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Latent proliferative sickle cell retinopathy in sickle cell trait
Abstract
To describe a patient with sickle cell trait who developed latent proliferative sickle cell retinopathy after mild blunt trauma.
Case Report. A 20-year-old man with unilateral Stage 3 sickle retinopathy associated with an ischaemic ridge presenting three years after the initial mild blunt ocular trauma.
Fundus examination of the left eye showed an ischaemic ridge delineating avascular from vascular retina. Fluorescein angiography of the left eye showed an avascular peripheral retina and multiple sea fan neovascularization. Blood studies showed him to be Hb AS.
In our patient the proliferative changes were the result of his initial mild trauma associated with an increase in the intraocular pressure. The latent development of the sea-fan neovascularization associated with an ischaemic ridge is unusual. Advice about potential complications to patients with Hb AS after ocular trauma is advocated.
... Outros autores sugerem também que o traço falciforme foi o fator que predispôs ao acometimento de carcinoma de medula renal; morte intraparto por cardiomiopatia peripartal; infarto renal por hematoma perirrenal; infarto de glândula pituitária durante a gravidez; retinopatia após leve trauma ocular; cegueira em paciente com leptospirose e necrose asséptica da cabeça do fêmur (MURAO; FERRAZ, 2007;MEHTA;WHITTAKER;TSALOUMAS, 2001;COSTA et al., 2000;TOLLIN;SEELY, 1994;PASTOREK;SEILER, 1985). ...
... Outros autores sugerem também que o traço falciforme foi o fator que predispôs ao acometimento de carcinoma de medula renal; morte intraparto por cardiomiopatia peripartal; infarto renal por hematoma perirrenal; infarto de glândula pituitária durante a gravidez; retinopatia após leve trauma ocular; cegueira em paciente com leptospirose e necrose asséptica da cabeça do fêmur (MURAO; FERRAZ, 2007;MEHTA;WHITTAKER;TSALOUMAS, 2001;COSTA et al., 2000;TOLLIN;SEELY, 1994;PASTOREK;SEILER, 1985). ...
... Outros autores sugerem também que o traço falciforme foi o fator que predispôs ao acometimento de carcinoma de medula renal; morte intraparto por cardiomiopatia peripartal; infarto renal por hematoma perirrenal; infarto de glândula pituitária durante a gravidez; retinopatia após leve trauma ocular; cegueira em paciente com leptospirose e necrose asséptica da cabeça do fêmur (MURAO; FERRAZ, 2007;MEHTA;WHITTAKER;TSALOUMAS, 2001;COSTA et al., 2000;TOLLIN;SEELY, 1994;PASTOREK;SEILER, 1985). ...
SEIXAS, F. A. V.; CASTALDO, A.; BIANCONI, A. L.; NILSON, L. G. Interação entre traço falciforme e alfa-talassemia: relato de um caso no noroeste do paraná. Arq. Ciênc. Saúde Unipar, Umuarama, v. 13, n. 1, p. 51-54, jan./abr. 2009. RESUMO: O traço falciforme associado à alfa-talassemia (AS/α-talassemia) é uma característica rara na população do sul do Brasil. Em função deste e de outros motivos, casos dessa interação são confundidos e muitas vezes subdiagnosticados como sendo de anemia ferropriva, o que pode levar pacientes a tratamentos desnecessários e, muitas vezes prejudiciais à sua saúde. Este trabalho relata o caso de uma paciente de 80 anos de idade que, após participar de um estudo populacional sobre incidência de hemoglobinopatias, descobriu ser portadora da interação AS/α-talassemia. Até então vinha recebendo tratamento para anemia ferropriva, apesar de não apresentar melhora. Este trabalho discute ainda como os índices hematimétricos, associados aos achados eletroforéticos, contribuíram para um diagnóstico diferencial da interação AS/α-talassemia, o que pode auxiliar médicos e profissionais da saúde a um diagnóstico mais preciso, visando à melhoria da qualidade de vida do paciente e, consequentemente, a diminuição da incidência destas doenças genéticas na população. ABSTRACT: Sickle cell trait, associated to alpha-thalassemia (AS/α-talassemia), is a rare characteristic in the population living in the