Proliferative Sickle Retinopathy Research Articles

Screening for Multiple Organ Damage in Indian Sickle Cell Disease Cohort- a Step Towards Comprehensive Care

Introduction: Sickle cell disease (SCD) is the most common hereditary monogenic disorder and is a major health burden in India. Meagre information is available on multiple organ damage among Indian SCD population. The present study attempts to understand the spectrum of organ damage in a group of Indian SCD cohorts. Objectives: To investigate the spectrum of early organ dysfunction and chronic organ damage among SCD patients at different age groups. To study the association of haematological and biochemical parameters with organ dysfunction or chronic organ damage. To understand the implication of genetic modifies with clinical profiles of SCD patients. Methodology: Clinical investigations of SCD individuals such as MRI of brain, ultrasonography of abdomen, spirometry of lung, 2 D echo of heart and ophthalmology. Laboratory investigations of SCD individuals such as haematological parameters by cell counter (Sysmax XP100), HbF & HbS fractionization by HPLC method (Biorad Variant 2), liver function test and kidney function test by automated biochemistry analyser (Roche Cobas C111). Co-inheritance of α-thalassemia and Xmn-1 polymorphism by multiplex PCR and PCR-RFLP respectively. 100 SCD individuals were recruited with informed consent by a consecutive sampling for the study at ICMR-Centre for Research Management and Control of Haemoglobinopathies (ICMR-CRMCH), Chandrapur. SCD individuals at non-crisis, steady state; with no blood transfusion history prior 3 months or not admitted in hospital for vaso-occlusive crisis prior 1 month were enrolled in the period Jan'2021-Jan'2022. Result: One hundred SCD individuals (44 males: 56 females) were enrolled. The median age of individuals was 18 years (Interquartile range (IQR): 13-29 years). Individuals were categorized into two groups based on their ages. Children and adolescents group (6-17 years): 46 individuals, and Adults (18-52 years): 54 individuals. Out of 100, 65 were drug hydroxyurea (HU) are on HU, while remaining 35 were not taking HU. The median dosage of at 11.9 mg/kg/day (IQR: 9.17-13.5 mg/kg/day). The current study reports the spectrum of organ damage involving onset of organ dysfunction to end organ damage such as ischemia/sclerosis/atrophy 12/58 (20.7%) to stroke 2/58 (3.4%), mild restriction/obstruction 55/96 (57.3%) to mixed blockage lung disease 6/96 (6.2%), cholelithiasis 24/100 (24%) to chronic cholecystitis/cholecystectomy 6/100 (6%), shrunken spleen 16/100 (16%) to autosplenoctomy 24/100 (24%). No pulmonary hypertension determined by tricuspid valve regurgitation (TRV) >2.5 m/s was observed among 100 SCD individuals. No case of proliferative sickle retinopathy was detected in the cohort. Laboratory investigations: The mean ± standard deviation (S.D.) hemoglobin and HbF% levels among 100 SCD individuals were found to be 9.7±1.6 gm/dl and 21.2±6.6% respectively. Hematological and biochemical parameters showed association with liver and splenic dysfunction. Four out of 76 (5.3%) individuals were tested positive for microalbuminuria. No individual showed higher levels of estimated glomerular filtration rate. Molecular investigations: Ninety three HbS homozygous and 7 HbS-β thalassemia compound heterozygous were identified by ARMS-PCR method. The co-inheritance of α-gene mutations was observed in 45/94 (47.9%) SCD individuals, while the remaining 49/94 (52.3%) were normal. The Xmn1 polymorphism present in the Gγ globin promoter region -158 C→T (HBG2 c.-211 C→T) position, showed 88 as homozygous for mutant allele [+/+], while 12 as heterozygous[ +/-]. No association of α-thalassemia and Xmn1 polymorphism with organ dysfunction was observed. Conclusion: Though, vaso-occlusive crisis is the main clinical manifestation in SCD, sickle related organ damage is an important determinant for clinical severity of the disease. The progression of organ dysfunction/damage is evident as the age progresses. The comprehensive check-up at regular interval is required for the identification of early organ dysfunction and to prevent the chronic organ damage in SCD individuals.

