To describe the clinical course of a pediatric patient with sickle cell disease (SCD) presenting with isolated bilateral paracentral acute middle maculopathy (PAMM) in the setting of influenza A. Fundus photography, fundus autofluorescence, optical coherence tomography (OCT) and OCT-angiography (OCTA) were obtained. An 8-year-old male with a history of HbSS SCD, ADHD and no prior sickle cell retinopathy presented with new onset blurred vision, headache, photopsia, and metamorphopsia along with symptoms of an upper respiratory infection. Fundus examination showed bilateral placoid whitening of the temporal macula and corresponding OCT imaging revealed hyperreflectivity and thickening of the inner nuclear layer (INL), consistent with bilateral PAMM lesions. Thought to be a harbinger of a sickle crisis, the patient received hydroxyurea 500 mg daily and demonstrated partial recovery of symptoms at 2-month follow-up. The bilaterality and symmetry of this patient's presentation suggests a systemic vaso-occlusive state, whereby sickled red blood cells occluded the retinal capillaries as a function of the location and organization of the retinal capillary vasculature. The patient's risk factors for the development of a sickling event included recent viral infection and use of sympathomimetic medication. PAMM lesions can often be harbingers of larger ischemic events such as retinal artery or vein occlusions. Therefore, in SCD patients, presentation of PAMM warrants urgent evaluation of sickling triggers, treatment and prophylaxis.

To investigate the potential utility of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for stages 3 and 4 proliferative sickle cell retinopathy (PSR). Retrospective review of anatomic and visual acuity outcomes after intravitreal anti-VEGF therapy for stages 3 and 4 PSR eyes. There were 45 PSR eyes (17 stage 3 and 28 stage 4) treated with anti-VEGF agents (bevacizumab (37 eyes), aflibercept (6 eyes), ranibizumab (3 eyes), one eye received 2 both bevacizumab and aflibercept). Follow-up ranged from 1 to 120 months (mean= 21 months). Within 1 month after anti-VEGF treatment, VA improved > 2 lines in 17/45 eyes, remained stable in 27/45 eyes and worsened in 1/45 eyes. Median visual acuity remained 20/20 for stage 3 and improved from 20/200 to 20/30 for stage 4 PSR eyes. More stage 4 PSR eyes had VA improvement post-treatment than stage 3 PSR eyes (P=0.003). There were no cases of endophthalmitis. Visual acuity outcomes were similar for anti-VEGF with and without laser treatment. Control of PSR was achieved in 42/45 (93%) of eyes without the need for pars plana vitrectomy. Within one month of treatment, administration of anti-VEGF therapy of PSR eyes resulted in seafan regression, clearing of vitreous hemorrhage, and stable or improved vision in most eyes.

To analyze clinical, laboratory, and Doppler vascular parameters in pediatric sickle cell disease (SCD) patients and identify correlations and predictive factors for sickle cell retinopathy (SCR) and proliferative SCR (PSR). A retrospective study included pediatric SCD patients screened for SCR between December 2023 and August 2024. Systemic, transcranial-cervical Doppler, and ophthalmologic evaluations were performed. Correlation analyses explored relationships between clinical, laboratory, and ophthalmologic parameters and SCR. Logistic regression identified predictive factors for SCR and PSR. We included 172 eyes from 86 pediatric SCD patients (mean age: 11.1 years; 57% male). SCR was diagnosed in 20 patients (23.3%), including 15 with non-proliferative (NPSR) and 5 with PSR. SCR correlated significantly with higher vaso-occlusive crises (VOC) frequency (ρ = 0.379, p < 0.001), lower fetal hemoglobin (HbF) (ρ = -0.363, p = 0.001), older age (r = 0.295, p = 0.006), and glucose-6-phosphate dehydrogenase (G6PD) deficiency (ρ = 0.428, p < 0.001). Doppler evaluations showed reduced velocities associated with SCR (p < 0.05). Logistic regression identified G6PD deficiency (OR = 8.34, p = 0.014), increased VOC (OR = 2.22, p = 0.011), older age (OR = 1.26, p = 0.04), and lower HbF (OR = 0.89, p = 0.047) as predictors of SCR. An age cut-off of 11.5 years yielded 65% sensitivity and 64% specificity. For PSR, significant correlations included SC genotype (r = 0.728, p < 0.001) and higher hemoglobin (Hb) (r = 0.518, p = 0.019). Lower hydroxyurea doses were linked to PSR (r = -0.548, p = 0.012). Hb levels predicted PSR, with a 9.2g/dL cut-off (80% sensitivity, 86% specificity). Early detection of SCR is crucial in pediatric SCD patients. Key risk factors include older age (cut-off 11.5 years), higher VOC frequency, G6PD deficiency, and lower HbF for SCR, and SC genotype, reduced hydroxyurea doses, and higher Hb (cut-off 9.2g/dL) for PSR. Regular ophthalmologic screening and targeted management may help prevent vision loss and improve clinical outcomes.

