Retinopathy In Sickle Cell Disease Research Articles

Laser therapy for retinopathy in sickle cell disease.

Laser therapy for retinopathy in sickle cell disease.

Plasma levels of E-selectin are associated with retinopathy in sickle cell disease.

The vascular endothelium is markedly disrupted in sickle cell disease (SCD) and is the converging cascade of the complex pathophysiologic processes linked to sickle cell vasculopathy. Circulating endothelial activation and/or apoptotic markers may reflect this endothelial activation/damage that contributes to the pathophysiology of the SCD vascular complications. Plasmatic levels of circulating endothelial cells (CECs), E-selectin, progenitor's endothelial cells (EPCs), and circulating extracellular vesicles (EVs) were evaluated in 50 SCD patients, 16 with vasculopathy. The association between these markers and the occurrence of disease-related microvascular injuries of the eye (retinopathy), kidney (nephropathy), and skin (chronic active ulcers) was explored. Among the endothelial activation markers studied, only higher plasma levels of E-selectin were found in SCD patients with vasculopathy (p=.015). Increased E-selectin levels were associated with retinopathy (p < .001) but not with nephropathy or leg ulcers. All patients, at steady state, with or without vasculopathy, did not display a high count of CEC and EPC, markers of endothelial injury and repair. We did not show any significant differences in EVs levels between vasculopathy and not vasculopathy SCD patients. Further studies will be required to determine whether the E-selectin could be used as an early biomarker of retinopathy sickle cell development.

The Impact of Optical Coherence Tomography in the Early Identification of Children with Sickle Cell Retinopathy.

Introduction Sickle cell disease is characterized by the production of abnormal hemoglobin, which affects hemoglobin molecule stability during hypoxia and leads to the formation of sickle cells, resulting in increased hematic viscosity, hemolysis, and microvascular blockage. Vasoocclusion is assumed to be the primary cause of vision-threatening retinopathy in sickle cell disease. The aim of this study was to improve the early detection of sickle cell retinopathy (SCR) in children with sickle cell disease (SCD) and investigate the link between systemic and ocular symptoms. Methods This cross-sectional study comprised children with SCD. The patient files provided a detailed medical history. The laboratory tests included a blood count, reticulocyte count, and Hb electrophoresis. The slit lamp, fundus, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) were all part of the ophthalmological examination. Results The study comprised 15 children with sickle cell disease who met the inclusion and exclusion criteria, with a mean age of 11.15 ± 1.29 years. Nine of the children were males (60%) and six were females (40%). 8 (53.3%) of the children had Hb SS, three (20%) had Hb SC, three (20%) had Hb SB+, and one (6.7%) had Hb SB0. Four children (26.7%) had poor visual acuity. A fundus examination revealed significant abnormal findings in 12 of the 7 children's eyes (40 percent). Macular thinning was detected by OCT in 10 eyes of 7 children (33.3%). Flow voids at the deep retinal capillary plexus were detected by OCTA in 10 eyes of 7 children (33.3%). Longer disease duration, higher reticulocytic percent, more painful crises, and noncompliance with hydroxyurea medication were all linked to the existence of eye abnormalities on fundus examination and OCT. Conclusion OCTA can show early retinal damage in sickle cell patients with macular changes. Sickle cell retinopathy is usually associated with more severe disease.

High Systolic Blood Pressure, Anterior Segment Changes and Visual Impairment Independently Predict Sickle Cell Retinopathy

Sickle cell disease is often complicated by retinopathy, which can be proliferative or non proliferative. Proliferative sickle cell retinopathy potentially leads to blindness. There is a paucity of data on sickle cell disease-related retinopathy from Africa, where the disease is most prevalent. We aimed to determine the clinical, ophthalmic, and laboratory predictors of sickle cell retinopathy in an African population. We conducted a cross-sectional study of 262 participants, aged 13 years and above, with sickle cell disease. Demographic and clinical data were collected using a structured questionnaire and standard physical examinations. Vitreo-retinal specialists performed eye examinations on all the participants. Hematological and biochemical assessments were conducted using standard methods. A multivariate stepwise forward logistic regression was performed to determine the predictors of retinopathy. The median age of the participants was 20 years (interquartile range: 17–25 years). Most of the participants had a homozygous Hb S (HBB: c.20A>T) genotype (96.9%), with 3.1% who carried a Hb S/Hb C (HBB: c.19G>A) genotype. The prevalence of non proliferative sickle cell retinopathy was 24.4%. Only 1.9% had proliferative sickle cell retinopathy (PSCR). Elevated systolic blood pressure (BP) [odds ratio (OR): 6.85, 95% confidence interval (95% CI): 1.05–44.45, p = 0.059], moderate visual impairment (OR: 5.2, 95% CI: 1.39–19.63, p = 0.015), and anterior segment changes (OR: 2.21, 95% CI: 1.19–4.13, p = 0.012) were independently predictive of retinopathy. This study provides new insight into predictors of retinopathy in sickle cell disease, with implications on early screening and prevention.

