Sickle cell retinopathy

Sickle cell retinopathy is a major ocular complication of the sickle cell disease (SCD) which causes permanent loss of vision. Retinopathy can occur in sickling hemoglobinopathies like sickle cell disease, sickle cell C disease, and sickle cell thalassaemia disease.[1]

Sickle cell retinopathy
Specialty	Ophthalmology
Complications	Blindness
Causes	Sickle cell disease
Risk factors	Heredity
Diagnostic method	Eye examination
Treatment	Medical, laser and surgery

Classification

Sickle cell retinopathy can be classified as non-proliferative or proliferative forms.

Non-proliferative sickle cell retinopathy (NPSCR)

The retinal changes in non-proliferative sickle cell retinopathy or background sickle cell retinopathy occur secondary to retinal ischemia due to vascular occlusion. Ocular manifestations NPSCR includes venous tortuosity, salmon-patches, schisis cavity, iridescent spots and the black sunburst spots.[2]

• Arteriovenous shunting from the retinal periphery may cause venous tortuosity.[3] Since the same occur in many other ocular diseases, it has no diagnostic value.[2]
• Salmon patches occur due to retinal hemorrhages, especially in mid-peripheral retina, adjacent to a retinal arteriole.[4] Since they are located in peripheral retina, there will not be any visual symptoms.
• The schisis cavity represents the space created by the reconstruction of the intra-retinal portion of the hemorrhage. The refractive bodies that glow in the schisis cavity are known as iridescent spots.
• Migration and proliferation of retinal pigment epithelium may cause black sunburst spots.[4] Since sunburst spots are also located in peripheral retina, these lesions usually do not produce any visual symptoms.[2]
• Angioid streaks: Angioid streaks may be seen in upto 6% of cases.[1]

Proliferative sickle cell retinopathy (PSCR)

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.[5]

Goldberg classification[4]

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]
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.[2]
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.

Signs and symptoms

• Comma sign: Comma shaped vessels in the bulbar conjunctiva is due to vascular occlusion of conjunctival vessels.[4]
• Vitreoretinal traction or retinal detachment cause flashes, floaters or dark shadows.[4]
• Sudden loss of vision may occur due to retinal artery occlusion, vitreous hemorrhage or retinal detachment.
• Intravascular occlusions may be seen in optic disc vessels.[2]

Cause

Normal adult hemoglobin A molecule comprises two α and two β globin chains associated with a heme ring. Mutation at the 6th position of the beta chain is the cause of sickle cell disease.[4] Due to sickle cell disease, vascular occlusion may occur in the conjunctiva, iris, retina, or choroid. Retinal changes occur due to blockage of retinal blood vessels by abnormal RBCs.[6]

Diagnosis

Diagnosisis usually done in a multidiciplinary manner. Patient may have history of sickle cell disease. External eye examination may show comma sign in the conjunctiva. Vascular changes in the retina and choroid can be diagnosed by ophthalmoscopy, fluorescein angiography or indocyanine green angiography. Combination of OCT and angiography is considered as a gold standard in detecting retinal ischemia in patients with sickle cell disease.[7]

Differential diagnosis

Sickle cell retinopathy should be differentiated from other retinal conditions like:

• Diabetic retinopathy
• Retinal vascular occlusions like Central retinal vein occlusion (CRVO), Branch retinal vein occlusion (BRVO) etc.
• Retinopathy of prematurity (ROP)
• Eales disease
• Familial exudative vitreoretinopathy
• Chronic myelogenous leukemia
• Scleral buckle

Prevention

To prevent blindness due to sickle cell retinopathy, complete ophthalmic examination twice a year is recommended for all sickle cell patients.[4] Since the use of carbonic anhydrase inhibitors increase the chance of sickling and vascular occlusions, its use is contraindicated in sickle cell patients.[1]

Treatment

Medical

Hydroxycarbamide may be used to prevent sickle cell retinopathy in children.[4] Intravitreal injection of anti-vascular endothelial growth factor may be used to treat neovascularization.[4]

Laser

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.[5]

Surgery

Surgical procedures may be performed to treat complications like retinal detachments, nonclearing vitreous hemorrhage, and epiretinal membranes.[3] Pars plana vitrectomy may be advised in complications like vitreous hemorrhage and retinal detachment.[7]

References

1. John F, Salmon (13 December 2019). "Retinal vascular disease". Kanski's clinical ophthalmology : a systematic approach (9th ed.). p. 533. ISBN 978-0-7020-7711-1.
2. "Sickle-Cell Retinopathy". Albert & Jakobiec's principles and practice of ophthalmology (3rd ed.). Saunders Elsevier. ISBN 9781416000167.
3. "Ophthalmologic Manifestations of Sickle Cell Disease (SCD)". 21 November 2019.
4. "Sickle Cell Retinopathy". eyewiki.aao.org.
5. Bonanomi, Maria Teresa Brizzi Chizzotti; Lavezzo, Marcelo Mendes (October 2013). "Sickle cell retinopathy: diagnosis and treatment". Arquivos Brasileiros de Oftalmologia. 76 (5): 320–327. doi:10.1590/S0004-27492013000500016. PMID 24232951.
6. Khurana, AK (2015). "Diseases of Retina". Comprehensive ophthalmology (6th ed.). Jaypee, The Health Sciences Publisher. ISBN 978-93-86056-59-7.
7. Menaa, Farid; Khan, Barkat Ali; Uzair, Bushra; Menaa, Abder (30 August 2017). "Sickle cell retinopathy: improving care with a multidisciplinary approach". Journal of Multidisciplinary Healthcare. 10: 335–346. doi:10.2147/JMDH.S90630. ISSN 1178-2390. PMC 5587171. PMID 28919773.