Abstract
Introduction:
Antiphospholipid syndrome (APS) is an acquired, systemic autoimmune disorder characterized by macrovascular arterial or venous thrombosis, pregnancy morbidly, and/or microvascular phenomena in the setting of antiphospholipid antibodies. There are no strict diagnostic criteria for the clinical diagnosis of APS, but multiple classification criteria were introduced for research purposes. The 2006 Revised Sapporo Classification Criteria requires clinical manifestations as well as persistent positivity of anticardiolipin (aCL), lupus anticoagulant (LAC), or anti-beta2-glycoprotein 1 (anti-β2GPI) antibodies. The 2023 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) Classification Criteria captures new clinical domains including microvascular manifestations, cardiac valve thickening or vegetation, and thrombocytopenia.
The ACR/EULAR Classification Criteria includes retinal vascular occlusions as macrovascular complications of APS. However, the ophthalmology literature contains a broader range of potential manifestations including retinal vascular pruning, central serous chorioretinopathy (CSCR), and ocular inflammation. ACR/EULAR Classification Criteria only include clinical manifestations that have supporting literature and expert consensus. Therefore, unlisted criteria do not imply a definitive lack of association. This study aims to describe the spectrum of ophthalmic conditions associated with APS.
Methods:
A Mass General Brigham Research Patient Data Registry search was conducted to identify patients with APS who underwent an ophthalmic exam at Massachusetts Eye and Ear. Medical records were reviewed by a hematologist to confirm classification of APS based on the 2006 Revised Sapporo and 2023 ACR/EULAR Classification Criteria. Patients were excluded if clinical data was unavailable to the investigators, if the nature of laboratory assay and interpretation could be not verified, or if patients had insufficient titers/were not persistently positive after 12-week interval between testing. Patients not strictly meeting classification criteria were excluded even if they had a clinical diagnosis of APS or were being managed as APS. LAC testing met the recommendations of the International Society of Thrombosis and Haemostasis. ACL and anti-β2GPI IgM and IgG thresholds of moderate (40–79 units) and high (>80 units) were used for results from standardized enzyme-linked immunosorbent assays. Ophthalmic history was reviewed by ophthalmologists to identify retinal vascular, ocular inflammatory, and neuro-ophthalmic findings among patients with confirmed APS.
Results:
Of 75 patients meeting classification criteria for APS, 26 (34.7%) patients exhibited relevant retinal vascular, ocular inflammatory, or neuro-ophthalmic conditions. 19 (73.1%) patients were positive for LAC, 18 (69.2%) for aCL, and 14 (53.8%) for anti-β2GPI antibodies. Peripheral retinal non-perfusion was observed in five of 12 patients for whom widefield fluorescein angiogram was available, predominately in the temporal peripheral retina. Nine patients had CSCR, all of whom were previously exposed to corticosteroids. Four patients had a severe form of CSCR with evidence of extensive subretinal exudation, which correlated to the burden of steroid exposure. Four patients had ocular inflammatory disease (retinal vasculitis, scleritis, interstitial keratitis). Five patients had transient visual obscurations. Six patients with arterial occlusions and two patients with venous occlusions were identified.
Conclusion:
The spectrum of ophthalmic conditions related to APS remains poorly characterized. This study reports retinal vascular, ocular inflammatory, and neuro-ophthalmic conditions observed among a cohort of confirmed APS patients. Few of these conditions are included in the current classification criteria and further investigation will be required to determine true association with APS. A prospective study would help to characterize the full prevalence and spectrum of the ophthalmic manifestations in APS, potentially incorporating correlative biomarkers such as cell-line based complement biosensor assays, markers of immunothrombosis, pro-inflammatory cytokines, and thrombin generation.
