Peripapillary microcirculation in Leber hereditary optic neuropathy

Abstract

Purpose In this prospective observational comparative case series, we aimed to study the peripapillary capillary network with spectral‐domain optical coherence tomography angiography (OCT‐A) in Leber hereditary optic neuropathy (LHON). Methods Twelve eyes of six individuals, of these three males (five eyes) after clinical onset of visual impairment were imaged by OCT‐A with scans centred on optic discs. Control group consisted of 6 eyes with no visual impairment. Results The three affected individuals lost vision 6 years (at age 22 years), 2 years and 3 months (at age 26 years) and 1 year and 2 months (at age 30 years) prior to OCT‐A examination. All five affected eyes had alterations in density of the radial peripapillary microvascular network at the level of retinal nerve fibre layer, including an eye of a patient treated with idebenone that underwent almost full recovery (best corrected visual acuity 0.87). Interestingly, the other eye showed normal ocular findings 14 months after onset. Results of OCT‐A examination in this eye were unfortunately inconclusive due to a delineation error. At the level of the ganglion cell layer differences could be also noted, but only in two severely affected individuals. There were no differences between unaffected mutation carriers and control eyes. Conclusion Optical coherence tomography angiography scans confirmed that the peripapillary microvascular network is highly abnormal in eyes manifesting visual impairment due to LHON. These findings support the hypothesis that microangiopathy contributes to the development of vision loss in this mitochondrial disorder.

Changes in Retinal Perfusion in Leber’s Hereditary Optic Neuropathy: An Optical Coherence Tomography-Angiography Study

“…Only 3 studies and a few case reports have quantitatively evaluated the peripapillary or parafoveal microvascular changes in LHON [21-24]. Kousal et al [23] and Balducci et al [21] found that the RPC vessel density in the peripapillary area is reduced in the chronic stage of LHON [21, 23], and Borrelli et al [22] showed that the parafoveal vessel density in the macular area was lower in 29 eyes of LHON patients than in the controls. In the present study, we found that the RGCs (IRT and RNFL) and the retinal vessels supplying the RGCs (SCP and RPC vessel density) were both reduced in patients with chronic-stage LHON compared with those in the controls.…”

Optical Coherence Tomography Angiography in Neurodegenerative Disorders

“…The disease is associated with distinctive abnormalities of peripapillary blood vessels including telangiectatic microangiopathy and small vessel tortuosity [ 109 ]. A prospective multicenter study reported a reduction in vascular blood flow in the temporal sector of the optic nerve in the subacute phase of Leber’s hereditary optic neuropathy, and a reduction in all sectors in the chronic phase [ 110 ]. Borrelli et al showed that eyes with Leber’s hereditary optic neuropathy present SCP and DCP changes that are mainly confined to the nasal and inferior parafoveal sectors corresponding to the papillomacular bundle.…”

Exploiting hiPSCs in Leber's Hereditary Optic Neuropathy (LHON): Present Achievements and Future Perspectives

“…This amelioration of the reprogramming efficiency is relevant not only to obtain enough biological material for further investigations but could also unravel an insight into pathogenic mechanisms, relevant for the disease, and for the development of targeted effective therapy. Remarkably, the subacute phase of LHON is hallmarked by well-known vascular changes, and ongoing discussions revolve around the issue of pseudo-hypoxic signaling that RGCs may produce as their metabolic unbalance reaches the threshold for triggering the disease, possibly underlying the microangiopathy in LHON ( 3 , 4 , 47 , 48 ).…”