Patterns of treatment in patients with sickle cell retinopathy in the United States.

BackgroundThis study aimed to evaluate the spectrum of ocular manifestations in sickle cell disease (SCD) patients, with a particular emphasis on retinal involvement, to improve early diagnosis and management strategies.MethodologyA cross-sectional, observational study was conducted over one year at Assam Medical College and Hospital, Dibrugarh, recruiting 96 SCD patients aged 10 and above. Comprehensive ophthalmological evaluations included best-corrected visual acuity, slit-lamp biomicroscopy, direct/indirect ophthalmoscopy, spectral-domain optical coherence tomography (OCT), and, in selected cases, fundus fluorescein angiography. Sickle cell retinopathy (SCR) was graded using Goldberg’s classification.ResultsThe mean age of the participants was 31.00 ± 13.89 years, with 52 (54.17%) males and 71 (76.04%) from the tea tribe community. Systemic features included pallor in 85 (88.54%) and generalized weakness in 83 (86.46%) participants. Visual acuity of 6/6 to 6/9 was found in 32 (33.33%) (right eye) and 33 (34.38%) (left eye) participants. Anterior segment involvement (corkscrew vessels) was noted in 50 (52.08%) participants, and posterior segment changes were noted in 51 (53.13%) participants. Non-proliferative SCR was present in 46 (47.92%) and proliferative SCR in 5 (5.21%) participants. OCT revealed vitreomacular traction, epiretinal membranes, and full-thickness macular holes. Patient age correlated with retinopathy severity (R² = 0.76, p < 0.01), and systemic severity correlated with retinopathy (R² = 0.94, p < 0.001).ConclusionsSCD patients exhibit significant ocular manifestations, particularly retinal pathology, which correlates with age and systemic disease severity. Early and routine ophthalmologic screening is crucial for timely management and preventing vision loss.

Global publication trends on sickle cell and diabetic retinopathy over eight decades: a highlight on information disparity: SCRnet consortium paper 1

The purpose of this study was to report the rates of ophthalmic complications and interventions in patients diagnosed with sickle cell disease (SCD) and sickle cell retinopathy (SCR), while reviewing current management strategies within the literature. This retrospective cohort study included patients ≥ 18 years of age with the diagnosis of SCD and SCR. The electronic health record system TriNetX was utilized to identify patients diagnosed with SCD and SCR. The main outcome measures included rates of ophthalmic complications and interventions. We identified 1,249 patients with the diagnosis of both SCD and SCR. The mean age at diagnosis of SCR was 34.9 ± 14.8 years. The most common ocular complication was vitreous hemorrhage (VH) (19.5%) followed by cataracts (17.8%), rhegmatogenous retinal detachment (12.4%), and tractional retinal detachment (4.7%). The most common ocular intervention was retinal laser photocoagulation (13.6%). In a large, contemporary population-based study for SCD patients with SCR, the rates of preventable visually significant complications are high. Timely screening, diagnosis, and management strategies can help prevent these complications.

