Author: Christine Bourke (Ireland)
Co-authors: Kirk A.J Stephenson, James J. O'Byrne, David Keegan
The purpose of this study was to evaluate the ocular manifestations in a cohort of Fabry patients referred to a teritary referral centre in Dublin, Ireland. Fabry disease is type of lysosomal storage disease caused by an inability to metabolize globotriaosylceramide due to a deficiency of α-galactoside A, resulting in the accumulation of globotriaosylceramide in lysosomes. The disease is an incredibly rare X-linked disorder, neither dominant or recessive. Ophthalmic findings in Fabry disease include corneal verticillata, conjunctival intracellular inclusions, retinal vessel tortuosity, retinal microaneurysms and optic disc edema. Posterior subcapsular cataracts are so common that they are sometimes termed Fabry cataracts. Non-ocular manifestations of Fabry disease are neuropathic pain, angiokeratomas, renal failure and deafness. Patients frequently do not live beyond the fourth or fifth decade of life. Fabry disease is common in certain geographically isolated populations (e.g.Finland, Iceland, Irish travellers). There are an estimated 51 patients in Ireland with Fabry disease . Here we describe the ophthalmic findings of an Irish Fabry disease cohort.
Mater Clinical Ophthalmic Genetics Unit, Mater Misericordiae University Hospital, Dublin, Ireland. National Centre for Inherited Metabolic Disease, Mater Misericordiae University Hospital
The patient cohort was identified from referrals to the inherited retinal disease clinic from the national centre for Inherited Metabolic Conditions during the years 2017-2020. All patients provided informed consent and the study abided by the Declaration of Helsinki. A thorough clinical history was complemented by examination including LogMAR VA, dilated slit lamp biomicroscopy, corneal tomography (Pentacam, Oculus Gmbh, Germany) widefield retinal colour imaging and autofluorescence (Optos California, Optos plc, UK), and optical coherence tomography (OCT, Cirrus 600 OCT, Carl Zeiss MediTec, Dublin, USA). Genotyping records were available from an accredited laboratory (Manchester Centre for Genomic Medicine, Manchester, UK). Data was entered onto an Excel worksheet as well as the target 5000 genetic database for Ireland.
12 patients with Fabry disease (8 females 4 males) were included in the population to be assessed. Due to the nature of the Covid-19 pandemic at the time of commencing the study, non-attendance was a predominant but understandable issue. Of the 12 patients 3 did not want to be included in the study amid covid fears and due to a lack of any eye symptoms. Thus the sample size was reduced to 9 patients (4 M 5 F). Mean visual acuity was 0.00. All 9 patients had corneal verticillata. 67% (6) had posterior subcapsular cataracts, only one patient was experiencing symptoms of scotopic glare. 22% (2) had retinal arteriolar attenuation.One patient had an entropion causing severe corneal surface disease and was referred for surgery. No patients had significant visual loss. We will show imaging of our findings in the poster.
Corneal verticillata presents early and is seen in up to 70% of patients with Fabry disease; this finding is borne out in our patient cohort. The presence of verticillata requires further evaluation if observed in an otherwise asymptomatic patient. Of note there were a significantly higher number of females in our patient cohort, Fabry disease is an X linked condition with high penetrance in females, at least 70% of females show clincal manifestations of the disease. Fortunately this patient cohort didn’t suffer from many ocular comorbidities, one patient was listed for cataract surgery with all others being reviewed routinely at two yearly intervals. Due to the Covid19 pandemic non-attendance was an issue. In Ireland, Fabry disease is well-managed by a paediatric and adult national metabolic service coordinating the multitude of subspecialty multidisciplinary input for these patients from cardiology, audiology, ophthalmology, clinical genetics and beyond. This provides an ideal conduit for ophthalmic assessment and optimization of visual function.