thalassemia, another blood disorder, were reported in about 41.3% to 85% of cases in different studies.

Approximately 7% of the global population carry blood disorders known as hemoglobinopathies.
300,000 to 400,000 babies are born with a severe form of these disorders annually.
Proliferative sickle cell retinopathy, a complication that can harm vision significantly, is observed in around 0.5% of patients with HbSS sickle cell disease and about 2.5% of patients with HbSC sickle cell disease.
In various studies, eye complications in beta-thalassemia, another type of blood disorder, were reported in 41.3% to 85% of cases.

Signs and Symptoms of Retinopathy Hemoglobinopathies

Sickle cell retinopathy is a common eye problem in people with sickle cell disease. Most of the time, it doesn’t cause symptoms, as it mainly affects the outskirts of the retina, the light-sensitive tissue in the back of our eyes. Sickle cell retinopathy comes in two forms: nonproliferative and proliferative.

Nonproliferative sickle retinopathy is marked by salmon patches, shiny spots, and black sunbursts in the eye. Salmon patches are hemorrhages, or bleeding, in certain parts of the retina caused by sickled red blood cells blocking and breaking blood vessels. The blood that leaks out changes color from red to white over time. When the patch clears up, a scar or a cavity filled with shiny spots, a sign of trapped blood residue, forms. The scarring can potentially lead to complications like impaired vision or alterations to the retina’s structure.

Proliferative sickle retinopathy, on the other hand, can lead to vision loss and is characterized by new blood vessels growing wildly. The growth of these blood vessels can cause a range of problems, such as internal bleeding in the eye or even the retina detaching. This stage of the disease has five different levels:

Stage 1: Blockage of peripheral arteries
Stage 2: Formation of interconnections between arteries and veins
Stage 3: New blood vessels form in shapes resembling sea fans, an ocean organism
Stage 4: Internal bleeding in the eye
Stage 5: The retina separates or detaches, potentially due to the pull from the growing blood vessels

It’s quite common for the sea fan shape of new blood vessels to die off on their own. This is due to repeated blockages in its tiny blood vessels – funny enough, this can lead to the growth disappearing without causing any other problems.

Sickle cell thalassemia patients also have a unique terrain of eye conditions. The retina, the light-sensing tissue at the back of the eye, can display two types of abnormalities both looking like and not looking like pseudoxanthoma elasticum, a genetic disorder affecting the skin, eyes, and blood vessels.

Pseudoxanthoma elasticum-like changes have features like Peau d’Orange, which are dark yellow spots on the retina, and angioid streaks, which are irregular cracks in the Bruch’s membrane of the eye. Even though they usually do not cause symptoms, they could lead to vision problems if they grow towards the center of the retina or lead to the formation of new blood vessels.

The non-pseudoxanthoma elasticum-like changes lead to the degeneration of the retinal pigment epithelium, which is a layer of cells in the retina. These changes can show up as an abnormal, autofluorescent and dysplastic retinal pigment epithelium. This could potentially cause symptoms like reduced clarity of vision and a restricted field of vision, and signs of retinal pigment epithelium damage. Certain medications like desferrioxamine mesylate, which is used to relieve iron overload, can cause these changes.

Testing for Retinopathy Hemoglobinopathies

If you have sickle cell disease, it’s important to have regular eye check-ups with an ophthalmologist. This involves a specialist examining the outer parts of your retina (the back of your eye) using a method called indirect ophthalmoscopy. To get the best view, your pupil (the black circle in the centre of your eye) will be enlarged or ‘dilated’. This check-up should start when you are 10 years old and continue every year.

A test called fluorescein angiography is the best way to check the blood flow in your retina and spot any new blood vessels growing (a process known as ‘neovascularization’). Another test, called an OCT (Optical Coherence Tomography), can help identify areas of your retina that may have become thin.

For anyone with thalassemia, it’s recommended to get your eyes checked every year after you turn 20. If you have ‘angioid streaks’ (tiny breaks in an elastic-like layer under your retina) you’ll need to have more regular check-ups using a simple eye test (fundoscopy) and fluorescein angiography. This will enable early detection of any new blood vessels growing in your choroid (layer beneath the retina) and ensure you get the appropriate treatment.

If your doctor suspects you might have DFO (Deferoxamine) retinopathy (a type of damage to your retina caused by a certain medication), they may use a number of tests. These include fluorescein angiography, OCT, Microperimetry (a device that measures light sensitivity of your retina), ERG (which measures the electrical responses of various cells in your eyes), and EOG (a diagnostic test that measures the function of your eye’s retina). These tests can all reveal damage to your retina. A notable test for DFO retinopathy is called ‘fundus autofluorescence’; it can detect abnormal changes in your eyes (either increased or decreased autofluorescence) related to the extent of damage to the RPE (Retinal Pigment Epithelium, a layer of cells that nourishes retinal visual cells).

Treatment Options for Retinopathy Hemoglobinopathies

At present, there’s no known treatment to stop the development of a condition known as sickle cell retinopathy, which is a complication of sickle cell disease that affects the retina in your eyes.

Similarly, individuals who have thalassemia (a type of inherited blood disorder) can also develop two types of irregularities in the retina. These irregularities are called pseudoxanthoma elasticum-like and non-pseudoxanthoma elasticum-like retinal abnormalities.

When these retinal abnormalities reach a certain stage (stage 3, particularly when large ‘sea fans’ are present, stage 4 and stage 5), doctors recommend treatment. ‘Sea fans’ are abnormal blood vessels that can form in the retina of people with certain blood disorders, including sickle cell disease and thalassemia.