Identifying Clinical Predictors of Proliferative Sickle Cell Retinopathy

Purpose To identify systemic and/or ophthalmologic predictors of proliferative sickle retinopathy. Methods Cross-sectional study comparing clinical, laboratory, and structural choriorretinal aspects between sickle cell disease patients with and without proliferative retinopathy. Patients underwent complete systemic and ophthalmologic evaluation. Enhanced depth spectral domain optical coherence tomography with choroidal binarization and optic coherence tomography angiography were performed and choriorretinal vascular components were compared. Results Forty-five eyes from 45 sickle cell patients were included. Ninety-one percent of patients were diagnosed with sickle cell retinopathy, 29% with proliferative retinopathy. Mean corpuscular volume, lactate dehydrogenase, and percentage of fetal hemoglobin were reduced in the subgroup of patients with proliferative retinopathy when compared with patients without proliferative retinopathy (p ≤ 0.001; p = 0.04; p ≤ 0.001, respectively). The best predictor of proliferative retinopathy was mean corpuscular volume (AUC = 0.842; p = 0.001), followed by the percentage of fetal hemoglobin (AUC = 0.763, p = 0.009) and lactate dehydrogenase (AUC curve = 0.706; p = 0.039). No differences were found between groups in the quantitative analysis of retinal vascularization using OCTA and choroidal vascularization using OCT (p ≥ 0.05). Conclusion Fetal hemoglobin and mean corpuscular volume may be good predictors of proliferative sickle retinopathy. The association between proliferative retinopathy and reduced levels of lactate dehydrogenase and mean corpuscular volume points to hypoxia and not hemolysis as a possible driving force in its pathophysiology.

5596911 RETINAL AND MACULAR AFFECTION IN EGYPTIAN SICKLE CELL DISEASE PATIENTS USING SPECTRAL DOMAIN OCT AND OCT-ANGIOGRAPHY: A SINGLE CENTER STUDY

Background: Sickle vasculopathy results from a complex interaction between sickles erythrocytes, white blood cells, platelets, activated endothelium, vasoactive factors and inflammation. Improved life expectancy of sickle cell disease (SCD) patients in recent years has led to emergence of more disease-related complications as ocular complications. Sickle maculopathy, an emerging subtle complication, characterized by local macular thinning secondary to ischemia is not always evident by indirect ophthalmoscope. In an earlier study of an Egyptian SCD cohort using flourscein angiography, we detected proliferative sickle retinopathy (PSR) in 32.5% of enrolled patients; youngest being 15 years old. Discrepancies in reported prevalences among pediatric SCD patients are attributed to different definitions of retinopathy, examining methods used, examiner’s ability, patients’ age and treatment modalities. Spectral domain- Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCT-A) are more recent non- invasive tools that allow for early detection of signs of PSR. Aim: This study aimed to assess for retinopathy and maculopathy among an Egyptian cohort of SCD patients using SD-OCT and OCT-A. Methods: This prospective observational cross-sectional study, conducted in Pediatric Hematology Unit, Cairo University Children Hospital, included 80 Egyptian steady state SCD patients (aged 10 years or more) and 20 unrelated healthy age and sex matched subjects as control group. Informed consents were given willingly by all subjects/ guardians before enrollment in the study. SD-OCT (Optovue OCT machine) and OCT-A (Optovue Octa machine) were performed for all enrolled subjects at Opthalmolgy Department, Cairo University. Results: All subjects had normal slit lamp examination. No statistically significant difference was found in best corrected visual acuity (BCVA) of RT eye, Lt eye, slit lamp bio-microscopy or indirect ophthalmoscopy between SCD and control groups (p= 0.059, 0.057, 0.159 & 0.159 respectively). Using SD-OCT, SCD patients had significantly lower mean Rt macular thickness than control group (218.05±19.13 vs 232.1±14.55 micrometer with p-value =0.003). Twelve SCD patients (15%) showed evidence of retinopathy by OCT-A. There was a significant relationship between OCT-A findings and both Rt and Lt macular thickness by SD-OCT (p-value <0.0001 and <0.0001 respectively). OCT-A findings well correlated with Rt BCVA, Lt BCVA, slit lamp bio-microscopy and indirect ophthalmoscope (p-value <0.0001 for all). SCD patients having abnormal OCT-A findings or with macular abnormalities by SD-OCT showed statistically significant higher mean transfusions/ lifetime and longer duration of Deferiprone chelation therapy (p=0.011, 0.014, 0.028 and 0.038 respectively). No significant difference was noted among SCD patients with abnormal vs normal OCT-A findings regarding their studied demographic, clinical or hematologic characteristics. Conclusion: Sickle retinopathy and maculopathy are subtle disease related complications that might affect SCD children and adolescents. SD-OCT and OCT-A are non-invasive useful tools for early timely detection of these complications thus minimizing the risk of sight- threatening retinopathy. Keywords: Retinopathy- Sickle- Egyptian- SD-OCT- OCT-A

Laser therapy for retinopathy in sickle cell disease.

