Insights into Sickle Cell Disease through the Retinal Microvasculature

Pinhas, Alexander; Migacz, Justin; Zhou, Davis B.; Castanos, Maria V.; Otero-Marquez, Oscar; Israel, Sharon; Sun, Vincent; Gillette, Peter N.; Sredar, Nripun; Dubra, Alfredo; Glassberg, Jeffrey; Rosen, Richard B.; Chui, Toco Y. P.

doi:10.1016/j.xops.2022.100196

Cited by 13 publications

(9 citation statements)

References 53 publications

(52 reference statements)

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“…These findings suggest that occlusions could occur predominantly in small-caliber terminal vascular branches, as observed in the retinal periphery: in the terminal capillaries forming the ring surrounding the avascular region and in the terminal branches supplying temporally the macula along the horizontal raphe (at the junction of the upper and lower temporal quadrants, vessels that follow the distribution of the nerve fiber layer). 4,28 Previous cross-sectional OCTA studies have shown a lower VD in the macular temporal area compared with other regions, corresponding in most cases to areas of retinal thinning on OCT. 5,10,27 Although our results suggest a worsening of macular nonperfusion over time in SCD predominantly involving the terminal capillaries, it remains unclear whether the pathophysiology of the macular and peripheral involvement is comparable. In our cohort, we did not observe any worsening of peripheral retinopathy, except for one eye that progressed from Stage 2 to Stage 3, and no sea-fans appeared in eyes with already a proliferative disease at baseline.…”

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 97%

“…Although the lesions of sickle cell retinopathy (SCR) have been mainly described in the peripheral retina, a macular involvement has also been documented in SCD, initially using fluorescein angiography (FA) and optical coherence tomography (OCT), [1][2][3] and more recently using optical coherence tomography angiography (OCTA). [4][5][6][7][8][9][10][11][12] Sickle cell maculopathy develops from the occlusion of the macular capillary network, resulting in an enlargement of the foveal avascular zone (FAZ), perifoveal capillary rarefaction, nerve fiber layer infarcts, microaneurysm-like dots, and hairpin-shaped venular loops. Optical coherence tomography angiography studies have reported a prevalence of macular microangiopathy in patients with SCD ranging from 20% (in patients younger than 18 years) to 100% (in older patients).…”

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confidence: 99%

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Longitudinal analysis of microvascular changes in sickle cell disease using swept-source optical coherence tomography angiography

ENJALBERT,

GIOCANTI-AUREGAN,

FAJNKUCHEN

et al. 2023

Retina

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Purpose: To analyze the changes in macular vascular densities (VD) and foveal avascular zone (FAZ) over a 6-year period using swept-source optical coherence tomography angiography (OCTA) in sickle cell patients compared to unaffected controls. Methods: Thirty eyes of sickle cell patients and 12 eyes of unaffected controls matched for age and ethnicity were examined at a 6-year interval using the same imaging protocol, including ultra-wide-field angiography, swept-source OCT and 3x3mm OCTA. The macular VD and FAZ were measured on ImageJ software according to previously reported algorithms. Results: In sickle cell eyes, the mean FAZ significantly increased (p <0.01), and the VD decreased in the foveal (within a circle of 1.5 mm in diameter around the foveal center) and temporal areas in both the superficial and deep capillary plexuses (p <0.01). The VD did not change over time in the parafoveal area (annulus between two circles of 1.5 and 3 mm in diameter) and in the superior, inferior, and nasal sectors. No worsening of peripheral retinopathy was observed in the cohort during the follow-up, except for one eye that developed sea-fan. In the control eyes, no microvascular change was observed over time in terms of FAZ size and VD. Conclusion: These longitudinal OCTA findings in sickle cell patients showed an enlargement of the FAZ and a decrease in VD in the temporal and perifoveal regions despite the absence of progression of peripheral retinopathy, suggesting a worsening of the macular non-perfusion over time in sickle cell disease.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

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Longitudinal analysis of microvascular changes in sickle cell disease using swept-source optical coherence tomography angiography

