Fabry disease (FD) is characterized by a deficiency in α-galactosidase A activity that leads to the cumulative deposition of unmetabolized glycosphingolipids within organs, including the vascular endothelium and the eyes. The purpose of this study was to assess the effects of FD on the retinal microvasculature, foveal avascular zone (FAZ), macular thickness and retinal nerve fiber layer (RNFL) using optical coherence tomography angiography (OCT-A).
Twenty-five patients (14 female and 11 male; mean age 33.16 ± 11.44) with genetically verified FD were compared with 37 age- and sex-matched healthy controls (mean age 32.36 ± 15.54). The vessel density (VD) values of the superficial and deep capillary plexuses (SCP and DCP), the area of the FAZ, the density of radial peripapillary capillaries (RPC), the macular thickness and the retinal nerve fiber layer thickness were measured by OCT-A examination.
The patients showed significantly lower VD values than controls in the foveal regions of both SCP and the DCP (21.15 ± 5.56 vs. 23.79 ± 4.64 (p = 0.048), 37.92 ± 6.78 vs. 41.11 ± 5.59 (p = 0.048), respectively). The FAZ was significantly larger in the FD group than in the control group (0.3 ± 0.1 vs. 0.24 ± 0.08 (p = 0.011)). No significant difference was identified in measurements of RPC density, peripapillary RNFL thickness or macular thickness between the two groups (p > 0.05 for all).
Decreased VD and an enlarged foveal avascular area suggest possible changes in the retinal microvasculature of patients with FD. OCT-A can serve as a useful, noninvasive, quantitative tool for diagnosing FD and monitoring its progression.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Germain DP (2010) Fabry disease. Orphanet J Rare Dis 5(1):30
Germain DP (2002) Fabry’s disease (alpha-galactosidase-A deficiency): recent therapeutic innovations. J Soc Biol 196(2):183–190
Poorthuis BJ, Wevers RA, Kleijer WJ, Groener JE, de Jong JG, van Weely S, Niezen-Koning KE, van Diggelen OP (1999) The frequency of lysosomal storage diseases in the Netherlands. Hum Genet 105(1–2):151–156
Spada M, Pagliardini S, Yasuda M, Thiagarajan G, Sakuraba H, Ponzone A, Desnick RJ (2006) High incidence of later onset Fabry disease revealed by newborn screening. Am J Hum Genet 79(1):31–40
Mehta A, Beck M, Elliott P, Giugliani R, Linhart A, Sunder-Plassmann G, Schiffmann R, Barbey F, Ries M, Clarke JT, Fabry Outcome Survey İnvestigators (2009) Enzyme replacement therapy with agalsidase alfa in patients with Fabry’s disease: an analysis of registry data. Lancet 374(9706):1986–1996
Samiy N (2008) Ocular features of Fabry disease: diagnosis of a treatable life-threatening disorder. Surv Ophthalmol 53(4):416–423
Bitirgen G, Turkmen K, Malik RA, Ozkagnici A, Zengin N (2018) Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease. Sci Rep 8(1):12244
Sodi A, Ioannidis A, Mehta A, Davey C, Beck M, Pitz S (2007) Ocular manifestations of Fabry disease: data from the Fabry Outcome Survey. Br J Ophthalmol 91(2):210–214
Morrier AM, Minteer J, Tyszko R, McCann R, Clarke MV, Browning MF (2010) Ocular manifestations of Fabry disease within in a single kindred. Optometry 81(9):437–449
Michaud L (2019) Longitudinal study on ocular manifestations in a cohort of patients with Fabry disease. PLoS ONE 14(6):e0213329
Sher NA, Letson RD, Desnick RJ (1979) The ocular manifestations in Fabry’s disease. Arch Ophthalmol 97(4):671–676
Franceschetti AT (1976) Fabry disease: ocular manifestations. Birth Defects Orig Artic Ser 12(3):195–208
Nguyen TT, Gin T, Nicholls K, Low M, Galanos J, Crawford A (2005) Ophthalmological manifestations of Fabry disease: a survey of patients at the Royal Melbourne Fabry Disease Treatment Centre. Clin Exp Ophthalmol 33(2):164–168
Libert J, Toussaint D (1982) Tortuosities of retinal and conjunctival vessels storage diseases. Birth Defects Orig Artic Ser 18(6):347–358
Sivley MD (2013) Fabry disease: a review of ophthalmic and systemic manifestations. Optom Vis Sci 90(2):e63–e78
Ramaswami U, Wendt S, Pintos-Morell G, Parini R, Whybra C, Leon Leal JA, Santus F, Beck M (2007) Enzyme replacement therapy with agalsidase alfa in children with Fabry disease. Acta Paediatr 96(1):122–127
Huang D, Jia Y, Gao SS, Lumbroso B, Rispoli M (2016) Optical coherence tomography angiography using the optovue device. Dev Ophthalmol 56:6–12
Lavia C, Bonnin S, Maule M, Erginay A, Tadayoni R, Gaudric A (2019) Vessel density of superficial, ıntermediate, and deep capillary plexuses using optical coherence tomography angiography. Retina 39(2):247–258