Laser therapy for retinopathy in sickle cell disease.

Nonmydriatic Ultra-Widefield Fundus Photography in a Hematology Clinic Shows Utility for Screening of Sickle Cell Retinopathy

To determine the feasibility and accuracy of nonmydriatic ultra-widefield (UWF) fundus photographs taken in a hematology clinic setting for screening of sickle cell retinopathy (SCR) DESIGN: Prospective cohort study. This single-site study took place at the Johns Hopkins Sickle Cell Center for Adults and the Wilmer Eye Institute. The study population was 90 eyes of 46 consecutive adults with sickle cell disease (SCD). Bilateral nonmydriatic fundus photos taken by clinic personnel during the participants' routine hematology appointment were graded by 2 masked retina specialists at the Wilmer Eye Institute for the presence of nonproliferative SCR (NPSR) and proliferative sickle retinopathy (PSR). A third retina specialist adjudicated in cases of grader disagreement. All participants underwent the standard dilated fundus examination (DFE) within 2 years of acquisition of UWF photographs. The main outcome measure was the sensitivity and specificity of nonmydriatic UWF images for the detection of NPSR and PSR RESULTS: PSR was noted in 19 of 90 eyes that underwent DFE and in 9 of 67 gradable UWF images. Interrater agreement between the 2 graders was moderate, with κ=0.65 (range 0.43-0.87) for PSR. For gradable UWF photos, the sensitivity and specificity of detecting SCR using the nonmydriatic photos compared with the DFE were 85.2% and 62.5% for NPSR, respectively, and 69.2% and 100% for detection of PSR, respectively. One participant required ophthalmic therapy in both eyes for active sea-fan neovascularization. UWF imaging shows utility in screening for SCR and may help identify patients with PSR who require a DFE and who may benefit from treatment.

Retinopathy in patient with AC hemoglobinopathy

Abstract Hemoglobin C is the second most frequent Hb variant in Brazil and the world. Hemoglobin C trait is described as a benign and asymptomatic condition. There is little information in the literature about the association of retinal vascular disease and the presence of hemoglobin AC, being this information restricted to a few case reports. This case report describes a 26-year-old female patient with hemoglobin C trait. She presents areas of non-perfusion and arteriovenous shunts in the retinal temporal periphery of the left eye, like changes in Goldberg’s stage II of proliferative sickle retinopathy. After three years of follow-up, the patient exhibits the same the alteration in right eye as well.

&lt;p&gt;Hemoglobin level and macular thinning in sickle cell disease&lt;/p&gt;

Purpose: To study the relationship between complete blood count (CBC) indices over time, particularly serum hemoglobin (Hb) levels, and severity of macular thinning on spectral domain optical coherence tomography (SD-OCT) in patients with sickle cell disease (SCD).Methods: This is a single-center, retrospective analysis of 141 consecutive SCD patients over a 10-year period, of which 40 patients (79 eyes) had SD-OCT imaging of the macula and 29 (58 eyes, mean age 17.5 years) were eligible for the study. Investigators reviewed electronic medical records for documentation of retinopathy stage, disease genotype, CBC values, and SD-OCT imaging. SD-OCT parameters and CBC values were compared between different retinopathy stages and disease genotypes. Regression analyses were performed on SD-OCT parameters and CBC values.Results: Of the 58 eligible eyes (34HbSS, 18HbSC, 4HbSβ +thal, 2HbS βthal), 18 had PSR (proliferative sickle retinopathy), 14 had NPSR (nonproliferative sickle retinopathy), and 26 had NSR (no sickle retinopathy). Hb values were higher in SC group compared to SS group. Macular thickness in the temporal inner (Δ=26±33 um, p=0.01) and outer (Δ=21±30 um, p=0.02) subfields was higher in SC compared to SS group. Patients with SD-OCT thinning below the 5th percentile in the temporal outer subfields had lower recorded Hb nadirs (6.0±0.9) compared to those with thickness within the top 95th percentile (9.1±2.3). Regression analysis showed temporal macular thickness to be positively correlated with Hb values in the SS group.Conclusion: Macular thinning observed on SD-OCT in SCD patients with SS genotype may be related to the level of anemia in this population.