Analysis of the foveal microvasculature in sickle cell disease using swept-source optical coherence tomography angiography

Ischemic microangiopathy was clearly identified in sickle cell disease (SCD) using fluorescein angiography. A prospective observational clinical study was conducted to assess the foveal avascular zone (FAZ) area and explore perifoveal microvasculature changes in the superficial (SCP) and deep (DCP) capillary plexus using optical coherence tomography angiography (OCTA) and compare two genotypes—HbS/HbS (HbSS) and HbS/HbC (HbSC)-to control. All consecutive patients with electrophoretic confirmation of SCD were included. Swept-source OCTA scans (Triton Plus, Topcon, Tokyo, Japan) with a 3 × 3-mm scanning area and ultra-wide field (UWF) retinography (California, Optos, Fife, Scotland) were recorded for all patients. For OCTA analysis, preset parameters were used to segment the SCP and DCP. The FAZ area was manually assessed. The number of vascular branching points was automatically assessed based on the vascular skeletonization using ImageJ software. Eyes were staged based on Goldberg’s classification of SCD retinopathy (SCDR) using UWF imaging. Forty-six eyes of 24 patients were included in the HbSS (n = 27) and HbSC (n = 19) groups and 16 eyes of 8 unaffected patients in a control group. In the DCP, the FAZ was significantly larger in the HbSC (p = 0.0001) and HbSS (p = 0.0004) groups compared to controls. The FAZ area in the SCP, CRT and number of superficial vascular branching points did not significantly differ between both genotypes. There were less branching points in the HbSC (p = 0.034) and HbSS (p = 0.0014) groups than in controls. The Goldberg stage was significantly higher in the HbSC group than in the HbSS group (2.21 vs. 1.22, p = 0.0062). OCTA provides useful information on macular microvasculature and structural alterations associated with SCDR. Ischemic abnormalities are more predominant in the DCP in case of SCDR and no difference was found between genotypes of patients visually asymptomatic.

Preservation of Organ Function after Transplantation for Sickle Cell Disease

Background Recipients of successful allogeneic hematopoietic stem cell transplant (HSCT) for sickle cell disease (SCD) have hemoglobin S levels that reflect those of the donor. SCD related organ damage targets vital organs and is variable based on age and disease severity, and can be further compromised by transplant related complications. Organ function parameters are generally not primary end-points for clinical trials but need longitudinal follow up. This study aims to describe organ function in transplant recipients followed for one or more years after HSCT for SCD. Methods Following Institutional Review Board approval, a retrospective chart review was undertaken of SCD patients >1-year from HSCT with donor engraftment. Demographic data and organ functions (lung, brain and eyes) pre, at one-year, and at most recent assessment were compared for each patient. Organ functions reviewed included, creatinine, brain imaging, intelligence quotient (IQ), pulmonary function, retinal examination, and ferritin levels. Results Twenty-two patients were included in this review. There were 10 matched sibling donor, 8 matched or mismatched unrelated donor, 1 haploidentical, and 3 cord blood transplant recipients. Four patients received repeat donor cell infusion for waning donor chimerism followed by stabilization. Median age at first HSCT was 10 years (range 4-21 years). Eleven patients had MRI changes pre-HSCT. At 1-year, 4 of 17 transplant recipients had new MRI changes (2 patients with PRES and 2 with worsening infarction). At last follow up 3 of 18 patients demonstrated new MRI changes: bilateral temporal mesial sclerosis (1) and silent infarcts (2). IQ testing was available both at baseline and anytime beyond 1 year in 7 patients. IQ improved or remained stable in 5 patients and was lower in 2 patients, but remained in the average range. Pulmonary function tests were available for 21 patients of which 4 patients had restrictive lung disease. Ferritin levels decreased in 13 of 18 patients beyond the first year post-HSCT. Ophthalmologic exams at baseline and after transplant were performed in 12 patients. While SCD retinopathy was detected at baseline in two patients, no retinopathy was noted after HSCT. Follow up is in progress for additional organs such as the heart and kidneys. Discussion Long-term follow up of SCD related parameters post-HSCT demonstrates the effect of the intervention on disease manifestations. Our data demonstrates stability or improvement in organ function in the majority of patients after HSCT. This retrospective analysis is limited by the lack of uniform assessment of SCD related parameters and by obstacles such as provider changes and insurance denials. Though our data indicates improvement in SCD parameters post-HSCT, it also underscores the importance of systematic follow up prospectively through clinical trials and registries following curative therapy for SCD.

