Occurrence and pattern of ocular disease in children with cholestatic disorders

Abstract

ABSTRACT.Purpose: To describe visual function and ocular manifestations in patients with onset of cholestasis during the neonatal period. Methods: Patients with neonatal cholestasis, either transitory or chronic, who came for assessment to our tertiary referral centre were included in a crosssectional study and underwent ophthalmological examinations including fundus photography. A total of 57 patients (24 girls and 33 boys), aged 0.4-18.0 years, were included. Of these, 28 patients had biliary atresia, 11 had Alagille's syndrome, five had progressive familiar intrahepatic cholestasis and nine had different disorders such as pituitary insufficiency, alpha-1-antitrypsin deficiency, mitochondriopathy, congenital infections or cholestasis caused by unknown reasons. Results: Visual dysfunction and ⁄ or one or several ocular manifestations occurred in 39 out of 57 patients. Major ocular malformations occurred in five patients. Out of three patients with biliary atresia, one patient had severe visual impairment caused by microphthalmia and chorioretinal coloboma, one patient with Cat Eye syndrome had bilateral uveochorioretinal coloboma and one patient had Rieger's anomaly. Two patients, both with pituitary deficiency and transient cholestasis, had severe unilateral visual impairment caused by optic nerve hypoplasia. Conclusion: The majority (68%) of the patients with cholestasis had ocular manifestations. Although the severity of ocular complications varied with diagnosis, and was most apparent among patients with biliary atresia or pituitary deficiency, no conclusion can be drawn regarding the connections between these conditions from the present study. Nevertheless, ocular assessment is important for diagnostic purposes and for early intervention in patients with cholestasis.

Clinical practice

“…Ocular manifestations which can be found are posterior embryotoxon in Alagille syndrome, optic nerve hypoplasia which can be associated with panhypopituitarism, chorioretinitis in congenital infections, cataract in intra-uterine infections or galactosaemia and ocular coloboma in Cat Eye syndrome [9].…”

Sex differences and risk factors for bleeding in Alagille syndrome

“…Dolichoectasia is fairly common in Alagille syndrome: vascular neuroimaging of a cohort of 19 patients identified neurovascular defects in six patients, of which four were dolichoectasia (4/19 = 21%) 10 . Previous reports qualitatively described retinal vasculature from patients with ALGS as tortuous or with abnormally angulated vessels 128,129,146 . In our study, five of six patients with ALGS (83%) had tortuous venules (tortuosity above 5%), while patients with BA and control patients were consistently under 5%, suggesting venous vessel tortuosity as a suitable additional diagnostic feature.…”

“…Finally, we analyzed retinal fundus photographs from pediatric patients with ALGS, biliary atresia (BA, as cholestatic controls), and age-matched healthy control patients (previously reported in 128,135 ) (Figure 8A). Similar to the Jag1 Ndr/Ndr mice (Figure 4A, B), arteriovenous crossings were significantly increased in patients with ALGS compared to the control group (Figure 8G).…”

“…The retina fundus photographs were analyzed from seven healthy pediatric control patients (median age 8 years, range 7 -8 years; 1 male, 6 females), six patients with ALGS (median age 7.5 years, range 2 -11 years; 1 male, 5 females), four patients with BA (median age 10.5 years, range 8 -16 years; 1 male, 3 females). The patients included in this study and/or their guardians gave written informed consent, and were previously reported in part 128,135 .…”

“…Vascular defects identified in Jag1 Ndr/Ndr mice can be quantified non-invasively in patients with Alagille syndrome using retina fundus photography. Previous reports have shown that patients with ALGS have abnormal retinal vasculature [128][129][130][131] , but the degree of tortuosity and patterning defects have not been quantified, nor compared to animal models, or CADASIL. We first analyzed retinal vasculature in a previously reported cohort of CADASIL patients 132,133 .…”