The past, present and future management of sickle cell retinopathy within an African context.

Sickle cell retinopathy is a potentially blinding condition that affects young people in the working age group. This review looks at the past, present and future management of sickle cell retinopathy within an African context. After Sickle cell disease was first reported in 1910, some reports from Africa were pivotal in describing the retinal changes associated with the disease. It soon became obvious that there was a varied clinical picture and clinical course. Several landmark studies were carried out in Jamaica to help elucidate the complexities of the disease and outline appropriate clinical management. In most of the developed world, the clinical management of sickle cell disease has improved with concurrent improvement in outcomes. Currently resource constraints in most Sub-Saharan African countries where there is a high burden of disease means that the management of sickle cell retinopathy is fraught with numerous challenges. Future large scale trials in Africa shall hopefully help to better elucidate the mechanisms behind proliferative sickle retinopathy and help in the development of new and improved therapeutic pathways. The use of technology can help immensely in the screening of patients with sickle cell to detect early proliferative changes and if necessary treat accordingly.

A comparison of 23-gauge and 20-gauge vitrectomy for proliferative sickle cell retinopathy - clinical outcomes and surgical management.

To report anatomical and functional outcomes in patients with proliferative sickle retinopathy (PSR) who underwent 23-gauge (23G) and 20-gauge (20G) vitrectomy. Retrospective consecutive case series of patients who underwent vitreoretinal intervention for complications of PSR between April 2009 and February 2015. Operations were performed at a tertiary referral centre, Moorfields Eye Hospital. Visual acuity and anatomical success rates were evaluated for PSR complicated by retinal detachment, tractional vitreous haemorrhage and macular hole. Proliferative diabetic retinopathy cases were excluded. A total of 71 eyes (63 patients) underwent vitreoretinal surgery for PSR complications with 26 months mean follow-up. Primary indications were: tractional retinal detachment (TRD, n = 17), TRD with rhegmatogenous retinal detachment (n = 16), rhegmatogenous retinal detachment (n = 5, macula-on: 1, macula-off: 4), vitreous haemorrhage (n = 19), epiretinal membrane (n = 6), and full thickness macula hole (n = 8). Thirty-nine cases underwent 20G vitrectomy, and 23G surgery was performed in 32 eyes. Mean best corrected visual acuity (BCVA) improved from pre-operative 1.30 LogMAR to final BCVA of 0.74 LogMAR (p < 0.01, paired t-test). 23G vitrectomy yielded slightly better 32 vs. 25 ETDRS-letter improvement compared with 20G vitrectomy (p = 0.60, NS, unpaired t-test). 23G was associated with fewer per-operative complications (23G, 18% vs. 20G,13%). The subset of 38 eyes with retinal detachment demonstrated 79% primary reattachment rate, and a smaller BCVA improvement of 3 lines (p = 0.07, paired t-test). Surgical intervention for complicated PSR can preserve and/or improve vision although the degree of visual acuity stabilisation remains guarded in tractional/rhegmatogenous detachments. 23G vitrectomy may give a better functional outcome with lower per-operative complication rates.

Sickle cell retinopathy and other chronic complications of sickle cell anemia: A clinical study of 84 Sub-Saharan African cases (Cameroon)

Sickle retinopathy is a severe complication of sickle cell disease than can lead to blindness. We aim to describe the epidemiology of sickle retinopathy in homozygous sickle cell (SS) African patients and to analyze its association with non-ophthalmologic disease complications of sickle cell anemia. We conducted a nested study within the CADRE cohort in Cameroon. Eighty-four consecutive SS outpatients, aged 10 years and older, with no visual symptoms, underwent an ophthalmologic examination. Mean age was 23±10 years. Clinical and biological features were compared between patients with and without sickle retinopathy. We compared the prevalence of the clinical complications and main biological characteristics in patients with and without sickle retinopathy using a univariate logistic regression. The same analysis was used to compare the patients with non-proliferative sickle retinopathy to those with proliferative sickle retinopathy. Statistical analyses were done using the R software (version 3.1.2). Fifty-two patients (62%) displayed sickle retinopathy, among them 23 (27%) had a non-proliferative sickle retinopathy, and 29 (35%) had proliferative sickle retinopathy. Patients with proliferative sickle cell retinopathy had a mean age of 28±11 years. Sickle retinopathy was associated with higher hemoglobin level (P=0.047) and fewer leg ulcers (P=0.018). Proliferative SR was associated with increasing age (P=0.008) and male sex (P=0.025) independently of the hemoglobin level. Sickle retinopathy is particularly frequent in sub-Saharan sickle cell SS patients, which advocates for early systematic screening.

