Raised Intraocular Pressure as a Potential Risk Factor for Visual Loss in Leber Hereditary Optic Neuropathy

Abstract

Leber Hereditary Optic Neuropathy (LHON) is an important cause of inherited mitochondrial blindness among young adults. The majority of patients carry one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A and m.14484T>C, all of which affect critical complex I subunits of the mitochondrial respiratory chain. LHON is characterised by marked incomplete penetrance, clearly implying that the mtDNA mutation is insufficient on its own to trigger retinal ganglion cell dysfunction and visual loss. In this case series of three affected patients harbouring the m.11778G>A mutation, we provide evidence suggesting that raised intraocular pressure could be a risk factor triggering visual loss in at-risk LHON carriers.

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

“…Another possible connection has been suggested between Leber Heraditary Optic Neuropathy (LHON) and glaucoma Thouin et al, 2013). In this regard, optic nerve head cupping (Mashima et al, 2003;Inagaki et al, 2006) and delayed VF loss (Newman, 1993) have been described in people carrying mtDNA mutation.…”

Leber’s hereditary optic neuropathy is multiorgan not mono-organ

“…The non-ophthalmologic manifestations in LHON may manifest before or after the occurrence of optic atrophy. Some patients with LHON have been reported in whom in addition to optic atrophy, other ocular manifestations were present, such as increased ocular pressure,32 retinopathy, and cataract 5…”

Leber Hereditary Optic Neuropathy Associated with Bilateral Macular Holes

“…An onset of LHON can be not only associated with but also triggered by many factors, including diabetes, 11,21 optic neuritis, 22 anti-tuberculous medications, 10,23,24 antiretroviral therapy for human immunodeficiency virus, 25,26 carbon monoxide poisoning, 27 solvent exposure, 28 smoking, 1,11,14,29–31 trauma, 11,12,14,32,33 and even an increase in the intraocular pressure. 11,12 For example, a 58-year-old man had an onset of visual loss 1 year after an elevation in his intraocular pressures was first recorded, and a 11778G→A mutation was identified.…”

“…11,12 For example, a 58-year-old man had an onset of visual loss 1 year after an elevation in his intraocular pressures was first recorded, and a 11778G→A mutation was identified. 12 In our patient, a number of events, including an intraocular pressure fluctuation that was induced by the surgery, intraocular tamponade, and postoperative posturing, might have induced the late onset of LHON.…”

“…1 Cases of late-onset LHON have been reported—for instance, 11778G→A mutation in 50-, 2 58-, 3 59-, 4 62-, 5 63-, 6,7 64-, 8 67-, 9 70-, 10,11 72-, 12 73-, 13 75-, 14 81-, 15 and 87- 16 year-old men, 14484T→C in 59- 5 and 81- 17 year-old men, and 3460G→A mutation in a 62-year-old woman 5 and in 75- 18 and 81- 19 year-old men. Onset in older age ranges increases the likelihood that the patients will previously have had other systemic 7 , 10 or eye 13 diseases, which can make the diagnosis of LHON more challenging.…”