South of Brazil. Because of such a rare condition and other reasons, cases of that interaction are confusing and most of the times sub-diagnosed as iron deficiency anemia, thus submitting the disease carrier to unnecessary treatments which, most of the time, are harmful to the patient's health. The present study reports the case of an 80-year-old patient, who after taking part in a study on the incidence of hemoglo-binopathies on population, discovered to carry the interaction AS/α-thalassemia. Up to then the patient had been submitted to treatments to control iron deficiency anemia, although not presenting any improvement. Moreover, the present study discusses how hematimeter indexes, associated to electrophoretic findings, have contributed for a differential diagnosis of AS/α-talassemia interaction, what may aid physicians and health professionals to obtain a more precise diagnosis, aiming at improving the patient's life-quality, and consequently, leading to a decrease in the incidence of such genetic diseases in the population. Introdução O traço falciforme (AS) é um distúrbio gené-tico da hemoglobina bastante comum na população brasileira, principalmente a da região nordeste. Este distúrbio, de caráter co-dominante, raramente está as-sociado a manifestações clínicas e hematológicas sig-nificativas. Como os pacientes portadores convivem com a doença desde o seu nascimento, os mesmos não notam diferença em seu modo de vida, comparando-se com indivíduos de genótipo normal (LEE et al., 1998). Sendo assim, episódios de cansaço mediante esforços físicos que são decorrentes da doença, passam desper-cebidos e, dessa maneira, o paciente nascido antes do estabelecimento da portaria GM/MS nº 822/GM de 06 de junho de 2001, a qual torna obrigatória a triagem neonatal para doenças falciformes e outras hemoglo-binopatias, só descobre que é portador quando realiza um hemograma, geralmente solicitado para investigar outras doenças, ou nos procedimentos para triagem de doadores em bancos de sangue. Frequentemente suas manifestações hematoló-gicas são confundidas, e muitas vezes subdiagnostica-das, como as de anemia ferropriva (WAGNER et al., 2005; MATOS et al., 2008), o que expõe os pacientes a tratamentos inadequados e muitas vezes por longos períodos de tempo. O traço falciforme, por si só, é menos frequente na região sul, em relação às outras regiões do país e, quando associado à alfa-talassemia, torna-se uma carac-terística rara nessa população. Estudos populacionais na região sul do Brasil têm demonstrado que a frequência de indivíduos portadores da interação AS/α-talassemia é baixíssima, sendo de 0,17% no Noroeste do Paraná, enquanto que no Rio Grande do Sul é de 0%, porém, esta freqüência aumenta para 1,02% em portadores de anemia a esclarecer (SEIXAS et al., 2008). Pacientes portadores desta interação podem transmitir um, outro, ou ambos os genes relacionados a essas hemoglobi-nopatias a seus descendentes, aumentando ainda mais a frequência destes genes na população. Por motivos como estes, trabalhos que correlacionam as manifesta-ções clínicas e hematológicas desta interação, visando a um diagnóstico mais preciso desta patologia, se tornam necessários e devem ser estimulados. Este trabalho visa relatar um caso ocorrido na cidade, de Umuarama-PR, onde uma paciente, na oca-sião com 80 anos de idade descobriu ser portadora do
... The frequency of retinopathy is greatest in adulthood, but retinopathy has also been described in children [6]. Individuals with sickle-cell trait comprise 8% of the African-Caribbean [7]. Although these individuals often show no relevant clinical manifestations, they may present various retinal changes such as hemorrhages, exudates, angioid streaks, acute chorioretinal infarction, chorioretinitis, and vitreous hemorrhage, retinal vascular abnormalities such as tortuous / dilated retinal veins, microaneurysms, central retinal artery occlusion and retinal proliferation [7]. ...