Intravitreal Bevacizumab for Proliferative Sickle Retinopathy: A Case Series

Purpose: To report outcomes of intravitreal bevacizumab therapy for proliferative sickle retinopathy (PSR). Methods: A retrospective, interventional case series. Five eyes of 5 patients with PSR were managed with intravitreal bevacizumab therapy over a 13-year period at a single institution. Results: Four patients had sickle cell-hemoglobin SC disease and 1 had sickle cell-beta thalassemia disease. Four of the patients treated with intravitreal bevacizumab injection were treated for recurrent vitreous hemorrhage and 1 was treated for new peripheral sea fan neovascularization. In those patients treated for vitreous hemorrhage, there was improvement in visual acuity as early as 2 weeks after treatment. Only 2 of the patients had documented recurrent vitreous hemorrhage during the period of follow-up after the initial injection. In 1 patient, the vitreous hemorrhage did not recur until 13 months after the injection. All patients showed an anatomic response to intravitreal bevacizumab therapy with partial regression of the peripheral sea fan neovascularization. All patients tolerated the injections without any complications. Conclusions: Intravitreal bevacizumab injections appear to be well tolerated and may be an effective treatment of PSR. Regression of peripheral sea fan neovascularization and decreased duration of vitreous hemorrhage may be observed. Large-scale randomized controlled trials are needed to further clarify the role of bevacizumab in PSR.

Expression of the angiogenic mediator, angiopoietin-like 4, in the eyes of patients with proliferative sickle retinopathy.

The recent success of therapies directly targeting the angiogenic mediator, vascular endothelial growth factor (VEGF), for the treatment of proliferative diabetic retinopathy has encouraged clinicians to extend the use of anti-VEGF therapies for the treatment of another ischemic retinal vascular disease, proliferative sickle cell retinopathy (PSR), the most common cause of irreversible blindness in patients with sickle cell disease. However, results from case reports evaluating anti-VEGF therapies for PSR have been mixed. This highlights the need to identify alternative therapeutic targets for the treatment of retinal neovascularization in sickle cell patients. In this regard, angiopoietin-like 4 (ANGPTL4) is a novel angiogenic factor regulated by the transcription factor, hypoxia-inducible factor 1, the master regulator of angiogenic mediators (including VEGF) in ischemic retinal disease. In an effort to identify alternative targets for the treatment of sickle cell retinopathy, we have explored the expression of ANGPTL4 in the eyes of patients with PSR. To this end, we examined expression and localization of ANGPTL4 by immunohistochemistry in autopsy eyes from patients with known PSR (n = 5 patients). Complementary studies were performed using enzyme-linked immunosorbent assays in aqueous (n = 8; 7 patients, 2 samples from one eye of same patient) and vitreous (n = 3 patients) samples from a second group of patients with active PSR. We detected expression of ANGPTL4 in neovascular tissue and in the ischemic inner retina in PSR, but not control, eyes. We further observed elevated expression of ANGPTL4 in the aqueous and vitreous of PSR patients compared to controls. These results suggest that ANGPTL4 could contribute to the development of retinal neovascularization in sickle cell patients and could therefore be a therapeutic target for the treatment of PSR.

Expression Pattern of HIF-1α and VEGF Supports Circumferential Application of Scatter Laser for Proliferative Sickle Retinopathy.

