HAL Id: hal-03196834
https://hal.sorbonne-universite.fr/hal-03196834
Submitted on 13 Apr 2021
HAL is a multi-disciplinary open access archive for the deposit and dissemination of sci- entific research documents, whether they are pub- lished or not. The documents may come from
L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de
Retinal Arteriolar Occlusions and Exudative Retinal Detachments in Malignant Hypertension: More Than
Meets the Eye
Tristan de Nattes, Rana Saad, David Buob, Charles Verney, Alice Doreille, Yosu Luque, Laurent Mesnard, Michel Pâques, Cédric Rafat
To cite this version:
Tristan de Nattes, Rana Saad, David Buob, Charles Verney, Alice Doreille, et al.. Retinal Arteriolar Occlusions and Exudative Retinal Detachments in Malignant Hypertension: More Than Meets the Eye. American Journal of Hypertension, Oxford University Press (OUP), 2021, 34 (1), pp.30-33.
�10.1093/ajh/hpaa138�. �hal-03196834�
Title page:
WORD COUNTS: 1371.
TABLES: 1 Supplementary tables: 3 Supplementary figure: 1
REFERENCES: 17 Complete Title :
Retinal arteriolar occlusions and exudative retinal detachments in Malignant Hypertension:
more than meets the Eye.
Running head:
Retinal exploration in Malignant Hypertension.
Authorship :
Tristan de Nattes1, 2*, Rana Saad3,4*, David Buob5, Charles Verney1, Alice Doreille1, Yosu Luque1, Laurent Mesnard1, Michel Pâques3,4, Cédric Rafat1
* Both authors equally contributed to the work
1: Urgences Néphrologiques et Transplantation Rénale. Hôpital Tenon. Assistance Publique Hôpitaux de Paris, Sorbonne Université, Paris, France
2: Nephrology – Kidney Transplant Unit, Rouen University Hospital, 76031, Rouen, France, 3: Department of Ophthalmology, PARIS Group, Quinze-Vingts Hospital, Paris, France 4: Institut hospitalo-universitaire FOReSIGHT, Hôpital des Quinze-Vingts, Paris, France 5: Pathology Department, Hôpital Tenon. Assistance Publique Hôpitaux de Paris, Sorbonne Université, Paris, France.
Corresponding author : Tristan de Nattes,
Nephrology – Kidney Transplant Unit, Rouen University Hospital, 1 rue de Germont, 76031, Rouen, France
tristan.de-nattes@chu-rouen.fr
Orcid: 0000-0002-3714-8768 Disclosure:
All the authors declared no competing interests.
Keywords:
Malignant Hypertension; Retinal arteriolar occlusion; Retinal Wall-to-Lumen Ratio;
Exudative Retinal Detachment; Acute Kidney Injury; Optic Disc Swelling
Abstract: 245 words.
BACKGROUND
Malignant hypertension is macrovascular and microvascular endothelial injury responsible for multiple organ damage. Considering the anatomical and functional homologies between the posterior pole of the eye and the kidney, ophthalmological explorations may inform clinicians on the mechanisms underpinning concurrent kidney injury in this condition. More specifically, we investigated whether the wall-to-lumen ratio (WLR) of retinal arterioles measured by adaptive optics ophthalmoscopy could be correlated to WLR of kidney arterioles as determined by pathology. We sought to estimate the incidence of retinal arteriole occlusion a supposedly uncommon complication of malignant hypertension.
METHODS
All patients hospitalized in our renal Intensive Care Unit for malignant hypertension between 2016 and 2019 were referred to ophthalmological examinations.
RESULTS
Twenty-seven patients were included. Median retinal WLR was 0.39 [0.31-0.47] and was correlated with initial systolic (r=0.56, p=0.003) and mean blood pressure (r=0.46, p=0.02) upon admission. The retinal WLR was not correlated to renal pathological findings, as assessed by juxtaglomerular WLR (r=0.38, p=0.2), ratio of glomerulosclerosis (r=-0.39, p=0.2) or tubulo-interstitial fibrosis (r=-0.45, p=0.08). Retinal WLR was not associated with neurological or cardiovascular end-organ damage.
