@article{08074165a2fc412180b4e87c00617ae8,
title = "Peripapillary vessel density changes in Leber's hereditary optic neuropathy: a new biomarker",
abstract = "Importance: The contribution of the microvascular supply to the pathogenesis of Leber's hereditary optic neuropathy (LHON) is poorly understood. Background: We aimed at measuring the peripapillary capillary vessel density (VD) using optical coherence tomography angiography (OCT-A) at different stages of LHON. Design: Prospective, cross-sectional, multicenter, observational study. Participants: Twenty-two LHON patients divided in four groups: unaffected mutation carriers (LHON-u); early sub-acute stage (LHON-e); late sub-acute stage (LHON-l); chronic stage (LHON-ch). Methods: OCT-A scans centred on the optic disc were obtained by spectral domain OCT system. Main Outcome Measures: VD, retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were compared between groups. Results: Significant VD changes were detected in every sector (P <0.0001). In LHON-e, the VD was reduced in the temporal sector compared with LHON-u and in the temporal and inferotemporal sectors compared with controls. In LHON-l, VD was reduced in whole, temporal, superotemporal and inferotemporal sectors compared with LHON-u and controls. In LHON-ch, the VD was reduced in all sectors compared to the other groups. An asynchronous pattern emerged in the temporal sector with VD changes occurring earlier than RNFL thickness changes and together with GC-IPL thinning. Conclusions and Relevance: Significant peripapillary miscrovascular changes were detected over the different stages of LHON. Studying the vascular network separately from fibres revealed that microvascular changes in the temporal sector preceded the changes of RNFL and mirrored the GC-IPL changes. Measurements of the peripapillary vascular network may become a useful biomarker to monitor the disease process, evaluate therapeutic efficacy and elucidate pathophysiology. {\textcopyright} 2018 Royal Australian and New Zealand College of Ophthalmologists",
keywords = "Leber hereditary optic atrophy, OCT-A, optic nerve, optical coherence tomography angiography",
author = "N. Balducci and M.L. Cascavilla and A. Ciardella and {La Morgia}, C. and G. Triolo and V. Parisi and F. Bandello and A.A. Sadun and V. Carelli and P. Barboni",
note = "Cited By :2 Export Date: 25 January 2019 CODEN: CEOPB Correspondence Address: Balducci, N.; Studio Oculistico d'AzeglioItaly; email: balduccinicole@gmail.com Funding text 1: Funding sources: The contribution of GB Bietti Foundation IRCCS was supported by the Italian Ministry of Health and Fondazione Roma. References: Carelli, V., Ross-Cisneros, F.N., Sadun, A.A., Mitochondrial dysfunction as a cause of optic neuropathies (2004) Prog Retin Eye Res, 23, pp. 53-89; Yu-Wai-Man, P., Griffiths, P.G., Chinnery, P.F., Mitochondrial optic neuropathies – disease mechanisms and therapeutic strategies (2011) Prog Retin Eye Res, 30, pp. 81-114; Barboni, P., Carbonelli, M., Savini, G., Natural history of Leber's hereditary optic neuropathy: longitudinal analysis of the retinal nerve fiber layer by optical coherence tomography (2010) Ophthalmology, 117, pp. 623-627; Smith, J.L., Hoyt, W.F., Susac, J.O., Ocular fundus in acute Leber optic neuropathy (1973) Arch Ophthalmol, 90, pp. 349-354; Nikoskelainen, E., Sogg, R.L., Rosenthal, A.R., Friberg, T.R., Dorfman, L.J., The early phase in Leber hereditary optic atrophy (1977) Arch Ophthalmol, 95, pp. 969-978; Nikoskelainen, E., Hoyt, W.F., Nummelin, K., Ophthalmoscopic findings in Leber's hereditary optic neuropathy: I. Fundus findings in asymptomatic family members (1982) Arch Ophthalmol, 100, pp. 1597-1602; Nikoskelainen, E., Hoyt, W.F., Nummelin, K., Ophthalmoscopic findings in Leber's hereditary optic neuropathy: II. The fundus findings in the affected family members (1983) Arch Ophthalmol, 101, pp. 1059-1068; Carelli, V., La Morgia, C., Valentino, M.L., Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders (2009) Biochim Biophys Acta, 1787, pp. 518-528. , Barboni P, Ross-Cisneros FN, Sadun AA; Jia, Y., Morrison, J.C., Tokayer, J., Quantitative OCT angiography of optic nerve blood flow (2012) Biomed Opt Express, 3, pp. 3127-3137; Liu, L., Jia, Y., Takusagawa, H.L., Optical