PB2313 OCULAR MANIFESTATIONS OF SICKLE CELL DISEASE: A SINGLE CENTRE STUDY

Background:Sickle cell disease (SCD) is an inherited haemolytic disorder that affects virtually all body systems including the eye. Ocular complications of SCD could have dire consequences if not detected early.Aims:We aimed at determining the prevalence of ocular complications of SCD in our patients.Methods:This study was carried out on patients attending both the adult and Paediatric Sickle cell clinic at Chukwuemeka Odumegwu Ojukwu teaching Hospital, Akwa, Anambra State, Nigeria, over a 6 month period. A structured questionnaire was administered to consenting patients to determine their sociodemographic variables and other characteristics. Visual acuity was determined with multiple optotype Snellen's chart at 6 metres in natural daylight. Using pen‐torch, the face, external eye examination, anterior segment examination and pupillary reaction to light were assessed. Magnified anterior segment examination was performed with slit‐lamp biomicroscope. All subjects underwent dilated fundoscopy (after instillation of tropicamide 0.5% eye drop) using Welch Allyn indirect ophthalmoscope.Results were analysed using SPSS version 22.0 Inc Chicago Illinois and represented in tables. Statistically significant P value was set at &lt; 0.05Results:A total of 28 patients with age range of 6‐42 years were seen. 17(60.7%) were males, while 11(39.3%) were females. 8(28.6%) had at least one ocular anomaly comprising of refractory errors 3(10.8%), sickle cell retinopathy 4(14.3%) and glaucoma 2(7.1%). Only 2(7.1%) routinely visit eye clinic. SCD retinopathy was found to increase with age (P value = 0.005)Summary/Conclusion:SCD retinopathy was found more in the older age group despite the small sample size at a prevalence rate of 14.3%. Early initiation of routine ocular examination for SCD patients will be beneficial to avert these complications. More efforts should be made at educating the patients. Larger studies will be required to determine the actual prevalence of ocular anomaly in SCD patients in Anambra State.

Laser therapy for retinopathy in sickle cell disease.

Sickle cell disease includes a group of inherited haemoglobinopathies affecting multiple organs including the eyes. Some people with the disease develop ocular manifestations due to vaso-occlusion. Vision-threatening complications of sickle cell disease are mainly due to proliferative sickle retinopathy which is characterized by proliferation of new blood vessels. Laser photocoagulation is widely applicable in proliferative retinopathies such as proliferative sickle retinopathy and proliferative diabetic retinopathy. It is important to evaluate the efficacy and safety of laser photocoagulation in the treatment of proliferative sickle retinopathy to prevent sight-threatening complications. To evaluate the effectiveness of various techniques of laser photocoagulation therapy in sickle cell disease-related retinopathy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 21 September 2015.We also searched the following resources (24 March 2015): Latin American and Carribean Health Science Literature Database (LILACS); WHO International Clinical Trials Registry Platforms (ICTRP); and ClinicalTrials.gov. Randomised controlled trials comparing laser photocoagulation to no treatment in children and adults. Two authors independently assessed trial eligibility, the risk of bias of the included trials and extracted and analysed data. We contacted the trial authors for additional information. Two trials (341 eyes of 238 children and adults) were included comparing efficacy and safety of laser photocoagulation to no therapy in people with proliferative sickle retinopathy. There were 121 males and 117 females with an age range from 13 to 67 years. The laser photocoagulation technique used was different in the two trials; one single-centre trial employed sectoral scatter laser photocoagulation using an argon laser; and the second, two-centre trial, employed feeder vessel coagulation using argon laser in one centre and xenon arc in the second centre. The follow-up period ranged from a mean of 21 to 32 months in one trial and 42 to 47 months in the second. Both trials were at risk of selection bias (random sequence generation) because of the randomisation method employed for participants with bilateral disease. One study was considered to be at risk of reporting bias.Using sectoral scatter laser photocoagulation, one trial (174 eyes) reported that complete regression of proliferative sickle retinopathy was seen in 30.2% in the laser group and 22.4% in the control group (no difference between groups). The same trial reported the development of new proliferative sickle retinopathy in 34.3% of laser-treated eyes and in 41.3% of eyes given no treatment; again, there was no difference between treatment groups. The second trial, using feeder vessel coagulation, did not present full data for either treatment group for these outcomes.There was evidence from both trials (341 eyes) that laser photocoagulation using scatter laser or feeder vessel coagulation may prevent the loss of vision in eyes with proliferative sickle retinopathy (at median follow up of 21 to 47 months). Data from both trials indicated that laser treatment prevented the occurrence of vitreous haemorrhage with both argon and xenon laser; with the protective effect being greater with feeder vessel laser treatment compared to scatter photocoagulation.Regarding adverse effects, the incidence of retinal tear was minimal, with only one event reported. Combined data from both trials were available for 341 eyes; there was no difference between the laser and control arms for retinal detachment. In relation to choroidal neovascularization, treatment with xenon arc was found to be associated with a significantly higher risk, but visual loss related to this complication is uncommon with long-term follow up of three years or more.Data regarding quality of life and other adverse effects were not reported in the included trials. Our conclusions are based on the data from two trials conducted over 20 years ago. In the absence of further evidence, laser treatment for sickle cell disease-related retinopathy should be considered as a one of therapeutic options for preventing visual loss and vitreous haemorrhage. However, it does not appear to have a significant different effect on other clinical outcomes such as regression of proliferative sickle retinopathy and development of new ones. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence). There is limited evidence on safety, overall, scatter argon laser photocoagulation is superior in terms of adverse effects, although feeder vessel coagulation has a better effect in preventing vitreous haemorrhage. Further research is needed to examine the safety of laser treatment compared to other interventions such as intravitreal injection of anti-vascular endothelial growth factors. In addition, patient-important outcomes as well as cost-effectiveness should be addressed.