Branch retinal artery occlusion were detected in 18.5% of patients and exudative retinal detachment in 29.6% of patients, without any significant correlation with canonical signs of retinal hypertension including optic disc swelling.
CONCLUSIONS
In the setting of malignant hypertension, we failed to demonstrate a significant relationship between WLR and other meaningful end-organ injuries. However, branch retinal artery occlusion and exudative retinal detachment may have been hitherto underestimated.
Abbreviations
AOO: Adaptive optics ophthalmoscopy ERD: Exudative Retinal Detachment OCT: Optical Coherence Tomography ODS: Optic Disc Swelling
WLR: Wall-to-lumen ratio
Manuscript.
Introduction
Malignant hypertension is macrovascular and microvascular endothelial injury responsible for organ damage, including thrombotic microangiopathy, acute kidney injury, acute heart failure, posterior leukoencephalopathy reversible syndrome, stroke and hypertensive retinopathy 1. Eye fundus examination offers a unique standpoint on the microvasculature, as retinal and choroidal microvascular alterations are meant to reflect systemic changes 2. Furthermore, anatomical and functional homologies between the eye and the kidney 3 drive the concept whereby ophthalmological explorations may provide insights on kidney injury in the setting of malignant hypertension. Using, spectral-domain optical coherence tomography and optical coherence tomography angiography, we sought to estimate the incidence of retinal vascular occlusions, a rare occurrence which has mostly been documented in a handful of single case studies 4. Based on adaptive optics ophthalmoscopy, a novel technique that offers in vivo evaluation of wall-to- lumen ratio (WLR) of retinal arterioles with near-histological definition 5, we also investigated whether the WLR of retinal arterioles could be correlated to WLR of kidney arterioles based on pathological examination.
We conducted a retrospective study single center from January 2016 to March 2019. A total of 27 patients admitted into our renal Intensive Care Unit for malignant hypertension (defined as
recommended: diastolic blood pressure above 130 mmHg associated with organ damage 6) were referred to ophthalmological department for retinal examination.
Methods
All patients admitted into our renal Intensive Care Unit for malignant hypertension (defined as recommended: diastolic blood pressure above 130 mmHg associated with end-organ damage 6) between January 2016 and March 2019 and referred to ophthalmological department for retinal examination were retrospectively included, totaling 27 patients. Malignant hypertension was defined as recommended by a diastolic blood pressure above 130 mmHg associated with organ damage. Ophthalmological examinations were conducted at the Retina National Center, Institut hospitalo-universitaire FOReSIGHT, Hôpital des Quinze-Vingts. It included a fundus photography, spectral-domain optical coherence tomography, Optical Coherence Tomography (OCT) angiography and adaptive optics ophthalmoscopy.
Spectral-domain optical coherence tomography provides both qualitative (morphology and reflectivity) and quantitative (thickness, mapping and volume) analyses of the examined tissues in-situ and in real time. Foveal thickness, serous macular detachment, macular oedema, Optic Disc Swelling (ODS) and retinal nerve fiber layer thickness are evaluated using Spectral- domain optical coherence tomography.
Foveal avascular zone area and the vessel density of the superficial capillary plexus and deep capillary plexus were assessed using OCT angiography. The OCT is able to document to document post-occlusion atrophy and is a powerful method to detect both acute and late stage branch retinal artery occlusion. OCT were performed using the PlexElite 900, Carl Zeiss Meditec, Iena, Germany.
Adaptive optics ophthalmoscopy (AOO) offers the possibility to measure directly the thickness of the wall and hence to calculate the wall-to-lumen ratio (WLR) in vivo. In addition to determining WLR, AOO allows for vascular morphological examination and to detect the
existence of focal vascular lesions such as arteriovenous nickings and focal arteriolar narrowing. AOO were performed with the rtx1, Imagine Eye, Orsay, France.
The diagnosis of nephrosclerosis was based on pathology findings according to usual criteria
27: intrarenal arterial stiffening, arteriolar sclerosis and hyalinosis, ischemic glomeruli, tubular atrophy and interstitial fibrosis. In all other cases patients were categorized as “idiopathic malignant hypertension”. Quantitative data are presented with median with [25th-75th percentile]. Qualitative data are presented with number of patients and percentages. The Mann- Whitney U test was used for continuous variables. A two-sided p-value < 0.05 was considered statistically significant. Statistical analyses were conducted using GraphPad Prism version 6.04, GraphPad Software, La Jolla California USA.
