Case Report
Retinopathy Arises From Sickle Cell Trait

This otherwise healthy patient had a suspected branch retinal vein occlusion that tipped doctors off to the diagnosis.

by Todd R. Brantley, O.D. and Christopher D. Allee, O.D., Houston

A 43-year-old black male was referred to our clinic for evaluation of a suspected branch retinal vein occlusion of the right eye. An optometrist noted the suspected occlusion four days earlier.

1. Posterior pole of the right eye with multiple hemorrhages next to the optic nerve head, with an inferior preretinal hemorrhage and tortuous vessels superiorly.

The patient reported intermittent episodes of "stringy" floaters in his right eye for the past six months. General health and family histories were unremarkable. He reported being in excellent condition, was not taking any medications and had no known drug allergies.

Diagnostic Data
Entering distance visual acuity without correction was 20/20 O.U. Preliminary findings were unremarkable, and there was no afferent pupillary defect. Intraocular pressure was 17mm Hg in both eyes. Biomicroscopy was normal for both eyes.

A dilated fundus exam of the left eye was normal. The right eye, however, showed multiple blot hemorrhages nasal to the optic nerve and along the inferior arcade (figure 1). Also evident was a preretinal hemorrhage at the major bifurcation of the inferior arcade. Mild venous tortuosity extended superiorly from the optic nerve. We found a slightly elevated area of neovascularization superiorly near the equator, bordering a large area of discolored, ischemic retinal tissue (figure 2).

2. Areas of neovascularization bordering peripheral retinal ischemia and "silver-wiring" adjacent to the neovascular nets.

We also saw prominent arteriolar "silver-wiring" in this region, and a large vascular loop along the superior nasal arcade (figure 3), pointing to more peripheral hypoxic ret- inal tissue. Fluorescein angiography revealed arteriolar thinning and superior neovascularization (figure 4), and a large zone of severe peripheral nonperfusion with associated areas of neovascularization in the superior nasal quadrant (figure 5).

Further testing was necessary to determine the underlying disease and to rule out other potential systemic disorders. We ordered a chest X-ray and blood tests, including a complete blood count with differential, hemoglobin electrophoresis, angiotensin-converting enzyme (ACE), and a rapid plasma reagin test (RPR).

Diagnosis
The hemoglobin electrophoresis returned positive for sickle cell trait. All other findings were unremarkable. We diagnosed proliferative sickle cell retinopathy of the right eye secondary to sickle cell trait, and instructed the patient to return in three weeks for circumferential retinal scatter photocoagulation using the argon laser.

Treatment and Follow-up

3. Geographical retinal ischemia with associated vascular loop located in the nasal fundus.

At the three-week follow up, the black lines in the patient's vision were still present, and he denied any change in acuity. His distance visual acuities at this visit were 20/25 O.D. and 20/20 O.S. An ophthalmologist performed circumferential scatter photocoagulation using moderate argon laser intensity. The goal was regression of the active neovascularization while minimizing the risk of future neovascularization, vitreous hemorrhages and retinal detachments.

The ophthalmologist educated the patient on the etiology, risks and differentiation of sickle cell trait from sickle cell anemia, and stressed the importance of an an-nual dilated retinal evaluation. The doctor also told the patient that his children should be tested for sickle cell disorders, and instructed him to return in three months for a comprehensive retinal evaluation.

Discussion

4. Fluorescein angiography of the right eye reveals arteriolar thinning and neovascularization from Figure 2.

Sickle cell hemoglobinopathy is one of the most common genetic diseases that affects men and women equally.1 Approximately 10 percent of Caribbean islanders of African descent living in North America are af-fected by sickle cell.2 Eighty percent of them have the sickle cell trait (AS), 10 percent have sickle cell thalassemia (SThal), four percent have sickle cell anemia (SS), and 12 percent ex-hibit sickle cell hemoglobin C disease (SC).2 While sickle cell hemoglobinopathies can occur throughout Saudi Arabia and Asia,3 the highest incidences of sickle cell disorders are found in Africa and the West Indies.1

The ocular manifestations of sickle cell disorders are collectively grouped under the broad term "sickle cell retinopathy." The ophthalmoscopic abnormalities result from the occlusion of peripheral retinal microvasculature. Sickle cell retinopathy is classified as nonproliferative or proliferative based on funduscopic observations and fluorescein angiography.