... Individuals with sickle-cell trait comprise 8% of the African-Caribbean [7]. Although these individuals often show no relevant clinical manifestations, they may present various retinal changes such as hemorrhages, exudates, angioid streaks, acute chorioretinal infarction, chorioretinitis, and vitreous hemorrhage, retinal vascular abnormalities such as tortuous / dilated retinal veins, microaneurysms, central retinal artery occlusion and retinal proliferation [7]. ...
Retinopathy is a one of the major clinical manifestation of Hemoglobinopathy. It is acquired secondary to another retinal disorder. Retinopathy especially retinal occlusions are painless loss of monocular vision it’s from a vascular disorder. Ocular stroke caused by embolism in a retinal artery, that may emboli travel to distal branches of the retinal artery, causing loss of other section in the visual eld. e manifestations of Sickle cell disease ocular manifestations came due to vascular occlusion, which may exist in the conjunctiva, iris, retina, and choroid. Because the ocular changes produced by SCD could be shown in other diseases, it’s important to except other occlusions’ causes, which have included central retinal vein occlusion, Eales disease, and retinopathy secondary to other chronic disorders. Other ocular changes cause that includes polycythemia vera, familial exudative vitreoretinopathy, talc and cornstarch emboli, and uveitis. Diagnosis of hemoglobenopathies is performed exclusively through Hb electrophoresis. e treatments and their results vary from one condition to the other.
... 169,215 In the majority of reported cases, these complications occurred in patients with concomitant systemic disease such as hypertension, tuberculosis, diabetes, sarcoidosis, syphilis, or rheumatoid arthritis. A few cases were associated with blunt ocular trauma in the absence of systemic disease, 151 suggesting a role for environmental modifiers. Many ocular findings reported in sickle cell trait may be coincidental in view of the large number of patients that have this finding. ...
... Mathews et al concluded that adhesion molecules might play an important role in the vaso-occlusive phase of sickle cell retinopathy, and in autoinfarction of sea fan formations. 151 Recently, Kim et al reported that changes in VEGF and PEDF are minimal before proliferative changes occur in the sickle cell retina. However, although both PEDF and VEGF are significantly elevated in viable sea fan formations in SCD, only PEDF is present in non-viable sea fans, demonstrating that PEDF might play an important role in inhibiting angiogenesis and inducing sea fan regression. ...
The pathophysiology of sickle cell disease is not limited to abnormal red blood cells. The clinical manifestations of sickle cell disease include complex pathways and processes such as endothelial activation, inflammation, bioavailability of nitric oxide, oxidative stress, and the adhesiveness of a variety of blood cells. Increasingly, distinct subphenotypes and genetic modifiers of sickle cell disease are being recognized. We apply recent advances in sickle cell disease to ocular biology to highlight translational research in this field and encourage additional studies on the ocular manifestations of sickle cell disease.
... If left untreated, the incidence of blindness from PSR is about 12%. [10] Advancements in awareness, early screening and diagnosis and systemic therapy as well as modern day laser and vitrectomy techniques have greatly reduced the risk of vision loss. ...
... Numerous case studies have reported on individuals with SCT who present with retinopathy (Pandey 2015;Reynolds, Besada, and Winter-Corella 2007). However, these articles describe retinopathy developing after blunt ocular trauma (Jackson et al. 1995;Mehta, Whittaker, and Tsaloumas 2001;Pandey 2015), or in association with a systemic disease such as diabetes, syphilis, tuberculosis, or sarcoidosis (Jackson et al. 1995;Nagpal et al. 1977). ...
