In the acute stage, lasting a few weeks, the affected eye demonstrates an oedematous appearance of the nerve fiber layer, especially in the arcuate bundles and enlarged or telangiectatic and tortuous peripapillary vessels (microangiopathy). The main features are seen on fundus examination, just before or after the onset of visual loss. A pupillary defect may be visible in the acute stage as well. Examination reveals decreased visual acuity, loss of color vision and a cecocentral scotoma on visual field examination. LHON with demyelinating lesions or LHON Plus
LHON Plus is a rare variant of the disorder with eye disease together with other conditions. Its symptoms include loss of the brains ability to control the movement of muscles, tremors, and cardiac arrhythmia. Many cases of LHON plus have been compared to multiple sclerosis because of the lack of muscular control and the presence of demyelinating lesions in the CNS. It is therefore a subtype of MS, according to McDonalds definition. Genetics
Leber hereditary optic neuropathy is a condition related to changes in mitochondrial DNA. Although most DNA is packaged in chromosomes within the nucleus, mitochondria have a distinct mitochondrial genome composed of mtDNA.Mutations in the MT-ND1, MT-ND4, MT-ND4L, and MT-ND6 genes cause Leber hereditary optic neuropathy. These genes code for the NADH dehydrogenase protein involved in the normal mitochondrial function of oxidative phosphorylation. Oxidative phosphorylation uses a series of four large multienzyme complexes, all embedded in the inner mitochondrial membrane, to convert oxygen and simple sugars to energy.
Lebers hereditary optic neuropathy (LHON) is a mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; it predominantly affects young adult males. LHON is  transmitted only through the mother, as it is primarily due to mutations in the mitochondrial (not nuclear) genome, and only the egg contributes mitochondria to the embryo. LHON is usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations are at nucleotide positions 11778 G to A, 3460 G to A and 14484 T to C, respectively in the ND4, ND1 and ND6 subunit genes of complex I of the oxidative phosphorylation chain in mitochondria. Men cannot pass on the disease to their offspring. Signs and symptoms
Clinically, there is an acute onset of visual loss, first in one eye, and then a few weeks to months later in the other. Onset is usually young adulthood, but age range at onset from 7-75 is reported. The age of onset is slightly higher in females (range 19–55 years: mean 31.3 years) than males (range 15–53 years: mean 24.3). The male-to-female ratio varies between mutations: 3:1 for 3460 G>A, 6:1 for 11778 G>A and 8:1 for 14484 T>C.This typically evolves to very severe optic atrophy and a permanent decrease of visual acuity. Both eyes become affected either simultaneously (25% of cases) or sequentially (75% of cases) with a median inter-eye delay of 8 weeks. Rarely, only one eye is affected.