Results
Clinical characteristics of patients are summarized in table 1, and detailed ophthalmological results in supplementary table 1. There was only one diabetic patient in the study, with coexisting diabetic retinopathy. No other patient had any preexisting eye disease.
Median time from hospitalization to retinal examination was 9.5 days [6.25-14.5]. The major finding is the unexpected incidence of rare manifestations of retinal hypertensive lesions in the form of vascular occlusions or choroidopathy across a wide range of causes of malignant hypertension. Indeed, branch retinal artery occlusion was found in 5 patients (18.5%), and 8 patients presented with exudative retinal detachment (ERD) (29.6%). Only one patient presented with both branch retinal artery occlusion and serous detachment (supplemental figure 1). The small size of the cohort meant that the study was underpowered to detect any association between the occurrence of retinal arteriolar occlusion and a specific cause of malignant hypertension. Moreover, no ophthalmologic sign was associated with the need for acute or chronic hemodialysis.
The second point is that median WLR was 0.39 [0.31-0.47] and was positively correlated with initial systolic (r=0.56, p=0.003) and mean blood pressure (r=0.46, p=0.02) upon admission, suggesting that WLR mirrors blood pressure levels in close temporal fashion.
However, retinal WLR was not correlated to renal pathological findings evaluated by juxtaglomerular WLR (r=0.38, p=0.2), percent of glomerulosclerosis (r=-0.39, p=0.2) or tubulo-interstitial fibrosis (r=-0.45, p=0.08) (supplementary table 2). WLR was not associated with other end-organ damage, specifically the existence of left ventricular hypertrophy, or a specific retinal sign, retinal signs of severity or a wider spectrum of retinal injury (Supplementary table 3).
It may be posited that WLR is more intimately associated with acute changes of blood pressure and reciprocally more loosely connected to pathological features depicting chronic alterations of the kidney. Ex vivo pathological examination may also fail to capture acute vascular lumen modifications. Finally, as autonomic innervation is a feature of the choroidal vasculature –and not the retinal vessels- choroidal WLR may be more tightly correlated to renal vascular metrics
3,8.
Discussion
Keith and Wagener classical classification of hypertensive retinopathy provides for a stepwise grading system starting with arteriolar narrowing at the onset and ODS as the sign of utmost severity. At variance, we found that ODS was detected in the absence of arterial narrowing (patient 4, 6, 7, 13, 15, 16) and was even the only sign found in patient 7. Although none of these patients exhibited thinning of the nerve fiber layer, a finding which does not support the hypothesis of an anterior optic nerve ischemia, the role of an overly aggressive blood pressure lowering in patients with a vulnerable microvasculature cannot be formally excluded. In aggregate, ERD and vascular occlusions were evidenced in 50% of the patients. None of these
signs are accounted for either by the Keith and Wagener, or the more recent Mitchell Wong classification of hypertensive retinopathy 9,10. These retinal patterns did not strictly concord with the presence of ODS, yet were found to always co-occur with at least one sign of hypertensive retinopathy, entertaining the possibility that these signs may provide novel insights on modes and severity of microvascular injury. Indeed, one of the mechanism underpinning ERD is injury to the choroidal circulation which is more vulnerable to acute changes in arterial pressure due to restricted autoregulatory properties. The choriocapillaris is also supplied by short direct vessels which means that once the rise in arterial pressure overrides the sympathetic tone, the surge in pressure cannot be dissipated in a network of branched arteries as in the retina 10. To date, ERD had been chiefly reported as a complication of thrombotic thrombocytopenic purpura and preeclampsia 11–13. Our series highlight the fact that idiopathic malignant hypertension (n=5) and glomerular disease (n=1; focal segmental glomerular sclerosis) may also be associated with ERD with (n=3) or without (n=3) concurrent biological signs of thrombotic microangiopathy.