Rates of type 2 diabetes (T2D) are rapidly increasing worldwide, including in regions, and among populations, of the globe where sickle cell trait (SCT) is prevalent. SCT, the heterozygote form of sickle cell disease, is generally considered a benign condition. However, evidence shows that vascular function is more severely impaired in people with combined T2D and SCT (T2D-SCT) than in those with T2D only. Furthermore, evidence suggests that SCT could complicate screening for T2D, thereby increasing the risk of delayed diagnosis of T2D. In light of this information, the main objectives of this thesis were to study the challenges related to diagnosing and monitoring T2D in individuals with SCT, and to evaluate the mechanisms and consequences of the amplified vascular dysfunction observed in T2D-SCT. Study 1 compared the agreement between two standard measures of glycemia, HbA1c and fasting glucose, and one alternative measure of glycemia, fructosamine, in Senegalese adults with and without SCT. The findings revealed substantial disparities between the markers of glycemia, and these differences were exaggerated in individuals with SCT. Study 2 illustrated that SCT could potentially augment the risk of developing retinopathy, nephropathy, and hypertension in T2D, and demonstrated that AGEs are likely implicated in the vascular dysfunction observed in T2D-SCT. Studies 3 and 4 studied microvascular function in a mouse model of T2D-SCT. Study 3 showed that T2D-SCT mice had significantly impaired endothelium-dependent vasodilation in-vivo. Study 4 revealed that ACH-mediated vasodilation in-vivo was significantly elevated in the microvasculature of mice with combined T2D and SCT due to cyclooxygenase-2 dependent mechanisms. Overall these findings deepen our understanding about the complexities related to diagnosing and managing T2D in individuals with SCT
... Environmental factors may confound these studies. For example, Mehta et al. described a patient with SCT who developed PSR after mild ocular blunt trauma [36]. The reported prevalence of PSR in various genotypes is summarized in Table 1. ...
Purpose
To provide a focused review of sickle cell retinopathy in the light of recent advances in the pathogenesis, multimodal retinal imaging, management of the condition, and migration trends, which may lead to increased prevalence of the condition in the Western world.
Methods
Non-systematic focused literature review.
Results
Sickle retinopathy results from aggregation of abnormal hemoglobin in the red blood cells in the retinal microcirculation, leading to reduced deformability of the red blood cells, stagnant blood flow in the retinal precapillary arterioles, thrombosis, and ischemia. This may be precipitated by hypoxia, acidosis, and hyperosmolarity. Sickle retinopathy may result in sight threatening complications, such as paracentral middle maculopathy or sequelae of proliferative retinopathy, such as vitreous hemorrhage and retinal detachment. New imaging modalities, such as wide-field imaging and optical coherence tomography angiography, have revealed the microstructural features of sickle retinopathy, enabling earlier diagnosis. The vascular growth factor ANGPTL-4 has recently been identified as a potential mediator of progression to proliferative retinopathy and may represent a possible therapeutic target. Laser therapy should be considered for proliferative retinopathy in order to prevent visual loss; however, the evidence is not very strong. With recent development of wide-field imaging, targeted laser to ischemic retina may prove to be beneficial. Exact control of intraoperative intraocular pressure, including valved trocar vitrectomy systems, may improve the outcomes of vitreoretinal surgery for complications, such as vitreous hemorrhage and retinal detachment. Stem cell transplantation and gene therapy are potentially curative treatments, which may prevent retinopathy.
Conclusions
There is lack of evidence regarding the optimal management of sickle retinopathy. Further study is needed to determine if recent progress in the understanding of the pathophysiology and diagnosis of sickle retinopathy may translate into improved management and outcome.
... However vaso-occlusive disease of the choroid and chorioretinal infarctions have been also reported [14] . The clinical manifestations of the disease are considered the result of the sickling of red blood cells, which are rigid and unable to alter their shape, so they become impacted in capillaries and arterioles leading to vascular occlusion [15][16] . The development of these changes seems to depend on the quantity of abnormal hemoglobin present [17] . ...
... Sickle cell trait is a significant risk factor for complicated traumatic hyphemas following blunt trauma, because of increased risk of secondary hemorrhage, anterior and posterior synechiae, increased intraocular pressure, and glaucomatous optic atrophy, and permanent visual impairment [54,55]. ...
Sickle cell trait (SCT), the heterozygous state of the sickle hemoglobin beta globin gene (HbAS) is carried by as many as 100 million individuals including up to 25% of the population in some regions of the World. Sickle cell trait is the best-characterized genetic polymorphism known to protect against falciparum malaria. Although SCT was initially considered as a benign condition, data are accumulating of serious morbidities in SCT individuals including increased incidence of hematuria, renal papillary necrosis, renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related rhabdomyolysis and sudden death. Despite these associations, the average life span of individuals with sickle cell trait is similar to that of the general population. Nonetheless, given the large number of people with sickle cell trait, it is important that physicians be aware of these associations. The aim of this article is to review publications reporting and discussing morbidities in SCT individuals.
