Evaluation of retinal microvascular perfusion in hereditary angioedema: a case-control study

Abstract

Evidence supports that hereditary angioedema (HAE) may be considered as a paroxysmal permeability disorder with defective but self-limiting endothelial barrier dysfunction. A potential subclinical abnormal vascular permeability at retinal capillaries could induce damage resulting in retinopathy. We aimed at exploring for the first time the presence of microangiopathy at retinal level from a highly selective cohort of patients with HAE due to C1 esterase inhibitor protein (C1INH) deficiency (type I). We conducted a pilot, prospective, case-control study including 20 type I HAE patients and 20 age−/sex-matched healthy controls (HC). All participants underwent standard ophthalmological examination including visual fields. Superficial and deep capillary plexi in the retina were analyzed by using new optical coherence tomography angiography (OCT-A). A total of 40 eyes from 20 HAE patients and 20 eyes from HC were evaluated. Perimetric indices of visual field were slightly worse in HAE than in controls. OCT-angiograms documented in HAE patients a lower retinal capillary density in both superficial and deep scans and a higher retinal thickness compared to healthy eyes. Our findings firstly documented subclinical abnormalities in retinal microvascular network in type I HAE patients that might be associated with early subtle functional changes. This preliminary evidence supports the hypothesis of a recurrent endothelial barrier failure at retinal level in HAE patients potentially resulting in chronic damage.

Subclinical Signs of Retinal Involvement in Hereditary Angioedema

“…Inclusion criteria were: (1) diagnosis of type I HAE with subcutaneous non-inflammatory self-limiting angioedema, and with both low serum levels of C1INH antigen and C1-INH function below 50% of normal [25,26,30]; (2) age ≥ 18 years old and ≤75 years old;…”

“…(5) spherical equivalent refractive error between −6.0 and +4.0 diopters [30,34]. Exclusion criteria were: (1) established primary ocular diseases including ocular trauma or surgery;…”

“…(5) pregnancy or lactation; (6) neoplasia; and (7) systemic treatments that may affect retinal function. Subjects were also excluded if they presented with a glaucomatous optic nerve configuration [30,32,34].…”

“…We recently documented, for the first time, subclinical abnormalities in the retinal microvascular network in type I HAE that could be related to early subtle functional changes [30].…”

“…Starting from that intriguing evidence, we aimed at exploring morphologic retinal status from a highly selective cohort of type I HAE patients by using new spectral-domain optical coherence tomography (SD-OCT) [31][32][33]. Furthermore, retinal capillary plexi have been analyzed using OCT-angiography (OCT-A) from all the subjects in the study [30].…”