Leber's hereditary optic neuropathy: Shifting our attention to the macula

Abstract

PurposePeripapillary vascular alterations have been classically described as hallmarks of Leber's Hereditary Optic Neuropathy (LHON). We recently demonstrated microvascular pathology involving the macula in patients affected with chronic LHON using optical coherence tomography angiography (OCTA). Macular vascular pathology in acute LHON has not previously been reported.MethodsThe macular superficial vasculature of an asymptomatic carrier and an affected patient with acute LHON, mitochondrial DNA mutation 3460, was assessed by OCTA.ResultsSimilar findings of peripapillary microangiopathy and vascular telangiectasias were seen the affected patient, but in the parafoveal macula. These changes were most prominent nasally and inferiorly, corresponding to the proximal portions of the papillomacular bundle. The foveal avascular zone was markedly enlarged in the affected patient relative to the asymptomatic mother.ConclusionsThese findings in acute LHON further supports the clinical utility of vascular parameters and suggest that further studies focused on macular pathology may be warranted to assess the natural history of LHON.

OCTA in neurodegenerative optic neuropathies: emerging biomarkers at the eye–brain interface

“…In contrast, the patient's right eye revealed increased perfusion for both temporal and nasal regions relative to both the patient's left eye (l) and the unaffected eye (j) from Asanad and colleagues. 82,83 Consequently, diagnostic work-up commonly follows incidental visual field findings, pertinent family history, or optic atrophy on funduscopic examination. 89 DOA pathophysiology has been suggested to involve a neurodegenerative etiology.…”

“…In contrast, the patient’s right eye revealed increased perfusion for both temporal and nasal regions relative to both the patient’s left eye (l) and the unaffected eye (j) from Asanad and colleagues. 82 , 83 …”

“…81 In addition to the peripapillary region, OCTA studies have also provided evidence of pathology associated with the macular vasculature in different disease stages of LHON. [82][83][84] OCTA in acute LHON showed increased vascular perfusion along with microangiopathic vascular telangiectasias (Figure 2), whereas subacute LHON featured vascular attrition of the FAZ, which was markedly enlarged. 84 Borrelli and colleagues showed quantitative differences in the macular retinal and choroidal circulation in chronic LHON.…”

Improving the visual outcome in Leber's hereditary optic neuropathy: Framework for the future

“…Intriguingly, vessel attrition corresponded with loss of the retinal ganglion cell-inner plexiform layer (RGC-IPL) and preceded thinning of the retinal nerve fiber layer (RNFL) 4 . In addition to the peripapillary vasculature, recent OCTA studies conducted by our laboratory revealed vascular pathology also in the macula for both chronic and acute disease stages of LHON 1, 5. Borrelli et al.…”

“…Intriguingly, OCTA of the subacute stage showed vascular attrition with marked enlargement of the foveal avascular zone. In contradistinction, the acute stage exhibited increased vascular perfusion with evidence of microangiopathy and vascular telangiectasias 5 . Similar to chronic LHON, these early vascular changes coincided with loss of the PMB,6, 7 which contains the smallest RGC fibers that are the most vulnerable to mitochondrial dysfunction 8, 9.…”