... Individuals with sicklecell trait comprise 8% of the African Ca ribbean (11) population and over 10% of the Brazilian population (1) . Although these individuals often show no relevant clinical manifesta tions, they may present various retinal changes such as hemorrhages, exudates, angioid streaks, acute chorioretinal infarction, choriore ti nitis, vitreous hemorrhage, retinal vascular abnormalities such as tor tuous/dilated retinal veins, microaneurysms, central retinal artery occlu sion and retinal proliferation (1114) . ...
Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients.
Sickle cell trait (SCT) is a common hemoglobin variant, particularly in patients of African descent. Patients with SCT have an increased risk of adverse ocular events following trauma with subsequent elevated intraocular pressure (IOP). The authors describe three cases of young males with peripheral vaso-occlusive events following ocular trauma with subsequent elevated IOP. These cases demonstrate the importance of careful peripheral exams in young patients with SCT following trauma.
[ Ophthalmic Surg Lasers Imaging Retina . 2019;50:e84–e87.]
Background: Sea fan neovascularization is a well established finding in sickle cell retinopathy, but it is usually not associated with sickle cell trait. Under ordinary circumstances, those with sickle cell trait do not develop sickling or anemia and thus do not present with clinical signs or symptoms. However, retinopathy may occur in those individuals with sickle cell trait when there are other precipitating factors present. Under conditions that contribute to hypoxia, patients who have sickle cell trait may develop sickle cell retinopathy and other ocular complications. Case Reports: Two cases in which the individual had what appeared to be sea fan neovascularization are presented. Both were found to have sickle cell trait. Both had other systemic vascular diseases that were believed to have contributed to the development of the sea fan neovascularization. Conclusions: Sea fan neovascularization can occur in patients without sickle cell anemia. In such cases, an investigation for hemoglobinopathies in conjunction with other systemic conditions which may be contributing to hypoxia must be conducted. Those patients who are known to have both sickle cell trait and other systemic vascular disease should undergo regular ophthalmic examination.
The authors present the youngest reported child with proliferative sickle retinopathy. A 3-year, 6-month-old boy presented with leukocoria in the left eye, left esotropia, and dense free-floating white vitreous cells obscuring the fundus, suspicious for endophytic retinoblastoma. Ultrasonography depicted dense debris in the vitreous with no distinct calcific echo or retinal mass. Transcorneal, transzonular fine-needle aspiration biopsy of the vitreous confirmed the presence of dehemoglobinized vitreous red blood cells without tumor. The opposite eye showed peripheral retinal pigment epithelial proliferation and fibrosis with angiographic peripheral ischemia. Hemoglobin electrophoresis disclosed sickle trait (AS). The findings were classified as proliferative sickle cell retinopathy with vitreous hemorrhage in the left eye and non-proliferative sickle cell retinopathy in the right eye. Leukocoria generally raises warnings for retinoblastoma, but can also reflect chronic vitreous hemorrhage.
We review the current knowledge of the pathophysiology of sickle cell disease (SCD), the clinical complications and the state of the art in SCD diagnostics. Today, a flexible laboratory concept allows the fast and economic clarification of the patients' sickle cell hemoglobin (HbS) status, e.g. additional compound heterozygosities. In contrast to a well-investigated pathophysiology of the disease, factors influencing the severity of symptoms as well as some laboratory findings in SCD still lack a final explanation. In this review, we focus on red cell lysis resistance as an additional diagnostic tool in SCD. There is a need for further studies regarding lysis resistance in blood samples from patients with HbS.
Sickle hemoglobinopathies are among the most prevalent genetic disorders in the United States. Sickle cell trait (hemoglobin AS) is the most common genotype and has traditionally been considered a benign condition. Systemic and ocular complications are seen infrequently in patients with sickle cell trait. In the presence of concomitant systemic diseases or trauma, however, marked retinopathy can occur. The presence of retinopathy in patients with sickle cell trait necessitates a comprehensive medical workup, including serologic testing to rule out systemic conditions.