"Vitreal Tornado" in Sickle Cell Retinopathy Assessment by Widefield Optical Coherence Tomography Angiography.

Evaluation of macular thickness by optical coherence tomography in homozygous SS sickle cell subjects in Yaoundé

RWC Update: Management of Persistent Peripheral Avascular Retina in Retinopathy of Prematurity Survivors; Giant Macular Hole Leading to a Total Retinal Detachment; Proliferative Sickle Cell Retinopathy: Intraoperative Fluorescein Angiography Guided Management.

Iris heterochromia is a congenital anomaly of iris colouration that occurs rarely. Whatever its intensity or laterality, it is often indicative of a malformative syndrome. The aim of this study was to investigate the epidemiological, clinical and therapeutic features of Waardenburg syndrome in the ophthalmology department of the Thies regional hospital. We report three cases of iris heterochromia including this syndrome diagnosed over a period of 4 years. Irial heterochromia was the main reason for consultation in the two girls, while the boy was consulted for sickle cell retinopathy. Auditory evoked potentials were carried out in all the children, revealing bilateral sensorineural hearing loss, thus making it possible to establish the association between congenital iris heterochromia, sensorineural hearing loss and Waardenburg syndrome. The diagnostic criteria of the Waardenburg consortium were used to classify the first and third patients as type 1 and the second patient as type 4. The absence of diagnostic certainty due to the contribution of genetics should never lead to a misdiagnosis. Ultimately, congenital iris heterochromia is a reality; however, its unilateral manifestation is rare. Ideally, clinicians should look for associated anomalies, as this heterochromia could conceal a malformative syndrome, as the management of these patients requires multidisciplinary consultation. Keywords: syndrome, Waardenburg, heterochromia, hearing loss, Thies.

SummarySickle cell disease (SCD), encompassing genotypes such as HbSS and HbSC, causes chronic haemolysis and microvascular occlusion, leading to organ damage. The retina is particularly vulnerable, often resulting in sickle cell retinopathy (SCR) or sickle cell maculopathy (SCM). The precise underlying mechanisms are unclear, though various factors are suggested to contribute. This study explored the role of whole blood viscosity and red blood cell (RBC) deformability in SCR and SCM. Adult HbSS (n = 34) and HbSC patients (n = 34) were offered an ophthalmic examination to determine SCR stage. A venous ethylenediaminetetraacetic acid (EDTA) sample was collected from each participant. Whole blood viscosity was measured using a Brookfield viscometer and RBC deformability was assessed using the Oxygenscan feature of the Laser Optical Rotational Red Cell Analyser as a function of the (varying) partial oxygen pressure. HbSC patients with proliferative sickle cell retinopathy (PSCR) had a lower delta elongation index (p = 0.012) and point of sickling (p = 0.002) than those without PSCR, suggesting that RBC sickling might not play a central role in the pathogenesis of PSCR in HbSC patients. Despite hyperviscosity being a commonly proposed mechanism, no associations were found between blood viscosity, SCR and SCM. These results point to alternative mechanisms contributing to SCR and SCM, highlighting the complexity and need for further research to fully understand the underlying factors.

To determine the microvascular changes of the retina and choroid in sickle cell anemia (SCA) patients and to investigate the relationship between the severity of sickle cell retinopathy and sickle cell maculopathy (SCM). In this cross-sectional study, 78 eyes of 39 patients with SCA were included in the patient group and 68 eyes of 34 healthy participants were included in the control group. Differences in foveal avascular zone (FAZ), retinal and subfoveal choroidal thickness (SFCT), and choroidal vascularity index (CVI) between the patient group and the control group were evaluated by swept source optical coherence tomography (OCT) and OCT angiography (OCTA) imaging. In addition, systemic and biological parameters were compared in patients with and without SCM. SCM was detected in 16 eyes of 8 patients. Proliferative sickle cell retinopathy (PSCR) was present in 10 patients. In logistic regression analysis, PSCR was found to be a risk factor for the development of SCM (p=0.015, odds ratio: 17.25, 95% confidence interval: 1.73-172.02). The temporal inner retinal layers were significantly thinner in the patient group compared to the control group. The patient group also exhibited significantly greater FAZ enlargement in both the superficial and deep capillary plexus when compared with the control group (p<0.001 for both). CVI was higher in the control group than in the patient group (p<0.001). SFCT was significantly thinner in the patient group (p=0.013). There was no significant difference between patients with and without SCM in terms of FAZ enlargement, CVI values, or systemic and biological factors. In our study, PSCR was found to be a risk factor for the development of SCM. OCT and OCTA provide valuable information about microvascular changes in the retina and choroid in patients with SCM. Structural changes demonstrated by OCTA before the development of SCM are very important for follow-up and treatment in terms of visual prognosis of patients.