Besides ODS, retinal haemorrhage and exudates, recognized as retinal lesion portending the worst survival prognosis in the setting of acute hypertension 10,14,15, our brief report underscores the existence of other reputedly rare lesional patterns associated with dismal ophthalmological prognosis such as macular ischemia, retinal vascular occlusions and ERD 16–18. Future investigations will be required to determine how these signs may enrich current retinal hypertensive classifications and provide for enhanced end-organ damage prediction and if their detection helps predict the underlying cause of hypertension. Moreover, these cases exemplify the role of new technique of retinal exploration in detecting lesions which would have otherwise gone unnoticed, and provide WLR measurements.
A major limitation of this study resides in the time elapsed between the initial surge in blood pressure and WLR measurements. Hence, WLR measurements may reflect greater blood pressure control but also other therapeutic interventions which may have exerted a meaningful impact over the retinal microvasculature namely, the choice of blood pressure lowering agents and fluid and electrolyte removal via renal replacement therapy (n = 10, 37.0 %). From this standpoint, anti-hypertensive agents with vasodilatory properties represented the most significant pharmacological intervention given their proven short term effects on WLR mediated by lumen dilatation 19,20. Other therapies likely to impact the retinal vasculature such as therapeutic anticoagulation, plasma exchanges and complement blockade were not implemented in any case. Another significant impediment to the generalization and applicability of these investigations is that they require specialized equipment hitherto restricted to specialized centers. Technical advances related to digital retinal photography may perhaps in a near future circumvent these obstacles by offering bedside, repeated retinal examination outside the confines of ophthalmology departments.
Clinicians may ultimately take advantage of this to monitor the systemic impact of antihypertensive and/or vasodilatory therapy.
Disclosure:
All the authors declared no competing interests.
Acknowledgments:
This study was not funded.
References
1. Shantsila A, Lip GYH. Malignant Hypertension Revisited-Does This Still Exist? Am J Hypertens. 2017; 30:543-549. <https://doi.org/10.1093/ajh/hpx008>.
2. Cheung Carol Yim-lui, Ikram M. Kamran, Sabanayagam Charumathi, Wong Tien Yin.
Retinal Microvasculature as a Model to Study the Manifestations of Hypertension.
Hypertension. 2012; 60:1094-1103.
<https://doi.org/10.1161/HYPERTENSIONAHA.111.189142>.
3. Farrah TE, Dhillon B, Keane PA, Webb DJ, Dhaun N. The eye, the kidney, and cardiovascular disease: old concepts, better tools, and new horizons. Kidney Int. 2020; 0.
<https://doi.org/10.1016/j.kint.2020.01.039>.
4. Kawashima M, Nakajima M, Kawamura A. INDOCYANINE GREEN ANGIOGRAPHIC FINDINGS OF HYPERTENSIVE CHOROIDOPATHY. Retin Cases Brief Rep. 2008;
2:154–157. <https://doi.org/10.1097/ICB.0b013e318030a98d>.
5. Koch E, Rosenbaum D, Brolly A, Sahel J-A, Chaumet-Riffaud P, Girerd X, Rossant F, Paques M. Morphometric analysis of small arteries in the human retina using adaptive optics imaging: relationship with blood pressure and focal vascular changes. J Hypertens.
2014; 32:890-898. <https://doi.org/10.1097/HJH.0000000000000095>.
6. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement D, Coca A, De Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen S, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder R, Shlyakhto E, Tsioufis K, Aboyans V, Desormais I, List of authors/Task Force members: 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC Task Force for the Management of Arterial
Hypertension. J Hypertens. 2018; 36:2284-2309.
<https://doi.org/10.1097/HJH.0000000000001961>.
7. Meyrier A. Nephrosclerosis: update on a centenarian. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2015; 30:1833-1841.
<https://doi.org/10.1093/ndt/gfu366>.
8. Nickla DL, Wallman J. THE MULTIFUNCTIONAL CHOROID. Prog Retin Eye Res.
2010; 29:144-168. <https://doi.org/10.1016/j.preteyeres.2009.12.002>.
9. Keith NM, Wagener HP, Barker NW. Some different types of essential hypertension: their course and prognosis. Am J Med Sci. 1974; 268:336-345.
<https://doi.org/10.1097/00000441-197412000-00004>.
10. Wong TY, Mitchell P. Hypertensive retinopathy. N Engl J Med. 2004; 351:2310-2317.
<https://doi.org/10.1056/NEJMra032865>.