coherence tomography angiography of the peripapillary retina in glaucoma (2015) JAMA Ophthalmol, 133, pp. 1045-1052; Wang, X., Jiang, C., Ko, T., Correlation between optic disc perfusion and glaucomatous severity in patients with open-angle glaucoma: an optical coherence tomography angiography study (2015) Graefes Arch Clin Exp Ophthalmol, 253, pp. 1557-1564; Mwanza, J.C., Budenz, D.L., Optical coherence tomography platforms and parameters for glaucoma diagnosis and progression (2016) Curr Opin Ophthalmol, 27, pp. 102-110; Wang, X., Jia, Y., Spain, R., Optical coherence tomography angiography of optic nerve head and parafovea in multiple sclerosis (2014) Br J Ophthalmol, 98, pp. 1368-1373; Balducci, N., Ciardella, A., Gattergna, R., Optical coherence tomography angiography of the peripapillary retina and optic nerve head in dominant optic atrophy (2017) Mitochondrion, 36, pp. 60-65; Chen, J.J., AbouChehade, J.E., Iezzi, R., Jr., Optical coherence angiographic demonstration of retinal changes from chronic optic neuropathies (2017) Neuro-Ophthalmology, 41, pp. 76-83. , Leavitt JA, Kardon RH; De Rojas, J.O., Rasool, N., Chen, R.W., Optical coherence tomography angiography in Leber hereditary optic neuropathy (2016) Neurology, 87, pp. 2065-2066. , Horowitz J, Odel JG; Takayama, K., Ito, Y., Kaneko, H., Optical coherence tomography angiography in Leber hereditary optic neuropathy (2017) Acta Ophthalmol, 95, pp. e344-e345. , Kataoka K, Ra E, Terasaki H; Falavarjani, G.K., Tian, J.J., Akil, H., Swept source optical coherence tomography angiography of the optic disk in optic neuropathy (2016) Retina, 36, pp. S168-S177. , Garcia GA, Sadda SR, Sadun AA; Matsuzaki, M., Hirami, Y., Uyama, H., Kurimoto, Y., Optical coherence tomography angiography changes in radial peripapillaries in Leber hereditary optic neuropathy (2018) Am J Ophthalmol Case Rep, 9, pp. 51-55; Gaier, E.D., Gittinger, J.W., Cestari, D.M., Miller, J.B., Peripapillary capillary dilatation in Leber hereditary optic neuropathy revealed by optical coherence tomography angiography (2016) JAMA Ophthalmol, 134, pp. 1332-1334; Rao, H.L., Pradhan, Z.S., Weinreb, R.N., Regional comparisons of optical coherence tomography angiography vessel density in primary open angle glaucoma (2016) Am J Ophthalmol, 171, pp. 75-83; Garway-Heath, D.F., Poinoosawmy, D., Fitzke, F.W., Hitchings, R.A., Mapping the visual field to the optic disc in normal tension glaucoma eyes (2000) Ophthalmology, 107, pp. 1809-1815; Balducci, N., Savini, G., Cascavilla, M.L., Macular nerve fibre and ganglion cell layer changes in acute Leber's hereditary optic neuropahy (2016) Br J Ophthalmol, 100, pp. 1232-1237; Sadun, F., De Negri, A.M., Carelli, V., Ophthalmologic findings in a large pedigree of 11778/Haplogroup J Leber hereditary optic neuropathy (2004) Am J Ophthalmol, 137, pp. 271-277; Barboni, P., Savini, G., Feuer, W.J., Retinal nerve fiber layer thickness variability in Leber hereditary optic neuropathy carriers (2012) Eur J Ophthalmol, 22, pp. 985-991; Jia, Y., Simonett, J.M., Wang, J., Wide-field OCT angiography investigation of the relationship between radial Peripapillary capillary plexus density and nerve fiber layer thickness (2017) Invest Ophthalmol Vis Sci, 58, pp. 5188-5194; Ramos Cdo, V., Bellusci, C., Savini, G., Association of optic disc size with development and prognosis of Leber's hereditary optic neuropathy (2009) Invest Ophthalmol Vis Sci, 50, pp. 1666-1674; Sadun, A.A., Win, P.H., Ross-Cisneros, F.N., Leber's hereditary optic neuropathy differentially affects smaller axons in the optic nerve (2000) Trans Am Ophthalmol Soc, 98, pp. 223-232. , Walker SO, Carelli V; Pan, B.X., Ross-Cisneros, F.N., Carelli, V., Mathematically modeling the involvement of axons in Leber's hereditary optic neuropathy (2012) Invest Ophthalmol Vis Sci, 53, pp. 7608-7617; Borrelli, E., Triolo, G., Cascavilla, M.L., Changes in choroidal thickness follow the RNFL changes in Leber's hereditary optic neuropathy (2016) Sci Rep, 6. , 37332",
year = "2018",
doi = "10.1111/ceo.13326",
language = "English",
volume = "46",
pages = "1055--1062",
journal = "Clinical and Experimental Ophthalmology",
issn = "1442-6404",
publisher = "Blackwell Publishing",
number = "9",
}