History
Check for personal or family history of sickle cell trait or disease.
Inquire about painful systemic crises.
Patients may have visual complaints, varying in nature and intensity. Symptoms may range from transient flashes and floaters to sudden profound decrease in vision.
Physical
Complete eye examination
Rule out hyphema.
Check intraocular pressure (IOP).
Perform dilated fundus examination (DFE) via indirect ophthalmoscopy. (B-scan ultrasound can be performed if vitreous hemorrhage prevents DFE.)
Rule out differential diagnoses (see Differentials).
Retinal findings
Changes in the posterior segment are divided into four major categories, as follows: optic disc changes, macular changes, nonproliferative retinal changes, and proliferative retinal changes. [14, 6]
Classically, posterior segment changes are classified by either nonproliferative retinal changes (nonproliferative sickle retinopathy [NPSR]) or proliferative retinal changes (proliferative sickle retinopathy [PSR]). In NPSR, the retinal changes do not involve neovascularization as they do in PSR. [1]
Optic disc
Vascular changes in the optic disc can be seen secondary to intravascular occlusions. These intravascular occlusions primarily affect the small vessels on the surface of the optic disc.
These lesions appear as dark red spots or clumps on the nerve head, often called the disc sign of sickling. The proposed mechanism for this sign is the transient plugging of sickled (deoxygenated) erythrocytes.
Fluorescein angiography (FA) reveals segments of linear or Y-configuration of hypofluorescence that correspond to the dark red spots. Blood flow through these vessels (as seen on angiography) is not impaired. [15] Like conjunctival vascular changes, these lesions are transient and do not produce any appreciable visual symptoms.
Optic nerve neovascularization is a rare complication of hemoglobinopathies.
Optic disc changes appear to be more common in patients with sickle cell anemia than in those with sickle cell C disease or sickle cell-thalassemia disease.
Macula
Sickle cell retinopathy commonly occurs in the periphery, but macular changes also have been well documented.
Macular changes or sickling maculopathy can manifest acutely or chronically, occurring in patients with sickle cell disease, sickle cell C disease, and sickle cell-thalassemia disease.
Acute sickling maculopathy generally arises from acute vascular occlusion to the retina.
Involved vessels include the central retinal artery and its branches.
Acute vascular occlusion, although infrequent, can lead to acute retinal ischemia with subsequent infarction.
Acute retinal infarction may result in the complete loss of vision or can lead to central or paracentral scotomas, which may become incapacitating.
Chronic sickling maculopathy is more common and can be seen in up to 30% of the sickle cell C disease population. Clinically, signs of chronic sickling maculopathy are difficult to detect because these changes represent architectural alterations of the fine macular vasculature. These changes are insidious; therefore, conduct a thorough ocular examination.
Clinically, macular depression may be seen. This results when thinning and atrophy of the retina occurs secondary to retinal ischemia. This concave-shaped lesion, located next to the macula, presents on retinal biomicroscopy as a dark circle with a bright central reflex.
Although uncommonly seen, another PSR-associated sign is the macula hole. Predisposing factors are traction on the macula and vasoocclusive events. Traction on the macula results from neovascularization in the periphery and in the optic nerve. Vasoocclusive events in the macular, peripapillary, and perifoveal vessels (ie, capillaries) lead to local ischemia, infarction, retinal thinning, atrophy, and, ultimately, macula hole formation. Other signs include microaneurysms, enlarged segments of terminal arterioles, hairpin-shaped vascular loops, and an abnormal foveal avascular zone. [16, 55]
Nonproliferative retinal changes
While abnormal, nonproliferative sickle retinal changes generally are asymptomatic and do not require treatment. [1]
Venous tortuosity
Although common, it is not pathognomonic of sickle cell disease.
Venous tortuosity is due to decreased perfusion/circulation (ie, venous stasis, arteriolar-venous shunting).
Salmon patch hemorrhage
An intraretinal hematoma develops when sickled erythrocytes suddenly occlude the arterioles, with subsequent blowout of the vessel wall.
Often found in the mid periphery, it varies in size and is round or ovoid in shape.
The hemorrhage often is confined to the neural retina, but it occasionally leaks through the internal limiting membrane or into the subretinal space.
The hemorrhage immediately appears bright red; over several days, it becomes an orange-red, salmon color for which it is named. [1]
Black sunburst
This pigmented chorioretinal scar usually is found in the peripheral retina. [1]
On ophthalmoscopy, these scars appear round or ovoid, measuring 1.5 to 2 disk diameters, have stellate or spiculate borders, and often are associated with iridescent spots.
Hemorrhage from retinal arteriolar occlusion can dissect between the neural retina and the retinal pigment epithelium (RPE), resulting in irritation and hypertrophy of the pigment epithelium and migration of pigmented cells into the area. [1]
Angioid streaks
In 1959, Lieb et al associated angioid streaks with sickle cell disease.
Appearing as pigmented striae that lie under the retinal vessels, angioid streaks are breaks in the Bruch membrane. They usually surround the disc, extending radially.
Angioid streaks are not specific to hemoglobinopathies but are seen in patients with other hemolytic anemia, Paget disease, Ehlers-Danlos syndrome, and pseudoxanthoma elasticum.
In hemoglobinopathies, incidence ranges from 1% to 6%.
