User:TeHilla98/Sickle cell retinopathy

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Sickle cell retinopathy can be defined as retinal changes due to blood vessel damage in the eye of a person with a background of sickle cell disease. It can likely progress to loss of vision in late stages due to vitreous hemorrhage or retinal detachment. Sickle cell disease is a structural red blood cell disorder leading to consequences of multiple systemic proportions. It is characterized by chronic red blood cell destruction, vascular injury and tissue ischemia causing damage to the brain, eyes, heart, lungs, kidneys, spleen and musculoskeletal system.

People affected by sickle cell disease are commonly of African or Asian descent. Emigration patterns towards the Western Hemisphere have lead to increased numbers of persons affected by sickle cell disease. Knowledge and understanding of sickle cell disease and it’s management are now increasingly relevant in areas such as the European Union. At a young age, a great proportion of people living with sickle cell disease can develop retinal changes. Sickle cell disease is comprised of several subtypes however, the Haemoglobin type C (HbSC) subtype carries the gravest prognosis for sickle cell retinopathy and vision changes.

Regular retinal examinations can aid in early detection and treatment thus reducing the impact of the condition and the risk of vision loss. Development and progression of retinopathy can be favorably modified through management of the underling sickle cell disease. Treatment of the general disease can ameliorate its systemic effects.

Classification

Sickle cell retinopathy can be classified as non-proliferative or proliferative forms based on retinal changes due to the underlying sickle cell disease.

Non-proliferative sickle cell retinopathy (NPSCR)[edit]

Non-proliferative sickle cell retinopathy (NPSCR) can feature the following retinal manifestations.

• Non proliferative retinopathy can feature small bleeds of the retina known as intraretinal hemorrhages. The bleeding is elicited due to blockage of blood vessels by the sickled blood cells, thus triggering vessel wall necrosis. The resulting hemorrhages are initially bright red and oval shaped. As the hemorrhage ages over a period of days to weeks, the color then changes to a salmon hue known as a salmon patch.

• Bleeding in the deeper layers of the retina leads to the appearance of dark lesions known as black sunburst spots. These oval or round shaped pigmented spots are formed due to RPE proliferation.

• As the haemoglobin within the hemorrhage breaks down over time, yellow spots known as iridescent bodies are formed within the layers of the sensory retina.

• Iridescent bodies and black sunburst spots are manifestations of older hemorrhages compared to salmon patches which are acute in nature.
• Maculopathy occurs in a significant portion of patients affected by sickle cell retinopathy. It is more prevalent in homozygous HbSS type sickle cell disease. The fovea can be found within the macula and is known as the center of the visual field. Maculopathy in sickle cell retinopathy is due to long term changes of capillaries that interact at the fovea. Although ischemic changes may be apparent on the retina, maculopathy may be asymptomatic at first leaving visual acuity unchanged.
• Central retinal artery occlusion is a known feature that has a low incidence in patients with non proliferative sickle cell retinopathy.
• Optic nerve sign is represented by dilated capillaries that can be visualized in the nerve using fluoroscein angiography. Visual acuity often remains unchanged with this finding.

Proliferative sickle cell retinopathy (PSCR)[edit]

Proliferative sickle retinopathy is the most severe ocular complication of sickle cell disease. Even though PSCR begins in the first decade of life, the condition remains asymptomatic and unnoticed until visual symptoms occur due to vitreous hemorrhage or retinal detachment.

Goldberg classification[edit]

Goldberg classified PSR into following 5 different self-explanatory stages:

1. Stage of peripheral arterial occlusion and ischemia: It is the earliest abnormality that can be visualized by fundus examination. The occluded arterioles can be seen as dark red lines. They eventually turn into white silver-wire vessels.
2. Stage of peripheral arteriolar-venular anastomoses: Arteriolar-venular anastomoses develop as blood is diverted from blocked arteries to nearby venules.
3. Stage of neovascularization and fibrous proliferation: Neovascularization starts from the arteriolar-venular anastomoses, and grow into the ischemic retina. Characteristic fan-shaped appearance due to neovasularization is known as sea fan neovascularization.
4. Stage of vitreous hemorrhage. Peripheral neovascular tufts bleed and cause vitreous hemorrhage.
5. Stage of vitreoretinal traction bands and tractional retinal detachment: Traction on the sea fan and adjacent retina causes traction retinal detachment.

