Elsevier

Thrombosis Research

Volume 190, June 2020, Pages 63-68
Thrombosis Research

Full Length Article
Antiphospholipid syndrome and antiphospholipid antibody profile in patients with retinal vein occlusion

https://doi.org/10.1016/j.thromres.2020.04.005Get rights and content

Highlights

  • Data on APS in patients with RVO are scarce.

  • We found aPLs to be more prevalent in RVO-patients than in population-based controls.

  • A more unfavorable aPL profile was found in patients with RVO and APS compared to population-based controls.

  • In most of our RVO-patients with APS, low-dose aspirin was effective to prevent relapses or new thrombotic events.

  • Besides atherosclerosis, APS may play an independent role in RVO pathogenesis.

Abstract

Introduction

Data on prevalence, association with vascular risk factors, clinical management and outcome of antiphospholipid syndrome (APS) in retinal vein occlusion (RVO) are scarce.

Methods

Patients diagnosed with RVO at a tertiary-care hospital, and two additional groups; population-based controls and patients with APS (RVO-APS) were studied. Prevalence, association with vascular risk factors, antiphospholipid antibody profile, clinical management, genetic thrombophilia profile, carotid ultrasound and outcome of RVO-APS patients were assessed and compared with controls.

Results

Some 331 consecutive patients with RVO and 281 controls were included. Overall, aPLs were more prevalent in RVO-patients than in controls (33, 10% vs. 12, 4.3%; adjusted OR 2.47; 95% CI 1.25–4.88; p = 0.009). Patients with RVO-APS showed a high-risk “aPL profile” (lupus anticoagulant or triple-positive). We did not find any difference regarding classic vascular risk factors, hyperhomocysteinemia, prior vascular events, and carotid plaque, in RVO-patients with or without APS. The phenotype of RVO-APS also differed from APS. Seven patients received anticoagulation and 24 were on low-dose aspirin. After a median follow-up of 62 months, 7 patients suffered a RVO relapse (4 of them had APLs) and no RVO-APS patient had a new thrombotic or vascular event outside the retina.

Conclusions

aPLs were more prevalent in RVO-patients than in controls, and in all patients, APS was not associated with any connective-tissue disease. RVO in the setting of APS seems not only related to atherosclerosis, but also to the “aPL profile”. In most of our RVO-patients with APS, low-dose aspirin was effective to prevent new or recurrent thrombotic events outside the retinal vessels. In these patients, we suggest that RVO could behave as an organ-specific manifestation of APS.

Introduction

Retinal venous occlusion (RVO) represents a common ophthalmological disorder that untreated often leads to severely impaired vision, and, besides, it has been associated with increased cardiovascular mortality [1,2]. Aging and classical vascular risk factors represent the main etiopathogenic factors for RVO, to the extent that, it may be considered as a manifestation of systemic atherosclerosis [2].

A hypercoagulable state has also been involved, as a pathogenic factor, in some patients with RVO [3,4]. Thus, several studies have suggested that antiphospholipid antibodies (aPLs) could play a role in the development of RVO, leading to a prothrombotic vascular endothelial microenvironment [5]. In line with this, we have recently suggested, although based on a minor sample of our RVO-patients and without long-term follow-up, that acquired thrombophilia (antiphospholipid syndrome - APS) should be considered in the clinical assessment of patients with RVO, whereas genetic thrombophilia might be only ruled out in patients aged <50 years [6].

APS is an autoimmune disease characterized by thrombosis and/or pregnancy morbidity in the presence of persistent aPLs [[7], [8], [9]]. The aPL type, their titer, the presence of a single, double or triple type, and the persistence of positive aPLs in repeated samples, has been defined as the “aPL profile” [7,8]. This profile has been related to the risk of thrombotic events and obstetric complications and, therefore, may modulate the intensity of treatment [10]. APS can occur either as an isolated condition or in the setting of another systemic autoimmune disease [10]. Ocular manifestations of APS typically include thromboembolic and neuro-ophthalmic complications [9,11,12]. In this sense, RVO has been reported as an infrequent disorder in APS [9,13,14]. Nevertheless, whether ocular manifestations are directly related or not to the “aPL profile”, and the optimal treatment scheme for these patients, still represent a matter of intense debate [3]. These facts make it often difficult to know the best approach to apply in daily clinical practice for these patients.

Taking into account these considerations, the aim of our study was to assess the prevalence, the association with vascular risk factors, the “aPL profile”, the clinical management and outcome of APS in a large cohort of patients with RVO, with a long-term follow-up, compared with a sample of population-based controls and, for the sake of completeness, with another group of patients with thrombotic non-obstetric APS.

Section snippets

Study participants

We conducted a case-control study of all consecutive patients diagnosed with RVO from December 2008 to March 2019 (“Valdecilla cohort”), and a randomly selected sample of controls of similar age and sex taking part in a population-based prospective cohort in the same geographic area [15,16]. The study was carried out at the University Hospital Marqués de Valdecilla, a tertiary-care center that serves as a reference hospital for a population of 350.000 inhabitants in Northern Spain. According to

General features

During the study period, 331 consecutive patients with RVO (175 men and 156 women; mean age, 68 ± 13 years) and 281 (126 men and 155 women; mean age, 68 ± 9 years) were assessed. Branch RVO was observed in 226 (68%) cases (220 temporal and 6 nasal), and central RVO in 105 (32%). At the time of the initial evaluation, RVO was the first episode in 317 (96%) of our patients and was a relapse in 14 (4%). None of the participants had neither a family history of thrombophilia nor systemic lupus

Discussion

The “Valdecilla cohort” represents a large cohort of patients diagnosed with RVO with ongoing long-term follow-up (up to 11 years). In this study, we have found that 10% of the patients with RVO fulfilled APS criteria and had a higher prevalence of a high-risk “aPL profile” (either LA alone or triple positive: LA plus ACL plus antiβ2GP1) than population-based controls. Furthermore, we have confirmed that RVO-patients have an increased prevalence of classic vascular risk factors and

Conclusion

In conclusion, we found that aPLs were more prevalent in RVO-patients than in population-based controls. RVO as a manifestation of APS could be related not only to atherosclerosis but also to a high-risk “aPL profile”. In these patients, we suggest that RVO could behave as an organ-specific manifestation of the APS. According to our data, we recommend searching for APS in patients newly diagnosed with RVO. Previous and present data point out that in most of the patients with RVO and APS,

Author contribution

JLH, VMT and JJN designed the research, were involved in patient management and collected clinical data; IS, RPM, JMO, ZS, IS, EE collected clinical data. JLH analyzed the data and wrote the manuscript. RPM, VMT, JMO, and JJN critically revised the manuscript. All authors discussed the results and contributed to the final paper.

Funding

The study has been funded in part by the Carlos III Health Institute (PI18/00762) which includes FEDER funds from the EU (Ministry of Economy and Competitiveness, Spain). The funding organization had no role in the design or conduct of this research.

Data availability statement

Due to research still being conducted on the project in our research group full data are not available. Additional data is available upon reasonable request to the corresponding author.

Declaration of competing interest

The authors declare no conflict of interest regarding this paper.

Dr. Hernández reports speaker fees or grants from AMGEM, MSD and Bayer outside the submitted work. Dr. Olmos has received speaker fees form AMGEN and STADA outside the submitted work. The others authors have no disclosure.

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