Electrophysiological and Structural Changes in Chinese Patients with LHON

Abstract

Objective. To review retrospectively the electrophysiological and structural changes in 13 Chinese patients with Leber hereditary optic neuropathy (LHON). Methods. 26 eyes of 13 patients with a genetically confirmed diagnosis of LHON were categorized into two groups according to the duration of the disease: group 1 (duration less than 3 months) and group 2 (duration between 3 months and 18 years). Clinical history, comprehensive visual electrophysiology, optical coherence tomography (OCT), and color fundus photography were performed. Results. Fundoscopy showed optic disc hyperemia in group 1 and optic atrophy in group 2. OCT measures of retinal nerve fiber layer (RNFL) thickness around the optic disc and surrounding macula were normal in group 1 but reduced in group 2 (10 of 10 eyes). The thickness of the retinal ganglion cell layer (GCL) plus inner plexiform layer (IPL) surrounding the macula reduced significantly in group 1 and group 2 compared with a healthy control group. Pattern ERG (PERG) P50 amplitude was normal, but the N95/P50 ratio reduced in most of group 1 (4 of 5 eyes) and in all of group 2 (11 eyes). PERG P50 peak time was abnormally short in group 2. Multifocal electroretinography (mfERG) showed subnormal responses associated with ring 1 (the central area) and ring 2 in group 1 and reductions in rings 1, 2, and 3 in group 2. Conclusion. The study highlights differences in retinal structure and function between the acute and chronic stages of LHON in a group of Chinese patients. There is PERG evidence of retinal ganglion cell dysfunction and OCT evidence of GCL + IPL thinning in both groups, but there is additional peripapillary RNFL loss in the chronic stage, associated with more severe RGC dysfunction. There is multifocal ERG evidence of localized macular dysfunction in both acute and chronic groups. The study highlights the importance of comprehensive electrophysiological and structural assessments of the retina in LHON and is pertinent to studies that aim to monitor disease progression or the effects of future therapeutic interventions.

Very Early Onset of Leber’s Mitochondrial Optic Neuropathy in Pediatric Females: Case Report and Review of the Literature

“…In our study the female/male ratio was of about 1:1,8. Diversity between pediatric and adult age is explainable by being more heavily genetically determined by nuclear modi ers, and by lower hormonal and environmental in uences in childhood LHON [4,5,13,104].…”

“…The LHON diagnosis needs to be con rmed by detection of mutations in mtDNA: methods such as direct DNA sequencing, polymerase chain reaction, restriction fragment length polymorphism and next generation sequencing techniques can be used to nd mtDNA mutations [13]. One of the possible reasons for the rarity of disease onset at very early age is that the signi cant complex I dysfunction, needed for mitochondrial related optic nerve damage, requires time and usually does not occur before school-age [102].…”

“…Males are mostly affected in their second or third decade of life: patients with classic LHON experience visual loss between 15 to 35 years of age, childhood onset occurs in 11,5% of the cases [3]. The age limit for childhood onset is variable according to different studies: mean age at onset of the disease is about 6,8 years of age (range 2-11y) in European centers and about 10 years (mean 8,7 years, range 3,[4][5][6][7][8][9][10][11][12][13][14][15][16][17] in the Chinese population [4,5,6]. In childhood also, males are more affected than females [4,6].…”

Neuroanatomical Changes in Leber’s Hereditary Optic Neuropathy: Clinical Application of 7T MRI Submillimeter Morphometry

“…Nevertheless, DTI studies focused on optic nerve quantitative assessment between chronic LHON patients and normal control subjects showed no correlation between illness duration and DTI parameters and suggest that damage along the visual pathways may occur relatively early from the disease’s clinical onset, or could be already present when the first symptoms are reported by the patient [ 46 ]. Ophthalmologic studies focused on the progressive changes in LHON patients showed structural changes in the ganglion cell layer and inner plexiform layer [ 47 ], as well as RNFL thickening [ 27 ]. Ventricle enlargement and increased CSF volume are reliable morphometric features of neural atrophy.…”

Idebenone – a new drug for patients with Leber's hereditary optic neuropathy

“…Electrophysiologic studies (pattern electroretinogram [PERG], multifocal electroretinogram [mfERG], and visual evoked potentials [VEP]) may be helpful in unclear cases. Genetic testing is the conclusive test [5][6][7]. Sometimes, ophthalmic symptoms are accompanied by osteoarticular, cardiac (arrhythmia), or neurological pathologies such as neuropathy, dystonia, dysarthria, or myopathy.…”