+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Leber’s hereditary optic neuropathy - Case report

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Leber’s hereditary optic neuropathy is the most common mitochondrial condition and is characterized by bilateral, painless, subacute visual loss that develops during young adult life. LHON is a rare condition and this lack of knowledge can make doctors suspect and treat for other causes of vision loss. Typically, a series of tests are performed to confirm LHON diagnosis or exclude any other conditions. We presented the case of two brothers, HB, of 40 years old and HF, of 38 years old, who presented with a decrease in visual acuity in both eyes. The patients had been diagnosed with optic atrophy of unknown cause a long time ago, but no further investigations were made. They were treated with corticosteroids, antioxidants and vasodilators, but with no significant benefit. A blood test of the mitochondrial DNA, a magnetic resonance imaging and an optic coherence tomography of the optic nerve and macula were part of the following assessment of our patients. The mitochondrial DNA analyses revealed the 3460 G>A mutation on the mtND1 gene in both patients. Based on the medical history, the fundus aspect, the optic coherence tomography and the paraclinical investigations of the diagnosis of Leber’s hereditary optic neuropathy were established in both patients. We started the treatment with idebenone and we evaluated the patients after three months.

          Abbreviations: LHON = Leber’s hereditary optic neuropathy, mtDNA = mitochondrial DNA, VA = visual acuity, CF = count fingers, OCT = optical coherence tomography, RNFL = retinal nerve fiber layer, GCL = ganglion cells layer, MS = multiple sclerosis, MRI = magnetic resonance imaging, MTI = magnetization transfer imaging, MTR = magnetization transfer ratio

          Related collections

          Most cited references 12

          • Record: found
          • Abstract: found
          • Article: not found

          Retinal nerve fiber layer evaluation by optical coherence tomography in Leber's hereditary optic neuropathy.

          To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (StratusOCT) in patients with Leber's hereditary optic neuropathy (LHON). Cross-sectional study. Thirty-eight patients with LHON were analyzed and compared with an age-matched control group of 75 patients. Patients with LHON were classified as having early LHON (E-LHON, n = 8) when the duration of the disease was shorter than 6 months and atrophic LHON (A-LHON, n = 30) when the duration was longer than 6 months. The fast RNFL thickness (3.4) scan acquisition protocol was used. Retinal nerve fiber layer thickness as measured by StratusOCT. Compared with the control group, eyes with E-LHON showed a thicker RNFL in the 360 degrees average measurement (P<0.01) and in the superior (P<0.01), nasal (P<0.05), and inferior quadrants (P<0.05); no significant changes were detected in the temporal quadrant. Eyes with A-LHON revealed a thinner RNFL in all measurements (P<0.001); the fibers of the nasal quadrant showed the lowest amount of reduction (38% vs. 42%-49.8% in the other quadrants). In cases with A-LHON and visual recovery, RNFL was significantly thicker in all measurements (P<0.001), except the temporal quadrant, with respect to A-LHON without visual recovery. On the basis of OCT data, the RNFL is thickened in E-LHON and severely thinned in A-LHON. RNFL is likely to be partially preserved in A-LHON with visual recovery. The temporal fibers (papillomacular bundle) are the first and most severely affected; the nasal fibers seem to be partially spared in the late stage of the disease.
            • Record: found
            • Abstract: found
            • Article: not found

            Mathematically modeling the involvement of axons in Leber's hereditary optic neuropathy.

            Leber's hereditary optic neuropathy (LHON), a mitochondrial disease, has clinical manifestations that reflect the initial preferential involvement of the papillomacular bundle (PMB). The present study seeks to predict the order of axonal loss in LHON optic nerves using the Nerve Fiber Layer Stress Index (NFL-S(I)), which is a novel mathematical model. Optic nerves were obtained postmortem from four molecularly characterized LHON patients with varying degrees of neurodegenerative changes and three age-matched controls. Tissues were cut in cross-section and stained with p-phenylenediamine to visualize myelin. Light microscopic images were captured in 32 regions of each optic nerve. Control and LHON tissues were evaluated by measuring axonal dimensions to generate an axonal diameter distribution map. LHON tissues were further evaluated by determining regions of total axonal depletion. A size gradient was evident in the control optic nerves, with average axonal diameter increasing progressively from the temporal to nasal borders. LHON optic nerves showed an orderly loss of axons, starting inferotemporally, progressing centrally, and sparing the superonasal region until the end. Values generated from the NFL-S(I) equation fit a linear regression curve (R(2) = 0.97; P < 0.001). The quantitative histopathologic data from this study revealed that the PMB is most susceptible in LHON, supporting clinical findings seen early in the course of disease onset. The present study also showed that the subsequent progression of axonal loss within the optic nerve can be predicted precisely with the NFL-S(I) equation. The results presented provided further insight into the pathophysiology of LHON.
              • Record: found
              • Abstract: found
              • Article: not found

              Pathogenic expression of homoplasmic mtDNA mutations needs a complex nuclear-mitochondrial interaction.

              Here we define a category of human, maternally inherited disorders that are characterized by a homoplasmic mtDNA pathogenic mutation with variable penetrance and a stereotypical clinical expression, usually restricted to a single tissue. Examples of such disorders include Leber's hereditary optic neuropathy, mitochondrial non-syndromic sensorineural hearing loss, and a form of mitochondrial hypertrophic cardiomyopathy. The mtDNA mutation is necessary, but not sufficient to induce the pathology, and multiple lines of evidence suggest a two-locus genetic model involving a primary mitochondrial mutation and a nuclear modifier. The nuclear modifier does not induce any pathology per se, but it contributes to the pathogenic effect of the mitochondrial mutation. The nuclear modifier could be a common functional polymorphism in a tissue-specific protein, possibly with mitochondrial location.

                Author and article information

                Rom J Ophthalmol
                Rom J Ophthalmol
                Romanian Journal of Ophthalmology
                Romanian Society of Ophthalmology (Romania )
                Jan-Mar 2018
                : 62
                : 1
                : 64-71
                [* ]Department of Ophthalmology, ”N. Oblu” Clinical Emergency Hospital, Iaşi, Romania
                [** ]Department of Ophthalmology, ”Gr. T. Popa” University of Medicine and Pharmacy, Iaşi, Romania
                Author notes
                Correspondence to: Iorga Raluca Eugenia, MD, PhD, Department of Ophthalmology, ”N. Oblu” Clinical Emergency Hospital, Iaşi 35 Lascăr Catargiu Street, Code 700107, Iaşi, Romania, Mobile phone: +40733 792 259, E-mail: ralucadanulescu@yahoo.com
                ©Romanian Society of Ophthalmology

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Case Reports


                Comment on this article