Severe proliferative retinopathy is associated with blood hyperviscosity in sickle cell hemoglobin-C disease but not in sickle cell anemia

Little is known about the impact of blood rheology on the occurrence of retinopathy in sickle cell disease (SCD). Fifty-nine adult SCD patients in steady-state condition participated to the study: 32 with homozygous SCD (sickle cell anemia; SCA) and 27 with sickle cell hemoglobin-C disease (SCC). The patients underwent retinal examination and were categorized according to the classification of Goldberg: 1) no retinopathy (group 1), 2) non-proliferative or proliferative stage I-II retinopathy (group 2) and 3) proliferative stage III-IV-V retinopathy (group 3). Hematological and hemorheological (whole blood viscosity, RBC deformability and aggregation properties) measurements were performed for each patient. In the whole SCD group (SCA + SCC patients) and in SCC patients, the group 3 had higher platelets count than group 2 but the difference between group 3 and group 1 did not reach statistical significance. No difference was observed for the other parameters between the three groups. SCC patients from the group 3 exhibited higher whole blood viscosity than SCC patients from the group 1. No significant difference was observed between the three groups in SCA patients. This study revealed that severe sickle proliferative retinopathy is associated with blood hyperviscosity in SCC patients but not in SCA patients.

Ocular findings in children with severe clinical symptoms of homozygous sickle cell anaemia in Kaduna, Nigeria

Sight-threatening retinopathy in Sickle Cell Disease is thought to be due mainly to vasoocclusion. Yet it is reportedly rarely found in children with Haemoglobin SS, (who most often suffer from vasoocclusion). However, earlier reports included patients with a wide range of clinical severity. To document ocular pathology in children with Haemoglobin SS with severe clinical disease. Thirty-seven children with severe clinical disease (at least 3 vaso-occlusive episodes in one year) had detailed ocular examinations over a one-year period. No child (aged 3 to 13 years) had ocular symptoms. Visual acuity was abnormal in one child. Retinal pathology was found only in patients over 8 years. Neovascularization was observed in 3 eyes of 2 patients both of whom had higher than average irreversibly sickled cell counts and haemoglobin levels. Retinal and choroidal infarcts were found in 11 and 2 eyes respectively; sunburst lesions and salmon patch haemorrhages in 5 eyes each. Changes observed over the one-year period in the 32 survivors, were photocoagulation scars in one eye of a child who had undergone laser therapy and resolution of the salmon patch haemorrhages. Despite lack of visual symptoms, young children with haemoglobin SS with severe clinical symptoms can develop sight-threatening retinopathy. The possible role of autoinfarction in the causation of these lesions is discussed. Our study shows that routine yearly ophthalmological examinations are essential for children over 8 years.

Relationship between peripheral vascular closure and proliferative retinopathy in sickle cell disease

In a study involving 97 patients with hemoglobin SC sickle cell disease (Hb SC) and 87 subjects with hemoglobin SS sickle cell disease (Hb SS) on the island of Curaçao, we found a higher incidence of peripheral retinal vascular closure and proliferative retinopathy in the former as compared with the latter. Examination of composite fluorescein angiograms obtained from 15 Hb SS and 36 Hb SC patients, whose mean and median age were the same and in whom more advanced stages of sickle retinopathy were equally represented, revealed statistically significantly smaller measurements of perfused retina (indicative of larger areas of non-perfusion) in Hb SC patients as compared with Hb SS patients (P = 0.002, P = 0.014) as well as in subjects exhibiting neovascularization as compared with those who did not (P = 0.022, P = 0.004). This suggests that a vaso-occlusive tendency in the retina is greater in individuals with Hb SC than in those with Hb SS; the more extensive ischemic areas provide a stimulus for neovascularization, explaining the higher prevalence of proliferative retinopathy in the former patients as compared with the latter.