11. Lee CS, Choi EY, Lee M, Kim H, Chung H. Serous retinal detachment in preeclampsia and malignant hypertension. Eye. 2019; 33:1707-1714. <https://doi.org/10.1038/s41433-
12. Aseem F, Zamora BG, Kauffman L, Miller PJ, John VJ. Bilateral exudative retinal detachments due to thrombotic microangiopathy associated with intravenous abuse of Opana ER. Am J Ophthalmol Case Rep. 2018; 11:72-74.
<https://doi.org/10.1016/j.ajoc.2018.06.001>.
13. Sampo M, Yin GHW, Hoffart L, Denis D, Soler V, Matonti F. Exudative Retinal Detachment Treatment in a Patient with Thrombotic Thrombocytopenic Purpura. Case Rep Ophthalmol. 2016; 7:90-95. <https://doi.org/10.1159/000444291>.
14. McGregor E, Isles CG, Jay JL, Lever AF, Murray GD. Retinal changes in malignant hypertension. Br Med J Clin Res Ed. 1986; 292:233-234.
<https://doi.org/10.1136/bmj.292.6515.233>.
15. Breslin DJ, Gifford RW, Fairbairn JF, Kearns TP. Prognostic importance of ophthalmoscopic findings in essential hypertension. JAMA. 1966; 195:335-338.
16. Coscas G, Cunha-Vaz J, Soubrane G. Macular Edema: Definition and Basic Concepts.
Dev Ophthalmol. 2017; 58:1-10. <https://doi.org/10.1159/000455264>.
17. McLeod D. Misery Perfusion, Diffusive Oxygen Shunting and Interarterial Watershed Infarction Underlie Oxygenation-Based Hypoperfusion Maculopathy. Am J Ophthalmol.
2019; 205:153-164. <https://doi.org/10.1016/j.ajo.2019.03.015>.
18. Ahn SJ, Woo SJ, Park KH. Retinal and choroidal changes with severe hypertension and their association with visual outcome. Invest Ophthalmol Vis Sci. 2014; 55:7775-7785.
<https://doi.org/10.1167/iovs.14-14915>.
19. Rosenbaum D, Mattina A, Koch E, Rossant F, Gallo A, Kachenoura N, Paques M, Redheuil A, Girerd X. Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics. J Hypertens. 2016; 34:1115- 1122. <https://doi.org/10.1097/HJH.0000000000000894>.
20. Rizzoni D, Agabiti Rosei C, De Ciuceis C, Semeraro F, Rizzoni M, Docchio F. New Methods to Study the Microcirculation. Am J Hypertens. 2018; 31:265-273.
<https://doi.org/10.1093/ajh/hpx211>.
Keith-Wagener classification
Grade 1 Grade 2 Grade 3 Grade 4
Patient Biological TMA
Myocardial involvement
Cerebral
involvement Acute RRT Chronic RRT Arterial narrowing
Arteriovenous crossing changes
Retinal haemorrhage
Hard exudates
Cotton wool spots
Optic disc swelling
Exudative retinal detachment
Arteriolar
occlusion Diagnosis
22 No Yes Yes Yes Yes Yes Yes No No Yes No No Yes C3 glomerulopathy
2 No No No Yes Yes Yes No Yes No Yes No No No Diabetic nephropathy
26 No No Yes No NA Yes No Yes Yes Yes Yes Yes No Focal segmental
glomerulosclerosis
4 Yes Yes No Yes Yes No No No Yes No Yes Yes No Idiopathic malignant
hypertension
10 No No No No No Yes Yes No Yes Yes Yes No No Idiopathic malignant
hypertension
5 Yes No Yes No No No No No Yes Yes No No No Idiopathic malignant