PurposeRetinal vascular occlusions in sickle cell anemia patients cause tissue ischemia and the release of angiogenic mediators that promote the development of retinal neovascularization, initiating proliferative sickle retinopathy (PSR). Laser photocoagulation (LPC) has emerged as the most common treatment for PSR. Nonetheless, only two randomized controlled clinical trials have evaluated the use of LPC for PSR, and both failed to definitively demonstrate efficacy of this approach. This may be due to a lack of knowledge regarding the appropriate location for placement of laser coagulations in PSR eyes. To help address this question, we examined the expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in PSR eyes.MethodsThe expression pattern of HIF-1α and VEGF in PSR (n = 5) and control (n = 3) eyes was examined by immunohistochemistry in different retinal regions defined by the presence or absence of retinal vessels.ResultsHypoxia-inducible factor 1α and VEGF were expressed in the inner retina of 5/5 untreated PSR eyes adjacent to retinal neovascularization; expression of HIF-1α was not detected (and VEGF only lightly detected) in normal retinal and choroidal vasculature of 3/3 control eyes. Hypoxia-inducible factor 1α and VEGF were strongly expressed in retinal cells within avascular (nonperfused) retina, anterior to the boundary between perfused and nonperfused retina, as well as in posterior ischemic retina in the presence or absence of neovascular sea fans.ConclusionsIf the goal of LPC in PSR is to quench the expression of HIF-1–driven angiogenic mediators, our results support broad application of peripheral laser for its treatment.

Risk factors for visual impairment in patients with sickle cell disease in London.

Dramatically improved health care in recent years has increased the life expectancy of patients with sickle cell disease (SCD) as well as the prognosis for its ocular complications. We sought to identify risk factors for visual impairment in patients with SCD in London 4 decades after Goldberg's seminal studies. Patients 16 years and older with SCD (genotypes HbSS, HbSC, HbSβ-thalassemia) attending hematology and ophthalmology services were offered ocular examination. Retinopathy was graded according to the Goldberg classification. Visual impairment was defined as corrected distance visual acuity of 20/40 or poorer. In total, 182 eyes of 182 patients (mean ± SD age, 37.2 ± 12.8 years; female, 65.9%) were included. Women were significantly older than men (mean ± SD age, 38.8 ± 13.1 vs 34.2 ± 11.8 years; p = 0.0174). There was no difference in mean age of each genotype group (p&gt;0.15). Risk factors for sight-threatening proliferative sickle retinopathy (PSR) were age over 35 years (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.05-3.89; p = 0.0359) and HbSC genotype (OR 4.06; 95% CI 2.07-7.98; p&lt;0.0001). Although visual impairment was related to the presence of sight-threatening PSR (OR 7.23; 95% CI 1.50-35.0; p = 0.0138), it was not related to hemoglobin genotype (p&gt;0.50). We present the largest study of ocular findings in SCD in the United Kingdom. Sight-threatening PSR is a risk factor for visual impairment, but hemoglobin genotype status is not.

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.

Macular and peripapillary spectral domain optical coherence tomography changes in sickle cell retinopathy.

To assess peripapillary retinal nerve fiber layer, macular ganglion cell complex, and total macular thicknesses using spectral domain optical coherence tomography on sickle cell disease patients with and without sickle retinopathy. Nineteen eyes of 11 patients with hemoglobin sickle cell disease, 65 eyes of 36 patients with hemoglobin SS disease, and 48 eyes of 24 healthy subjects underwent spectral domain optical coherence tomography scanning (RTVue). Eyes of patients with sickle cell disease were classified into 3 groups according to posterior segment changes: no retinopathy (n = 64), nonproliferative retinopathy (n = 12), and proliferative retinopathy (n = 8). The central fovea in eyes with proliferative retinopathy was thickened compared with control group, sickle cell disease without retinopathy, and nonproliferative retinopathy (P = 0.004); a difference between proliferative retinopathy and sickle cell disease without retinopathy groups was still present after age adjustment (P = 0.014). Eyes with proliferative changes showed higher ganglion cell complex focal loss of volume compared with control group (P = 0.002), even after age adjustment (P = 0.004). Thinning of the nasal retinal nerve fiber layer quadrant was observed in eyes with proliferative retinopathy (P < 0.001); however, no retinal nerve fiber layer thickness difference was observed after age correction (P > 0.05). Peripheral changes secondary to proliferative sickle retinopathy were associated with thinning of macular inner retinal layers and thickening of central fovea.