Prevention

Screening

Screening is an important pillar of prevention of sickle cell retinopathy as it provides the benefit of early detection and treatment thus reducing complications. Screening also provides an opportunity for education of families predisposed to retinopathy as a result of a family history of sickle cell disease. It can take the form of DNA screening at birth and Ophthalmology-related examinations later in life.

1. DNA screening in newborns at risk of having sickle cell disease allows the early diagnosis of the disease. Families can then be educated on the possible effects of sickle cell disease at each stage of life.
2. Ophthalmology-related examinations - dilated fundoscopic examination is recommended from the age of 10 and biannually thereafter in patients with no abnormal retinal findings. Fluoroscein angiography and angioscopy is recommended for patients with abnormal findings that may be indicative of proliferative sickle cell retinopathy. The frequency of follow up appointments is determined by the ophthalmologist based on the severity of the findings.

Care of systemic disease

Sickle cell disease is a systemic disease that affects several organs in the body. Management of the underlying disease can therefore prevent the development of retinopathy and slow its progression.

1. Fetal haemoglobin transfusion - Fetal haemoglobin (HbF) is a form of haemoglobin that is found in children up to 6 months after birth. This type of haemoglobin is beneficial in sickle cell patients as it resists modification to the sickled shape. As a result, transfusion of HbF in younger populations can prevent and slow the progression of sickle cell retinopathy.
2. Hydoxyurea administration - Hydroxyurea is a drug that can be used as an alternative method of increasing fetal haemoglobin levels in the blood of a patient with sickle cell disease. Hydroxyurea also provides the benefit of reducing inflammation.
3. Haematopoetic stem cell transplantation - This process is more commonly known as a bone marrow transplant. It is useful in the management of sickle cell disease. However, access to this method is limited due to cost and the need for a donor that is biologically compatible with the person requiring the transplant.
4. Anti inflammatory and anti adhesive drugs reduce the likelihood of occlusions in the small blood vessels of the retina therefore preventing the development of sickle cell retinopathy. There drugs include anti adhesive antibodies, anti-integrin antibodies, anti-Willebrand factor, sulfasalazine and statins.
5. Gene therapy has also been proven beneficial in the prevention of sickle cell retinopathy.

Diagnosis

Diagnosis is conducted in a multidiciplinary manner. The diagnosis of sickle cell disease can be confirmed by cation high performance liquid chromatography (HPLC), haemoglobin electrophoresis in adolescents and adults and molecular genetic diagnosis in prenatal and neonatal populations. Anterior segment signs including the conjunctival sign and iris atrophy are ocular manifestations that are strongly indicative of sickle cell disease. Early stages of sickle cell retinopathy are asymptomatic. However, retinal changes that are diagnostic of sickle cell retinopathy can be visualized using fundoscopic examinations, retinography, fluoroscscein angiography and coherence tomography. Ultra Widefield Fluorescein Angiography is the gold standard for diagnosis of proliferative sickle cell retinopathy. It is an invasive method that assesses both anterior and posterior segment structures. Spectral Domain Optical Coherence Tomography and Coherence Tomography Angiography are non invasive methods of diagnosing proliferative retinopathy. Visual acuity and intraocular pressure assessments can also yield results that are diagnostic of sickle cell retinopathy.

Treatment

Medical[edit]

Vascular endothelial growth factor (VEGF) is known to be associated with sea fan lesions which are types of neovascularization. Bevacizumab is an anti-VEGF drug used in intravitreal injection that is known to cause reversal of sea fan lesions and reduce the duration of vitreous hemorrhage. Intravitreal injection of anti-VEGF drugs can also be used prior to surgery to aid separation of tissues involved in the sea fan lesion and to reduce intraoperative and postoperative hemorrhage. It is useful in combination with photocoagulation.

Laser[edit]

Laser photocoagulation is the most widely used treatment method in proliferative sickle cell retinopathy. Argon laser or xenon laser photocoagulation is used in sea fan treatment.

Surgery[edit]

Surgical procedures may be performed to treat complications like retinal detachments, nonclearing vitreous hemorrhage, and epiretinal membranes.Pars plana vitrectomy may be advised in complications like vitreous hemorrhage and retinal detachment.