hypertension
6 Yes No No Yes Yes No No Yes Yes No Yes No Yes Idiopathic malignant
hypertension
7 No No No Yes Yes No No No No No Yes No No Idiopathic malignant
hypertension
13 Yes No No Yes Yes No No Yes No No Yes No No Idiopathic malignant
hypertension
15 Yes No No No No No No Yes Yes Yes Yes Yes No Idiopathic malignant
hypertension
24 Yes No Yes No No Yes No Yes Yes No Yes Yes No Idiopathic malignant
hypertension
25 No Yes No No No Yes Yes Yes No No Yes Yes No Idiopathic malignant
hypertension
17 No No No No No Yes Yes Yes Yes Yes Yes Yes No Idiopathic malignant
hypertension
20 No No No No Yes No No No No No No No No IgAN
23 No No No No NA No No No No No No No No IgAN
27 No No No No No Yes No Yes Yes Yes Yes No No IgAN
3 Yes No No No No Yes No Yes Yes Yes No Yes Yes Nephrosclerosis
11 Yes Yes No Yes Yes NA NA NA NA NA NA NA NA Nephrosclerosis
12 Yes No No Yes Yes NA NA NA NA NA NA NA NA Nephrosclerosis
14 No No No No Yes Yes No Yes No No Yes No Yes Nephrosclerosis
21 No No No No Yes Yes No No No Yes No No No Nephrosclerosis
19 No No No No No Yes Yes No Yes Yes Yes No No Nephronophthisis
18 Yes No No No No No No Yes No No No No No Polyarteritis nodosa
Supplemental Table 1: Detailed hypertension-associated and retinal clinical variables. IgAN: IgA Nephropathy, HUS: Haemolytic Uraemic Syndrome, NA: Not Available. RRT: Renal Replacement Therapy, TMA: Thrombotic Microangiopathy, UMOD: Uromodulin-Related
Autosomal Dominant Tubulointerstitial Kidney Disease.
1 No No No No No NA NA NA NA NA NA NA NA Preeclampsia
8 No No No Yes Yes No No No Yes Yes No No Yes Preeclampsia
9 Yes No No Yes No Yes Yes Yes No Yes No No No Shigatoxin-induced
HUS
16 No No No No No No Yes No Yes Yes Yes Yes No UMOD
Clinical variable r value p value
Age 0.31 [-0.11 – 0.64] 0.13
BMI 0.05 [-0.39 – 0.48] 0.81
Initial systolic blood pressure 0.56 [0.21 – 0.79] 0.003 Initial diastolic blood pressure 0.33 [-0.09 – 0.65] 0.11 Initial mean blood pressure 0.46 [0.07 – 0.73] 0.02 Time to withdrawal from
intravenous antihypertensive therapies
0.26 [-0.20 – 0.62] 0.25
Lowest platelet count during hospitalization
-0.20 [-0.56 – 0.23] 0.35
Maximum LDH value during hospitalization
0.31 [-0.11 – 0.63] 0.14
Initial plasma creatinine -0.05 [-0.45 – 0.36] 0.82 Left Ventricular Ejection
Fraction
0.01 [-0.39 – 0.55] 0.68
Interventricular Septum Thickness
0.23 [-0.30 – 0.65] 0.38
Left Ventricular Mass Index 0.38 [-0.14 – 0.74] 0.13 Delay between hospitalization
and ophthalmological examination
0.09 [-0.41 – 0.56] 0.72
Juxtaglomerular WLR 0.38 [-0.23 – 0.78] 0.20
% of tubulo-interstitial fibrosis -0.45 [-0.79 – 0.10] 0.09
% of glomerulosclerosis -0.39 [-0.76 – 0.17] 0.15
Supplemental table 2: Correlations between retinal Wall to Lumen Ratio (WLR), clinical and biological data. BMI: Body Mass Index. LDH: Lactate Dehydrogenase.