The frequency of angioid streaks increases with age. [17]
The pathogenesis of angioid streaks is generally controversial but that of sickle cell disease is even more confusing. The four most commonly proposed and accepted mechanisms of angioid streak development include the following:
-
Diffuse elastic degeneration
-
Iron deposition in the Bruch membrane secondary to hemolysis of retinal and subretinal hemorrhage
-
Impaired nutrition caused by sickling and stasis
-
Calcification of the Bruch membrane
Fibrovascular ingrowth can occur at the breaks.
Secondary changes may include the following:
-
Thickening of the retinal pigment epithelium basement membrane
-
Retinal pigment epithelium atrophy, hypertrophy, or hyperplasia
-
Choriocapillaris damage
-
Photoreceptor loss
-
Serous retinal detachment
-
Disciform scar formation [18]
These lesions are usually asymptomatic; however, in the presence of choroidal neovascularization (CNVM) and macular degeneration, these lesions can lead to visual loss.
Treatment of the CNVM is laser photocoagulation. Recurrence rates are high.
Proliferative sickle retinopathy
This retinopathy is characterized by neovascularization that results from repeated episodes of ischemia secondary to repetitive or successive peripheral arterial occlusions. Although neovascularization may be seen in the optic disc and the macula, proliferative sickle retinopathy (PSR) is primarily a peripheral retinal disease. Goldberg proposed the universally accepted classification for PSR in 1971, which is divided into five discrete stages. [1]
Stage I - Peripheral arteriolar occlusion [1]
Seen by ophthalmoscopy, areas of retinal ischemia secondary to nonperfusion become an abnormal grayish brown color.
The exact pathogenesis is not known, but it is theorized and accepted that sickled erythrocytes cause occlusion secondary to increased viscosity, followed by stasis and subsequent thrombosis.
Why the peripheral retina more commonly is affected than the posterior pole remains unclear. Vessel luminal diameter, critical closing pressure, and oxygen tension in the peripheral retinal appear to play important roles in development.
Fluorescein angiography helps delineate areas of avascular and abnormal capillary bed from the normally perfused retina.
Stage II - Arteriolar-venular anastomoses [1]
These anastomoses are characterized by the shunting of blood from the occluded arterioles to the nearest venules.
Following peripheral arteriolar occlusions, vascular remodeling ensues at the junction between the perfused posterior and nonperfused peripheral neural retina.
Unoccluded arterioles develop collateral circulation through the preexisting capillaries, resulting in arteriolar-venular anastomoses.
This is not neovascularization.
Clinically, these anastomoses may be difficult to view via ophthalmoscopy. Fluorescein angiography can demonstrate arteriovenous anastomoses that do not leak dye.
Stage III - Neovascular proliferation [1]
Repeated ischemic events lead to neovascular proliferation.
In the early stage of development, these neovascular fronds are small and lie flat on the retinal surface. With time, these abnormal vascular fronds grow in size and take on the characteristic appearance that resembles the marine invertebrate Gorgonia flabellum, hence the name "sea fan neovascularization." Sea fans are not pathognomonic.
Fluorescein angiography can help identify very small sea fan lesions. Unlike arteriolar-venular anastomoses, which do not leak, sea fan lesions leak profusely.
Patients with sea fan neovascularizations are at increased risk for vitreous hemorrhage and retinal detachment.
Epidemiologically, patients with sickle cell C disease are more likely to present with neovascularization than patients with sickle cell-thalassemia disease.
Sea fans often autoinfarct or spontaneously regress (20-60%). [1]
Supposedly, these neovascular fronds are strangulated by fibroglial tissue. The acute occlusion of the sea fan feeding arteriole may result in autoinfarction.
Stage IV - Vitreous hemorrhage [1]
Vitreous hemorrhage can result from PSR or trauma; it may be spontaneous secondary to vitreous collapse and/or traction of the adherent neovascular tissue.
When the vitreous collapses, either from liquefaction that is associated with aging or degenerative changes secondary to chronic leakage from sea fans, traction is exerted on the neovascular tissue.
The force exerted on the sea fans by the vitreous can tear the neovascularized and retinal vessels, leading to vitreous hemorrhage.
The degree of hemorrhage varies (ie, small or large, bleeding can occur at irregular intervals for several years). Vitreous hemorrhage may be small and localized or large enough to cloud the entire center of the vitreous cavity, giving rise to visual symptoms.
Patients with sickle cell C disease are most likely to develop neovascular proliferation, and they are more likely to present with vitreous hemorrhage.
Stage V - Retinal detachment [1]
Retinal detachments may be rhegmatogenous and/or tractional. Traction from bands and membranes on the neovascular tufts can lead to sufficient retinal traction with or without retinal tears, both of which may lead to retinal detachment.
Another proposed theory for retinal detachment in hemoglobinopathies is retinal atrophy. Retinal ischemia can result in retinal thinning, retinal hole formation, and, subsequently, retinal detachment.
Clinically, the retinal tears that lead to retinal detachment are small to moderate in size and ovoid or horseshoe in shape.
The pathogenesis of hemoglobinopathy retinal tears and detachment is similar to proliferative diabetic retinopathy and other proliferative retinopathies.
Patients with sickle cell C disease are more likely to develop retinal detachment than patients with other forms of hemoglobinopathies. [19, 20]
Causes
See Pathophysiology.
Complications
Potential complications include the following:
