Mitochondrial dysfunction affecting visual pathways.

Mitochondrial dysfunction leads to cellular energetic impairment, which may affect the visual pathways, from the retina to retrochiasmal structures. The most common mitochondrial optic neuropathies include Leber's hereditary optic neuropathy and autosomal dominant optic atrophy, but the optic nerve can be affected in other syndromic conditions, such as Wolfram syndrome and Friedreich's ataxia. These disorders may result from mutations in either the mitochondrial DNA or in the nuclear genes encoding mitochondrial proteins. Despite the inconstant genotype-phenotype correlations, a clinical classification of mitochondrial disorders may be made on the basis of distinct neuro-ophthalmic presentations such as optic neuropathy, pigmentary retinopathy and retrochiasmal visual loss. Although no curative treatments are available at present, recent advances throw new light on the pathophysiology of mitochondrial disorders. Current research raises hopes for novel treatment of hereditary optic neuropathies, particularly through the use of new drugs and mitochondrial gene therapy.

Microcystic macular degeneration in autosomal hereditary optic neuropathies: A cross-sectional retrospective study.

OBJECTIVE: Patients with autosomal optic neuropathies (AON) may develop microcystic macular degeneration (MMD), observed on retinal optical coherence tomography (OCT) examination. This study aimed to report the prevalence of MMD in AON patients and to assess the consequences of MMD on retinal architecture. METHODS: Retrospective single-center study conducted between 2001 and 2018. Patients affected by AON secondary to OPA1 or WFS1 gene mutations were included. The following data were collected: visual acuity, macular volume, vitreomacular interface and presence or absence of MMD. RESULTS: Forty-two subjects (34 OPA1, 8 WFS1) were included. MMD was found in 12 (29%) patients, i.e. 6 of the 8 WFS1 patients (75%) and 6 of the 34 OPA1 patients (17%). In cases with MMD, total retinal volume was greater (P=0.02) in accordance with thickening of the inner nuclear layer (P<0.001). WFS1 subjects had the highest total retinal volume (P=0.01), in relation to a thickening of the inner plexiform layer (P=0.02), inner nuclear layer (P<0.001) and outer plexiform layer (P=0.002). MMD was significantly associated with the WFS1 mutation (P<0.001). No significant association was found between the presence of vitreomacular adhesion and MMD. CONCLUSION: MMD was found in 29% of patients affected by AON and was more frequent in cases with a WFS1 gene mutation. MMD appears to be related to primary ganglion cell degeneration and Müller cell dysfunction. The vitreomacular interface does not appear to play a role in the occurrence of MMD.

[Hereditary optic neuropathies in pediatric ophthalmology]. / Neuropathies optiques héréditaires en ophtalmo-pédiatrie.

INTRODUCTION: Hereditary optic neuropathies (HON) often begin in adulthood. However, some of them can have an early onset. These may have specific clinical features and natural histories. PATIENTS AND METHODS: Retrospective study of HON patients with onset before the age of 14 years seen in a referral center. In addition to the age of onset, we evaluated the genetic etiology, visual acuity at 15 years, last best corrected visual acuity, optic disc appearance, visual field and extra-ophthalmological manifestations. RESULTS: Forty-four patients (16 women) were included; i.e. 27.8% of all patients followed for HON. The mean age of onset was 8.5±3.3 years, with an onset earlier than 3 years in 5 patients. An etiology was not found in 8 patients. Of the remaining 36 patients, 12 had Leber's hereditary optic neuropathy (LHON), 11 had dominant optic atrophy, 12 had WS/WS-like syndrome, 2 had recessive optic atrophy and 1 had spastic paraplegia type 7. For 78 eyes of 40 patients (mean age 26.9±14.5 years), the mean last visual acuity was 0.80±0.33 LogMAR, with differences according to genetic forms. Visual acuity was less than or equal to counting fingers for 7 eyes (29.1%) of 4 WS/WS-like patients and one LHON patient. CONCLUSION: Early onset NOH are not unusual. Their visual prognosis is as severe as adult onset NOH, with variations depending on the underlying genetic causes.

[Hereditary optic neuropathies: from clinical signs to diagnosis]. / Les neuropathies optiques héréditaires: du signe clinique au diagnostic.

Inherited optic atrophy must be considered when working up any optic nerve involvement and any systemic disease with signs of optic atrophy, even with a negative family history. There are two classical forms: dominant optic atrophy, characterized by insidious, bilateral, slowly progressive visual loss and temporal disc pallor, and Leber's optic atrophy, characterized by acute loss of central vision followed by the same event in the fellow eye within a few weeks to months, with disc hyperemia in the acute phase. Family history is critical for diagnosis. In the absence of family history, the clinician must rule out an identifiable acquired cause, i.e. toxic, inflammatory, perinatal injury, traumatic or tumoral, with orbital and brain imaging (MRI). Recessive optic atrophies are more rare and more severe and occur as part of multisystemic disorders, particularly Wolfram syndrome (diabetes mellitus, diabetes insipidus, and hearing loss). Effective treatments are limited; alcohol and smoking should be avoided. A cyclosporine trial (taken immediately upon visual loss in the first eye) is in progress in Leber's optic atrophy to prevent involvement of the fellow eye.