5. Fluorescein angiography of Figure 3 reveals leakage from several neovascular networks in the supernasal area.

Nonproliferative sickle cell retinopathy consists of a constellation of funduscopic abnormalities such as black sunbursts, venous tortuosity, "salmon patch" intraretinal hemorrhages, "silver-wiring" of retinal arterioles and glistening refractile spots.² Patients with these manifestations require no treatment and are rarely symptomatic, unless the lesions are large enough to re-duce vision. Less common, potentially sight-threatening complications of nonproliferative retinopathy include angioid streaks, central retinal artery and vein occlusions, and retinal holes.^2,5

Proliferative sickle cell retinopathy (PSR) is characterized by pre-retinal neovascularization resulting from retinal ischemia. PSR is classified into five stages based on fundus appearance and fluorescein angiography (see "The Five Stages of PSR," page 106).⁶ The potential for visual impairment increases as the disorder progresses to higher stages.

Many diseases present with funduscopic findings similar to sickle cell. Here are the most common differentials with potential to cause proliferative retinopathy:

• Diabetes. Diabetics have elevated blood glucose levels.

• Sarcoidosis. Patients with sarcoidosis typically test positive for angiotensin-converting enzyme (ACE) and have hilar adenopathies that manifest on chest X-rays.

• Branch retinal vein occlusion (BRVO). Usually the result of hypertension or arteriosclerosis.

• Eales' disease. A diagnosis of exclusion.

• Retinopathy of prematurity. You can rule this out based on birth history and funduscopic appearance (avascular peripheral retina).

Sickle cell retinopathy is one of the most common causes of peripheral proliferative retinopathy.¹ Al-though sickle cell trait was once thought to be a benign condition, it can result in PSR with or without associated

The Five Stages of PSR6 Stage I Peripheral arteriolar occlusion Stage II Peripheral arteriolar-venular anastomoses Stage III Neovascularization, Stage IV Vitreous hemorrhage Stage V Retinal detachment

underlying systemic diseases. Retinal vascular occlusive disease has been reported along with PSR in patients with trauma, diabetes, hypertension and rheumatoid arthritis.^4,7 The most severe systemic complications result in patients with sickle cell anemia, but very few of these patients progress past Stage II-PSR. Patients with sickle cell hemoglobin C disease and sickle cell thalassemia have consistently shown the highest incidence of visual impairments secondary to proliferative retinopathy.^1,2,7-9 Severe visual impairment results from the progression of neovascularization to vitreous hemorrhage, vitreous traction and, ultimately, retinal detachment.

Treatment of proliferative sickle retinopathy must commence once you identify active, preretinal neovascularization ("sea fans") either by ophthalmoscopy or fluorescein angiography.⁶ The goal of therapy is to prevent the progression of sea fans and preclude the possibility of new vessel growth while limiting the iatrogenic complications.^10-12 One study re-ports excellent results using the peripheral circumferential retinal scatter photocoagulation (PCRP) technique, achieving complete or partial neovascular regression in 83 percent of eyes, and stabilization in 17 percent of eyes.⁴ Other treatments for PSR are diathermy, cryotherapy, focal xenon arc photocoagulation and focal argon laser photocoagulation, but these are less effective.

Postsurgical complications frequently occur with these methods. These include preretinal hemorrhage, vitreous hemorrhage, retinal detachment, peripheral field loss, chorioretinal neovascular membranes and macular traction.^11-16 Better results are consistently ac-complished using the laser techniques at low to moderate powers. PCRP seems to be the treatment of choice in most cases. Although spontaneous sea-fan autoinfarction has been well documented in previous studies,¹⁷ most ophthalmologists will not hesitate to treat areas of retinal ischemia because of the potential sight-threatening complications.

As optometrists, we play a vital role in the proper diagnosis and management of patients with sickle cell retinopathy. Sickle cell retinopathy is one disease where patients can be on the verge of severe vision loss, but still maintain good visual acuity. This case is a prime example of why, as eye care professionals, it is our responsibility to dilate patients routinely, allowing for thorough fundus evaluations.

Dr. Brantley, a recent graduate of the University of Houston College of Optometry, now works in a group practice in Dallas. Dr. Allee is the assistant director of Vision America of Houston.

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