Mo S, Phillips E, Krawitz BD, Garg R, Salim S, Geyman LS et al (2017) Visualization of radial peripapillary capillaries using optical coherence tomography angiography: the effect of ımage averaging. PLoS ONE 12(1):e0169385
Hilz MJ, Kolodny EH, Brys M, Stemper B, Haendl T, Marthol H (2004) Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease. J Neurol 251(5):564–570
Kolodny EH, Pastores GM (2002) Anderson-Fabry disease: extrarenal, neurologic manifestations. J Am Soc Nephrol 13(2):S150–S153
Desnick RJ, Ioannou YA, Eng CM (2001) Alpha-galactosidase A deficiency: Fabry’s disease. In: Scriever CR, Beaudet AL, Sly WS, Valle D (eds) Metabolic and molecular bases of ınherited disease, 8th edn. McGraw-Hill, New York, pp 3733–3774
Utsumi K, Ueda K, Watanabe M, Sakamaki M, Arii K, Yamazaki M, Komaba Y, Katsura K, Iino Y, Katayama Y (2009) Thrombosis in Japanese patients with Fabry disease. J Neurol Sci 283(1–2):83–85
Sher NA, Reiff W, Letson RD, Desnick RJ (1978) Central retinal artery occlusion complicating Fabry’s disease. Arch Ophthalmol 96(5):815–817
Ersoz MG, Ture G (2018) Cilioretinal artery occlusion and anterior ischemic optic neuropathy as the initial presentation in a child female carrier of Fabry disease. Int Ophthalmol 38(2):771–773
Abe H, Sakai T, Sawaguchi S, Hasegawa S, Takagi M, Yoshizawa T, Usui T, Horikawa Y (1992) Ischemic optic neuropathy in a female carrier with Fabry’s disease. Ophthalmologica 205:83–88
Pitz S, Grube-Einwald K, Renieri G, Reinke J (2009) Subclinical optic neuropathy in Fabry disease. Ophthalmic Genet 30(4):165–171
Cennamo G, Di Maio LG, Montorio D, Tranfa F, Russo C, Pontillo G, Cocozza S, Esposito R, Di Risi T, Imbriaco M, Spinelli L, Riccio E, Pisani A (2019) Optical coherence tomography angiography findings in Fabry disease. J Clin Med 8:528
Baur J, Al-Sheikh M, Barthelmes D, Nowak A, Böni C, Zweifel AS (2018) Optical Coherence Tomography Angiography findings in patients with Fabry’s disease. Investig Ophthalmol Vis Sci 59:4249
Finocchio L, Sodi A, Bacherini D et al (2018) Optical coherence tomography angiography in Fabry disease. Investig Ophthalmol Vis Sci 59:2838
Utsumi K, Yamamoto N, Kase R, Takata T, Okumiya T, Saito H, Suzuki T, Uyama E, Sakuraba H (1997) High incidence of thrombosis in Fabry’s disease. Intern Med 36(5):327–329
San Román I, Rodríguez ME, Caporossi O, Zoppetti C, Sodi A, Mecocci A, López D, Rodríguez B, Gimeno JR (2017) Computer assisted retinal vessel tortuosity evaluation in novel mutation Fabry disease: towards new prognostic markers. Retina 37(3):592–603
Pitz S, Kalkum G, Arash L, Karabul N, Sodi A, Larroque S, Beck M, Gal A (2015) Ocular signs correlate well with disease severity and genotype in Fabry disease. PLoS ONE 10(3):e0120814
Orssaud C, Dufier J, Germain D (2003) Ocular manifestations in Fabry disease: a survey of 32 hemizygous male patients. Ophthalmic Genet 24(3):129–139
Liasis A, Ioannidis A, Thompson D, Davey C, Nischal K (2006) Visual electrophysiology in patients with Anderson-Fabry disease. Acta Paediatr Suppl 451:119
Hufendiek K, Kaufeld J, Volkmann I, Brockmann D, Awe M, Kromer R, Hufendiek K, Junker B, Framme C (2018) Density of the retinal blood flow and thickness mapping by spectralis OCT in patients with Fabry disease. Investig Ophthalmol Vis Sci 59:5460
Minnella AM, Barbano L, Verrecchia E, Martelli F, Pagliei V, Gambini G et al (2019) Macular impairment in Fabry disease: a morphofunctional assessment by sweptsource OCT angiography and focal electroretinography. Invest Ophthalmol Vis Sci 60:2667–2675
Scientific Research Projects Management Unit of Hatay Mustafa Kemal University (TR).
This study was supported and funded by grants from the Scientific Research Projects Management Unit of Hatay Mustafa Kemal University (TR). The Grant number is 18.A.006.
Conflict of interest
The authors declare that there is no conflict of interest.
The present study was approved by the Ethics Committee of Hatay Mustafa Kemal University Tayfur Ata Sokmen Medical Faculty. All procedures in the study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Written informed consent was obtained from all participants.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Cakmak, A.I., Atalay, E., Cankurtaran, V. et al. Optical coherence tomography angiography analysis of fabry disease. Int Ophthalmol (2020). https://doi.org/10.1007/s10792-020-01486-2
- Fabry disease
- Optical coherence tomography angiography
- Retinal vessel density
- Radial peripapillary capillaries
- Peripapillary retinal nerve fiber layer