Vitreoretinal Management and Surgical Outcomes in Proliferative Sickle Retinopathy: A Case Series

To report the outcomes of current vitreoretinal surgical management of proliferative sickle retinopathy and to compare current methods to previous studies. A retrospective, interventional case series. Fifteen eyes of 14 patients with proliferative sickle retinopathy were managed with vitreoretinal surgery over a 12-year period at a single institution. Nine patients had a sickle cell-hemoglobin C (SC) profile, 1 was sickle cell-beta(+) thalassemia (S beta(+)-thal), and 4 were sickle cell trait (AS). All 15 eyes underwent pars plana vitrectomy (PPV): 6 for vitreous hemorrhage (VH), 1 for epiretinal membrane (ERM), and an additional 8 for tractional retinal detachment (RD) and/or rhegmatogenous RD. In addition, an encircling scleral buckle (SB) was used in 2 cases. In 7 cases, 20 gauge PPV was used; 23 gauge was used in 3; and 25 gauge was used in 5. All 7 eyes with VH or ERM had improved vision postoperatively. Four of the 8 patients with traction and/or rhegmatogenous RD developed recurrent detachments and required a second operation. All retinas were attached at last follow-up, and visual acuity was 20/400 or better in all eyes. No cases of anterior segment ischemia were encountered. Anterior segment ischemia is no longer a common occurrence in eyes undergoing surgery for proliferative sickle retinopathy. Although PPV has replaced the use of SB in many situations, an encircling SB may still be used in this population when necessary. Surgery for VH and ERM generally results in favorable outcomes, but eyes undergoing surgery for traction/rhegmatogenous RD carry a more guarded prognosis.

The Impact of Hydroxyurea Therapy on the Prevalence of Retinopathy in a Pediatric Sickle Cell Cohort

Abstract 1057 Introduction:Approximately 15–17% of children with HbSS and 11% of those with HbSβ0thalassemia (HbSβ0thal) develop sickle retinopathy (SR) by 18 years of age. Sickle retinopathy is a spectrum of vascular lesions that insidiously evolve as a result of ischemia from vaso-occlusion of capillary and precapillary arterioles in the peripheral retina. These lesions are usually clinically silent but can progress to spontaneous vitreous hemorrhage or retinal detachment and lead to blindness. Therefore, periodic screening retinal exams are recommended for children and adults with sickle cell disease (SCD). Prior reports from Jamaica identified low fetal hemoglobin (HbF) concentration as a potential risk factor for retinopathy in HbSS patients. Hydroxyurea (HU), an increasingly utilized treatment in children with HbSS/HbSB0thal, increases %HbF levels. However, there are no reports describing the effects of HU therapy on the prevalence of retinopathy in children with SCD. In our institution, all children with SCD are referred to ophthalmology for a screening dilated fundoscopic exam (DFE) beginning at 10 years of age and then every 2 years. Objective:Define the prevalence of retinopathy in children with HbSS/HbSβ0thal and analyze the effects of treatment with HU and %HbF levels on the prevalence of retinopathy. Methods:After IRB approval, a retrospective chart review was performed on children with HbSS/HbSβ0thal who received a DFE without fluorescein angiography at St Jude Children’s Research Hospital between 2003 and 2010. Children who received chronic transfusion therapy or hematopoietic stem cell transplantation were excluded from analysis. Records of DFEs were reviewed for a diagnosis of non-proliferative or proliferative SR. Laboratory data were collected at multiple time points from patients’ electronic medical records, including: prior to initiation of HU, following two years of therapy with HU, and immediately prior to diagnosis of retinopathy. Time of observation was defined as birth to diagnosis of SR or to date of last DFE. Summary statistics are reported and the HU and non-HU groups are compared with the Wilcoxon-Mann-Whitney Exact test. Results:Of 182 children referred to ophthalmology, 142 (78%; 126 HbSS, 16 HbSβ0thal) received an initial DFE at a median age of 13.1 ± 3.3 years (range: 1.6–18.7 years). The median number of DFEs per patient was 1.7 ± 1.4 (range: 1–12) during the time of observation. Sickle retinopathy was diagnosed in 9.9% (14/142) of children, at an average age of 15 ± 2.5 years. Of the children who received a DFE, 63% (90/142) had initiated HU therapy at an average age of 9.8 ±4.8 years. The average age at initial DFE was not different in patients receiving HU (13.1 ± 3.2 years) and those who did not (13 ± 3.5 years). The total number of DFEs performed in both groups was also similar (1 ± 1.2 in HU-treated group vs. 1 ± 1.6 in untreated group). Retinopathy was diagnosed in 7.8% (7/90) of children who received HU and 13.5% (7/52) of children who did not (p=0.27). The median age at diagnosis of SR was similar for patients treated with HU (15.4 ± 2.5 years, range: 11.3–18.2 years) compared to untreated children (14.6 ± 2.6 years, range: 10.8–17.3 years; p=0.6). Among patients receiving HU, those who developed retinopathy started treatment at a later age, however the difference was not statistically significant (12.2 ± 5 years vs. 9.3 ± 4.5 years; p=0.23). Among the HU treated group, %HbF following 2 years of HU therapy was similar in those who developed SR (16.1 ± 7.7%) and those who did not (20.0 ± 6.8%; p=0.24). Conclusion:Although the average age at diagnosis with retinopathy in these children with HbSS/HbSβ0thal was similar to previously reported untreated pediatric cohorts, the overall prevalence of retinopathy was lower. Treatment with HU did not affect the development of retinopathy nor did %HbF levels in those treated with HU. More studies are necessary to analyze the effects of HU treatment on development of SR. In the meantime, continued adherence to screening guidelines for ophthalmology evaluations are necessary for children with HbSS and HbSβ0thal being treated with hydroxyurea. Disclosures:Off Label Use: Use of hydroxyurea in children with sickle cell anemia.