Investigation of Sickle Cell Retinopathy in Pediatric and Adolescent Patients Enrolled in a Large Cohort Study.

To determine the outcomes of patients with sickle cell retinopathy who experienced at least one episode of being lost to follow-up (LTFU) compared with those who attended all appointments. Adult patients with sickle cell retinopathy who visited Wills Eye Hospital Retina service (January 2012-December 2021) with >2 visits were reviewed for LTFU events, defined as failure to return for a follow-up appointment within 6 months of the scheduled date. One hundred and eighty-one eyes of 94 patients were included. Fifty-one patients (99 eyes) attended all appointments ("attended group"), whereas 43 patients (82 eyes), or 46%, had at least one LTFU event ("LTFU group"). The mean (SD) LTFU duration was 470 (329) days. In the LTFU group, mean (SD) VA was significantly worse at the final visit (logMAR 0.45 (0.63), Snellen 20/56) and at the post-LTFU visit (0.36 (0.59), 20/46) compared with the pre-LTFU visit (0.3 (0.47), 20/40, P = 0.001). In the attended group, mean (SD) VA was significantly better at the final visit (0.41 (0.63), 20/51) compared with the initial visit (0.52 (0.78), 20/66, P = 0.038). Patients with sickle cell retinopathy with an LTFU event have worse visual outcomes compared with patients who attend all appointments.

Automated Quantitative Assessment of Retinal Vascular Tortuosity in Patients with Sickle Cell Disease

Sickle cell disease (SCD) is an autosomal recessive disease. Clinical presentation depends on mutation of hemoglobin protein. The complication due to SCD is variable, as it affects vascular bed of different organs due to accumulation of sickle hemoglobin in arteries. This vaso-occlusive event may affect vascular bed in the eye, causes sickle cell retinopathy. A 22-year-old female, known case of sickle cell anemia, presented with a sudden loss of vision in her left eye 2 days back with generalized myalgia for 5 days. The ocular examination revealed acute central retinal artery occlusion (CRAO). She underwent laboratory and radiological investigations. The blood investigations revealed normal biochemical parameters and normal coagulation profile. On ocular examination, the fundus fluorescein angiography revealed CRAO along with central serous retinopathy. This report advocates that the disease may result in life affecting complication like vision loss due to CRAO. This case indicates that only prompt management toward such cases will be beneficial for such patients. We need a proper approach for the management of SCD patients.