WLR value when condition is present
WLR value when condition is absent
p value
Known pre-existing arterial hypertension
0.37 [0.28 – 0.42] 0.46 [0.34 - 0.49] 0.29
Acute hemodialysis 0.42 [0.34 – 0.49] 0.37 [0.28 – 0.49] 0.41 Chronic
hemodialysis
0.46 [0.34 – 0.54] 0.37 [0.28 – 0.44] 0.24
Left Ventricular Hypertrophy
0.46 [0.36 – 0.52] 0.37 [0.29-0.48] 0.21
Ischemic Myocardial Injury
0.54 [0.26 – 0.63] 0.38 [0.30 – 0.47] 0.40
Posterior
leukoencephalopathy reversible syndrome
0.46 [0.28 – 0.60] 0.39 [0.30 – 0.47] 0.71
Severe neurological involvement
0.42 [0.34 – 0.57] 0.37 [0.28 – 0.47] 0.38
Arterial narrowing 0.36 [0.30 – 0.43] 0.40 [0.29 – 0.49] 0.55 Arteriovenous
crossing changes
0.41 [0.31 – 0.47] 0.37 [0.26 – 0.47] 0.67
Retinal hemorrhages 0.34 [0.27 – 0.43] 0.42 [0.34 – 0.49] 0.15 Hard exudates 0.37 [0.27 – 0.43] 0.39 [0.33 – 0.49] 0.39 Cotton wool spots 0.38 [0.28 – 0.52] 0.38 [0.32 – 0.47] 0.91 Optic disc swelling 0.32 [0.27 – 0.43] 0.42 [0.35 – 0.49] 0.14
ERD 0.39 [0.27 – 0.47] 0.37 [0.33 – 0.54] 0.59
Arteriolar occlusion 0.40 [0.33 – 0.48] 0.31 [0.27 – 0.42] 0.25 Severe retinal
involvement
0.37 [0.33 – 0.47] 0.39 [0.27 – 0.47] 0.80
More than two retinal signs
0.39 [0.33 – 0.47] 0.34 [0.27 – 0.42] 0.50
Supplemental table 3: Value of retinal Wall to Lumen Ratio according to clinical and biological parameters. Severe neurological involvement was defined by the occurrence of Posterior Leukocencephalopathy Reversible Syndrome and/or abnormabiility of cerebral Magnetic Resonance Imaging. Severe retinal involvement was defined by the occurrence of optic disc swelling and/or ERD and/or arteriolar occlusion. ERD: Exudative Retinal Detachment.
N=27
Age, year 39.4 [30.7-45.3]
Female 7 (25.9)
African
African-American Afro-Carribean Asian
Caucasian Hispanic
6 (22.2) 4 (14.8) 3 (11.1) 2 (7.4) 11 (40.7) 1 (3.7)
BMI, kg/m2 25.9 [24.3-29.4]
Previous history of hypertension, n (%) 11 (40.7) Initial blood pressure, mmHg
Systolic Diastolic Mean
220 [185-240]
130 [113-163]
153 [136-187]
Plasma creatinine, mg/dL
Acute haemodialysis, n (%) Chronic haemodialysis, n (%)
5.9 [3.3-8.9]
10 (37) 12 (44.4) Organ involvement, n (%)
Biological TMA
Posterior Reversible Encephalopathy Syndrome Myocardial
11 (40.7) 4 (14.8) 4 (14.8) Cardiac imaging
Left Ventricular Mass (g) LVM index (g/m2)
Interventricular septum thickness in diastole (mm) LV Ejection Fraction (%)
309 [215.3-342.8]
152 [101.1-182.8]
12 [10-14]
60 [50-65]
Kidney pathology,
Glomerulosclerosis, n (%) Tubulo-interstitial fibrosis, n (%) WLR
17 (63)
31 [16.5-48.5]
50 [30-60]
2.9 [2.3-3.2]
Retinal explorations WLR
Arteriolar occlusion, n (%)
Exudative retinal detachment, n (%) Papilledema, n (%)
Retinal haemorrhage, n (%) Cotton wool spots, n (%) Macular ischemia, n (%) Hard exudates, n (%) Arterial narrowing, n (%)
Arteriovenous crossing changes, n (%)
0.39 [0.30-0.49]
5 (18.5) 8 (29.6) 14 (51.9) 13 (48.1) 14 (51.9) 1 (3.7) 13 (48.1) 13 (48.1) 7 (25.9)
Idiopathic malignant hypertension Nephrosclerosis
IgA nephropathy Preeclampsia Typical-HUS
C3 associated glomerulopathy Nephronophthisis
Other*
10 (37.2) 5 (18.5) 3 (11.1) 2 (7.4) 1 (3.7) 1 (3.7) 1 (3.7) 4 (14.8) Table 1: clinical characteristics of patients.
Results are medians [25th-75th]. *Other: diabetic nephropathy, polyarteritis nodosa, UMOD genetic variant, focal segmental glomerulosclerosis: 1 patient each. TMA: Thrombotic Microangiopathy; LV: Left Ventricular; LVM: Left Ventricular Mass; HUS: Hemolytic and Uremic Syndrome