Leukocoria and Vitreous Hemorrhage as the Initial Manifestation of Sickle Retinopathy in a 3-Year, 6-Month-Old Child With Sickle Trait (AS)

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.

Prevalence of Sickle Cell Anemia In Eastern India

AbstractAbstract 4822 Background:Sickle cell disease is an inherited disorder of hemoglobin synthesis. This is due to replacement of Valine for Glutamic Acid in position six of the Beta globin chain of hemoglobin. This genetic alteration yields unstable RBC which lasts for 10–20 days. In stressful conditions the cells become sickle shaped and get lysed. There are about 20 million people with sickle cell disease in India. During January 2009- May2010 camps were held in various parts of West Bengal, Jharkhand, Chattisgarh. Along with various mutations of thalassemia, we also observed sickle cell anemia among them. This triggered our interest to study the spectrum of the sickle mutation co-inheritant with different mutations such as Homozygous Sickle Cell, Sickle Cell-Beta0 Thalassemia, Sickle Cell-Beta+ Thalassemia, Severe β+ thalassemia genes, Moderate β+ thalassemia genes, Mild β+ thalassemia genes Sickle cell-HbE Thalassaemia, Sickle cell-HPFH Thalassaemia, in said part of India. Since Indian patients with SS disease had higher hemoglobin, red cell counts and higher HbF levels and lower HbA2, MCHC, MCV, and reticulocyte counts, hence a high hemoglobin is a risk factor for painful crises and may also be a risk factor for avascular necrosis of the femoral head, proliferative sickle retinopathy, and acute chest syndrome. Methods:We have screened 332 individuals in eastern part of India during the period January 2009- May 2010. 3ml of peripheral blood was collected in EDTA vial from each individual. NESTROFT (Naked Eye Single Tube Red Cell Osmotic Fragility Test) was performed on spot. Then Complete Blood Count was done within 24 hours of collection. HPLC (High Performance Liquid Chromatography) was performed to identify the samples for confirmation. In our observation in case of sickle cell anaemia HbF (Fetal haemoglobin), Hb (haemoglobin), MCV (mean corpuscular volume) values ranges between 0–10 %, ≤7-10g/dl, 65–90fl respectively. ARMS (Amplification Refractory Mutation System) PCR (polymerase chain reaction) was done to confirm the mutation. Result:LocationTotal no. of IndividualNumber of carrier with mutationNumber of patient with mutationJharkand1032917Chattisgarh115279West Bengal114317 Conclusion:Of the total samples collected in the camps held at various places of Jharkand, Chattisgarh & West Bengal 87 of them was carriers of sickle cell anemia. There was 7 homozygous (SS), 14 sickle beta, 12 double heterozygous for HPFH (High Persistance of Fetal Hemoglobin) & sickle cell anemia. In conclusion, the manifestations of sickle cell disease are influenced by a variety of other genetic and environmental factors. The occurrence of the disease against different genetic and environmental backgrounds provides experimental models that contribute to understanding the variability in clinical and hematological expression of the disease. Disclosures:No relevant conflicts of interest to declare.