The most common treatment for these stages of retinopathy is a procedure known as laser photocoagulation. In this procedure, a surgeon uses a laser to seal or destroy abnormal blood vessels in the retina. In some cases, doctors might also inject a drug called anti-vascular endothelial growth factor into the vitreous, a gel-like substance that fills the eye.

In certain cases, if there’s blood in the vitreous that doesn’t clear up on its own, a procedure called vitrectomy may be needed. This surgery involves removing the vitreous and any blood that’s inside it. If the retina detaches, a vitrectomy or another procedure known as scleral buckling might be performed.

Patients with thalassemia should get regular eye screenings for early detection of any changes in the retina. In addition, there are newer medications known as chelating agents, such as deferiprone, which have fewer side effects than older drugs and can help manage the disease if taken properly under a doctor’s supervision.

Here are some medical conditions that could potentially develop as acute complications of sarcoidosis:

Branch retinal vein occlusion
Central retinal vein occlusion
Chronic kidney disease
Colonic polyps
Eales disease
Hypertension
Retinopathy of prematurity
Systemic lupus erythematosus (SLE)

Frequently asked questions

Proliferative sickle cell retinopathy is observed in around 0.5% of patients with HbSS sickle cell disease and about 2.5% of patients with HbSC sickle cell disease.

The signs and symptoms of Retinopathy Hemoglobinopathies include: - Salmon patches: These are hemorrhages or bleeding in certain parts of the retina caused by sickled red blood cells blocking and breaking blood vessels. The blood that leaks out changes color from red to white over time. When the patch clears up, a scar or a cavity filled with shiny spots, a sign of trapped blood residue, forms. - Shiny spots: These are trapped blood residue in the retina, which can form as a result of scarring from nonproliferative sickle retinopathy. - Black sunbursts: These are also a characteristic feature of nonproliferative sickle retinopathy and are caused by sickled red blood cells blocking and breaking blood vessels in the retina. - Vision loss: Proliferative sickle retinopathy can lead to vision loss. This can occur due to complications such as internal bleeding in the eye or the detachment of the retina. - New blood vessel growth: Proliferative sickle retinopathy is characterized by the growth of new blood vessels in the eye. These blood vessels can cause problems such as internal bleeding or retinal detachment. - Sea fan-shaped blood vessels: In proliferative sickle retinopathy, new blood vessels can form in shapes resembling sea fans. These blood vessels may die off on their own due to repeated blockages in their tiny blood vessels. - Retinal abnormalities: Sickle cell thalassemia patients may display abnormalities in the retina. These can include dark yellow spots called Peau d'Orange and irregular cracks in the Bruch's membrane of the eye called angioid streaks. - Degeneration of the retinal pigment epithelium: Non-pseudoxanthoma elasticum-like changes in the retina can lead to the degeneration of the retinal pigment epithelium. This can cause symptoms such as reduced clarity of vision, a restricted field of vision, and signs of retinal pigment epithelium damage. It's important to note that these signs and symptoms may vary in severity and can potentially lead to complications and vision problems if left untreated. Regular eye examinations and medical management are crucial for individuals with Retinopathy Hemoglobinopathies.

Retinopathy Hemoglobinopathies can be acquired through conditions such as sickle cell disease and beta-thalassemia.

The doctor needs to rule out the following conditions when diagnosing Retinopathy Hemoglobinopathies: - Branch retinal vein occlusion - Central retinal vein occlusion - Chronic kidney disease - Colonic polyps - Eales disease - Hypertension - Retinopathy of prematurity - Systemic lupus erythematosus (SLE)

The types of tests needed for Retinopathy Hemoglobinopathies include: - Indirect ophthalmoscopy: A specialist examines the outer parts of the retina using this method. - Fluorescein angiography: This test checks the blood flow in the retina and detects any new blood vessels growing. - Optical Coherence Tomography (OCT): This test helps identify areas of the retina that may have become thin. - Fundoscopy: This simple eye test is used to check for angioid streaks and detect any new blood vessels growing in the choroid. - Microperimetry: This device measures the light sensitivity of the retina. - ERG (Electroretinography): This test measures the electrical responses of various cells in the eyes. - EOG (Electrooculography): This diagnostic test measures the function of the eye's retina. - Fundus autofluorescence: This test detects abnormal changes in the eyes related to damage to the Retinal Pigment Epithelium (RPE).

Retinopathy in hemoglobinopathies, such as sickle cell disease and thalassemia, can be treated through various methods. The most common treatment for advanced stages of retinopathy is laser photocoagulation, where a surgeon uses a laser to seal or destroy abnormal blood vessels in the retina. In some cases, a drug called anti-vascular endothelial growth factor may be injected into the vitreous, the gel-like substance in the eye. If there is blood in the vitreous that does not clear up on its own, a procedure called vitrectomy may be necessary to remove the vitreous and any blood inside it. If the retina detaches, a vitrectomy or another procedure called scleral buckling may be performed. Regular eye screenings are also recommended for early detection of any changes in the retina. Additionally, newer medications known as chelating agents, like deferiprone, can help manage the disease with fewer side effects when taken properly under a doctor's supervision.

Proliferative sickle cell retinopathy, a complication of sickle cell disease, affects approximately 0.5% of patients with HbSS disease and about 2.5% of patients with HbSC disease. Eye complications in beta-thalassemia, another blood disorder, were reported in about 41.3% to 85% of cases in different studies.

An ophthalmologist.

Eye Health Retinal Disorders Sickle Cell Thalassemia