ENJALBERT,

GIOCANTI-AUREGAN,

FAJNKUCHEN

et al. 2023

Retina

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“…Similarly, the review has been limited purposely to the Four Horsemen of chronic disease. It must be noted that there are other chronic diseases that may be addressed through oculomics, such as sickle cell disease [ 141 ]. Moreover, oculomics is likely to have utility in detecting and monitoring other systemic conditions that are not classed as chronic, such as sepsis [ 142 ], as well as the effects of certain treatments [ 143 ].…”

Section: Resultsmentioning

confidence: 99%

Oculomics: A Crusade Against the Four Horsemen of Chronic Disease

Patterson,

Bounds,

Wagner

et al. 2024

Ophthalmol Ther

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Chronic, non-communicable diseases present a major barrier to living a long and healthy life. In many cases, early diagnosis can facilitate prevention, monitoring, and treatment efforts, improving patient outcomes. There is therefore a critical need to make screening techniques as accessible, unintimidating, and cost-effective as possible. The association between ocular biomarkers and systemic health and disease (oculomics) presents an attractive opportunity for detection of systemic diseases, as ophthalmic techniques are often relatively low-cost, fast, and non-invasive. In this review, we highlight the key associations between structural biomarkers in the eye and the four globally leading causes of morbidity and mortality: cardiovascular disease, cancer, neurodegenerative disease, and metabolic disease. We observe that neurodegenerative disease is a particularly promising target for oculomics, with biomarkers detected in multiple ocular structures. Cardiovascular disease biomarkers are present in the choroid, retinal vasculature, and retinal nerve fiber layer, and metabolic disease biomarkers are present in the eyelid, tear fluid, lens, and retinal vasculature. In contrast, only the tear fluid emerged as a promising ocular target for the detection of cancer. The retina is a rich source of oculomics data, the analysis of which has been enhanced by artificial intelligence-based tools. Although not all biomarkers are disease-specific, limiting their current diagnostic utility, future oculomics research will likely benefit from combining data from various structures to improve specificity, as well as active design, development, and optimization of instruments that target specific disease signatures, thus facilitating differential diagnoses.

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“…Quantitative biomarkers using sequential OCT-A scans, measuring macular capillary density and intermittent perfusion indices, provide an indication of systemic SCD activity and treatment response [ 11 ]. Recently, adaptive optics scanning light ophthalmoscopy (AO-SLO) has been used for in vivo study of intermittent perfusion events detected by OCT-A and has revealed the role of sickled RBCs in promoting intravascular thrombus formations [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of CRISPR-Based Gene Editing in a Sickle Cell Disease Patient as Measured through the Eye

Pinhas

Zhou

Otero-Marquez

et al. 2022

Case Reports in Hematology

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Sickle cell disease (SCD) exists on a phenotypic spectrum with variable genetic expressivity, making it difficult to assess an individual patient’s risk of complications at any particular point in time. Current and emerging SCD treatments, including CRISPR-based gene editing, result in a variable proportion of affected red blood cells (RBCs) still vulnerable to sickling. Clinical serological indicators of disease such as hemoglobin, indirect bilirubin, and reticulocyte count and clinical metrics including number of emergency department visits and hospitalizations over time often fall short in their ability to objectively quantify ischemic disease activity and efficacy of treatments. Clearly, better clinical biomarkers are needed. The rapidly developing field of oculomics leverages the transparent nature of the ocular tissue to directly study the retinal microvasculature in order to characterize the status of systemic diseases. In this case report, we demonstrate the ability of optical coherence tomography angiography (OCT-A) to detect and measure micro-occlusive events within the retinal capillary bed before and after RBC exchange transfusion and following CRISPR-based gene editing, as an indicator of systemic ischemic disease activity and measure of treatment efficacy. The implications of these findings are discussed.

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Insights into Sickle Cell Disease through the Retinal Microvasculature

Cited by 13 publications

References 53 publications

Longitudinal analysis of microvascular changes in sickle cell disease using swept-source optical coherence tomography angiography

Longitudinal analysis of microvascular changes in sickle cell disease using swept-source optical coherence tomography angiography

Oculomics: A Crusade Against the Four Horsemen of Chronic Disease

Efficacy of CRISPR-Based Gene Editing in a Sickle Cell Disease Patient as Measured through the Eye

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