Sickle cell disease (SCD) can affect virtually any part of a patient’s eyes. The most significant changes seen in this patient population include proliferative sickle retinopathy (PSCR), the main cause of vision loss in patients with SCD, and nonproliferative retinal alterations.
However, according to a recent study at Zagazig University, Egypt, ocular involvement in patients with SCD may be overlooked.
The results of the study showed that a quarter of the patients (n=32) had proliferative retinopathy and 31% presented with tortuous retinal veins. Moreover, the authors observed macular thinning in all patients. Given the results, the authors concluded that “ocular manifestations and retinopathy were more prevalent in patients with SCD than expected and it correlated with frequent sickling crises and higher [sickle hemoglobin (HbS)] level.”
Beyond Sickle Cell Retinopathy
In addition to retinopathy, many ocular changes have been reported in patients with SCD. Complications may arise in the anterior segment, including conjunctival sign and hyphema. Conjunctival changes may differ depending on the oxygenation status of the patient. Hyphema of the anterior chamber can lead to increased intraocular pressure (IOP) which, in turn, may potentiate retinal artery occlusion, according to some studies.
“Studies have suggested surgical intervention for hyphemas of any size with IOP more than 24 mmHg for more than 24 hours in individuals with sickle cell trait or disease; however, there is little scientific evidence supporting surgical interventions in these case scenarios,” wrote Omar Moussa and Royce W.S. Chen from the Department of Ophthalmology of the Edward S. Harkness Eye Institute, New York, in Therapeutic Advances in Ophthalmology.
Orbital manifestations are less common, though equally important to identify due to the potential risk of vision loss. Vaso-occlusive crises may affect orbital walls, presenting as severe pain, lid edema, proptosis, ophthalmoplegia, and diplopia. In addition, orbital bone infarction may lead to orbital hematoma and, consequently, to orbital compartment syndrome. Involvement of lacrimal glands can be unilateral or bilateral, presenting as pain and swelling.
A recent study conducted by AlRyalat and colleagues found differences in the frequencies of ocular manifestations in genotypes associated with SCD. The study enrolled 1867 patients (mean age, 27.7±11.7 years, 55.5% females) whose data was accessed through the Cooperative Study of Sickle Cell Disease.
PSCR was more frequent in the heterozygous HbS/C genotype and less frequent in the HbS/β° thalassemia genotype. On the other hand, the homozygous HbS/S genotype had the highest frequency of conjunctival sign, whereas the HbS/β+ thalassemia genotype had the lowest.
Detecting Ocular Changes
Detecting SCD-associated retinal alterations can be challenging, particularly in asymptomatic patients. Among 9 patients with SCD analyzed by Almasoudi and colleagues at the King Abdulaziz Medical City in Jeddah, Saudi Arabia, 5 showed no symptoms of ocular complications. The other 4 had slight (n=2) or moderate (n=2) impairment in at least 1 eye. Moreover, the study team identified retinal ischemia in the right eye of a patient who presented with normal macular thickness.
“Routine ophthalmologic examination may not be able to detect or monitor macular or retinal abnormalities unless augmented with detailed imaging techniques,” Almasoudi et al concluded.
Recent advances in retinal imaging methodologies (eg, ultra-widefield fluorescein angiography [UWFA], spectral-domain optical coherence tomography [SD-OCT], and optical coherence tomography angiography [OCT-A]) have eased the task of detecting ocular manifestations.
For instance, UWFA was able to detect peripheral vascular changes missed by experienced ophthalmologists on clinical examination, as well as those overlooked on the classical 7-standard field photograph. SD-OCT showed promise for assessing subclinical macular thinning, whereas OCT-A performed better than fluorescein angiography in detecting microvascular abnormalities in the macula.
According to Moussa and Chen “preliminary data indicate that children with SCD commonly display retinal vascular abnormalities by these sensitive imaging techniques, including Goldberg stage-I and -II retinopathy identified on UWFA, temporal macular thinning on SD-OCT, and vessel dropout on OCT-A.”
In addition, recent studies have identified elevated systolic blood pressure, moderate visual impairment, and anterior segment changes as independent predictors of sickle cell retinopathy (SCR), and have highlighted the potential role of nonmydriatic ultra-widefield imaging in SCR screening.
Treatment May Be Required
Vision loss can occur as a consequence of PSCR. However, it is relatively rare, particularly in the pediatric population. Therefore, treatment of eye conditions in patients with SCD is usually left for advanced stages that tend to occur later in life.
For example, patients with large or multiple areas of neovascularization or vitreous hemorrhage are treated with scatter retinal laser photocoagulation or panretinal photocoagulation to prevent retinal detachment.
Vitrectomy may be useful in cases of nonclearing vitreous hemorrhage and retinal detachment. Some patients may benefit from combined surgery and intraoperative scatter laser photocoagulation or intravitreal injection of a vascular endothelial growth factor (VEGF) inhibitor, such as the monoclonal antibody bevacizumab (Avastin®). Some studies suggest that anti-VEGF agents may promote the involution of neovascularization, but further investigation is required.
Moussa O, Chen RWS. Hemoglobinopathies: ocular manifestations in children and adolescents. Ther Adv Ophthalmol. 2021;13:25158414211022880. doi:10.1177/25158414211022882
AlRyalat SA, Jaber BA-DM, Alzarea AA, Alzarea AA, Alosaimi WA, Al Saad M. Ocular manifestations of sickle cell disease in different genotypes. Ophthalmic Epidemiol. 2021;28(3):185-190. doi:10.1080/09286586.2020.1801762
Hassan T, Badr M, Hanna D, et al. Retinopathy in Egyptian patients with sickle cell disease: a cross-sectional study. Medicine. 2021;100(51):e28355. doi:10.1097/MD.0000000000028355
Almasoudi EA, Magliah SF, Alzwaihri AS, Aljuwaybiri AO, Alqahtani AS. Incidence of eye complications among sickle cell disease patients in Jeddah, Saudi Arabia: a cross-sectional study. Ann Med Surg. 2022;79:103999. doi:10.1016/j.amsu.2022.103999
Idris IM, Yusuf AA, Gwarzo DH, et al. High systolic blood pressure, anterior segment changes and visual impairment independently predict sickle cell retinopathy. Hemoglobin. 2021;45(4):228-233. doi:10.1080/03630269.2021.1957927
Ahmed I, Pradeep T, Goldberg MF, et al. Nonmydriatic ultra-widefield fundus photography in a hematology clinic shows utility for screening of sickle cell retinopathy. Am J Ophthalmol. 2022;236:241-248. doi:10.1016/j.ajo.2021.10.030