To evaluate the presence and progression of maculopathy in patients with sickle cell disease using optical coherence tomography and optical coherence tomography-angiography and to identify clinical/laboratory risk factors for progression during follow-up. Complete ophthalmic examination, including fundoscopy and macular spectral-domain-optical coherence tomography/optical coherence tomography angiography scans, was performed in consecutive patients with sickle cell disease (HbSS/HbSβ 0 /HbSβ + /HbSC genotype) during baseline and follow-up visits. Sickle cell retinopathy stage was based on fundoscopy instead of the Goldberg classification, as fluorescein angiography was not routinely used. Medical/ophthalmological history and hematologic characteristics were retrieved from medical records. One hundred and six eyes of 60 patients were analyzed. The median follow-up period was 34.5 months (range 8-70, interquartile range 25-55). Macular thinning was present in 41 eyes (38.7%) at baseline and in 52 eyes (49.1%) at follow-up. Progression of macular thinning was observed in 25.5% (27/106) of the eyes and sickle cell retinopathy progression in 15.1% (16/106) of the eyes. Predictors for the progression of macular thinning were proliferative retinopathy (adjusted odds ratio 3.40, P = 0.024), lower vessel density in the superior capillary plexus of the inferior parafoveal subfield (adjusted odds ratio 0.88, P = 0.003), and higher vessel density in the deep capillary plexus of the inferior parafoveal subfield (adjusted odds ratio 1.17, P = 0.001). No association was found between the progression of macular thinning and the worsening of other organ damage, sickle cell retinopathy progression, ocular complications, or laser treatment. Sickle cell disease-related maculopathy progresses in many patients without impairing visual acuity during short-term follow-up. Progression of maculopathy is correlated with proliferative retinopathy and vessel densities in inferior parafoveal subfields. Further research is needed to elucidate functional consequences of macular changes.

Purpose- To describe a case of central retinal artery occlusion following scleral buckling procedure combined with pneumoretinopexy in a patient with sickle cell (HbSC) retinopathy (SCR). Methods- Scleral buckling procedure, combined with injection of 0.3 ml of 100% perfluoropropane (C3F8) gas in the vitreous, was performed without intra-operative complications under general anaesthesia as treatment of two separate macula-sparing rhegmatogenous retinal detachments secondary to round holes, involving superior and inferior retina respectively, in the right eye of a 26-year-old Afro-Caribbean female with sickle cell disease. Results- On day one post-operatively, central retinal artery occlusion (CRAO) was detected in the operated eye. We hypothesize that the expansion of the gas in the postoperative period combined with the presence of a retinal explant might have caused a moderate elevation of the IOP that caused extensive retinal arteriolar shutdown in the backdrop of SCR. Conclusion- CRAO can be a devastating complication following scleral buckling procedure combined with gas insertion in SCR, caution is required when performing scleral explant combined with expansile gas in a patient with sickle cell vasculopathy.

Pathologies associated with retinal hypoxia, including diabetic retinopathy, central/branch retinal artery occlusion (CRAO/BRAO), central/branch retinal vein occlusion (CRVO/BRVO), retinopathy of prematurity, sickle cell retinopathy, etc., have limited effective therapeutic intervention strategies. To address this shortcoming, herein we propose a biocompatible and biodegradable poly (lactic-co-glycolic acid) shell-based oxygen nanobubbles (PLGA-ONBs) platform, formulated with PLGA, polyvinyl alcohol (PVA), and NaHCO3. The formulation of a novel PLGA-ONBs was proposed, and the synthesis process was optimized with respect to dependent (sonication power, PVA, and NaHCO3 concentrations) and response (hydrodynamic diameter and oxygen capacity) variables. The optimized formulation has a concentration of (13.8 ± 0.01) × 1010 particles per ml with a hydrodynamic diameter of 142.83 ± 11.46 nm, and oxygen loading capacity of 47.2 ± 2.4 mg L-1. After 4 weeks of storage, the ONBs were found to have an oxygen concentration of 38.9 ± 2.9 mg L-1, indicating excellent oxygen retention capability. The PLGA-ONBs tested in vitro in Muller and R28 retinal cell lines demonstrated excellent biocompatibility and potential to mitigate hypoxia. In addition, the PLGA-ONBs treatment on hypoxic cells demonstrated restoration of mRNA expression of three key hypoxic genes (HIF-1α, PAI-1, and VEGF-A) to normoxic states, indicating hypoxia reversal potential. Biosafety of the PLGA-ONBs was demonstrated in a rabbit model, demonstrating promise in clinical translation. The PLGA-ONBs developed exhibited excellent oxygen loading and retention, potential in hypoxia mitigation, and a safety profile that could be a promising route to treating ischemic diseases of the eye.