Peripapillary and macular morpho-vascular changes in patients with genetic or clinical diagnosis of autosomal dominant optic atrophy: a case-control study

  • Amélia MartinsEmail author
  • Tiago M. Rodrigues
  • Mário Soares
  • Michael-John Dolan
  • Joaquim N. Murta
  • Rufino Silva
  • João P. Marques



To evaluate the macular and peripapillary morpho-vascular changes in ADOA, using optical coherence tomography (OCT) and OCT angiography (OCTA).


Prospectively defined, cross-sectional case-control study. Consecutive patients with a genetic or clinical diagnosis of ADOA along with age- and sex-matched controls were included. The radial peripapillary capillary (RPC) density and vessel density (VD) in the parafoveal superficial and deep capillary plexuses (SCP and DCP, respectively) were evaluated with OCTA. The ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) thickness were determined using structural OCT. We applied a previously validated customized macro (Fiji, SciJava Consortium) to compute RPC density. The remaining parameters were calculated by the built-in software. Non-parametric methods were used for data analysis. The target α level was 0.05, which was adjusted through Bonferroni’s correction when multiple outcomes were tested.


Fifty-eight eyes (n = 29 control; n = 29 ADOA) from 30 subjects (mean age 42.43 ± 15.30 years; 37.93% male) were included. Parafoveal SCP VD, GCC thickness, RPC VD in the temporal quadrant, as well as RNFL thickness in the nasal and temporal quadrants were decreased in ADOA eyes (all p < 0.001). When only patients with genetically confirmed diagnosis were included, capillary dropout in the circumpapillary superior and inferior quadrants also became evident (both p < 0.001). The GCC/parafoveal SCP ratio was increased in ADOA, relatively to matched controls. In contrast, none of the circumpapillary morpho-vascular ratios was significantly different in ADOA eyes.


The microvascular and structural changes found in ADOA suggest that both the macular and peripapillary regions are involved, although the threshold for damage of the structural and vascular components may be different for each region. Larger series with longitudinal follow-up may validate OCTA biomarkers helpful for disease monitoring.


Autosomal dominant optic atrophy Morpho-vascular changes Optical coherence tomography angiography Radial peripapillary capillary Parafoveal capillary plexus 



This was an academic research project, with no specific funding available.

Compliance with ethical standards

Conflict of interest

J.P.M. performs consulting services for Bayer. J.N.M. is a member of the scientific Advisory Board of Alcon. R.S. is a member of the Advisory Board for Bayer, Allergan, Novartis, Alcon, THEA and Alimera. The remaining authors have no conflict of interest to disclose. None of the authors has any financial or non-financial interest in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments and this research project was approved by the institutional research committee of Centro Hospitalar e Universitário de Coimbra (CHUC).

Informed consent

Oral and written informed consent was obtained from all individual participants included in this study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of OphthalmologyCentro Hospitalar e Universitário de Coimbra (CHUC)CoimbraPortugal
  2. 2.Instituto de Medicina Molecular, Faculdade de MedicinaUniversidade de Lisboa (FMUL)LisbonPortugal
  3. 3.Institute of Molecular and Clinical Ophthalmology Basel (IOB)BaselSwitzerland
  4. 4.Janelia Research Campus, Howard Hughes Medical InstituteAshburnUSA
  5. 5.Stanley Center for Psychiatric ResearchBroad Institute of MIT and HarvardCambridgeUSA
  6. 6.Coimbra Institute for Clinical and Biomedical Research, Faculty of MedicineUniversity of Coimbra (iCBR-FMUC)CoimbraPortugal
  7. 7.Association for Innovation and Biomedical Research on Light and Imaging (AIBILI)CoimbraPortugal

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