Two cases are presented. The patient in case 1 is a 44-year-old black man with a positive history of sickle cell trait and uncontrolled hypertension. Best-corrected visual acuities (BCVAs) were 20/20 in the right eye (O.D.) and the left eye (O.S.). Retinal evaluation found vitreo-retinal fibrotic scaffolding and "sea-fan" neovascularization. The patient in case 2 is a 45-year-old black woman who presented after a stroke 1-month prior. Her medical history was positive for hypertension, hypercholesterolemia, a recently diagnosed aneurismal dilation of the ascending thoracic aorta, and sickle cell trait. BCVAs were 20/20 O.D., and 20/20 O.S. A single dot hemorrhage was evident O.D., and an inferior-temporal branch retinal artery occlusion with an adjacent area of sea-fan neovascularization was observed O.S.
Sickle cell disease remains a major public health concern because of its associated significant morbidity and mortality. Sickle cell trait is considered benign in a healthy patient. However, under conditions of stress, concomitant systemic diseases, or trauma leading to hypoxia, sickle cell trait can become a pathologic risk factor.
Occlusion of a central artery of the retina is a not uncommon occurrence. It is usually associated with arteriosclerosis, or less often with embolization from endocarditis, but may also be seen with syphilis, periarteritis nodosa, polycythemia vera, thromboangiitis obliterans, and temporal arteritis. A much rarer condition, however, is the occlusion of both central retinal arteries. The following is a case report of a Negro woman with proved systemic lupus erythematosus, sickle cell trait, and active pulmonary tuberculosis who suffered complete occlusion of the left central retinal artery, followed 13 days later by complete occlusion of the right central artery. This patient was treated with cortisone.REPORT OF A CASE
A 36-year-old Negro housewife was admitted to the University Division Chest Service of Kings County Hospital on May 21, 1954, because of malaise, fever, and productive cough. In 1951 the patient began to have mild temperature elevation, cervical adenopathy, and progressive
Seven patients had sickle cell trait (hemoglobin AS) and vasoproliferative retinopathy. The retinal abnormalities in these seven patients were indistinguishable from those seen in patients with clinically significant sickling hemoglobinopathies (sickle cell-hemoglobin C disease, hemoglobin S-thalassemia disease, and sickle cell anemia). All seven patients also had some evidence of associated systemic disease such as diabetes, syphilis, tuberculosis, or sarcoidosis. In the presence of an associated systemic disease, marked retinopathy can occur in the ordinarily benign condition of sickle cell trait.
(Arch Intern Med 137:325-328, 1977)
An 8-year-old black boy with sickle cell trait struck his left brow and globe on the edge of a table and had immediate blurring of vision. Six days later visual acuity was light projection, and traumatic iritis with secondary glaucoma and perimacular edema were present. Fluorescein angiography indicated obstructed peripheral and perimacular arterioles and dye leakage from the disk.
Following trauma and secondary glaucoma, retinal vascular occlusions occurred in two black patients, a nine-year-old girl and a 17-year-old boy with sickle-trait hemoglobin. Their cases were managed conservatively because of their youth and the fact that their susceptibility to vascular occlusions from increased intraocular pressure was not known. The incidence of sickle-cell trait and the frequency of ocular trauma and secondary glaucoma combine to make this disastrous complication of potential clinical and therapeutic importance. Sickle-cell trait, once considered a benign condition, may be the cause of systemic as well as ocular catastrophe under the proper set of circumstances.
Sickle trait is traditionally considered a benign condition by ophthalmologists. Three cases of sickle retinopathy in subjects with sickle trait are reported. In all cases the onset of retinopathy was related to other contributing factors: in one case a traumatic hyphaema and raised intraocular pressure, in two others diabetes mellitus. Patients with sickle trait are at risk of retinopathy if coincident ocular or systemic disease is present.